Tick-Borne and Chronic Illness Research:  Education, Prevention, and Treatment Methods

There has been much research done since the organisms that cause Lyme Disease were identified beginning in the late 1970’s.  Here is a generous sampling of research that is particularly relevant to patients and healthcare practitioners. The research is grouped into the following categories for easier searching.











Vital Signs: Trends in Reported Vectorborne Disease Cases — United States and Territories
Rosenberg R, Lindsey NP, Fischer M, et al. 2004–2016.
Centers for Disease Control, MMWR Morb Mortal Wkly Rep 2018;67:496–501.
Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004–2016. A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004–2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States.

Surveillance for Lyme Disease – United States, 2008-2015
Schwartz AM, Hinckley AF, Mead PS, Hook SA, Kugeler KJ.
Morbidity and Mortality Weekly Report 2017;66(No. SS-22):1–12.
Results: During 2008–2015, a total of 275,589 cases of Lyme disease were reported to CDC (208,834 confirmed and 66,755 probable). Although most cases continue to be reported from states with high incidence in the Northeast, mid-Atlantic, and upper Midwest regions, case counts in most of these states have remained stable or decreased during the reporting period. In contrast, case counts have increased in states that neighbor those with high incidence. Overall, demographic characteristics associated with confirmed cases were similar to those described previously, with a slight predominance among males and a bimodal age distribution with peaks among young children and older adults. Yet, among the subset of cases reported from states with low incidence, infection occurred more commonly among females and older adults. In addition, probable cases occurred more commonly among females and with a higher modal age than confirmed cases.

Incidence of clinician-diagnosed Lyme disease, United States, 2005–2010
Nelson CA, Saha S, Kugeler KJ, Delorey MJ, Shankar MB, Hinckley AP, et al.
Emerging Infectious Diseases, Vol 12, No 9, September 2015. (Cited August 12, 2015.)
Of 103,647,966 person-years, 985 inpatient admissions and 44,445 outpatient LD diagnoses were identified. Epidemiologic patterns were similar to US surveillance data overall. Outpatient incidence was highest among boys 5–9 years of age and persons of both sexes 60–64 years of age. On the basis of extrapolation to the US population and application of correction factors for coding, we estimate that annual incidence is 106.6 cases/100,000 persons and that ˜329,000 (95% credible interval 296,000–376,000) LD cases occur annually. LD is a major US public health problem that causes substantial use of health care resources.

Comparison of Lyme Disease Prevalence and Disease Reporting in an Endemic Area
Holly Ahern
Journal of Microbiology Research, Vol. 3 No. 6, 2013, pp. 261-265.
Thus, in a region endemic for Lyme disease, cases are diagnosed by physicians more frequently than cases are reported. Additionally, a significant proportion of the study population reported signs and symptoms consistent with late-stage Lyme disease. Together, these results indicate underestimation of Lyme disease risk and an increase in public health burden for people living in endemic areas.

Lyme Disease Testing by Large Commercial Laboratories in the United States
Alison F. Hinckley, Neeta P. Connally, James I. Meek, Barbara J. Johnson, Melissa M. Kemperman, Katherine A. Feldman, Jennifer L. White, and Paul S. Mead
Clinical Infectious Diseases. published 6 July 2014.
Seven participating laboratories performed approximately 3.4 million LD tests on approximately 2.4 million specimens nationwide at an estimated cost of $492 million. Two-tiered testing accounted for at least 62% of assays performed; alternative testing accounted for <3% of assays. The estimated frequency of infection among patients from whom specimens were submitted ranged from 10% to 18.5%. Applied to the total numbers of specimens, this yielded an estimated 240 000 to 444 000 infected source patients in 2008.

‘Lyme Disease’: ancient engine of an unrecognized boreliosis pandemic?
W. T. Harvey, P. Salvato
Summary Unexpectedly we have found large numbers of chronically ill Borrelia burgdorferi PCR- and seropositive patients in Houston, Texas, a zoonotically ‘non-endemic’ area. In order to understand this finding prior to sufficient data availability, we chose to examine critically currently accepted but troublesome ‘Lyme disease’ concepts. Our method was to analyze each foundation ‘Lyme disease’ premise within the context of available medical and veterinary literature, then to reconstruct the disease model consistent with the preponderance of that data. We find the present conceptualization of the illness seriously truncated, with a high likelihood of two distinct but connected forms of human B. burgdorferi infection. The yet-unrecognized form appears to have a broader clinical presentation, wider geographic distribution, and vastly greater prevalence. We conclude that ‘Lyme disease’ currently acknowledges only its zoonosis arm and is a limited conceptualization of a far more pervasive and unrecognized infection state that must be considered a global epidemic.

Blacklegged Ticks Found in Half of U.S. Counties
Entomological Society of America, Annapolis, Maryland
January 19, 2016
Lyme disease is transmitted by the blacklegged tick (Ixodes scapularis) and the western blacklegged tick (Ixodes pacificus), and the range of these ticks is spreading, according to research published in the Journal of Medical Entomology.
They found that the blacklegged tick has been reported in more than 45% of U.S. counties, compared to 30% of counties in 1998. Even more alarming, the blacklegged tick is now considered established in twice the number of counties as in 1998.

Evolution of Northeastern and Midwestern Borrelia burgdorferi, United States.
Emerging Infectious Disease, 2010 Jun;16(6):911-7.
Brisson D, Vandermause MF, Meece JK, Reed KD, Dykhuizen DE.
The per capita incidence of human Lyme disease in the northeastern United States is more than twice that in the Midwest. However, the prevalence of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the tick vector is nearly identical in the 2 regions. The disparity in human Lyme disease incidence may result from a disparity in the human invasiveness of the bacteria in the Northeast and Midwest caused by fundamentally different evolutionary histories.

Recent and rapid population growth and range expansion of the Lyme disease tick vector, Ixodes scapularis, in North America
Khatchikian, C. E., Prusinski, M. A., Stone, M., Backenson, P. B., Wang, I.-N., Foley, E., Seifert, S. N., Levy, M. Z. and Brisson, D.
Evolution, online first, July 6, 2015.
Populations of blacklegged ticks have established and flourished in areas of North America previously thought to be devoid of this species.

A Bayesian spatio-temporal model for forecasting the prevalence of antibodies to Borrelia burgdorferi, causative agent of Lyme disease, in domestic dogs within the contiguous United States
Stella C. Watson, Yan Liu, Robert B. Lund, Jenna R. Gettings, Shila K. Nordone, Christopher S. McMahan, Michael J. Yabsley
PLoS ONE 12(5): e0174428.
This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016.

Human pathogens associated with the blacklegged tick Ixodes scapularis: a systematic review
Nelder MP, Russell CB, Sheehan NJ, Sander B, Moore S, Li Y, Johnson S, Patel SN, Sider D.
Parasites Vectors, online first, 2016 May 5.
The blacklegged tick Ixodes scapularis transmits Borrelia burgdorferi (sensu stricto) in eastern North America; however, the agent of Lyme disease is not the sole pathogen harbored by the blacklegged tick. Seventy-eight studies were included in the final review, 72 were from the US and eight were from Canada (two studies included blacklegged ticks from both countries). Sixty-four (82 %) studies met = 75 % of the quality assessment criteria. Blacklegged ticks harbored 91 distinct taxa, 16 of these are tick-transmitted human pathogens, including species of Anaplasma, Babesia, Bartonella, Borrelia, Ehrlichia, Rickettsia, Theileria and Flavivirus. Organism richness was highest in the Northeast (Connecticut, New York) and Upper Midwest US (Wisconsin); however, organism richness was dependent on sampling effort.

The Use of Harvested White-Tailed Deer (Odocoileus virginianus) and Geographic Information System (GIS) Methods to Characterize Distribution and Locate Spatial Clusters of Borrelia burgdorferi and Its Vector Ixodes scapularis in Indiana
Lisa M. Keefe, Manuel H. Moro, Javier Vinasco, Catherine Hill, Ching C. Wu, and Eran A. Raizman. Vector-Borne and Zoonotic Diseases. December 2009, 9(6): 671-680. doi:10.1089/vbz.2008.0162.
Published in Volume: 9 Issue 6: December 9, 2009
Multiple spatial clusters of I. scapularis-infested deer were identified in western Indiana. B. burgdorferi was isolated from tick pools in 11 counties. In addition to the I. scapularis clusters, one spatial cluster of Bb-infected ticks was identified. Our current survey results and cluster analysis indicate that the western geographic regions of Indiana should be considered by the healthcare community to be at increased risk of LD compared with the rest of Indiana.

The Relationship Between Deer Density, Tick Abundance, and Human Cases of Lyme Disease in a Residential Community
Kilpatrick, Howard J.; Labonte, Andrew M.; Stafford, Kirby C.
Journal of Medical Entomology, Volume 51, Number 4, pp. 777-784(8).
Reducing deer density to 5.1 deer per square kilometer resulted in a 76% reduction in tick abundance, 70% reduction in the entomological risk index, and 80% reduction in resident-reported cases of Lyme disease in the community from before to after a hunt was initiated.

Lyme disease cases in Indiana experience an uptick of 82 percent
By John Terhune, Journal and Courier, Lafayette, Indiana
August 29, 2011
The number of Lyme disease cases has been escalating over the years in the state and county. In Indiana, the number of Lyme disease cases has increased 82 percent, rising from 34 cases in 2005 to 62 in 2009, according to the Indiana State Department of Health.

Forest and Surface Water As Predictors of Borrelia burgdorferi and Its Vector Ixodes scapularis (Acari: Ixodidae) in Indiana
E. A. Raizman, J. D. Holland, L. M. Keefe, and M. H. Moro
© 2010 Entomological Society of America
The objective of this study was to assess whether the distribution of Borrelia burgdorferi, the causative agent of Lyme disease, and its vector tick Ixodes scapularis Say (Acari: Ixodidae) across Indiana is influenced by large-scale landscape features, specifically the proportion of forest within the surrounding landscape and the distance to water features such as lakes and major streams

White-Tailed Deer (Odocoileus virginianus) as a Potential Sentinel for Human Lyme Disease in Indiana
E. A. Raizman, J. D. Holland, J. T. Shukle
Zoonoses and Public Health, Volume 60, Issue 3, pages 227–233, May 2013.
Lyme disease incident rate varied between 0.08 cases per 10,000 habitants (Johnson county) and 5.9 cases per 10,000 habitants (Warren county).

Long-term study on ticks reveals shifting migration patterns, disease risks
Indiana University, Bloomington, Indiana
May 11, 2015
“Just in the past 10 years, we’re seeing things shift considerably,” Clay said. “You used to never see lone star ticks in Indiana; now they’re very common. In 10 years, we’re likely to see the Gulf Coast tick here, too. There are several theories for why this is happening, but the big one is climate change.”

Prevalence of Borrelia miyamotoi in Ixodes ticks in Europe and the United States.
Crowder CD, Carolan HE, Rounds MA, Honig V, Mothes B, Haag H, et al.
Emerging Infectious Diseases. 2014 Oct [Cited: September 12, 2014].
Ticks were collected from California, New York, Connecticut, Pennsylvania, and Indiana in the United States and from Germany and the Czech Republic in Europe from 2008 through 2012. We found B. miyamotoi infection in ticks in 16 of the 26 sites surveyed, with infection prevalence as high as 15.4%. These results show the widespread distribution of the pathogen, indicating an exposure risk to humans in areas where Ixodes ticks reside.

Widespread distribution of ticks and selected tick-borne pathogens in Kentucky (USA).
Lockwood BH, Stasiak I, Pfaff MA, Cleveland CA, Yabsley MJ.
Ticks and Tick-Borne Diseases. 2018 Mar;9(3):738-741.
The geographical distribution of Ixodes scapularis and Amblyomma maculatum ticks is poorly understood in Kentucky.We conducted a convenience survey of wildlife species (white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis) and black bears (Ursus americanus)) for ticks from October 2015 to January 2017. We detected four tick species including Amblyomma americanum, Dermacentor albipictus, I. scapularis and A. maculatum. Although the former two tick species were previously known to be widely distributed in Kentucky, we also found that I. scapularis and A. maculatum were also widespread.Because of the limited data available for pathogens from I. scapularis and A. maculatum, we tested them for Borrelia and Rickettsia spp. by polymerase chain reaction assays. Prevalence of Borrelia burgdorferi sensu stricto and Rickettsia parkeri were 11% and 3%, respectively. These data indicate that public health measures are important to prevent tick-borne diseases in Kentucky.

Borrelia burgdorferi in small mammal reservoirs in Kentucky, a traditionally non-endemic state for Lyme disease
Buchholz MJ, Davis C, Rowland NS, Dick CW.
Parasitology Research, online first 2018 Feb 7.
Prevalence of B. burgdorferi (21.8%) in Kentucky small mammals was comparable to the lowest recorded prevalence in regions where Lyme disease is endemic. Moreover, infestation of small mammals by Ixodes scapularis, the primary vector of B. burgdorferi, was rare, while Dermacentor variabilis comprised the majority of ticks collected.

Infection Prevalences of Common Tick-borne Pathogens in Adult Lone Star Ticks (Amblyomma americanum) and American Dog Ticks (Dermacentor variabilis) in Kentucky
Authors: Charissa M. Fritzen, Junjun Huang, Kathleen Westby, James D. Freye, Brett Dunlap, Michael J. Yabsley, Mike Schardein, John R. Dunn, Timothy F. Jones, Abelardo C. Moncayo
View Affiliations
Publisher: The American Society of Tropical Medicine and Hygiene
During 2007–2008, we collected 287 ticks (179 D. variabilis and 108 A. americanum) from canine, feral hog, horse, raccoon, white-tailed deer, and human hosts in six counties in Kentucky. Ticks were screened for Rickettsia spp., Borrelia spp., and Ehrlichia spp. by using polymerase chain reaction. Forty-one (14.3%) ticks (31 A. americanum and 10 D. variabilis) were polymerase chain reaction–positive for a Rickettsia spp. Fourteen (4.9%) ticks (6 A. americanum and 8 D. variabilis) were positive for E. chaffeensis, and 4 A. americanum (1.4%) were positive for E. ewingii. One (0.4%) A. americanum was positive for Borrelia lonestari.

“The Lyme Disease Spirochete, Borrelia burgdorferi, in Tick Species Collected … in the Warren and Barren Counties of South Central Kentucky”
Tackett, Kristina
A total of 976 ticks were collected. Three different species were obtained from raccoons; Dermacentor variabilis, Amblyomma americanum, and Ixodes sp. Dermacentor variabilis was the only tick species found on opossums. Twenty-five percent (163/642) of the tick DNA samples were positive for Borrelia burgdorferi. Prevalence of B. burgdorferi by tick species was 24.4% (141/577) in D. variabilis, 40.6% (13/32) in A. americanum, and 27.6% (8/29) in I. scapularis. In the present study, 15.7% (8/51) of the total raccoon blood samples examined by PCR were positive for B. burgdorferi, while no opossum blood samples were positive. The high prevalence of B. burgdorferi in ticks common to raccoons and opossums observed in this study, as well as in a tick species that aggressively bites humans in the southeast U. S. (A. americanum), creates concern that there are ample opportunities for people to come in contact with the infected ticks on these animals.

Rickettsia parkeri and Rickettsia montanensis, Kentucky and Tennessee, USA.
Pagac BB, Miller MK, Mazzei MC, Nielsen DH, Jiang J, Richards AL.
Emerging Infectious Disease [Internet]. 2014 Oct [Cited: September 4, 2014].
We found that 14.3% (15/105) of Amblyomma maculatum and 3.3% (10/299) of Dermacentor variabilis ticks collected at 3 high-use military training sites in west-central Kentucky and northern Tennessee, USA, were infected with Rickettsia parkeri and Rickettsia montanensis.

Temporal and Spatial Distribution of Tick-Borne Disease Cases among Humans and Canines in Illinois (2000-2009).
Herrmann JA, Dahm NM, Ruiz MO, Brown WM.
Environmental Health Insights, available online, 2014 Nov 9; 8(Suppl 2):15-27. eCollection 2014.
Four tick-borne diseases (TBDs), anaplasmosis, ehrlichiosis, Lyme disease (LD), and Rocky Mountain spotted fever (RMSF), are endemic in Illinois. The prevalence of human and canine cases of all four TBDs rose over the study period with significant differences in geographic distribution within the state.

Ixodes scapularis and Borrelia burgdorferi Among Diverse Habitats Within a Natural Area in East-Central Illinois.
Rydzewski J, Mateus-Pinilla N, Warner RE, Hamer S, Weng HY.
Vector Borne and Zoonotic Diseases, online before print, 2011 Jun 20.
The minimum Bb infection prevalence of on-host I. scapularis collected in the natural area was 14% (n=56). Unlike previous studies solely focused on forested areas and Peromyscus leucopus, our study is the first to provide evidence of I. scapularis collected from prairie habitat and other reservoir hosts, particularly M. ochrogaster.

Ixodes scapularis (Acari: Ixodidae) distribution surveys in the Chicago metropolitan region.
Rydzewski J, Mateus-Pinilla N, Warner RE, Nelson JA, Velat TC.
Journal of Medical Entomology. 2012 Jul;49(4):955-9.
This study updates the I. scapularis distribution in northeast Illinois. Our random sampling of suitable tick habitats across a large geographic area of the Chicago metropolitan area suggests a widespread human exposure to I. scapularis, and, potentially, to their associated pathogens throughout the region. These results prompt continued monitoring and investigation of the distribution, emergence, and expansion of I. scapularis populations and Borrelia burgdorferi transmission within this heavily populated region of Illinois.

Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector and agent, in Ohio.
Wang P, Glowacki MN, Hoet AE, Needham GR, Smith KA, Gary RE, Li X.
Frontiers in Cellular Infection Microbiology, 2014 Jun 4;4:70.
Collectively, these data suggest that the enzootic life cycle of B. burgdorferi has become established in Ohio, which poses risk of Lyme disease to people and animals in the area.

Geographic Expansion of Lyme disease in Michigan, 2000-2014
Paul M. Lantos, Jean Tsao, Lise E. Nigrovic, Paul G. Auwaerter, Vance Fowler, Felicia Ruffin, Erik Foster, and Graham Hickling
Open Forum Infectious Diseases (2017) ofw269. Published 09 January 2017.
Most Lyme disease cases in the Midwestern United States are reported in Minnesota and Wisconsin. In recent years, however, a widening geographic extent of Lyme disease has been noted with evidence of expansion eastwards into Michigan and neighboring states with historically low incidence rates.

Prevalence of Borrelia burgdorferi in adult female ticks (Ixodes scapularis), Wisconsin 2010–2013
Lloyd W. Turtinen, Alyssa N. Kruger and Madeleine M. Hacker
Journal of Vector Ecology, Volume 40, Issue 1, pages 195-197, June 2015.
Published surveys completed overseas in various countries (Germany, Japan, China, Norway) have shown prevalence rates of Borrelia spp. infection ranging from about 30-40% in adult Ixodes spp. In Wisconsin, unpublished surveys also reveal that as many as 40-50% of Ixodes scapularis adults in some areas may be infected. In recently published studies from the eastern United States, prevalence rates of B. burgdorferi in adult I. scapularis ranged from 27% to 45.2%. In Wisconsin, the prevalence of B. burgdorferi in I. scapularis nymphs collected from managed red pine forests from 2009 to 2013 was approximately 30%.

The Emergence of Clinically Relevant Babesiosis in Southwestern Wisconsin
Kowalski TJ, Jobe DA, Dolan EC, Kessler A, Lovrich SD, Callister SM.
Wisconsin Medical Journal. 2015 Aug;114(4):152-7.
Babesiosis should be considered endemic in southwestern Wisconsin, and testing should be considered for patients with compatible clinical and laboratory features.

Babesiosis Surveillance – Wisconsin, 2001-2015
Stein E, Elbadawi LI, Kazmierczak J, Davis JP.
Morbidity and Mortality Weekly Report (MMWR). 2017 Jul 7;66(26):687-691.
Wisconsin babesiosis surveillance data for 2001–2015 were analyzed in 3-year intervals to compare demographic, epidemiologic, and laboratory features among patients with cases of reported babesiosis. To determine possible reasons for an increase in reported Babesia infection, trends in electronic laboratory reporting and diagnosis by polymerase chain reaction testing (PCR) were examined. Between the first and last 3-year analysis intervals, there was a 26-fold increase in the incidence of confirmed babesiosis, in addition to geographic expansion.

Range Expansion and Increasing Borrelia burgdorferi Infection of the Tick Ixodes scapularis (Acari: Ixodidae) in Iowa, 1990-2013.
Oliver JD, Bennett SW, Beati L, Bartholomay LC.
Journal of Medical Entomology. 2017 Nov 7;54(6):1727-1734.
In 2013, 23.5% of nymphal and adult I. scapularis were infected with B. burgdorferi, the highest proportion of any year. Active surveillance was performed at selected sites from 2007–2009. Ixodes scapularis nymphs collected at these sites were tested for the presence of B. burgdorferi, Anaplasma phagocytophilum, and spotted fever group Rickettsia spp. (likely representing Rickettsia buchneri).Nymphs tested were 17.3% positive for B. burgdorferi, 28.9% for A. phagocytophilum, and 67.3% for Rickettsia spp. The results of these surveillance programs indicate an increasing risk of disease transmission by I. scapularis in Iowa.

Increased diversity of zoonotic pathogens and Borrelia burgdorferi strains in established versus incipient Ixodes scapularis populations across the Midwestern United States.
Hamer SA, Hickling GJ, Walker ED, Tsao JI.
Infection, Genetics and Evolution, pii: S1567-1348(14)00206-8.
Online before print 2014 Jun 17.
Analysis of 1565 adult I. scapularis ticks from 13 sites across five Midwestern states revealed that tick infection prevalence with multiple microbial agents (Borrelia burgdorferi, Borrelia miyamotoi, Babesia odocoilei, Babesia microti, and Anaplasma phagocytophilum), coinfections, and molecular genetic diversity of B. burgdorferi all were positively correlated with the duration of establishment of tick populations, and therefore generally support the center of origin – pathogen diversity hypothesis. The observed differences across the gradient of establishment, however, were not strong and were nuanced by the high frequency of coinfections in tick populations at both established and recently-invaded tick populations.

Confirmation of Borrelia burgdorferi sensu stricto and Anaplasma phagocytophilum in Ixodes scapularis, Southwestern Virginia.
Herrin BH, Zajac AM, Little SE.
Vector-Borne and Zoonotic Diseases. 2014 Nov;14(11):821-823.
These data document the presence of I. scapularis and the agent of Lyme disease in a newly established area of the Appalachian region, providing further evidence of range expansion of both the tick and public and veterinary health risk it creates.

Detection of Borrelia burgdorferi and Anaplasma phagocytophilum in the black-legged tick, Ixodes scapularis, within southwestern Pennsylvania
Scott M. Brown, Preston M. Lehman, Ryan A. Kern and Jill D. Henning
Journal of Vector Ecology, Volume 40, Issue 1, pages 180-183, June 2015.
Of the ticks collected from Pennsylvania, B. burgdorferi (causative agent of Lyme disease) was present in 114/325 (35%) and Anaplasma phagocytophilum (causative agent of Human Granulocytic Anaplasmosis) was present in 48/325 (15%) as determined by PCR analysis.

Dramatic Rise in Lyme Disease Cases in Alabama Prompts State Health Officer to Deliver Warning to Medical Professionals in 7 Alabama Counties Endemic for the Disease
October 8, 2015
The Alabama Lyme Disease Association reports that, due to a Dramatic Rise in Lyme disease cases in Alabama, State Health Officer Don Williamson recently sent a letter to Medical Professionals in Seven Alabama Counties Endemic for the disease to be aware of the symptoms and to remain vigilant

Prevalence Rates of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae), Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and Babesia microti (Piroplasmida: Babesiidae) in Host-Seeking Ixodes scapularis (Acari: Ixodidae) from Pennsylvania.
Hutchinson ML, Strohecker MD, Simmons TW, Kyle AD, Helwig MW.
Journal of Medical Entomology. 2015 Jul;52(4):693-8.
Infection rates were highest for B. burgdorferi (47.4%), followed by Ba. microti (3.5%) and A. phagocytophilum (3.3%). Coinfections included B. burgdorferi + Ba. microti (2.0%), B. burgdorferi + A. phagocytophilum (1.5%) and one tick positive for A. phagocytophilum + Ba. microti.

Molecular identification of Ehrlichia species and host bloodmeal source in Amblyomma americanum L. from two locations in Tennessee, United States
Jessica R. Harmon, M. Cathy Scott, Ellen M. Baker, Carl J. Jones, Graham J. Hickling
Ticks and Tick-borne Diseases, online before print, February 11, 2015.
The 9.3% prevalence of Ehrlichia spp. in ticks from the retirement community was similar to that detected at the state park site (5.5%), suggesting that the 4-Poster treatment had not been sufficient to reduce Ehrlichia spp. cycling in the tick population.

Prevalence of Rickettsiales in ticks removed from the skin of outdoor workers in North Carolina
Lee S, Kakumanu M, Ponnusamy L, Vaughn M, Funkhouser S, Thornton H, Meshnick SR, Apperson CS.
Parasite Vectors, online before print, 2014 Dec 23;7(1):607.
The lone star tick (Amblyomma americanum) accounted for 95.0 and 92.9% of ticks submitted in 2011 (n=423) and 2012 (n=451), respectively. Specimens of American dog tick (Dermacentor variabilis), Gulf Coast tick (Amblyomma maculatum) and black-legged tick (Ixodes scapularis) were also identified. In both years of our study, 60.9% of ticks tested positive for 17-kDa. “Candidatus R. amblyommii”, identified in all four tick species, accounted for 90.2% (416/461) of the 23S-5S-positive samples and 52.9% (416/787) of all samples tested. Nucleotide sequence analysis of Rickettsia-specific 23S-5S IGS, ompA and gltA gene fragments indicated that ticks, principally A. americanum, contained novel species of Rickettsia. Other Rickettsiales, including Ehrlichia ewingii, E. chaffeensis, Ehrlichia sp. (Panola Mountain), and Anaplasma phagocytophilum, were infrequently identified, principally in A. americanum.

Geographic Expansion of Lyme Disease in the Southeastern United States, 2000–2014
Paul M. Lantos, Lise E. Nigrovic, Paul G. Auwaerter, Vance G. Fowler Jr., Felicia Ruffin, R. Jory Brinkerhoff, Jodi Reber, Carl Williams, James Broyhill, William K. Pan and David N. Gaines
Open Forum Infectious Diseases, Nov 2015; 2 (4).
The majority of Lyme disease cases in the United States are acquired on the east coast between northern Virginia and New England. In recent years the geographic extent of Lyme disease has been expanding, raising the prospect of Lyme disease becoming endemic in the southeast.

Bartonella is Everywhere, So Why Don’t We Know More About It?
By Stephanie Soucheray, North Carolina Health News, Chapel Hill, North Carolina
December 5, 2013
An N.C. State professor says Bartonella infection is one of the most important untold medical stories.

Rickettsiae and ehrlichiae within a city park: is the urban dweller at risk?
Blanton LS, Walker DH, Bouyer DH.
Vector Borne Zoonotic Dis. 2014 Feb;14(2):168-70.
A total of 273 ticks were collected during July, 2011. Amblyomma americanum was the predominant tick species, with 255 (93%) of those collected. The remaining 18 (7%) were Dermacentor variabilis. Ticks were separated and pooled into groups for further testing. Forty-two of the 43 (98%) A. americanum pools demonstrated molecular evidence for the presence of rickettsiae.

Human granulocytic anaplasmosis in the United States from 2008 to 2012: a summary of national surveillance data.
Dahlgren FS, Heitman KN, Drexler NA, Massung RF, Behravesh CB.
The American Journal of Tropical Medicine and Hygiene. 2015 Jul;93(1):66-72.
Cases were reported from 38 states and from New York City, with the highest incidence in Minnesota (IR = 97), Wisconsin (IR = 79), and Rhode Island (IR = 51). Thirty-seven percent of cases were classified as confirmed, almost exclusively by polymerase chain reaction.The reported case fatality rate was 0.3% and the reported hospitalization rate was 31%. IRs, hospitalization rates, life-threatening complications, and case fatality rates increased with age group. The IR increased from 2008 to 2012 and the geographic range of reported cases of anaplasmosis appears to have increased since 2000–2007.

Human infection with Ehrlichia muris–like pathogen, United States, 2007–2013
Hoang Johnson DK, Schiffman EK, Davis JP, Neitzel DF, Sloan LM, Nicholson WL, et al.
Emerging Infectious Diseases. 2015 Oct [Cited September 28, 2015].
During 2004–2013, blood samples from 75,077 patients from all 50 United States were tested by PCR from the groEL gene for Ehrlichia spp. and Anaplasma phagocytophilum. During 2007–2013, samples from 69 (0.1%) patients were positive for the EML pathogen; patients were from 5 states: Indiana (1), Michigan (1), Minnesota (33), North Dakota (3), and Wisconsin (31).

Detection of Borrelia, Ehrlichia, and Rickettsia spp. in ticks in northeast Missouri
Hudman DA, Sargentini NJ.
Ticks and Tick-borne Diseases, online first, 2016 Apr 20.
We evaluated Amblyomma americanum (lone star tick) and Dermacentor variabilis (American dog tick) in northeast Missouri for the presence of Borrelia, Ehrlichia, and Rickettsia bacteria. We collected actively questing ticks from four sites within Adair County, Missouri. A total of 15,162 ticks were collected, of which 13,980 were grouped in 308 pools (lone star ticks, 288 pools; American dog ticks, 20 pools) and tested for presence/absence of bacteria using polymerase chain reaction.Infection rates were calculated as the maximum likelihood estimation (MLE) with 95% confidence intervals (CI). Of the 308 pools tested, 229 (74.4%) were infected with bacteria and the overall MLE of the infection rate per 100 ticks was calculated as 2.9% (CI 2.61–3.21). Infection rates varied among life stages, 28.6% (CI 23.89–33.97) in adults, 7.0% (CI 5.10–9.86) in nymphs, and 1.0% (CI 0.75–1.20) in larvae.In the 116 adult lone star pools, infection rates were calculated for Borrelia lonestari (1.4%), Borrelia spp. (2.7%), Ehrlichia chaffeensis (6.1%), Ehrlichia ewingii (3.3%), Rickettsia amblyommii (18.3%), and Rickettsia montanensis (0.4%). Infection rates for the 52 nymphal lone star pools were calculated as B. lonestari (1.03%), Borrelia spp. (0.40%), E. chaffeensis (2.02%), E. ewingii (0.24%), and R. amblyommii (2.70%). In the 20 adult American dog tick pools, infection rates were determined as E. chaffeensis (9.47%), E. ewingii (5.47%), and R. montanensis (8.06%).

Geographic and genospecies distribution of Borrelia burgdorferi sensu lato DNA detected in humans in the United States
Kerry L Clark, Brian F Leydet and Clifford Threlkeld
Journal of Medical Microbiology, online ahead of print February 25, 2014.
The study findings suggest that human cases of Lyme disease in the southern U.S. may be more common than previously recognized, and may also be caused by more than one species of B. burgdorferi sensu lato. This study provides further evidence that B. burgdorferi sensu stricto is not the only species associated with signs and/or symptoms consistent with Lyme borreliosis in the USA.

Prevalence of Tick-Borne Pathogens in Host-Seeking Amblyomma americanum (Acari: Ixodidae) and Odocoileus virginianus (Artiodactyla: Cervidae) in Florida.
Sayler KA, Loftis AD, Beatty SK, Boyce CL, Garrison E, Clemons B, Cunningham M, Alleman AR, Barbet AF.
Journal of Medical Entomology, online first, 2016 Apr 26.
Amblyomma americanum (L.), the lone star tick, is an aggressive tick that is expanding its geographic range within the United States.In lone star ticks, 14.6, 15.6, and 57.1% were positive for E. chaffeensis, E. ewingii, and Rickettsia spp. DNA, respectively. Panola Mountain Ehrlichia or B. lonestari DNA were each detected in nearly 2% of tick specimens. In white-tailed deer, 7.3% were PCR positive for E. chaffeensis, 6.0% for E. ewingii, and 3.2% for rickettsial species. Approximately 45% of white-tailed deer specimens had antibodies to Ehrlichia spp., and <1% had antibodies to Borrelia burgdorferi.

Zoonotic Babesia microti in the northeastern U.S.: Evidence for the expansion of a specific parasite lineage
Goethert HK, Molloy P, Berardi V, Weeks K, Telford SR 3rd.
PLoS One. 2018 Mar 22;13(3):e0193837.
We conclude that a single B. microti genotype has expanded across the northeastern U.S. The biological attributes associated with this parasite genotype that have contributed to such a selective sweep remain to be identified.

Identification of Novel Viruses in Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis Ticks
Rafal Tokarz, Stephen Sameroff, Teresa Tagliafierro, Komal Jain, Simon H. Williams, D. Moses Cucura, Ilia Rochlin, Javier Monzon, Giovanna Carpi, Danielle Tufts, Maria Diuk-Wasser, Jory Brinkerhoff, W. Ian Lipkin
mSphere Mar 2018, 3 (2) e00614-17.
Ticks carry a wide range of known human and animal pathogens and are postulated to carry others with the potential to cause disease. Here we report a discovery effort wherein unbiased high-throughput sequencing was used to characterize the virome of 2,021 ticks, including Ixodes scapularis (n = 1,138), Amblyomma americanum (n = 720), and Dermacentor variabilis (n = 163), collected in New York, Connecticut, and Virginia in 2015 and 2016. We identified 33 viruses, including 24 putative novel viral species. The most frequently detected viruses were phylogenetically related to members of the Bunyaviridae and Rhabdoviridae families, as well as the recently proposed Chuviridae. Our work expands our understanding of tick viromes and underscores the high viral diversity that is present in ticks.

Impact of white-tailed deer on the spread of Borrelia burgdorferi
Roome A, Hill L, Al-Feghali V, Murnock CG, Goodsell JA, Spathis R, Garruto RM.
Medical and Veterinary Entomology, online first, 2016 Oct 4.
These data suggest that a mechanism in white-tailed deer may aid in clearing the pathogen from attached deer ticks, although white-tailed deer do contribute to the spatial distribution of deer tick populations and also serve as deadend host breeding sites for ticks.

A quantitative synthesis of the role of birds in carrying ticks and tick-borne pathogens in North America
Loss SR, Noden BH, Hamer GL, Hamer SA.
Oecologia, online first, 2016 Sep 26.
Birds play a central role in the ecology of tick-borne pathogens. They expand tick populations and pathogens across vast distances and serve as reservoirs that maintain and amplify transmission locally.

Wild Birds as Sentinels for Multiple Zoonotic Pathogens Along an Urban to Rural Gradient in Greater Chicago, Illinois.
Zoonoses and Public Health, online before print, February 22, 2012.
Hamer SA, Lehrer E, Magle SB.
Wild birds were captured using mist nets at five sites throughout greater Chicago, Illinois, and blood, faecal and ectoparasite samples were collected for diagnostic testing. A total of 289 birds were captured across all sites. A total of 2.8% of birds harboured Ixodes scapularis – the blacklegged tick – of which 54.5% were infected with the agent of Lyme disease.

Expanded geographic distribution and clinical characteristics of Ehrlichia ewingii infections, United States
Harris RM, Couturier BA, Sample SC, Coulter KS, Casey KK, Schlaberg R.
Emerging Infectious Diseases. 2016 May [cited April 20, 2016].
Ehrlichiosis is a bacterial zoonosis, spread through the bites of infected ticks, that is most commonly caused in the United States by infection with the bacterium Ehrlichia chaffeensis.We retrospectively reviewed samples from an 18-month study of ehrlichiosis in the United States and found that E. ewingii was present in 10 (9.2%) of 109 case-patients with ehrlichiosis, a higher rate of infection with this species than had previously been reported. Two patients resided in New Jersey and Indiana, where cases have not been reported. All patients with available case histories recovered.

Co-infection of Ticks: The Rule Rather Than the Exception
Moutailler S, Valiente Moro C, Vaumourin E, Michelet L, Tran FH, Devillers E, Cosson JF, Gasqui P, Van VT, Mavingui P, Vourc’h G, Vayssier-Taussat M.
PLOS Neglected Tropical Diseases, 10(3):e0004539. Online first, 2016 Mar 17.
Ticks transmit more pathogens than any other arthropod, and one single species can transmit a large variety of bacteria and parasites. Because co-infection might be much more common than previously thought, we evaluated the prevalence of 38 known or neglected tick-borne pathogens in Ixodes ricinus ticks. Our results demonstrated that co-infection occurred in almost half of the infected ticks, and that ticks could be infected with up to five pathogens.

Undetermined Human Ehrlichiosis and Anaplasmosis in the United States, 2008-2012: A Catch-All for Passive Surveillance
Dahlgren FS, Heitman KN, Behravesh CB.
The American Journal of Tropical Medicine and Hygiene, online first, 2015 Nov 30.
Human ehrlichiosis and anaplasmosis are potentially severe illnesses endemic in the United States. Several bacterial agents are known causes of these diseases: Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris-like agent, Panola Mountain Ehrlichia species, and Anaplasma phagocytophilum.

Increasing Incidence of Ehrlichiosis in the United States: A Summary of National Surveillance of Ehrlichia chaffeensis and Ehrlichia ewingii Infections in the United States, 2008-2012.
Heitman KN, Dahlgren FS, Drexler NA, Massung RF, Behravesh CB.
The American Journal of Tropical Medicine and Hygiene, online first, 2015 Nov 30.
Human ehrlichiosis is a potentially fatal disease caused by Ehrlichia chaffeensis and Ehrlichia ewingii. Cases of ehrlichiosis are reported to Centers for Disease Control and Prevention through two national surveillance systems: Nationally Notifiable Diseases Surveillance System (NNDSS) and Case Report Forms.

Human Babesiosis: Pathogens, Prevalence, Diagnosis and Treatment
Ord RL, Lobo CA.
Current Clinical Microbiology Reports. 2015 Dec;2(4):173-181.
Human babesiosis is a zoonotic disease caused by protozoan parasites of the Babesia genus, primarily in the Northeastern and Midwest USA due to Babesia microti and Western Europe due to Babesia divergens.

Virulence of the Lyme disease spirochete before and after the tick bloodmeal: a quantitative assessment
Irene N. Kasumba, Aaron Bestor, Kit Tilly and Patricia A. Rosa
Parasites & Vectors, 2016, 9:129, online first March 7, 2016.
Borrelia burgdorferi, the tick-transmitted agent of Lyme disease, adapts to different environments as it cycles between an arthropod vector and vertebrate host.Conditional priming of B. burgdorferi during tick feeding induces changes in addition to OspC that are required for infection of the mammalian host.

More stricken with Lyme disease in Franklin County, throughout Ohio
By Laura Arenschield, The Columbus Dispatch, Columbus, Ohio
January 5, 2016
Lyme disease cases are on the rise in Ohio, and this past year Franklin County residents bore the brunt of the bites.The number of people with the disease, spread by ticks, has steadily increased in the past six years, according to data from the Ohio Department of Health.From January through September 2015, 146 cases of Lyme disease were reported to the state agency. In all of 2014, 119 cases were reported. Ten years ago, 58 cases were reported.

Specifying Pathogen Associations of Amblyomma maculatum (Acari: Ixodidae) in Western Tennessee.
Mays SE, Houston AE, Trout Fryxell RT.
Journal of Medical Entomology, online first 2016 Jan 7.
Amblyomma maculatum Koch (Acari: Ixodidae) is established in western Tennessee, a region with increased risk for Rocky Mountain spotted fever and ehrlichiosis. This tick transmits Rickettsia parkeri to humans, likely contributing to cases of rickettsiosis in the region.The objective was to determine pathogen associations within questing and host-collected A. maculatum, and identify ecological factors associated with pathogen infection that may increase the effectiveness of surveillance methods. Of 265 ticks tested, 60 (22.6%) were infected with R. parkeri, and 15 (5.7%) with Candidatus Rickettsia andeanae, a Rickettsia of unknown pathogenicity. Two deer-collected ticks tested positive for Ehrlichia ewingii.

Rickettsia parkeri in Amblyomma americanum ticks, Tennessee and Georgia, USA.
Cohen SB, Yabsley MJ, Garrison LE, Freye JD, Dunlap BG, Dunn JR, et al.
Emerging Infectious Disease, 2009 Sep; [serial on the Internet].
To determine the geographic distribution of the newly recognized human pathogen Rickettsia parkeri, we looked for this organism in ticks from Tennessee and Georgia, USA. Using PCR and sequence analysis, we identified R. parkeri in 2 Amblyomma americanum ticks. This rickettsiosis may be underdiagnosed in the eastern United States.

Babesiosis Occurrence among the Elderly in the United States, as Recorded in Large Medicare Databases during 2006-2013.
Menis M, Forshee RA, Kumar S, McKean S, Warnock R, Izurieta HS, Gondalia R, Johnson C, Mintz PD, Walderhaug MO, Worrall CM, Kelman JA, Anderson SA.
PLoS One. 2015 Oct 15;10(10):e0140332.
A total of 10,305 elderly Medicare beneficiaries had a recorded babesiosis diagnosis during the eight-year study period, for an overall rate of about 5 per 100,000 persons. Study results showed a significant increase in babesiosis occurrence over time (p<0.05), with the largest number of cases recorded in 2013 (N = 1,848) and the highest rates (per 100,000) in five Northeastern states: Connecticut (46), Massachusetts (45), Rhode Island (42), New York (27), and New Jersey (14). About 75% of all cases were diagnosed from May through October. Babesiosis occurrence was significantly higher among males vs. females and whites vs. non-whites

Deciphering Babesia-Vector Interactions
Antunes S, Rosa C, Couto J, Ferrolho J, Domingos A.
Frontiers in Cellular and Infection Microbiology, online first 2017 Sep 29.
Understanding host-pathogen-tick interactions remains a vitally important issue that might be better understood by basic research focused on each of the dyad interplays.Pathogens gain access to either the vector or host during tick feeding when ticks are confronted with strong hemostatic, inflammatory and immune responses. A prominent example of this is the Babesia spp.—tick—vertebrate host relationship. Babesia spp. are intraerythrocytic apicomplexan organisms spread worldwide, with a complex life cycle. The presence of transovarial transmission in almost all the Babesia species is the main difference between their life cycle and that of other piroplasmida. With more than 100 species described so far, Babesia are the second most commonly found blood parasite of mammals after trypanosomes.

U.S. public’s experience with ticks and tick-borne diseases: Results from national HealthStyles surveys.
Hook SA, Nelson CA, Mead PS.
Ticks and Tick-borne Diseases. pii: S1877-959X(15)00054-0. Online first, 2015 Apr 14.
There were 4728 respondents in 2009, 4050 in 2011, and 3503 in 2012. Twenty-one percent of respondents reported that a household member found a tick on his or her body during the previous year; of these, 10.1% reported consultation with a health care provider as a result. Overall, 63.7% of respondents reported that Lyme disease (LD) occurs in the area where they live.

Filarial Nematode Infection in Ixodes scapularis Ticks Collected from Southern Connecticut
Pabbati Namrata, Jamie M. Miller, Madari Shilpa, Patlolla Raghavender Reddy, Cheryl Bandoski, Michael J. Rossi and Eva Sapi
Veterinary Sciences, 2014, 1(1), 5-15.
It was recently demonstrated that the lone star tick Amblyomma americanum could harbor filarial nematodes within the genus Acanthocheilonema. In this study, Ixodes scapularis (deer) ticks collected from Southern Connecticut were evaluated for their potential to harbor filarial nematodes.

Synanthropic rodents and their ectoparasites as carriers of a novel haemoplasma and vector-borne, zoonotic pathogens indoors.
Hornok S, Földvári G, Rigó K, Meli ML, Gönczi E, Répási A, Farkas R, Papp I, Kontschán J, Hofmann-Lehmann R.
Parasite & Vectors, online before print, 2015 Jan 15.
Fifty-two rodents (mainly house mice and brown rats) were caught alive in buildings and checked for blood-sucking ectoparasites; followed by molecular analysis of these, together with spleen samples, for the presence of vector-borne agents. Haemoplasma infection was significantly more prevalent among brown rats, than among house mice. A novel haemoplasma genotype (with only 92-93% similarity to Candidatus Mycoplasma turicensis and M. coccoides in its 16S rRNA gene) was detected in a harvest mouse and a brown rat. Sporadic occurrence of Rickettsia helvetica, Anaplasma phagocytophilum, Borrelia burgdorferi s.l. and Bartonella sp. was also noted in rodents and/or their ectoparasites. These results indicate that synanthropic rodents, although with low prevalence, may carry zoonotic and vector-borne pathogens indoors.

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Clinical approach to known and emerging tick-borne infections other than Lyme disease.
Shah RG, Sood SK.
Current Opinion in Pediatrics. 2013 Jun;25(3):407-18.
The incidence of tick-borne diseases in the United States has increased. New tick-borne diseases have emerged and will likely continue to be identified. Clinicians should maintain suspicion for tick-borne diseases in children with acute infectious illnesses, and consider treating such patients presumptively to prevent complications. Knowledge of common tick vectors in the United States and the infections they transmit will allow pediatricians to appropriately assess and manage patients with tick-borne diseases.

The expanding Lyme Borrelia complex – Clinical significance of genomic species?
G. Stanek, M. Reiter
Clinical Microbiology and Infection, published online before print, February 15, 2011.
Whilst B. burgdorferi remained the only human pathogen in North America, all three species are aetiologic agents of Lyme borreliosis in Europe. Another seven genospecies were described in the 1990s including species from Asia (B. japonica, B. turdi, B. tanukii), North America (B. andersonii), Europe (B. lusitaniae, B. valaisiana), and (B. bissettii) from Europe and Asia.Another eight species were delineated in the years up to 2010: B. sinica (Asia), B. spielmanii (Europe), B. yangtze (Asia), B. californiensis, B. americana, B. carolinensis (North America), B. bavariensis (Europe), and B. kurtenbachii (North America).

Biodiversity of Borrelia burgdorferi Strains in Tissues of Lyme Disease Patients.
Brisson D, Baxamusa N, Schwartz I, Wormser GP (2011)
PLoS ONE 6(8): e22926.
The biodiversity of B. burgdorferi strains is significantly greater in tick populations than in the skin of patients with erythema migrans. In turn, strains from skin are significantly more diverse than strains at any of the disseminated sites. The cerebrospinal fluid of patients with neurologic Lyme disease harbored the least pathogen biodiversity. These results suggest that human tissues act as niches that can allow entry to or maintain only a subset of the total pathogen population. These data help to explain prior clinical observations on the natural history of B. burgdorferi infection and raise several questions that may help to direct future research to better understand the pathogenesis of this infection.

Surveillance for and Discovery of Borrelia Species in US Patients Suspected of Tickborne Illness
Luke C Kingry, Melissa Anacker, Bobbi Pritt, Jenna Bjork, Laurel Respicio-Kingry,
Clinical Infectious Diseases, online first, December 20, 2017.
Among the 7,292 tested specimens tested, five different Borrelia species were identified: two causing LB, B. burgdorferi (n=25) and B. mayonii (n=9), and three RF borreliae, B. hermsii (n=1), B. miyamotoi (n=8), and CandidatusB. johnsonii (n=1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi positive specimens, with new STs identified primarily among synovial fluids.

Multistrain infections with Lyme borreliosis pathogens in the tick vector
Durand J, Herrmann C, Genné D, Sarr A, Gern L, Voordouw MJ.
Applied and Environmental Microbiology, 83:e02552-16.
Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens.

Molecular Typing of Borrelia burgdorferi
Wang G, Liveris D, Mukherjee P, Jungnick S, Margos G, Schwartz I.
Current Protocols in Microbiology, published online 2014 Aug 1.
Currently, 20 Lyme disease-associated Borrelia species and more than 20 relapsing fever-associated Borrelia species have been described. Identification and differentiation of different Borrelia species and strains is largely dependent on analyses of their genetic characteristics.

Public health impact of strain specific immunity to Borrelia burgdorferi
Khatchikian CE, Nadelman RB, Nowakowski J, Schwartz I, Levy MZ, Brisson D, Wormser GP.
BMC Infectious Diseases. 2015 Oct 26;15(1):472.
Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Although humans can be infected by at least 16 different strains of B. burgdorferi, the overwhelming majority of infections are due to only four strains. It was recently demonstrated that patients who are treated for early Lyme disease develop immunity to the specific strain of B. burgdorferi that caused their infection. The aim of this study is to estimate the reduction in cases of Lyme disease in the United States that may occur as a result of type specific immunity. Assuming a reinfection rate of 3% and a total incidence of Lyme disease per year of 300,000, the estimated number of averted cases of Lyme disease per year ranges from 319 to 2378 depending on the duration of type specific immunity and the model used.

First arrived takes all: inhibitory priority effects dominate competition between co-infecting Borrelia burgdorferi strains
Godefroy Devevey, Trang Dang, Christopher J Graves, Sarah Murray and Dustin Brisson
BMC Microbiology 2015, 15:61. Published: 7 March 2015
The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation. The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

Discovery of diverse Borrelia burgdorferi strains in a bird-tick cryptic cycle
Sarah A. Hamer, Graham J. Hickling, Jennifer L. Sidge, Michelle E. Rosen, Edward D. Walker, and Jean I. Tsao
Applied and Environmental Microbiology, published online ahead of print: 21 January 2011.
We identified 25 closely related B. burgdorferi strains using an rRNA gene intergenic spacer marker, the majority (68%) of which had not been reported previously. The presence of strains common to both cryptic and endemic cycles strongly implies bird-mediated dispersal. Given continued large-scale expansion of I. scapularis populations, we predict that its invasion into zones of cryptic transmission will allow for bridging of novel pathogen strains to humans and animals.

Remarkable diversity of tick or mammalian-associated Borreliae in the metropolitan San Francisco Bay Area, California.
Fedorova N, Kleinjan JE, James D, Hui LT, Peeters H, Lane RS.
Ticks Tick Borne Diseases. Online before print, 2014 Aug 13. pii: S1877-959X(14)00160-5.
Together, eight borrelial genospecies were detected in ticks or small mammals from a single Californian county, two of which were related phylogenetically to European spirochetes.

Ability to cause erythema migrans differs between Borrelia burgdorferi sensu lato isolates
Ellen Tijsse-Klasen, Nenad Pandak, Paul Hengeveld, Katsuhisa Takumi, Marion P Koopmans and Hein Sprong
Parasites and Vectors, 2013, 6(1):23, published online before print January 22, 2013.
Seven different B. burgdorferi sl genospecies were identified in 152 borrelia isolates from ticks and erythema migrans biopsies. B afzelii (51%) and B. garinii (27%) were the most common in ticks. B. burgdorferi sl isolates differ in their propensity to cause erythema migrans. These differences were also found within genospecies. In other words, although B. afzelii was mostly associated with erythema migrans, some B. afzelii isolates had a low ability to cause erythema migrans.

Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease.
Strle K, Jones KL, Drouin EE, Li X, Steere AC.
American Journal of Pathology. 2011 Jun;178(6):2726-39.
Evidence is emerging for differential pathogenicity among Borrelia burgdorferi genotypes in the United States.

New Cause for Lyme Disease Complicates Already Murky Diagnosis
Scientists claim a novel bacterium causes some different symptoms, adding to the body of research showing the complexity of the disease
By Melinda Wenner Moyer, Scientific
February 16, 2016
Tick-borne Lyme disease in the U.S. has long been thought to be caused by a single microbe, a spiral-shaped bacterium called Borrelia burgdorferi.Last week this notion was challenged when a team led by scientists at the Mayo Clinic discovered that Lyme could be caused, albeit rarely, by a different bacterial species that may incite more serious symptoms ranging from vomiting to neurological issues.

Recurrent evolution of host and vector association in bacteria of the Borrelia burgdorferi sensu lato species complex.
Becker NS, Margos G, Blum H, Krebs S, Graf A, Lane RS, Castillo-Ramírez S, Sing A, Fingerle V.
BMC Genomics. 2016 Sep 15;17(1):734.
Background The Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations.

Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States
Pritt BS, Respicio-Kingry LB, Sloan LM, Schriefer ME, Replogle AJ, Bjork J, Liu G, Kingry LC, Mead PS, Neitzel DF, Schiffman E, Hoang Johnson DK, Davis JP, Paskewitz SM, Boxrud D, Deedon A, Lee X, Miller TK, Feist MA, Steward CR, Theel ES, Patel R, Irish CL, Petersen JM
International Journal of Systematic and Evolutionary Microbiology, online first 2016 Aug 24.
Lyme borreliosis (LB) is a multisystem disease caused by spirochetes in the Borrelia burgdorferi sensu lato (Bbsl) genospecies complex. We previously described a novel Borrelia species (type strain MN14-1420T) that causes LB among patients with exposures to ticks in the upper midwestern United States. Patients infected with the novel species demonstrated high levels of spirochetemia and differing clinical symptoms as compared to other Bbsl genospecies.

Emerging borreliae – Expanding beyond Lyme borreliosis
Sally J. Cutlera, Eva Ruzic-Sabljicb, Aleksandar Potkonja
Molecular and Cellular Probes, online first, 12 August 2016.
Lyme borreliosis (or Lyme disease) has become a virtual household term to the exclusion of other forgotten, emerging or re-emerging borreliae. We review current knowledge regarding these other borreliae, exploring their ecology, epidemiology and pathological potential, for example, for the newly described B. mayonii.Many of the borreliae discussed here are currently considered exotic curiosities, whilst others, such as B. miyamotoi, are emerging as significant causes of morbidity. To elucidate their role as potential pathogenic agents, we first need to recognise their presence through suitable diagnostic approaches.

Chronic neuroborreliosis by B. garinii: an unusual case presenting with epilepsy and multifocal brain MRI lesions.
Matera G, Labate A, Quirino A, Lamberti AG, Borzà G, Barreca GS, Mumoli L, Peronace C, Giancotti A, Gambardella A, Focà A, Quattrone A.
New Microbiologica. 2014 Jul; 37(3):393-7.
The current case provides evidence that patients presenting with epileptic seizures and MRI-detected multifocal lesions, particularly when a facial palsy has also occurred, should raise the suspicion of LNB, as this diagnosis has important implications for treatment and prognosis.

Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms.
Meriläinen L, Herranen A, Schwarzbach A, Gilbert L.
Microbiology. pii: mic.0.000027. Online before print, 2015 Jan 6.
Here, we present a comprehensive analysis of B. burgdorferi pleomorphic formation in different culturing conditions at physiological temperature. Interestingly, human serum induced the bacteria to change its morphology to round bodies. In addition, biofilm-like colonies in suspension were found to be part of B. burgdorferi’s normal in vitro growth.Further studies provided evidence that spherical round bodies had an intact and flexible cell envelope demonstrating that they are not cell wall deficient, or degenerative as previously implied. However, the round bodies displayed lower metabolic activity compared to spirochetes.Furthermore, our results indicated that the different pleomorphic variants were distinguishable by having unique biochemical signatures. Consequently, pleomorphic B. burgdorferi should be taken into consideration as being clinically relevant and influence the development of novel diagnostics and treatment protocols.

Pleomorphic forms of Borrelia burgdorferi induce distinct immune responses
Meriläinen L, Brander H, Herranen A, Schwarzbach A, Gilbert L.
Microbes and Infection, online first 2016 Apr 29.
Borrelia burgdorferi is the causative agent of tick-borne Lyme disease. As a response to environmental stress B. burgdorferi can change its morphology to a round body form. The role of B. burgdorferi pleomorphic forms in Lyme disease pathogenesis has long been debated and unclear.Here, we demonstrated that round bodies were processed differently in differentiated macrophages, consequently inducing distinct immune responses compared to spirochetes in vitro. Colocalization analysis indicated that the F-actin participates in internalization of both forms. However, round bodies end up less in macrophage lysosomes than spirochetes suggesting that there are differences in processing of these forms in phagocytic cells.

Lyme disease caused by Borrelia burgdorferi with two homeologous 16S rRNA genes: a case report
Lee S
International Medical Case Reports Journal, online first, 21 April 2016.
Lyme disease (LD), the most common tick-borne disease in North America, is believed to be caused exclusively by Borrelia burgdorferi sensu stricto and is usually diagnosed by clinical evaluation and serologic assays.As reported previously in a peer-reviewed article, a 13-year-old boy living in the Northeast of the USA was initially diagnosed with LD based on evaluation of his clinical presentations and on serologic test results. The patient was treated with a course of oral doxycycline for 28 days, and the symptoms resolved. A year later, the boy developed a series of unusual symptoms and did not attend school for 1 year. A LD specialist reviewed the case and found the serologic test band patterns nondiagnostic of LD. The boy was admitted to a psychiatric hospital. After discharge from the psychiatric hospital, a polymerase chain reaction test performed in a winter month when the boy was 16 years old showed a low density of B. burgdorferi sensu lato in the blood of the patient, confirmed by partial 16S rRNA (ribosomal RNA) gene sequencing. Subsequent DNA sequencing analysis presented in this report demonstrated that the spirochete isolate was a novel strain of B. burgdorferi with two homeologous 16S rRNA genes, which has never been reported in the world literature.

Borrelia burgdorferi Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion
Hyde JA.
Frontiers in Immunology, 2017 Feb 21;8:114. eCollection 2017.
Borrelia burgdorferi is the etiological agent of Lyme disease, a multisystemic, multistage, inflammatory infection resulting in patients experiencing cardiac, neurological, and arthritic complications when not treated with antibiotics shortly after exposure.This review provides an overview of B. burgdorferi mechanisms for dissemination and invasion in the mammalian host, which are essential for pathogenesis and the development of persistent infection.

Lyme Disease Coinfections in the United States
Caulfield AJ, Pritt BS.
Clinics in Laboratory Medicine. 2015 Dec;35(4):827-46.
Lyme disease in North America is caused by infection with the spirochetal bacterium Borrelia burgdorferi and transmitted by Ixodes scapularis and Ixodes pacificus ticks.These ticks also have the potential to transmit a rapidly expanding list of other pathogenic bacteria, viruses, and parasites, including Anaplasma phagocytophilum, Babesia microti, deer tick (Powassan) virus, Borrelia miyamotoi, and the Ehrlichia muris-like organism.Coinfections with B burgdorferi and these other agents are often difficult to diagnose and may go untreated, and thus contribute significantly to patient morbidity and mortality from tick-borne infections.

Detection of Bartonella Species in the Blood of Veterinarians and Veterinary Technicians: A Newly Recognized Occupational Hazard?
Lantos, Paul M., Maggi, Ricardo G., Ferguson, Brandy, Varkey, Jay, Park, Lawrence P., Breitschwerdt, Edward B., and Woods, Christopher W.
Vector-Borne and Zoonotic Diseases. August 2014, 14(8): 563-570.
We detected DNA from at least one Bartonella species in 32 (28%) of the 114 veterinary subjects. After DNA sequencing, the Bartonella species could be determined for 27 of the 32 infected subjects, including B. henselae in 15 (56%), B. vinsonii subsp. berkhoffii in seven (26%), B. koehlerae in six (22%), and a B. volans–like sequence in one (4%). Seventy percent of Bartonella-positive subjects described headache compared with 40% of uninfected veterinarians (p=0.009). Irritability was also reported more commonly by infected subjects (68% vs. 43%, p=0.04).
Conclusions: Our study supports an emerging body of evidence that cryptic Bartonella bloodstream infection may be more frequent in humans than previously recognized and may induce symptoms. Longitudinal studies are needed to determine the natural course and clinical features of Bartonella infection.

Identification of novel zoonotic activity of Bartonella spp., France.
Vayssier-Taussat M, Moutailler S, Féménia F, Raymond P, Croce O, La Scola B, et al.
Emerging Infectious Diseases. March 2015 [cited February 4, 2016].
Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans.Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks.

High prevalence of Borrelia miyamotoi among adult blacklegged ticks from white-tailed deer
Han S, Hickling GJ, Tsao JI.
Emerging Infectious Disease, February 2016.
We compared the prevalence of Borrelia miyamotoi infection in questing and deer-associated adult Ixodes scapularis ticks in Wisconsin, USA.Prevalence among deer-associated ticks (4.5% overall, 7.1% in females) was significantly higher than among questing ticks (1.0% overall, 0.6% in females).

Frequency and distribution of rickettsiae, borreliae, and ehrlichiae detected in human-parasitizing ticks, Texas, USA
Mitchell EA, Williamson PC, Billingsley PM, Seals JP, Ferguson EE, Allen MS.
Emerging Infectious Disease, February 2016.
To describe the presence and distribution of tickborne bacteria and their vectors in Texas, USA, we screened ticks collected from humans during 2008–2014 for Rickettsia, Borrelia, and Ehrlichia spp.Thirteen tick species were identified, and 23% of ticks carried bacterial DNA from at least 1 of the 3 genera tested.

A real-time PCR assay for detection of the Ehrlichia muris-like agent, a newly recognized pathogen of humans in the upper Midwestern United States
Allerdice ME, Pritt BS, Sloan LM, Paddock CD, Karpathy SE.
Ticks and Tick-borne Diseases, online first, 2015 Oct 22.
The Ehrlichia muris-like agent (EMLA) is an emerging, tick-transmitted human pathogen that occurs in the upper Midwestern United States. Here, we describe the development and validation of a p13-based quantitative real-time PCR TaqMan assay to detect EMLA in blood or tissues of ticks, humans, and rodents.

Opening the black box of Anaplasma phagocytophilum diversity: current situation and future perspectives.
Dugat T, Lagrée AC, Maillard R, Boulouis HJ, Haddad N.
Frontiers in Cellular Infection Microbiology. 2015 Aug 14;5:61. eCollection 2015.
A. phagocytophilum epidemiological cycles are complex and involve different ecotypes, vectors, and mammalian host species. Moreover, the epidemiology of A. phagocytophilum infection differs greatly between Europe and the USA. These different epidemiological contexts are associated with considerable variations in bacterial strains

Anaplasma phagocytophilum: deceptively simple or simply deceptive?
Severo MS, Stephens KD, Kotsyfakis M, Pedra JH.
Future Microbiology, June 2012, Vol. 7, No. 6, Pages 719-731.
Anaplasma phagocytophilum is an obligate intracellular rickettsial pathogen transmitted by ixodid ticks. This bacterium colonizes myeloid and nonmyeloid cells and causes human granulocytic anaplasmosis – an important immunopathological vector-borne disease in the USA, Europe and Asia. Here, we provide an overview of the underlying events by which the immune system responds to A. phagocytophilum infection, how this pathogen counteracts host immunity and the contribution of the tick vector for microbial transmission.

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure.
Barbet AF, Al-Khedery B, Stuen S, Granquist EG, Felsheim RF, Munderloh UG.
Pathogens. 2013; 2(3):544-555.
The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections.

Prevalence of Human-Active and Variant 1 Strains of the Tick-Borne Pathogen Anaplasma phagocytophilum in Hosts and Forests of Eastern North America.
Keesing F, McHenry DJ, Hersh M, Tibbetts M, Brunner JL, Killilea M, LoGiudice K, Schmidt KA, Ostfeld RS.
American Journal of Tropical Medicine and Hygiene, online before print 2014 May 27.
Anaplasmosis is an emerging infectious disease caused by infection with the bacterium Anaplasma phagocytophilum. In the eastern United States, A. phagocytophilum is transmitted to hosts through the bite of the blacklegged tick, Ixodes scapularis.

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).
Molins CR, Ashton LV, Wormser GP, Andre BG, Hess AM, Delorey MJ, Pilgard MA, Johnson BJ, Webb K, Islam MN, Pegalajar-Jurado A, Molla I, Jewett MW, Belisle JT.
Science Translational Medicine, 2017 Aug 16;9(403).
The iconic bulls eye rash is associated with Lyme disease, but similar symptoms are observed in other illnesses not caused by Borrelia burgdorferi infection, such as southern tick–associated rash illness, which has not yet been tied to a specific pathogen.

A Roadmap for Tick-Borne Flavivirus Research in the “Omics” Era
Grabowski JM, Hill CA.
Frontiers in Cellular and Infection Microbiology. 2017 Dec 22;7:519. eCollection 2017.
Tick-borne flaviviruses (TBFs) affect human health globally. Human vaccines provide protection against some TBFs, and antivirals are available, yet TBF-specific control strategies are limited. Here we review the current state of genomic research on ticks and tick-borne viruses with an emphasis on TBFs.

Heartland virus neutralizing antibodies in vertebrate wildlife, United States, 2009–2014.
Riemersma KK, Komar N.
Emerging Infectious Diseases. 2015 Oct [Cited September 21, 2015].
This retrospective evaluation determined that HRTV is widespread within the central and eastern United States.

Southern Tick-Associated Rash Illness (STARI) in the North: STARI Following a Tick Bite in Long Island, New York.
Feder HM Jr, Hoss DM, Zemel L, Telford SR 3rd, Dias F, Wormser GP.
Clinical Infectious Diseases, First published online: September 21, 2011.
The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness).

‘Tick paralysis’ strikes girl, 2 Doctors initially stumped; her recovery is fast
By Shantal Parris Riley, Poughkeepsie Journal, Poughkeepsie, New York
May 18, 2012
Health professionals are looking into a rare case of a little girl who was paralyzed after being bitten by an American dog tick. The 2-year-old was unable to eat or drink – immobilized by a potentially fatal illness

Hidden in plain sight: Cryptic and endemic malaria parasites in North American white-tailed deer.
Ellen S. Martinsen, Nancy Mcinerney, Heidi Brightman, Ken Ferebee, Tim Walsh, William J. Mcshea, Tavis D. Forrester, Lisa Ware, Priscilla H. Joyner, Susan L. Perkins, Emily K. Latch, Michael J. Yabsley, Joseph J. Schall and Robert C. Fleischer.
Science Advances, 2016
DOI: 10.1126/sciadv.1501486
By chance, scientists have discovered a malaria parasite that infects white-tailed deer. It’s the first-ever malaria parasite known to live in a deer species and the only native malaria parasite found in any mammal in North or South America.

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The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern
Eisen RJ, Eisen L.
Trends in Parasitology. 2018 Jan 11. pii: S1471-4922(17)30311-2.
In the United States, the blacklegged tick, Ixodes scapularis, is a vector of seven human pathogens, including those causing Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis associated with Ehrlichia muris eauclarensis.In addition to an accelerated rate of discovery of I. scapularis-borne pathogens over the past two decades, the geographic range of the tick, and incidence and range of I. scapularis-borne disease cases, have increased. Despite knowledge of when and where humans are most at risk of exposure to infected ticks, control of I. scapularis-borne diseases remains a challenge.

Lyme Disease Propelled by Borrelia burgdorferi-Infected Blacklegged Ticks, Wild Birds and Public Awareness ─ Not Climate Change.
Scott JD, Scott CM.
Journal of Veterinary Science & Medicine. 2018;6(1): 8.
The blacklegged tick, Ixodes scapularis, is of major public health importance as a vector of Borrelia burgdorferi, the causal organism of Lyme disease. Migratory songbirds are involved in short- and longdistance transport of bird-feeding ticks, and play a vital role in the wide dispersal of I. scapularis and the epidemiology of Lyme disease. Because northern latitudes generally have a thick blanket of snow each winter, the blacklegged tick withstands phenomenal outdoor temperature fluctuations. However, when the snow cover is lost in the core months of winter, due to subtle periods of warmer temperatures, we discovered that overwinter survival declined significantly. Photoperiod is a limiting factor in the pole-ward expansion and establishment of I. scapularis because immature stages of I. scapularis will not molt in late summer when photoperiod shortens quickly.When it comes to I. scapularis ticks, climate change is a triviality. Health professionals must be aware that Lyme disease and tick-associated diseases are a significant public health burden, and include them in their differential diagnosis.

Bloodsucking Ticks Make Cement to Attach to Your Skin – The disease-carrying parasites’ natural glue could also hold a key to healing us.
By Joshua Rapp Learn, National Geographic, Washington, DC
January 19, 2018
Bloodsucking parasites that can carry deadly diseases create their own cement to glue themselves to our bodies, a new study says. Hard ticks – a family of 700 species that includes the Lyme-spreading deer tick – use pincer-like appendages and mouths to attach to a host’s skin. But sometimes this grip isn’t strong enough for the arachnid to hold on and feed while the host moves. Sylvia Nürnberger and colleagues discovered hard ticks have an extra tool to glom onto their hosts’ skin – a kind of glue made of proteins in their saliva.

Integrated Pest Management in Controlling Ticks and Tick-Associated Diseases
Kirby C Stafford, III, Scott C Williams, Goudarz Molaei
Journal of Integrated Pest Management, online first, 17 October 2017.
In this paper, we review surveyed human behaviors and risks for exposure to ticks, concepts pertinent to integrated pest management for ticks, simulation models, various tick control strategies, integrated tick management studies, and highlight what is needed going forward. Increased education and communication between physicians and veterinarians is essential to address tick-associated diseases in a ‘one health’ approach and unify the animal and human branches of medicine to identify, treat, and implement preventive measures.

Pet ownership increases human risk of encountering ticks
Jones EH, Hinckley AF, Hook SA, Meek JI, Backenson B, Kugeler KJ, Feldman KA.
Zoonoses and Public Health, online first 2017 Jun 19.
We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses.Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets.

An Up-Close Look at the Tiny Sensory Pits That Ticks Use to Smell
By Meredith Swett Walker, Entomology Today, Annapolis, Maryland

An Up-Close Look at the Tiny Sensory Pits That Ticks Use to Smell

If you ever find a tick before it finds you – that is when it’s still hanging out on vegetation hoping you’ll brush past it – you may notice the little bloodsucker waving its “arms in the air like it just don’t care.” But ticks aren’t fans of 1980’s hip hop. They’re waving their arms because they are trying to get a whiff of you. While insects primarily smell with their antennae, ticks are not insects; rather, they’re arachnids, and they don’t have antennae. Instead, a tick smells using a structure on its forelegs called the Haller’s organ.

Accelerated phenology of blacklegged ticks under climate warming
Taal Levi, Felicia Keesing, Kelly Oggenfuss, Richard S. Ostfeld
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 2015 Apr 5; 370(1665).
Here, we use 19 years of data on blacklegged ticks attached to small-mammal hosts to quantify the relationship between climate warming and tick phenology. Warmer years through May and August were associated with a nearly three-week advance in the phenology of nymphal and larval ticks relative to colder years, with little evidence of increased synchrony.Warmer Octobers were associated with fewer larvae feeding concurrently with nymphs during the following spring. Projected warming by the 2050s is expected to advance the timing of average nymph and larva activity by 8-11 and 10-14 days, respectively. If these trends continue, climate warming should maintain or increase transmission of persistent pathogens, while it might inhibit pathogens that do not produce long-lasting infections.

Effectiveness of Residential Acaricides to Prevent Lyme and Other Tickborne Diseases in Humans.
Hinckley AF, Meek JI, Ray JA, Niesobecki SA, Connally NP, Feldman KA, Jones EH, Backenson PB, White JL, Lukacik G, Kay AB, Miranda WP, Mead PS.
The Journal of Infectious Diseases, online first 2016 Jan 5.
In the northeastern United States, tickborne diseases are a major public health concern. In controlled studies, a single springtime application of acaricide has been shown to kill between 68 and 100% of ticks. Although public health authorities recommend use of acaricides to control tick populations in yards, the effectiveness of these pesticides to prevent tick bites or human tickborne diseases is unknown.Although abundance of questing ticks was significantly lower (63%) on acaricide-treated properties, there was no difference between treatment groups in human-tick encounters, self-reported or medical record-validated tickborne diseases.Used as recommended, acaricide barrier sprays do not significantly reduce household risk of tick exposure or tickborne disease. Measures for preventing tickborne diseases should be evaluated against human outcomes to confirm effectiveness.

Scientists Have Sequenced the Genome of the Tick that Transmits Lyme Disease
Entomology Today, Entomological Society of America, Annapolis, Maryland
February 29, 2016
An international team of scientists led by Purdue University has sequenced the genome of the tick that transmits Lyme disease, the most common vector-borne illness in North America. Ixodes scapularis, known as the blacklegged tick or the deer tick, is the first tick species to have its genome sequenced. The decade-long project, involving 93 authors from 46 institutions, decodes the biology of an arachnid with sophisticated spit, barbed mouthparts, and millions of years of successful parasitism. The genome of Ixodes scapularis also sheds light on how ticks acquire and transmit pathogens and offers tick-specific targets for control.

Different Populations of Blacklegged Tick Nymphs Exhibit Differences in Questing Behavior That Have Implications for Human Lyme Disease Risk.
Arsnoe IM, Hickling GJ, Ginsberg HS, McElreath R, Tsao JI.
PLoS One. 2015 May 21;10(5):e0127450.
We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

Meteorological Influences on the Seasonality of Lyme Disease in the United States
Moore SM, Eisen RJ, Monaghan A, Mead P.
American Journal of Tropical Medicine and Hygiene, online before print 2014 Jan 27.
An earlier beginning to the LD season was positively associated with higher cumulative growing degree days through Week 20, lower cumulative precipitation, a lower saturation deficit, and proximity to the Atlantic coast. The timing of the peak and duration of the LD season were also associated with cumulative growing degree days, saturation deficit, and cumulative precipitation, but no meteorological predictors adequately explained the timing of the end of the LD season.

The impact of temperature and precipitation on blacklegged tick activity and Lyme disease incidence in endemic and emerging regions
Burtis JC, Sullivan P, Levi T, Oggenfuss K, Fahey TJ, Ostfeld RS.
Parasites & Vectors. 2016 Nov 25;9(1):606.
Recently endemic regions showed an increase in Lyme disease incidence over time, while incidence in long-term endemic regions appears to have stabilized. Only within the stabilized areas were we able to detect reduced Lyme disease incidence in years with hot, dry summer weather. These patterns were reflected in our field data, which showed that questing activity of nymphal I. scapularis was reduced by hot, dry summer weather.

Bioassays to evaluate non-contact spatial repellency, contact irritancy, and acute toxicity of permethrin-treated clothing against nymphal Ixodes scapularis ticks
Lars Eisen, Dominic Rose, Robert Prose, Nicole E. Breuner, Marc C. Dolan, Karen Thompson, Neeta Connally
Ticks and Tick-borne Diseases, online first July 1, 2017.
Our results indicate that permethrin-treated textiles provide minimal non-contact spatial repellency but strong contact irritancy against ticks, manifesting as a “hot-foot” effect and resulting in ticks actively dislodging from contact with vertically oriented treated textile. Preliminary data suggest that the contact irritancy hot-foot response may be weaker for field-collected nymphs as compared with laboratory-reared nymphs placed upon permethrin-treated textile. We also demonstrate that contact with permethrin-treated textiles negatively impacts the vigor and behavior of nymphal ticks for >24 hr, with outcomes ranging from complete lack of movement to impaired movement and unwillingness of ticks displaying normal movement to ascend onto a human finger.

Flying ticks: anciently evolved associations that constitute a risk of infectious disease spread
de la Fuente J, Estrada-Peña A, Cabezas-Cruz A, Brey R.
Parasites & Vectors. 2015 Oct 15;8(1):538.
Birds are central elements in the ecological networks of ticks, hosts and TBP. The study of host-tick-pathogen associations reveals a prominent role for birds in the dissemination of Borrelia spp. and Anaplasma phagocytophilum, with little contribution to the possible dissemination of other TBP. Birds have played a major role during tick evolution, which explains why they are by far the most important hosts supporting the ecological networks of ticks and several TBP.

Deer, predators, and the emergence of Lyme disease
Taal Levi, A. Marm Kilpatrick, Marc Mangel, and Christopher C. Wilmers
Proceedings of the National Academy of Sciences of the
United States of America, online before print, June 18, 2012.
Across four states we find poor spatial correlation between deer abundance and Lyme disease incidence, but coyote abundance and fox rarity effectively predict the spatial distribution of Lyme disease in New York. These results suggest that changes in predator communities may have cascading impacts that facilitate the emergence of zoonotic diseases, the vast majority of which rely on hosts that occupy low trophic levels.

Rickettsia rickettsii Transmission by a Lone Star Tick, North Carolina
Edward B. Breitschwerdt, Barbara C. Hegarty, Ricardo G.
Maggi, Paul M. Lantos, Denise M. Aslett, and Julie M. Bradley
Emerging Infectious Diseases, Volume 17, Number 5 – May 2011.
Only indirect or circumstantial evidence has been published to support transmission of Rickettsia rickettsii by Amblyomma americanum (lone star) ticks in North America. This study provides molecular evidence that A. americanum ticks can function, although most likely infrequently, as vectors of Rocky Mountain spotted fever for humans.

Bartonella henselae and B. koehlerae DNA in birds
Mascarelli PE, McQuillan M, Harms CA, Harms RV, Breitschwerdt EB.
Emerging Infectious Diseases March 2014
There is growing evidence that migratory birds serve as reservoirs and/or mechanical vectors for pathogens such as tick-borne encephalitis virus and Rickettsia spp.. Birds have been implicated as reservoirs for several Borrelia spp. and for possible dispersion of other tick-borne pathogens (e.g., Anaplasma and Bartonella spp.)

Assessing the Contribution of Songbirds to the Movement of Ticks and Borrelia burgdorferi in the Midwestern United States During Fall Migration
Sarah C. Schneider, Christine M. Parker, James R. Miller, L. Page Fredericks, Brian F. Allan
EcoHealth, online before print, October 9, 2014.
Infestation of birds by Ixodes spp. differed significantly by region, while B. burgdorferi infection did not. These data suggest that migratory birds may play a larger role in the dispersal of B. burgdorferi than previously realized.

Multiflora rose invasion amplifies prevalence of Lyme disease pathogen, but not necessarily Lyme disease risk.
Adalsteinsson SA, Shriver WG, Hojgaard A, Bowman JL, Brisson D, D’Amico V, Buler JJ.
Parasites & Vectors, online first 2018 Jan 23;11(1):54.
Understory structure provided by non-native, invasive shrubs appears to aggregate ticks and reservoir hosts, increasing opportunities for pathogen transmission. However, when we consider pathogen prevalence among nymphs in context with relative abundance of questing nymphs, invasive plants do not necessarily increase disease risk. Although pathogen prevalence is greater among ticks in invaded forests, the probability of encountering an infected tick remains greater in uninvaded forests characterized by thick litter layers, sparse understories, and relatively greater questing tick abundance in urban landscapes.

Environmental Factors Affecting Survival of Immature Ixodes scapularis and Implications for Geographical Distribution of Lyme Disease: The Climate/Behavior Hypothesis
Howard S. Ginsberg, Marisa Albert, Lixis Acevedo, Megan C. Dyer, Isis M. Arsnoe, Jean I. Tsao, Thomas N. Mather, Roger A. LeBrun
PLOS One, published online, January 11, 2017
Recent reports suggest that host-seeking nymphs in southern populations of Ixodes scapularis remain below the leaf litter surface, while northern nymphs seek hosts on leaves and twigs above the litter surface. This behavioral difference potentially results in decreased tick contact with humans in the south, and fewer cases of Lyme disease. We studied whether north-south differences in tick survival patterns might contribute to this phenomenon.

Population and Evolutionary Genomics of Amblyomma americanum, an Expanding Arthropod Disease Vector
Javier D. Monzón, Elizabeth G. Atkinson, Brenna M. Henn, and Jorge L. Benach
Genome Biology and Evolution. 2016; 8:1351-1360. Online first, April 13, 2016.
The lone star tick, Amblyomma americanum, is an important disease vector and the most frequent tick found attached to humans in the eastern United States. The lone star tick has recently experienced a rapid range expansion into the Northeast and Midwest, but despite this emerging infectious threat to wildlife, livestock, and human health, little is known about the genetic causes and consequences of the geographic expansion.

Suppression of Host-Seeking Ixodes Scapularis and Amblyomma Americanum (Acari: Ixodidae) Nymphs After Dual Applications of Plant-Derived Acaricides in New Jersey
Jordan RA, Dolan MC, Piesman J, Schulze TL.
Journal of Economic Entomology, Volume 104, Number 2, April 2011, pp. 659-664.
Of the three compounds tested, 2% nootkatone provided the most consistent results, with 96.5 and 91.9% control of I. scapularis and A. americanum through 42 and 35 d, respectively. The ability of plant-derived natural products to quickly suppress and maintain significant control of populations of these medically important ticks may represent a future alternative to the use of conventional synthetic acaricides. In addition, the demonstrated efficacy of properly-timed backpack sprayer application may enable homeowner access to these minimal-risk acaricides.

Amblyomma americanum (Acari: Ixodidae) Ticks Are Not Vectors of the Lyme Disease Agent, Borrelia burgdorferi (Spirocheatales: Spirochaetaceae): A Review of the Evidence
Ellen Y Stromdahl, Robyn M Nadolny, Graham J Hickling, Sarah A Hamer, Nicholas H Ogden, Cory Casal, Garrett A Heck, Jennifer A Gibbons, Taylor F Cremeans. Mark A Pilgard
Journal of Medical Entomology, online first 31 January 2018.
In total, 54 surveys from more than 35 research groups, involving more than 52,000 ticks, have revealed a low prevalence of B. lonestari, and scarce B. burgdorferi, in A. americanum. In Lyme disease-endemic areas, A. americanum commonly feeds on B. burgdorferi-infected hosts; the extremely low prevalence of B. burgdorferi in this tick results from a saliva barrier to acquiring infection from infected hosts. At least nine transmission experiments involving B. burgdorferi in A. americanum have failed to demonstrate vector competency. Advancements in molecular analysis strongly suggest that initial reports of B. burgdorferi in A. americanum across many states were misidentified B. lonestari, or DNA contamination, yet the early reports continue to be cited without regard to the later clarifying studies. In this article, the surveillance and vector competency studies of B. burgdorferi in A. americanum are reviewed, and we conclude that A. americanum is not a vector of B. burgdorferi.

Repellence of essential oils and selected compounds against ticks – A systematic review
Benelli G, Pavela R.
Acta Tropica, online first, 2017 Dec 26.
The use of natural products as active ingredients in eco-friendly repellent formulations is currently a prominent research area, due to the wide diversity and high effectiveness of a number of plant-borne compounds, with special reference to essential oils (EOs) extracted from medicinal and aromatic species. Here, we reviewed current knowledge available on EOs tested as repellents against tick species of veterinary importance. Furthermore, we analysed the effectiveness of pure compounds isolated from EOs as tick repellents and their potential implications for practical use in the “real world”. A quantitative analysis of literature available is this research field was provided, along with its impact (i.e., in terms of citations over time) on the scientific community of researchers in tick control science and natural product chemistry.

Repelling Bugs With The Essence Of Grapefruit
by Richard Knox, National Public Radio, Washington, DC
April 18, 2011
That’s why the CDC is pushing hard to develop a completely natural insect repellent made from a chemical called nootkatone, which is found in Alaska yellow cedar trees and citrus fruit.

Pilot Study Assessing the Effectiveness of Long-Lasting Permethrin-Impregnated Clothing for the Prevention of Tick Bites
Meagan F. Vaughn, Steven R. Meshnick. Vector-Borne and
Zoonotic Diseases, online ahead of print, March 11, 2011.
Results: Subjects wearing Insect Shield-treated clothing had a 93% reduction (p<0.0001) in the total incidence of tick bites compared to subjects using standard tick bite prevention measures. Conclusion: This study provides preliminary evidence that long-lasting permethrin-impregnated clothing may be highly effective against tick bites.

Tick bite protection with permethrin-treated summer-weight clothing
Miller NJ, Rainone EE, Dyer MC, Gonzalez ML, Mather TN
Journal of Medical Entomology, 2011 Mar; 48(2):327-33.
Subjects wearing outfits treated with permethrin received 3.36 times fewer tick bites than subjects wearing untreated outfits. No statistically significant differences in number of tick bites were detected between commercial permethrin treatment (19.33%) and the do-at-home permethrin application method (24.67%). The success of permethrin-treated clothing in reducing tick bites varied depending on the specific article of clothing. Subjects wearing permethrin-treated sneakers and socks were 73.6 times less likely to have a tick bite than subjects wearing untreated footware. Subjects wearing permethrin-treated shorts and T-shirts were 4.74 and 2.17 times, respectively, less likely to receive a tick bite in areas related to those specific garments than subjects wearing untreated shorts and T-shirts. Ticks attached to subjects were classified as alive or dead before removal. On subjects wearing untreated outfits, 97.6% of attached nymphs were alive, whereas significantly fewer (22.6%) attached nymphs were alive onsubjects wearing repellent-treated outfits. Results of this study demonstrate the potential of permethrin-treated summer clothing for significantly reducing tick bites and tick-borne pathogen transmission.

The heat is on: Killing blacklegged ticks in residential washers and dryers to prevent tickborne diseases
Nelson CA, Hayes CM, Markowitz MA, Flynn JJ, Graham AC, Delorey MJ, Mead PS, Dolan MC
Ticks and Tick-borne Diseases, online first, 2016 Apr 28.
Reducing exposure to ticks can help prevent Lyme disease and other tickborne diseases. Although it is currently recommended to dry clothes on high heat for one hour to kill ticks on clothing after spending time outdoors, this recommendation is based on a single published study of tick survival under various washing conditions and a predetermined one-hour drying time.We conducted a series of tests to investigate the effects of temperature, humidity, and drying time on killing nymphal and adult blacklegged ticks (Ixodes scapularis). Muslin bags containing 5 ticks each were washed then dried or dried only with six cotton towels during each drying cycle. All nymphal and adult ticks were killed when exposed to wash cycles when the water temperature reached =54 °C (=130 °F); however, 50% of ticks survived hot water washes when the water temperature was <54 °C. The majority (94%) of ticks survived warm washes [temperature range, 27–46 °C (80–115 °F)] and all ticks survived cold washes [15–27 °C (59–80 °F)].When subsequently dried on high heat setting [54–85 °C (129–185 °F)], it took 50 min to kill all ticks (95% confidence limit, 55 min). Most significantly, we found that all adult and nymphal ticks died when placed directly in the dryer with dry towels and dried for 4 min on high heat (95% confidence limit, 6 min). We have identified effective, easily implemented methods to rid clothing of ticks after spending time outdoors.Placing clothing directly in a dryer and drying for a minimum of 6 min on high heat will effectively kill ticks on clothing. If clothing is soiled and requires washing first, our results indicate clothing should be washed with water temperature =54 °C (=130 °F) to kill ticks. When practiced with other tick-bite prevention methods, these techniques could further reduce the risk of acquiring tickborne diseases.

Tick Humoral Responses: Marching to the Beat of a Different Drummer
Oliva Chávez AS, Shaw DK, Munderloh UG, Pedra JH.
Frontiers in Microbiology, 2017 Feb 14;8:223. eCollection 2017.
Ticks transmit a variety of human pathogens, including Borrelia burgdorferi, the etiological agent of Lyme disease. Multiple pathogens that are transmitted simultaneously, termed “coinfections,” are of increasing importance and can affect disease outcome in a host. Arthropod immunity is central to pathogen acquisition and transmission by the tick.

Vector competence of the blacklegged tick, Ixodes scapularis, for the recently recognized Lyme borreliosis spirochete Borrelia mayonii
Marc C. Dolan, Andrias Hojgaard, J. Charles Hoxmeier, Adam J. Replogle, Laurel B. Respicio-Kingry, Christopher Sexton, Martin A. Williams, Bobbi S. Pritt, Martin E. Schriefer, Lars Eisen
Ticks and Tick-borne Diseases, online first, February 12, 2016.
A novel species within the Borrelia burgdorferi sensu lato complex, provisionally named Borrelia mayonii, was recently found to be associated with Lyme borreliosis in the Upper Midwest of the United States.Our results demonstrate that I. scapularis is capable of serving as a vector of B. mayonii. This finding, together with data showing that field-collected I. scapularis are infected with B. mayonii, indicate that I. scapularis likely is a primary vector to humans of this recently recognized Lyme borreliosis spirochete.

Characterizing the relationship between tick bites and Lyme disease in active component U.S. Armed Forces in the eastern United States
Rossi C, Stromdahl EY, Rohrbeck P, Olsen C, DeFraites RF.
Medical Surveillance Monthly Report. 2015 Mar;22(3):2-10.
In the population of service members in the study sample, mean annual LD incidence was 52.2 per 100,000 person-years (95% CI±; 7.6 per 100,000) between 1 January 2006 and 31 December 2012. A 10% increase in the rate of ticks submitted to the HTTKP corresponded to an increase in LD incidence of 5.7% (p<0.01). Where Borrelia burgdorferi infection of Ixodes scapularis ticks was high (20% or greater tick infection prevalence), tick removal rates explained 53.7% of the annual variation in LD incidence (p=0.01)

A Tick Vector Transmission Model of Monocytotropic Ehrlichiosis
Saito TB, Walker DH.
The Journal of Infectious Diseases, online before print, 2015 Mar 3.
For the first time we were able to develop a tick transmission model with an Ehrlichia that is pathogenic for humans.

Occurrence of soil- and tick-borne fungi and related virulence tests for pathogenicity to Ixodes scapularis (Acari: Ixodidae).
Greengarten PJ, Tuininga AR, Morath SU, Falco RC, Norelus H, Daniels TJ.
Journal of Medical Entomology, 2011 Mar; 48(2):337-44.
Currently, only a few entomopathogenic fungal species are considered virulent to ticks. We hypothesized that these species may not represent the most abundant local taxa that would be pathogenic to ticks in situ.In laboratory bioassays, 15 fungal taxa were found to be significantly virulent, although none of these were previously considered common pathogens of I. scapularis. Two species, Hypocrea lixii Patouillard 1891 and Penicillium soppii K. M. Zalessky 1927, were tested in field trials by spraying suspensions on forested plots. Mean tick mortality was 71% after treatment with H. lixii, 58% after treatment with P. soppii, and 32% in the control plots.

The Lyme Disease Pathogen Has No Effect on the Survival of Its Rodent Reservoir Host
Voordouw MJ, Lachish S, Dolan MC.
PLoS One. 2015 Feb 17;10(2):e0118265.
Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus.

Ecological factors influencing small mammal infection by Anaplasma phagocytophilum and Borrelia burgdorferi s.l. in agricultural and forest landscapes
Perez G, Bastian S, Chastagner A, Agoulon A, Plantard O, Vourc’h G, Butet A.
Environmental Microbiology, online first 2017 Aug 11.
Small mammals are key components of numerous tick-borne disease systems, as hosts for immature ticks and pathogen reservoirs. To study the factors influencing tick-borne infection in small mammals, we trapped small mammals and collected questing ticks in spring and autumn in 2012 and 2013 at 24 sites in a 10×15 km rural landscapes (Brittany, France).Tissue samples were screened by real-time PCR for Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato. Of the two dominant small mammal species captured, bank voles (Myodes glareolus) had higher prevalence than wood mice (Apodemus sylvaticus) for both infections, presumably because of specific differences in immunological defenses. Prevalence of infections was higher in 2013 than in 2012, likely because small mammals were fivefold less abundant in 2013, favoring tick aggregation.Bacterial prevalence, which was higher in autumn, was not associated to questing Ixodes ricinus nymph abundance which was 6 times higher in spring, but rather to the structure of the small mammal community. These findings suggest the involvement of endophilic tick species, I. trianguliceps and/or I. acuminatus, in bacterial transmission.

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Lyme borreliosis
Steere AC, Strle F, Wormser GP, Hu LT, Branda JA, Hovius JW, Li X, Mead PS.
Nature Reviews Disease Primers. 2016 Dec 15;2:16090
Lyme borreliosis is a tick-borne disease that predominantly occurs in temperate regions of the northern hemisphere and is primarily caused by the bacterium Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia. Infection usually begins with an expanding skin lesion, known as erythema migrans (referred to as stage 1), which, if untreated, can be followed by early disseminated infection, particularly neurological abnormalities (stage 2), and by late infection, especially arthritis in North America or acrodermatitis chronica atrophicans in Europe (stage 3).
However, the disease can present with any of these manifestations.

Chronic Lyme Disease: A Working Case Definition
Stricker RB and Fesler MC
International Lyme & Associated Diseases Society, Bethesda, MD; Union Square Medical Associates, San Francisco, CA, USA
Although Lyme disease is the most common tickborne illness in the USA and Eurasia, the pathophysiology and clinical course of chronic Lyme disease (CLD) have not been formally defined. The purpose of this paper is to present a working case definition of CLD based on analysis of more than 700 peerreviewed publications. According to this definition, CLD is a multisystem illness with diverse musculoskeletal, neuropsychiatric and/or cardiovascular manifestations that result from ongoing infection with pathogenic members of the Borrelia spirochete complex often associated with other tickborne disease (TBD) pathogens. To qualify for the diagnosis of CLD, patients must have Lymecompatible symptoms and signs that are either consistently or variably present for six or more months. Two subcategories of CLD include untreated chronic Lyme disease (CLD-U) and chronic Lyme disease following a limited course of antibiotic treatment (CLD-T). The symptom patterns and optimal therapy of CLD require further study.

Diagnostic challenges of early Lyme disease: Lessons from a community case series
John Aucott, Candis Morrison, Beatriz Munoz, Peter C Rowe, Alison Schwarzwalder and Sheila K West
BMC Infectious Diseases20099:79 Published: 01 June 2009©
The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.

“Proof That Chronic Lyme Disease Exists,”
Interdisciplinary Perspectives on Infectious Diseases, vol. 2010 Article ID 876450, 4 pages, 2010. doi:10.1155/2010/876450
Daniel J. Cameron
The evidence continues to mount that Chronic Lyme Disease (CLD) exists and must be addressed by the medical community if solutions are to be found. Four National Institutes of Health (NIH) trials validated the existence and severity of CLD. Despite the evidence, there are physicians who continue to deny the existence and severity of CLD, which can hinder efforts to find a solution. Recognizing CLD could facilitate efforts to avoid diagnostic delays of two years and durations of illness of 4.7 to 9 years described in the NIH trials.The risk to society of emerging antibiotic-resistant organisms should be weighed against the societal risks associated with failing to treat an emerging population saddled with CLD. The mixed long-term outcome in children could also be examined. Once we accept the evidence that CLD exists, the medical community should be able to find solutions. Medical professionals should be encouraged to examine whether: (1) innovative treatments for early LD might prevent CLD, (2) early diagnosis of CLD might result in better treatment outcomes, and (3) more effective treatment regimens can be developed for CLD patients who have had prolonged illness and an associated poor quality of life.

Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey.
Johnson L, Wilcox S, Mankoff J, Stricker RB. (2014) PeerJ 2:e322.
Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs.

The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome
Rebman AW, Bechtold KT, Yang T, Mihm EA, Soloski MJ, Novak CB, Aucott JN.
Frontiers in Medicine (Lausanne). 2017 Dec 14;4:224.
Although physical exam and clinical laboratory tests showed few objective abnormalities, standardized symptom questionnaires revealed that patients with PTLDS are highly and clinically significantly symptomatic, with poor health-related quality of life. PTLDS patients exhibited levels of fatigue, musculoskeletal pain, sleep disturbance, and depression which were both clinically relevant and statistically significantly higher than controls. Our study shows that PTLDS can be successfully identified using a systematic approach to diagnosis and symptom measurement. As the prevalence of PTLDS continues to rise, there will be an increased need for physician education to more effectively identify and manage PTLDS as part of integrated patient care.

Lyme Disease (Borrelia burgdorferi) 2017 Case Definition
Centers for Disease Control and Prevention, Council of State and Territorial Epidemiologists (CSTE) Position Statement(s)
Source: Clinical Description
A systemic, tick-borne disease with protean manifestations, including dermatologic, rheumatologic, neurologic, and cardiac abnormalities. The most common clinical marker for the disease is erythema migrans (EM), the initial skin lesion that occurs in 60%-80% of patients.

Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard
L.A. Crowder, V.A. Yedlin, E.R. Weinstein, K.B. Kortte, J.N. Aucott
Public Health, online before print Septtember 9, 2014.
A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed.

New Insights Into Stages of Lyme Disease Symptoms From a Novel Hospital-Based Registry
Jessika Lobraico, Amber Butler, Joann Petrini, Ramin Ahmadi
Journal of Primary Care and Community Health, October 2014, vol. 5, no. 4, 284-287.
The Lyme Disease Registry has enrolled 256 participants, 24% are acute cases, 45% are persistently symptomatic cases, and 31% are recovered cases. The symptoms experienced by the group of patients with persistent symptoms had unexpectedly strong overlap with those experienced by acutely infected patients.The difference between symptoms in the acutely infected patients and those experiencing persistent symptoms is not as large as initially thought.

Accuracy of Clinician Suspicion of Lyme Disease in the Emergency Department
Nigrovic LE, Bennett JE, Balamuth F, Levas MN, Chenard RL, Maulden AB, Garro AC; for Pedi Lyme Net.
Pediatrics, online first 2017 Nov 24. pii: e20171975.
We enrolled 1021 children with a median age of 9 years (interquartile range, 5–13 years). Of these, 238 (23%) had Lyme disease. Clinician suspicion had a minimal ability to discriminate between children with and without Lyme disease: area under the curve, 0.75 (95% confidence interval, 0.71–0.79). Of the 554 children who the treating clinicians thought were unlikely to have Lyme disease (score 1–3), 65 (12%) had Lyme disease, and of the 127 children who the treating clinicians thought were very likely to have Lyme disease (score 8–10), 39 (31%) did not have Lyme disease.

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research.
Waddell LA, Greig J, Mascarenhas M, Harding S, Lindsay R, Ogden N.
PLoS One. 2016 Dec 21;11(12):e0168613.
There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD.

To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis
Horowitz R, Lacout A, Marcy PY, Perronne C.
Clinical Microbiology and Infection, online first, 2017 Oct 10.
Formal serology in patients presenting with presumptive Lyme disease symptoms is not sufficient to definitively rule out Lyme disease. A broader laboratory panel approach such as including a polymerase chain reaction (PCR) or ELISPOT test can be more sensitive and specific. The search for an antibody intrathecal production may not be essential to the diagnosis in some neuroboreliosis cases (peripheral neuropathy).

Erythema Migrans: A Spectrum of Histopathologic Changes
Wilson, Thomas C.; Legler, Allison; Madison, Kathi C.; Fairley, Janet A.; Swick, Brian L.
American Journal of Dermatopathology, online before print, 20 June 2012
Herein, we describe 4 cases of erythema migrans, all biopsied at the periphery of the lesion and confirmed by serologic studies, demonstrating a variety of unconventional histopathologic patterns.

Atypical erythema migrans in Patients with PCR-positive Lyme disease
Schutzer SE, Berger BW, Krueger JG, Eshoo MW, Ecker DJ, Aucott JN.
Emerging Infectious Diseases, Volume 19, No. 5, May 2013.
The best diagnostic sign in patients with early Lyme disease is a skin lesion, erythema migrans (EM). However this sign may not occur or be recognized in 30% of cases. Furthermore, the EM rash may not display a classic bull’s-eye (ring-within-a-ring) appearance, a fact that may be underappreciated. Some studies noted uncharacteristic variants of EM in 25% – 30% of cases. One study reported the rash to be uniformly red in 60% of cases. Other atypical variants of EM are a blue-red appearance and, occasionally, a vesicular central region. We describe the occurrence of atypical EM in patients with microbiologically proven Borrelia burgdorferi infection.

Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme disease
Mazori, Daniel R; Orme, Charisse M; Mir, Adnan; Meehan, Shane A; & Neimann, Andrea L. (2015).
Dermatology Online Journal, 21(8). doj_28428.
Erythema migrans is the initial sign in the majority of patients infected with Borrelia, the genus of spirochetes that causes Lyme disease. Early identification and treatment decrease the risk of progression to later stages of disease. Although a “bull’s eye” appearance owing to lesional clearing is considered classic for erythema migrans, this feature is surprisingly often lacking among patients in the United States.

The Many Masks of Cutaneous Lyme Disease
Miraflor AP, Seidel GD, Perry AE, Castanedo-Tardan MP, Guill MA, Yan S.
Journal of Cutaneous Pathology, online first, 2015 Sep 8.
Early cutaneous Lyme disease, erythema migrans, may show different histopathologic patterns. The intent of this case series is to raise awareness of these findings to prevent misdiagnosis and keep this entity in the differential.

Early Lyme disease: a flu-like illness without erythema migrans.
Feder HM Jr, Gerber MA, Krause PJ, Ryan R, Shapiro ED.
The existence of a form of early Lyme disease characterized by a flu-like illness without erythema migrans is controversial. To confirm the existence and define the clinical characteristics of the flu-like illness without erythema migrans of localized Lyme disease, the authors studied patients from a Lyme disease endemic area of Connecticut who visited their primary care physicians with an undefined flu-like illness. Patients kept a diary of their symptoms. Acute and convalescent sera were obtained. The diagnosis of Lyme disease was based on the appearance of IgM or IgG antibodies to Borrelia burgdorferi as demonstrated by both enzyme-linked immunosorbent assay and immunoblot assay. Twenty-four untreated patients were studied. In five patients acute serologic evidence of Lyme disease developed. The flu-like illness in these five patients was characterized by fever and fatigue and resolved spontaneously in 5 to 21 days. Symptoms recurred in three of these five patients. The existence of a flu-like illness without erythema migrans of early Lyme disease has been clearly established. Prospective, controlled studies are needed to better define its incidence, characteristics, and prognosis so that appropriate diagnostic and therapeutic strategies can be developed.

Lyme Disease: Beyond Erythema Migrans
Allen HB, Vin H, Warner C, Joshi S.
Journal of Clinical & Experimental Dermatology Research, 7:2; Online first, February 22, 2016.
Background: With the recent discoveries of Borrelia burgdorferi and other spirochetes in the brains of Alzheimer’s patients and with a recent analysis showing the very same pathology in both syphilitic and Alzheimer’s dementia it seems both rational and urgent to consider all aspects of Lyme disease in a new light, especially the concept of “overdiagnosis”. The very presence of the organisms in the brains following supposedly effective treatment for Lyme disease is contradictory and should be the starting point for diagnosis and treatment. Also for consideration is the reliance on erythema migrans and serologies in the diagnosis of Lyme disease inasmuch as they occur in less than half the patients.

Gender Disparity between Cutaneous and Non-Cutaneous Manifestations of Lyme Borreliosis.
Strle F, Wormser GP, Mead P, Dhaduvai K, Longo MV,Adenikinju O, Soman S, Tefera Y, Maraspin V, Lotric-Furlan S, Ogrinc K, Cimperman J, Ruzic-Sabljic E, Stupica D.
PLoS One. 2013 May 30;8(5):e64110.
In conclusion, patients with cutaneous manifestations of Lyme borreliosis were predominantly female, whereas those with non-cutaneous manifestations were predominantly male. This provocative finding is unexplained but may have direct relevance to the pathogenesis of Lyme borreliosis.

Differential Diagnosis and the Suspension of Judgment
Ashley Graham Kennedy
Journal of Medicine and Philosophy, online before print 29 August 2013.
In this paper I argue that ethics and evidence are intricately intertwined within the clinical practice of differential diagnosis. Too often, when a disease is difficult to diagnose, a physician will dismiss it as being “not real” or “all in the patient’s head.” This is both an ethical and an evidential problem. In the paper my aim is two-fold. First, via the examination of two case studies (late-stage Lyme disease and Addison’s disease), I try to elucidate why this kind of dismissal takes place. Then, I propose a potential solution to the problem. I argue that instead of dismissing a patient’s illness as “not real,” physicians ought to exercise a compassionate suspension of judgment when a diagnosis cannot be immediately made. I argue that suspending judgment has methodological, epistemic, and ethical virtues and therefore should always be preferred to patient dismissal in the clinical setting.

Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease
Citera M, Freeman PR, Horowitz RI
International Journal of General Medicine, online first 4 September 2017.
Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses.

Borrelia burgdorferi tissue morphologies and imaging methodologies.
Macdonald AB.
European Journal of Clinical Microbiology and Infectious
Diseases, online before print, 2013 Mar 12
This manuscript offers an image presentation of diverse forms of Borrelia burgdorferi spirochetes which are not spiral or corkscrew shaped. Explanations are offered to justify the legitimacy of tissue forms of Borrelia which may confuse the inexperienced microscopic examiner and which may lead to the misdiagnosis of non-spiral forms as artifacts.

A Borrelia burgdorferi surface-exposed transmembrane protein lacking detectable immune responses supports pathogen persistence and constitutes a vaccine target.
Kung F, Kaur S, Smith AA, Yang X, Wilder CN, Sharma K, Buyuktanir O, Pal U.
The Journal of Infectious Diseases, online first 2016 Jan 7.
Borrelia burgdorferi harbors a limited set of transmembrane surface proteins, most of which constitute key targets of humoral immune responses. Taken together, these studies highlight the essential role of an apparently immune-invisible borrelial transmembrane protein in facilitating infection and its usefulness as a target of protective host immunity blocking the transmission of B. burgdorferi.

Evidence of in vivo existence of Borrelia biofilm in borrelial lymphocytomas
E. Sapi, K. Balasubramanian, A. Poruri, J. S. Maghsoudlou, K. M. Socarras, A. V. Timmaraju, K. R. Filush, K. Gupta, S. Shaikh, P. A. S. Theophilus, D. F. Luecke, A. MacDonald, B. Zelger
European Journal of Microbiology and Immunology, online before print, February 9, 2016.
Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues.

A short-term Borrelia burgdorferi infection model identifies tissue tropisms and bloodstream survival conferred by adhesion proteins.
Ritchie JA, Coburn J.
Infection and Immunity, pii: IAI.00349-15. Online first, 2015 May 26.
We have developed an in vivo model of vascular interaction of B. burgdorferi in which the bacteria are injected intravenously and allowed to circulate for 1 hour. This model has shown that the fibronectin binding protein BB0347 has a tropism for joint tissue. We have also shown an importance of the integrin binding protein, P66, in binding to vasculature of the ear and heart.

Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients
Alison W. Rebman, Lauren A. Crowder, Allison Kirkpatrick, John N. Aucott
Clinical Rheumatology, March 2015, Volume 34, Issue 3, pp 585-589.
Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Among the baseline variables included in the analysis, disseminated lesions (p?<?0.0001), a longer duration of illness (p?<?0.0001), and a higher number of reported symptoms (p?=?0.004) were highly significantly associated with positive final serostatus, while male sex (p? =?0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease.

Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts
Karen E. Tracy, Nicole Baumgarth
Front Immunol. 2017; 8: 116. Published online 2017 Feb 20.
doi: 10.3389/fimmu.2017.00116
Although B. burgdorferi infection induces both innate and adaptive immune responses, they are ultimately ineffective in clearing the infection from reservoir hosts, leading to bacterial persistence.

CD4+ T cells promote antibody production but not sustained affinity maturation during Borrelia burgdorferi infection
Elsner RA, Hastey CJ, Baumgarth N.
Infection and Immunity, online before print, 2014 Oct 13. pii: IAI.02471-14.
The data further suggest that Bb-infection drives humoral response away from protective, high-affinity and long-lived antibody responses and towards rapid induction of strongly induced, short-lived antibodies, of limited efficacy.

Serodiagnosis of Borreliosis: Indirect Immunofluorescence Assay, Enzyme-Linked Immunosorbent Assay and Immunoblotting
Iwona Wojciechowska-Koszko, Iwona Maczynska, Zbigniew Szych and Stefania Giedrys-Kalemba
Archivum Immunologiae et Therapiae Experimentalis, published onlinebefore print, 22 January 2011.
The IIFA screening test used for diagnosing Lyme borreliosis produced the highest percentage of positive results, which were then confirmed by immunoblot, but not by ELISA. Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable.

A comparison of Lyme disease serologic test results from four laboratories in patients with persistent symptoms after antibiotic treatment
Brian A. Fallon, Martina Pavlicova, Samantha W. Coffino, and Carl Brenner
Clinical Infectious Diseases, online before print September 2, 2014
In general there was little difference among the labs in the percentage of positive test results on the ELISAs and IgG WBs, although the number of discordant results was often high. The IgM WB performed poorly in our patient population of individuals with later stage illness, a result consistent with previous studies. While there was surprisingly little difference among the labs in percentage of positive results on most assays using CDC criteria, interlaboratory variability was considerable and remains a problem in LD testing.

Biofilms busters to improve the detection of Borrelia using PCR
Lacout A, Dacher V, El Hajjam M, Marcy PY, Perronne C.
Medical Hypotheses. 2018 Mar; 112:4-6.
The serology tests commonly used for diagnosis of Lyme Disease show a wide sensitivity varying from 34% to 70,5%, leaving many infected patients with false negative tests.
Alternative techniques such as polymerase chain reaction (PCR) could be helpful but not conclusive enough. Using biofilm busters, such as stevia and serratiopeptidase, could lead to bacterial blood release, thus increasing the spirochete load, making PCR test more sensitive, thus improving the patient’s diagnosis and management.

Development of a sensitive PCR-dot blot assay to supplement serological tests for diagnosing Lyme disease
Shah, J.S., D’ Cruz, I., Ward, S. et al.
European Journal of Clinical Microbiology & Infectious Diseases, online first December 27, 2017.
Results of the assay on 107 and 402 clinical samples from patients with suspected Lyme disease from Houston, Texas or received at the IGeneX laboratory in Palo Alto, California, respectively, were analyzed together with WB findings. The LM-PCR assay was highly specific for B. burgdorferi. In the Texas samples, 23 (21.5%) patients antibody-negative in WB assays by current US Centers for Disease Control (CDC) recommended criteria were positive by LM-PCR performed on urine, serum or whole blood samples. With IGeneX samples, of the 402 LM-PCR positive blood samples, only 70 met the CDC criteria for positive WBs, while 236 met IGeneX criteria for positive WB.
Use of the LM-PCR assay and optimization of current CDC serological criteria can improve the diagnosis of Lyme disease.

Antigens of Borrella burgdorferi Recognized during Lyme Disease – Appearance of a New Immunoglobulin M Response and Expansion of the Immunoglobulin G Response Late in the Illness
Joseph E. Craft, Duncan K. Fischer, Grant T. Shimamoto, and Allen C. Steere Departments of Internal Medicine and Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510
Using immunoblots, we identified proteins of Borrelia burgdorferi bound by IgM and IgG antibodies during Lyme disease. In 12 patients with early disease alone, both the IgM and IgG responses were restricted primarily to a 41-kD antigen. This limited response disappeared within several months. In contrast, among six patients with prolonged illness, the IgM response to the 41-kD protein sometimes persisted for months to years, and late in the illness during arthritis, a new IgM response sometimes developed to a 34-kD component of the organism. The IgG response in these patients appeared in a characteristic sequential pattern over months to years to as many as 11 spirochetal antigens. The appearance of a new IgM response and the expansion of the IgG response late in the illness, and the lack of such responses in patients with early disease alone,suggest that B. burgdorferi remains alive throughout illness.

Improved Sensitivity of Lyme disease Western Blots Prepared with a Mixture of Borrelia Burgdorferi Strains 297 and B31
Shah JS, Du Cruz I, Narciso W, Lo W and Harris NS
Chronic Diseases – International, published online, December 10, 2014.
A total of 364 control and patient sera (including 88 from treated patients with confirmed Lyme disease) were tested. The sensitivity of the combined IgG and IgM commercial WB using CDC criteria was 77.1%. When the in-house IgG and IgM WB and CDC criteria were used, the combined sensitivity improved to 88.6%, while use of the in-house IgG and IgM WB and in-house interpretation criteria resulted in a combined sensitivity that increased to 97.1%. Using CDC criteria, the specificity of the in-house IgG and IgM WB was 100% and 97.1%, respectively; using in-house criteria; the specificity was 95.3% and 93.1% respectively. By removal of patients who reacted to band 31kDa but tested negative for antibodies to recombinant OspA antigen, in-house IgG and IgM WB specificity increased to >97%.

Local Borrelia burgdorferi sensu stricto and Borrelia afzelii strains in a single mixed antigen improves Western blot sensitivity
Sally Mavin, Roger Evans, Rachel M Milner, Jean MW Chatterton and Darrel O Ho-Yen
J Clin Pathol. Published Online First: 23 February 2009.
The mixed antigen and revised interpretation criteria has successfully been incorporated into the routine diagnostic testing service, increasing the sensitivity of the in-house IgG Western blot test for Scottish patients.

Interpretation criteria in Western blot diagnosis of Lyme borreliosis.
Mavin S, McDonagh S, Evans R, Milner RM, Chatterton JM, Ho-Yen DO.
British Journal of Biomedical Science 2011; 68(1); 5-10.
In total, 76 patients who were negative/equivocal became positive, which may have led to a change in their management. Conversely, 33 patients who were weak-positive became equivocal but their management may not have been affected.

More specific bands in the IgG western blot in sera from Scottish patients with suspected Lyme borreliosis.
Evans R, Mavin S, McDonagh S, Chatterton JM, Milner R, Ho-Yen DO.
Journal of Clinical Pathology, published online before print, June 30, 2010.
Results suggest that the 20, 28 and 48 kDa bands should be regarded as specific.

Improving the Yield of Blood Cultures in Early Lyme Disease.
Liveris D, Schwartz I, Bittker S, Cooper D, Iyer R, Cox ME, Wormser GP.
Journal of Clinical Microbiology, online before print on 13 April 2011.
Approximately 45% of untreated United States patients with early Lyme disease associated with erythema migrans have a positive blood culture based on microscopic detection of Borrelia burgdorferi in Barbour-Stoenner-Kelly medium after 2-12 weeks of incubation.

Commercial test kits for detection of Lyme borreliosis: a meta-analysis of test accuracy
Cook MJ, Puri BK
International Journal of General Medicine, Volume 2016:9, Pages 427-440 (Online first, 18 November 2016).
The clinical diagnosis of Lyme borreliosis can be supported by various test methodologies; test kits are available from many manufacturers. Literature searches were carried out to identify studies that reported characteristics of the test kits.
Of 50 searched studies, 18 were included where the tests were commercially available and samples were proven to be positive using serology testing, evidence of an erythema migrans rash, and/or culture. Additional requirements were a test specificity of =85% and publication in the last 20 years.The weighted mean sensitivity for all tests and for all samples was 59.5%. Individual study means varied from 30.6% to 86.2%. Sensitivity for each test technology varied from 62.4% for Western blot kits, and 62.3% for enzyme-linked immunosorbent assay tests, to 53.9% for synthetic C6 peptide ELISA tests and 53.7% when the two-tier methodology was used.

Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis
Marija Djukic, Carsten Schmidt-Samoa, Peter Lange, Annette Spreer, Katja Neubieser, Helmut Eiffert, Roland Nau and Holger Schmidt
Journal of Neurology, Volume 259, Number 4 (2012), 630-63.
Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts.

Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy
Eckman EA, Pacheco-Quinto J, Herdt AR, Halperin JJ.
Clinical Infectious Diseases, online first 2018 Jan 11.
Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection
Rebecca A. Elsner, Christine J. Hastey, Kimberly J. Olsen, Nicole Baumgarth
Published: July 2, 2015
Infections with the Lyme Disease agent, Borrelia burgdorferi, often fail to generate long-term protective immunity. We show here that this is because the immune system of the Borrelia-infected host generates only short-lived, structurally abnormal and non-functional germinal centers. These germinal centers fail to induce memory B cells and long-lived antibody-producing plasma cells, leaving the host susceptible to reinfection with Bb. This inability to induce long-term immunity was not due to the nature of Borrelia antigens, as even T-dependent antigens of Borrelia were unable to induce such responses. Moreover, influenza vaccine antigens, when applied during Borrelia-infection, failed to induce strong antibody responses and immune-protection from influenza challenge.

Delayed diagnosis of lyme neuroborreliosis presenting with abducens neuropathy without intrathecal synthesis of Borrelia antibodies.
Radzišauskiene D, Ambrozaitis A, Marciuškiene E.
Medicina (Kaunas). 2013;49(2):89-94.
The intrathecal synthesis of Borrelia burgdorferi antibodies is of diagnostic importance, but in rare cases, immunoglobulins against the Borrelia burgdorferi antigen may not be detected. We report a case of possible Lyme neuroborreliosis presenting with sixth cranial nerve neuropathy at the onset of the disease further developing into typical meningoradiculitis and multiple mononeuropathy. Surprisingly, Borrelia burgdorferi antibodies were not detected in the cerebrospinal fluid.

Lyme Disease May Be Sexually Transmitted, Study Suggests
Online PR News, 20-January-2014
As expected, all of the control subjects tested negative for Borrelia burgdorferi in semen samples or vaginal secretions. In contrast, all women with Lyme disease tested positive for Borrelia burgdorferi in vaginal secretions, while about half of the men with Lyme disease tested positive for the Lyme spirochete in semen samples. Furthermore, one of the heterosexual couples with Lyme disease showed identical strains of the Lyme spirochete in their genital secretions. “The presence of the Lyme spirochete in genital secretions and identical strains in married couples strongly suggests that sexual transmission of the disease occurs,” said Dr. Mayne.

Culture and identification of Borrelia spirochetes in human vaginal and seminal secretions
Marianne J. Middelveen, Jennie Burke, Eva Sapi, Cheryl Bandoski, Katherine R. Filush, Yean Wang, Agustin Franco, Arun Timmaraju, Hilary A. Schlinger, Peter J. Mayne, Raphael B. Stricker
The culture of viable Borrelia spirochetes in genital secretions suggests that Lyme disease could be transmitted by intimate contact from person to person.

Changes in antibody reactivity to Borrelia burgdorferi three months after a tick bite. A cohort of 1,886 persons.
Dessau RB, Fryland L, Wilhelmsson P, Ekerfelt C, Nyman D, Forsberg P, Lindgren PE
Clinical and Vaccine Immunology, pii: CVI.00026-15. Online first, 2015 May 20.
In conclusion, 5.4% of people with tick bites developed a rise in borrelia-specific antibodies above the 2.5% percentile in either ELISA assay, but only 40 (2.1%) developed clinical Lyme borreliosis.

Synovial fluid findings in children with knee monoarthritis in lyme disease endemic areas.
Deanehan JK, Nigrovic PA, Milewski MD, Tan Tanny SP, Kimia AA, Smith BG, Nigrovic LE.
Pediatric Emergency Care. 2014 Jan;30(1):16-9.
There were no significant differences in the synovial fluid WBC, absolute neutrophil count, and percent neutrophils for children with Lyme and septic arthritis. In Lyme endemic areas, synovial fluid results alone do not differentiate septic from Lyme arthritis. Therefore, other clinical or laboratory indicators are needed to direct the care of patients with knee monoarthritis.

Burden and viability of Borrelia burgdorferi in skin or joints, of patients with erythema migrans or lyme arthritis
Xin Li, Gail McHugh, Nitin Damle, Vijay K. Sikand, Lisa Glickstein and Allen C. Steere
Arthritis & Rheumatism, online before print May 17, 2011.
B. burgdorferi in EM lesions were active and viable, whereas those in SF were moribund or dead at any time point. Thus, detection of B. burgdorferi DNA in SF is not a reliable test of active joint infection in Lyme disease.

Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity.
Soloski MJ, Crowder LA, Lahey LJ, Wagner CA, Robinson WH, et al. (2014)
PLoS ONE 9(4): e93243.
Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

SPECT Brain Imaging in Chronic Lyme Disease
Donta, Sam T. MD, Noto, Richard B. MD, Vento, John A. MD
Clinical Nuclear Medicine, September 2012, Volume 37, Issue 9, e219-e222.
Of all patients, 75% demonstrated abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes. Patients considered to be seropositive and those considered seronegative had similar rates, types, and severity of perfusion defects. Abnormalities of MRI of the brain were seen in 14% of patients. Treatment with antibiotics, especially those with intracellular-penetrating activity, resulted in resolution or improvement of abnormalities in 70% of patients over a 1- to 2-year period.

Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy
Brian A. Fallon, MD; Richard B. Lipkin, BA; Kathy M. Corbera, MD; Shan Yu, PhD; Mitchell S. Nobler, MD; John G. Keilp, PhD; Eva Petkova, PhD; Sarah H. Lisanby, MD; James R. Moeller, PhD; Iordan Slavov, PhD; Ronald Van Heertum, MD; Brett D. Mensh, MD, PhD; Harold A. Sackeim, PhD
Archives of General Psychiatry, May 2009, Volume 66, No. 5, p.554-563.
There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease. To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR). Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (P < .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements.Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease.

Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome.
Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, Adkins JN, et al.
(2011) PLoS ONE 6(2): e17287.
Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01). CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and healthy normals had 2,630 proteins.

Lyme Disease Presents Differently in Men and Women
By Sharon Worcester, Family Practice News Digital Network, Rockville, Maryland
March 22, 2012
Women with Lyme disease display more clinical symptoms than do men with the disease and also are less likely to seroconvert following treatment, according to findings from a prospective cohort study involving 77 patients. Numerous symptoms were reported more often by the 37 women in the study than by the 40 men. For example, significantly more women than men reported joint pain, muscle pain, headache, back pain, heart palpitations, nausea, vomiting, anxiety, numbness and tingling, and changes in vision during at least one of six preplanned study visits with a physician.

Tickborne diseases other than Lyme in the United States
Eickhoff C, Blaylock J.
Cleveland Clinic Journal of Medicine. 2017 Jul;84(7):555-567.
Tickborne diseases are increasing in the United States, and the geographic range of tick vectors is expanding. Tickborne diseases are challenging to diagnose, as they present with vague symptoms such as fever, constitutional symptoms, and nonspecific laboratory abnormalities. A high degree of clinical suspicion is required to make a diagnosis, as patients often do not recall a tick bite. The availability of laboratory testing for tickborne diseases is limited, especially in the acute setting. Therefore, if a tickborne disease is suspected, empiric therapy should often be initiated before laboratory confirmation of the disease is available.

Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 2
Garth L. Nicolson and Jorg Haier, British Journal of Medical Practitioners, 2010;3(1):301.
Chronically ill patients with neurodegenerative and neurobehavioural and psychiatric diseases commonly have systemic and central nervous system bacterial and viral infections. In addition, other chronic illnesses where neurological manifestations are routinely found, such as fatiguing and autoimmune diseases, Lyme disease and Gulf War illnesses, also show systemic bacterial and viral infections that could be important in disease inception, progression or increasing the types/severities of signs and symptoms. Evidence of Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, human herpesvirus-1, -6 and -7 and other bacterial and viral infections revealed high infection rates in the above illnesses that were not found in controls. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of progressive chronic diseases.

Severe Symptomatic Babesiosis Co-infection with Lyme Disease
Zaiem F, Alkawam H, Lee S, Fabisevich M.
QJM. pii: hcv168. Online first, 2015 Sep 14.
When patients presented with malaria-like illness in the areas endemic for Babesia infection, physicians should keep Babesiosis high on their differential list. Co-infection with Borrelia should be considered in patients with atypical presentation or with a poor response to proper therapy.

Seroprevalence of Babesia microti in Individuals with Lyme Disease
Curcio Sabino R., Tria Laurel P., and Gucwa Azad L.
Vector-Borne and Zoonotic Diseases, Online Ahead of Print: October 24, 2016.
Babesiosis is an emerging tick-borne disease (TBD) caused by Babesia microti, an intracellular parasite of red blood cells. Overall, 26.9% of the serum samples tested were positive for IgM and IgG antibodies against B. microti, suggesting exposure to TBD. Individuals who tested positive for Lyme disease as determined by two-tiered serological testing and the presence of both IgM and IgG antibodies directed against B. burgdorferi, were significantly increased for antibodies directed against B. microti (28.6%; p?<?0.05), suggesting the possibility of coinfection with both TBDs.

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis
Mareedu N, Schotthoefer AM, Tompkins J, Hall MC, Fritsche TR, Frost HM.
The American Journal of Tropical Medicine and Hygiene, online first 2017 Jul 10.
Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis, which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection (P < 0.01), require hospitalization (P < 0.01), or receive prolonged courses of antimicrobials (P < 0.01). Nausea or vomiting (P < 0.01) and diarrhea (P < 0.01) along with hyperbilirubinemia (P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy.

Vector Competence of the Tick Ixodes ricinus for Transmission of Bartonella birtlesii.
PLoS Neglected Tropical Diseases. 2011;5(5):e1186. Epub 2011 May 31.
Reis C, Cote M, Le Rhun D, Lecuelle B, Levin ML, Vayssier-Taussat M, Bonnet SI.
Histochemical staining showed the presence of bacteria in salivary glands and muscle tissues of partially engorged adult ticks, which had molted from the infected nymphs. These results confirm the vector competence of I. ricinus for B. birtlesii and represent the first in vivo demonstration of a Bartonella sp. transmission by ticks. Consequently, bartonelloses should be now included in the differential diagnosis for patients exposed to tick bites.

Cat Scratch Neuroretinitis: The Role of Acute and Convalescent Titers for Diagnosis
Gulati, Archit; Yalamanchili, Sushma; Golnik, Karl C.; Lee, Andrew G. MD
Journal of Neuro-Ophthalmology, online before print, 21 September 2011.
Cat scratch neuroretinitis (CSN) is a clinical diagnosis supported by serological testing. We present 2 cases of CSN in which initial acute titers were negative or equivocal for Bartonella henselae while convalescent titers were shown to be positive. We report these cases to emphasize that a single acute negative titer is insufficient to exclude the diagnosis of CSN and that convalescent titers should be obtained in patients for whom there is a high clinical suspicion of the disease.

Status Epilepticus Due to Cat Scratch Disease: Recognition, Diagnosis, and Thoughts on Pathogenesis
Schuster AL, Honeycutt TC, Hamrick HJ.
Pediatric Emergency Care. 2016 Nov;32(11):789-791.
Despite the publication of a number of case reports since the 1950s, physician awareness of the unique relationship between cat scratch disease (CSD) and acute encephalopathy remains limited. This report alerts emergency medicine physicians to include CSD encephalopathy (CSDE) in the differential diagnosis when a previously healthy child presents with status epilepticus. Prompt recognition of this relationship impacts the selection of initial diagnostic studies and antibiotic choices and permits reliable insight into prognosis.

Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease-endemic region.
Maggi RG, Mozayeni BR, Pultorak EL, Hegarty BC, Bradley JM, Correa M, et al.
Emerging Infectious Disease, Volume 18, Number 5, May 2012.
Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions. Among 296 patients examined by a rheumatologist, prevalence of antibodies against Bartonella henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii (185 [62%]) and Bartonella spp. bacteremia (122 [41.1%]) was high. Conditions diagnosed before referral included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%). B. henselae bacteremia was significantly associated with prior referral to a neurologist, most often for blurred vision, subcortical neurologic deficits, or numbness in the extremities.

Clinical Findings and Diagnosis in Human Granulocytic Anaplasmosis: A Case Series From Massachusetts
Mayo Clinic Proceedings, Volume 87, Issue 3 , Pages 233-239, March 2012.
Ana A. Weil, Elinor L. Baron, Catherine M. Brown, and Mark S. Drapkin
Thirty-three cases were confirmed during the 2009 transmission season, and 14 of these patients (42%) required hospitalization. Thrombocytopenia and/or leukopenia were observed at the time of presentation in 25 of 30 patients (86%) in whom both white blood cell and platelet counts were determined, and 28 of 33 patients (85%) reported fever. Rash occurred in only 2 of the 33 patients (6%), and 25 (76%) reported one or more respiratory or gastrointestinal symptom.

Comparison of a Real-time PCR Method with Serology and Blood Smear Analysis for Diagnosis of Human Anaplasmosis: Importance of Infection Time Course for Optimal Test Utilization.
Schotthoefer AM, Meece JK, Ivacic LC, Bertz PD, Zhang K,
Weiler T, Uphoff TS, Fritsche TR.
Journal of Clinical Microbiology, online before print, 2013 May 1.
There was poor agreement between the real-time PCR assay and serologic test results: 19.8% (19/96) and 13.7% (29/212) of seropositive and -negative patients, respectively, were PCR positive. Seropositivity increased with days of illness, demonstrating that serologic detection methods are best utilized during presumed convalescence. Our results indicated that optimal performance and utilization of laboratory tests for diagnosis of anaplasmosis requires knowledge regarding symptom onset or days of illness.

Infection with hemotropic Mycoplasma sp. in people with and without extensive arthropod and animal contact.
Maggi RG, Compton SM, Trull CL, Mascarelli PE, Mozayeni BR, Breitschwerdt EB.
Journal of Clinical Microbiolog, online before print 2013 Jul 17.
PCR amplification targeting the 16S rRNA gene was used to test individuals with and without extensive arthropod and animal contact for the possibility of hemotropic mycoplasma infection. The prevalence of hemotropic mycoplasma infection (4.7%) was significantly greater in previously reported cohorts of veterinarians, veterinary technicians, spouses of veterinary professionals, and others with extensive arthropod exposure and/or frequent animal contact, as compared to a previously reported cohort of patients examined by a rheumatologist because of chronic joint pain or evidence of small vessel disease (0.7%). Historical exposure to animals and arthropod vectors that can harbor hemotropic mycoplasma spp. should be considered during epidemiological investigations and when evaluating individual patients.

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease
Uhde M, Ajamian M, Li X, Wormser GP, Marques A, Alaedini A.
Clinical Infectious Diseases, online first, 2016 September 1.
These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection.

Effects of Borrelia on host immune system: Possible consequences for diagnostics
Mualla McManus, Ann Cincotta
Advances in Integrative Medicine, online before print, January 12, 2015.
Diagnosis is difficult not only due to multi-systemic and nonspecific nature of symptoms but also due to the indirect diagnostics assuming immuno-competence in all three stages of Borreliosis. Indirect diagnostics are the most common method of testing for Borreliosis as they are cheap and convenient. However due to wide variation in antigenicity of genospecies, the sensitivity and specificity of diagnostics can be questioned. Evidence is accumulating which suggests that immune dysregulation induced by Borrelia (and other tick borne infections) can impact the indirect diagnostics, especially in Stage 3. The immune status of the borreliosis patient needs to be considered, especially in Stage 3 in conjunction with clinical symptoms in the diagnosis. Borrelia has the ability to manipulate both the innate and active immunity and alter the cytokines secreted hence alter the path of the immune response. Immune parameters such as IFN-gamma/IL-10, lymphocyte markers, complement C3a, C4a, and total immunoglobulin levels may help to discriminate between stages and monitor treatment outcomes. The level of immune dysfunction in Stage 3 may depend on the number of co-infections delivered by a tick bite, such as Babesia, and Rickettsia, the genospecies of Borrelia, other pathogens, the patients’ biome and immunogenetics.

Lyme borreliosis: a review of data on transmission time after tick attachment.
Cook MJ.
International Journal of General Medicine. 2014 Dec 19;8:1-8. eCollection 2015.
A literature review has determined that in animal models, transmission can occur in <16 hours, and the minimum attachment time for transmission of infection has never been established. Mechanisms for early transmission of spirochetes have been proposed based on their presence in different organs of the tick. Studies have found systemic infection and the presence of spirochetes in the tick salivary glands prior to feeding, which could result in cases of rapid transmission. Also, there is evidence that spirochete transmission times and virulence depend upon the tick and Borrelia species.

Do Tick Attachment Times Vary between Different Tick-Pathogen Systems?
Stephanie L. Richards, Ricky Langley, Charles S. Apperson and Elizabeth Watson
Environments 2017, 4(2), 37; Online first, May 9, 2017.
Improvements to risk assessments are needed to enhance our understanding of tick-borne disease epidemiology. We review tick vectors and duration of tick attachment required for pathogen transmission for the following pathogens/toxins and diseases: (1) Anaplasma phagocytophilum (anaplasmosis); (2) Babesia microti (babesiosis); (3) Borrelia burgdorferi (Lyme disease); (4) Southern tick-associated rash illness; (5) Borrelia hermsii (tick-borne relapsing fever); (6) Borrelia parkeri (tick-borne relapsing fever); (7) Borrelia turicatae (tick-borne relapsing fever); (8) Borrelia mayonii; (9) Borrelia miyamotoi; (10) Coxiella burnetii (Query fever); (11) Ehrlichia chaffeensis (ehrlichiosis); (12) Ehrlichia ewingii (ehrlichiosis); (13) Ehrlichia muris; (14) Francisella tularensis (tularemia); (15) Rickettsia 364D; (16) Rickettsia montanensis; (17) Rickettsia parkeri (American boutonneuse fever, American tick bite fever); (18) Rickettsia ricketsii (Rocky Mountain spotted fever); (19) Colorado tick fever virus (Colorado tick fever); (20) Heartland virus; (21) Powassan virus (Powassan disease); (22) tick paralysis neurotoxin; and (23) Galactose-a-1,3-galactose (Mammalian Meat Allergy-alpha-gal syndrome). Published studies for 12 of the 23 pathogens/diseases showed tick attachment times. Reported tick attachment times varied (<1 h to seven days) between pathogen/toxin type and tick vector. Not all studies were designed to detect the duration of attachment required for transmission. Knowledge of this important aspect of vector competence is lacking and impairs risk assessment for some tick-borne pathogens.

Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks
Lars Eisen
Ticks and Tick-borne Diseases, online first, January 31, 2018.
The blacklegged tick, Ixodes scapularis, is the primary vector to humans in the eastern United States of the deer tick virus lineage of Powassan virus (Powassan virus disease); the protozoan parasite Babesia microti (babesiosis); and multiple bacterial disease agents including Anaplasma phagocytophilum (anaplasmosis), Borrelia burgdorferi and Borrelia mayonii (Lyme disease), Borrelia miyamotoi (relapsing fever-like illness, named Borrelia miyamotoi disease), and Ehrlichia muris eauclairensis (a minor causative agent of ehrlichiosis). With the notable exception of Powassan virus, which can be transmitted within minutes after attachment by an infected tick, there is no doubt that the risk of transmission of other I. scapularis-borne pathogens, including Lyme disease spirochetes, increases with the length of time (number of days) infected ticks are allowed to remain attached. This review summarizes data from experimental transmission studies to reinforce the important disease-prevention message that regular (at least daily) tick checks and prompt tick removal has strong potential to reduce the risk of transmission of I. scapularis-borne bacterial and parasitic pathogens from infected attached ticks.

Transmission of Borrelia miyamotoi sensu lato relapsing fever group spirochetes in relation to duration of attachment by Ixodes scapularis nymphs
Nicole E.Breuner, Marc C.Dolan, Adam J.Replogle, Christopher Sexton, Andrias Hojgaard, Karen A.Boegler, Rebecca J.Clark, Lars Eisen
Ticks and Tick-borne Diseases, Volume 8, Issue 5, August 2017, Pages 677-681.
We conclude that (i) single I. scapularis nymphs effectively transmit B. miyamotoi relapsing fever group spirochetes while feeding,(ii) transmission can occur within the first 24 h of nymphal attachment, and (iii) the probability of transmission increases with the duration of nymphal attachment.

Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial
Schwameis M, Kündig T, Huber G, et al.
The Lancet Infectious Diseases, available online 20 December 2016.
Lyme borreliosis develops in 1–5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks.

Single dose prophylactic treatment of a tick bite only prevents a Lyme rash

Blog: All Things Lyme, by Daniel Cameron, MD, MPH, a nationally recognized leader for his expertise in the diagnosis and treatment of Lyme disease and other tick-borne illnesses. March 19, 2017

In a recent review entitled “Lyme Disease: Emergency Department Considerations,” the authors recommend using a one-time, single dose of doxycycline for the prophylactic treatment of a tick bite, despite the fact that there has been only one study exploring the effectiveness of such a limited dosage. The article also neglects to mention that there are doctors who take a different approach and advise against a one-time, single dose

Tick Bite Prophylaxis: Results From a 2012 Survey of Healthcare Providers

Perea, A. E., Hinckley, A. F. and Mead, P. S.
Zoonoses and Public Health, online before print, September 22, 2014.
In a recent national survey, over 30% of healthcare providers (HCPs) reported prescribing tick bite prophylaxis in the previous year.

Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis
Journal of Antimicrobial Chemotherapy 2010 65(6):1137-1144.
Warshafsky S, Lee DH, Francois LK, Nowakowski J, Nadelman RB, Wormser GP.
Published online before print on April 9, 2010.
Conclusions: The available evidence to date supports the use of antibiotic prophylaxis for the prevention of Lyme disease in endemic areas following an Ixodes tick bite. Pooled data from four placebo-controlled trials suggests that one case of Lyme disease is prevented for about every 50 patients who are treated with antibiotics.

Human Coinfection with Borrelia burgdorferi and Babesia microti in the United States
Knapp KL, Rice NA.
Journal of Parasitology Research, online first November 30, 2015.
Borrelia burgdorferi, the causative agent of Lyme disease, and Babesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern United States. These pathogens are transmitted via the bite of an infected tick vector, Ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously.

A prospective evaluation of chronic Babesia microti infection in seroreactive blood donors
Bloch, E. M., Levin, A. E., Williamson, P. C., Cyrus, S., Shaz, B. H., Kessler, D., Gorlin, J., Bruhn, R., Lee, T.-H., Montalvo, L., Kamel, H. and Busch, M. P.
Transfusion, online first May 17, 2016.
Thirty-seven (61.67%; 24 NY, seven MN, six NM) of 60 eligible RR donors enrolled in the study; 20 of 37 (54%) completed the 12-month follow-up visit of which 15 (75%) were still seroreactive. Nine PCR-positive donors were identified during index screening; five participated in the follow-up study, three were PCR positive at 6 months, and two remained positive at final follow-up (378 and 404 days).

Distribution and survival of Borrelia miyamotoi in human blood components
Thorp AM, Tonnetti L.
Transfusion, online first, 2015 Dec 21.
Borrelia miyamotoi, the agent of relapsing fever, is a tick-borne spirochete first isolated in Japan in 1994. Since then, the spirochete has been detected in ticks globally, generally in the same vectors as the Lyme disease agent. This study demonstrated that B. miyamotoi can survive standard storage conditions of most human blood components, suggesting the possibility of transmission by blood transfusion.

Gender Bias in Chronic Lyme Disease
Raphael B. Stricker and Lorraine Johnson.
Journal of Women’s Health.
Published in Volume: 18 Issue 10: October 26, 2009
Findings that among patients with confirmed early Lyme disease, just one-third of the women, compared to half of the men, had a positive result on the CDC-approved tests. This explanation is reinforced by the fact that men are overrepresented (by as much as 2-to-1) in studies of patients with late Lyme, a diagnosis that is even stricter than PTLDS, requiring not only a positive test result but an objective clinical sign like arthritis.

Implications of Gender in Chronic Lyme Disease
Journal of Women’s Health. June 2009, 18(6): 831-834.
Gary P. Wormser, Eugene D. Shapiro
Patients with chronic Lyme disease were significantly more likely to be female than were patients diagnosed with either Lyme disease (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.98 – 2.94, p<0.0001) or with post-Lyme disease syndrome (OR 2.32, 95% CI 1.62 – 3.34, p<0.0001).

Sex differences in the clinical and serologic presentation of early lyme disease: Results from a retrospective review
Schwarzwalder A, Schneider MF, Lydecker A, Aucott JN.
Gender Medicine, 2010 Aug;7(4):320-9.
Results: In a total of 125 patients, there were no significant differences in clinical presentation by sex. The initial self-misdiagnosis rates for men and women were 10% and 18%, respectively (P = NS). Among the 62 patients with a serologic test as part of their clinical evaluation, 50% of men had a positive, 2-tier result compared with 32% of women (P = NS). Among the 41 patients with a positive ELISA, median ELISA values (3.4 vs 2.0; P = 0.03) and median number of immunoglobulin G (IgG) bands (4 vs 2; P = 0.03) were significantly higher among men. In this small, retrospective sample, we found evidence for sex-based differences in the magnitude of ELISA and IgG serologic response to early Lyme disease. Such differences could have implications for appropriate diagnosis, treatment, and disease classification. Larger, prospective studies are needed to replicate the results found in this study and to examine their relationship to sex-based immunologic variability.

Tickborne Relapsing Fever in a Mother and Newborn Child
Morbidity and Mortality Weekly Report (MMWR) 61(10);174-176. March 16, 2012
Reported by: Elisabeth W. Lawaczeck, DVM, Colorado Dept of Public Health and Environment. Paul S. Mead, MD, Martin E. Schriefer, PhD, Div of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases; Meghan E. Brett, MD, Jeffrey T. McCollum, DVM, EIS officers, CDC.
Tickborne relapsing fever (TBRF) is a bacterial infection caused by certain species of Borrelia spirochetes and transmitted through the bite of Ornithodoros ticks. Clinical illness is characterized by relapsing fever, myalgias, and malaise. On May 10, 2011, CDC and the Colorado Department of Public Health and Environment were notified of two patients with TBRF: a young woman and her newborn child. This report summarizes the clinical course of these patients and emphasizes the importance of considering a diagnosis of TBRF among patients with compatible clinical symptoms and residence or travel in a TBRF-endemic area. Pregnant women and neonates are at increased risk for TBRF-associated complications and require prompt diagnosis and treatment for optimal clinical outcomes. Public health follow-up of reported TBRF cases should include a search for persons sharing an exposure with the patient and environmental investigation with remediation measures to prevent additional infections. Blood and serum samples from the mother and her newborn were tested by CDC’s Bacterial Diseases Branch, Fort Collins, Colorado. Presence of spirochetes was visually confirmed from the newborn’s blood smear prepared May 7; a whole blood sample collected the same day yielded evidence of relapsing fever Borrelia species by polymerase chain reaction. Sequencing of polymerase chain reaction targets revealed 100% match to Borrelia hermsii.

Tick secret revealed: Westchester researchers first to prove baby got babesiosis before birth
By Jane Lerner, The Journal News, White Plains, New York
July 6, 2012
Westchester County researchers have confirmed for the first time a case of a pregnant woman passing on babesiosis, an increasingly common tick-borne illness, to her unborn baby.

Disease Caused By Insect Bites Can Be Transmitted To Children At Birth, NC State Researcher Finds
North Carolina State University, Raleigh, North Carolina 919.515.6142
May 5, 2010
Cat scratch disease was thought to be a self-limiting, or “one-time” infection; however, Breitschwerdt’s previous work discovered cases of children and adults with chronic, blood-borne Bartonella infections – from strains of the bacteria that are most often transmitted to cats (B. henselae) and dogs (B. vinsonii subsp. berkhoffii) by fleas and other insects. In his most recent case study, Breitschwerdt’s research group tested blood and tissue samples taken over a period of years from a mother, father and son who had suffered chronic illnesses for over a decade. Autopsy samples from their daughter – the son’s twin who died shortly after birth – contained DNA evidence of B. henselae and B. vinsonii subsp. berkhoffi infection, which was also found in the other members of the family.

Bartonella henselae infection in a family experiencing neurological and neurocognitive abnormalities after woodlouse hunter spider bites.
Mascarelli PE, Maggi RG, Hopkins S, Mozayeni BR, L Trull C, Bradley JM, Hegarty BC, Breitschwerdt EB.
Parasites and Vectors, 6:98. Online before print, April 15,2013.
Antibody titers to B. vinsonii subsp. berkhoffii (Bvb) genotypes I-III, B. henselae (Bh) and B. koehlerae (Bk) were determined using an IFA test. Management of the medical problems reported by these patiens was provided by their respective physicians. In this investigation, immediately prior to the onset of symptoms two children in a family experienced puncture-like skin lesions after exposure to and presumptive bites from woodlouse hunter spiders. Shortly thereafter, the mother and both children developed hive-like lesions. Over the ensuing months, the youngest son was diagnosed with Guillain-Barre (GBS) syndrome followed by Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The older son developed intermittent disorientation and irritability, and the mother experienced fatigue, headaches, joint pain and memory loss. When tested approximately three years after the woodlouse hunter spider infestation, all three family members were Bartonella henselae seroreactive and B. henselae DNA was amplified and sequenced from blood, serum or Bartonella alpha-proteobacteria (BAPGM) enrichment blood cultures from the mother and oldest son.

Vasculitis, cerebral infarction and persistent Bartonella henselae infection in a child
Balakrishnan N, Ericson M, Maggi R, Breitschwerdt EB.
Parasites & Vectors. 2016 May 10; 9(1):254.
The genus Bartonella is comprised of a rapidly increasing number of pathogenic species that induce a seemingly diverse spectrum of neurological symptoms. During the 12 year period that followed the initial onset of neurological and gastrointestinal symptoms, an 11 year-old girl experienced a spectrum of neurological complaints including frequent headaches, visual and auditory hallucinations, anxiety, vision loss involving the lower left quadrant of both eyes, episodic bouts of generalized paralysis, facial palsy, chronic insomnia, seizures, dizziness, cognitive dysfunction, and memory loss.

Bartonella henselae bacteremia in a mother and son potentially associated with tick exposure.
Maggi RG, Ericson M, Mascarelli PE, Bradley JM, Breitschwerdt EB.
Parasit Vectors. 2013 Apr 15;6:101. doi: 10.1186/1756-3305-6-101.
The mother and son were exhibiting symptoms including fatigue, headaches, memory loss, disorientation, peripheral neuropathic pain, striae (son only), and loss of coordination, whereas the father and daughter were healthy. The mother was seroreactive to multiple Bartonella spp. antigens and bacteremia was confirmed by PCR amplification of B. henselae DNA from blood, and from a BAPGM blood agar plate subculture isolate. The son was not seroreactive to any Bartonella sp. antigen, but B. henselae DNA was amplified from several blood and serum samples, from BAPGM enrichment blood culture, and from a cutaneous striae biopsy. The father and daughter were seronegative to all Bartonella spp. antigens, and negative for Bartonella DNA amplification.

In the Crucible of Chronic Lyme Disease
Physician, Dr. Kenneth B. Liegner, takes on Centers for Disease Control and Prevention (CDC) & Infectious Diseases Society of America (IDSA) dogma in new scientific book
April 20, 2016
Poughkeepsie, New York – Despite scientific studies, the CDC and IDSA dismiss any existence of chronic Lyme disease. Kenneth B. Liegner, M.D. has compiled into a single volume a compelling argument that the disease does exist in his book, “In the Crucible of Chronic Lyme Disease.” This body of work includes scientific articles, speeches and presentations, correspondence with legislators and principals in the field, and photographs of persons important in the history of the disease. It illustrates a rational, ethical and scientifically based approach to care of persons suffering from this still incompletely understood illness. “We are in the midst of paradigm change,” Dr. Liegner said. “Improved methods of diagnosis, treatment and prevention are urgently needed.” Dr. Liegner has spent more than 25 years working with Lyme and tick-borne diseases and has personally cared for many patients suffering from chronic Lyme disease. He calls for a “Manhattan Project” for better diagnosis, treatment and prevention of Lyme and other tick-borne diseases, and advocates for physician autonomy and patient rights. “It took medical science roughly 500 years to gain a good understanding of syphilis,” Dr. Liegner said. “We are but 40 years in to Lyme disease, caused by a spirochete considerably more genetically complex than Treponema pallidum, the organism causing syphilis.”

Tick-Borne Disease Preventive Practices and Perceptions in an Endemic Area
Amber D. Butlera, Tannaz Sedghib, Joann R. Petrinia, Ramin Ahmadia
Ticks and Tick-borne Diseases, Available online 7 December 2015.
Lyme disease is the most commonly reported vector-borne illness in the United States. Since the institution of Nationally Notifiable surveillance efforts for Lyme disease in the United States in 1991, there has been a consistent increase in the number of reported cases. Thus, the need for targeted prevention strategies is underscored. Overall, participants’ knowledge of tick-borne diseases was poor; the average knowledge score was only 57% (SD 22.6%). The reported frequency of performing preventive behaviors was variable. The most commonly reported behavior was performing a tick check (68%); use of tick repellent was the least commonly reported behavior (38%). Those who were more knowledgeable about Lyme disease were more likely to perform tick checks but knowledge score was not significantly associated with any of the other three behaviors studied.

Ability of Three General-Use Pesticides To Suppress Nymphal Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae)
Jordan RA, Schulze TL, Eisen L, Dolan MC.
Journal of the American Mosquito Control Association. 2017 Mar;33(1):50-55.
We evaluated 3 over-the-counter pesticides for their ability to suppress host-seeking Ixodes scapularis and Amblyomma americanum nymphs. We applied liquid concentrate and granular formulations of Bayer Advanced Complete Insect Killer, Spectracide Triazicide Insect Killer, and Ortho Bug-B-Gon to forest plots using equipment available for purchase at retail home improvement outlets. Granular formulations provided less consistent results, including lower 1-day knockdown rates for both species, due to very dry conditions, which prevented adequate release of the active ingredient from the carrier materials. After it rained in the study area, 7 and 14 days after application, we observed =99% suppression of both species. At 28 days posttreatment, control ranged between 87.5% and 95.6% for I. scapularis and between 89.3% and 94.4% for A. americanum. We show that these over-the-counter acaricides effectively suppressed 2 medically important tick vectors for at least 4 wk, and they provide a cost-effective tick control option for homeowners. In general, liquid formulations provided more rapid and greater and more consistent suppression than granular formulations.

Pilot study assessing the effectiveness of factory-treated, long-lasting permethrin-impregnated clothing for the prevention of tick bites during occupational tick exposure in highly infested military training areas, Germany.
Faulde MK, Rutenfranz M, Keth A, Hepke J, Rogge M, Görner A.
Parasitology Research, online before print, 2014 Nov 22.
Neither the tick density means from 2009 to 2011 nor associated B. burgdorferi s.l. prevalences differed significantly among the military locations investigated. The documented tick bite reductions clearly demonstrate the powerful protective effectiveness of properly worn PTBDUs against tick bites. Nevertheless, all apparel worn over PTBDUs should also be impregnated with permethrin in order to prevent tick infestation and subsequent bites.

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Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.
Daniel J Cameron, Lorraine B. Johnson, and Elizabeth L Maloney. Informa Healthcare, September 2014, Vol. 12, No. 9 , Pages 1103-1135.
ILADS is the first organization to issue guidelines on Lyme disease that were developed in accordance with the IOM standards. The document provides a detailed review of the pertinent medical literature and contains the first set recommendations for Lyme disease based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. This rigorous review format is also used by many other well-respected medical organizations including the World Health Organization (WHO), the American College of Physicians, and the National Institute for Health and Clinical Excellence (NICE) in the UK.

Analysis of Overall Level of Evidence Behind Infectious Diseases Society of America Practice Guidelines
Dong Heun Lee, MD; Ole Vielemeyer, MD
Archives of Internal Medicine. 2011;171(1):18-22. January 10, 2011
We analyzed the strength of recommendation and overall quality of evidence behind 41 Infectious Diseases Society of America (IDSA) guidelines released between January 1994 and May 2010. Individual recommendations were classified based on their strength of recommendation (levels A through C) and quality of evidence (levels I through III). Guidelines not following this format were excluded from further analysis. Evolution of IDSA guidelines was assessed by comparing 5 recently updated guidelines with their earlier versions. In the 41 analyzed guidelines, 4218 individual recommendations were found and tabulated. Fourteen percent of the recommendations were classified as level I, 31% as level II, and 55% as level III evidence. Among class A recommendations (good evidence for support), 23% were level I (> or = 1 randomized controlled trial) and 37% were based on expert opinion only (level III). Updated guidelines expanded the absolute number of individual recommendations substantially. However, few were due to a sizable increase in level I evidence; most additional recommendations had level II and III evidence. More than half of the current recommendations of the IDSA are based on level III evidence only. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

The Management of Ixodes scapularis Bites in the Upper Midwest
Elizabeth L. Maloney, MD
Wisconsin Medical Journal, Volume 110, Issue 2 (April 2011), pp. 78-81.
This paper reviews the prevailing antibiotic prophylaxis recommendation for Lyme disease and the evidence supporting it. Given the additional risk of acquiring anaplasmosis from an I scapularis bite in the upper Midwest, this paper proposes an alternative regimen for antibiotic prophylaxis in this region.

Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time
Kathleen T. Bechtold, Alison W. Rebman, Lauren A. Crowder, Doug Johnson-Greene and John N. Aucott
Archives of Clinical Neuropsychology, online first, November 23, 2016.
Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up.

Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis.
Department of Medicine, Turku University Central Hospital, Finland.
Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK.
A total of 165 patients with disseminated Lyme borreliosis (diagnosed in 1990-94, all seropositive except one culture-positive patient) were followed after antibiotic treatment, and 32 of them were regarded as having a clinically defined treatment failure. Of the 165 patients, 136 were tested by polymerase chain reaction (PCR) during the follow-up. PCR was positive from the plasma of 14 patients 0-30 months after discontinuation of the treatment, and 12 of these patients had a clinical relapse. In addition, Borrelia burgdorferi was cultured from the blood of three patients during the follow-up. All three patients belonged to the group with relapse, and two of them were also PCR positive. This report focuses on the 13 patients with clinical relapse and culture or PCR positivity. Eight of the patients had culture or PCR-proven initial diagnosis, the diagnosis of the remaining five patients was based on positive serology only. All 13 patients were primarily treated for more than 3 months with intravenous and/or oral antibiotics (11 of them received intravenous ceftriaxone, nine for 2 weeks, one for 3 weeks and one for 7 weeks, followed by oral antibiotics). The treatment caused only temporary relief in the symptoms of the patients. All but one of them had negative PCR results immediately after the first treatment. The patients were retreated usually with intravenous ceftriaxone for 4-6 weeks. None of them was PCR positive after the retreatment. The response to retreatment was considered good in nine patients. We conclude that the treatment of Lyme borreliosis with appropriate antibiotics for even more than 3 months may not always eradicate the spirochete. By using PCR, it is possible to avoid unnecessary retreatment of patients with ‘post-Lyme syndrome’ and those with ‘serological scars’ remaining detectable for months or years after infection.

Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack
Peter Kraiczy
Frontiers in Immunology, online first September 26, 2016.
Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully survive in diverse host environments for a prolonged period of time.

Something to Grapple with: How Wily Lyme Disease Prowls the Body
The sneaky germ uses a mechanism like that of white blood cells to reach vulnerable tissues and hide from antibiotics
By Knvul Sheikh,, Armonk, New York, August 25, 2016
Lyme disease is an incredibly evasive adversary. No one is entirely sure how the bacterium that causes it spreads so widely throughout the body or why symptoms sometimes persist after the infection has been treated with antibiotics. Now researchers at the University of Toronto may finally have an explanation: The tiny, spiral-shaped bacterium called Borrelia burgdorferi can quickly grapple along the inner surfaces of blood vessels to get to vulnerable tissues or to hiding places where it can hole up beyond the reach of drugs.

Immune escape strategies of Borrelia burgdorferi
Aslam B, Nisar MA, Khurshid M, Farooq Salamat MK.
Future Microbiology, 2017 Oct;12:1219-1237.
B. burgdorferi faces diverse environmental conditions of its vector and host during its life cycle. To circumvent the host immune system is a prominent feature of B. burgdorferi. To date, numerous studies have reported on the various mechanisms used by this pathogen to evade the host defense mechanisms. This current review attempts to consolidate this information to describe the immunological and molecular methods used by B. burgdorferi for its survival.

A Chromosomally Encoded Virulence Factor Protects the Lyme Disease Pathogen against Host-Adaptive Immunity.
Yang X, Coleman AS, Anguita J, Pal U (2009)
PLoS Pathog 5(3): e1000326. Public Library of Science Pathogens
These data identify the existence of a surface-located antigen of B. burgdorferi that helps the pathogen evade host-acquired immune defense and establish persistent infection and disease in mammals.

Protective value of prophylactic antibiotic treatment of tick bite for Lyme disease prevention: An animal model
Joseph Piesman, Andrias Hojgaard
Ticks and Tick-borne Diseases, Volume 3, Issue 3, June 2012, Pages 193–196.
Although the dynamics of antibiotic treatment in mice may differ from humans, and translation of animal studies to patient management must be approached with caution, we believe our results emphasize the point that antibiotic prophylactic treatment of tick bite to prevent Lyme disease is more likely to be efficacious if delivered promptly after potentially infectious ticks are removed from patients. There is only a very narrow window for prophylactic treatment to be effective post tick removal.

Treatment of Erythema Migrans With Doxycycline for 10 Days Versus 15 Days.
Stupica D, Lusa L, Ruzic-Sabljic E, Cerar T, Strle F.
Clinical Infectious Diseases, online before print, 2012 Apr 20.
117 (52%) patients were treated with doxycycline for 15 days and 108 (48%) with doxycycline for 10 days. At 12 months post-enrollment, 85/91 (93.4%) patients in the 15-day group and 79/86 (91.9%) in the 10-day group had complete response.

Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells.
Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K.
Antimicrobial Agents And Chemotherapy, pii: AAC.00864-15. Online first, 2015 May 26.
In this study, we examined the ability of B. burgdorferi to form persisters. Killing of growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from exponential to stationary phase. Combinations of antibiotics did not improve killing.

Persister mechanisms in Borrelia burgdorferi: implications for improved intervention
Jie Feng, Wanliang Shi, Shuo Zhang and Ying Zhang
Emerging Microbes & Infections, 4: e51; Published online, August 19, 2015.
Consistent with the persisting organisms not killed by current antibiotics, experiments in various animal models such as mice, dogs and monkeys have shown B. burgdorferi could still be detected after treatment with different Lyme antibiotics though viable organisms could not be cultured. In vitro studies also demonstrated that B. burgdorferi could develop antibiotic tolerant persisters. Although persister mechanisms have been reported in the model organism E. coli, the mechanisms of B. burgdorferi persisters remain unknown.

Doctor says you are cured, but you still feel the pain. Borrelia DNA persistence in Lyme disease
Jorge Cervantes
Microbes and Infection, Volume 19, Issues 9-10, September-October 2017, Pages 459-463.
Lyme disease is a zoonosis caused by infection with Borrelia burgdorferi (Bb). A great amount of research has attempted to elucidate the mechanisms by which Bb causes inflammation and chronic symptomatology in some patients. Patients often seek unconventional treatments that lack scientific evidence, as medical care is unable to effectively explain and treat their illness. Bb-DNA can persist for long periods of time in some individuals, even after antibiotic therapy. Herein, scientific rationale is presented for a new therapeutic approach against remaining bacterial DNA, and/or increasing the ability of human macrophages to remove extracellular Bb DNA.

Review of evidence for immune evasion and persistent infection in Lyme disease
Berndtson K
International Journal of General Medicine, April 2013,
Volume 2013:6, Pages 291-306.
Is chronic illness in patients with Lyme disease caused by persistent infection? Three decades of basic and clinical research have yet to produce a definitive answer to this question. This review describes known and suspected mechanisms by which spirochetes of the Borrelia genus evade host immune defenses and survive antibiotic challenge. Accumulating evidence indicates that Lyme disease spirochetes are adapted to persist in immune competent hosts, and that they are able to remain infective despite aggressive antibiotic challenge.

Borrelia burgdorferi Aggrecanase Activity: More Evidence for Persistent Infection in Lyme Disease
Raphael B. Stricker and Lorraine Johnson
Frontiers in Cellular and Infection Microbiology, online before print July 23, 2013.
Lyme disease is the most common tickborne illness in the world today. A recent study describes for the first time an enzyme produced by the spirochetal agent of Lyme disease, Borrelia burgdorferi, that cleaves aggrecan, a proteoglycan found in joints and connective tissue. Discovery of the spirochetal aggrecanase raises many questions about the pathogenesis of Lyme arthritis and lends support to the concept of persistent B. burgdorferi infection in patients with chronic Lyme disease symptoms.

Persistent infection in chronic Lyme disease: does form matter?
Stricker RB and Johnson L
Research Journal of Infectious Diseases 2013, 1:2
Lyme disease remains a controversial illness. The controversy is based on a profound disagreement over the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, and the ability of this persistent infection to cause chronic symptoms in patients who are untreated or undertreated for the initial spirochetal disease. In this article, we summarize evidence from animal models, human studies and in vitro experiments that support persistent spirochetal infection as the cause of chronic Lyme disease. Specifically, the role of cysts and biofilms in this process is outlined, and the need for better treatment options for patients with chronic Lyme disease is defined.

DNA persistence after treatment of Lyme borreliosis
D. Pícha, L. Moravcová, D. Vanousová, J. Hercogová, Z. Blechová
Folia Microbiologica, August 2013
In 124 patients, The frequency of PCR positives was comparable in CSF and urine, and it was lower by approximately 50 % in plasma. Specific DNA was also found in a significant number of patients in later testing periods: 48 patients after treatment, 29 patients after 3 months, and 6 patients after 6 months. The prolonged PCR positivity was not explainable by persistent infection according to the clinical manifestations of the disease. Possible explanations of the problem are discussed.

Sleeper cells: The stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle.
Cabello FC, Godfrey HP, Bugrysheva J, Newman SA.
Environmental Microbiology, online first, 2017 Aug 24.
Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them.

Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques.
Clinical and Vaccine Immunology, online before print, 2012 Jun 20.
Embers ME, Hasenkampf NR, Jacobs MB, Philipp MT.
Infection with B. burgdorferi elicits robust, yet disparate antibody responses in infected individuals. A longitudinal assessment of antibody responses to multiple diagnostic antigens following experimental infection and treatment has not previously been reported. Because the rhesus macaque recapitulates the hallmark signs and disease course of human Lyme disease, we examined the specific antibody responses to multiple antigens of B. burgdorferi following infection of macaques.

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection.
Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, et al.
(2012) PLoS ONE 7(1): e29914.
Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys.

Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Treatment in Rhesus Macaques.
Crossland NA, Alvarez X, Embers ME.
The American Journal of Pathology, online first, 2017 Dec 11.
Rare morphologically intact spirochetes were observed in the brains of two treated Rm, the heart of one treated Rm, and adjacent to a peripheral nerve of an untreated animal. Borrelia antigen staining of probable spirochete cross-sections was also observed in heart, skeletal muscle, and near peripheral nerves of both treated and untreated animals. These findings support the notion that chronic Lyme disease symptoms can be attributable to residual inflammation in and around tissues that harbor a low burden of persistent host-adapted spirochetes and/or residual antigen.

Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding.
Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, Hodzic E.
PLoS One. 2017 Dec 13;12(12):e0189071. (eCollection 2017)
Our results demonstrate host-dependent signs of infection and variation in antibody responses. In addition, we observed evidence of persistent, intact, metabolically-active B. burgdorferi after antibiotic treatment of disseminated infection and showed that persistence may not be reflected by maintenance of specific antibody production by the host.

Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans
Turk SP, Williams C, Marques A.
Methods in Molecular Biology. 2018;1690:337-346.
Part of the Methods in Molecular Biology book series (MIMB, volume 1690).
Xenodiagnosis is the use of a natural vector to detect the presence of an organism, and xenodiagnosis using Ixodes ticks has long been used by entomologists in Lyme disease research to provide evidence of the host’s infectious status with Borrelia burgdorferi. We developed the methodology and performed the first human research study using uninfected larval Ixodes scapularis ticks to assess evidence of B. burgdorferi infection.

Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy
Linda K. Bockenstedt, David G. Gonzalez, Ann M. Haberman and Alexia A. Belperron
Journal of Clinical Investigation, 2012;122(7): 2652-2660.
This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease.

Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment
Heta Yrjanainen, Jukka Hytonen, Pauliina Hartiala, Jarmo Oksi and Matti K. Viljanen
APMIS, (Acta Pathologica, Microbiologica et Immunologica Scandinavica, official journal of the Scandinavian Societies for Medical Microbiology and Pathology), online in advance of print July 2, 2010.
All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30-100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.

Characterization of Biofilm Formation by Borrelia burgdorferi In Vitro.
Sapi E, Bastian SL, Mpoy CM, Scott S, Rattelle A, et al. (2012) PLoS ONE 7(10): e48277.
In summary, we have found substantial evidence that Borrelia burgdorferi is capable of forming biofilm in vitro. Biofilm formation by Borrelia species might play an important role in their survival in diverse environmental conditions by providing refuge to individual cells.

Biofilm formation by Borrelia sensu lato
Arun Timmaraju, Priyanka A.S. Theophilus, Kunthavai Balasubramanian, Shafiq Shakih, David F. Leucke, and Eva Sapi
FEMS Microbiology Letters, online first, 24 July 2015.
Using various histochemistry and microscopy techniques, we show that Borrelia afzelii and Borrelia garinii form biofilms, which resemble biofilms formed by Borrelia burgdorferi sensu stricto. High-resolution atomic force microscopy revealed similarities in the ultra-structural organization of the biofilms form by three Borrelia species.

Adaptive immunity to Anaplasma pathogens and immune dysregulation: Implications for bacterial persistence
Wendy C. Brown
Comparative Immunology, Microbiology and Infectious Diseases, published online before print, January 4, 2012.
Anaplasma phagocytophilum infects neutrophils and causes disease in many mammals, including ruminants, dogs, cats, horses, and humans. Both bacteria cause persistent infection – infected cattle never clear A. marginale and A. phagocytophilum can also cause persistent infection in ruminants and other animals for several years. This review describes correlates of the protective immune response to these two pathogens as well as subversion and dysregulation of the immune response following infection that likely contribute to long-term persistence.

Statistical analysis questions evidence discouraging retreatment, coverage
Published on August 31, 2012 at 9:50 AM
Most doctors treat Lyme disease with antibiotics for two to four weeks after diagnosis, but if symptoms persist after that, medical guidelines recommend against antibiotic retreatment. That recommendation may not be warranted. A newly published statistical review of the four studies upon which those guidelines are based reports flaws in design, analysis, and interpretation that call into question the strength of the evidence against retreatment.

Medical guidance on retreatment of persistent Lyme disease may be flawed
Brown University, Providence, Rhode Island Contact: David Orenstein, 401-863-1862
A new statistical review calls into question studies that have been taken as proof that antibiotic retreatment for chronic Lyme disease is futile. That misunderstanding has led to medical guidance that discourages retreatment and insurance coverage for it. Instead, the authors of the review suggest, the proper reading of the studies and their data is that they prove nothing. “The goal of the paper is to clarify what was actually found from these clinical trials and what could be said and what couldn’t be said,” DeLong said. “A lack of evidence should not be used to deny treatment when the studies have serious flaws.”

Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study
Johanna Sjowall, Anna Ledel, Jan Ernerudh, Christina Ekerfelt, Pia Forsberg
BMC Infectious Diseases 2012, 12:186 (10 August 2012)
Persistent symptoms after treatment of neuroborreliosis (NB) are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB.

Potential Benefits of Retreatment Highlight the Need for Additional Lyme Disease Research
Allison K., DeLong, MS, Barbara, Blossom, BA, Elizabeth Maloney, MD, Steven E. Phillips, MD
The American Journal of Medicine, Volume 127, Issue 2, Pages e9-e10, February 2014.
We are responding to Klempner etal regarding our statistical review of the National Institutes of Health-sponsored antibiotic retreatment trials for Lyme disease. Our primary finding is that the trials did not prove retreatment is ineffective. A basic concept in statistical science regarding randomized controlled trials is that one can only??conclude treatment is ineffective when the treatment effect and confidence interval exclude and are below the minimum clinically important difference. None of the trials showed this.

Sixteenth Edition, Copyright October, 2008
A very important issue is the definition of “Chronic Lyme Disease”. Based on my clinical data and the latest published information, I offer the following definition. To be said to have chronic LB, these three criteria must be present:
1. Illness present for at least one year (this is approximately when immune breakdown attains clinically
significant levels).
2. Have persistent major neurologic involvement (such as encephalitis/encephalopathy, meningitis, etc.)
or active arthritic manifestations (active synovitis).
3. Still have active infection with B. burgdorferi (Bb), regardless of prior antibiotic therapy (if any).

One-year follow-up of tick-borne central nervous system infections in childhood
Engman ML, Lindstrom K, Sallamba M, Hertz C, Sundberg B, Hansson ME, Lindquist L, Orvell C, Lidefelt KJ, Sundin M.
Pediatric Infectious Disease Journal, June 2012, Volume 31, Issue 6, p 570-574.
Children diagnosed with TBE displayed significantly more long-term subjective complaints (ie, fatigue, headache and irritability) compared with the NB and control groups. Significantly higher frequency of disabilities was also detected by the Five-to-Fifteen Questionnaire in the TBE group. Both TBE and NB cause consequences (eg, prolonged convalescence, worries and financial loss) for the families. Markers for genetic susceptibility and brain damage had no prognostic values in this cohort. Pediatric TBE results in long-lasting residual symptoms and neurologic deficits affecting daily life. Vigilance for TBE-related morbidity among pediatricians and long-term clinical follow-up with assessment of cognitive dysfunctions and appropriate interventions seems reasonable for these children.

Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice.
Hodzic E, Imai D, Feng S, Barthold SW
PLoS ONE 9(1): e86907. (2014)
Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice.

The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis – the experience from one year of a university hospital’s Lyme neuroborreliosis outpatients clinic.
Djukic M, Schmidt-Samoa C, Nau R, Von Steinbuchel N, Eiffert H, Schmidt H.
European Journal of Neurology, online before print, October 27, 2010.
Conclusion: Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g. autoimmune diseases). One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later. These data should encourage further studies with new experimental parameters.

Antibiotics, Acne, and Staphylococcus aureus Colonization
Matthew Fanelli, MD; Eli Kupperman, BA; Ebbing Lautenbach, MD, MPH; Paul H. Edelstein, MD;
Archives of Dermatology, published online before print, April 11, 2011.
Unlike current dogma about the long-term use of antimicrobial agents, the prolonged use of tetracycline antibiotics commonly used to treat acne lowered the prevalence of colonization by S aureus and did not increase resistance to the tetracycline antibiotics.

Risk factors for a non-favorable outcome after treated European neuroborreliosis
Eikeland R, Mygland A, Herlofson K, Ljostad U.
Acta Neurologica Scandinavica, online before print, 2012 Jun 12.
Delayed treatment start, more symptoms and findings before treatment, and non-complete recovery at 4 months after treatment are possible predictors of a poorer HRQoL and more fatigue 30 months after treated LNB. We did not find age, gender, educational level, involvement of the central nervous system, coexisting diseases, or cerebrospinal fluid findings to be associated with reduced HRQoL or fatigue.

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library
Jie Feng, Wanliang Shi, Shuo Zhang, David Sullivan, Paul Auwaerter and Ying Zhang
Frontiers in Microbiology, 7:743 2016. Online first, May 3, 2016.
Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA) drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI) viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies.

Azithromycin is Equally Effective as Amoxicillin in Children with Solitary Erythema Migrans.
Arnež M, Ružic-Sabljic E.
The Pediatric Infectious Disease Journal, Online first, 2015 Jul 16.
Comparison of azithromycin and amoxicillin for the treatment of children with solitary EM revealed comparable efficacy and adverse effects of treatment.

Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review
Carris NW, Pardo J, Montero J, Shaeer KM.
Open Forum Infectious Diseases. 2015 Nov 25;2(4):ofv178. eCollection 2015.
Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline’s continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.

Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro
Feng J, Zhang S, Shi W, Zhang Y.
Antibiotics, 2017 Mar 22;6(1). pii: E10.
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations.

Ineffectiveness of Tigecycline against Persistent Borrelia burgdorferi
Written by: Lorraine Johnson, JD, MBA and Executive Director of the California Lyme Disease Association
December 15, 2009
An important study by Dr. Stephen Barthold and Dr. Ben Luft was recently published. The title sounds a bit bleak, but this study is about how the little guy (Borrelia burgdorferi) always wins and survives despite antibiotic treatment – here tigecycline. To my mind, the findings on persistence are much more important than the finding that tigecycline doesn’t do the job. When one antibiotic doesn’t work, you try another, and if that one doesn’t work, well, you try another or you kick it up a notch and start trying combination antibiotics, like they do with tuberculosis. You don’t fold up the tent and go home because active infection requires antibiotic treatment. And, you won’t ever find out which antibiotic or combinations of antibiotic work, until you try them. So, roll up your sleeves, we have some work to do here.

Benefits of repeated IV Antibiotics: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy
Fallon et al, Neurology, March 25, 2008, vol. 70 no. 13, 992-1003.
Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models.

Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease
Stricker et al, Int J Gen Med. 2011; 4: 639–646. Published online 2011 September 6.
Prolonged intravenous antibiotic therapy is associated with improved cognition, fatigue, and myalgias in patients referred for treatment of neurologic Lyme disease. Treatment for 25-52 weeks may be necessary to obtain symptomatic improvement in these patients.

A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome
Brian A. Fallon, Eva Petkova, John G Keilp, Carolyn Barley Britton
Published 2012 in The open neurology journal
DOI: 10.2174/1874205X01206010079
Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence. The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated. 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures.

Oral antibiotic treatment and long-term outcomes of Lyme facial nerve palsy.
Kowalski TJ, Berth WL, Mathiason MA, Agger WA.
Infection, online before print April 27, 2011.
Lyme facial nerve palsy patients were treated with oral antibiotics for a median duration of 21 days (range 7-30 days). Only three patients underwent lumbar puncture and each demonstrated lymphocytic pleocytosis. Fourteen of 15 patients with Lyme facial nerve palsy completely regained nerve function. The long-term outcomes were similar between patients with Lyme facial nerve palsy and controls after a median follow-up duration of 4.6 years. Patients with Lyme facial nerve palsy had significantly higher reported rates of fatigue (60%) than controls (27%) (p = 0.019), but similar energy and vitality scores on the SF-36 questionnaire (55.0 vs. 58.4, p = 0.621). SF-36 social functioning domain scores were significantly lower in patients with Lyme facial nerve palsy (77.5) than in controls (88.6) (p = 0.044).

Progression of Lyme disease to Bell’s Palsy despite treatment with doxycycline
Luis A. Marcos, Zengmin Yan
International Journal of Infectious Diseases, online first July 10, 2017
On day #10 of doxycycline, she woke up and noticed that her right face was paralyzed and unable to close the right eye so she went to the local emergency department. The EM was improved from 4 to 2 cm residual rash. Because of her headaches, a lumbar puncture and brain MRI were recommended. Cerebrospinal spinal fluid analysis revealed only 3 WBCs, protein 30.2 g/dL, glucose 62 mg/L, Lyme serology pair CSF fluid O.D. = 0.114 (borderline), serum Lyme serology pair O.D. = 0.409 (reactive), serum IgM western blot was positive (bands present: 23 and 41 kDa), serum IgG western blot was indeterminate (bands: 41,58 and 93 kDa), CRP remained less than 0.1 mg/dL. MRI of brain showed new increased enhancement involving right facial nerve.

Benefit of Courses of Antibiotics Beyond Two Months
Macrolide therapy of chronic Lyme Disease
Donta ST. Med Sci Monit .2003 Nov ;9 (11):PI136-42. PMID : 14586290
235 patients with a multi-symptom complex typical of chronic Lyme disease, ie fatigue, musculoskeletal pain, and neurocognitive dysfunction and with serologic reactivity against B.burgdorferi were treated with a macrolide antibiotic (eg clarithromycin) and hydroxychloroquine. Eighty % of patients had self-reported improvement of 50% or more at the end of 3 months. After 2 months of treatment, 20% of patients felt markedly improved (75–100% of normal); after 3 months of treatment, 45% were markedly improved. Improvement frequently did not begin until after several weeks of therapy. There were no differences among the three macrolide antibiotics used. Patients who had been on hydroxychloroquine or macrolide antibiotic alone had experienced little or no improvement. Compared to patients ill for less than 3 years, the onset of improvement was slower, and the failure rate higher in patients who were ill for longer time periods.

Maternal Lyme borreliosis and pregnancy outcome
Lakos A, Solymosi N.
International Journal of Infectious Diseases, published online 19 November 2009.
Treatment was administered parenterally to 66 (69.5%) women and orally to 19 (20%). Infection remained untreated in 10 (10.5%) pregnancies. Adverse outcomes were seen in 8/66 (12.1%) parentally treated women, 6/19 (31.6%) orally treated women, and 6/10 (60%) untreated women. In comparison to patients treated with antibiotics, untreated women had a significantly higher risk of adverse pregnancy outcome (odds ratio (OR) 7.61, p=0.004). While mothers treated orally had an increased chance (OR 3.35) of having an adverse outcome compared to those treated parenterally, this difference was not statistically significant (p=0.052). Erythema migrans did not resolve by the end of the first antibiotic course in 17 patients. Adverse pregnancy outcome was more frequent among these ‘slow responder’ mothers (OR 2.69), but this was not statistically significant (p=0.1425). Loss of the pregnancy (n=7) and cavernous hemangioma (n=4) were the most prevalent adverse outcomes in our series. The other complications were heterogeneous.

Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti
Saetre K, Godhwani N, Maria M, Patel D, Wang G, Li KI, Wormser GP, Nolan SM.
Journal of the Pediatric Infectious Diseases Society, online first 2017 Sep 16.
We describe the cases of 2 infants with congenital babesiosis born to mothers with prepartum Lyme disease and subclinical Babesia microti infection. The infants both developed anemia, neutropenia, and thrombocytopenia, and 1 infant required red blood cell transfusion. Both infants recovered with treatment. Additional studies are warranted to define the optimal management strategy for pregnant women with early Lyme disease in geographic areas in which B microti infection is endemic.

Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and Autism Spectrum Disorder.
Kuhn M, Grave S, Bransfield R, Harris S.
Medical Hypotheses, online before print, February 21, 2012.
The five children tested positive for Lyme disease and their SAP-O score was evaluated before and after 6 months of antibiotic therapy. Each child was prescribed 200 mg of amoxicillin three times per day and three of the five children were prescribed an additional 50 mg of Azithromycin once per day. All of the children’s scores on the SAP-O assessment improved after 6 months of antibiotic therapy. The assessors also reported anecdotal data of improved speech, eye contact, sleep behaviors, and a reduction of repetitive behaviors.

Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, David Sullivan and Ying Zhang
Antibiotics 2015, 4(3), 397-410.
Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved.

Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi
Sapi E, Kaur N, Anyanwu S, Luecke DF, Datar A, Patel S, Rossi M, Stricker RB
Infection and Drug Resistance, May 2011, Volume 4, pp. 97 – 113.
Doxycycline reduced spirochetal structures ~90% but increased the number of round body forms about twofold. Amoxicillin reduced spirochetal forms by ~85%-90% and round body forms by ~68%, while treatment with metronidazole led to reduction of spirochetal structures by ~90% and round body forms by ~80%. Tigecycline and tinidazole treatment reduced both spirochetal and round body forms by ~80%-90%. When quantitative effects on biofilm-like colonies were evaluated, the five antibiotics reduced formation of these colonies by only 30%-55%. In terms of qualitative effects, only tinidazole reduced viable organisms by ~90%. Following treatment with the other antibiotics, viable organisms were detected in 70%-85% of the biofilm-like colonies. Antibiotics have varying effects on the different morphological forms of B. burgdorferi. Persistence of viable organisms in round body forms and biofilm-like colonies may explain treatment failure and persistent symptoms following antibiotic therapy of Lyme disease.

Inhibitory effects of 19 antiprotozoal drugs and antibiotics on Babesia microti infection in BALB/c mice.
Yao JM, Zhang HB, Liu CS, Tao Y, Yin M.
Journal of Infection in Developing Countries. 2015 Sep 27;9(9):1004-1010.
The results showed that 15 of the 19 drugs had little or no in vivo effect against B. microti. The inhibitory rates of atovaquone and azithromycin were high at all doses, but the microscopy-negative blood of recovered mice was still infectious. Similar to robenidine hydrochloride at 25 and 50 mg/kg, primaquine at 100 mg/kg had a 100% inhibitory rate. Robenidine hydrochloride achieved a 100% inhibitory rate at 100 mg/kg, and the blood of recovered mice did not result in parasitemia in subpassage experiments. Parasite-negative blood from mice treated with antimalarial drugs (clinically used for babesiosis) still caused parasitemia in subpassage experiments. This suggests that these drugs cannot eradicate the parasites.

In vitro susceptibility of the relapsing fever spirochete Borrelia miyamotoi to antimicrobial agents
Koetsveld J, Draga ROP, Wagemakers A, Manger A, Oei A, Visser CE, Hovius JW.
Antimicrobial Agents and Chemotherapy, online first 2017 Jul 3.
We were able to show that both B. miyamotoi strains and B. hermsii demonstrated greater susceptibility to doxycycline and azithromycin, equal susceptibility to ceftriaxone and proved to be resistant to amoxicillin in vitro as compared to the B. burgdorferi s.l. isolates. The MIC and MBC of amoxicillin for B. miyamotoi evaluated by microscopy were 16-32 mg/L and 32-128 mg/L, respectively. Since B. miyamotoi is susceptible to doxycycline, azithromycin and ceftriaxone in vitro, our data suggests that these antibiotics can be used for treatment of HTBRF.

Pathogenicity and treatment of Bartonella infections.
Angelakis E, Raoult D.
International Journal of Antimicrobial Agents. 2014 Jul;44(1):16-25.
To date, no single treatment is effective for all Bartonella-associated diseases. In the absence of systematic reviews, treatment decisions for Bartonella infections are based on case reports that test a limited number of patients. Antibiotics do not significantly affect the cure rate in patients with Bartonella lymphadenopathy. Patients with Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline, but chloramphenicol has been proposed for the treatment of B. bacilliformis bacteraemia. Gentamicin in combination with doxycycline is considered the best treatment regimen for endocarditis, and erythromycin is the first-line antibiotic therapy for the treatment of angioproliferative lesions. Rifampicin or streptomycin can be used to treat verruga peruana.

Successful Treatment of Human Monocytic Ehrlichiosis with Rifampin
Abusaada K, Ajmal S, Hughes L.
Cureus. 2016 Jan 1;8(1):e444.
Currently recommended treatment regimens for human monocytic ehrlichiosis (HME) include doxycycline or tetracycline. Antibiotic susceptibility studies demonstrate that rifampin has in vitro bactericidal activity against Ehrlichia. Case reports have suggested clinical response with rifampin treatment of human granulocytic anaplasmosis (HGA). We report the first case of HME successfully treated with rifampin.

Researchers investigate four promising new treatments for Lyme disease
By Thea Singer, news@Northeastern, Northeastern University, Boston, Massachusetts March 29, 2016
The ticks that transmit Lyme dis­ease have mul­ti­plied aggres­sively over the past 20 years, and now thrive in half of all coun­ties in the U.S., according to a recent study in the Journal of Med­ical Entomology. So it’s no sur­prise that when North­eastern researchers reported last May how the bac­terium that causes the dis­ease evades antibi­otics, sug­gesting new treat­ments, the media and the gen­eral public took notice.

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii
Goc A, Niedzwiecki A, Rath M.
Journal of Applied Microbiology, online first, 2015 Oct 12.
Little is known about the effects of phytochemicals against Borrelia sp. causing Lyme disease. Current therapeutic approach to this disease is limited to antibiotics. This study examined the anti-borreliaea efficacy of several plant-derived compounds and micronutrients. The most effective antimicrobial compounds against all morphological forms of the two tested Borrelia sp. were baicalein and monolaurin. This might indicate that the presence of fatty acid and phenyl groups is important for comprehensive antibacterial activity.

The anti-borreliae efficacy of phytochemicals and micronutrients: an update
Anna Goc and Matthias Rath
Therapeutic Advances in Infectious Disease, first published on July 4, 2016.
Naturally occurring substances have been used for centuries to fight against various pathogens. They serve as a source for new chemical entities or provide options to already existing therapeutics.

Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp.
Goc A, Niedzwiecki A, Rath M.
International Journal of Biological Sciences. 2016 Jul 22;12(9):1093-103. eCollection 2016.
Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

Reciprocal cooperation of phytochemicals and micronutrients against typical and atypical forms of Borrelia spp.
Goc A, Niedzwiecki A, Rath M.
Journal of Applied Microbiology, online first 2017 Jun 23.
We tested 28 combinations of phytochemicals such as polyphenols (baicalein, luteolin, rosmarinic acids), fatty acids (monolaurin, cis-2-decenoic acid), and micronutrients (ascorbic acid, cholecalciferol, and iodine). The results showed that the combinations of baicalein with luteolin as well as monolaurin with cis-2-decenoic acid expressed synergistic anti-spirochetal effects. Moreover, baicalein and luteolin, when combined with rosmarinic acid or iodine, produced additive bacteriostatic and bactericidal effects against typical corkscrew motile spirochetes and persistent knob/round-shaped forms, respectively. An additive anti-biofilm effect was noticed between baicalein with luteolin as well as monolaurin with cis-2-decenoic acid. Finally, application of the combination of baicalein with luteolin increased cytoplasmic permeability of Borrelia spp. but did not cause DNA damage.

Treatment-Related Complications in Children Hospitalized With Disseminated Lyme Disease
Chang C, Feemster KA, Coffin S, Handy LK.
Journal of the Pediatric Infectious Diseases Society, 2017 Sep 1;6(3):e152-e154.
We describe here treatment approaches and treatment-related complications in 138 hospitalized children with disseminated Lyme disease.The patients who received parenteral antibiotics had a higher rate of complications than those who received oral therapy (15.4 vs 4.2 per 1000 days of therapy, respectively; P < .05).

No Visible Dental Staining in Children Treated with Doxycycline for Suspected Rocky Mountain Spotted Fever
Suzanne R. Todd, DVM, F. Scott Dahlgren, MSPH, Marc S. Traeger, MD, Eugenio D. Beltrán-Aguilar, DMD, DrPH, Donald W. Marianos, DDS, Charlene Hamilton, MPH, Jennifer H. McQuiston, DVM, Joanna J. Regan, MD
The Journal of Pediatrics, May 2015;166:1246-51.
Fifty-eight children who received an average of 1.8 courses of doxycycline before 8 years of age and who now had exposed permanent teeth erupted were compared with 213 children who had never received doxycycline. No tetracycline-like staining was observed in any of the exposed children’s teeth.

Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/Doxycycline/Cefuroxime Drug Combination without Pulse Dosing
Feng Jie, Zhang Shuo, Shi Wanliang, Zhang Ying
Frontiers in Microbiology, online first 19 October 2016.
Although the majority of Lyme disease patients can be cured, at least 10-20% of the patients continue to suffer from persisting symptoms such as fatigue, muscular and joint pain, and neurologic impairment after standard 2-4 week antibiotic treatment. While the causes for this post-treatment Lyme disease symptoms are unclear, one possibility is due to B. burgdorferi persisters that are not effectively killed by current antibiotics such as doxycycline or amoxicillin used to treat Lyme disease.

Vancomycin Reduces Cell Wall Stiffness and Slows Swim Speed of the Lyme Disease Bacterium
Harman MW, Hamby AE, Boltyanskiy R, Belperron AA, Bockenstedt LK, Kress H, Dufresne ER, Wolgemuth CW.
Biophysical Journal. 2017 Feb 28;112(4):746-754.
We found that in the presence of vancomycin, cell wall stiffness gradually decreased over time, with a 40% reduction in the bending stiffness after 36 h. Under the same conditions, the swimming speed of wild-type B. burgdorferi slowed by ~15%, with only marginal changes to cell morphology. Interestingly, our biophysical model for the swimming dynamics of B. burgdorferi suggested that cell speed should increase with decreasing cell stiffness.

Effects of intravenous ketamine in a patient with post-treatment Lyme disease syndrome
Hanna AF, Abraham B, Hanna A, Smith AJ.
International Medical Case Reports Journal, 2017 Aug 18;10:305-308. eCollection 2017.
Post-treatment Lyme disease syndrome (PTLDS) is a pain disorder for which there remains no gold standard treatment option. Here, we report a case of PTLDS in a female patient whose pain was refractory to treatment options such as radiofrequency ablation, vitamin infusion therapy, opioid analgesics, and other pharmacotherapies.The patient commenced an experimental intravenous ketamine infusion therapy at the Florida Spine Institute (Clearwater, FL, USA) and achieved relief from her chronic pain, an improved quality of life, reduced depression and suicidal ideation, and reduced opioid consumption.

Novel Diamidines with Activity against Babesia divergens In Vitro and Babesia microti In Vivo.
Nehrbass-Stuedli A, Boykin D, Tidwell RR, Brun R.
Antibacterial Agents and Chemotherapy, online before print, ay 2, 2011.
Dicationic diamidines, such as diminazene and pentamidine, are well-studied chemotherapeutic agents with significant activity against parasitic diseases. The in vitro activity of novel diamidine compounds was investigated against the Babesia divergens strains 1903B and 4201. The most potent compound, a diphenyl furan, had an IC(50) of 1.5 ng/ml.

Cat-scratch disease: a wide spectrum of clinical pictures
Katarzyna Mazur-Melewska, Anna Mania, Pawel Kemnitz, Magdalena Figlerowicz, and Wojciech Sluzewski
Advances in Dermatology and Allergology/Postepy Dermatologii i Alergologii, 2015 Jun; 32(3): 216-220.
The aim of this review is to present an emerging zoonotic disease caused by Bartonella henselae. The wide spectrum of diseases connected with these bacteria varies from asymptomatic cases, to skin inflammation, fever of unknown origin, lymphadenopathy, eye disorders, encephalitis and endocarditis. If an antibiotic is chosen, however, azithromycin has been shown to speed recovery.

Neurological Manifestations of Bartonellosis in Immunocompetent
Patients: A Composite of Reports from 2005–2012
E. B. Breitschwerdt,1 S. Sontakke,1,2 and S. Hopkins3
Received 8 October 2012; Revised 2 November 2012; Accepted 4 November 2012
For severe or persistent neurobartonellosis, there is minimal evidence upon which to base treatment decisions. Expert opinion often recommends a combination of doxycycline plus rifampin for 10 to 14 days [8,62]. Based upon in vitro testing, numerous antibiotics appear to be effective for the treatment of Bartonella infections [8]. However, as Bartonella spp. induce both intracellular, as well as extracellular infection, in vitro test results can identify antibiotics that are not effective and can also be used to select antibiotics that should be tested in clinical trials of in vivo efficacy. Doxycycline, erythromycin, and rifampin are the most frequently recommended antibiotics for treating Bartonella spp. infection in people, but clinical improvement has been reported following the use of penicillin, gentamicin, ceftriaxone, ciprofloxacin, and azithromycin.

The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis
Thomas Butler
The American Journal of Tropical Medicine and Hygiene, Volume 96, Issue 1, Jan 2017, p. 46-52.
Within 24 hours after antibiotic treatment of the spirochetal infections syphilis, Lyme disease, leptospirosis, and relapsing fever (RF), patients experience shaking chills, a rise in temperature, and intensification of skin rashes known as the Jarisch–Herxheimer reaction (JHR) with symptoms resolving a few hours later. Case reports indicate that the JHR can also include uterine contractions in pregnancy, worsening liver and renal function, acute respiratory distress syndrome, myocardial injury, hypotension, meningitis, alterations in consciousness, seizures, and strokes. Experimental evidence indicates it is caused by nonendotoxin pyrogen and spirochetal lipoproteins.

Controversies in Persistent (Chronic) Lyme Disease
Maloney EL.
Journal of Infusion Nursing, online first, 2016 Oct 13.
The Centers for Disease Control and Prevention estimates that more than 300 000 new cases of Lyme disease occur each year in the United States and that 10% to 20% of these patients will remain symptomatic despite receiving appropriate antibiotic therapy.Many elements of the disease are poorly understood and have generated considerable controversy.This paper discusses the medical controversies related to posttreatment manifestations and their potential impact on infusion nurses.

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
GB Rogers, DJ Keating, RL Young M-L Wong, J Licinio and S Wesselingh
The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association betweenenteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies. Molecular Psychiatry (2016) 21, 738–748; doi:10.1038/mp.2016.50; published online 19 April 2016

Steroid use in Lyme disease-associated facial palsy is associated with worse long-term outcomes
Jowett, N., Gaudin, R. A., Banks, C. A. and Hadlock, T. A.
The Laryngoscope, online first September 6, 2016.
The purpose of this study was to determine whether differences in long-term facial function outcomes following acute Lyme disease-associated facial palsy (LDFP) exist between patients who received antibiotic monotherapy (MT); dual therapy (DT) with antibiotics and corticosteroids; and triple therapy (TT) with antibiotics, corticosteroids, and antivirals. An association between corticosteroid use in acute LDFP and worse long-term facial function outcomes has been demonstrated. Care should be taken in differentiating viral or idiopathic facial palsy (e.g., Bell palsy) from LDFP.

Are Mycobacterium Drugs Effective for Treatment Resistant Lyme Disease, Tick-Borne Co-Infections, and Autoimmune Disease?
Richard I. Horowitz and Phyllis R. Freeman
JSM Arthritis, online first, July 16, 2016.
PTLDS/chronic Lyme disease may cause disabling symptoms with associated overlapping autoimmune manifestations, with few clinically effective published treatment options. We recently reported on the successful use of a mycobacterium drug, Dapsone, for those with PTLDS. We now report on the novel use of another mycobacterium drug, pyrazinamide, (PZA), in relieving resistant symptomatology secondary to Lyme disease and associated co-infections, while decreasing autoimmune manifestations with Behçet’s syndrome.

Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.
Gyllemark P, Forsberg P, Ernerudh J, Henningsson AJ.
Journal of Neuroinflammation, 2017 Feb 1;14(1):27.
B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated. By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis
Raffalli J, Wormser GP
Diagnostic Microbiology & Infectious Disease, online first, 2016 Feb 21.
We report a patient who was being treated with rituximab for rheumatoid arthritis who developed Babesia microti infection that persisted for 26 months despite prolonged anti-babesia drug therapy. The explanation for the persistence was likely to have been the long-term immunocompromising effects of rituximab, as evidenced by seronegativity for B. microti antibodies that lasted for more than 1 year after onset of infection.

A longitudinal study of Babesia microti infection in seropositive blood donors.
Leiby DA, Johnson ST, Won KY, Nace EK, Slemenda SB, Pieniazek NJ, Cable RG, Herwaldt BL.
Transfusion, online before print, 2014 Mar 28.
Three of nine persons who had more than one specimen with evidence of parasitemia had nonconsecutive positives. Several enrollees likely had been infected at least 1 year when their last positive specimen was collected. The final three specimens for seven persons tested negative by all study methods, including IFA. Seropositive blood donors can have protracted low-level parasitemia that is variably and intermittently detected by parasitologic and molecular methods.

The effect of artesunate on short-term memory in Lyme borreliosis
Puri BK, Hakkarainen-Smith JS, Monro JA.
Medical Hypotheses, 2017 Aug; 105: 4-5.
Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria.

Treatment outcomes of human bartonellosis: a systematic review and meta-analysis
Prutsky G, Domecq JP, Mori L, Bebko S, Matzumura M, Sabbouni A, Shahrour A, Erwin PJ, Boyce TG, Montori VM, Malaga G, Murad MH.
International Journal of Infectious Diseases, online before print, 2013 Apr 17.
We found two randomized and seven non-randomized studies at high risk of bias. For cat scratch disease, antibiotics did not significantly affect the cure rate or time to achieve cure. In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate. The recommended treatment was not better than other regimens for infectious endocarditis and bacillary angiomatosis.

Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review
R. Dersch, H. Sommer, S. Rauer, J. J. Meerpohl
Journal of Neurology, online first, 12 October 2015.
Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the “probable/definite” case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28%. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the “probable/definite” case definition.

Vitamin C Protects Chondrocytes against Monosodium Iodoacetate-Induced Osteoarthritis by Multiple Pathways
Pu-Rong Chiu, Yu-Chen Hu, Tzu-Ching Huang, Bau-Shan Hsieh, Jou-Pei Yeh, Hsiao-Ling Cheng, Li-Wen Huang, and Kee-Lung Chang, David Arráez-Román, Academic Editor and Ana Maria Gómez Caravaca, Academic Editor
Int J Mol Sci. 2017 Jan; 18(1): 38.
Published online 2016 Dec 27. doi: 10.3390/ijms18010038 PMCID: PMC5297673
Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression levels of the pro-inflammatory cytokines IL-6, IL-17A, and TNF-α and matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with treatment of 100 μM vitamin C. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, and treatment of vitamin C could lessen these changes. Unexpectedly, vitamin C’s effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Vitamin C possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation.

Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function
R Sinha1, I Sinha, A Calcagnotto, N Trushin, J S Haley, T D Schell and J P Richie Jr
European Journal of Clinical Nutrition advance online publication 30 August 2017
GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05). GSH increases were accompanied by reductions in oxidative stress biomarkers, including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05). Enhancements in immune function markers were observed with liposomal GSH administration including Natural killer (NK) cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated by up to 60% after 2 weeks (P<0.05). Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting the immune function and levels of oxidative stress.

Does phytoestrogen supplementation improve cognition in humans? A systematic review.
Ann N Y Acad Sci. 2017 Sep;1403(1):150-163. doi: 10.1111/nyas.13459.
Thaung Zaw JJ1, Howe PRC1,2, Wong RHX1.
Recent evidence indicates that resveratrol, a phytoestrogen, can improve cognitive function in postmenopausal women by enhancing cerebral vasodilator responsiveness. We examine the effects of phytoestrogen supplementation on cognition and compare resveratrol with other phytoestrogens.

Hyperbaric oxygen therapy as an effective adjunctive treatment for chronic Lyme disease.
Huang CY, Chen YW, Kao TH, Kao HK, Lee YC, Cheng JC, Wang JH.
Journal of the Chinese Medical Association, pii: S1726-4901(14)00042-2. Online before print, 2014 Apr 9.
The mechanisms of CLD remain unclear and the symptoms related to CLD are difficult to manage. Hyperbaric oxygen therapy (HBOT) was applied in CLD therapy in the 1990s. However, reported information regarding the effectiveness of HBOT for CLD is still limited. Here, we present a patient with CLD who was successfully treated with HBOT.

Treatment of Lyme neuroborreliosis with plasmapheresis
Çelik, T., Çelik, Ü., Kömür, M., Tolunay, O., Dönmezer, Ç. and Yildizdas, D.
Journal of Clinical Apheresis, online before print, September 10, 2015.
The effect of plasmapheresis in pediatric neuroborreliosis has not been documented before. This study highlights that plasmapheresis could be a useful alternative for pediatric neuroborreliosis cases.

Inhibitory effect of allicin on the growth of Babesia and Theileria equi parasites.
Salama AA, Aboulaila M, Terkawi MA, Mousa A, El-Sify A, Allaam M, Zaghawa A, Yokoyama N, Igarashi I.
Parasitology Research, online before print, 2013 Oct 31.
Allicin is an active ingredient of garlic that has antibacterial, antifungal, antiviral, and antiprotozoal activity. These results indicate that allicin might be beneficial for the treatment of babesiosis, particularly when used in combination with diminazene aceturate.

Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi
Feng J, Zhang S, Shi W, Zubcevik N, Miklossy J, Zhang Y.
Frontiers in Medicine, 2017 Oct 11;4:169. eCollection 2017.
Although the majority of patients with acute Lyme disease can be cured with the standard 2-4 week antibiotic treatment, about 10-20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity.

In Vitro Effectiveness of Samento and Banderol Herbal Extracts on the Different Morphological Forms of Borrelia Burgdorferi
by Akshita Datar, Navroop Kaur, Seema Patel, David F. Luecke, and Eva Sapi, PhD
Lyme Disease Research Group, University of New Haven
Townsend Letter for Doctors & Patients, July 2010
Our results demonstrated that both herbal agents, but not doxycycline, had very significant effects on all forms of B. burgdorferi, especially when used in combination, suggesting that herbal agents could provide an effective therapeutic approach for Lyme disease patients.

Effectiveness of Stevia rebaudiana whole leaf extract against the various morphological forms of Borrelia burgdorferi in vitro
P. A. S. Theophilus, M. J. Victoria, K. M. Socarras, K. R. Filush, K. Gupta, D. F. Luecke, E. Sapi
European Journal of Microbiology and Immunology, online first, November 12, 2015.
Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters.

Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria.
Maisuria VB, Hosseinidoust Z, Tufenkji N.
Applied & Environmental Microbiology, pii: AEM.00239-15. Online first, 2015 Mar 27.
Phenolic compounds are believed to be promising candidates as complementary therapeutics. Maple syrup, prepared by concentrating the sap from the North American maple tree, is a rich source of natural and process-derived phenolic compounds.

Antimicrobial Activity of Bee Venom and Melittin against Borrelia burgdorferi
Socarras, K.M.; Theophilus, P.A.S.; Torres, J.P.; Gupta, K.; Sapi, E.
Antibiotics 2017; 6(4):31. Online first, November 29, 2017.
Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form.  These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use.

Apheresis for babesiosis: Therapeutic parasite reduction or removal of harmful toxins or both?
Saifee NH, Krause PJ, Wu Y.
Journal of Clinical Apheresis, online first, 2015 Oct 20.
Babesiosis is a potentially life-threatening illness caused by intraerythrocytic protozoan parasites of the genus Babesia that are transmitted most commonly by Ixodes ticks, and rarely from blood transfusion or congenitally. Clinical presentations of babesiosis include asymptomatic infection, mild to moderate disease, or severe disease. Antibiotics such as atovaquone plus azithromycin or clindamycin and quinine can be used effectively to treat this disease in most cases, however in high risk populations, the mortality rate can be as high as 20% despite therapy.

Massage therapy for lyme disease symptoms: a prospective case study.
Thomason MJ, Moyer CA.
International Journal of Therapeutic Massage and Bodywork. 2012;5(4):9-14. Online before print, 2012 Dec 19.
LD symptoms decreased during treatment periods and increased during nontreatment periods. Positive affect was increased at every MT session. MT is a promising treatment for the symptoms pain, fatigue, and impaired concentration associated with LD.

A case report of human granulocytic anaplasmosis (ehrlichiosis) in pregnancy and a literature review of tick-borne diseases in the United States during pregnancy.
Qasba N, Shamshirsaz AA, Feder HM, Campbell WA, Egan JF, Shamshirsaz AA.
Obstetrical & Gynecological Survey, 2011 Dec;66(12):788-96.
There is paucity of data regarding tick-borne diseases during pregnancy. Here, we report a case of human granulocytic anaplasmosis during pregnancy with successful treatment and a favorable neonatal outcome. We also review diagnosis, treatment, and outcomes of published case reports from 1983 to 2010 of human granulocytic anaplasmosis, Lyme disease, babesiosis, and human monocytic ehrlichiosis in the United States.

Medical Biomagnetism tested in 265 patients at clinic in Spain on May 2009.
Centro Médico Hilu ( Hilu Stem Center) and Biomagnetic Pair Therapy:
Sra. Julia Anuna, the therapists Juan Carlos Albendea from Madrid and Agueda from Pamplona, Dra Mary Staggs.
According to Dr. Isaac Goiz’s theory, the fundamental elements on which the bio magnetic pair treatment is based are the following: the pH of the organism, the role played by the micro organisms in the production of illness, the presence of a series of energy points in the body related between one another (like the two poles of a battery), the use of magnetic fields produced by magnets with a power greater than 1.000 gauss, creating a magnetic current, which pushes the positive poles against the negative ones, the pH is neutralised and thus instantaneously eliminating all the micro organisms which produce disease.

A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis.
Trock DH , Bollet AJ , Dyer RH Jr , Fielding LP , Miner WK , Markoll R
The Journal of Rheumatology [01 Mar 1993, 20(3):456-460]
Further evaluation of pulsed electromagnetic fields (PEMF), which have been observed to produce numerous biological effects, and have been used to treat delayed union fractures for over a decade. The decreased pain and improved functional performance of treated patients suggests that this configuration of PEMF has potential as an effective method of improving symptoms in patients with OA. This method warrants further clinical investigation.

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Severe, lingering symptoms seen in some patients after Lyme disease treatment
By Marin Hedin, John Hopkins Magazine, Baltimore, Maryland
February 4, 2018
In a study of 61 people treated for the bacteria that causes Lyme disease, Johns Hopkins researchers conclude that fatigue, pain, insomnia, and depression do indeed persist over long periods of time for some people, despite largely normal physical exams and clinical laboratory testing. “Post-treatment Lyme disease syndrome (PTLDS) is a real disorder that causes severe symptoms in the absence of clinically detectable infection,” says John N. Aucott, associate professor of medicine at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Lyme Disease Clinical Research Center.

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability.
Morris G, Berk M, Walder K, Maes M.
Molecular Neurobiology, online first, 2015 Jun 17.
Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure.

Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses
Garth L. Nicolson and Jorg Haier, British Journal of Medical
Practitioners, 2010;3(1):301.
Part 1
Part 2
Chronically ill patients with neurodegenerative and neurobehavioural and psychiatric diseases commonly have systemic and central nervous system bacterial and viral infections. In addition, other chronic illnesses where neurological manifestations are routinely found, such as fatiguing and autoimmune diseases, Lyme disease and Gulf War illnesses, also show systemic bacterial and viral infections that could be important in disease inception, progression or increasing the types/severities of signs and symptoms. Evidence of Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, human herpesvirus-1, -6 and -7 and other bacterial and viral infections revealed high infection rates in the above illnesses that were not found in controls. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of progressive chronic diseases.

The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome
Rebman AW, Bechtold KT, Yang T, Mihm EA, Soloski MJ, Novak CB, Aucott JN.
Frontiers in Medicine. 2017 Dec 14;4:224. eCollection 2017.
Although physical exam and clinical laboratory tests showed few objective abnormalities, standardized symptom questionnaires revealed that patients with PTLDS are highly and clinically significantly symptomatic, with poor health-related quality of life. PTLDS patients exhibited levels of fatigue, musculoskeletal pain, sleep disturbance, and depression which were both clinically relevant and statistically significantly higher than controls. Our study shows that PTLDS can be successfully identified using a systematic approach to diagnosis and symptom measurement. As the prevalence of PTLDS continues to rise, there will be an increased need for physician education to more effectively identify and manage PTLDS as part of integrated patient care.

Sleep Quality in Well-defined Lyme Disease
Weinstein ER, Rebman AW, Aucott JN, Johnson-Greene D, Bechtold KT.
Sleep, online first 2018 Feb 14.
Participants with early LD experienced poor sleep quality, which is associated with typical LD symptoms of pain and fatigue. In the subset of patients who developed PTLDS, sleep quality remains affected for up to one year post-treatment and is commonly associated with pain. Sleep quality should be considered in the clinical picture for LD and PTLDS.

Isolation of live Borrelia burgdorferi sensu lato spirochetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis
N. Rudenko, M. Golovchenko ,M. Vancova, K. Clark, L. Grubhoffer, J.H. Oliver Jr.
Clinical Microbiology and Infection, online first, December 7, 2015.
It is known that Lyme borreliosis is mimicking multiple diseases that were never proven to have a spirochete etiology. Using complete modified Kelly-Pettenkofer medium we succeeded in cultivation of live B. burgdorferi sensu lato spirochetes from samples of humans who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but undergone antibiotic treatment due to suspicion of having Lyme disease even though they were seronegative.

Retrospective Analysis of a Cohort of Internationally Case Defined Chronic Fatigue Syndrome Patients in a Lyme Endemic Area
Samuel Shor, Bulletin of the IACFS/ME. 2011;18(4):109-123.
Of the total 210 included in the analysis, 209 or 99% were felt to represent a high likelihood of “seronegative Lyme disease.” Initiating various antimicrobial regimen, involved at least a 50% improvement in clinical status in 130 or 62%. Although not achieving the 50% threshold according to the criteria discussed, another 55 patients subjectively identified a beneficial clinical response to antimicrobials, representing a total of 188 or 88% of the total identified as having a high potential for seronegative Lyme disease. A potentially substantial proportion of patients with what would otherwise be consistent with internationally case defined CFS in a Lyme endemic environment actually have a perpetuation of their symptoms driven by a persistent infection by Borrelia burgdorferi. By treating this cohort with appropriately directed antimicrobials, we have the ability to improve outcomes.

Factors Affecting Duration of Chronic Fatigue Syndrome in Pediatric Patients
Dmitriy Petrov, Daniel Marchalik, Michael Sosin and Aswine Bal
Indian Journal of Pediatrics, online before print, May 27, 2011.
A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria.

Long-Term Assessment of Fatigue in Patients with Culture-Confirmed Lyme Disease
Gary P. Wormser, M.D, Erica Weitzner, B.S, Donna McKenna, N.P, Robert B. Nadelman, M.D, Carol Scavarda, R.N, John Nowakowski, M.D
The American Journal of Medicine, online before print, 15 October 2014
Severe fatigue was found in 9 (9%) patients with culture-confirmed early Lyme disease at 11 to 20 years after presentation.

Correlates of Perceived Health-Related Quality of Life in Post-treatment Lyme Encephalopathy.
Chandra AM, Keilp JG, Fallon BA.
Psychosomatics, online before print, 2013 Jul 8. pii: S0033-3182(13)00078-9.
Marked functional impairment has been reported by patients with post-treatment Lyme disease syndrome (PTLDS). Fatigue was the most important contributor to perceived impairments in overall physical functioning, and fatigue and depression significantly predicted perceived impairments in overall mental functioning.

A Case of Early Disseminated Neurological Lyme Disease Followed by Atypical Cutaneous Manifestations
Kantamaneni V, Sunder V, Bilal M, Vargo S.
Case Reports in Infectious Diseases, online first, 2017 Apr 23.
Not all patients have the classic “targetoid” EM rash on initial presentation, rash could develop after neurological manifestations, and prompt initiation of antibiotics without awaiting serology is paramount to making a quick and a full recovery. There should be a high index of suspicion for early disseminated LD, as presentations can be atypical.

Inflammation and Central Nervous System Lyme Disease
Brian A. Fallon, Elizabeth S. Levin, Pernilla J. Schweitzer and David Hardesty
Lyme disease, caused by the bacterium Borrelia burgdorferi, can cause multi-systemic signs and symptoms, including peripheral and central nervous system disease. This review examines the evidence for and mechanisms of inflammation in neurologic Lyme disease, with a specific focus on the central nervous system, drawing upon human studies and controlled research with experimentally infected rhesus monkeys. Directions for future human research are suggested that may help to clarify the role of inflammation as a mediator of the chronic persistent symptoms experienced by some patients despite antibiotic treatment for neurologic Lyme disease.

Estimation of cognitive and affective disorders occurrence in patients with Lyme borreliosis
Oczko-Grzesik B, Kepa L, Puszcz-Matlinska M, Pudlo R, Zurek A, Badura-Glabik T.
Annals of Agricultural and Environmental Medicine, 2017 Mar 1;24(1):33-38.
An increased frequency of depressive and neurotic disorders was observed in patients with LB, particularly in patients with neuroborreliosis. Neurotic disorders, mainly adaptive, were most common in males with LB, while depressive disorders were more frequent in females. An increased frequency of cognitive deficits was observed in patients with neuroborreliosis, particularly in females.

Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease
Weitzner E, McKenna D, Nowakowski J, Scavarda C, Dornbush R, Bittker S, Cooper D, Nadelman RB, Visintainer P, Schwartz I, Wormser GP.
Clinical Infectious Diseases, pii: civ735. Online before print, 2015 Sep 18.
PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.

Lyme arthritis in children presenting with joint effusions
Milewski MD, Cruz AI Jr, Miller CP, Peterson AT, Smith BG.
The Journal of Bone and Joint Surgery (American). 2011 Feb;93(3):252-60.
For any child presenting with a joint effusion in a Lyme-endemic area of the Northeastern United States, the likely prevalence of Lyme arthritis is 31% overall and 45% in the presence of knee effusion. Children with joint effusions resulting from Lyme disease are more likely to have knee involvement, a lower peripheral white blood-cell count, and a lower joint fluid cell count, and they are less likely to have fever or complete refusal to bear weight, when compared with children with septic arthritis.

Divergent opinions of proper Lyme disease diagnosis and implications for children co-morbid with autism spectrum disorder.
Kuhn M, Bransfield R.
Medical Hypotheses. 2014 Jun 16. pii: S0306-9877(14)00233-3.
Through an online survey parents of 48 children who have a diagnosis of an ASD and have been diagnosed with Lyme disease were asked to fill out the Autism Treatment Evaluation Checklist (ATEC) before they started antibiotic therapy and after treatment. Of the 48 parents surveyed 45 of them (94%) indicated their child initially tested negative using the two-tiered CDC/IDSA approved test. Protein bands OSP-A and/or OSP-B (Western Blot band 31) and (Western Blot band 34) were found in 44 of 48 patients. These two bands are so specific to Borrelia burgdorferi that they were targeted for use in vaccine trials, yet are not included in the IDSA interpretation of the Western Blot.

Uncommon manifestations of neuroborreliosis in children
Baumann M, Birnbacher R, Koch J, Strobl R, Rostásy K.
European Journal of Paediatric Neurology, Volume 14, Issue 3, May 2010, Pages 274-277.
We report four unusual cases of childhood neuroborreliosis and show that seizures with regional leptomeningeal enhancement, acute transverse myelitis, meningoradiculitis with pain and paraesthesia and cranial nerve palsies other than facial nerve palsy can be the leading symptoms of children with neuroborreliosis.

Suicide and Lyme and associated diseases
Bransfield RC
Neuropsychiatric Disease and Treatment, online first, June 16, 2017.
LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital–urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year.

A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide
Helene Lund-Sørensen, BM1,2; Michael E. Benros, PhD1,2; Trine Madsen, PhD1,2; et al Holger J. Sørensen, MD1,2; William W. Eaton, PhD3; Teodor T. Postolache, MD4,5,6; Merete Nordentoft, DrMedSc1,2,7; Annette Erlangsen, PhD2,3
JAMA Psychiatry. 2016;73(9):912-919. September 2016
Findings suggest that infections might be linked to the development of psychiatric disorders and suicidal behavior. Large-scale studies are needed to investigate the effect of infection on the risk of suicide.

People with rage disorder twice as likely to have latent Toxoplasma gondii Infection.
Emil F. Coccaro, Royce Lee, Maureen W. Groer, Adem Can, Mary Coussons-Read, Teodor T. Postolache.
The Journal of Clinical Psychiatry, 2016; 334
DOI: 10.4088/JCP.14m09621
Individuals with a psychiatric disorder involving recurrent bouts of extreme, impulsive anger — road rage, for example — are more than twice as likely to have been exposed to a common parasite than healthy individuals with no psychiatric diagnosis. In a study involving 358 adult subjects, researchers found that toxoplasmosis, a relatively harmless parasitic infection carried by an estimated 30 percent of all humans, is associated with intermittent explosive disorder and increased aggression.

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study
Psychosomatic Medicine. 79(8):936–946, OCT 2017
Publication Date: 2017/10/01
Sian M.J. Hemmings; Stefanie Malan-Müller; Leigh L. van den Heuvel; Brittany A. Demmitt; Maggie A. Stanislawski; David G. Smith; Adam D. Bohr; Christopher E. Stamper; Embriette R. Hyde; James T. Morton; Clarisse A. Marotz; Philip H. Siebler; Maarten Braspenning; Wim Van Criekinge; Andrew J. Hoisington; Lisa A. Brenner; Teodor T. Postolache; Matthew B. McQueen; Kenneth S. Krauter; Rob Knight; Soraya Seedat; Christopher A. Lowry
Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

Cervical Radiculopathy as the Initial Presentation for Lyme neuroborreliosis
Anas Hannoun and Jeffrey Gudin
Neurology, April 18, 2017, 88:16 Supplement P1.311; 1526-632X.
Abstracts: American Academy of Neurology, 69th Annual Meeting, Boston.
21-year-old male with no past history of spinal or neurological disease, presented with acute right cervical neck pain radiating to the right trapezius and right occipital and temporal regions. Lyme studies showed the IgM antibody level for Borrelia burgdorferi elevated with normal IgG levels. Oral Doxycycline 100mg twice a day was started. The following day, the patient re-presented to the ED with acute right lower motor neuron facial droop. Other symptoms included intermittent fevers, myalgias, and neck stiffness. Lumbar puncture demonstrated cell count of 268 with lymphocytic predominance. Protein level was elevated at 114. IgM antibody level for Borrelia burgdorferi was positive. He was diagnosed with Lyme disease complicated by neurological symptoms and meningitis and started on 2gm of ceftriaxone IV daily.

The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia
Geeta Ramesh, Lenay Santana-Gould, Fiona M Inglis, John D England and Mario T Philipp
Journal of Neuroinflammation, 2013, 10:88. Published online July 18, 2013.
In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.

Validation of a Clinical Prediction Rule to Distinguish Lyme Meningitis From Aseptic Meningitis
Cohn KA, Thompson AD, Shah SS, Hines EM, Lyons TW, Welsh EJ, Nigrovic LE.
Pediatrics, online before print, December 19, 2011.
We identified 423 children, of whom 117 (28% [95% confidence interval (CI): 24%–32%]) had Lyme meningitis, 306 (72% [95% CI: 68%–76%]) had aseptic meningitis, and 0 (95% CI: 0%–1%) had bacterial meningitis.

I Can’t Move My Face! A Case of Bilateral Facial Palsy
Marna Rayl Greenberg, DO, MPH; Megan C. Urquhart, DO; Jessica K. Eygnor, DO; Charles C. Worrilow, MD; Nicole Ceccacci Gesell, DO; Bernadette Glenn Porter, BS; Andrew C. Miller, DO
Journal of the American Osteopathic Association, October 1, 2013 vol. 113 no. 10, 788-790.
The authors present a case of bilateral facial palsy in a 52-year-old man. The patient presented to an emergency department in Pennsylvania, describing left-sided neck pain and headache from “sleeping wrong,” symptoms which eventually progressed to facial diplegia by his fourth visit in 2 weeks. His admitting diagnosis was Bell palsy; he was ultimately tested for and found to have Lyme disease.

Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation.
Tunev SS, Hastey CJ, Hodzic E, Feng S, Barthold SW, et al.
(2011) PLoS Pathog 7(5): e1002066.
Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy.

The association of lyme disease with loss of sexual libido and the role of urinary bladder detrusor dysfunction.
Puri BK, Shah M, Julu PO, Kingston MC, Monro JA.
International Neurourology Journal. 2014 Jun;18(2):95-7.
The 2 groups were matched with respect to age, sex, body mass index, and mean arterial blood pressure. None of the 34 subjects was taking medication that might affect sexual libido or had undergone a previous operative procedure involving the genitourinary tract. Of the 16 Lyme disease patients, 8 (50%) had no loss of libido, and of the 18 controls, none had loss of libido (P<0.001). In the Lyme disease patient group, there was no statistically significant relationship between loss of libido and urinary bladder detrusor dysfunction (P=0.61). This pilot study suggested an association between Lyme disease and loss of libido. Moreover, this loss of libido did not seem to be associated with urinary bladder detrusor dysfunction.

Post-Treatment Lyme Syndrome and Central Sensitization
Batheja S, Nields JA, Landa A, Fallon BA.
The Journal of Neuropsychiatry and Clinical Neurosciences, online before print, 2013 Feb 27.
Central sensitization is a process that links a variety of chronic pain disorders that are characterized by hypersensitivity to noxious stimuli and pain in response to non-noxious stimuli.

Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia
Arseny A. Sokolov, MD, Reto Lienhard, MSc, Renaud Du Pasquier, MD, Véronique Erard, MD
Annals of Emergency Medicine, published online February 25, 2015.
This report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution.

The association between infectious burden and Parkinson’s disease: A case-control study.
Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, Jiao SS, Wang YR, Cao HY, Yi X, Liu CH, Deng B, Yao XQ, Xu ZQ, Zhou HD, Wang YJ.
Parkinsonism Related Disorders, pii: S353-800(5)0033-3. Online first, 05 May 30.
Higher infectious burden was found in PD patients. Individuals with higher infectious burden had higher alpha-synuclein levels in serum. Subjects with higher infectious burden had higher IL-1beta and IL-6 levels in serum. This study supports the role of infection in the etiology of PD.

A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients with Lyme Disease
Crowley JT, Drouin EE, Pianta A, Strle K, Wang Q, Costello CE, Steere AC.
Journal of Infectious Diseases, online first, 2015 May 26.
A subset of LA patients have high levels of apoB-100 in their joints and autoreactive T and B cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA.

Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection.
Kuchynka P, Palecek T, Havranek S, Vitkova I, Nemecek E, Trckova R, Berenová D, Krsek D, Podzimkova J, Fikrle M, Danek BA, Linhart A.
Herz. Online first, 2015 May 5.
Several recent small studies have suggested a causal link between Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent-onset DCM. The aim of this study was to further investigate the effect of targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort of patients.

Brainstem abnormalities and vestibular nerve enhancement in acute Neuroborreliosis
Nadja A Farshad-Amacker, Hans Scheffel, Thomas Frauenfelder and Hatem Alkadh
BMC Research Notes 2013, 6:551.
Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

Cerebrovascular Manifestations of Lyme Neuroborreliosis – A Systematic Review of Published Cases
Garkowski A, Zajkowska J, Zajkowska A, Kulakowska A, Zajkowska O, Kubas B, Jurgilewicz D, Hladunski M, Lebkowska U.
Frontiers in Neurology. 2017 Apr 20;8:146. eCollection 2017.
This study included 88 patients with a median age of 46 years. The median interval from onset of symptoms suggesting Lyme disease to first symptoms of cerebrovascular manifestations of LNB was 3.5 months. The most common cerebrovascular manifestation of LNB was ischemic stroke (76.1%), followed by TIA (11.4%). The posterior circulation was affected alone in 37.8% of patients, the anterior circulation in 24.4% of patients, and in 37.8% of cases, posterior and anterior circulations were affected simultaneously. The most common affected vessels were middle cerebral artery—in 19 cases, basilar artery—in 17 cases, and anterior cerebral artery—in 16 cases. A good response to antibiotic treatment was achieved in the vast number of patients (75.3%). The overall mortality rate was 4.7%. Cerebral vasculitis and stroke due to LNB should be considered, especially in patients who live in or have come from areas with high prevalence of tick-borne diseases, as well as in those without cardiovascular risk factors, but with
troke-like symptoms of unknown cause.

Complete AV block in Lyme carditis: an important differential diagnosis.
Semmler D, Blank R, Rupprecht HJ.
Clinical Research in Cardiology, published ahead of print on May 13, 2010.
We report on a 37-year old male, who was admitted to the emergency department because of dizziness and generalized tiredness. Physical examination and the initial laboratory values revealed no abnormalities. The patient’s electrocardiogram on admission revealed newly diagnosed bradycardia due to atrioventricular heart block. The ventricular heart rate was 35/min. The patient was admitted to the ICU. Lyme serology and Western blot were positive for Borrelia antibodies. After institution of antibiotic therapy with ceftriaxone, atrioventricular heart block resolved rapidly. We therefore have to assume that in this patient Lyme carditis was the cause of third-degree AV block.

Lyme disease presenting with facial palsy and myocarditis mimicking myocardial infarction
Gilson J, Khalighi K, Elmi F, Krishnamurthy M, Talebian A, Toor RS.
Journal of Community Hospital Internal Medicine Perspectives, 2017 Dec 14;7(6):363-365.
This is a rare case of Lyme myocarditis associated with markedly elevated Troponin I, normal left ventricle function, and an absence of conduction abnormalities. To the best of our knowledge, Lyme myocarditis mimicking acute coronary syndrome with such high levels of Troponin I and neurologic compromise has not been previously described. Lyme myocarditis may be a challenging diagnosis in endemic areas especially in patients with coronary artery disease risk factors, presenting with typical chest pain, EKG changes and positive cardiac biomarkers. Therefore, it should be considered a differential diagnosis in patients presenting with clinical symptoms suggestive of acute coronary syndrome.

Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life.
Back T, Grunig S, Winter Y, Bodechtel U, Guthke K, Khati D, von Kummer R.
Journal of Neurology, online before print, 2013 Jan 18.
Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis.

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview
Rhee H, Cameron DJ
International Journal of General Medicine, February 2012,
Volume 2012:5, pages 163-174.
The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection.

Cerebral vasculitis and intracranial multiple aneurysms in a child with Lyme neuroborreliosis
Kortela E, Hytönen J, Numminen J, Overmyer M, Saxen H, Oksi J.
JMM Case Reports. 2017 Apr 21;4(4):e005090.
We describe a paediatric patient with sensorineural auditory dysfunction, headache, fatigue and epileptic seizures as sequelae of meningoencephalitis/Lyme neuroborreliosis (LNB) caused by B. burgdo rferi. Brain magnetic resonance imaging revealed widespread enhancement of the leptomeninges, cranial nerves and artery walls compatible with vasculitis and disturbances in cerebrospinal fluid (CSF) circulation. The patient was treated with ceftriaxone for 2 weeks. Two years later, the patient had an ischemic stroke. Brain magnetic resonance angiography revealed multiple aneurysms, which were not present previously. The largest aneurysm was operated rapidly. The patient was treated with another course of intravenous ceftriaxone for 4 weeks and pulse therapy with corticosteroids. He recovered well. This unique case demonstrates complications of LNB that can result in serious morbidity or even mortality. Lumbar puncture and analysis should be considered for paediatric patients with epileptic seizures or cerebrovascular events living in a Lyme borreliosis endemic area.

Lyme disease presenting as multiple ischaemic strokes
Sui Li, Michal Vytopil, Kinan Hreib, Donald E Craven
Practical Neurology, 2015;15:284-288.
Central nervous system Lyme disease occasionally presents with ischaemic strokes; this case is unusual in showing vasculopathy on brain imaging, supporting meningovasculitis as the likely mechanism.

Postural orthostatic tachycardia syndrome following Lyme disease.
Khalil Kanjwal, Beverly Karabin, Yousuf Kanjwal, Blair P. Grubb
Cardiology Journal (formerly Folia Cardiologica), Vol. 18 No. 1, 2011
All of the patients in this report had suffered from LD in the past and were successfully treated with antibiotics. All patients were apparently well, until years later when they presented with fatigue, cognitive dysfunction and orthostatic intolerance. These patients were diagnosed with POTS on the basis of clinical features and results of the tilt table (HUTT) testing. In an appropriate clinical setting, evaluation for POTS in patients suffering from post LD syndrome may lead to early recognition and treatment, with subsequent improvement in symptoms of orthostatic intolerance.

A Tale of Two Syndromes: Lyme Disease Preceding Postural Orthostatic Tachycardia Syndrome.
Noyes AM, Kluger J.
Annals of Noninvasive Electrocardiology, online before print 2014 May 15.
The pathogenesis of postural orthostatic tachycardia syndrome (POTS) is poorly understood. However, it has been suggested that altered immune activity or denervation of the autonomic system following illness may be an important trigger. Patients infected with Lyme disease have a small incidence of post-Lyme disease syndrome that share similar characteristics to POTS.

Clinical association: Lyme disease and Guillain-Barre syndrome
Patel, Kinner et al.
The American Journal of Emergency Medicine, online first, July 6, 2017.
In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1 week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality.

Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager.
Ghatalia P, Porter J, Wroblewski D, Carlson JA.
Journal of Cutaneous Pathology, 2013 May;40(5):477-84.
Primary cutaneous marginal zone lymphoma (PCMZL) has rarely been reported in teenagers and is occasionally associated with Borrelia burgdorferi infection. Juxta-articular fibrotic nodules represent a unique, localized fibrosing response to spirochete infections, namely Borreliosis.

Lyme Disease Manifestations in the Foot and Ankle: A Retrospective Case Series
Miller JR, Dunn KW, Braccia D, Ciliberti LJ Jr, Becker DK, Hollinger JK, Brand SM.
Journal of Foot & Ankle Surgery, 2016 Nov – Dec; 55(6):1241-1244.
We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing.

Long-term intrathecal infusion of outer surface protein C from Borrelia burgdorferi causes axonal damage.
Tauber SC, Ribes S, Ebert S, Heinz T, Fingerle V, Bunkowski S, Kugelstadt D, Spreer A, Jahn O, Eiffert H, Nau R.
Journal of Neuropathology and Experimental Neurology. 2011 Sep;70(9):748-57.
Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of the central nervous system. In acute LNB and the rare chronic state of infection, patients can experience cognitive deficits such as attention and memory disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are released into the subarachnoid space. Continuous exposure to intrathecal B. burgdorferi OspC led to activation of microglia and axonal damage without demonstrable cognitive impairment in experimental mice. These results suggest that long-term intrathecal exposure to OspC resulted in axonal damage that may underlie the neurologic manifestations in chronic LNB.

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report
Tumminello R, Glaspey L, Bhamidipati A, Sheehan P, Patel S.
The Journal of Emergency Medicine online first, 2017 Oct 25.
We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease.

Lyme Disease and MS Can Overlap
Conference Coverage – Americas Committee for Treatment and Research in Multiple Sclerosis – ACTRIMS 2016
By Gale Scott, MD Magazine, Plainsboro, New Jersey February 19, 2016
Lyme Disease can cause neurological symptoms, some of which overlap with clinical and radiological findings in multiple sclerosis. Of the 90 patients, 7.8% were positive for Lyme.

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics
BO Frykholm
Medical Hypotheses, available online 6 March 2009.
Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Lyme neuroborreliosis and dementia
Blanc F, Philippi N, Cretin B, Kleitz C, Berly L, Jung B, Kremer S, Namer IJ, Sellal F, Jaulhac B, de Seze J.
Journal of Alzheimers Disease. 2014;41(4):1087-93.
Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years. Results: We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics.

Do Infections Cause Alzheimers Disease
By Lauren Ingeno, Drexel News Blog, Drexel University, Philadelphia, Pennsylvania, February 10, 2016
Do Infections Cause Alzheimer’s Disease?
A study from Drexel researchers offers new evidence to support a controversial hypothesis: Alzheimer’s disease results from the body’s inflammatory response to chronic infections. The scientists believe that bacteria create slimy, impenetrable biofilms in the brain, prompting the immune system to destroy surrounding tissue. This intriguing idea — though supported by a growing body of documentation — is still contested by many in the scientific community.

Alzheimer’s Disease: a novel hypothesis integrating spirochetes, biofilm, and the immune system
Herbert B. Allen, Diego Morales, Krister Jones, Suresh Joshi
Journal of Neuroinfectious Diseases 2016, 7:200.
In the light of recent studies showing the presence of spirochetes in the brains of Alzheimer’s disease (AD) patients, we have studied (post mortem) the hippocampus region in the brains of similarly affected AD patients utilizing both pathology and immunohistochemistry. Our findings demonstrate that the plaques, which are characteristically found in AD brains, reveal the presence of biofilms.

Do Microbes Trigger Alzheimer’s Disease? The once fringe idea is gaining traction among the scientific community.
By Jill U. Adams, The Scientist, Midland, Ontario, Canada
September 1, 2017
In late 2011, Drexel University dermatology professor Herbert Allen was astounded to read a new research paper documenting the presence of long, corkscrew-shape bacteria called spirochetes in postmortem brains of patients with Alzheimer’s disease. Combing data from published reports, the International Alzheimer Research Center’s Judith Miklossy and colleagues had found evidence of spirochetes in 451 of 495 Alzheimer’s brains. In 25 percent of cases, researchers had identified the spirochete as Borrelia burgdorferi, a causative agent of Lyme disease. Control brains did not contain the spirochetes.

A study on the association between infectious burden and Alzheimer’s disease.
Bu XL, Yao XQ, Jiao SS, Zeng F, Liu YH, Xiang Y, Liang CR, Wang QH, Wang X, Cao HY, Yi X, Deng B, Liu CH, Xu J, Zhang LL, Gao CY, Xu ZQ, Zhang M, Wang L, Tan XL, Xu X, Zhou HD, Wang YJ
European Journal of Neurology, online before print, 2014 Jun 9.
IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.

Growing list of eye problems in Lyme disease
Blog: All Things Lyme, by Daniel Cameron, MD, MPH, a nationally recognized leader for his expertise in the diagnosis and treatment of Lyme disease and other tick-borne illnesses.
October 23, 2016
Ophthalmic manifestations of tick-borne diseases are increasing in the United States, according to a review published recently in Current Opinion in Ophthalmology. And, “although ocular involvement can be self-limited, delays in diagnosis may result in vision impairment and even blindness,” stated Sathiamoorthi from the Mayo Clinic.

The eye and tick-borne disease in the United States
Sathiamoorthi S, Smith WM.
Current Opinion in Ophthalmology 2016 Nov;27(6):530-537.
Purpose of review Tick-borne diseases are increasing in incidence and geographic distribution. Several diseases endemic to the United States have ophthalmic manifestations, including the most common tick-borne disease, Lyme borreliosis. As ocular complaints may lead a patient to seek medical evaluation, it is important to be aware of the systemic and ophthalmic manifestations of tick-borne diseases in order to make the correct diagnosis. Recent findings Vision-threatening ophthalmic manifestations are relatively common in Lyme disease and Rocky Mountain spotted fever. Ocular involvement is rare in babesiosis, tick-borne relapsing fever, Powassan encephalitis, ehrlichiosis, anaplasmosis, and Colorado tick fever.There are clear guidelines for diagnosis and treatment of Lyme disease; however, confusion and misinformation among the general public as well as controversy about chronic or late-stage Lyme disease can impact the evaluation of ophthalmic disease. Furthermore, there are many gaps in our knowledge regarding the pathophysiology of ocular borreliosis although it seems likely that Lyme uveitis is rare in the United States.

Seroprevalence against Rickettsia and Borrelia Species in Patients with Uveitis: A Prospective Survey
Madsen KB, Wallménius K, Fridman Å, Påhlson C, Nilsson K.
Journal of Ophthalmology. 2017;2017:9247465. Online first, 2017 Nov 26.
The findings are indicative for an association between infection or exposure to Rickettsia spp. and uveitis with a seropositivity among patients with recurrent uveitis in concordance with the spread of rickettsial exposure in a tick-exposed population.

Isolated trochlear palsy secondary to Lyme neuroborreliosis
Bababeygy SR, Quiros PA.
International Ophthalmology, online before print, December 20, 2011.
The objective of the study is to report the first case of isolated trochlear palsy secondary to Lyme neuroborreliosis in an adult. A 22-year-old male presented with history of flu-like illness and headache, accompanied by vertical binocular diplopia, worse on downgaze and better in upgaze and right head tilt. Physical examination revealed trochlear palsy on the left side with a compensatory head tilt to the opposite side. Immunoglobulin (Ig)M and IgG antibodies against Borrelia burgdorferi were positive in serum and cerebral spinal fluid (CSF). Symptoms of double vision completely resolved after 3 weeks of antibiotic treatment with intravenous ceftriaxone.

Bacterial tick-borne diseases caused by Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, and Rickettsia spp. among patients with cataract surgery.
Chmielewski T, Brydak-Godowska J, Fiecek B, Rorot U, Sedrowicz E, Werenowska M, Kopacz D, Hevelke A, Michniewicz M, Kecik D, Tylewska-Wierzbanowska S.
Medical Science Monitor. 2014 Jun 5;20:927-31.
Presence of DNA of yet uncultured and undescribed species of Bartonella in eye liquid indicates past infection with this pathogen. Specific antibodies to B. burgdorferi sensu lato and Bartonella sp. are detected more frequently in patients with cataract compared to the control group. This could indicate a possible role of these organisms in the pathological processes within the eyeball, leading to changes in the lens. Further studies are needed to identify Bartonella species, as well as to recognize the infectious mechanisms involved in cataract development.

Lyme neuroborreliosis: a treatable cause of acute ocular motor disturbances in children
M H Correll, N Datta, H S S Arvidsson, H A Melsom, A K Thielberg, M Bjerager, M C Brodsky, J P Saunte
British Journal of Ophthalmology, online first, April 13, 2015.
LNB can present as acute ocular motor disorders in conjunction with fatigue and other clinical manifestations. In endemic areas, children with unexplained, acquired ocular motor abnormalities should be evaluated for LNB, a treatable medical condition.

Lyme disease: sudden hearing loss as the sole presentation.
Espiney Amaro C, Montalvão P, Huins C, Saraiva J.
The Journal of Laryngology & Otology, online before print, 2015 Jan 26.
In this report, a very unusual presentation of this condition is described, in which sudden onset sensorineural hearing loss was the sole presenting symptom.

Lyme Disease Associated With Sudden Sensorineural Hearing Loss: Case Report and Literature Review.
Peeters N, van der Kolk BY, Thijsen SF, Colnot DR.
Otology and Neurotology, online bofore print, 2013 Jan 7.
Literature suggests that sudden sensorineural hearing loss may coincide with Borrelia burgdorferi infection. A higher incidence of confirmed positive serology for Borrelia burgdorferi in patients with sudden deafness seems to be depending on the country and on the tests used to confirm Lyme disease. This should be taken into account if serologic testing for Lyme disease in patients with sudden deafness is considered.

Hyperosmia in Lyme disease
Puri BK, Monro JA, Julu PO, Kingston MC, Shah M.
Arquivos de Neuro-Psiquiatria. 2014 Aug;72(8):596-7.
Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied.

Pediatric otolaryngological manifestations of systemic diseases
Pignataro L, Torretta S, Capaccio P, Esposito S, Marchisio P.
International Journal of Pediatric Otorhinolaryngology, Vol 73, Supplement 1, December 2009, Pages S33-S37.
Systemic bacterial and fungal infections may sometimes present local manifestations within otolaryngological district whose early detection may be useful in establishing a correct diagnosis and more appropriate treatment. This paper reviews certain systemic bacterial and fungal diseases presenting ENT manifestations in the pediatric population from an otolaryngological perspective.

Exacerbation of chronic pain after dental extractions in a patient with post-treatment Lyme disease syndrome
Lim S, Kinjo S.
Saudi Journal of Anesthesia 2018;12:112-4.
A subset of patients who had Lyme disease experience postinfectious signs or symptoms called post-treatment Lyme disease syndrome (PTLDS). PTLDS is a chronic condition including pain in joints and muscles, neurological symptoms including demyelinating diseases, peripheral neuropathy, headaches, sleep disturbances, fatigue, and cardiac conditions. We report a case of difficult acute pain management in a patient with PTLDS who underwent dental extractions and required admission to an intensive care unit for pain control.

Unilateral phrenic nerve lesion in Lyme neuroborreliosis.
Djukic M, Larsen J, Lingor P, Nau R.
BMC Pulmonary Medicine. 2013 Jan 18;13:4.
Among a variety of more common differential diagnoses, the aetiology of acute respiratory failure includes Lyme neuroborreliosis. Diaphragmatic weakness should be considered in the differential workup because of its potentially treatable nature.

Urinary bladder detrusor dysfunction symptoms in lyme disease.
Puri BK, Shah M, Julu PO, Kingston MC, Monro JA.
International Neurourology Journal, 2013 Sep;17(3):127-9.
This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

Dysarthria and thrombocytopenia after tick bite
Muhammad A. Mir
Blood, Oct 2013; 122: 2538.
A 63-year-old woman presented with fever, confusion, dysarthria (slurred speech), new-onset thrombocytopenia and mild transaminitis 2 weeks after a tick bite to the left thigh.

Pancytopenia in Lyme disease
Raman Mehrzad, Joseph Bravoco
British Medical Journal Case Reports, online March 4, 2014
We present a 49-year-old man with subacute onset of fever, weakness, shortness of breath, unilateral lower extremity oedema and pancytopenia who was found to have positive serology for Lyme disease. The patient presented with an intravascular haemolytic pattern on laboratory findings where an extensive infectious disease and haematological workup ruled out ehrlichiosis, anaplasmosis, babesiosis, Rocky Mountain spotted fever, HIV, hepatitis B and other parasitic infections. This left a very atypical presentation of Lyme disease.

A Cluster of Startling Lyme Disease Cases in the Upper Midwest
Press Release: The American Council on Science and Health
By Julianna LeMieux, Washington, DC
January 26, 2018
Rarely, Lyme disease manifests as a neuroinvasive condition called Garin-Bujadoux-Bannwarth syndrome or, more frequently, just Bannwarth syndrome. This complicated version of Lyme Disease is characterized by a few telltale signs. They are, painful meningoradiculoneuritis (inflammation of one or more roots of the spinal nerve) that leads to motor weakness, facial nerve palsy and neuropathy usually in the hands and feet. The other is lymphocytic pleocytosis (an abnormally large number of lymphocytes) in the cerebrospinal fluid (CSF). Because it is not a reportable disease, it is not well understood how much of the disease is popping up across the country. That said, five cases in the same few weeks seemed strange enough for these authors to report it.

Case Report: Bilateral diaphragmatic dysfunction due to Borrelia Burgdorferi.
Basunaid S, van der Grinten C, Cobben N, Otte A, Sprooten R, Gernot R.
F1000Research. 2014 Oct 6;3:235. eCollection 2014.
Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis.

A case of CNS Lyme disease presenting with multiple cranial neuropathies and mimicking a B cell lymphoma
Christopher Perrone, Denise Xu, Taneeta Ganguly, Donna Kurowski, Michael Mullen and Amy Pruitt
Neurology, April 18, 2017, 88:16 Supplement P1.312.
Abstracts: American Academy of Neurology, 69th Annual Meeting, Boston.
This case highlights how Lyme disease should be considered in the differential diagnosis for multiple cranial neuropathies. Further, as prior case reports of CNS Lyme patients have shown polyclonal and monoclonal lymphocyte expansion, this case demonstrates the diagnostic uncertainty regarding whether flow cytometry reflects a reactive process to infection or a new lymphoma. Treatment with antibiotics and clinical improvement helped to clarify the etiology in this case.

Ticks and salt: an atypical case of neuroborreliosis
Siddiqui N, St Peter DM, Marur S.
Journal of Community Hospital Internal Medicine Perspectives, 7(6):358-362.
It is well documented that central nervous system (CNS) infections may lead to syndrome of inappropriate anti-diuretic hormone secretion (SIADH), but diagnosing these can prove difficult in patients with atypical presentations. Our case demonstrates the need to screen for Lyme disease in endemic areas in patients presenting with neurologic symptoms and SIADH.

American neuroborreliosis presenting as cranial polyneuritis and radiculoneuritis
Erwin Wang, Prasad R. Shirvalkar, Carolina B. Maciel, Alexander E. Merkler, Joseph Safdieh, and Ajay Gupta
Neurology: Neuroimmunology & Neuroinflammation, online before print, October 1, 2014.
While facial nerve involvement represents about 80% of cranial neuritis in Lyme neuroborreliosis (LNB), other cranial nerves may also be individually involved.

Borrelia infection and risk of celiac disease
Alaedini A, Lebwohl B, Wormser GP, Green PH, Ludvigsson JF.
BMC Medicine, 2017 Sep 15;15(1):169.
Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

Septolobular Panniculitis in Disseminated Lyme Borreliosis
Dittmer M, Willis M, Selby J, Liu V.
Journal of Cutaneous Pathology, online first, 2018 Jan 2.
A rare cutaneous manifestation that is increasingly reported in Lyme patients is panniculitis, which develops after dissemination of the spirochete. We present such a case in a patient who was initially treated for cellulitis as well as neck and radicular leg pain, thereby expanding the cutaneous spectrum of Lyme disease.

Disseminated Lyme Disease Presenting With Nonsexual Acute Genital Ulcers
Finch JJ, Wald J, Ferenczi K, Khalid S, Murphy M.
JAMA Dermatology. Online before print, 2014 Aug 27.
Importance Nonsexual acute genital ulceration (NAGU) is a rare vulvar skin condition typically affecting girls and young women, characterized by acute onset of singular or multiple painful vaginal ulcers. The etiology of this ulcerative dermatosis has not been identified, although it has been associated with systemic infections. To our knowledge, this is the first report of an association with Lyme disease.

Lobular panniculitis due to Borrelia burgdorferi infection mimicking subcutaneous panniculitis-like T-cell lymphoma.
Kempf W, Kazakov DV, Kutzner H.
The American Journal of Dermatopathology. 2013 Apr;35(2):e30-3.
The authors present an unusual case of lobular panniculitis caused by Borrelia burgdorferi senso latu infection in a 56-year-old man.

Exploring the Association Between Morgellons Disease and Lyme Disease.Identification of Borrelia Burgdorferi in Morgellons Disease Patients
Marianne J Middelveen, Cheryl Bandoski, Jennie Burke, Eva Sapi, Katherine R Filush, Yean Wang, Agustin Franco, Peter J Mayne, Raphael B Stricker
BMC Dermatology, 2015;15(1).
Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.

Disseminated Lyme borreliosis preceded by hepatitis in an African American male.
Fathi R, Huang WW, Brown K.
Dermatology Online Journal. 2012 Oct 15;18(10):4.
Lyme disease is the most common tick-borne disease in the United States and has a multitude of systemic effects. Infrequently, however, Lyme disease is seen to cause liver dysfunction. Dermatologists should be aware that early, disseminated borreliosis can present with multiple erythema migrans plaques and hepatitis.

Babesiosis Presenting as Acute Liver Failure
Nassar Y, Richter S.
Case Reports in Gastroenterology. 2017 Dec 18;11(3):769-773. eCollection 2017 Sep-Dec.
Babesiosis is a zoonotic, tick-borne infection caused by the protozoan Babesia. It is transmitted by the Ixodes ticks which transmit the infection to humans. Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum are species that have been identified as being infectious to humans worldwide. The most common species causing infection to humans is B. microti which is endemic to the Northeast and Midwestern United States with most infections occurring between the months of May and October. We report a case of an elderly man with acute liver failure due to an infection with B. microti.

A New Perspective on the Possible Cause of Alzheimer’s Disease: Microbes
Press Release: Journal of Alzheimer’s Disease
15 March 2016
A landmark Editorial issued by 33 senior scientists and clinicians from a dozen countries across the world has been published in the highly regarded peer-reviewed journal, Journal of Alzheimer’s Disease. This major call for action is based on substantial evidence indicating that some microbes – a specific virus and particular bacteria – are likely major causes of the disease. Almost all research in the field has focused on alternative hypotheses – over 400 clinical trials of such anti-Alzheimer agents have been carried out, but all have failed.

Aggressiveness, violence, homicidality, homicide, and Lyme disease
Bransfield RC.
Neuropsychiatric Disease and Treatment, 2018 Mar 9;14:693-713.
No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD). LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

Obsessive-compulsive symptoms in adults with Lyme disease
Johnco C, Kugler BB, Murphy TK, Storch EA.
General Hospital Psychiatry. 2018 Jan 31;51:85-89.
OCS were common, with 84% endorsing clinically significant symptoms, 26% of which endorsed symptoms onset during the six months following their Lyme disease diagnosis. This study highlights the common co-occurrence of OCS in patients with Lyme disease. It is unclear whether OCS are due to the direct physiological effects of Lyme disease or associated immunologic response, a psychological response to illness, a functional somatic syndrome, or some combination of these.

Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?
Mattingley DW, Koola MM.
Indian Journal of Psychological Medicine. 2015 Apr-Jun;37(2):243-6.
Lyme disease has been reported to be associated with various psychiatric presentations. Borrelia burgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations.

Chronic Lyme Disease Linked to ADHD in Adults
By Megan Brooks, Medscape Medical News
“The association between ADHD and CLD has not been identified previously,” principal investigator Joel L. Young, MD, medical director, Rochester Center for Behavioral Medicine, Rochester, Minnesota, told Medscape Medical News. The survey results also corroborate earlier findings of a relationship between CLD and anxiety and depression, he said.

Perineuritis in acute lyme neuroborreliosis
Marwa Elamin, Yazan Alderazi, Gerard Mullins, Michael A. Farrell, Sue O’Connell, Timothy J. Counihan
Muscle & Nerve, Volume 39, Issue 6, Pages 851 – 854. Published Online: 13 May 2009
Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis.

Inflammation in the Pathogenesis of Lyme Neuroborreliosis
Geeta Ramesh, Peter J. Didier, John D. England, Lenay Santana-Gould, Lara A Doyle-Meyers, Dale S. Martin, Mary B. Jacobs, and Mario T. Philipp
American Journal of Pathology, Online first, April 16, 2015.
Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis.

Acute transverse myelitis in Lyme neuroborreliosis
Bigi S, Aebi C, Nauer C, Bigler S, Steinlin M.
Infection, online before print, May 27, 2010.
Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosis.

Diastolic heart murmur, nocturnal back pain, and lumbar rigidity in a 7-year girl: an unusual manifestation of lyme disease in childhood.
Kameda G, Vieker S, Hartmann J, Niehues T, Langler A.
Case Reports in Pediatrics. 2012(2012):976961. Published online 2012 Sep 29.
A 7-year-old girl presented with nocturnal pain in her back and legs. The physical examination revealed a loud opening sound of the mitral valve and lumbar rigidity. With the exception of significantly increased anti-nuclear antibody (ANA) levels, the immunological findings did not show any other abnormal parameters, also spinal magnetic resonance imaging (MRI) and ultrasound examination of the abdomen and pelvis yield no pathological findings.

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain.
Ramesh G, Maclean AG, Philipp MT.
Mediators of Inflammation, vol. 2013, Article ID 480739, 20 pages, 2013.
This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.

Neuroborreliosis Mimicking Leptomeningeal Carcinomatosis in a Patient With Breast Cancer: A Case Report
Stefanie Fischer, Johannes Weber, Isabelle Senn-Schonenberger, Thomas Cerny, and Thomas Hundsberger
Journal of Investigative Medicine High Impact Case Reports January 2014 2: 2324709614529417
Online before print, March 28, 2014.
Leptomeningeal carcinomatosis is a serious complication of advanced cancer. Various clinical manifestations may present, such as headache, nausea, seizures, cranial neuropathies. In this article, we report the case of a 65-year-old woman with metastatic breast cancer who was admitted to hospital suffering from facial palsy, which was suspected to be caused by leptomeningeal tumor infiltration. Assessment of cerebrospinal fluid found no malignant cells but investigation for infectious diseases established the diagnosis of neuroborreliosis. Antibiotic treatment with doxycycline was performed. After completion of treatment, follow-up MRI scans found complete regression of meningeal enhancement. Hence, initial diagnosis of leptomeningeal carcinomatosis was rejected. This case report should alert oncologists to carefully rule out infectious diseases before leptomeningeal carcinomatosis is diagnosed.

Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease
Middelveen MJ, Stricker RB
Clinical, Cosmetic and Investigational Dermatology 2011, 4:167-17.
Morgellons disease is an emerging human dermopathy characterized by the presence of filamentous fibers of undetermined composition, both in lesions and subdermally. While the etiology of Morgellons disease is unknown, there is serological and clinical evidence linking this phenomenon to Lyme borreliosis and coinfecting tick-borne agents.

Babesiosis-associated immune thrombocytopenia
Narurkar R, Mamorska-Dyga A, Agarwal A, Nelson JC, Liu D.
Stem Cell Investigation, 2017 Jan 17;4:1. eCollection 2017.
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP).

Neutropenia in Congenital and Adult Babesiosis
Wormser GP, Villafuerte P, Nolan SM, Wang G, Lerner RG, Saetre KL, Maria MH, Branda JA.
American Journal of Clinical Pathology. 2015 Jul;144(1):94-6.
Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia.

Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection. Severe human monocytic ehrlichiosis presenting with altered mental status and seizures
Geier C, Davis J, Siegel M.
BMJ Case Reports 2016 Oct 6;2016. pii: bcr2016215967.
A previously healthy 66-year-old woman living in the Mid-Atlantic USA presented to the hospital with lethargy, ataxia and slurred speech. 2 weeks prior she had removed a tick from her right groin. She reported malaise, fevers, diarrhoea, cough and a rash.

Babesiosis-Induced Acute Kidney Injury With Prominent Urinary Macrophages.
Luciano RL, Moeckel G, Palmer M, Perazella MA.
American Journey of Kidney Diseases, online before print, 2013 May 2, pii: S0272-6386(13)00674-4.
We present a case of severe babesiosis complicated by dialysis-requiring AKI with the unique finding of large macrophages containing engulfed erythrocyte fragments in urine sediment. This urinary finding raised the possibility of another diagnosis distinct from acute tubular injury.

Is Localized Scleroderma Caused by Borrelia burgdorferi?
Zinchuk AN, Kalyuzhna LD, Pasichna IA.
Vector-Borne and Zoonotic Diseases, online first, 2016 Jul 7.
Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi—the agent of Lyme disease—is suggested to be one of the possible etiological factors of localized scleroderma. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p? <?0.01).

Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma “en coup de sabre” with CNS tumor.
Bergler-Czop B, Lis-Swiety A, Brzezinska-Wcislo L.
BioMed Central Neurology 2009, 9:39
Published: 27 July 2009
We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an “en coup de sabre” scleroderma and with CNS tumor.
CONCLUSION: We described typical cases of a rare diseases, hemifacial atrophy and “en coup de sabre” scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor.

State: Tick bite can be deadly
By Cynthia McCormick, Cape Cod Times, Hyannis, Massachusetts
December 22, 2013
Public health officials report that at least 10 people in Massachusetts died last year after contracting diseases carried by the freckle-sized tick. One was a young adult who, as reported last week by the Centers for Disease Control and Prevention, collapsed in November 2012 after suffering a rare cardiac event known as Lyme carditis.

New insights into Lyme disease
Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH.
Redox Biology, 5:66-70. Online first, 2015 Mar 16.
– Positivity of Borrelia burgdorferi infection was assessed by a Lyme ELISPOT assay.
– Assessed levels of mitochondrial superoxide and cytosolic calcium in patient PBMCs.
– Lyme borreliosis patients showed a marked increase in mitochondrial superoxide.
– Levels of cytosolic calcium were significantly lower in Lyme borreliosis patients.
– Suggesting that Lyme borreliosis may lead to a state of mitochondrial dysfunction

Acute Babesiosis in Pregnancy: A Novel Imitator of Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome
Gulersen M, Brost BC, Bobrovnikov V, Bornstein E.
Obstetrics & Gynecology, 2016 Jul;128(1):197-200.
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious complication of pregnancy associated with significant maternal and fetal morbidity and mortality.

Babesiosis-associated immune thrombocytopenia
Narurkar R, Mamorska-Dyga A, Agarwal A, Nelson JC, Liu D.
Stem Cell Investigation, 2017 Jan 17;4:1. eCollection 2017.
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP).

Atraumatic splenic rupture from Babesia: A disease of the otherwise healthy patient
F.R. Farber, A. Muehlenbachs, T.E. Robey
Ticks and Tick-borne Diseases, Volume 6, Issue 5, July 2015, Pages 649-652.
We describe a case of spontaneous splenic rupture in an otherwise healthy woman that required emergent splenectomy. Recent case reports suggest that splenic rupture occurs in people without known risk factors for severe babesiosis. Physicians should be aware of this acute presentation in otherwise healthy individuals.

Neurological manifestations of human babesiosis.
Usmani-Brown S, Halperin JJ, Krause PJ.
Handbook of Clinical Neurology, 2013;114:199-203.
Babesiosis is a worldwide emerging infectious disease caused by intraerythrocytic protozoa that are transmitted by Ixodid ticks, or less commonly through blood transfusion or transplacentally. Although headache and lethargy are common symptoms, babesiosis is uncommonly associated with specific neurological dysfunction in humans. Decreased level of consciousness or coma are rare complications that are associated with severe and often fatal disease but the pathogenesis is unclear.

Autoimmune hemolytic anemia associated with babesiosis
Narurkar R, Mamorska-Dyga A, Nelson JC, Liu D.
Biomarker Research, 2017 Apr 8;5:14. eCollection 2017.
Babesia infection is commonly associated with anemia, thrombocytopenia, hyponatremia and elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused by parasitic and viral infections but has not been well characterized.

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias: A case report.
Mozayeni BR, et al.
Medicine (Baltimore). 2018.
Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp. To facilitate early and directed medical interventions, systemic bartonellosis should potentially be considered as a differential diagnosis in patients with incalcitrant rheumatological symptoms and frequent arthropod exposures or extensive animal contact.

Bartonella henselae osteoarthritis of the upper cervical spine in a 14-year-old boy.
Mirouse G, Journe A, Casabianca L, Moreau PE, Pannier S, Glorion C.
Orthopaedics & Traumatology: Surgery & Research. pii: S1877-0568(15)00092-4. Online first, 2015 Apr 13.
We report a case of Bartonella henselae, an agent of cat scratch disease, C1-C2 osteoarthritis with osteolysis of the lateral mass of C2 in a 14-year-old boy. Oral antibiotics did not successfully treat the infection and surgery was necessary to treat the septic arthritis. The case opens discussion about bacterial osteoarthritis of the cervical spine and bone involvement in disseminated bartonellosis.

Ophthalmic manifestations of bartonella infection
Amer R, Tugal-Tutkun I.
Current Opinion in Ophthalmology. 2017 Nov;28(6):607-612.
The eye is commonly affected in disseminated cat scratch disease (CSD) caused by Bartonella species. This article reviews recently published data on epidemiology of CSD, clinical features of ocular involvement, diagnosis and treatment.

Onset of cutaneous vasculitis and exacerbation of IgA nephropathy after Bartonella henselae infection
E. Cozzani, E. Cinotti, P. Ameri, A. Sofia, G. Murialdo and A. Parodi
Clinical and Experimental Dermatology, online before print October 10, 2011.
Bartonella henselae is the aetiological agent of cat-scratch disease. Recently, there have been reports of other conditions associated with this bacterium, including leucocytoclastic vasculitis, thrombocytopenic purpura, maculopapular and urticarial eruptions, granuloma annulare, erythema nodosum, erythema marginatum and erythema annulare.

A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease
Nakamura C, Inaba Y, Tsukahara K, Mochizuki M, Sawanobori E, Nakazawa Y, Aoyama K.
Brain and Development, online first 2017 Sep 18.
Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown.

Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report
Sophie Edouard, Khira Gonin, Yves Turc, Emmanouil Angelakis, Cristina Socolovschi and Didier Raoult
Journal of Medical Case Reports 2011, 5:108 Published: 19 March 2011.
Francisella tularensis DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia. This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by F. tularensis.

Rhabdomyolysis-induced Acute Kidney Injury Secondary to Anaplasma phagocytophilum and Concomitant Statin Use
Stephen R. Talsness, BA; Sanjay K. Shukla, PhD; Joseph J. Mazza, MD; Steven H. Yale, MD
Wisconsin Medical Journal, Volume 110, Issue 2 (April 2011), pp. 82-84.
We report the case of a patient with rhabdomyolysis-induced acute renal failure occurring in the setting of Anaplasma phagocytophilum infection based on the presence of morulae in neutrophils and concomitant statin use. Although the pathogenesis is unknown, we believe the combination of concurrent statin use in the setting of the infection promoted this complication.

Multiorgan Involvement Confounding the Diagnosis of Bartonella henselae Infective Endocarditis in Children With Congenital Heart Disease
Ouellette CP, Joshi S, Texter K, Jaggi P.
Pediatric Infectious Disease Journal. 2017 May;36(5):516-520.
These 2 cases highlight the potential multiorgan involvement that may confound the diagnosis of culture-negative infective endocarditis caused by B. henselae.

Meningitis Due to a Bartonella washoensis-like Human Pathogen
Will Probert, Janice K. Louie, James R. Tucker, Rose Longoria, Robin Hogue, Silvia Moler, Margot Graves, Heather J. Palmer, Joseph Cassady, and Curtis L. Fritz
Journal of Clinical Microbiology, published online ahead of print on 13 May 2009.
We report the second human case of infection caused by an organism identified as the proposed Bartonella species, B. washoensis. The organism was isolated from the blood of a patient presenting with meningitis and early sepsis. Oropsylla montana fleas were implicated as the vector for disease transmission in this case.

Clinical Presentation and Outcomes of Children With Human Granulocytic Anaplasmosis
Schotthoefer AM, Hall MC, Vittala S, Bajwa R, Frost HM.
Journal of the Pediatric Infectious Diseases Society, online first 2017 May 16.
Of 187 children identified with possible HGA, 17 (9%) had confirmed, 75 (40%) had probable, and 91 (49%) had suspected infections. The number of cases rose sharply in 2010 and has remained between 16 and 36 cases per year since that time. A minority of children with confirmed or probable infections had elevated liver transaminase levels (33%), leukopenia (24%), thrombocytopenia (17%), or anemia (8%); 6 (7%) of these children required hospitalization. Children with evidence of concurrent HGA and Lyme disease (27% of confirmed or probable cases) had a higher risk of hospitalization (odds ratio, 6.55 [95% confidence interval, 1.11–38.78]). None of these children had life-threatening disease or died.

Severe Human Granulocytic Anaplasmosis With Significantly Elevated Ferritin Levels in an Immunocompetent Host
Camacci ML, Panganiban RP, Pattison Z, Haghayeghi K, Daly A, Ojevwe C, Munyon RJ.
Journal of Investigative Medicine High Impact Case Reports, published online 2018 Feb 13.
Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum that generally presents with nonspecific symptoms such as fever, chills, headache, malaise, and myalgia. If not treated immediately, HGA can cause hemophagocytic lymphohistiocytosis (HLH), a well-documented but underrecognized sequela of severe HGA. Our case shows the challenges in the timely diagnosis of HGA and highlights the role of serum ferritin in aiding this diagnosis. Although our patient did not fulfill the HLH diagnostic criteria, our report demonstrates the importance of recognizing HGA as a reversible cause of HLH.

Tick Bite Alopecia (hair loss/bladness): A Report and Review
Lynch MC, Milchak MA, Parnes H, Ioffreda MD.
The American Journal of Dermatopathology. 2016 Nov;38(11):e150-e153.
Tick bites can cause a number of local inflammatory reactions, which are often difficult to differentiate from those induced by other arthropod bites or stings. These include erythematous nodular or pustular lesions, erosive plaques, annular lesions of erythema chronicum migrans, and both scarring and nonscarring inflammatory alopecia.

Association between Borrelia burgdorferi antibodies and amyotrophic lateral sclerosis in a case-control study.
Visser AE, Verduyn Lunel FM, Veldink JH, van den Berg LH.
European Journal of Neurology. 2017 Jan;24(1):227-230.
Previous studies, mostly case reports and uncontrolled studies, provide a low level of evidence for the hypothesized link between Lyme disease and amyotrophic lateral sclerosis (ALS). No difference in seroprevalence of Borrelia was found between patients (4.1%) and controls (5.9%). Clinical characteristics and survival were similar between seropositive and seronegative patients.

The Lyme disease pathogen Borrelia burgdorferi infects murine bone and induces trabecular bone loss
Tang TT, Zhang L, Bansal A, Grynpas M, Moriarty TJ.
Infection and Immunity, online first, 2016 Dec 12.
Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice.
Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice, and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Notes from the field: update on lyme carditis, groups at high risk, and frequency of associated sudden cardiac death – United States.
Forrester JD, Meiman J, Mullins J, Nelson R, Ertel SH, Cartter M, Brown CM, Lijewski V, Schiffman E, Neitzel D, Daly ER, Mathewson AA, Howe W, Lowe LA, Kratz NR, Semple S, Backenson PB, White JL, Kurpiel PM, Rockwell R, Waller K, Johnson DH, Steward C, Batten B, Blau D, DeLeon-Carnes M, Drew C, Muehlenbachs A, Ritter J, Sanders J, Zaki SR, Molins C, Schriefer M, Perea A, Kugeler K, Nelson C, Hinckley A, Mead P.
Morbidity and Mortality Weekly Report (MMWR). 2014 Oct 31;63(43):982-3.
Of cases with this information available, 69% were diagnosed during the months of June–August, and 42% patients had an accompanying erythema migrans, a characteristic rash. Relative to patients aged 55–59 years, carditis was more common among men aged 20–39 years, women aged 25–29 years, and persons aged =75 years.

Cardiac Tropism of Borrelia burgdorferi
Muehlenbachs, Atis et al.
The American Journal of Pathology, online first March 8, 2016.
Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

Presence of Borrelia burgdorferi sensu lato antibodies in the serum of patients with abdominal aortic aneurysms
European Journal of Clinical Microbiology & Infectious
Diseases, Vol. 31, No. 5 (2012), 781-789.
Our findings suggest a relationship between AAAs and B. burgdorferi sl. We hypothesize that the underlying mechanism for B. burgdorferi sl in AAA formation is similar to that by the spirochete Treponema pallidum; alternatively, AAAs could develop due to induced autoimmunity via molecular mimicry due to similarities between some of the B. burgdorferi sl proteins and aortic proteins.

Infections and cardiovascular disease: is Bartonella henselae contributing to this matter?
Salvatore P, Zullo A, Sommese L, Colicchio R, Picascia A, Schiano C, Mancini FP, Napoli C.
Journal of Medical Microbiology, pii: jmm.0.000099. Online first, 2015 Jun 11.
In this review, we summarize the rationale to suggest that Bartonella henselae could favor atherogenesis by infecting and damaging endothelial progenitor cells, thus reducing their vascular repair potential. These mechanisms suggest a novel link between communicable and non-communicable human diseases, and put forward the possibility that Bartonella henselae could enhance the susceptibility and worsen the prognosis in cardiovascular disease.

Parry-Romberg syndrome: a case with a possible association with Lyme disease
di Meo N, Stinco G, Nan K, Pinzani C, Trevisan G.
Acta Dermatovenerologica Alpina Pannonica et Adriatica 2015 Dec;24(4):77-9.
Parry–Romberg syndrome is an acquired slowly progressive disease characterized by an atrophy mostly involving half of the face. The pathogenesis of this disfiguring condition is still controversial. The relationship between Parry–Romberg syndrome and Lyme disease needs to be considered in depth. We cannot exclude a coincidence, however, of the bacteriological and serological evidence. Moreover, the interruption of the disease progression after the antibiotic therapy is difficult to ignore without claiming that this association is at least suggestive.

Evaluating the Child with Acute Hip Pain (“Irritable Hip”) in a Lyme Endemic Region
Richard G. Bachur, Cynthia M. Adams, Michael C. Monuteaux
The Journal of Pediatrics, online before print, October 25, 2014.
Lyme infection occurred in approximately 5% of children with acute, nontraumatic hip pain who were evaluated in a pediatric emergency department in a Lyme endemic region.

Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study
Tiveron MG, Pomerantzeff PMA, de Lourdes Higuchi M, Reis MM, de Jesus Pereira J, Kawakami JT, Ikegami RN, de Almeida Brandao CM, Jatene FB.
BMC Infectious Diseases. 2017 Apr 21;17(1):297.
The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with myxomatous mitral valve degeneration. Despite of low percentage of Borrelia burgdorferi in MD group, this agent was correlated with myxomatous degeneration and this may occour due synergistic actions between these infectious agents likely contribute to collagen degradation.

Emerging Cases of Powassan Virus Encephalitis in New England: Clinical Presentation, Imaging, and Review of the Literature.
Piantadosi A, Rubin DB, McQuillen DP, Hsu L, Lederer PA, Ashbaugh CD, Duffalo C, Duncan R, Thon J, Bhattacharyya S, Basgoz N, Feske SK, Lyons JL.
Clinical Infectious Diseases, online first, 2015 Dec 13.
Background. Powassan virus is a rarely diagnosed cause of encephalitis in the United States. In the Northeast, it is transmitted by Ixodes scapularis, the same vector that transmits the causative agent of Lyme disease, and the prevalence of Powassan virus among animal hosts and vectors has been increasing. Here we present eight cases of Powassan virus encephalitis from Massachusetts and New Hampshire in 2013-2015.

Multiorgan failure related to human monocytic ehrlichiosis.
Yachoui R.
BMJ Case Reports. 2013May 22;2013. pii: bcr2013008716.
Human monocytic ehrlichiosis (HME) is a tick-born disease that presents predominantly as a mild to moderate acute illness. Severe life-threatening disease has been reported with a case death rate of approximately 3%, often in immunosuppressed persons. A delay in therapy initiation has been proven to increase the morbidity of the disease.

First reported case of Ehrlichia ewingii involving human bone marrow
Allen MB, Pritt BS, Sloan LM, Paddock CD, Musham CK, Ramos JM, Cetin N, Rosenbaum ER.
Journal of Clinical Microbiology. 2014 Nov;52(11):4102-4.
A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

Ticks Can Spread Allergy to Red Meat
Blog: D-brief, A Blog About Energy and the Environment
Written by: Lisa Raffensperger, Discover Magazine, Kalmbach
Publishing Coompany, Waukesha, Wisconsin
We’re in the thick of tick season, and that tends to trigger mental associations with Lyme disease. But as the arachnids emerge this year, attention is also being paid to a rare allergy that ticks may be spreading, and it’s a carnivore’s worst nightmare: itchy hives every time you eat red meat.

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Priorities for Lyme Disease Research
Written by Sherrill Franklin, Focus – Opinions and Features item from, Chico, California
Almost 40 years have passed since the Lyme disease bacterium was identified, yet there are still no reliable diagnostics and no definitive treatments, especially for those with persistent symptoms. While Lyme disease research funding has always languished somewhere between hay fever and headaches, CDC/NIH grant money did add up to over $450 million between 1998 and 2016. Over 18 years, that’s about $25 million annually.

Lyme Disease: A Bioethical Morass
Neha Jariwala, Erum Ilyas and Herbert B Allen
Journal of Clinical Research & Bioethics, online first October 24, 2016.
“Primum non nocere”, “first do no harm” is a medical dictum based in antiquity. Yet, in nearly everything related to Lyme disease, it seems almost entirely disregarded. How ethical is it that we follow the guidelines of the CDC regarding diagnosis when those guidelines require erythema migrans that is clearly recognizable only in one (“bullseye rash”) of its multiple presentations? Further, how ethical is it that we are held to guidelines regarding a positive serology that is positive (at best) only 40% of the time? Another questionable ethical situation is the use of a bacteriostatic antibiotic that barely meets the MIC for Borrelia burgdorferi in its ordinarily prescribed regimen. It is also dependent on compliance which is a huge issue because of the gastrointestinal side effects. This antibiotic may clear the rash, but seemingly does little to prevent late findings of the disease. The sub lethal antibiotic dose can be important in the subsequent development of biofilms that lead to a chronic disease state. Lastly, how ethical is it that we have nearly abandoned our patient advocacy and permitted the insurance companies to dictate allowable treatment? And, in as much as Borrelia organisms were found in the brains of Alzheimer’s disease patients over 25 yrs ago and those spirochetes have recently been shown to produce biofilms, how ethical is it that we ignore research underpinning the pathogenesis of this disease?

The fight against Lyme disease
James G. Logan
It occurs in more than 80 countries and is the most commonly reported vectorborne disease in the Northern Hemisphere. In the United States alone, it spawns 300,000 new cases each year. Yet Lyme disease—caused by species of Borrelia bacteria carried by ticks of the Ixodes genus — remains one of the most poorly understood infections. It has divided researchers, clinicians and patients, and triggered intense public suspicion and confusion.

Lyme and associated tick-borne diseases: global challenges in the context of a public health threat.
Running title: Global challenges of Lyme disease
Christian Perronne
Frontiers in Cellular and Infection Microbiology, 4:74.
The lack of a gold standard for diagnosis makes producing accurate statistics difficult. Some pathogenic strains belonging to the B. burgdorferi sensu lato complex have a worldwide distribution, yet they are rarely considered or tested for. Borrelia miyamotoi, for instance, phylogenetically close to relapsing fever borreliae, is now recognized as a cause of Lyme-like disease and relapsing fever in Asia, Europe and North America. It usually does not cross react with B. burgdorferi tests. A novel isolate of Borrelia has been isolated by PCR in a post-treatment serum from a patient with neurologic Lyme disease. These recent historical, geographical and microbial data should prompt the medical community to realize that cases of persisting post tick-bite syndromes are probably due to multiple pathogens and that these occult infections will require a new approach if not an actual paradigm shift.

Genomic insights into the ancient spread of Lyme disease across North America
Katharine S. Walter, Giovanna Carpi, Adalgisa Caccone & Maria A. Diuk-Wasser
Nature Ecology & Evolution, 1569–1576 (2017) doi:10.1038/s41559-017-0282-8 Published online:28 August 2017
Here, we show that B. burgdorferi s.s. has a complex evolutionary history with previously undocumented levels of migration. Diversity is ancient and geographically widespread, well pre-dating the Lyme disease epidemic of the past ~40 years, as well as the Last Glacial Maximum ~20,000 years ago. This means the recent emergence of human Lyme disease probably reflects ecological change—climate change and land use changes over the past century—rather than evolutionary change of the bacterium.

Lyme disease: the next decade.
Stricker RB, Johnson L.
Infection and Drug Resistance, 2011; 4:1-9. Online before print, January 7, 2011.
Recognition of the importance of CWD forms and biofilms in persistent B. burgdorferi infection should stimulate pharmaceutical research into new antimicrobial agents that target these mechanisms of chronic infection with the Lyme spirochete. Concurrent clinical implementation of proteomic screening offers a chance to correct significant deficiencies in Lyme testing. Advances in these areas have the potential to revolutionize the diagnosis and treatment of Lyme disease in the coming decade.

Seven provocative findings on Lyme disease, brains and placentas …and what they mean to Medicine and Patients
Dr. Paul Duray Research Fellowship Endowment Inc, Naples, Florida
By Thomas Grier, Microbiologist
July 27, 2016
The Seven Provocative Findings of the Dr. Paul Duray Research Fellowship Foundation
1. Mother-to-child transmission of Borrelia across the womb
2. Finding Borrelia burgdorferi and miyamotoi associated with Amyloid Plaques in Alzheimer’s disease brains
3. Finding Borrelia in Lewy Body Dementia
4. Nematode worms found in the CSF (spinal fluid) of Multiple Sclerosis patients
5. Nematode worms found in Alzheimer’s brains
6. Borrelia found in five deadly brain tumors (Glioblastoma multiforme)
7. Borrelia Mayonii and Borrelia burgdorferi found in human testicle
Since 1975 when Lyme disease was first introduced to the medical literature, it has been surrounded by controversy and misunderstandings. Much of the problem stemmed from trying to understand this disease entirely through antibody tests (serology) based entirely on just one species – Borrelia burgdorferi.

Lyme Bacteria Hides Inside Parasitic Worms, Causing Chronic Brain Diseases
Patient Centered Care Advocacy Group
May 19, 2016, 07:00 ET
The examination of autopsied brain tissues from patients who died of serious neurological conditions has revealed that many tick-borne infections, such as Lyme disease, go undiagnosed and untreated. Board-certified pathologist, Alan B. MacDonald, MD, says his research shows “tick infections are not easily detected with routine tests, nor are they easily cured with short courses of antibiotics.” MacDonald found two Borrelia pathogens, including B. burgdorferi the causative agent of Lyme disease, thriving inside parasitic nematode worms, worm eggs or larvae in the brain tissue of nineteen deceased patients. These microscopic worms are endosymbionts, meaning the Borrelia bacteria dwell inside the worms. A tick bite delivers the nematode into the human body.

Non-viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes.
Parthasarathy G, Fevrier HB, Philipp MT.
Neuroscience Letters, online before print 2013 Oct 21. pii: S0304-3940(13)00936-1.
In previous studies, exposure to live Borrelia burgdorferi was shown to induce inflammation and apoptosis of human oligodendrocytes. In this study we assessed the ability of non-viable bacteria (heat killed or sonicated) to induce inflammatory mediators and cell death. Both heat-killed and sonicated bacteria induced release of CCL2, IL-6, and CXCL8 from oligodendrocytes in a dose dependent manner. In addition, non-viable B. burgdorferi also induced cell death as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and another cell viability assay. These results suggest that spirochetal residues left after bacterial demise, due to treatment or otherwise, may continue to be pathogenic to the central nervous system.

Health Care Costs, Utilization and Patterns of Care following Lyme Disease
Adrion ER, Aucott J, Lemke KW, Weiner JP.
PLoS One. 2015 Feb 4;10(2):e0116767. eCollection 2015.
Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome – a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Lyme disease is associated with $2,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with $3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses.

Healthcare access and burden of care for patients with Lyme disease: A large United States survey.
Johnson L, Aylward A, Stricker RB.
Health Policy. published online before print, 2011 Jun 13.
Responses from 2424 patients were included in the study. Half of the respondents reported seeing at least seven physicians before the diagnosis of Lyme disease was made. Nearly half had Lyme disease for more than 10 years and traveled over 50 miles to obtain treatment. Most respondents experienced symptoms lasting six months or more despite receiving at least 21 days of antibiotic treatment. A quarter of respondents had been on public support or received disability benefits due to Lyme disease symptoms, and over half had visited an emergency room at least once as a result of these symptoms.

Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review
Liesbeth Borgermans, Geert Goderis, Jan Vandevoorde, and Dirk Devroey
International Journal of Family Medicine, Volume 2014 (2014), Article ID 138016.
Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.

Tick-borne pathogen – reversed and conventional discovery of disease
Tijsse-Klasen E, Koopmans MP, Sprong H.
Frontiers in Public Health. 2014 Jul 7;2:73. eCollection 2014.
Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing.

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes
Marcinkiewicz AL, Kraiczy P, Lin YP.
Frontiers in Microbiology. 2017 Mar 2;8:328. eCollection 2017.
Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis.

A Novel Multivalent OspA Vaccine against Lyme Borreliosis is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi sensu lato.
Wressnigg N, Barrett PN, Pöllabauer EM, O’Rourke M, Portsmouth D, Schwendinger MG, Crowe BA, Livey I, Dvorak T, Schmitt B, Zeitlinger M, Kollaritsch H, Esen M, Kremsner PG, Jelinek T, Aschoff R, Weisser R, Naudts IF, Aichinger G.
Clinical and Vaccine Immunology, online before print 2014 Sep 3. pii: CVI.00406-14.
Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to re-infection with Borrelia burgdorferi sensu lato (s.l.). There is limited information available about OspA vaccines in this population. Participants received three, monthly, priming immunizations, with either 30µg or 60µg alum-adjuvanted OspA antigen, and a booster vaccination either 6 months or 9-12 months after the first immunization. Antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient, and were similar in the seronegative and seropositive populations.

Lyme bacteria settled in North America far earlier than we thought
Insight into the disease’s ancient origins points toward the causes of the current epidemic
By Jen Monnier, Science Line, New York University, New York City, New York
November 29, 2017

Lyme bacteria settled in North America far earlier than we thought

While the Lyme disease outbreak in people dates back only about 40 years, the bacterium that causes this disease has called North America home for more than 20,000 years, according to a study published in August in the journal Nature Ecology and Evolution.

Future Microbiology
May 2009, Vol. 4, No. 4, Pages 457-469.
Dean T Nardelli?, Erik L Munson?, Steven M Callister? & Ronald F Schell
The development of a vaccine for Lyme disease was intensely pursued in the 1990s. However, citing a lack of demand, the first human Lyme disease vaccine was withdrawn from the market less than 5 years after its approval. The public’s concerns about the vaccine’s safety also likely contributed to the withdrawal of the vaccine. Nearly a decade later, no vaccine for human Lyme disease exists. The expansion of Lyme disease’s endemic range, as well as the difficulty of diagnosing infection and the disease’s steady increase in incidence in the face of proven preventative measures, make the pursuit of a Lyme disease vaccine a worthwhile endeavor. Many believe that the negative public perception of the Lyme disease vaccine will have tarnished any future endeavors towards its development. Importantly, many of the drawbacks of the Lyme disease vaccine were apparent or foreseeable prior to its approval. These pitfalls must be confronted before the construction of a new, effective and safe human Lyme disease vaccine.

Borrelia burgdorferi: Cell Biology and Clinical Manifestations in Latent Chronic Lyme.
Smith, A. , Oertle, J. and Prato, D.
Open Journal of Medical Microbiology, 4, 210-223,(2014).
Chronic Lyme disease is predicated by an infection with Borrelia burgdorferi via tick vector. B. burgdorferi has been extensively researched with regard to its genome and cell biology. There are many unique characteristics to the bacteria itself; however, serological diagnostics and diagnosis based on symptoms can be complicated and potentially misleading. Other promising diagnostics were also evaluated in this review. Treatment of the chronic Lyme disease can be complicated and at times ineffective.

Whole-Genome Sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii.
Schutzer SE, Fraser-Liggett CM, Qiu WG, Kraiczy P, Mongodin EF, Dunn JJ, Luft BJ, Casjens SR.
Journal of Bacteriology, January 2012, vol. 194, no. 2, 545-54.
It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

Gifted Students and Lyme Disease What Educators, Counselors, and Parents Need to Know
Patricia A. Schuler, PhD
Gifted Child Today, January 2013, vol. 36, no. 1, 35-46.
Gifted and talented students, like all students, are susceptible to the effects of Lyme disease. However, their experiences may be more intense and life altering, depending on the severity of the Lyme disease. In this article, the phenomenological experience of two gifted boys with Lyme disease gives educators, counselors, and parents insight into how this disease impacts the intellectual functioning, social status, and identity of gifted children with this bacterial illness.

“Antibiotics give rise to new communities of harmful bacteria.”
ScienceDaily. ScienceDaily, 23 February 2015.
University of North Carolina at Chapel Hill.
“For a long time we’ve thought that bacteria make antibiotics for the same reasons that we love them — because they kill other bacteria,” said Shank, whose work appears in the February 23 Early Edition of the Proceedings of the National Academy of Sciences. “However, we’ve also known that antibiotics can sometimes have pesky side-effects, like stimulating biofilm formation.” Shank and her team now show that this side-effect — the production of biofilms — is not a side-effect after all, suggesting that bacteria may have evolved to produce antibiotics in order to produce biofilms and not only for their killing abilities.

The Brief case: Probable transfusion-transmitted babesiosis in a transplant recipient
Kitt E, Keaton AA, Graf EH.
Journal of Clinical Microbiology 54:2632–2634.
A 3-year-old immunocompromised male who had been hospitalized for 7 months in the cardiac intensive care unit developed fever and tachycardia in December. He was prenatally diagnosed with hypoplastic left heart syndrome and received right ventricle to pulmonary artery conduit surgery days after delivery. Due to worsening right ventricular function, after a hemi-Fontan procedure, he received an orthotopic heart transplant at the beginning of his 3rd year of life.

Screening for Babesia microti in the U.S. Blood Supply
Erin D. Moritz, Ph.D., Colleen S. Winton, S.B.B. (A.S.C.P.), Laura Tonnetti, Ph.D., Rebecca L. Townsend, B.A., Victor P. Berardi, Mary-Ellen Hewins, B.S., Karen E. Weeks, B.S., Roger Y. Dodd, Ph.D., and Susan L. Stramer, Ph.D.
New England Journal of Medicine 2016; 375:2236-2245. Online first, December 8, 2016.
Babesia microti, a tickborne intraerythrocytic parasite that can be transmitted by means of blood transfusion, is responsible for the majority of cases of transfusion-transmitted babesiosis in the United States. However, no licensed test exists for screening for B. microti in donated blood. Of 89,153 blood-donation samples tested, 335 (0.38%) were confirmed to be positive.

Bartonella henselae transmission by blood transfusion in mice
da Silva MN, Vieira-Damiani G, Ericson ME, Gupta K, Gilioli R, de Almeida AR, Drummond MR, Lania BG, de Almeida Lins K, Soares TC, Velho PE
Transfusion, online first, 2016 Mar 10.
Bartonella spp. are neglected fastidious Gram-negative bacilli. We isolated Bartonella henselae from 1.2% of 500 studied blood donors and demonstrated that the bacteria remain viable in red blood cell units after 35 days of experimental infection.

Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report.
Shields K, Cumming M, Rios J, Wong MT, Zwicker JI, Stramer SL, Alonso CD.
Transfusion, online before print, 2014 Nov 11.
Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion.

Two Cases of Transfusion-Transmitted Anaplasma phagocytophilum.
American Journal of Clinical Pathology. 2012 Apr;137(4):562-5.
Annen K, Friedman K, Eshoa C, Horowitz M, Gottschall J, Straus T.
We report 2 additional cases of transfusion-transmitted A phagocytophilum in which leukocyte reduction of all transfused units failed to prevent microbial transmission.

A confirmed Ehrlichia ewingii infection likely acquired through platelet transfusion.
Regan J, Matthias J, Green-Murphy A, Stanek D, Bertholf M, Pritt B, Sloan L, Kelly A, Singleton J, McQuiston J, Hocevar SN, Whittle J.
Clinical Infectious Diseases, online before print, 2013 Mar 19.
Ehrlichiosis is a tick-borne disease that ranges in severity from asymptomatic infection to fatal sepsis. Ehrlichiosis acquired from transfusion of blood products has not been documented in the literature to date. A case of Ehrlichia ewingii infection likely transmitted by transfusion of leukoreduced platelets is described and public health implications discussed.

Is there a place for xenodiagnosis in the clinic?
Telford SR 3rd, Hu LT, Marques A.
Expert Review of Anti-infective Therapy. 2014 Nov;12(11):1307-10.
Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist after antibiotic therapy is an area of ongoing controversy. Our recent safety trial of xenodiagnosis demonstrates that ticks may be successfully fed on patients and may help determine the biological basis for post-treatment Lyme disease syndrome.

Protesting CDC’s biased reporting in PubMed Commons, Chico, California
June 18, 2017

Protesting CDC’s biased reporting in PubMed Commons

The CDC’s June 15 article in MMWR, which slams “chronic Lyme” treatments—and by extension, Lyme patients and the doctors who treat them—continues to draw sharp responses from the Lyme disease community. ILADS physician Raphael Stricker, MD, and his frequent co-author, CEO Lorraine Johnson, posted their rebuttal on PubMed Commons on June 17. Now, when anyone accesses the original article on PubMed, Stricker and Johnson’s reply will be shown right along with it.

Tick-borne infections–a growing public health threat to school-age children. Prevention steps that school personnel can take.
Hamlen R.
National Association of School Nurses: School Nurse. 2012 Mar; 27(2): 94-100.
School nurses are experts in school health services and frequently front-line providers of care for school-age children presenting with symptoms of physical illness or behavioral, cognitive, learning, and/or psychological problems possibly due to tick-borne infections. School nurses need to know how to protect children on school property and during school sponsored outdoor activities from being bitten by ticks that can transmit diseases.

Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia
Martin J. Herrmann’Correspondence information about the author Martin J. HerrmannEmail the author Martin J. Herrmann, Andrea Katzorke, Yasmin Busch, Daniel Gromer, Thomas Polak, Paul Pauli, Jürgen Deckert
PlumX Metrics
This study provides first clinical evidence that high-frequency rTMS over the vmPFC improves exposure therapy response of acrophobia symptoms.

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration
Jane A. Lindborg, Matthias Mack and Richard E. Zigmond
Journal of Neuroscience 25 October 2017, 37 (43) 10258-10277;
The accepted view in the basic and clinical neurosciences is that the clearance of axonal and myelin debris after a nerve injury is directed primarily by inflammatory CCR2+ macrophages. However, we demonstrate that this clearance is nearly identical in WT and Ccr2−/− mice, and that neutrophils replace CCR2+ macrophages as the primary phagocytic cell. We find that neutrophils play a major role in myelin clearance not only in Ccr2−/− mice but also in WT mice, highlighting their necessity during nerve degeneration in the peripheral nervous system. These degeneration studies may propel improvements in nerve regeneration and draw critical parallels to mechanisms of nerve degeneration and regeneration in the CNS and in the context of peripheral neuropathies.

Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy.
von Schenck, Bender-Götze C, Koletzko B.
Arch Dis Child. 1997 Aug;77(2):137-9.
A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother’s vegan diet. Clinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms.

A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection
Yesseinia I. Angleró-Rodríguez, Benjamin J. Blumberg, Yuemei Dong, Simone L. Sandiford, Andrew Pike, April M. Clayton & George Dimopoulos
Scientific Reports 6, Article number: 34084 (2016)10.1038/srep34084
12 June 2016
Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non-entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat-stable factor.

Impact of GeneSight Psychotropic on Response to Psychotropic Treatment in Outpatients Suffering From a Major Depressive Disorder (MDD) and Having Had an Inadequate Response to at Least One Psychotropic Medication Included in GeneSight Psychotropic (RCT) Last Update Posted: September 18, 2017
Principal Investigator: John Greden, Ph.D, University of Michigan
This was the largest ever pharmacogenomics depression trial and primarily assessed Hamilton Depression Rating Scale 17 (HAMD-17) scores from baseline to eight weeks in patients receiving GeneSight-guided therapy compared to those receiving treatment-as-usual. The study was designed to evaluate three key endpoints relative to HAMD-17 scores: remission (HAMD-17 score ≤7), response (HAMD-17 reduction >50%), and symptom reduction.
Patients receiving the GeneSight test achieved a clinically meaningful and statistically significant improvement in both remission rates (p<0.01) and response rates (p=0.01) at eight weeks compared to the treatment-as-usual group.

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New Research Discovers That Depression Is An Allergic Reaction To Inflammation

New Research Discovers That Depression Is An Allergic Reaction To Inflammation

New research is revealing that many cases of depression are caused by an allergic reaction to inflammation. Tim de Chant of NOVA writes: “Inflammation is our immune system’s natural response to injuries, infections, or foreign compounds. When triggered, the body pumps various cells and proteins to the site through the blood stream, including cytokines, a class of proteins that facilitate intercellular communication. It also happens that people suffering from depression are loaded with cytokines.” Inflammation is caused by obesity, high sugar diets, high quantities of trans fats, unhealthy diets in general, and other causes. By treating the inflammatory symptoms of depression — rather than the neurological ones — researchers and doctors are opening up an exciting new dimension in the fight against what has become a global epidemic.

Aerosolization of Mycotoxins after Growth of Toxinogenic Fungi on Wallpaper
Brankica Aleksica,b, Marjorie Draghic, Sebastien Ritouxc, Sylviane Baillya, Marlène Lacroixa, Isabelle P. Oswalda, Jean-Denis Baillya and Enric Robinec
Scientific and Technical Centre for Building, Airborne Pollutants and Bioaerosol Division, Marne-la-Vallée, France
Dan Cullen, Editor
Many fungi can develop on building material in indoor environments if the moisture level is high enough. Among species that are frequently observed, some are known to be potent mycotoxin producers. This presence of toxinogenic fungi in indoor environments raises the question of the possible exposure of occupants to these toxic compounds by inhalation after aerosolization. This study investigated mycotoxin production by Penicillium brevicompactum, Aspergillus versicolor, and Stachybotrys chartarum during their growth on wallpaper and the possible subsequent aerosolization of produced mycotoxins from contaminated substrates. The possible colonization of building material by toxinogenic fungi in cases of moistening raises the question of the subsequent exposure of occupants to aerosolized mycotoxins. In this study, we demonstrated that three different toxinogenic species produce mycotoxins during their development on wallpaper. These toxins can subsequently be aerosolized, at least partly, from moldy material. This transfer to air requires air velocities that can be encountered under real-life conditions in buildings.

Pillows: A Hot Bed Of Fungal Spores.
University of Manchester. ScienceDaily. ScienceDaily, 15 October 2005.
Researchers at The University of Manchester funded by the Fungal Research Trust have discovered millions of fungal spores right under our noses — in our pillows. Aspergillus fumigatus, the species most commonly found in the pillows, is most likely to cause disease; and the resulting condition Aspergillosis has become the leading infectious cause of death in leukaemia and bone marrow transplant patients. Fungi also exacerbate asthma in adults.

Cilantro Detoxifying and Delicious!
Designs for Health Research and Education
January 21, 2015
In the past two decades one quality of cilantro that has captured the attention of many is its ability to detoxify heavy metals such as mercury and lead. This discovery was first made public in a study where 400 mg of cilantro was used daily to remove excess mercury that was deposited in various organs after the removal of amalgam dental fillings. In more recent years the use of cilantro has become more widely recognized as an adjunct treatment for detoxifyng heavy metals and some chemicals such as phthalates plasticizers and insecticides. In a recent animal study cilantro was able to significantly decrease lead deposition in bone and kidneys while also reducing lead-induced inhibition of enzyme activity. Such examples show how cilantro has earned its place among natural plant-based chelating agents although more rigorous clinical trials are needed to determine its therapeutic efficacy as a sole heavy metal detoxifier.

Low magnesium levels make vitamin D ineffective. Role of Magnesium in Vitamin D Activation and Function.
February 26, 2018
The Journal of the American Osteopathic Association, American Osteopathic Association, 2018; 118 (3): 181
Anne Marie Uwitonze, Mohammed S. Razzaque.
DOI: 10.7556/jaoa.2018.037
Vitamin D can’t be metabolized without sufficient magnesium levels, meaning Vitamin D remains stored and inactive for as many as 50 percent of Americans. In addition, Vitamin D supplements can increase a person’s calcium and phosphate levels even while they remain Vitamin D deficient. People may suffer from vascular calcification if their magnesium levels aren’t high enough to prevent the complication.

Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis.
Vanessa Garcia-Larsen, Despo Ierodiakonou, Katharine Jarrold, Sergio Cunha, Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Alisha Ruparelia, Pooja Devani, Marialena Trivella, Jo Leonardi-Bee, Robert J. Boyle.
PLOS Medicine, 2018; 15 (2): e1002507
DOI: 10.1371/journal.pmed.1002507
Women who take fish oil supplements and probiotics in later pregnancy may reduce their child’s risk of food allergy and eczema, according to new research.

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration.
Jane A. Lindborg, Matthias Mack, Richard E. Zigmond.
The Journal of Neuroscience, 2017; 37 (43): 10258
DOI: 10.1523/JNEUROSCI.2085-17.2017
Immune cells are normally associated with fighting infection but in a new study, scientists have discovered how they also help the nervous system clear debris, clearing the way for nerve regeneration after injury. Researchers have recently shown certain immune cells — neutrophils — can clean up nerve debris, while previous models have attributed nerve cell damage control to other cells entirely.

Gut microbiome alterations in Alzheimer’s disease
Nicholas M. Vogt, Robert L. Kerby, Kimberly A. Dill-McFarland, Sandra J. Harding, Andrew P. Merluzzi, Sterling C. Johnson, Cynthia M. Carlsson, Sanjay Asthana, Henrik Zetterberg, Kaj Blennow, Barbara B. Bendlin & Federico E. Rey
Scientific Reportsvolume 7, Article number: 13537 (2017)
Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.

β-Amyloid accumulation in the human brain after one night of sleep deprivation.
Shokri-Kojori E, Wang GJ, et al.
Proc Natl Acad Sci USA. 2018 Apr 9. pii: 201721694.
doi: 10.1073/pnas.1721694115.
Alzheimer’s disease and related disorders (ADRD) are a group of conditions that cause mild cognitive impairment (MCI) or dementia. These conditions affect one’s ability to function socially, personally, and professionally. According to a new study published last week, researchers demonstrate how sleep disruption increases amyloid beta and tau proteins, which are associated with ADRD. Nutrients to consider to help restore sleep include magnesium l-threonate, valerian root, passionflower, lemon balm, and melatonin.

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.
Paul M Ridker, Brendan M. Everett, Tom Thuren, Jean G. MacFadyen, William H. Chang, Christie Ballantyne, Francisco Fonseca, Jose Nicolau, Wolfgang Koenig, Stefan D. Anker, John J.P. Kastelein, Jan H. Cornel, Prem Pais, Daniel Pella, Jacques Genest, Renata Cifkova, Alberto Lorenzatti, Tamas Forster, Zhanna Kobalava, Luminita Vida-Simiti, Marcus Flather, Hiroaki Shimokawa, Hisao Ogawa, Mikael Dellborg, Paulo R.F. Rossi, Roland P.T. Troquay, Peter Libby, Robert J. Glynn.
New England Journal of Medicine, 2017;
DOI: 10.1056/NEJMoa1707914
Investigators have announced results of a clinical trial culminating from 25 years of cardiovascular research work. The team reports a significant reduction in risk of recurrent heart attacks, strokes and cardiovascular death among participants who received a targeted anti-inflammatory drug that lowered inflammation but had no effects on cholesterol.

Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia.
Martin J. Herrmann, Andrea Katzorke, Yasmin Busch, Daniel Gromer, Thomas Polak, Paul Pauli, Jürgen Deckert.
Brain Stimulation, 2017; 10 (2): 291
DOI: 10.1016/j.brs.2016.11.007
It is possible to unlearn fears and anxiety. And this works even better when a specific region of the brain has previously been stimulated magnetically.

Fungus makes mosquitoes much more likely to become infected with malaria. A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection
Yesseinia I. Angleró-Rodríguez, Benjamin J. Blumberg, Yuemei Dong, Simone L. Sandiford, Andrew Pike, April M. Clayton, George Dimopoulos.
Scientific Reports, 2016; 6: 34084
DOI: 10.1038/srep34084
A fungus that compromises the immune system of mosquitoes, making them more susceptible to infection with the parasite that causes malaria, has been discovered by scientists. Because environmental microorganisms can vary greatly from region to region, the researchers say the findings may help explain variations in the prevalence of malaria in different geographic areas.

A Look at Cat’s Claw Herb
April 17, 2018 – 08:17
Research and Education Blog
In vitro studies indicate cat’s claw may stimulate the immune system, help relax smooth muscles (including the intestines), dilate blood vessels, and act as a diuretic. The latter two effects may mean cat’s claw could be beneficial for lowering blood pressure. As it contains coumarins, it may also have natural blood thinning effects. Cat’s claw is also a potent antioxidant and anti-inflammatory, and has been used to address inflammatory conditions such as arthritis, gastritis and osteoarthritis.

Garlic extract favorably modifies markers of endothelial function in obese patients.
Szulinska M, Kregielska-Narozna M, et al.
Biomed Pharmacother. 2018 Mar 28; 102-792-292.
doi: 10.1016/j.biopha.2018.03.131.
Garlic extract improves biomarkers associated with cardiovascular risk specifically related to endothelial function and arterial stiffness in obese patients. Garlic has a broad range of health benefits, from antimicrobial properties to supporting cardiovascular health.

Nutrition: Review on Possible Treatment of Alzheimer’s Disease.
Botchway B, Moore M, et al.
J Alzheimers Dis. 2018;61(3):867-883.
doi: 10.3233/JAD-170874.
According to this review, patients with Alzheimer’s disease had significantly lower plasma levels of folate and vitamins B12, C and E. This is not surprising, as antioxidants have been found to be depleted in the brain of those with neurodegenerative disorders. Providing antioxidant support is essential for mitigating some of the damage seen in neurodegenerative disorders. In addition, the body’s cells are more susceptible to damage and death in older adults. Folate and B12 are significant as they play a large role in the metabolism of homocysteine and elevated levels are a risk factor for cognitive decline. Curcumin also plays an important role. There are only a few natural products that have demonstrated the wide range of protective properties as curcumin. There have been connections with vitamin D deficiency and Alzheimer’s as it correlates with almost all conditions, however, curcumin and vitamin D work together to enhance the brain’s immune system to protect against amyloid-induced toxicity. Other brain supportive nutrients to consider include GPC, CDP-choline (citicoline), ginkgo biloba, and phosphatidylserine. GPC and CDP-choline are water soluble forms of choline that can cross the blood brain barrier and support brain health. These help make more acetylcholine, neurotransmitters, and phosphatidylcholine in the cell membranes. Daily intake of fish oil has been found to lower the incidence of Alzheimer’s disease. One study found that daily dietary supplementation with 900 mg DHA resulted in a 7 year age improvement in cognition over 24 weeks in elderly patients with cognitive decline.

Role of glutathione metabolism in host defense against Borrelia burgdorferi infection
Kerstholt M, Vrijmoeth H, Lachmandas E, Oosting M, Lupse M3, Flonta M, Dinarello CA, Netea MG, Joosten LAB.
Proceedings of the National Academy of Sciences of the United States of America. 2018 Mar 6;115(10):E2320-E2328.
We found that the GSH pathway is essential for Bb-induced cytokine production and identified glutathionylation as a potential mediating mechanism. Taken together, these data indicate a central role for the GSH pathway in the host response to Bb. GSH metabolism and glutathionylation may therefore be important factors in the pathogenesis of Lyme disease and potentially other inflammatory diseases as well.

CBD Oil: The Basics
Designs for Health: Research and Education
February 27, 2018
CBD is cannabidiol – a cannabinoid compound extracted from the cannabis plant. Various Cannabis species supply over 100 cannabinoids but medicine has focused primarily on either tetrahydrocannabinol (THC) or cannabidiol (CBD). Interest in cannabinoids has surged in the last 20 years for their pharmacological effects on the neurological system and especially, as possible modulators of pain, inflammation, addiction, mood and psychosis, mental health disorders, and most recently, cancer.

All’s Well with Boswellia
Designs for Health: Research and Education
February 23, 2018
boswellia (Boswellia serrata), an herb that has been employed in Ayurvedic medicine for a variety of ailments. (Boswellia also goes by its more common name, frankincense.) Boswellia is particularly recognized for its efficacy in ameliorating the pain and stiffness associated with inflammatory conditions, such as osteo- and rheumatoid arthritis. Moreover, rather than potentially damaging the GI tract, evidence suggests boswellia improves inflammatory conditions of the gastrointestinal tract, such as Crohn’s disease and ulcerative colitis.

The ‘Odd’ Repercussions of Low Magnesium
Designs for Health: Research and Education
February 9, 2018
With mood disorders such as depression reaching epidemic levels, not to mention being difficult to cope with, it’s interesting to note that magnesium insufficiency may be a contributing factor. Some healthcare practitioners have suggested that marginally low magnesium levels (as opposed to overt clinical deficiency) may lead to hyper-excitability, ultra-sensitivity to noise, and being “high-strung” in general.

Bacopa Monnieri – Time-Honored Nootropic
Designs for Health: Research and Education
January 18, 2018
Bacopa monnieri—or Bacopa—has over 1400 years of use in Ayurvedic medicine, where it is recognized to “sharpen intellect and attenuate mental deficits. Bacopa works via multiple mechanisms, including antioxidant neuroprotection, inhibiting acetylcholinesterase, increasing cerebral blood flow, and modulating the neurotransmitters serotonin, dopamine, and acetylcholine. In vivo and in vitro studies show that Bacopa inhibits the release of inflammatory cytokines from mouse microglial cells and inhibits enzymes associated with inflammation in the brain.

Boost Brain Health with American Ginseng
Designs for Health: Research and Education
December 29, 2017
American ginseng has some impressive properties for supporting healthy cognitive function and mental focus. The primary active constituents in this plant are called ginsenosides. American ginseng is rich in ginsenoside Rb1 (Rb1), a compound shown to improve spatial learning and memory in hippocampus-dependent tasks.

New study demonstrates enhanced cognition and cerebrovascular function with resveratrol
Designs for Health: Research and Education
April 6, 2017
Resveratrol has been widely publicized for its cardiovascular health benefits. However researchers believe it also has positive effects on the hippocampus an area of the brain that is critical to functions such as memory learning and mood. In a recent study published in Nutrients researchers demonstrated oral supplementation with resveratrol enhanced both cerebrovascular function and cognition in post-menopausal women which can potentially reduce the risk of cognitive decline.

New study demonstrates glutamine decreases intestinal permeability
Designs for Health: Research and Education
October 26, 2017
In a study published last Friday in the European Journal of Applied Physiology researchers demonstrated that acute supplementation with glutamine mitigates intestinal permeability in runners. It makes sense to consider BCAAs and/or glutamine powder prior to or during exercise to help prevent gastrointestinal barrier dysfunction. In addition other studies have demonstrated that oral supplementation with colostrum decreases intestinal permeability. These findings demonstrate the importance of colostrum and glutamine in helping to prevent leaky gut and are important nutrients to consider for athletes. For those individuals who have a sensitivity to dairy and cannot use colostrum serum-derived bovine immunoglobulin/protein isolate (SBI) is a great alternative to normalize the gut microbiota and decrease gut permeability.

Multispecies probiotic may have a significant effect on mood
Designs for Health: Research and Education
April 16, 2015
Brain Behavior and Immunity researchers found that multispecies probiotics have an effect on mood after four weeks of supplementation.

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