Research

Lyme Disease Research for Education 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 sampling of research that is particularly relevant to patients and healthcare practioners.

 

 

TICK-BORNE ILLNESS PREVALENCE

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.) http://dx.doi.org/10.3201/eid2109.150417
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.  http://article.sapub.org/10.5923.j.microbiology.20130306.11.html
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.  http://doi.org/10.1093/cid/ciu397
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,  http://www.ilads.org/files/harvey.pdf
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
http://www.entsoc.org/press-releases/blacklegged-ticks-found-half-us-counties
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.
http://www.cdc.gov/eid/content/16/6/911.htm

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.

http://doi.org/10.1111/evo.12690
Populations of blacklegged ticks have established and flourished in areas of North America previously thought to be devoid of this species.

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.

http://doi.org/10.1186/s13071-016-1529-y
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
http://www.liebertonline.com/doi/abs/10.1089/vbz.2008.0162
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).

http://dx.doi.org/10.1603/ME13232
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.

Forest and Surface Water As Predictors of Borrelia burgdorferi and Its Vector Ixodes scapularis (Acari: Ixodidae) in Indiana
No Access
E. A. Raizman, J. D. Holland, L. M. Keefe, and M. H. Moro
© 2010 Entomological Society of America
http://www.bioone.org/doi/abs/10.1603/ME09094
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.

http://dx.doi.org/10.1111/j.1863-2378.2012.01518.x
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
Press Release – FOR IMMEDIATE RELEASE
http://news.indiana.edu/releases/iu/2015/05/tick-microbiome.shtml
“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].

http://dx.doi.org/10.3201/eid2010.131583
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.

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
http://www.ajtmh.org/content/85/4/718
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
http://digitalcommons.wku.edu/theses/118

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].

http://dx.doi.org/10.3201/eid2010.140175
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.

http://dx.doi.org/10.4137/EHI.S16017
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.

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.

http://doi.org/10.3389/fcimb.2014.00070
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.

https://doi.org/10.1093/ofid/ofw269
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.

http://doi.org/10.1111/jvec.12152
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.

http://www.ncbi.nlm.nih.gov/pubmed/26436184
Babesiosis should be considered endemic in southwestern Wisconsin, and testing should be considered for patients with compatible clinical and laboratory features.

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.

http://doi.org/10.1016/j.meegid.2014.06.003
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.

http://doi.org/10.1089/vbz.2014.1661
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.

http://doi.org/10.1111/jvec.12148
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
http://www.prweb.com/releases/2015/10/prweb13009591.htm
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.

http://dx.doi.org/10.1093/jme/tjv037
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.

http://dx.doi.org/10.1016/j.ttbdis.2015.01.004
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.

http://doi.org/10.1186/s13071-014-0607-2
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).

http://doi.org/10.1093/ofid/ofv143
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
http://tinyurl.com/l69ovj6
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.

http://doi.org/10.1089/vbz.2013.1473
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.

http://doi.org/10.4269/ajtmh.15-0122
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].

http://dx.doi.org/10.3201/eid2110.150143
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.

http://doi.org/10.1016/j.ttbdis.2016.04.010
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.

http://doi.org/10.1099/jmm.0.073122-0
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.

http://dx.doi.org/10.1093/jme/tjw054
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.

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.

http://doi.org/10.1111/mve.12191
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.

http://doi.org/10.1007/s00442-016-3731-1
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.
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].

http://dx.doi.org/10.3201/eid2205.152009
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.

http://doi.org/10.1371/journal.pntd.0004539
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.

http://doi.org/10.4269/ajtmh.15-0691
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.

http://doi.org/10.4269/ajtmh.15-0540
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.

http://doi.org/10.1007/s40588-015-0025-z
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.

http://doi.org/10.1186/s13071-016-1380-1
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
http://www.dispatch.com/content/stories/local/2016/01/04/0104-more-stricken-with_lyme-disease.html
or http://tinyurl.com/hvmqotx
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.

http://dx.doi.org/10.1093/jme/tjv238
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.

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.

http://doi.org/10.1371/journal.pone.0140332
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
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.

http://doi.org/10.1016/j.ttbdis.2015.03.017
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.

Swarming deer flies could quickly expose people to Lyme disease and Anaplasmosis
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.

December 1, 2016

Retraction: Still no evidence that deer flies or deer keds transmit B. burgdorferi or A. phagocytophilum

Deer ticks transmit Lyme disease (LD) to people in 24 to 36 hours. Partly fed deer ticks can transmit LD to people in less than 6 hours. Now, researchers have discovered that swarming deer flies could expose people to Lyme disease and Anaplasmosis in as little as 15 to 20 minutes.

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.

http://www.mdpi.com/2306-7381/1/1/5
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.

http://dx.doi.org/10.1186/s13071-014-0630-3
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.

MULTIPLE STRAINS OF TICK-BORNE PATHOGENS

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.

http://dx.doi.org/10.1097/MOP.0b013e328360dc49
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.

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.

https://doi.org/10.1128/AEM.02552-16
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.

http://doi.org/10.1002/9780471729259.mc12c05s34
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.

http://doi.org/10.1186/s12879-015-1190-7
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

http://doi.org/10.1186/s12866-015-0381-0
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.

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.

http://doi.org/10.1016/j.ttbdis.2014.07.015
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.
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 American.com

February 16, 2016
http://www.scientificamerican.com/article/new-cause-for-lyme-disease-complicates-already-murky-diagnosis1/
or http://tinyurl.com/jztrgy7
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.

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.

http://doi.org/10.1099/ijsem.0.001445
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.

http://dx.doi.org/10.1016/j.mcp.2016.08.003
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.
http://www.newmicrobiologica.org/PUB/allegati_pdf/2014/3/393.pdf
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.

http://doi.org/10.1099/mic.0.000027
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.

http://doi.org/10.1016/j.micinf.2016.04.002
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.

http://dx.doi.org/10.2147/IMCRJ.S99936
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.

http://doi.org/10.3389/fimmu.2017.00114
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.

http://dx.doi.org/10.1016/j.cll.2015.07.006
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.

http://doi.org/10.1089/vbz.2013.1512
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].

http://dx.doi.org/10.3201/eid2203.150269
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.

http://doi.org/10.3201/eid2202.151218
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.

http://dx.doi.org/10.3201/eid2202.150469
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.

http://doi.org/10.1016/j.ttbdis.2015.10.004
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.

http://doi.org/10.3389/fcimb.2015.00061
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
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.

http://dx.doi.org/10.3390/pathogens2030544
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.

http://doi.org/10.4269/ajtmh.13-0525
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.

Heartland virus neutralizing antibodies in vertebrate wildlife, United States, 2009–2014.
Riemersma KK, Komar N.
Emerging Infectious Diseases. 2015 Oct [Cited September 21, 2015].

http://dx.doi.org/10.3201/eid2110.150380
This retrospective evaluation determined that HRTV is widespread within the central and eastern United States.
BEHAVIOR OF TICKS

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).

http://doi.org/10.1098/rstb.2013.0556
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.

http://doi.org/10.1093/infdis/jiv775
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
Scientists Have Sequenced the Genome of the Tick that Transmits Lyme Disease
or http://tinyurl.com/zwzg5h3
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.

http://doi.org/10.1371/journal.pone.0127450
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.

http://doi.org/10.4269/ajtmh.13-0180
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.

http://doi.org/10.1186/s13071-016-1894-6
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.
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.

http://doi.org/10.1186/s13071-015-1154-1
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.

Bartonella henselae and B. koehlerae DNA in birds
Mascarelli PE, McQuillan M, Harms CA, Harms RV, Breitschwerdt EB.
Emerging Infectious Diseases March 2014

http://dx.doi.org/10.3201/eid2003.130563
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.

http://dx.doi.org/10.1007/s10393-014-0982-3
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.

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

http://dx.doi.org/10.1371/journal.pone.0168723
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.

http://doi.org/10.1093/gbe/evw080
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.
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.

http://doi.org/10.1016/j.ttbdis.2016.04.016
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.

https://dx.doi.org/10.3389/fmicb.2017.00223
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.

http://dx.doi.org/10.1016/j.ttbdis.2016.02.012
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.

http://www.ncbi.nlm.nih.gov/pubmed/25825928
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.

http://doi.org/10.1093/infdis/jiv134
For the first time we were able to develop a tick transmission model with an Ehrlichia that is pathogenic for humans.
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.

http://doi.org/10.1371/journal.pone.0118265
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.
TICK-BORNE ILLNESS PREVENTION, TESTING AND DIAGNOSIS

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

https://www.ncbi.nlm.nih.gov/pubmed/27976670
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
http://austinpublishinggroup.com/chronic-diseases/online-first.php

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.
“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
http://www.hindawi.com/journals/ipid/2010/876450.html

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.

http://dx.doi.org/10.7717/peerj.322
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.

Lyme Disease (Borrelia burgdorferi) 2017 Case Definition
Centers for Disease Control and Prevention

Council of State and Territorial Epidemiologists (CSTE) Position Statement(s)
Source: https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/

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.

http://doi.org/10.1016/j.puhe.2014.06.016
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.

http://doi.org/10.1177/2150131914540693
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.

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.

http://doi.org/10.1371/journal.pone.0168613
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.

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.

http://dx.doi.org/10.3201/eid1905.120796
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.

http://escholarship.org/uc/item/9cs1x7r5
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.

http://doi.org/10.1111/cup.12620
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.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8424027&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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.

http://dx.doi.org/10.4172/2155-9554.1000330
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.

http://dx.doi.org/10.1371/journal.pone.0064110
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.

http://doi.org/10.1093/jmp/jht043
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.

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.

http://doi.org/10.1093/infdis/jiw013
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.

http://dx.doi.org/10.1556/1886.2015.00049
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.

http://doi.org/10.1128/IAI.00349-15
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.

http://doi.org/10.1007/s10067-014-2706-z
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.

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.

http://doi.org/10.1128/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.

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.

http://doi.org/10.1093/cid/ciu703
n 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.

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC423723/pdf/jcinvest00109-0086.pdf

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.

http://tinyurl.com/mn5cxdr
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%.

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).

https://doi.org/10.2147/IJGM.S122313
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.

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
http://dx.plos.org/10.1371/journal.ppat.1004976
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.

http://www.ncbi.nlm.nih.gov/pubmed/23888345
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
http://www.onlineprnews.com/news/454866-1390261507-lyme-disease-may-be-sexually-transmitted-study-suggests.html
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
https://f1000research.com/articles/3-309/v3
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.

http://doi.org/10.1128/CVI.00026-15
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.

http://doi.org/10.1097/PEC.0000000000000028
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.

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.

http://doi.org/10.1371/journal.pone.0093243
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.

Severe Symptomatic Babesiosis Co-infection with Lyme Disease
Zaiem F, Alkawam H, Lee S, Fabisevich M.
QJM. pii: hcv168. Online first, 2015 Sep 14.

http://dx.doi.org/10.1093/qjmed/hcv168
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.

http://doi.org/10.1089/vbz.2016.2020
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.

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.

http://doi.org/10.1097/PEC.0000000000000367
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.
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.

http://dx.doi.org/10.1128/JCM.00347-13
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.

http://doi.org/10.1128/JCM.01125-13
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.

http://doi.org/10.1093/cid/ciw599
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.

http://dx.doi.org/10.1016/j.aimed.2014.11.002
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.

http://dx.doi.org/10.2147/IJGM.S73791
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.

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.

http://dx.doi.org/10.1016/S1473-3099(16)30529-1
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

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


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.

http://doi.org/10.1111/zph.12159
In a recent national survey, over 30% of healthcare providers (HCPs) reported prescribing tick bite prophylaxis in the previous year.

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.

http://dx.doi.org/10.1155/2015/587131
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.

http://doi.org/10.1111/trf.13617
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.

http://doi.org/10.1111/trf.13398
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.

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.

http://dx.doi.org/10.1186/1756-3305-6-98
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.

http://doi.org/10.1186/s13071-016-1547-9
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.
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
http://www.prweb.com/releases/2016/04/prweb13354473.htm
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.

http://dx.doi.org/10.1016/j.ttbdis.2015.12.003
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.

https://doi.org/10.2987/16-6610.1
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.

http://doi.org/10.1007/s00436-014-4232-y
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.

TICK-BORNE ILLNESS TREATMENT

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.

http://informahealthcare.com/doi/abs/10.1586/14787210.2014.940900
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.

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.

http://acn.oxfordjournals.org/content/early/2016/11/23/arclin.acw098.abstract
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. jarmo.oksi@utu.fi
Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10442678&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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.

http://dx.doi.org/10.3389/fimmu.2016.00385
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, ScientificAmerican.com, Armonk, New York

August 25, 2016
http://www.scientificamerican.com/article/something-to-grapple-with-how-wily-lyme-disease-prowls-the-body/
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.

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.

http://doi.org/10.1128/AAC.00864-15
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.

http://doi.org/10.1038/emi.2015.51
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.

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.

http://dx.doi.org/10.2147/IJGM.S44114
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.

http://goo.gl/6sAi2S
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

http://dx.doi.org/10.7243/2052-5958-1-2
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

http://dx.doi.org/10.1007/s12223-013-0272-4
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.

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.

http://doi.org/10.1093/femsle/fnv120
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.

Statistical analysis questions evidence discouraging retreatment, coverage

Published on August 31, 2012 at 9:50 AM
http://www.news-medical.net/news/20120831/Study-reports-flaws-in-design-analysis-and-interpretation-of-Lyme-disease.aspx
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.

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.

http://www.amjmed.com/article/S0002-9343%2813%2900824-3/fulltext
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.
ADVANCED TOPICS IN LYME DISEASE DIAGNOSTIC AND TREATMENT GUIDELINES FOR LYME AND OTHER TICK BORNE ILLNESSES, Sixteenth Edition, Copyright October, 2008
JOSEPH J. BURRASCANO JR., M.D.
http://www.lyme-disease-research-database.com/lyme_disease_blog_files/burrascano-treatment.html

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).

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)

http://doi.org/10.1371/journal.pone.0086907
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.

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.

http://journal.frontiersin.org/article/10.3389/fmicb.2016.00743/full
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.

http://doi.org/10.1097/INF.0000000000000804
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.

http://doi.org/10.1093/ofid/ofv178
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.

http://doi.org/10.3390/antibiotics6010010
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.

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.
https://www.ncbi.nlm.nih.gov/pubmed/17928580

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.
https://www.ncbi.nlm.nih.gov/pubmed/21941449

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.

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
http://www.medscimonit.com/fulltxt_free.php?ICID=13388

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.

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.

http://dx.doi.org/10.3390/antibiotics4030397
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.

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.

http://doi.org/10.3855/jidc.5500
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.

Pathogenicity and treatment of Bartonella infections.
Angelakis E, Raoult D.
International Journal of Antimicrobial Agents. 2014 Jul;44(1):16-25.

http://doi.org/10.1016/j.ijantimicag.2014.04.006
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.

http://doi.org/10.7759/cureus.444
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
http://www.northeastern.edu/news/2016/03/researchers-investigate-four-promising-new-treatments-for-lyme-disease/
or http://tinyurl.com/zrmvgj8
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.

http://doi.org/10.1111/jam.12970
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.

http://doi.org/10.1177/2049936116655502
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.

http://doi.org/10.7150/ijbs.16060
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.

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.

http://dx.doi.org/10.1016/j.jpeds.2015.02.015
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.

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/abstract
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.

http://dx.doi.org/10.1016/j.bpj.2016.12.039
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.
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.

http://doi.org/10.5114/pdia.2014.44014
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
http://www.onehealthinitiative.com/publications/Breitschwerdt%20J%20Neuroparasitol%20Review%202012.pdf
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.

http://doi.org/10.4269/ajtmh.16-0434
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.

http://doi.org/10.1097/NAN.0000000000000195
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
http://www.nature.com/mp/journal/v21/n6/full/mp201650a.html
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.

http://doi.org/10.1002/lary.26273
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.

https://www.jscimedcentral.com/Arthritis/arthritis-1-1008.pdf
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.

http://doi.org/10.1186/s12974-017-0789-6
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.

http://dx.doi.org/10.1016/j.diagmicrobio.2016.02.016
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.

http://doi.org/10.1111/trf.12622
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.

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.

http://dx.doi.org/10.1016/j.ijid.2013.02.016
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.

http://dx.doi.org/10.1007/s00415-015-7923-0
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.

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.

http://doi.org/10.1016/j.jcma.2014.02.001
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.

http://doi.org/10.1002/jca.21430
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.

http://doi.org/10.1007/s00436-013-3654-2
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.

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.

http://doi.org/10.1556/1886.2015.00031
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.

http://doi.org/10.1128/AEM.00239-15
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.

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.

http://doi.org/10.1002/jca.21429
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.

ASSOCIATION BETWEEN TICK-BORNE ILLNESS AND OTHER CHRONIC CONDITIONS
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.

http://doi.org/10.1007/s12035-015-9262-7
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

http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioral-psychiatric-au

Part 2

http://www.bjmp.
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role-chronic-
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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.

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.

http://dx.doi.org/10.1016/j.cmi.2015.11.009
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.

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

http://doi.org/10.1016/j.amjmed.2014.09.022
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.

http://dx.doi.org/10.1016/j.psym.2013.04.003
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.

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.

https://doi.org/10.5604/12321966.1229002
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.

http://doi.org/10.1093/cid/civ735
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.

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.

http://dx.doi.org/10.1016/j.mehy.2014.06.005
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.

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.

http://doi.org/10.1186/1742-2094-10-88
In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.

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.

http://doi.org/10.7556/jaoa.2013.048
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.

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.

http://dx.doi.org/10.5213/inj.2014.18.2.95
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.

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.

http://dx.doi.org/10.1016/j.annemergmed.2015.01.011
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.

http://dx.doi.org/10.1016/j.parkreldis.2015.05.015
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.

http://doi.org/10.1093/infdis/jiv310
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.

http://doi.org/10.1007/s00059-015-4308-1
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.

http://doi.org/10.1186/1756-0500-6-5
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.

https://doi.org/10.3389/fneur.2017.00146
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 stroke-like symptoms of unknown cause.

Lyme disease presenting as multiple ischaemic strokes
Sui Li, Michal Vytopil, Kinan Hreib, Donald E Craven
Practical Neurology, 2015;15:284-288.

http://doi.org/10.1136/practneurol-2014-001072
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.

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.

http://doi.org/10.1111/anec.12158
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.

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.

http://dx.doi.org/10.1111/cup.12102
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.

http://doi.org/10.1053/j.jfas.2015.06.006

We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing.
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
http://www.hcplive.com/conference-coverage/actrims-2016/lyme-disease-and-ms-can-overlap
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.
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.

http://doi.org/10.3233/JAD-130446
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.

http://www.omicsonline.com/open-access/neuroinfectious-diseases-abstract.php?abstract_id=67274
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.

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.

http://doi.org/10.1111/ene.12477
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

Growing list of eye problems in Lyme disease

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.

http://doi.org/10.1097/ICU.0000000000000308

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.
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.

http://doi.org/10.12659/MSM.890149
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.

http://doi.org/10.1136/bjophthalmol-2015-306855
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.

http://dx.doi.org/10.1017/S0022215114003417
In this report, a very unusual presentation of this condition is described, in which sudden onset sensorineural hearing loss was the sole presenting symptom.

Hyperosmia in Lyme disease
Puri BK, Monro JA, Julu PO, Kingston MC, Shah M.
Arquivos de Neuro-Psiquiatria. 2014 Aug;72(8):596-7.

http://dx.doi.org/10.1590/0004-282X20140109
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.

Unilateral phrenic nerve lesion in Lyme neuroborreliosis.
Djukic M, Larsen J, Lingor P, Nau R.
BMC Pulmonary Medicine. 2013 Jan 18;13:4.

http://doi.org/10.1186/1471-2466-13-4
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.

http://doi.org/10.5213/inj.2013.17.3.127
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.

http://doi.org/10.1182/blood-2013-06-506410
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

http://doi.org/10.1136/bcr-2013-201079
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.

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.

http://doi.org/10.12688/f1000research.5375.1
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.

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.

http://doi.org/10.1212/NXI.0000000000000030
While facial nerve involvement represents about 80% of cranial neuritis in Lyme neuroborreliosis (LNB), other cranial nerves may also be individually involved.

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.

http://doi.org/10.1001/jamadermatol.2014.1072
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.

http://doi.org/10.1097/DAD.0b013e31827132cb
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).

http://www.medscape.com/viewarticle/841141
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.

http://escholarship.org/uc/item/9d7813rh
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.

A New Perspective on the Possible Cause of Alzheimer’s Disease: Microbes
Press Release: Journal of Alzheimer’s Disease

15 March 2016
http://www.j-alz.com/content/new-perspective-possible-cause-alzheimers-disease-microbes
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.

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.

http://doi.org/10.4103/0253-7176.155660
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.

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.

http://dx.doi.org/10.1016/j.ajpath.2015.01.024
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.
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.

http://dx.doi.org/10.1155/2013/480739
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.

http://doi.org/10.1177/2324709614529417
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.

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.

http://doi.org/10.21037/sci.2017.01.02
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.

http://doi.org/10.1309/AJCP2PHH4HBVHZFS
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.

http://doi.org/10.1136/bcr-2016-215967
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.

http://dx.doi.org/10.1053/j.ajkd.2013.02.376
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.

http://doi.org/10.1089/vbz.2016.2004
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).
State: Tick bite can be deadly
By Cynthia McCormick, Cape Cod Times, Hyannis, Massachusetts

December 22, 2013
http://www.capecodonline.com/apps/pbcs.dll/article?AID=/20131222/NEWS/312220338
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.

http://doi.org/10.1016/j.redox.2015.03.002
– 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.

http://doi.org/10.1097/AOG.0000000000001445
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.

http://doi.org/10.21037/sci.2017.01.02

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.

http://dx.doi.org/10.1016/j.ttbdis.2015.05.010
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.

http://dx.doi.org/10.1016/B978-0-444-53490-3.00014-5
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.

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.

http://doi.org/10.1016/j.otsr.2015.02.007
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.
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.

https://doi.org/10.1097/INF.0000000000001510
These 2 cases highlight the potential multiorgan involvement that may confound the diagnosis of culture-negative infective endocarditis caused by B. henselae.

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.

http://doi.org/10.1097/DAD.0000000000000598

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.

http://doi.org/10.1111/ene.13197

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.

http://doi.org/10.1128/IAI.00781-16

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.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6343a4.htm?s_cid=mm6343a4_w
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.

http://dx.doi.org/10.1016/j.ajpath.2015.12.027
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.

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.

http://doi.org/10.1099/jmm.0.000099
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.

http://dx.doi.org/10.15570/actaapa.2015.20
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.

http://dx.doi.org/10.1016/j.jpeds.2014.09.040
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.

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.

http://www.ncbi.nlm.nih.gov/pubmed/26668338
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.

http://dx.doi.org/10.1136/bcr-2013-008716
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.

http://doi.org/10.1128/JCM.01670-14
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
http://goo.gl/eOuim
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.

GENERAL TICK-BORNE ILLNESS RESEARCH ISSUES

Priorities for Lyme Disease Research
Written by Sherrill Franklin
Focus – Opinions and Features item from LymeDisease.org, Chico, California

Here are my Top Priorities for Lyme Disease Research

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.

http://www.omicsonline.org/clinical-research-bioethics-abstract.php?abstract_id=81033
“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?

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.

http://doi.org/10.3389/fcimb.2014.00074
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.

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.

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.

http://dx.doi.org/10.1016/j.neulet.2013.10.032
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.

http://doi.org/10.1371/journal.pone.0116767
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.

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.

http://dx.doi.org/10.1155/2014/138016
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.

http://doi.org/10.3389/fpubh.2014.00073
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.
https://doi.org/10.3389/fmicb.2017.00328
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.

http://doi.org/10.1128/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.
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).

http://www.scirp.org/journal/PaperInformation.aspx?PaperID=51411
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.

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.

http://dx.doi.org/10.1177/1076217512465288
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.

The Brief case: Probable transfusion-transmitted babesiosis in a transplant recipient
Kitt E, Keaton AA, Graf EH.
Journal of Clinical Microbiology 54:2632–2634.

http://dx.doi.org/10.1128/JCM.00981-16

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.

http://doi.org/10.1056/NEJMoa1600897

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.

http://doi.org/10.1111/trf.13545
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.

http://doi.org/10.1111/trf.12908
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.

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.

http://doi.org/10.1586/14787210.2014.966084
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.