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Clinical Microbiology and Infection :... Dec 2018Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against...
OBJECTIVES
Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) has been performed experimentally but has not been extensively clinically validated. Because we had previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls.
METHODS
We assessed seroreactivity against GlpQ and four Vmps in a well-described, longitudinal cohort of sera from BMD patients (n=182), healthy blood donors (n=136) and controls (n=68). All samples were tested by ELISA and positive sera were tested by western blot, and antibody dynamics and diagnostic value were assessed.
RESULTS
IgM antibodies against GlpQ and Vmps peaked between 11 and 20 days, and IgG between 21 and 50 days, after disease onset. Various combinations of GlpQ and Vmps increased sensitivity and/or specificity compared to single antigens. Notably, the GlpQ or variable large protein (Vlp)-15/16 combination yielded a sensitivity of 94.7% (95% CI: 75.4-99.7) 11-20 days after disease onset and a specificity of 96.6% (92.7-98.4) for IgM. A specificity of 100% (97.8-100) for IgM, and 98.3% for IgG (95.2-100), was found when positivity was defined as reactivity to GlpQ and any Vmp, with maximum sensitivities of 79% (56.7-91.5) for IgM and 86.7% (62.1-97.6) for IgG.
CONCLUSIONS
We clearly demonstrate here the diagnostic potential of these seromarkers. Our findings will facilitate future epidemiological and clinical studies on BMD and lead to the development of a serologic test to be used in clinical practice.
Topics: Antibodies, Bacterial; Bacterial Proteins; Borrelia; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Immunoglobulin M; Longitudinal Studies; Lyme Disease; Phosphoric Diester Hydrolases; Polymerase Chain Reaction; Sensitivity and Specificity; Serologic Tests; Tick-Borne Diseases
PubMed: 29550499
DOI: 10.1016/j.cmi.2018.03.009 -
Emerging Infectious Diseases Dec 2021During 2013-2019, Borrelia miyamotoi infection was detected in 19 US states. Infection rate was 0.5%-3.2%; of B. miyamotoi-positive ticks, 59.09% had concurrent...
During 2013-2019, Borrelia miyamotoi infection was detected in 19 US states. Infection rate was 0.5%-3.2%; of B. miyamotoi-positive ticks, 59.09% had concurrent infections. B. miyamotoi is homogeneous with 1 genotype from Ixodes scapularis ticks in northeastern and midwestern states and 1 from I. pacificus in western states.
Topics: Animals; Borrelia; Borrelia Infections; Humans; Ixodes; United States
PubMed: 34808077
DOI: 10.3201/eid2712.204646 -
Ticks and Tick-borne Diseases Feb 2018Borrelia miyamotoi is a spirochete bacterium related to Borrelia burgdorferi sensu lato, the cause of Lyme borreliosis, and vectored by ticks. In 2014, B. miyamotoi was...
Borrelia miyamotoi is a spirochete bacterium related to Borrelia burgdorferi sensu lato, the cause of Lyme borreliosis, and vectored by ticks. In 2014, B. miyamotoi was identified in three questing Ixodes ricinus collected in the UK. We sought to confirm the presence of B. miyamotoi in the UK. Ticks were collected from four locations not previously investigated for B. miyamotoi or B. burgdorferi s.l. and of which two are considered as Lyme borreliosis "hotspots" based on hospital records of the disease. We independently confirm that B. miyamotoi is present in the UK and support the view that B. miyamotoi is likely to have a broad geographic distribution, at low levels. Our study also adds to the existing data on the distribution of B. burgdorferi s.l. in the UK and demonstrates that although the two "hotspots" had relatively high tick densities, they did not have the highest proportion of infected ticks.
Topics: Animals; Borrelia; Borrelia burgdorferi; England; Ixodes; Multiplex Polymerase Chain Reaction; Population Density; Prevalence
PubMed: 28939383
DOI: 10.1016/j.ttbdis.2017.09.007 -
Emerging Infectious Diseases Jul 2014Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in...
Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all Lyme disease-endemic areas of the United States. To determine the seroprevalence of IgG against B. miyamotoi sensu lato in the northeastern United States and assess whether serum from B. miyamotoi sensu lato-infected persons is reactive to B. burgdorferi antigens, we tested archived serum samples from area residents during 1991-2012. Of 639 samples from healthy persons, 25 were positive for B. miyamotoi sensu lato and 60 for B. burgdorferi. Samples from ≈10% of B. miyamotoi sensu lato-seropositive persons without a recent history of Lyme disease were seropositive for B. burgdorferi. Our results suggest that human B. miyamotoi sensu lato infection may be common in southern New England and that B. burgdorferi antibody testing is not an effective surrogate for detecting B. miyamotoi sensu lato infection.
Topics: Antibodies, Bacterial; Borrelia; Borrelia Infections; Female; Humans; Immunoglobulin G; Lyme Disease; Male; Middle Aged; New England; Seroepidemiologic Studies
PubMed: 24960072
DOI: 10.3201/eid2007.131587 -
Ticks and Tick-borne Diseases Mar 2018The blacklegged tick, Ixodes scapularis, is the primary vector to humans in the eastern United States of the deer tick virus lineage of Powassan virus (Powassan virus... (Review)
Review
The blacklegged tick, Ixodes scapularis, is the primary vector to humans in the eastern United States of the deer tick virus lineage of Powassan virus (Powassan virus disease); the protozoan parasite Babesia microti (babesiosis); and multiple bacterial disease agents including Anaplasma phagocytophilum (anaplasmosis), Borrelia burgdorferi and Borrelia mayonii (Lyme disease), Borrelia miyamotoi (relapsing fever-like illness, named Borrelia miyamotoi disease), and Ehrlichia muris eauclairensis (a minor causative agent of ehrlichiosis). With the notable exception of Powassan virus, which can be transmitted within minutes after attachment by an infected tick, there is no doubt that the risk of transmission of other I. scapularis-borne pathogens, including Lyme disease spirochetes, increases with the length of time (number of days) infected ticks are allowed to remain attached. This review summarizes data from experimental transmission studies to reinforce the important disease-prevention message that regular (at least daily) tick checks and prompt tick removal has strong potential to reduce the risk of transmission of I. scapularis-borne bacterial and parasitic pathogens from infected attached ticks. The most likely scenario for human exposure to an I. scapularis-borne pathogen is the bite by a single infected tick. However, recent reviews have failed to make a clear distinction between data based on transmission studies where experimental hosts were fed upon by a single versus multiple infected ticks. A summary of data from experimental studies on transmission of Lyme disease spirochetes (Bo. burgdorferi and Bo. mayonii) by I. scapularis nymphs indicates that the probability of transmission resulting in host infection, at time points from 24 to 72 h after nymphal attachment, is higher when multiple infected ticks feed together as compared to feeding by a single infected tick. In the specific context of risk for human infection, the most relevant experimental studies therefore are those where the probability of pathogen transmission at a given point in time after attachment was determined using a single infected tick. The minimum duration of attachment by single infected I. scapularis nymphs required for transmission to result in host infection is poorly defined for most pathogens, but experimental studies have shown that Powassan virus can be transmitted within 15 min of tick attachment and both A. phagocytophilum and Bo. miyamotoi within the first 24 h of attachment. There is no experimental evidence for transmission of Lyme disease spirochetes by single infected I. scapularis nymphs to result in host infection when ticks are attached for only 24 h (despite exposure of nearly 90 experimental rodent hosts across multiple studies) but the probability of transmission resulting in host infection appears to increase to approximately 10% by 48 h and reach 70% by 72 h for Bo. burgdorferi. Caveats to the results from experimental transmission studies, including specific circumstances (such as re-attachment of previously partially fed infected ticks) that may lead to more rapid transmission are discussed.
Topics: Anaplasma phagocytophilum; Anaplasmosis; Animals; Babesia microti; Babesiosis; Bacterial Infections; Borrelia; Ehrlichia; Ehrlichiosis; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Female; Humans; Ixodes; Lyme Disease; Relapsing Fever; Time Factors
PubMed: 29398603
DOI: 10.1016/j.ttbdis.2018.01.002 -
PloS One 2016Based on chromosome sequences, the human pathogen Borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. But atypically for relapsing...
Based on chromosome sequences, the human pathogen Borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. But atypically for relapsing fever agents, B. miyamotoi is transmitted not by soft ticks but by hard ticks, which also are vectors of Lyme disease Borrelia species. To further assess the relationships of B. miyamotoi to species that cause relapsing fever, I investigated extrachromosomal sequences of a North American strain with specific attention on plasmid-borne vsp and vlp genes, which are the underpinnings of antigenic variation during relapsing fever. For a hybrid approach to achieve assemblies that spanned more than one of the paralogous vsp and vlp genes, a database of short-reads from next-generation sequencing was supplemented with long-reads obtained with real-time DNA sequencing from single polymerase molecules. This yielded three contigs of 31, 16, and 11 kb, which each contained multiple and diverse sequences that were homologous to vsp and vlp genes of the relapsing fever agent B. hermsii. Two plasmid fragments had coding sequences for plasmid partition proteins that differed from each other from paralogous proteins for the megaplasmid and a small plasmid of B. miyamotoi. One of 4 vsp genes, vsp1, was present at two loci, one of which was downstream of a candiate prokaryotic promoter. A limited RNA-seq analysis of a population growing in the blood of mice indicated that of the 4 different vsp genes vsp1 was the one that was expressed. The findings indicate that B. miyamotoi has at least four types of plasmids, two or more of which bear vsp and vlp gene sequences that are as numerous and diverse as those of relapsing fever Borrelia. The database and insights from these findings provide a foundation for further investigations of the immune responses to this pathogen and of the capability of B. miyamotoi for antigenic variation.
Topics: Amino Acid Sequence; Animals; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Base Sequence; Borrelia; Mice; Mice, SCID; Molecular Sequence Data; Plasmids; Ticks
PubMed: 26785134
DOI: 10.1371/journal.pone.0146283 -
Pathogens (Basel, Switzerland) Feb 2020In Europe, ticks transmit pathogens such as sensu lato and tick-borne encephalitis virus (TBEV). In addition, there is evidence for transmission to humans from of , ,... (Review)
Review
In Europe, ticks transmit pathogens such as sensu lato and tick-borne encephalitis virus (TBEV). In addition, there is evidence for transmission to humans from of , , , , and . However, whether infection with these potential tick-borne pathogens results in human disease has not been fully demonstrated for all of these tick-borne microorganisms. To evaluate the available evidence for a causative relation between infection and disease, the current study analyses European case reports published from 2008 to 2018, supplemented with information derived from epidemiological and experimental studies. The evidence for human disease causality in Europe found in this review appeared to be strongest for . and . Nonetheless, some knowledge gaps still exist. Importantly, comprehensive evidence for pathogenicity is lacking for the remaining tick-borne microorganisms. Such evidence could be gathered best through prospective studies, for example, studies enrolling patients with a fever after a tick bite, the development of specific new serological tools, isolation of these microorganisms from ticks and patients and propagation in vitro, and through experimental studies.
PubMed: 32102367
DOI: 10.3390/pathogens9020150 -
International Journal For Parasitology.... Apr 2019sensu lato (s.l.) DNA was detected by PCR in Schulze, 1930, Koch, 1844 Nuttall et Warburton, 1915 and Olenev, 1932 ticks collected in the Amur region, the Jewish...
sensu lato (s.l.) DNA was detected by PCR in Schulze, 1930, Koch, 1844 Nuttall et Warburton, 1915 and Olenev, 1932 ticks collected in the Amur region, the Jewish Autonomous region, the Sakhalin region and on the Khabarovsk territory. Infection rate of with s.l. 10-69% exceeded the corresponding values of three other tick species in all examined regions during 1999-2014 despite different tick abundance and dominance structure. Bacterial loads estimated on the base of quantitative real time PCR varied from 10 to 10 genome-equivalents per a tick with maximal values for and Phylogenetic analysis of 16S rRNA gene and 5S-23S rRNA intergenic spacer nucleotide sequences revealed two species: 1) of Asian type NT29 with several isolates of European type 20047; 2) with identical sequences of the majority of studied isolates and VS461 reference strain in all regions except the Sakhalin Island where was not found of the relapsing fever group was detected as monoinfection or in combination with s.l. in 4.0 ± 0.9% and 4.8 ± 0.9% ticks, respectively. Multiple locus sequence analysis of three fragments of 16S rRNA, glpQ and p66 genes proved that all the Far Eastern isolates belonged to the Asian type identical to FR64b strain (GenBank CP004217) from Japan. Wide distribution of DNA in ticks, relative genetic homogeneity with similar sequences of the coding regions and the intergenic spacer of wild isolates and temporal stability with high homology levels of the Far Eastern isolates of , and with previously described spirochetes from the surrounding regions of Russia, China and Japan allowed us to suggest multiple ecological niches as the stability factor of the parasitic system.
PubMed: 30891399
DOI: 10.1016/j.ijppaw.2019.01.005 -
Ticks and Tick-borne Diseases Jan 2020Borrelia miyamotoi is an emerging tick-borne spirochete transmitted by ixodid ticks. Current serologic assays for B. miyamotoi are impacted by genetic similarities to...
Borrelia miyamotoi is an emerging tick-borne spirochete transmitted by ixodid ticks. Current serologic assays for B. miyamotoi are impacted by genetic similarities to other Borrelia and limited understanding of optimal antigenic targets. In this study, we employed the TBD-Serochip, a peptide array platform, to identify new linear targets for serologic detection of B. miyamotoi. We examined a wide range of suspected B. miyamotoi antigens and identified 352 IgM and 91 IgG reactive peptides, with the majority mapping to variable membrane proteins. These included peptides within conserved fragments of variable membrane proteins that may have greater potential for differential diagnosis. We also identified reactive regions on FlaB, and demonstrate crossreactivity of B. burgdorferi s.l. C6 with a B. miyamotoi C6-like peptide. The panel of linear peptides identified in this study can be used to enhance serodiagnosis of B. miyamotoi.
Topics: Borrelia; Epitopes; Serologic Tests
PubMed: 31636001
DOI: 10.1016/j.ttbdis.2019.101314 -
IDCases 2022An adult male presented to a hospital in southwestern Connecticut with tachypnea, generalized weakness, altered mental status, and relapsing fever with maximum recorded...
An adult male presented to a hospital in southwestern Connecticut with tachypnea, generalized weakness, altered mental status, and relapsing fever with maximum recorded temperature of 106 °F. He required active cooling, antipyretic therapy, broad spectrum antibiotics, and intubation for airway protection after an episode of emesis. Initial laboratory and imaging workup were remarkable for elevated inflammatory markers, acute kidney injury, and bilateral lower lobe infiltrates. Further workup with lumbar puncture and electroencephalography were unrevealing. Extensive testing for causes of relapsing fever including tickborne diseases revealed that the patient was seropositive for Borrelia miyamotoi. Notably, he had no rash, and workup found no evidence of coinfection by other Borrelia, Ehrlichia or Anaplasma species. This case illustrates the need for clinicians to test for tick-borne diseases when evaluating for cases of relapsing fever in New England and is among the first case reports to demonstrate Borrelia miyamotoi as a cause of severe pyrexia.
PubMed: 36110291
DOI: 10.1016/j.idcr.2022.e01614