The Variety 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.

The expanding Lyme Borrelia complex – Clinical significance of genomic species?
G. Stanek, M. Reiter
Clinical Microbiology and Infection, published online before print, February 15, 2011.
http://dx.doi.org/10.1111/j.1469-0691.2011.03492.x
Whilst B. burgdorferi remained the only human pathogen in North America, all three species are aetiologic agents of Lyme borreliosis in Europe. Another seven genospecies were described in the 1990s including species from Asia (B. japonica, B. turdi, B. tanukii), North America (B. andersonii), Europe (B. lusitaniae, B. valaisiana), and (B. bissettii) from Europe and Asia.Another eight species were delineated in the years up to 2010: B. sinica (Asia), B. spielmanii (Europe), B. yangtze (Asia), B. californiensis, B. americana, B. carolinensis (North America), B. bavariensis (Europe), and B. kurtenbachii (North America).

Biodiversity of Borrelia burgdorferi Strains in Tissues of Lyme Disease Patients.
Brisson D, Baxamusa N, Schwartz I, Wormser GP (2011)
PLoS ONE 6(8): e22926.
http://dx.doi.org/10.1371/journal.pone.0022926
The biodiversity of B. burgdorferi strains is significantly greater in tick populations than in the skin of patients with erythema migrans. In turn, strains from skin are significantly more diverse than strains at any of the disseminated sites. The cerebrospinal fluid of patients with neurologic Lyme disease harbored the least pathogen biodiversity. These results suggest that human tissues act as niches that can allow entry to or maintain only a subset of the total pathogen population. These data help to explain prior clinical observations on the natural history of B. burgdorferi infection and raise several questions that may help to direct future research to better understand the pathogenesis of this infection.

Surveillance for and Discovery of Borrelia Species in US Patients Suspected of Tickborne Illness
Luke C Kingry, Melissa Anacker, Bobbi Pritt, Jenna Bjork, Laurel Respicio-Kingry, et.al.
Clinical Infectious Diseases, online first, December 20, 2017.
https://doi.org/10.1093/cid/cix1107
Among the 7,292 tested specimens tested, five different Borrelia species were identified: two causing LB, B. burgdorferi (n=25) and B. mayonii (n=9), and three RF borreliae, B. hermsii (n=1), B. miyamotoi (n=8), and CandidatusB. johnsonii (n=1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi positive specimens, with new STs identified primarily among synovial fluids.

Multistrain infections with Lyme borreliosis pathogens in the tick vector
Durand J, Herrmann C, Genné D, Sarr A, Gern L, Voordouw MJ.
Applied and Environmental Microbiology, 83:e02552-16.
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.

Discovery of diverse Borrelia burgdorferi strains in a bird-tick cryptic cycle
Sarah A. Hamer, Graham J. Hickling, Jennifer L. Sidge, Michelle E. Rosen, Edward D. Walker, and Jean I. Tsao
Applied and Environmental Microbiology, published online ahead of print: 21 January 2011.
http://dx.doi.org/10.1128/AEM.02479-10
We identified 25 closely related B. burgdorferi strains using an rRNA gene intergenic spacer marker, the majority (68%) of which had not been reported previously. The presence of strains common to both cryptic and endemic cycles strongly implies bird-mediated dispersal. Given continued large-scale expansion of I. scapularis populations, we predict that its invasion into zones of cryptic transmission will allow for bridging of novel pathogen strains to humans and animals.

Remarkable diversity of tick or mammalian-associated Borreliae in the metropolitan San Francisco Bay Area, California.
Fedorova N, Kleinjan JE, James D, Hui LT, Peeters H, Lane RS.
Ticks Tick Borne Diseases. Online before print, 2014 Aug 13. pii: S1877-959X(14)00160-5.
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.

Ability to cause erythema migrans differs between Borrelia burgdorferi sensu lato isolates
Ellen Tijsse-Klasen, Nenad Pandak, Paul Hengeveld, Katsuhisa Takumi, Marion P Koopmans and Hein Sprong
Parasites and Vectors, 2013, 6(1):23, published online before print January 22, 2013.
http://dx.doi.org/10.1186/1756-3305-6-23
Seven different B. burgdorferi sl genospecies were identified in 152 borrelia isolates from ticks and erythema migrans biopsies. B afzelii (51%) and B. garinii (27%) were the most common in ticks. B. burgdorferi sl isolates differ in their propensity to cause erythema migrans. These differences were also found within genospecies. In other words, although B. afzelii was mostly associated with erythema migrans, some B. afzelii isolates had a low ability to cause erythema migrans.

Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease.
Strle K, Jones KL, Drouin EE, Li X, Steere AC.
American Journal of Pathology. 2011 Jun;178(6):2726-39.
http://dx.doi.org/10.1016/j.ajpath.2011.02.018
Evidence is emerging for differential pathogenicity among Borrelia burgdorferi genotypes in the United States.

New Cause for Lyme Disease Complicates Already Murky Diagnosis
Scientists claim a novel bacterium causes some different symptoms, adding to the body of research showing the complexity of the disease
By Melinda Wenner Moyer, Scientific 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.

Recurrent evolution of host and vector association in bacteria of the Borrelia burgdorferi sensu lato species complex.
Becker NS, Margos G, Blum H, Krebs S, Graf A, Lane RS, Castillo-Ramírez S, Sing A, Fingerle V.
BMC Genomics. 2016 Sep 15;17(1):734.
https://doi.org/10.1186/s12864-016-3016-4
Background The Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations.

Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States
Pritt BS, Respicio-Kingry LB, Sloan LM, Schriefer ME, Replogle AJ, Bjork J, Liu G, Kingry LC, Mead PS, Neitzel DF, Schiffman E, Hoang Johnson DK, Davis JP, Paskewitz SM, Boxrud D, Deedon A, Lee X, Miller TK, Feist MA, Steward CR, Theel ES, Patel R, Irish CL, Petersen JM
International Journal of Systematic and Evolutionary Microbiology, online first 2016 Aug 24.
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

Anaplasma phagocytophilum: deceptively simple or simply deceptive?
Severo MS, Stephens KD, Kotsyfakis M, Pedra JH.
Future Microbiology, June 2012, Vol. 7, No. 6, Pages 719-731.
http://dx.doi.org/10.2217/fmb.12.45
Anaplasma phagocytophilum is an obligate intracellular rickettsial pathogen transmitted by ixodid ticks. This bacterium colonizes myeloid and nonmyeloid cells and causes human granulocytic anaplasmosis – an important immunopathological vector-borne disease in the USA, Europe and Asia. Here, we provide an overview of the underlying events by which the immune system responds to A. phagocytophilum infection, how this pathogen counteracts host immunity and the contribution of the tick vector for microbial transmission.

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure.
Barbet AF, Al-Khedery B, Stuen S, Granquist EG, Felsheim RF, Munderloh UG.
Pathogens. 2013; 2(3):544-555.
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.

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).
Molins CR, Ashton LV, Wormser GP, Andre BG, Hess AM, Delorey MJ, Pilgard MA, Johnson BJ, Webb K, Islam MN, Pegalajar-Jurado A, Molla I, Jewett MW, Belisle JT.
Science Translational Medicine, 2017 Aug 16;9(403).
https://doi.org/10.1126/scitranslmed.aal2717
The iconic bulls eye rash is associated with Lyme disease, but similar symptoms are observed in other illnesses not caused by Borrelia burgdorferi infection, such as southern tick–associated rash illness, which has not yet been tied to a specific pathogen.

A Roadmap for Tick-Borne Flavivirus Research in the “Omics” Era
Grabowski JM, Hill CA.
Frontiers in Cellular and Infection Microbiology. 2017 Dec 22;7:519. eCollection 2017.
https://doi.org/10.3389/fcimb.2017.00519
Tick-borne flaviviruses (TBFs) affect human health globally. Human vaccines provide protection against some TBFs, and antivirals are available, yet TBF-specific control strategies are limited. Here we review the current state of genomic research on ticks and tick-borne viruses with an emphasis on TBFs.

Heartland virus neutralizing antibodies in vertebrate wildlife, United States, 2009–2014.
Riemersma KK, Komar N.
Emerging Infectious Diseases. 2015 Oct [Cited September 21, 2015].
http://dx.doi.org/10.3201/eid2110.150380
This retrospective evaluation determined that HRTV is widespread within the central and eastern United States.

Southern Tick-Associated Rash Illness (STARI) in the North: STARI Following a Tick Bite in Long Island, New York.
Feder HM Jr, Hoss DM, Zemel L, Telford SR 3rd, Dias F, Wormser GP.
Clinical Infectious Diseases, First published online: September 21, 2011.
http://dx.doi.org/10.1093/cid/cir553
The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness).

‘Tick paralysis’ strikes girl, 2 Doctors initially stumped; her recovery is fast
By Shantal Parris Riley, Poughkeepsie Journal, Poughkeepsie, New York
May 18, 2012
http://www.poughkeepsiejournal.com/article/20120518/NEWS01/305180030/-Tick-paralysis-strikes-girl-2
Health professionals are looking into a rare case of a little girl who was paralyzed after being bitten by an American dog tick. The 2-year-old was unable to eat or drink – immobilized by a potentially fatal illness

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

Bartonella quintana and Bartonella vinsonii subsp. vinsonii bloodstream co-infection in a girl from North Carolina, USA.
Breitschwerdt EB, Maggi RG.
Medical Microbiology and Immunology, online first, 2018 Sep 24.
https://doi.org/10.1007/s00430-018-0563-0
The genus Bartonella consists of globally distributed and highly diverse alpha-proteobacteria that infect a wide-range of mammals. Medically, Bartonella spp. constitute emerging, vector-borne, zoonotic, intravascular organisms that induce long-lasting bacteremia in reservoir-adapted (passive carrier of a microorganism) hosts.
At times, these bacteria are accidentally transmitted by animal scratches, bites, needles sticks or vectors to animal or human hosts. We report the first documented human case of blood stream infection with Bartonella vinsonii subsp. vinsonii in a girl from North Carolina, USA, who was co-infected with Bartonella quintana.
Limitations of Bartonella spp. serology and the challenges of microbiological culture and molecular diagnostic confirmation of co-infection with more than one Bartonella spp. are discussed. When and where these infections were acquired is unknown; however, exposure to rodents, fleas and cats in the peri-equestrian environment was a suspected source for transmission of both organisms.

Report of Non-Lyme, Erythema Migrans Rashes from New Jersey with a Review of Possible Role of Tick Salivary Toxins
Kannangara DW, Patel P.
Vector-Borne and Zoonotic Diseases, online first, 2018 Aug 21.
https://doi.org/10.1089/vbz.2018.2278
Erythema migrans (EM) rashes once considered pathognomonic of Lyme disease (LD) have been reported following bites of arthropods that do not transmit LD and in areas with no LD. Also, EM rashes have been reported in association with organisms other than members of Borrelia burgdorferi sensu lato complex. Arthropod saliva has chemicals that have effects on the host and pathogen transmission. Tick saliva has protein families similar to spiders and scorpions and even substances homologous to those found in snakes and other venomous animals. Ticks “invertebrate pharmacologists” have a sophisticated arsenal of chemicals that assist in blood feeding, pathogen transmission, and suppressing host defenses. No organisms have been isolated from many EM rashes. We propose that tick salivary toxins may play a role in the causation of rashes and laboratory abnormalities in tick-borne diseases. The role of tick salivary toxins needs further exploration.
Cases of Lyme-like EM rashes referred to as STARI (Southern Tick-Associated Rash Illness) following bites of the lone star tick, Amblyomma americanum, in the United States have been reported predominantly in Southeastern Missouri and a few in South Carolina, North Carolina, Georgia, and one case each in Mississippi and Long Island, New York. Although there is one report of Borrelia lonestari in a patient with a rash, biopsies of 31 cases of STARI, with cultures and PCR, failed to show a relationship. Distribution of A. americanum, whose bites are associated with STARI, now extends along the East Coast of the United States, including New Jersey, up to the Canadian border. As far as we are aware, there have been no prior reports of Lyme-like rashes in New Jersey. In this study, we present case examples of 2 Lyme-like rashes, variations of EM rashes, and a brief review of studies that suggest a role of tick salivary toxins in tick-borne diseases.

Co-Infection Patterns in Individual Ixodes scapularis Ticks Reveal Associations between Viral, Eukaryotic and Bacterial Microorganisms
Cross ST, Kapuscinski ML, Perino J, Maertens BL, Weger-Lucarelli J, Ebel GD, Stenglein MD.
Viruses. 2018 Jul 22;10(7). pii: E388.
https://doi.org/10.3390/v10070388
Ixodes scapularis ticks harbor a variety of microorganisms, including eukaryotes, bacteria and viruses. Some of these can be transmitted to and cause disease in humans and other vertebrates. Others are not pathogenic, but may impact the ability of the tick to harbor and transmit pathogens.
A growing number of studies have examined the influence of bacteria on tick vector competence but the influence of the tick virome remains less clear, despite a surge in the discovery of tick-associated viruses. In this study, we performed shotgun RNA sequencing on 112 individual adult I. scapularis collected in Wisconsin, USA. We characterized the abundance, prevalence and co-infection rates of viruses, bacteria and eukaryotic microorganisms.
We identified pairs of tick-infecting microorganisms whose observed co-infection rates were higher or lower than would be expected, or whose RNA levels were positively correlated in co-infected ticks. Many of these co-occurrence and correlation relationships involved two bunyaviruses, South Bay virus and blacklegged tick phlebovirus-1. These viruses were also the most prevalent microorganisms in the ticks we sampled, and had the highest average RNA levels.
Evidence of associations between microbes included a positive correlation between RNA levels of South Bay virus and Borrelia burgdorferi, the Lyme disease agent. These findings contribute to the rationale for experimental studies on the impact of viruses on tick biology and vector competence.

Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy
Crispell G, Commins SP, Archer-Hartman SA, Choudhary S, Dharmarajan G, Azadi P, Karim S.
Frontiers in Immunology. 2019 May 17;10:1056. eCollection 2019.
https://doi.org/10.3389/fimmu.2019.01056
Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.

Ticks and Tularemia: Do We Know What We Don’t Know?
Zellner B, Huntley JF.
Frontiers in Cellular and Infection Microbiology, 2019 May 8;9:146. eCollection 2019.
https://doi.org/10.3389/fcimb.2019.00146
Francisella tularensis, the causative agent of the zoonotic disease tularemia, is characterized by high morbidity and mortality rates in over 190 different mammalian species, including humans. Based on its low infectious dose, multiple routes of infection, and ability to induce rapid and lethal disease, F. tularensis has been recognized as a severe public health threat—being designated as a NIH Category A Priority Pathogen and a CDC Tier 1 Select Agent.
Despite concerns over its use as a bioweapon, most U.S. tularemia cases are tick-mediated and ticks are believed to be the major environmental reservoir for F. tularensis in the U.S. The American dog tick (Dermacentor variabilis) has been reported to be the primary tick vector for F. tularensis, but the lone star tick (Amblyomma americanum) and other tick species also have been shown to harbor F. tularensis.

Multistate Infestation with the Exotic Disease-Vector Tick Haemaphysalis longicornis 
Beard CB, Occi J, Bonilla DL, et al.
Morbidity and Mortality Weekly Report (MMWR) 2018;67:1310–1313.http://dx.doi.org/10.15585/mmwr.mm6747a3
During 2017–2018, H. longicornis has been detected in Arkansas, Connecticut, Maryland, New Jersey, New York, North Carolina, Pennsylvania, Virginia, and West Virginia on various species of domestic animals and wildlife, and from two humans.
The presence of H. longicornis in the United States represents a new and emerging disease threat. Characterization of the tick’s biology and ecology are needed, and surveillance efforts should include testing for potential indigenous and exotic pathogens

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