278 < Back to Research Top Published Date 25/12/2010 Prevalence of Borrelia infection in ticks from wildlife in south-west England Journal Veterinary Record Citation Vet Rec. 2010 Dec 25;167(26):1012-4 DOI 10.1136/vr.c5285 Authors Couper D, Margos G, Kurtenbach K, Turton S Abstract Borrelia species DNA was identified in 31 of 75 ticks examined (41 per cent). Twenty-three Borrelia - positive ticks (16 I hexagonus and seven I canisuga) were recovered from the five badgers, five Borrelia positive I hexagonus were recovered from four of the eight hedgehogs, two Borrelia positive I canisuga were recovered from the fox and one Borrelia- positive I ricinus was recovered from the roe deer. URL Previous https://veterinaryrecord.bmj.com/content/167/26/1012.short No Review Needed? Next

272 < Back to Research Top Published Date 17/05/2011 Burden and viability of Borrelia burgdorferi in skin and joints of patients with erythema migrans or Lyme arthritis Journal Arthritis and Rheumatism Citation Arthritis Rheum. 2011 Aug;63(8):2238-47 DOI 10.1002/art.30384 Authors Li X, McHugh GA, Damle N, Sikand VK, Glickstein L, Steere AC Abstract OBJECTIVE: To determine the burden and viability of Borrelia burgdorferi in the skin and joints of patients with Lyme disease. METHODS: Standard and quantitative polymerase chain reaction (PCR) techniques were used to detect B burgdorferi DNA in skin samples from 90 patients with erythema migrans (EM) and in synovial fluid (SF) from 63 patients with Lyme arthritis (LA) and in synovial tissue from 9 patients. Quantitative PCR determinations of B burgdorferi DNA, messenger RNA (mRNA), and ribosomal RNA (rRNA) were made in 10 skin samples from EM patients and 11 SF samples from LA patients. RESULTS: Skin lesions in most patients with EM had positive PCR results for B burgdorferi DNA. In the majority of patients with LA, a late disease manifestation, PCR results in pretreatment SF samples were positive. In patients with antibiotic-refractory arthritis, positive PCR results persisted for as long as 11 months, but positive results in samples taken during the postantibiotic period did not correlate with relapse or with the subsequent duration of arthritis, and at synovectomy, all results of PCR of synovial tissue were negative. B burgdorferi mRNA, a marker of spirochetal viability, was detected in 8 of 10 skin samples from EM patients, but in none of 11 SF samples from LA patients, even when obtained prior to antibiotic administration. Moreover, the median ratio of spirochetal rRNA to DNA, a measure of ribosomal activity, was 160 in the 10 EM skin samples, but only 0.15 in the 3 LA SF samples with positive results. CONCLUSION: B burgdorferi in the skin lesions of EM patients were active and viable, whereas those in the SF of LA patients were moribund or dead at any time point. Thus, detection of B burgdorferi DNA in SF is not a reliable test of active joint infection in Lyme disease URL Previous https://onlinelibrary.wiley.com/doi/full/10.1002/art.30384 No Review Needed? Next

292 < Back to Research Top Published Date 01/04/2010 Assessment of polymicrobial infections in ticks in New York state Journal Vector-Borne and Zoonotic Diseases Citation Vector Borne Zoonotic Dis. 2010 Apr;10(3):217-21 DOI 10.1089/vbz.2009.0036 Authors Tokarz R, Jain K, Bennett A, Briese T, Lipkin WI Abstract Ixodes scapularis ticks are clinically important hematophagous vectors. A single tick bite can lead to a polymicrobial infection. We determined the prevalence of polymicrobial infection with Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan virus in 286 adult ticks from the two counties in New York State where Lyme disease is endemic, utilizing a MassTag multiplex polymerase chain reaction assay. Seventy-one percent of the ticks harbored at least one organism; 30% had a polymicrobial infection. Infections with three microbes were detected in 5% of the ticks. One tick was infected with four organisms. Our results show that coinfection is a frequent occurrence in ticks in the two counties surveyed. URL Previous https://www.liebertpub.com/doi/abs/10.1089/vbz.2009.0036 No Review Needed? Next

175 < Back to Research Top Published Date 25/03/2016 The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis Journal BMC Infectious Diseases Citation BMC Infect Dis. 2016 Mar 25;16:140 DOI 10.1186/s12879-016-1468-4 Authors Leeflang MM, Ang CW, Berkhout J, Bijlmer HA, Van Bortel W, Brandenburg AH, Van Burgel ND, Van Dam AP, Dessau RB, Fingerle V, Hovius JW, Jaulhac B, Meijer B, Van Pelt W, Schellekens JF, Spijker R, Stelma FF, Stanek G, Verduyn-Lunel F, Zeller H, Sprong H Abstract BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the erological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice. URL Previous https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1468-4 No Review Needed? Next

174 < Back to Research Top Published Date 01/04/2016 Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening Journal Drug Design, Development and Therapy Citation Drug Des Devel Ther. 2016 Apr 1;10:1307-22 DOI 10.2147/DDDT.S101486 Authors Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim KM, Samineni AV, Parekh MB, Tayebi L, Rajadas J Abstract Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%-20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with post-treatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited >90% of B. burgdorferi growth at a concentration of <25 ?M. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies. URL Previous https://www.dovepress.com/identification-of-new-drug-candidates-against-borrelia-burgdorferi-usi-peer-reviewed-article-DDDT No Review Needed? Next

94 < Back to Research Top Published Date 31/10/2019 Sheep as Host Species for Zoonotic Babesia venatorum, United Kingdom Journal Emerging Infectious Diseases Citation Emerg Infect Dis. 2019 Dec;25(12):2257-2260 DOI 10.3201/eid2512.190459 Authors Gray A, Capewell P, Loney C, Katzer F, Shiels BR, Weir W Abstract Babesia venatorum is an increasingly prominent zoonotic parasite that predominantly infects wild deer. Our molecular examination of Babesia infecting mammals in the United Kingdom identified 18S sequences in domestic sheep isolates identical to zoonotic B. venatorum. Identification of this parasite in livestock raises concerns for public health and farming policy in Europe. URL Previous https://wwwnc.cdc.gov/eid/article/25/12/19-0459_article No Review Needed? Next

238 < Back to Research Top Published Date 18/02/2013 Improved culture conditions for the growth and detection of Borrelia from human serum Journal International Journal of Medical Sciences Citation Int J Med Sci. 2013;10(4):362-7 DOI 10.7150/ijms.5698 Authors Sapi E, Pabbati N, Datar A, Davies EM, Rattelle A, Kuo BA Abstract In this report we present a method to cultivate Borrelia spirochetes from human serum samples with high efficiency. This method incorporates improved sample collection, optimization of culture media and use of matrix protein. The method was first optimized utilizing Borrelia laboratory strains, and later by demonstrating growth of Borrelia from sera from fifty seropositive Lyme disease patients followed by another cohort of 72 Lyme disease patients, all of whom satisfied the strict CDC surveillance case definition for Lyme disease. The procedure resulted in positive cultures in 47% at 6 days and 94% at week 16. Negative controls included 48 cases. The positive identification of Borrelia was performed by immunostaining, PCR, and direct DNA sequencing. URL Previous https://www.medsci.org/v10p0362.htm No Review Needed? Next

54 < Back to Research Top Published Date 16/06/2020 Interrupted Blood Feeding in Ticks: Causes and Consequences Journal Microorganisms Citation 8(6):910 DOI 10.3390/microorganisms8060910 Authors Tahir D, Meyer L, Fourie J, Jongejan F, Mather T, Choumet V, Blagburn B, Straubinger RK, Varloud M Abstract Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne viruses, such as Powassan virus and tick-borne encephalitis virus, are transmissible within 15-60 min after tick attachment. However, a minimum of 3-24 h of tick attachment is necessary to effectively transmit bacterial agents such as Ehrlichia spp., Anaplasma spp., and Rickettsia spp. to a new host. Longer transmission periods were reported for Borrelia spp. and protozoans such as Babesia spp., which require a minimum duration of 24-48 h of tick attachment for maturation and migration of the pathogen. Laboratory observations indicate that the probability of transmission of tick-borne pathogens increases with the duration an infected tick is allowed to remain attached to the host. However, the transmission time may be shortened when partially fed infected ticks detach from their initial host and reattach to a new host, on which they complete their engorgement. For example, early transmission of tick-borne pathogens (e.g., Rickettsia rickettsii, Borrelia burgdorferi, and Brucella canis) and a significantly shorter transmission time were demonstrated in laboratory experiments by interrupted blood feeding. The relevance of such situations under field conditions remains poorly documented. In this review, we explore parameters of, and causes leading to, spontaneous interrupted feeding in nature, as well as the effects of this behavior on the minimum time required for transmission of tick-borne pathogens. Keywords: interrupted blood feeding; ixodid ticks; pathogens; transmission time. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355616/ No Review Needed? Next

224 < Back to Research Top Published Date 13/12/2013 Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013 Journal Morbidity and Mortality Weekly Report ? Centre for Disease Control & Prevention Citation MMWR Morb Mortal Wkly Rep. 2013 Dec 13;62(49):993-6 DOI Authors Ray G, Schulz T, Daniels W, Daly ER, Andrew TA, Brown CM, Cummings P, Nelson R, Cartter ML, Backenson PB, White JL, Kurpiel PM, Rockwell R, Rotans AS, Squires LS, Linden JV, Prial M , House J , Pontones P, Batten B, Blau D, DeLeon-Carnes M, Muehlenbachs A, Ritter J , Sanders J, Zaki SR , Mead P , Hinckley A, Nelson C, Perea A, Schriefer M, Molins C, Forrester D, Hertzog C Abstract Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin). Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012-July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections. URL Previous https://www.ncbi.nlm.nih.gov/pubmed/24336130 No Review Needed? Next

195 < Back to Research Top Published Date 08/03/2015 Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis Journal The American Journal of Pathology Citation Am J Pathol. 2016 May;186(5):1195-205 DOI 10.1016/j.ajpath.2015.12.027 Authors Muehlenachs A, Bollweg BC, Schulz TJ, Forrester JD, DeLeon Carnes M, Molins C, Ray GS, Cummings PM, Ritter JM, Blau DM, Andrew TA, Prial M, Ng DL, Prahlow JA, Sanders JH, Shieh WJ, Paddock CD, Schriefer ME, Mead P, Zaki SR Abstract Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. 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. URL Previous https://www.sciencedirect.com/science/article/pii/S0002944016000997 No Review Needed? Next

93 < Back to Research Top Published Date 31/10/2019 Characterization of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease Journal Biochimica et Biophysica Acta General Subjects Citation 1864(1):129455 DOI 10.1016/j.bbagen.2019.129455 Authors Cornell KA, Knippel RJ, Cortright GR, Fonken M, Guerrero C, Hall AR, Mitchell KA, Thurston JH, Erstad P, Tao A, Xu D, Parveen N Abstract Background: Borrelia burgdorferi causes Lyme disease, the most common tick-borne illness in the United States. The Center for Disease Control and Prevention estimates that the occurrence of Lyme disease in the U.S. has now reached approximately 300,000 cases annually. Early stage Borrelia burgdorferi infections are generally treatable with oral antibiotics, but late stage disease is more difficult to treat and more likely to lead to post-treatment Lyme disease syndrome. Methods: Here we examine three unique 5'-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidases (MTNs or MTANs, EC 3.2.2.9) responsible for salvage of adenine and methionine in B. burgdorferi and explore their potential as antibiotic targets to treat Lyme disease. Recombinant Borrelia MTNs were expressed and purified from E. coli. The enzymes were extensively characterized for activity, specificity, and inhibition using a UV spectrophotometric assay. In vitro antibiotic activities of MTN inhibitors were assessed using a bioluminescent BacTiter-Glo™ assay. Results: The three Borrelia MTNs showed unique activities against the native substrates MTA, SAH, and 5'-deoxyadenosine. Analysis of substrate analogs revealed that specific activity rapidly dropped as the length of the 5'-alkylthio substitution increased. Non-hydrolysable nucleoside transition state analogs demonstrated sub-nanomolar enzyme inhibition constants. Lastly, two late stage transition state analogs exerted in vitro IC50 values of 0.3-0.4 μg/mL against cultured B. burgdorferi cells. Conclusion: B. burgdorferi is unusual in that it expresses three distinct MTNs (cytoplasmic, membrane bound, and secreted) that are effectively inactivated by nucleoside analogs. General significance: The Borrelia MTNs appear to be promising targets for developing new antibiotics to treat Lyme disease. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881558/ No Review Needed? Next

71 < Back to Research Top Published Date 01/03/2020 Passive Tick Surveillance: Exploring Spatiotemporal Associations of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae), Babesia microti (Piroplasmida: Babesiidae), and Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) Infection in Ixodes scap Journal Vector-Borne and Zoonotic Diseases Citation 20(3):177-186 DOI 10.1089/vbz.2019.2509 Authors Little EAH, Molaei G Abstract Ixodes scapularis transmits a group of pathogens, including Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum, the causative agents for Lyme disease, babesiosis, and anaplasmosis, respectively. I. scapularis ticks submitted by state residents to the Connecticut Agricultural Experiment Station-Tick Testing Laboratory between 2015 and 2018 were screened using standard PCR and pathogen-specific primers. Infection and coinfection prevalence in I. scapularis was estimated to assess differences in infection status by life stage (nymph or adult female), county, and year, as well as whether infection with B. burgdorferi changes the likelihood of infection with either B. microti or A. phagocytophilum. Of the 11,254 I. scapularis acquired in Connecticut, 40.7% tested positive for at least one pathogen and the remaining 59.3% were negative. Most I. scapularis ticks tested positive for a single pathogen (33.6%), and only 7.2% were infected with more than one pathogen, of which 93.2% were identified with dual infection and 6.8% tested positive for all three pathogens. Adults were more likely than nymphs to be infected or coinfected with these pathogens. Furthermore, we found that ticks were 74% more likely to be infected with B. microti and 98% more likely to be infected with A. phagocytophilum if infected with B. burgdorferi compared with those not infected. We did not find spatial differences in infection or coinfection prevalence, but between 2015 and 2018, the likelihood that a tick was coinfected increased with time. These results from Connecticut, an endemic state for Lyme disease with long-established populations of I. scapularis, suggest that the increased likelihood of coinfection prevalence over time may have significant implications for clinical diagnosis, course, severity, and treatment of human disease cases. Keywords: Anaplasma phagocytophilum; Babesia microti; Borrelia burgdorferi; Connecticut; Ixodes scapularis; passive surveillance. URL Previous https://pubmed.ncbi.nlm.nih.gov/31580216/ No Review Needed? Next