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PLoS Neglected Tropical Diseases Feb 2023Borrelia miyamotoi is a relapsing fever spirochete that shares the same vector as Lyme disease causing Borrelia. This epidemiological study of B. miyamotoi was conducted...
Borrelia miyamotoi is a relapsing fever spirochete that shares the same vector as Lyme disease causing Borrelia. This epidemiological study of B. miyamotoi was conducted in rodent reservoirs, tick vectors and human populations simultaneously. A total of 640 rodents and 43 ticks were collected from Phop Phra district, Tak province, Thailand. The prevalence rate for all Borrelia species was 2.3% and for B. miyamotoi was 1.1% in the rodent population, while the prevalence rate was quite high in ticks collected from rodents with an infection rate of 14.5% (95% CI: 6.3-27.6%). Borrelia miyamotoi was detected in Ixodes granulatus collected from Mus caroli and Berylmys bowersi, and was also detected in several rodent species (Bandicota indica, Mus spp., and Leopoldamys sabanus) that live in a cultivated land, increasing the risk of human exposure. Phylogenetic analysis revealed that the B. miyamotoi isolates detected in rodents and I. granulatus ticks in this study were similar to isolates detected in European countries. Further investigation was conducted to determine the serological reactivity to B. miyamotoi in human samples received from Phop Phra hospital, Tak province and in rodents captured from Phop Phra district using an in-house, direct enzyme-linked immunosorbent assay (ELISA) assay with B. miyamotoi recombinant glycerophosphodiester-phosphodiesterase (rGlpQ) protein as coated antigen. The results showed that 17.9% (15/84) of human patients and 9.0% (41/456) of captured rodents had serological reactivity to B. miyamotoi rGlpQ protein in the study area. While a low level of IgG antibody titers (100-200) was observed in the majority of seroreactive samples, higher titers (400-1,600) were also detected in both humans and rodents. This study provides the first evidence of B. miyamotoi exposure in human and rodent populations in Thailand and the possible roles of local rodent species and Ixodes granulatus tick in its enzootic transmission cycle in nature.
Topics: Animals; Humans; Relapsing Fever; Phylogeny; Thailand; Borrelia; Ixodes; Murinae
PubMed: 36809255
DOI: 10.1371/journal.pntd.0011159 -
Clinical Microbiology and Infection :... Apr 2020Borrelia miyamotoi is a relapsing fever Borrelia, transmitted by hard (Ixodes) ticks, which are also the main vector for Borrelia burgdorferi. A widely used test for...
OBJECTIVES
Borrelia miyamotoi is a relapsing fever Borrelia, transmitted by hard (Ixodes) ticks, which are also the main vector for Borrelia burgdorferi. A widely used test for serodiagnosis of Lyme borreliosis is an enzyme immunoassay (EIA) based on the C6 peptide of the B. burgdorferi sl VlsE protein. We set out to study C6 reactivity upon infection with B. miyamotoi in a large well-characterized set of B. miyamotoi disease (BMD) patient sera and in experimental murine infection.
METHODS
We performed in silico analyses, comparing the C6-peptide to immunodominant B. miyamotoi variable large proteins (Vlps). Next, we determined C6 reactivity in sera from mice infected with B. miyamotoi and in a unique longitudinal set of 191 sera from 46 BMD patients.
RESULTS
In silico analyses revealed similarity of the C6 peptide to domains within B. miyamotoi Vlps. Cross-reactivity against the C6 peptide was confirmed in 21 out of 24 mice experimentally infected with B. miyamotoi. Moreover, 35 out of 46 BMD patients had a C6 EIA Lyme index higher than 1.1 (positive). Interestingly, 27 out of 37 patients with a C6 EIA Lyme index higher than 0.9 (equivocal) were negative when tested for specific B. burgdorferi sl antibodies using a commercially available immunoblot.
CONCLUSIONS
We show that infection with B. miyamotoi leads to cross-reactive antibodies to the C6 peptide. Since BMD and Lyme borreliosis are found in the same geographical locations, caution should be used when relying solely on C6 reactivity testing. We propose that a positive C6 EIA with negative immunoblot, especially in patients with fever several weeks after a tick bite, warrants further testing for B. miyamotoi.
Topics: Animals; Antibodies, Bacterial; Bacterial Proteins; Borrelia; Computer Simulation; Cross Reactions; Female; Humans; Immunoblotting; Ixodes; Longitudinal Studies; Lyme Disease; Mice; Mice, Inbred C3H; Peptides; Reagent Kits, Diagnostic; Relapsing Fever; Serologic Tests
PubMed: 31404672
DOI: 10.1016/j.cmi.2019.07.026 -
Emerging Infectious Diseases May 2018We investigated whether Borrelia miyamotoi disease can be detected in its early stage by using PCR for borrelial 16S rRNA, which molecule (DNA or RNA) is the best choice...
We investigated whether Borrelia miyamotoi disease can be detected in its early stage by using PCR for borrelial 16S rRNA, which molecule (DNA or RNA) is the best choice for this test, and whether spirochetes are present in blood during the acute phase of B. miyamotoi disease. A total of 473 patients with a suspected tickborne infection in Yekaterinburg, Russia, in 2009, 2010, and 2015 were enrolled in this study. Blood samples were analyzed by using quantitative PCR or ELISA, and a diagnosis of borreliosis was confirmed for 310 patients. For patients with erythema migrans, 5 (3%) of 167 were positive for B. miyamotoi by PCR; for patients without erythema migrans, 65 (45%) of 143 were positive for B. miyamotoi by PCR. The median concentration for RNA was 3.8 times that for DNA. Median time for detection of B. miyamotoi in blood was 4 days.
Topics: Bacteremia; Borrelia; Borrelia Infections; DNA, Bacterial; Erythema Chronicum Migrans; False Negative Reactions; Humans; Polymerase Chain Reaction; RNA, Bacterial; RNA, Ribosomal, 16S
PubMed: 29664394
DOI: 10.3201/eid2405.170829 -
Microbiology Spectrum Dec 2022Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array...
Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array simultaneously screening for IgM and IgG reactivity against multiple recombinant B. miyamotoi antigens. The array included six B. miyamotoi antigens: glycerophosphodiester phosphodiesterase (GlpQ), multiple variable major proteins (Vmps), and flagellin. Sera included samples from cases of PCR-proven Borrelia miyamotoi disease (BMD), multiple potentially cross-reactive control groups (including patients with culture-proven Lyme borreliosis, confirmed Epstein-Barr virus, cytomegalovirus, or other spirochetal infections), and several healthy control groups from regions where is endemic and regions where it is nonendemic. Based on receiver operating characteristic (ROC) analyses, the cutoff for reactivity per antigen was set at 5 μg/mL for IgM and IgG. The individual antigens demonstrated high sensitivity but relatively low specificity for both IgM and IgG. The best-performing single antigen (GlpQ) showed a sensitivity of 88.0% (95% confidence interval [CI], 78.9 to 93.5) and a specificity of 94.2% (95% CI, 92.7 to 95.6) for IgM/IgG. Applying the previous published diagnostic algorithm-defining seroreactivity as reactivity against GlpQ and any Vmp-revealed a significantly higher specificity of 98.5% (95% CI, 97.6 to 99.2) but a significantly lower sensitivity of 79.5% (95% CI, 69.3 to 87.0) for IgM/IgG compared to GlpQ alone. Therefore, we propose to define seroreactivity as reactivity against GlpQ and any Vmp or flagellin which resulted in a comparable sensitivity of 84.3% (95% CI, 74.7 to 90.8) and a significantly higher specificity of 97.9% (95% CI, 96.9 to 98.7) for IgM/IgG compared to GlpQ alone. In conclusion, we have developed and validated a novel serological tool to diagnose BMD that could be implemented in clinical practice and epidemiological studies. This paper describes the protein array as a novel serological test for the diagnosis of Borrelia miyamotoi disease (BMD), by reporting the methodology, the development of a diagnostic algorithm, and its extensive validation. With rising numbers of ticks and tick bites, tick-borne diseases, such as BMD, urgently deserve further societal and medical attention. B. miyamotoi is prevalent in ticks across the northern hemisphere. Humans are exposed to, and infected by, B. miyamotoi and develop BMD in Asia, in North America, and to a lesser extent in Europe. However, the burden of infection and disease remains largely unknown, due to the noncharacteristic clinical presentation, together with the lack of awareness and availability of diagnostic tools. With this paper, we offer a novel diagnostic tool which will assist in assessing the burden of disease and could be implemented in clinical care.
Topics: Animals; Humans; Borrelia; Flagellin; Immunoglobulin G; Immunoglobulin M; Ixodes; Protein Array Analysis; Borrelia Infections; Antibodies, Bacterial
PubMed: 36314925
DOI: 10.1128/spectrum.02036-22 -
Journal of Medical Entomology Jul 2023Blacklegged ticks (Ixodes scapularis Say, Acari: Ixodidae) were collected from 432 locations across New York State (NYS) during the summer and autumn of 2015-2020 to...
Spatiotemporal distribution of Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) and coinfection with other tick-borne pathogens in host-seeking Ixodes scapularis (Acari: Ixodidae) from New York State, USA.
Blacklegged ticks (Ixodes scapularis Say, Acari: Ixodidae) were collected from 432 locations across New York State (NYS) during the summer and autumn of 2015-2020 to determine the prevalence and geographic distribution of Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) and coinfections with other tick-borne pathogens. A total of 48,386 I. scapularis were individually analyzed using a multiplex real-time polymerase chain reaction assay to simultaneously detect the presence of Bo. miyamotoi, Borrelia burgdorferi (Spirochaetales: Spirochaetaceae), Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and Babesia microti (Piroplasmida: Babesiidae). Overall prevalence of Bo. miyamotoi in host-seeking nymphs and adults varied geographically and temporally at the regional level. The rate of polymicrobial infection in Bo. miyamotoi-infected ticks varied by developmental stage, with certain co-infections occurring more frequently than expected by chance. Entomological risk of exposure to Bo. miyamotoi-infected nymphal and adult ticks (entomological risk index [ERI]) across NYS regions in relation to human cases of Bo. miyamotoi disease identified during the study period demonstrated spatial and temporal variation. The relationship between select environmental factors and Bo. miyamotoi ERI was explored using generalized linear mixed effects models, resulting in different factors significantly impacting ERI for nymphs and adult ticks. These results can inform estimates of Bo. miyamotoi disease risk and further our understanding of Bo. miyamotoi ecological dynamics in regions where this pathogen is known to occur.
Topics: Humans; Animals; Ixodes; Coinfection; Ixodidae; Spirochaetaceae; New York; Borrelia; Borrelia burgdorferi; Nymph
PubMed: 37156099
DOI: 10.1093/jme/tjad054 -
Parasites & Vectors Apr 2020Borrelia miyamotoi is a relapsing fever Borrelia species transmitted by ticks of the Ixodes ricinus complex. Human disease caused by B. miyamotoi was first described in...
BACKGROUND
Borrelia miyamotoi is a relapsing fever Borrelia species transmitted by ticks of the Ixodes ricinus complex. Human disease caused by B. miyamotoi was first described in Russia and later in the USA and Japan. Additionally, five cases of meningoencephalitis in immunocompromised patients and one case in an apparently immunocompetent patient were described.
METHODS
We investigated the presence of B. miyamotoi in I. ricinus nymphs and in patients suspected of human granulocytic anaplasmosis, in Alsace (France), an endemic area for I. ricinus ticks and Lyme borreliosis, using direct (PCR) and indirect diagnosis (glycerophosphoryldiester-phosphodiesterase (GlpQ) serology).
RESULTS
Borrelia miyamotoi was found in 2.2% of 4354 ticks collected between 2013 and 2016. None of the 575 blood samples, collected from the patients suspected of HGA, was found positive for B. miyamotoi by PCR. Acute and late sera from 138 of these 575 patients were available. These paired sera were tested for IgM and IgG antibodies against the B. miyamotoi GlpQ antigen. A total of 14 out of 138 patients had at least one positive parameter (i.e. anti-GlpQ IgG and/or IgM). One patient seroconverted for IgG, and three had isolated IgM in the acute serum. These three patients were treated with doxycycline which could have prevented seroconversion. After reviewing clinical data and other biological tests performed, co-exposure among different microorganisms vectored by ticks or serological cross-reactivity could not be ruled out in these different cases. One patient had persistent IgG, which strongly suggests previous exposure to B. miyamotoi.
CONCLUSIONS
Humans can be exposed to B. miyamotoi through tick bites in Alsace. We present serological data for possible B. miyamotoi exposure or infection of patients with fever after tick bite. Future studies should determine the incidence, clinical course and burden of this emerging tick-borne disease in other parts of Western Europe.
Topics: Animals; Arachnid Vectors; Borrelia; DNA, Bacterial; Disease Reservoirs; Fever; France; Humans; Ixodes; Lyme Disease; Male; Nymph; Polymerase Chain Reaction; Serologic Tests; Tick Bites; Tick-Borne Diseases
PubMed: 32303256
DOI: 10.1186/s13071-020-04071-9 -
Veterinary Microbiology Nov 2023Ticks are the main vectors for the transmission of bacterial, protist and viral pathogens in Europe affecting wildlife and domestic animals. However, some of them are... (Review)
Review
Exploring the diversity of tick-borne pathogens: The case of bacteria (Anaplasma, Rickettsia, Coxiella and Borrelia) protozoa (Babesia and Theileria) and viruses (Orthonairovirus, tick-borne encephalitis virus and louping ill virus) in the European continent.
Ticks are the main vectors for the transmission of bacterial, protist and viral pathogens in Europe affecting wildlife and domestic animals. However, some of them are zoonotic and can cause serious, sometimes fatal, problems in human health. A systematic review in PubMed/MEDLINE database was conducted to determine the spatial distribution and host and tick species ranges of a selection of tick-borne bacteria (Anaplasma spp., Borrelia spp., Coxiella spp., and Rickettsia spp.), protists (Babesia spp. and Theileria spp.), and viruses (Orthonairovirus, and flaviviruses tick-borne encephalitis virus and louping ill virus) on the European continent in a five-year period (November 2017 - November 2022). Only studies using PCR methods were selected, retrieving a total of 429 articles. Overall, up to 85 species of the selected tick-borne pathogens were reported from 36 European countries, and Anaplasma spp. was described in 37% (159/429) of the articles, followed by Babesia spp. (34%, 148/429), Borrelia spp. (34%, 147/429), Rickettsia spp. (33%, 142/429), Theileria spp. (11%, 47/429), tick-borne flaviviruses (9%, 37/429), Orthonairovirus (7%, 28/429) and Coxiella spp. (5%, 20/429). Host and tick ranges included 97 and 50 species, respectively. The highest tick-borne pathogen diversity was detected in domestic animals, and 12 species were shared between humans, wildlife, and domestic hosts, highlighting the following zoonotic species: Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Borrelia afzelii, Borrelia burgdorferi s.s., Borrelia garinii, Borrelia miyamotoi, Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, Rickettsia monacensis and tick-borne encephalitis virus. These results contribute to the implementation of effective interventions for the surveillance and control of tick-borne diseases.
Topics: Animals; Humans; Babesia; Encephalitis Viruses, Tick-Borne; Anaplasma; Theileria; Coxiella; Ixodes; Borrelia; Rickettsia; Animals, Domestic; Tick-Borne Diseases; Animals, Wild
PubMed: 37866329
DOI: 10.1016/j.vetmic.2023.109892 -
Ticks and Tick-borne Diseases May 2023Borrelia miyamotoi is a tick-borne zoonotic agent that causes hard tick-borne relapsing fever, an emerging disease in humans. Some small mammalian and bird species are...
Borrelia miyamotoi is a tick-borne zoonotic agent that causes hard tick-borne relapsing fever, an emerging disease in humans. Some small mammalian and bird species are reported to be reservoirs of B. miyamotoi. This study aims to examine Borrelia species present in rodents captured from rural areas of Turkey. Blood samples of rodents were initially screened with Borrelia 16S rRNA qPCR. The Borrelia flaB gene was subsequently amplified by conventional PCR, after which all positive samples were sequenced. Borrelia miyamotoi was observed in nine out of 536 blood samples (1.7%) collected from wild rodents. Phylogenetic analysis showed that all positive samples belonged to the European genotype clade of B. miyamotoi. PCR positivity was 5.3%, 3.7%, and 1.8% in Apodemus uralensis, Apodemus flavicollis, and Myodes glareolus, respectively. Borrelia burgdorferi sensu lato that causes Lyme borreliosis in humans could not be detected in the rodents. In this study, presence of B. miyamotoi DNA is reported for the first time in rodents in Turkey.
Topics: Humans; Animals; Ixodes; Turkey; Phylogeny; RNA, Ribosomal, 16S; Borrelia; Murinae
PubMed: 36857879
DOI: 10.1016/j.ttbdis.2023.102143 -
Frontiers in Immunology 2017The emerging pathogen, , is a relapsing fever spirochete vectored by the same species of ticks that carry the causative agents of Lyme disease in the US, Europe, and... (Review)
Review
The emerging pathogen, , is a relapsing fever spirochete vectored by the same species of ticks that carry the causative agents of Lyme disease in the US, Europe, and Asia. Symptoms caused by infection with are similar to a relapsing fever infection. However, has adapted to different vectors and reservoirs, which could result in unique physiology, including immune evasion mechanisms. Lyme utilize a combination of -produced inhibitors and native proteins [i.e., factor H-binding proteins (FHBPs)/complement regulator-acquiring surface proteins, p43, BBK32, BGA66, BGA71, CD59-like protein] to inhibit complement, while some relapsing fever spirochetes use C4b-binding protein and likely -produced inhibitors. To evade the humoral response, utilize antigenic variation of either outer surface proteins (Osps) and the Vmp-like sequences (Vls) system (Lyme borreliae) or variable membrane proteins (Vmps, relapsing fever borreliae). possesses putative FHBPs and antigenic variation of Vmps has been demonstrated. This review summarizes and compares the common mechanisms utilized by Lyme and relapsing fever spirochetes, as well as the current state of understanding immune evasion by .
PubMed: 28154563
DOI: 10.3389/fimmu.2017.00012 -
MBio Sep 2019Tick-borne diseases have doubled in the last 12 years, and their geographic distribution has spread as well. The clinical spectrum of tick-borne diseases can range...
Tick-borne diseases have doubled in the last 12 years, and their geographic distribution has spread as well. The clinical spectrum of tick-borne diseases can range from asymptomatic to fatal infections, with a disproportionate incidence in children and the elderly. In the last few years, new agents have been discovered, and genetic changes have helped in the spread of pathogens and ticks. Polymicrobial infections, mostly in , can complicate diagnostics and augment disease severity. ticks have expanded their range, resulting in a dynamic and complex situation, possibly fueled by climate change. To document these changes, using molecular biology strategies for pathogen detection, an assessment of 12 microbes (9 pathogens and 3 symbionts) in three species of ticks was done in Suffolk County, New York. At least one agent was detected in 63% of was the most prevalent pathogen (57% in adults; 27% in nymphs), followed by (14% in adults; 15% in nymphs), (14% in adults; 2% in nymphs), (3% in adults), and Powassan virus (2% in adults). Polymicrobial infections were detected in 22% of ticks, with coinfections of and (9%) and of and (7%). Three species were detected in 4% of ticks. The rickettsiae constituted the largest prokaryotic biomass of all the ticks tested and included , , and The high rates of polymicrobial infection in ticks present an opportunity to study the biological interrelationships of pathogens and their vectors. Tick-borne diseases have increased in prevalence in the United States and abroad. The reasons for these increases are multifactorial, but climate change is likely to be a major factor. One of the main features of the increase is the geographic expansion of tick vectors, notably , which has brought new pathogens to new areas. The clinical spectrum of tick-borne diseases can range from asymptomatic to fatal infections, with a disproportionate incidence in children and the elderly. In addition, new pathogens that are cotransmitted by have been discovered and have led to difficult diagnoses and to disease severity. Of these, , the agent of Lyme disease, continues to be the most frequently transmitted pathogen. However, , (another spirochete), , and Powassan virus are frequent cotransmitted agents. Polymicrobial infection has important consequences for the diagnosis and management of tick-borne diseases.
Topics: Anaplasma phagocytophilum; Animals; Babesia microti; Borrelia; Borrelia burgdorferi; Climate Change; Encephalitis Viruses, Tick-Borne; Humans; Ixodes; Lyme Disease; New York; Nymph; Prevalence; Rickettsia; Tick-Borne Diseases
PubMed: 31506314
DOI: 10.1128/mBio.02055-19