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Ticks and Tick-borne Diseases May 2023Characterizing the diversity of genes associated with virulence and transmission of a pathogen across the pathogen's distribution can inform our understanding of host...
Characterizing the diversity of genes associated with virulence and transmission of a pathogen across the pathogen's distribution can inform our understanding of host infection risk. Borrelia burgdorferi is a vector-borne bacterium that causes Lyme disease in humans and is common in the United States. The outer surface protein C (ospC) gene of B. burgdorferi exhibits substantial genetic variation across the pathogen's distribution and plays a critical role in virulence and transmission in vertebrate hosts. In fact, B. burgdorferi infections that disseminate across host tissues in humans are associated with only a subset of ospC alleles. Delaware has a high incidence of Lyme disease, but the diversity of ospC in B. burgdorferi in the state has not been evaluated. We used PCR to amplify ospC in B. burgdorferi-infected blacklegged ticks (Ixodes scapularis) in sites statewide and used short-read sequencing to identify ospC alleles. B. burgdorferi prevalence in blacklegged ticks varied across sites, but not significantly so. We identified 15 previously characterized ospC alleles accounting for nearly all of the expected diversity of alleles across the sites as estimated using the Chao1 index. Nearly 40% of sequenced infections (23/58) had more than one ospC allele present suggesting mixed strain infections and the relative frequencies of alleles in single infections were positively correlated with their relative frequencies in mixed infections. Turnover of ospC alleles was positively related to distance between sites with closer sites having more similar allele compositions than more distant sites. This suggests a degree of B. burgdorferi dispersal limitation or habitat specialization. OspC alleles known to cause disseminated infections in humans were found at the highest frequencies across sites, corresponding to Delaware's high incidence of Lyme disease.
Topics: Animals; Humans; Borrelia burgdorferi; Ixodes; Alleles; Prevalence; Delaware; Lyme Disease
PubMed: 36780839
DOI: 10.1016/j.ttbdis.2023.102139 -
Microbiology Spectrum Jan 2023Borrelia miyamotoi is a relapsing fever spirochete that is harbored by spp. ticks and is virtually uncharacterized, compared to other relapsing fever vectored by spp....
Borrelia miyamotoi is a relapsing fever spirochete that is harbored by spp. ticks and is virtually uncharacterized, compared to other relapsing fever vectored by spp. ticks. There is not an immunocompetent mouse model for studying B. miyamotoi infection or for transmission in the vector-host cycle. Our goal was to evaluate B. miyamotoi infections in multiple mouse breeds/strains as a prelude to the ascertainment of the best experimental infection model. Two B. miyamotoi strains, namely, LB-2001 and CT13-2396, as well as three mouse models, namely, CD-1, C3H/HeJ, and BALB/c, were evaluated. We were unable to observe B. miyamotoi LB-2001 spirochetes in the blood via darkfield microscopy or to detect DNA via real-time PCR post needle inoculation in the CD-1 and C3H/HeJ mice. However, LB-2001 DNA was detected via real-time PCR in the blood of the BALB/c mice after needle inoculation, although spirochetes were not observed via microscopy. CD-1, C3H/HeJ, and BALB/c mice generated an antibody response to B. miyamotoi LB-2001 following needle inoculation, but established infections were not detected, and the I. scapularis larvae failed to acquire spirochetes from the exposed CD-1 mice. In contrast, B. miyamotoi CT13-2396 was visualized in the blood of the CD-1 and C3H/HeJ mice via darkfield microscopy and detected by real-time PCR post needle inoculation. Both mouse strains seroconverted. However, no established infection was detected in the mouse organs, and the I. scapularis larvae failed to acquire after feeding on CT13-2396 exposed CD-1 or C3H/HeJ mice. These findings underscore the challenges in establishing an experimental B. miyamotoi infection model in immunocompetent laboratory mice. Borrelia miyamotoi is a causative agent of hard tick relapsing fever, was first identified in the early 1990s, and was characterized as a human pathogen in 2011. Unlike other relapsing fever species, B. miyamotoi spread by means of ticks. The relatively recent recognition of this human pathogen means that B. miyamotoi is virtually uncharacterized, compared to other species. Currently there is no standard mouse-tick model with which to study the interactions of the pathogen within its vector and hosts. We evaluated two B. miyamotoi isolates and three immunocompetent mouse models to identify an appropriate model with which to study tick-host-pathogen interactions. With the increased prevalence of human exposure to ticks, having an appropriate model with which to study B. miyamotoi will be critical for the future development of diagnostics and intervention strategies.
PubMed: 36715531
DOI: 10.1128/spectrum.04301-22 -
Ticks and Tick-borne Diseases Jan 2023Lyme borreliosis, caused by Borrelia burgdorferi sensu lato (s.l.) spirochaetes, is the most common tick-borne disease (TBD) in the Northern Hemisphere. Rising...
Lyme borreliosis, caused by Borrelia burgdorferi sensu lato (s.l.) spirochaetes, is the most common tick-borne disease (TBD) in the Northern Hemisphere. Rising incidences indicate that its epidemiology may be affected by global changes. Therefore, the current study aimed to assess changes in tick infection rates with Borrelia spp. over a 15-year monitoring period in the city of Hanover, Germany, as a follow-up to previous prevalence studies (years 2005, 2010 and 2015). To assess the epidemiological risk, ticks of the Ixodes ricinus/inopinatus-complex were sampled from April to October 2020 by the flagging method at 10 frequently visited recreation areas in Hanover. Analysis by quantitative real-time PCR of 2100 individual ticks revealed an overall Borrelia prevalence of 25.5% (535/2100). Regarding different tick developmental stages, nymphs showed a significantly lower Borrelia prevalence (18.4% [193/1050]) than adult ticks (32.6% [342/1050]). Comparison with previous years revealed a stable total Borrelia prevalence along with consistent infection rates in the different developmental stages over the 15-year monitoring period. Borrelia species differentiation by Reverse Line Blot was successful in 67.3% of positive ticks collected in 2020, with B. afzelii being the dominating species (59.2% of the differentiated infections), besides B. burgdorferi sensu stricto (s.s.), B. garinii, B. valaisiana, B. spielmanii, B. bavariensis and B. bissettiae and the relapsing fever spirochaete B. miyamotoi. Additionally, the proportion of infections attributed to B. afzelii showed a significant increase in 2020 compared to 2005 and 2015 (59.2% vs. 37.6% and 32.0% of successfully differentiated infections, respectively). Coinfections with Anaplasma phagocytophilum and Rickettsia spp. stayed stable comparing 2020 with previous years. Therefore, although changes in the Borrelia prevalence in questing ticks were not observed throughout the 15-year monitoring period, shifts in Borrelia species distribution may alter the epidemiological risk.
Topics: Animals; Borrelia; Ixodes; Germany
PubMed: 36335680
DOI: 10.1016/j.ttbdis.2022.102074 -
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 -
Frontiers in Veterinary Science 2022Ticks transmit a broad spectrum of pathogens, threatening both animal and human health. Tick survival and proliferation are strongly dependent on host selection and...
Ticks transmit a broad spectrum of pathogens, threatening both animal and human health. Tick survival and proliferation are strongly dependent on host selection and suitability. The hard tick , which is widespread throughout most of Europe, is a host generalist capable of feeding on many different vertebrate species. Pasture-kept exotic farm animals may be at a high risk for tick and tick-borne pathogens infestations but research characterizing this is currently lacking. This study focused on the detection of spirochetes (including ) in exotic farm animals. Using nested-PCR with -specific primers, 121 serum samples from 54 exotic farm animals of several species bred in four different farms in Bohemia and Moravia (Czechia) were tested. Positive samples were sequenced for the identification of species. The prevalence of DNA in the samples ranged from 13 to 67%, depending on the sampling site. The sequencing results confirmed the DNA presence of multiple spirochete species from the sensu lato complex. Only one sample from an ostrich () was found to be positive for . The results show that exotic farm animals can serve as hosts for hard ticks and can be infected by spirochetes, transmitted by hard ticks. Therefore, these animals could play a relevant role in maintaining spirochetes in nature.
PubMed: 36246336
DOI: 10.3389/fvets.2022.996015 -
Emerging Microbes & Infections Dec 2022We identified relapsing fever (RF) in 1.45% (145/10426) of the ticks and 1.40% (40/2850) of the wild mammals in a field investigation in China. Three RF species,...
We identified relapsing fever (RF) in 1.45% (145/10426) of the ticks and 1.40% (40/2850) of the wild mammals in a field investigation in China. Three RF species, including human-pathogenic , a and unclassified sp. were determined. Main species determined from ticks was (44.14%), followed by the unclassified sp. (42.76%), and (13.10%). In wild mammals, main species found was (57.50%), followed by the unclassified sp. (40.00%), and (2.50%). We determined and in China for the first time The coexistence of RF species in one tick species in a given region was observed, with the most frequent coexistence seen for and the unclassified sp. in respectively. The wide distribution and high variety of RF in China pose a potential threat to public health.
Topics: Animals; Humans; Relapsing Fever; Borrelia; Ixodes; Ixodidae; China; Mammals
PubMed: 36214427
DOI: 10.1080/22221751.2022.2134054 -
The Lancet. Microbe Oct 2022Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various studies have evaluated the infection of Ixodes ticks and humans with the relapsing fever spirochaete Borrelia miyamotoi. However, to our knowledge, the prevalence of infection and disease has not been assessed systematically. We aimed to examine the prevalence of B miyamotoi in Ixodes ticks and humans, and the disease it can cause, in the northern hemisphere.
METHODS
For this systematic review and meta-analysis, we searched PubMed and Web of Science up to March 1, 2021. Studies assessing Ixodes tick infection published since Jan 1, 2011 were eligible, whereas no time limitation was placed on reports of human infection and disease. We extracted B miyamotoi test positivity ratios and used a random-effects model to calculate estimated proportions of infected ticks, infected humans, and human disease with 95% CI. This study was registered with PROSPERO, CRD42021268996.
FINDINGS
We identified 730 studies through database searches and 316 additional studies that referenced two seminal articles on B miyamotoi. Of these 1046 studies, 157 were included in the review, reporting on 165 637 questing ticks, 45 608 unique individuals, and 504 well described cases of B miyamotoi disease in humans. In ticks, the highest prevalence of B miyamotoi was observed in Ixodes persulcatus (2·8%, 95% CI 2·4-3·1) and the lowest in Ixodes pacificus (0·7%, 0·6-0·8). The overall seroprevalence in humans was 4·4% (2·8-6·3), with significantly (p<0·0001) higher seroprevalences in the high-risk group (4·6%, 2·6-7·1), participants with confirmed or suspected Lyme borreliosis (4·8%, 1·8-8·8), and individuals suspected of having a different tick-borne disease (11·9%, 5·6-19·9) than in healthy controls (1·3%, 0·4-2·8). Participants suspected of having a different tick-borne disease tested positive for B miyamotoi by PCR significantly more often than did the high-risk group (p=0·025), with individuals in Asia more likely to test positive than those in the USA (odds ratio 14·63 [95% CI 2·80-76·41]).
INTERPRETATION
B miyamotoi disease should be considered an emerging infectious disease, especially in North America and Asia. Prospective studies and increased awareness are required to obtain further insights into the burden of disease.
FUNDING
ZonMW and the European Regional Development Fund (Interreg).
Topics: Animals; Borrelia; Humans; Ixodes; Nymph; Prevalence; Prospective Studies; Seroepidemiologic Studies; Tick-Borne Diseases
PubMed: 36113496
DOI: 10.1016/S2666-5247(22)00157-4 -
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 -
Tick-Borne Pathogens in Questing Blacklegged Ticks (Acari: Ixodidae) From Pike County, Pennsylvania.Journal of Medical Entomology Sep 2022Active surveillance was conducted by collecting questing ticks from vegetation through a 2-yr survey in Pike County, Pennsylvania. Over a thousand blacklegged ticks...
Active surveillance was conducted by collecting questing ticks from vegetation through a 2-yr survey in Pike County, Pennsylvania. Over a thousand blacklegged ticks (Ixodes scapularis Say) and American dog ticks (Dermacentor variabilis Say) were collected. A single specimen of the following species was collected: lone star tick (Amblyomma americanum L.), rabbit tick (Haemaphysalis leporispalustris Packard), and an Asian longhorned tick (Haemaphysalis longicornis Neumann). This study represents the largest county-wide study in Pennsylvania, surveying 988 questing I. scapularis adult and nymphs. Molecular detection of five distinct tick-borne pathogens was screened through real-time PCR at a single tick resolution. Respectively, the overall 2-yr adult and nymph prevalence were highest with Borrelia burgdorferi (Spirochaetales: Spirochaetacceae) (45.99%, 18.94%), Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) (12.29%, 7.95%) where the variant-ha (8.29%, 3.03%) was overall more prevalent than the variant-v1 (2.49%, 4.17%), Babesia microti (Piroplasmida: Babesiidae) (4.97%, 5.30%), Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) (1.38%, 1.89%), and Powassan virus lineage II [POWV]/deer tick virus (DTV) (2.07%, 0.76%). Adult and nymph coinfection prevalence of B. burgdorferi and B. microti (3.03%, 4.97%) and adult coinfection of B. burgdorferi and A. phagocytophilum or A. phagocytophilum and B. microti were significantly higher than the independent infection rate expected naturally. This study highlights the urgency to conduct diverse surveillance studies with large sample sizes to better understand the human risk for tick-borne diseases within small geographical areas.
Topics: Anaplasma phagocytophilum; Animals; Borrelia burgdorferi; Coinfection; Humans; Ixodes; Ixodidae; Nymph; Pennsylvania; Rabbits
PubMed: 35920050
DOI: 10.1093/jme/tjac107 -
Open Forum Infectious Diseases Jul 2022is an underdiagnosed cause of tick-borne illness in endemic regions and, in rare cases, causes neurological disease in immunocompetent patients. Here, we present a case...
is an underdiagnosed cause of tick-borne illness in endemic regions and, in rare cases, causes neurological disease in immunocompetent patients. Here, we present a case of serologically confirmed meningoencephalitis in an otherwise healthy patient who rapidly improved following initiation of antibiotic therapy.
PubMed: 35873293
DOI: 10.1093/ofid/ofac295