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Vertical transmission rates of Borrelia miyamotoi in Ixodes scapularis collected from white-tailed deer
Abstract
Borrelia miyamotoi is a relapsing fever spirochete transmitted by ticks in the Ixodes ricinus complex. In the eastern United States, B. miyamotoi is transmitted by I. scapularis, which also vectors several other pathogens including B. burgdorferi sensu stricto. In contrast to Lyme borreliae, B. miyamotoi can be transmitted vertically from infected female ticks to their progeny. Therefore, in addition to nymphs and adults, larvae can vector B. miyamotoi to wildlife and human hosts. Two widely varying filial infection prevalence (FIP) estimates - 6% and 73% - have been reported previously from two vertically infected larval clutches; to our knowledge, no other estimates of FIP or transovarial transmission (TOT) rates for B. miyamotoi have been described in the literature. Thus, we investigated TOT and FIP of larval clutches derived from engorged females collected from hunter-harvested white-tailed deer in 2015 (n = 664) and 2016 (n = 599) from Maine, New Hampshire, Tennessee, and Wisconsin. After engorged females oviposited in the lab, they (n = 492) were tested for B. miyamotoi infection by PCR. Subsequently, from each clutch produced by an infected female, larval pools, as well as 100 individual eggs or larvae, were tested. The TOT rate of the 11 infected females was 90.9% (95% CI; 57.1–99.5%) and the mean FIP of the resulting larval clutches was 84.4% (95% CI; 68.1–100%). Even though the overall observed vertical transmission rate (the product of TOT and FIP; 76.7%, 95% CI; 44.6–93.3%) was high, additional horizontal transmission may be required for enzootic maintenance of B. miyamotoi based on the results of a previously published deterministic model. Further investigation of TOT and FIP variability and the underlying mechanisms, both in nature and the laboratory, will be needed to resolve this question. Meanwhile, studies quantifying the acarological risk of Borrelia miyamotoi disease need to consider not only nymphs and adults, but larval I. scapularis as well.
... In contrast, B. miyamotoi was detected in these cattle-associated ticks. A high detection frequency and vertical transmission rate of B. miyamotoi in ticks collected from white-tailed deer further support that the relapsing-fever spirochaete, in contrast to B. burgdorferi s.l., could be resistant to ruminant complement (Han et al., 2016;Han et al., 2019). ...
... Moreover, this could indicate replication of B. miyamotoi during the feeding process, resulting in a higher detection probability towards the end of the bloodmeal. It has also been proposed that deer might act as a reservoir for B. miyamotoi based on high detection rates in feeding ticks (Han et al., 2016;Han et al., 2019), however, to the authors' knowledge this has so far not been confirmed by testing deer tissue or blood for the pathogen. Replication also seems more likely given the fact that a significant increase of infections attributed to B. miyamotoi was also observed in ticks feeding on dogs (Probst et al., 2024), which are unlikely B. miyamotoi reservoirs. ...
... Unlike B. burgdorferi that is lysed by deer blood complement upon tick ingestion, it appears that B. miyamotoi remains viable in the tick upon ingestion of deer blood. A study found that engorged female I. scapularis ticks collected from white-tailed deer produced infected offspring [114][115][116]. Reservoir competence has not been characterized in whitetailed deer. ...
... Another group saw 10/11 infected I. scapularis females produce infected clutches, with infection in progeny being 36-100%. This study also saw similar oviposition rates in B. miyamotoi-infected I. scapularis females compared with uninfected females, indicating that B. miyamotoi infection does not appear to impact tick fecundity [115]. These studies support that vertical transmission is relied on more heavily for B. miyamotoi maintenance than horizontal transmission. ...
Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern Hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). Borrelia miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus, has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein, we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.
... This finding, coupled with our results, suggests that larvae, and potentially nymphs, are not ideal for the acquisition of B. miyamotoi via bloodmeal. Previous investigations have shown that B. miyamotoi has high transovarial transmission rates (12,61,62). Therefore, infection maintenance in ticks may not depend entirely on the acquisition of B. miyamotoi via bloodmeal engorgement from reservoir hosts. ...
... Lynn et al. found that there is a correlation between a high spirochete burden in the female I. scapularis and successful transovarial transmission (42). Field collections of Ixodes ticks have shown that infected larvae, nymphs, and adults persist in nature, but the primary route of infection is unknown (43,(62)(63)(64)(65). Different tick life stages may be more conducive to B. miyamotoi acquisition and maintenance due to the larger bloodmeal imbibed. ...
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 Borrelia species, B. miyamotoi spread by means of Ixodes ticks.
... Unlike B. burgdorferi that is lysed by deer blood complement upon tick ingestion, it appears that B. miyamotoi remains viable in the tick upon ingestion of deer blood. A study found that engorged female I. scapularis ticks collected from white-tailed deer produced infected offspring [114][115][116]. Reservoir competence has not been characterized in whitetailed deer. ...
... Another group saw 10/11 infected I. scapularis females produce infected clutches, with infection in progeny being 36-100%. This study also saw similar oviposition rates in B. miyamotoi-infected I. scapularis females compared with uninfected females, indicating that B. miyamotoi infection does not appear to impact tick fecundity [115]. These studies support that vertical transmission is relied on more heavily for B. miyamotoi maintenance than horizontal transmission. ...
Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). B. miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.
... capable of transovarian transmission, such as Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) and DTV , Han et al. 2019, Pokutnaya et al. 2020. Acquisition and maintenance of the other pathogens are primarily through blood meals and thus only life stages that have fed previously, nymphs and adults, are competent vectors . ...
... Borrelia miyamotoi disease is not reportable in PA, despite concerns of transovarial transmission and the risk of cross reactivity with the C6 peptide ELISA LD test (Barbour et al. 2009, Molloy et al. 2018, Han et al. 2019. Overall prevalence of B. miyamotoi was 1.52% (95% CI: 1.52-2.49). ...
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.
... Only a few previous studies have investigated the efficiency of transmission of B. miyamotoi from infected ticks to naïve hosts and/or from infectious hosts to feeding ticks (Scoles et al., 2001;van Duijvendjik et al., 2016;Breuner et al., 2017;Breuner et al., 2018). Similarly, there exist only a few reports where PCR was used to determine B. miyamotoi infection rates in transovarially-infected larval clutches, comprising a total of 15 I. scapularis clutches (Scoles et al., 2001;Breuner et al., 2018;Han et al., 2019) and a single I. ricinus clutch (Richter et al., 2012). To compare transovarial and horizontal transmission routes, we used a combination of I. scapularis ticks infected experimentally by feeding on infected mice in the laboratory and I. scapularis with transovarially acquired infections, descended from naturally infected field-collected females. ...
... We observed transovarial transmission to the larval progeny in seven of 10 clutches produced by B. miyamotoi-infected females and filial infection prevalence ranged from 3.3 to 100%, consistent with reported ranges for transovarial transmission in captive, field-collected I. scapularis (Scoles et al., 2001;Han et al., 2019). Infection was detected in two thirds of larvae from positive clutches and over 60% of total larvae tested from positive females. ...
Borrelia miyamotoi is a relapsing fever spirochete carried by Ixodes spp. ticks throughout the northern hemisphere. The pathogen is acquired either transovarially (vertically) or horizontally through blood-feeding and passed transtadially across life stages. Despite these complementary modes of transmission, infection prevalence of ticks with B. miyamotoi is typically low (<5%) in natural settings and the relative contributions of the two transmission modes have not been studied extensively. Horizontal transmission of B. miyamotoi (strain CT13-2396 or wild type strain) was initiated using infected Ixodes scapularis larvae or nymphs to expose rodents, which included both the immunocompetent CD-1 laboratory mouse (Mus musculus) and a natural reservoir host, the white-footed mouse (Peromyscus leucopus), to simulate natural enzootic transmission. Transovarial transmission was evaluated using I. scapularis exposed to B. miyamotoi as either larvae or nymphs feeding on immunocompromised SCID mice (M. musculus) and subsequently fed as females on New Zealand white rabbits. Larvae from infected females were qPCR-tested individually to assess transovarial transmission rates. Tissue tropism of B. miyamotoi in infected ticks was demonstrated using in situ hybridization. Between 1 and 12% of ticks were positive (post-molt) for B. miyamotoi after feeding on groups of CD-1 mice or P. leucopus with evidence of infection, indicating that horizontal transmission was inefficient, regardless of whether infected larvae or nymphs were used to challenge the mice. Transovarial transmission occurred in 7 of 10 egg clutches from infected females. Filial infection prevalence in larvae ranged from 3 to 100% (median 71%). Both larval infection prevalence and spirochete load were highly correlated with maternal spirochete load. Spirochetes were disseminated throughout the tissues of all three stages of unfed ticks, including the salivary glands and female ovarian tissue. The results indicate that while multiple transmission routes contribute to enzootic maintenance of B. miyamotoi, transovarial transmission is likely to be the primary source of infected ticks and therefore risk assessment and tick control strategies should target adult female ticks.
... The most common tick species in Denmark, the castor bean tick (Ixodes ricinus) only feeds once per life cycle (larva-nymph-adult, Estrada-Peña and de la Fuente, 2014), and thus pathogens found within larvae may come from this first blood meal taken from the raccoon dogs. Naturally, this only pertains to pathogens that are not vertically transmitted within the tick vector (Han et al., 2019;Michelitsch et al., 2019;Oechslin et al., 2017;Sprong et al., 2009). ...
... In the larvae, we found a relatively high percentage of the raccoon dogs with R. helvetica and A. phagocytophilum. Vertical transmission from mother to offspring has been documented for R. helvetica and B. myiamotoi in Ixodid ticks (Breuner et al., 2017;Han et al., 2019;Socolovschi et al., 2009;Sprong et al., 2009), thus we cannot conclude that these pathogens were transmitted from the raccoon dog host to the tick larvae. Many of the Babesia species also exhibit transovarial transmission from female to offspring (Bonnet et al., 2007;Øines et al., 2012), and the one B. venatorum positive larva we found, could have obtained the pathogen through the adult female tick. ...
Raccoon dogs have successfully invaded Europe, including Denmark. Raccoon dogs are potential vectors and reservoir hosts of several zoonotic pathogens and thus have the potential for posing a threat to both human and animal health. This study includes analysis of four zoonotic parasites, 16 tick-borne pathogens and two pathogen groups from 292 raccoon dogs collected from January 2017 to December 2018. The raccoon dogs were received as a part of the Danish national wildlife surveillance program and were hunted, found dead or road killed. The raccoon dogs were screened for Alaria alata and Echinococcus multilocularis eggs in faeces by microscopy and PCR, respectively, Trichinella spp. larvae in muscles by digestion, antibodies against Toxoplasma gondii by ELISA and screening of ticks for pathogens by fluidigm real-time PCR.
All raccoon dogs tested negative for E. multilocularis and Trichinella spp., while 32.9% excreted A. alata eggs and 42.7% were T. gondii sero-positive. Five tick-borne pathogens were identified in ticks collected from 15 raccoon dogs, namely Anaplasma phagocytophilum (20.0%), Babesia venatorum (6.7%), Borrelia miyamotoi (6.7%), Neoehrlichia mikurensis (6.7%) and Rickettsia helvetica (60.0%).
We identified raccoon dogs from Denmark as an important reservoir of T. gondii and A. alata infection to other hosts, including humans, while raccoon dogs appear as a negligible reservoir of E. multilocularis and Trichinella spp. infections. Our results suggest that raccoon dogs may be a reservoir of A. phagocytophilum.
... In neither of these studies were the ovipositing females tested for infection, so the efficiency of transovarial transmission by infected females could not be determined. Han et al. [68] collected engorged female I. scapularis from carcasses of white-tailed deer (Odocoileus virginianus) and allowed these ticks to oviposit in the laboratory. During two hunting seasons in 2015 and 2016 in four midwest and eastern States, 33 of 1263 (2.6%) females were infected with B. miyamotoi, and of those females infected, 11 ticks laid eggs with 10 of the clutches (90.9%) infected transovarially. ...
... Such ticks would be falsely positive if considering transovarial passage as the source of infection. However, the results reviewed above for studies with unfed larvae produced by females in the laboratory are unequivocal [65][66][67][68][69]. ...
Transovarial passage of relapsing fever spirochetes (Borrelia species) by infected female argasid ticks to their progeny is a widespread phenomenon. Yet this form of vertical inheritance has been considered rare for the North American tick Ornithodoros hermsi infected with Borrelia hermsii. A laboratory colony of O. hermsi was established from a single infected female and two infected males that produced a population of ticks with a high prevalence of transovarial transmission based on infection assays of single and pooled ticks feeding on mice and immunofluorescence microscopy of eggs and larvae. Thirty-eight of forty-five (84.4%) larval cohorts (groups of larvae originating from the same egg clutch) transmitted B. hermsii to mice over four and a half years, and one hundred and three single and one hundred and fifty-three pooled nymphal and adult ticks transmitted spirochetes during two hundred and fourteen of two hundred and fifty-six (83.6%) feedings on mice over seven and a half years. The perpetuation of B. hermsii for many years by infected ticks only (without acquisition of spirochetes from vertebrate hosts) demonstrates the reservoir competence of O. hermsi. B. hermsii produced the variable tick protein in eggs and unfed larvae infected by transovarial transmission, leading to speculation of the possible steps in the evolution of borreliae from a tick-borne symbiont to a tick-transmitted parasite of vertebrates.
... However, brief infectivity and low transmission efficiency of white-footed mice for B. miyamotoi suggest that mice are not highly competent reservoirs for the spirochete (Scoles et al. 2001). Vertical transmission, however, is probably insufficient to fully support B. miyamotoi maintenance in tick populations (Han et al. 2019), such that occasional horizontal transmission involving wildlife reservoirs or cofeeding transmission is required for persistence of B. miyamotoi (Han et al. 2016, Sambado et al. 2020). ...
... Dunning Hotopp et al. 2006, Rikihisa 2011, Stuen et al. 20132 Levin and Fish 2000a;3 Telford et al. 1996, Des Vignes andFish 1997;4 Levin andFish 2000b, Keesing et al. 2012;5 Levin and Ross 2004;6 Oliveira and Kreier 1979;7 Friedhoff 1988, Tufts andDiuk-Wasser 2018;8 Spielman et al. 1981, Mather et al. 19909 Spielman et al. 1981, Telford and Spielman 1993, Hersh et al. 201210 Spielman et al. 1981, Dunn et al. 201411 Dunn et al. 2014;12 Rollend et al. 2013;13 Patrican 1997, Piesman and Happ 2001,Voordouw 2015, States et al. 201714 Donahue et al. 1987;15 Levine et al. 1985, Donahue et al. 1987, LoGiudice et al. 2003, Hanincová et al. 200616 Donahue et al. 198717 Breuner et al. 2018;18 Breuner et al. 2018;19 Parise et al. 2020;20 Johnson et al. 2017;21 Dolan et al. 2017;22 Parise et al. 2020;23 Scoles et al. 2001, Han et al. 201924 Scoles et al. 2001, van Duijvendijk et al. 201625 Scoles et al. 2001;26 Scoles et al. 2001;27 Scoles et al. 2001;28 Dunning Hotopp et al. 2006;29 Lynn et al. 2015;30 Karpathy et al. 2016, Lynn et al. 201731 Saito and Walker 2015, Karpathy et al. 2016, Lynn et al. 201732 Castillo et al. 2015;33 Lynn et al. 2017;34 Costero and Grayson 1996;35 Ebel 2010, Hermance andThangamani 2018;36 Costero and Grayson 1996, Telford III et al. 1997, Ebel and Kramer 200437 McLean and Larke 1963, McLean et al. 1964, Main et al. 197938 Telford III et al. 1997, Ebel et al. 200039 Ebel 2010, Hermance and Thangamani 2018, Mlera and Bloom 2018 capacity. Given the evidence from other deer-targeted approaches, broad vaccine coverage of the deer population is necessary for an epidemiologically meaningful reduction of disease risk. ...
Wildlife vertebrate hosts are integral to enzootic cycles of tick-borne pathogens, and in some cases have played key roles in the recent rise of ticks and tick-borne diseases in North America. In this forum article, we highlight roles that wildlife hosts play in the maintenance and transmission of zoonotic, companion animal, livestock, and wildlife tick-borne pathogens. We begin by illustrating how wildlife contribute directly and indirectly to the increase and geographic expansion of ticks and their associated pathogens. Wildlife provide blood meals for tick growth and reproduction; serve as pathogen reservoirs; and can disperse ticks and pathogens-either through natural movement (e.g., avian migration) or through human-facilitated movement (e.g., wildlife translocations and trade). We then discuss opportunities to manage tick-borne disease through actions directed at wildlife hosts. To conclude, we highlight key gaps in our understanding of the ecology of tick-host interactions, emphasizing that wildlife host communities are themselves a very dynamic component of tick-pathogen-host systems and therefore complicate management of tick-borne diseases, and should be taken into account when considering host-targeted approaches. Effective management of wildlife to reduce tick-borne disease risk further requires consideration of the 'human dimensions' of wildlife management. This includes understanding the public's diverse views and values about wildlife and wildlife impacts-including the perceived role of wildlife in fostering tick-borne diseases. Public health agencies should capitalize on the expertise of wildlife agencies when developing strategies to reduce tick-borne disease risks.
... Borrelia miyamotoi can be passed transovarially from infected female ticks to their progeny (Scoles et al., 2001;Breuner et al., 2017;Han et al., 2019). Transmission of B. miyamotoi to laboratory mice by vertically-infected I. ricinus larvae and by I. scapularis nymphs (molted from vertically-infected larvae) has been demonstrated (Scoles et al., 2001;van Duijvendijk et al., 2016;Breuner et al., 2017). ...
... One possibility is that we have underestimated larval prevalence, because our methods assumed that infected larvae would be distributed randomly amongst our larval pools. Infected larvae, however, may be highly clustered spatially; Han et al. (2019) estimated that an average of 84 % of larvae in an infected clutch are infected. In most cases, our larval pools consisted of individuals collected from one 15 m section and so potentially could have included multiple infected larvae from the same infected clutch. ...
Measures of acarological risk of exposure to Ixodes scapularis-borne disease agents typically focus on nymphs; however, the relapsing fever group spirochete Borrelia miyamotoi can be passed transovarially, and I. scapularis larvae are capable of transmitting B. miyamotoi to their hosts. To quantify the larval contribution to acarological risk, relative to nymphs and adults, we collected questing I. scapularis for 3 yr at Fort McCoy, Wisconsin (WI, n = 23,367 ticks), and Cape Cod, Massachusetts (MA, n = 4190) in the United States. Borrelia miyamotoi infection prevalence was estimated for I. scapularis larvae, nymphs, females, and males, respectively, as 0.88, 2.05, 0.63, and 1.22 % from the WI site and 0.33, 2.32, 2.83, and 2.11 % from the MA site. Densities of B. miyamotoi-infected ticks (DIT, per 1000 m 2) were estimated for larvae, nymphs, females, and males, respectively, as 0.36, 0.14, 0.01, and 0.03 from the WI site and 0.05, 0.06, 0.03, and 0.02 from the MA site. Thus, although larval infection prevalence with B. miyamotoi was significantly lower than that of nymphs and similar to that of adults, because of their higher abundance, the larval contribution to the overall DIT was similar to that of nymphs and trended towards a greater contribution than adults. Assuming homogenous contact rates with humans, these results suggest that eco-epidemiological investigations of B. miyamotoi disease in North America should include larvae. A fuller appreciation of the epidemiological implications of these results, therefore, requires an examination of the heterogeneity in contact rates with humans among life stages.
... All these diseases can be spread through the bite of an I. scapularis tick, which has increased dramatically in range in Maine and moderately in abundance. 25 increase. 27 The climate in Maine is changing, leading to milder winters, earlier springs, and an expanded timeframe when humans might come into contact with host-seeking ticks. ...
... These pathogens exist in enzootic cycles between tick vectors and vertebrate reservoirs. Although some tick-borne pathogens are maintained through vertical transmission [2,3], most tick-borne pathogens of human concern are maintained through horizontal transmission. For these pathogens, the predominant transmission pathway consists of transmission from ...
Many tick-borne pathogens are maintained in enzootic cycles passing from nymphs of one tick cohort to larvae of the next via vertebrate hosts. As such, the phenology of larval and nymphal host-seeking, questing, partially determines pathogen persistence. Across the range of the blacklegged tick (Ixodes scapularis), the timing of larval phenology varies due to differences in climate and local adaptation in the timing of temperature-independent diapause. In this study, an elevation gradient was used to isolate climate as temperature varies with elevation over small geographic scales where local adaptation should be absent. The ability of a mechanistic, temperature-driven, literature-parametrized model to explain variation in larval I. scapularis phenology was tested. Over 7 years, I. scapularis ticks were collected using drag-cloth sampling along a > 500 m elevation gradient in western Vermont, USA. At low elevation, more larval ticks quested in late summer, while at high elevation, more quested in early summer. The literature-parametrized model reproduced these differences better than competing models. This validated model provides an explicit, mechanistic connection between temperature and larval phenology, a key determinant of tick-borne disease persistence.
... by direct immunofluorescence microscopy (DFA) [18]. DFA did not discriminate between B. burgdorferi and B. miyamotoi Fukunaga, but we believe this would not affect our inferences because the prevalence of B. miyamotoi in Maine is low, approximately 3.6% in female I. scapularis [19]. Nymphs collected in 2019 (MHIR) and in 2020-2021 (University of Maine) were tested individually for multiple pathogens at the University of Maine Cooperative Extension Diagnostic and Research Laboratory using a single real-time quantitative PCR (qPCR) multiplex reaction [20]. ...
Background
The incidence of tick-borne diseases is increasing across the USA, with cases concentrated in the northeastern and midwestern regions of the country. Ixodes scapularis is one of the most important tick-borne disease vectors and has spread throughout the northeastern USA over the past four decades, with established populations in all states of the region.
Methods
To better understand the rapid expansion of I. scapularis and the pathogens they transmit, we aggregated and analyzed I. scapularis abundance and pathogen prevalence data from across the northeastern USA, including the states of Connecticut, Maine, New Hampshire, New York and Vermont, from 1989 to 2021. Maine was the only state to collect data during the entire time period, with the other states collecting data during a subset of this time period starting in 2008 or later. We harmonized I. scapularis abundance by county and tick season, where the nymph season is defined as May to September and the adult season is October to December, and calculated I. scapularis pathogen infection prevalence as the percentage of ticks that tested positive for Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, and Borrelia miyamotoi. We then explored temporal trends in I. scapularis abundance and pathogen prevalence data using linear models.
Results
The resulting dataset is one of the most spatially and temporally comprehensive records of tick abundance and pathogen prevalence in the USA. Using linear models, we found small or insignificant changes in the abundance of nymphs and adults over time; however, A. phagocytophilum, B. microti and B. burgdorferi prevalence in both nymphs and adults has increased over time. For the period 2017–2021, the statewide average prevalence of B. burgdorferi ranged from 19% to 25% in I. scapularis nymphs and from to 49% to 54% in I. scapularis adults. The statewide average prevalence of all other pathogens in I. scapularis for 2017–2021, including A. phagocytophilum (4–6% for nymphs, 4–9% for adults), B. microti (4–8% for nymphs, 2–13% for adults) and B. miyamotoi (1–2% for nymphs, 1–2% for adults), was considerably less.
Conclusions
Our efforts revealed the complications of creating a comprehensive dataset of tick abundance and pathogen prevalence across time and space due to variations in tick collection and pathogen testing methods. Although tick abundance has not changed along the more southern latitudes in our study over this time period, and only gradually changed in the more northern latitudes of our study, human risk for exposure to tick-borne pathogens has increased due to increased pathogen prevalence in I. scapularis. This dataset can be used in future studies of I. scapularis and pathogen prevalence across the northeastern USA and to evaluate models of I. scapularis ecology and population dynamics.
Graphical Abstract
... B. miyamotoi belongs to the class Spirochaetia, order Spirochaetales, family Borreliaceae and genus Borrelia [7]. It can be transmitted in ticks both horizontally and transovarially (vertically) [8]. Interestingly, an experimental study found that the transovarial transmission of B. miyamotoi in hard ticks is much more efficient than horizontal transmission [9], indicating the primary role in the natural history of the pathogen. ...
Background
Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation.
Methods
For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed.
Results
A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings.
Conclusions
Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.
... Mixed mode of transmission of the dominating endosymbionts in S. dumicola is consistent with the limited information available for their transmission (or that of their close relatives) in other systems, which all point to tightly controlled but not necessarily transovarian routes: many mycoplasmas are horizontally transmitted either via direct contact or vectors, while in certain subgroups, e.g., the genus Spiroplasma, transmission can be vertical or even transovarian [56]. Some Borrelia can be transmitted vertically through the ovaries of ticks or insects [57] but most show horizontal transmission via vertebrate hosts [58][59][60], which may include mixing of several Borrelia strains via co-feeding of the arthropod on the same host [61]. The mite pathogen Acaricomes [62] is transmitted vertically within a given species but horizontally between different mite and insect species [63]; the transmission mode of the obligate intracellular tick symbiont Diplorickettsia is unknown [64]. ...
Disentangling modes and fidelity of symbiont transmission are key for understanding host–symbiont associations in wild populations. In group-living animals, social transmission may evolve to ensure high-fidelity transmission of symbionts, since non-reproducing helpers constitute a dead-end for vertical transmission. We investigated symbiont transmission in the social spider Stegodyphus dumicola , which lives in family groups where the majority of females are non-reproducing helpers, females feed offspring by regurgitation, and individuals feed communally on insect prey. Group members share temporally stable microbiomes across generations, while distinct variation in microbiome composition exists between groups. We hypothesized that horizontal transmission of symbionts is enhanced by social interactions, and investigated transmission routes within (horizontal) and across (vertical) generations using bacterial 16S rRNA gene amplicon sequencing in three experiments: (i) individuals were sampled at all life stages to assess at which life stage the microbiome is acquired. (ii) a cross-fostering design was employed to test whether offspring carry the microbiome from their natal nest, or acquire the microbiome of the foster nest via social transmission. (iii) adult spiders with different microbiome compositions were mixed to assess whether social transmission homogenizes microbiome composition among group members. We demonstrate that offspring hatch symbiont-free, and bacterial symbionts are transmitted vertically across generations by social interactions with the onset of regurgitation feeding by (foster)mothers in an early life stage. Social transmission governs horizontal inter-individual mixing and homogenization of microbiome composition among nest mates. We conclude that temporally stable host–symbiont associations in social species can be facilitated and maintained by high-fidelity social transmission.
... Thus, the pathogen can be at least partially maintained through vertical transmission in the tick vector. 19,20 Tick surveillance studies around the globe provide varied estimates of prevalence, but generally fall in the range of 1%-6%, with a few studies showing isolated tick populations highly enriched with B. miyamotoi, such as Napa county, northern California (15.4%). 7,10,15 A recent study in the United States assessing nearly 40,000 humanbiting ticks detected B. miyamotoi-infected ticks in 19 states with a 1%-1.8% ...
In North America, several hard tick-transmitted Borrelia species other than Borrelia burgdorferi cause human disease, including Borrelia miyamotoi, Borrelia mayonii, and possibly Borrelia bissettii. Due to overlapping clinical syndromes, nonspecific tickborne disease (TBD) testing strategies, and shared treatment approaches, infections with these lesser known Borrelia are likely under-reported. In this article, we describe the epidemiology, clinical manifestations, diagnosis, and treatment of these less common Borrelia pathogens.
... There have been minimal phenological studies performed that have reported on the activity of I. scapularis larvae and none within the state of Virginia. While transovarial transmission of B. burgdorferi does not occur, I. scapularis larvae can vector other pathogens such as Borrelia miyamotoi (Han et al. 2019). Therefore, the significantly higher collection rates of I. scapularis larvae in southwestern Virginia indicate higher risk in this region of the state for human infections associated with pathogens vectored by I. scapularis larvae such as B. miyamotoi. ...
To better understand tick ecology in Virginia and the increasing Lyme disease incidence in western Virginia, a comparative phenological study was conducted in which monthly collections were performed at twelve sampling locations in southwestern Virginia (high Lyme disease incidence) and 18 equivalent sampling locations in southeastern Virginia (low Lyme disease incidence) for one year. In western Virginia, we also explored the effect of elevation on collection rates of Ixodes scapularis Say (Acari: Ixodidae) and Amblyomma americanum (L.) (Acari: Ixodidae). In total, 35,438 ticks were collected (33,106 A. americanum; 2,052 I. scapularis; 134 Ixodes affinis Neumann [Acari: Ixodidae]; 84 Dermacentor variabilis [Say] [Acari: Ixodidae]; 49 Dermacentor albipictus [Packard] [Acari: Ixodidae]; 10 Haemaphysalis leporispalustris [Packard] [Acari: Ixodidae]; 2 Ixodes brunneus Koch [Acari: Ixodidae]; 1 Haemaphysalis longicornis Neumann [Acari: Ixodidae]). Within southwestern Virginia, Ixodes scapularis collection rates were not influenced by elevation, unlike A. americanum which were collected more frequently at lower elevations (e.g., below 500 m). Notably, I. scapularis larvae and nymphs were commonly collected in southwestern Virginia (indicating that they were questing on or above the leaf litter) but not in southeastern Virginia. Questing on or above the leaf litter is primarily associated with northern populations of I. scapularis. These findings may support the hypothesis that I. scapularis from the northeastern United States are migrating into western Virginia and contributing to the higher incidence of Lyme disease in this region. This comparative phenological study underscores the value of these types of studies and the need for additional research to further understand the rapidly changing tick-borne disease dynamics in Virginia.
... Infection prevalence of B. burgdorferi in white footed mice (Peromyscus leucopus) can be as high as 90% in endemic areas (Mather et al. 1989). However, P. leucopus is infrequently infected with B. miyamotoi (Barbour et al. 2009), and studies have instead implicated other species, including white-tailed deer (Odocoileus virginianus), as potential reservoirs (Han et al. 2016) along with some perpetuation of the pathogen in tick populations via transovarial transmission (Rollend et al. 2013a, 2013b, Han et al. 2019. One recent study reported that I. scapularis nymphs infected with B. miyamotoi were most likely to have fed as larvae on short-tailed shrews, red squirrels, or opossums (although deer were not included in the comparison) (Keesing et al. 2021). ...
Tick-borne diseases are a growing public health problem in the United States, and the US northeast has reported consistently high case rates for decades. Monmouth County, New Jersey, was one of the earliest jurisdictions to report Lyme disease cases in 1979 and reports several hundred cases per year nearly 40 yr later. In the time since, however, tick-borne health risks have expanded far beyond Lyme disease to include a variety of other bacterial pathogens and viruses, and additional vectors, necessitating a continually evolving approach to tick surveillance. In 2017, Monmouth County initiated an active surveillance program targeting sites across three ecological regions for collection of Ixodes scapularis Say (Acari: Ixodidae) and Amblyomma americanum L. (Acari: Ixodidae) as well as testing via qPCR for associated bacterial pathogens. During the first five years of this program (2017–2021), we report high levels of spatiotemporal variability in nymphal density and infection prevalence in both species, limiting the granularity with which human risk can be predicted from acarological data. Nonetheless, broader patterns emerged, including an ongoing trend of A. americanum dominance, risks posed by Borrelia miyamotoi, and the frequency of coinfected ticks. We present some of the first county-level, systematic surveillance of nymphal A. americanum density and infection prevalence in the northeastern US. We also documented a temporary decline in Borrelia burgdorferi that could relate to unmeasured trends in reservoir host populations. We discuss the implications of our findings for tick-borne disease ecology, public health communication, and tick surveillance strategies in endemic areas.
... Research so far indicates that the prevalence of B. miyamotoi-infected ticks is much lower than that of B. burgdorferi (Barbour et al. 2009). The current geographic distribution of B. miyamotoi is potentially much larger than B. burgdoferi due to the spirochete's ability to transmit transovarially within ticks (Han et al. 2019). Powassan virus lineage II (POWV) or DTV is a tick-borne encephalitic virus from the family Flaviviridae. ...
Odocoileus virginianus (white-tailed deer) is the primary host of adult Ixodes scapularis (deer tick). Most of the research into I. scapularis has been geographically restricted to the northeastern United States, with limited interest in Oklahoma until recently as the I. scapularis populations spread due to climate change. Ticks serve as a vector for pathogenic bacteria, protozoans, and viruses that pose a significant human health risk. To date, there has been limited research to determine what potential tick-borne pathogens are present in I. scapularis in central Oklahoma. Using a one-step multiplex real-time reverse transcription-PCR, I. scapularis collected from white-tailed deer was screened for Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi, Babesia microti, and deer tick virus (DTV). Ticks (n = 394) were pooled by gender and life stage into 117 samples. Three pooled samples were positive for B. miyamotoi and five pooled samples were positive for DTV. This represents a minimum infection rate of 0.8% and 1.2%, respectively. A. phagocytophilum, B. burgdorferi, and B. microti were not detected in any samples. This is the first report of B. miyamotoi and DTV detection in Oklahoma I. scapularis ticks. This demonstrates that I. scapularis pathogens are present in Oklahoma and that further surveillance of I. scapularis is warranted.
... Ticks acquire Borrelia burgdorferi infections by feeding from infected hosts. While some Borrelia species such as Borrelia miyamotoi are capable of vertical transmission from an infected female into her eggs, this has not been found for B. burgdorferi, so larvae would not be expected to be infected with B. burgdorferi until they had fed from an infected host [54][55][56]. This is consistent with our results, although finding of infected larvae is not impossible; larvae can become infected after feeding from an infected host and might be collected prior to molting. ...
Ticks are vectors of many diseases, including Lyme disease (Ld). Lyme disease is an emerging disease in Canada caused by infection with the Lyme borreliosis (Lb) members of the Borrelia genus of spirochaete bacteria, of which Borrelia burgdorferi is regionally the most prevalent. The primary tick vector in central and eastern Canada, Ixodes scapularis, is increasing in numbers and in the geographical extent of established populations. This study documents the distribution of ticks recovered by passive surveillance, and their B. burgdorferi infection prevalence, in three Canadian Maritime provinces from 2012–2020. These regions represent areas in which tick populations are widely established, establishing, and considered non-established. Using a community science approach by partnering with veterinarians and members of the public, we collected over 7000 ticks from the 3 provinces. The three species found most often on companion animals and humans were I. scapularis (76.9%), Ixodes cookei (10.4%) and Dermacentor variabilis (8.9%). The most common hosts were dogs (60.5%), cats (16.8%) and humans (17.6%). As is typical of passive surveillance tick collections, the majority of ticks recovered were adult females; for I. scapularis 90.2%, 5.3%, 3.9% and 0.6% of the total of 5630 ticks recovered for this species were adult females, adult males, nymphs and larvae, respectively. The majority of B. burgdorferi-infected ticks were I. scapularis, as expected. Borrelia infection prevalence in I scapularis was higher in Nova Scotia (20.9%), the province with the most endemic regions, than New Brunswick (14.1%) and Prince Edward Island (9.1%), provinces thought to have established and non-established tick populations, respectively. The province-wide Borrelia infection prevalence generally increased in these latter tow provinces over the course of the study. The host did not have a significant effect on B. burgdorferi infection prevalence; I. scapularis ticks from dogs, cats, humans was, 13.3% (n = 3622), 15.6% (n = 817), 17.9% (n = 730), respectively. No I. scapularis larvae were found infected (n = 33) but B. burgdorferi was detected in 14.8% of both adults (n = 5140) and nymphs (n = 215). The incidence of B. burgdorferi infection also did not differ by engorgement status 15.0% (n = 367), 15.1% (n = 3101) and 14.4% (n = 1958) of non-engorged, engorged and highly engorged ticks, respectively, were infected. In New Brunswick, at the advancing front of tick population establishment, the province-wide infection percentages generally increased over the nine-year study period and all health district regions showed increased tick recoveries and a trend of increased percentages of Borrelia-infected ticks over the course of the study. Within New Brunswick, tick recoveries but not Borrelia infection prevalence were significantly different from endemic and non-endemic regions, suggesting cryptic endemic regions existed prior to their designation as a risk area. Over the 9 years of the study, tick recoveries increased in New Brunswick, the primary study region, and I. scapularis recoveries spread northwards and along the coast, most but not all new sites of recoveries were predicted by climate-based models, indicating that ongoing tick surveillance is necessary to accurately detect all areas of risk. Comparison of tick recoveries and public health risk areas indicates a lag in identification of risk areas. Accurate and timely information on tick distribution and the incidence of Borrelia and other infections are essential for keeping the public informed of risk and to support disease prevention behaviors.
... Transovarial transmission of Borrelia species occurs in hard ticks as well as soft ticks. The former include B. theileri in R. microplus (Smith et al. 1978), B. lonestari in Amblyomma americanum (L.) (Ixodida: Amblyomminae) (Killmaster et al. 2014), and B. miyamotoi in I. scapularis (Scoles et al. 2001, Han et al. 2019. Older reports of transovarial transmission of Borreliella species in Ixodes spp. ...
Spirochetes of the family Borreliaceae are, with one exception, tick-borne pathogens of a variety of vertebrates. The family at present comprises two genera: Borrelia (Swellengrebel), which includes the agents of relapsing fever, avian spirochetosis, and bovine borreliosis, and Borreliella (Gupta et al.), which includes the agents of Lyme disease and was formerly known as 'Borrelia burgdorferi sensulato complex'. The two genera are distinguished not only by their disease associations but also biological features in the tick vector, including tissue location in unfed ticks and transovarial transmission. Borrelia species transmitted by argasid (soft) ticks tend to have more exclusive relationships with their tick vectors than do other Borrelia species and all Borreliella species that have ixodid (hard) ticks as vectors. The division of genera is supported by phylogenomic evidence from whole genomes and by several specific molecular markers. These distinguishing phylogenetic criteria also applied to three new species or isolates of Borrelia that were discovered in ixodid ticks of reptiles, a monotreme, and birds. Although the deep branching of the family from other spirochetes has been a challenge for inferences about evolution of the family, the discovery of related microorganisms in the gut microbiota of other arachnids suggests an ancestral origin for the family as symbionts of ticks and other arachnids.
... Vertical transmission of B. miyamotoi. B. miyamotoi is known to be vertically transmitted in Ixodes scapularis (18,19), has been observed in I. pacificus larvae (36), and is able to infect small mammals that ticks feed on (18,25,36,37). It is unclear whether infection dynamics in natural populations require amplification by horizontal transmission from the vertebrate hosts. ...
Tick-borne diseases in California include Lyme disease (caused by Borrelia burgdorferi ), infections with Borrelia miyamotoi , and human granulocytic anaplasmosis (caused by Anaplasma phagocytophilum ). We surveyed multiple sites and habitats (woodland, grassland, coastal chaparral) in California to describe spatial patterns of tick-borne pathogen prevalence in western black-legged ticks ( Ixodes pacificus ). We found that several species of Borrelia – B. burgdorferi , B. americana and B. bissettiae - were observed in habitats such as coastal chaparral that does not harbor obvious reservoir host candidates. Describing tick-borne pathogen prevalence is strongly influenced by the scale of surveillance: aggregating data from individual sites to match jurisdictional boundaries (e.g., county or state) can lower the reported infection prevalence. Considering multiple pathogen species in the same habitat allows a more cohesive interpretation of local pathogen occurrence.
Importance
Understanding the local host ecology and prevalence of zoonotic diseases is vital for public health. Using tick-borne diseases in California, we show that there is often a bias to our understanding and that studies tend to focus on particular habitats e.g., Lyme disease in oak woodlands. Other habitats may harbor a surprising diversity of tick-borne pathogens but have been neglected, e.g., coastal chaparral. Explaining pathogen prevalence requires descriptions of data at a local scale; otherwise, aggregating the data can misrepresent the local dynamics of tick-borne diseases.
... are transmitted mostly transovarially in the tick, with some exceptions, such as B. duttonni transmitted by Ornithodoros moubata and B. hermsii transmitted by Ornithodoros hermsi (33)(34)(35). Borrelia crucidurae was shown to have a transovarial transmission rate of 33.3 to 53.3% in the soft tick Ornithodoros erraticus (36), and Borrelia miyamotoi, a TBRF transmitted by the hard tick Ixodes scapularis, was shown to have a transovarial transmission rate of 90.9% (37). ...
Borrelia persica transmitted by the argasid tick Ornithodoros tholozani causes human tick-borne relapsing fever in the Middle East and Central Asia. Infection is acquired often when visiting tick-infested caves and reported to be transmitted mainly transovarially between ticks occasionally infecting humans. To study the epidemiology of this infection, ticks were trapped in 24 caves in 12 geographic zones covering all of Israel and identified morphologically. DNA was extracted from larvae, nymphs and adult stages from each location and PCR followed by DNA sequencing was performed to identify Borrelia infection, tick species, and tick blood-meal sources. 51,472 argasid ticks were collected from 16 of 24 caves surveyed. 2,774 O. tholozani were analyzed and 72 (2.6%) from nine caves were PCR-positive for B. persica. Infection rates in male, female and nymphal ticks (4.4%, 3% and 3.2%, respectively) were higher than in larva ( p <0.001) with only 3 (0.04%) positive larvae. Presence of blood-meal was associated with B. persica infection in ticks ( p =0.003), and blood-meals of golden jackals, red foxes and Cairo spiny mouse were associated with infection ( p ≤0.043). PCR survey of 402 wild mammals revealed B. persica infection with the highest rate in social voles (22%), red foxes (16%), golden jackals (8%) and Cairo spiny mice (3%). In conclusion, although transovarial tick transmission of B. persica occurs at low levels, ticks apparently acquire infection mainly from wildlife canid and rodents and may eventually transmit relapsing fever borreliosis to humans who enter their habitat.
Importance
Borrelia persica is a spirochete that causes tick-borne relapsing fever in humans in an area that spans from India to the Mediterranean. Until now it was thought that the soft tick vector of this infection, Orhinthodoros tholozani , is also its main reservoir and it transmits B. persica mostly transovarially between tick generations. This study showed that tick infection with B. persica is associated with feeding blood from wild jackals, foxes and rodents, and that transovarial transmission is minimal. Since O. tholozani ticks are found in isolated caves and ruins, it is assumed that wild canids who migrate over long distances have a major role in the transmission of B. persica between remote tick populations, and its then maintained locally also by rodents and eventually transferred to humans during tick bites. Prevention of human infection could be achieved by restricting entrance of canines and humans to habitats with O. tholozani populations.
... The main Ixodes vectors for both Borrelia species live in the temperate climate zones of the Northern hemisphere: Ixodes pacificus and Ixodes scapularis (North-America), Ixodes ricinus (Europe and Asia) and Ixodes pacificus (Russia and Asia). In contrast to B. burgdorferi sensu lato, which is not transmitted from the female adult tick to her offspring (Steere et al., 2016), B. miyamotoi is efficiently transmitted transovarially (Han et al., 2019). Infection rates of nymphs, the Ixodes life stage that is most notorious to bite humans, differ for B. miyamotoi and B. burgdorferi sensu lato, with for instance average infection rates of I. ricinus nymphs with B. burgdorferi sensu lato of approximately 12% (Strnad et al., 2017) compared to approximately 2% for B. miyamotoi in Europe (Cutler et al., 2019;Wagemakers et al., 2015). ...
Relapsing fever (RF) is caused by several species of Borrelia; all, except two species, are transmitted to humans by soft (argasid) ticks. The species B. recurrentis is transmitted from one human to another by the body louse, while B. miyamotoi is vectored by hard-bodied ixodid tick species. RF Borrelia have several pathogenic features that facilitate invasion and dissemination in the infected host. In this article we discuss the dynamics of vector acquisition and subsequent transmission of RF Borrelia to their vertebrate hosts. We also review taxonomic challenges for RF Borrelia as new species have been isolated throughout the globe. Moreover, aspects of pathogenesis including symptomology, neurotropism, erythrocyte and platelet adhesion are discussed. We expound on RF Borrelia evasion strategies for innate and adaptive immunity, focusing on the most fundamental pathogenetic attributes, multiphasic antigenic variation. Lastly, we review new and emerging species of RF Borrelia and discuss future directions for this global disease.
... 1.9%-2.5% of host seeking I.dammini from Lyme disease endemic sites in New York, Connecticut, Rhode Island and New Jersey were infected and infected female ticks provided filial infection rates of 6%-73%. A study of engorged female ticks removed from deer in 4 different states demonstrated a TOTR of 57%-100%, with FIR of 68%-100%, resulting in a VTR of 44%-93%(Han et al., 2019). Thus, inheritance is likely the main mode of perpetuation if VTR remains stable through additional generations. ...
With one exception (epidemic relapsing fever), borreliae are obligately maintained in nature by ticks. Although some Borrelia spp. may be vertically transmitted to subsequent generations of ticks, most require amplification by a vertebrate host because inheritance is not stable. Enzootic cycles of borreliae have been found globally; those receiving the most attention from researchers are those whose vectors have some degree of anthropophily and, thus, cause zoonoses such as Lyme disease or relapsing fever. To some extent, our views on the synecology of the borreliae has been dominated by an applied focus, viz., analyses that seek to understand the elements of human risk for borreliosis. But, the elements of borrelial perpetuation do not necessarily bear upon risk, nor do our concepts of risk provide the best structure for analyzing perpetuation. We identify the major global themes for the perpetuation of borreliae, and summarize local variations on those themes, focusing on key literature to outline the factors that serve as the basis for the distribution and abundance of borreliae.
... The prevalence of B. miyamotoi in ticks was found to be usually lower than that of B. burgdorferi s.l. although prevalences of~15% have been reported in some regions [3,7,10,16,17,21,22]. Rodents have been implicated as reservoir hosts for B. miyamotoi [23,24], but transovarial transmission is also known to occur [25,26] and may contribute to the persistence of this Borrelia in nature. ...
Background:
The genus Borrelia comprises spirochaetal bacteria maintained in natural transmission cycles by tick vectors and vertebrate reservoir hosts. The main groups are represented by a species complex including the causative agents of Lyme borreliosis and relapsing fever group Borrelia. Borrelia miyamotoi belongs to the relapsing fever group of spirochetes and forms distinct populations in North America, Asia, and Europe. As all Borrelia species B. miyamotoi possess an unusual and complex genome consisting of a linear chromosome and a number of linear and circular plasmids. The species is considered an emerging human pathogen and an increasing number of human cases are being described in the Northern hemisphere. The aim of this study was to produce a high quality reference genome that will facilitate future studies into genetic differences between different populations and the genome plasticity of B. miyamotoi.
Results:
We used multiple available sequencing methods, including Pacific Bioscience single-molecule real-time technology (SMRT) and Oxford Nanopore technology (ONT) supplemented with highly accurate Illumina sequences, to explore the suitability for whole genome assembly of the Russian B. miyamotoi isolate, Izh-4. Plasmids were typed according to their potential plasmid partitioning genes (PF32, 49, 50, 57/62). Comparing and combining results of both long-read (SMRT and ONT) and short-read methods (Illumina), we determined that the genome of the isolate Izh-4 consisted of one linear chromosome, 12 linear and two circular plasmids. Whilst the majority of plasmids had corresponding contigs in the Asian B. miyamotoi isolate FR64b, there were only four that matched plasmids of the North American isolate CT13-2396, indicating differences between B. miyamotoi populations. Several plasmids, e.g. lp41, lp29, lp23, and lp24, were found to carry variable major proteins. Amongst those were variable large proteins (Vlp) subtype Vlp-α, Vlp-γ, Vlp-δ and also Vlp-β. Phylogenetic analysis of common plasmids types showed the uniqueness in Russian/Asian isolates of B. miyamotoi compared to other isolates.
Conclusions:
We here describe the genome of a Russian B. miyamotoi clinical isolate, providing a solid basis for future comparative genomics of B. miyamotoi isolates. This will be a great impetus for further basic, molecular and epidemiological research on this emerging tick-borne pathogen.
... In North America, vectors include Ixodes scapularis and I. pacificus, which are also hosts for the causative agent of Lyme disease (LD), Borrelia burgdorferi. Prevalence in ticks ranges from 0.02 to 10% in I. scapularis and Ixodes pacificus populations in the United States [1][2][3][4] . Though the true burden of B.miyamotoi disease (BMD) on human disease is still being realized, current research has estimated human prevalence to be approximately 0.84-17% among individuals parasitized by ticks 1,3,5-8 . ...
The tick-borne spirochete, Borrelia miyamotoi, is an emerging pathogen of public health significance. Current B. miyamotoi serodiagnostic testing depends on reactivity against GlpQ which is not highly sensitive on acute phase serum samples. Additionally, anti-B. miyamotoi antibodies can cross-react with C6 antigen testing for B. burgdorferi, the causative agent of Lyme disease, underscoring the need for improved serological assays that produce accurate diagnostic results. We performed an immunoproteomics analysis of B. miyamotoi proteins to identify novel serodiagnostic antigens. Sera from mice infected with B. miyamotoi by subcutaneous inoculation or tick bite were collected for immunoblotting against B. miyamotoi membrane-associated proteins separated by 2-dimensional electrophoresis (2DE). In total, 88 proteins in 40 2DE immunoreactive spots were identified via mass spectrometry. Multiple variable large proteins (Vlps) and a putative lipoprotein were among those identified and analyzed. Reactivity of anti-B. miyamotoi sera against recombinant Vlps and the putative lipoprotein confirmed their immunogenicity. Mouse anti-B. burgdorferi serum was cross-reactive to all recombinant Vlps, but not against the putative lipoprotein by IgG. Furthermore, antibodies against the recombinant putative lipoprotein were present in serum from a B. miyamotoi-infected human patient, but not a Lyme disease patient. Results presented here provide a comprehensive profile of B. miyamotoi antigens that induce the host immune response and identify a putative lipoprotein as a potentially specific antigen for B. miyamotoi serodetection.
... Hard-tick relapsing fever typically manifests as a nonspecific febrile illness (3,4). Han et al. (5) found a B. miyamotoi infection prevalence of 3.7% in adult I. scapularis ticks in Maine, ≈10-fold less than that for B. burgdorferi infection (50%, range 32%-65%) (6). ...
We conducted a serosurvey of 230 persons in Maine, USA, who had been bitten by Ixodes scapularis or I. cookei ticks. We documented seropositivity for Borrelia burgdorferi (13.9%) and B. miyamotoi (2.6%), as well as a single equivocal result (0.4%) for Powassan encephalitis virus.
Due to their hematophagous life cycle, hard-bodied ticks including the genus Ixodes are a potential vector for numerous pathogenic organisms including bacteria, protozoa, viruses, and infectious prions. The natural geographic range of several hard tick species, includig Ixodes scapularis, has expanded over recent decades. Consequently, there is an ongoing need to maintain, feed, and propagate ticks for host-pathogen interaction studies to better understand and mitigate their impact on human and animal health. Artificial membrane feeding of hard ticks has advanced in recent years, has study design advantages, and should be used, when possible, to reduce animal use, but it also has several limitations that require the continued use of mammalian hosts including mice, guinea pigs, and rabbits. In this overview, we discuss the best management practices for these relevant species with respect to biosafety, health, and optimal host comfort when used in studies that depend on tick feeding. The capsule-jacket method is preferred over the ear sock-E-collar method of tick feeding on rabbit hosts because of better host health, comfort, and increased study versatility.
Borrelia miyamotoi is an emerging Ixodes tick-borne human pathogen in the Northern hemisphere. The aim of the current study was to compare whole genome sequences of B. miyamotoi isolates from different continents. Using a combination of Illumina and PacBio platforms and a novel genome assembly and plasmid typing pipeline, we reveal that the 21 sequenced B. miyamotoi isolates and publically available B. miyamotoi genomes from North America, Asia, and Europe form genetically distinct populations and cluster according to their geographical origin, where distinct Ixodes species are endemic. We identified 20 linear and 17 circular plasmid types and the presence of specific plasmids for isolates originating from different continents. Linear plasmids lp12, lp23, lp41, and lp72 were core plasmids found in all isolates, with lp41 consistently containing the vmp expression site. Our data provide insights into the genetic basis of vector competence, virulence, and pathogenesis of B. miyamotoi.
Borrelia miyamotoi disease is an emerging tick-borne human illness in the United States caused by Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) bacterium. With Pennsylvania reporting thousands of tick-borne disease cases annually, determining the minimum infection rate (MIR) of B. miyamotoi in Ixodes scapularis (Say, Acari: Ixodidae) adults within Pennsylvania is of utmost importance. Active surveillance was performed from October 2019 to April 2020 to collect a minimum of 50 I. scapularis ticks from every county within Pennsylvania and then screened for B. miyamotoi via qPCR. Ticks were collected from all 67 counties with the majority of those being adult I. scapularis. Additional ticks collected were Dermacentor albipictus (Packard, Acari: Ixodidae), Haemaphysalis longicornis (Neumann, Acari: Ixodidae), and immature I. scapularis. Adult I. scapularis were pooled and tested for B. miyamotoi. MIR for positive B. miyamotoi pools and density of infected adult I. scapularis varied by county, with positive pools from 38 Pennsylvania counties. This is the first statewide evaluation of B. miyamotoi in Pennsylvania in questing adult I. scapularis. These prevalence and distribution data will aid health care practitioners within the state of Pennsylvania and the northeast United States to understand potential risk and bring awareness to the lesser known human Borrelia illness, Borrelia miyamotoi disease.
In North America, Lyme disease (LD) is primarily caused by the spirochetal bacterium Borrelia burgdorferi, transmitted to humans by Ixodes species tick bites, at an estimated rate of 476,000 patients diagnosed per year. Acute LD often manifests with flu-like symptoms and an expanding rash known as erythema migrans (EM) and less often with neurologic, neuropsychiatric, arthritic, or cardiac features. Most acute cases of Lyme disease are effectively treated with antibiotics, but 10–20% of individuals may experience recurrent or persistent symptoms. This chapter focuses on the neuropsychiatric aspects of Lyme disease, as these are less widely recognized by physicians and often overlooked. Broader education about the potential complexity, severity, and diverse manifestations of tick-borne diseases is needed.KeywordsBorreliosisLyme diseaseNeuropsychiatric symptomsPANSPTLDS
In the United States, surveillance has been key to tracking spatiotemporal emergence of blacklegged ticks [Ixodes scapularis Say (Ixodida:Ixodidae)] and their pathogens such as Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner (Spirochaetales: Spirochaetaceae), the agent of Lyme disease. On the Holt Research Forest in midcoastal Maine, collection of feeding ticks from live-trapped small mammal hosts allowed us to track the emergence and establishment of I. scapularis, 1989–2019. From 1989–1995, we collected only I. angustus Neumann (Ixodida: Ixodidae)(vole tick), Dermacentor variabilis Say (Ixodida: Ixodidae) (American dog tick), and I. marxi Banks (Ixodida: Ixodidae) (squirrel tick) from seven species of small mammals. The most abundant tick host was the white-footed mouse [Peromyscus leucopus Rafinesque (Rodentia:Cricetidae)] followed by the red-backed vole (Myodes gapperi Vigors (Rodentia: Cricetidae)). Emergence of I. scapularis was signaled via the appearance of subadult I. scapularis in 1996. Emergence of B. burgdorferi was signaled through its appearance in I. scapularis feeding on mice in 2005. There was a substantial increase in I. scapularis prevalence (proportion of hosts parasitized) and burdens (ticks/host) on white-footed mice and red-backed voles in 2007. The ~11-yr time-to-establishment for I. scapularis was consistent with that seen in other studies. White-footed mice comprised 65.9% of all captures and hosted 94.1% of the total I. scapularis burden. The white-footed mouse population fluctuated interannually, but did not trend up as did I. scapularis prevalence and burdens. There were concurrent declines in I. angustus and D. variabilis. We discuss these results in the broader context of regional I. scapularis range expansion.
Borrelia miyamotoi, a bacterium that causes relapsing fever, is found in ixodid ticks throughout the northern hemisphere. The first cases of human infection with B. miyamotoi were identified in 2011. In the eastern USA, blacklegged ticks (Ixodes scapularis) become infected by feeding on an infected vertebrate host, or through transovarial transmission. We surveyed B. miyamotoi prevalence in ticks within forested habitats in Dutchess County, New York, and identified possible reservoir hosts. To assess spatial variation in infection, we collected questing nymphal ticks at > 150 sites. To assess temporal variation in infection, we collected questing nymphs for 8 years at a single study site. We collected questing larval ticks from nine plots to estimate the amount of transovarial transmission. To evaluate potential reservoir hosts, we captured 14 species of mammal and bird hosts naturally infested with larval blacklegged ticks and held these hosts in the laboratory until ticks fed to repletion and molted to nymphs. We determined infection for all ticks using quantitative polymerase chain reaction. The overall infection prevalence of questing nymphal ticks across all sites was ~ 1%, but prevalence at individual sites was as high as 9.1%. We detected no significant increase in infection through time. Only 0.4% of questing larval ticks were infected. Ticks having fed as larvae from short-tailed shrews, red squirrels, and opossums tended to have higher infection prevalence than did ticks having fed on other hosts. Further studies of the role of hosts in transmission are warranted. The locally high prevalence of B. miyamotoi in the New York/New England landscape suggests the importance of vigilance by health practitioners and the public.
Graphical abstract
Deer keds (Diptera: Hippoboscidae: Lipoptena Nitzsch, 1818 and Neolipoptena Bequaert, 1942) are blood-feeding ectoparasites that primarily attack cervids and occasionally bite humans, while ticks may be found on cervids, but are more generalized in host choice. Recent detection of pathogens such as Anaplasma and Borrelia in deer keds and historical infections of tick-borne diseases provides reason to investigate these ectoparasites as vectors. However, previous methods employed to sample deer keds and ticks vary, making it difficult to standardize and compare ectoparasite burdens on cervids. Therefore, we propose a standardized protocol to collect deer keds and ticks from hunter-harvested deer, which combines previous methods of sampling, including timing of collections, dividing sections of the deer, and materials used in the collection process. We tested a three-section and a five-section sampling scheme in 2018 and 2019, respectively, and found that dividing the deer body into five sections provided more specificity in identifying where deer keds and ticks may be found on deer. Data from 2018 suggested that deer keds and ticks were found on all three sections (head, anterior, posterior), while data from 2019 suggested that more Ixodes scapularis were found on the head and deer keds were found on all body sections (head, dorsal anterior, dorsal posterior, ventral anterior, and ventral posterior). The protocol provides an efficient way to sample deer for deer keds and ticks and allows researchers to compare ectoparasite burdens across geographical regions. Furthermore, this protocol can be used to collect other ectoparasites from deer or other cervids.
Background The genus Borrelia comprises spirochaetal bacteria maintained in natural transmission cycles by tick vectors and vertebrate reservoir hosts. The main groups are represented by a species complex including the causative agents of Lyme borreliosis and relapsing fever group Borrelia . Borrelia miyamotoi belongs to the relapsing-fever group of spirochetes and forms distinct populations in North America, Asia, and Europe. As all Borrelia species B. miyamotoi possess an unusual and complex genome consisting of a linear chromosome and a number of linear and circular plasmids. The species is considered a relatively new human pathogen and an increasing number of human cases are being described in the Northern hemisphere. The aim of this study was to produce a high quality reference genome that will facilitate future studies into genetic differences between different populations and the genome plasticity of B. miyamotoi . Results We used multiple available sequencing methods, including Pacific Bioscience single-molecule real-time technology (SMRT) and Oxford Nanopore technology (ONT) supplemented with highly accurate Illumina sequences, to explore the suitability for whole genome assembly of the Russian B. miyamotoi isolate, Izh-4. Plasmids were typed according to their potential plasmid partitioning genes (PF32, 49, 50, 57/62). Comparing and combining results of both long-read methods (SMRT and ONT), we determined that the genome of the Izh-4 consisted of one linear chromosome, 12 linear and two circular plasmids. Whilst the majority of plasmids had corresponding assembly fragments in the Asian B. miyamotoi isolate FR64b, there were only four that matched plasmids of the North American isolate CT13-2396, indicating differences between B. miyamotoi populations. Several plasmids, e.g. lp41, lp29, lp23, and lp24, were found to carry variable major proteins. Amongst those were variable large proteins (Vlp) subtype Vlp-α, Vlp-γ, Vlp-δ and also Vlp-β. Phylogenetic analysis of common plasmids types showed the uniqueness in Russian/Asian isolates of B. miyamotoi compared to other isolates. Conclusions We here describe the genome of a Russian B. miyamotoi clinical isolate, providing a solid basis for future comparative genomics of B. miyamotoi isolates. This will be a great impetus for further basic, molecular and epidemiological research on this emerging tick-borne pathogen.
Lyme disease is the most commonly reported vector-borne disease in the United States, and the number of cases reported each year continues to rise. The complex nature of the relationships between the pathogen (Borrelia burgdorferi sensu stricto), the tick vector (Ixodes scapularis Say), multiple vertebrate hosts, and numerous environmental factors creates challenges for understanding and predicting tick population and pathogen transmission dynamics. LYMESIM is a mechanistic model developed in the late 1990s to simulate the life-history of I. scapularis and transmission dynamics of B. burgdorferi s.s. Here we present LYMESIM 2.0, a modernized version of LYMESIM, that includes several modifications to enhance the biological realism of the model and to generate outcomes that are more readily measured under field conditions. The model is tested for three geographically distinct locations in New York, Minnesota, and Virginia. Model-simulated timing and densities of questing nymphs, infected nymphs, and abundances of nymphs feeding on hosts are consistent with field observations and reports for these locations. Sensitivity analysis highlighted the importance of temperature in host finding for the density of nymphs, the importance of transmission from small mammals to ticks on the density of infected nymphs, and temperature-related tick survival for both density of nymphs and infected nymphs. A key challenge for accurate modeling of these metrics is the need for regionally representative inputs for host populations and their fluctuations. LYMESIM 2.0 is a useful public health tool that downstream can be used to evaluate tick control interventions and can be adapted for other ticks and pathogens.
Ixodes scapularis is currently known to transmit 7 pathogens responsible for Lyme disease, anaplasmosis, babesiosis, tick-borne relapsing fever, ehrlichiosis, and Powassan encephalitis. Ixodes scapularis can also be colonized by endosymbiotic bacteria including those in the genus of Rickettsia. We screened 459 I. scapularis ticks submitted to the Connecticut Agricultural Experiment Station Tick Testing Laboratory with the objectives to (1) examine differences in infection prevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi, (2) evaluate whether prevalence of co-infections occur at the same frequency that would be expected based on single infection, and (3) determine the presence of rickettsial endosymbionts in I. scapularis. The prevalence of infection in I. scapularis was highest with Bo. burgdorferi sensu lato (nymph = 45.8%; female = 47.0%), followed by A. phagocytophilum (nymph = 4.0%; female = 6.9%), Ba. microti (nymph = 5.7%; female = 4.7%), and Bo. miyamotoi (nymph = 0%; female = 7.3%). We also identified rickettsial endosymbionts in 93.3% of I. scapularis. Nymphs were significantly more likely to be infected with Bo. burgdorferi if they were infected with Ba. microti, whereas adult females were significantly more likely to be infected with Bo. burgdorferi if they were infected with A. phagocytophilum. Our study suggests that the infection prevalence of Bo. burgdorferi is not independent of other co-circulating pathogens and that there is a substantially higher infection of Bo. miyamotoi in I. scapularis females compared with nymphs in this study. High prevalence of infection and co-infection with multiple pathogens in I. scapularis highlights the public health consequences in Connecticut, a state endemic for Lyme and other tick-borne diseases.
The relapsing fever spirochete, Borrelia miyamotoi, is increasingly recognized as a cause of human illness (hard tick-borne relapsing fever) in the United States. We previously demonstrated that single nymphs of the blacklegged tick, Ixodes scapularis, can transmit B. miyamotoi to experimental hosts. However, two recent epidemiological studies from the Northeastern United States indicate that human cases of hard tick-borne relapsing fever peak during late summer, after the spring peak for nymphal tick activity but coincident with the peak seasonal activity period of larval ticks in the Northeast. These epidemiological findings, together with evidence that B. miyamotoi can be passed from infected I. scapularis females to their offspring, suggest that bites by transovarially-infected larval ticks can be an important source of human infection. To demonstrate experimentally that transovarially-infected larval I. scapularis ticks can transmit B. miyamotoi, outbred Mus musculus CD1 mice were exposed to 1 or 2 potentially infected larvae. Individual fed larvae and mouse blood taken 10 d after larvae attached were tested for presence of B. miyamotoi DNA, and mice also were examined for seroreactivity to B. miyamotoi 8 wk after tick feeding. We documented B. miyamotoi DNA in blood from 13 (57%) of 23 mice exposed to a single transovarially-infected larva and in 5 (83%) of 6 mice exposed to two infected larvae feeding simultaneously. All 18 positive mice also demonstrated seroreactivity to B. miyamotoi. Of the 11 remaining mice without detectable B. miyamotoi DNA in their blood 10 d after infected larvae attached, 7 (64%) had evidence of spirochete exposure by serology 8 wk later. Because public health messaging for risk of exposure to Lyme disease spirochetes focuses on nymphal and female I. scapularis ticks, our finding that transovarially-infected larvae effectively transmit B. miyamotoi should lead to refined tick-bite prevention messages.
We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.
Problem/condition:
Lyme disease is the most commonly reported vectorborne disease in the United States but is geographically focal. The majority of Lyme disease cases occur in the Northeast, mid-Atlantic, and upper Midwest regions. Lyme disease can cause varied clinical manifestations, including erythema migrans, arthritis, facial palsy, and carditis. Lyme disease occurs most commonly among children and older adults, with a slight predominance among males.
Reporting period:
2008-2015.
Description of system:
Lyme disease has been a nationally notifiable condition in the United States since 1991. Possible Lyme disease cases are reported to local and state health departments by clinicians and laboratories. Health department staff conduct case investigations to classify cases according to the national surveillance case definition. Those that qualify as confirmed or probable cases of Lyme disease are reported to CDC through the National Notifiable Diseases Surveillance System. States with an average annual incidence during this reporting period of ≥10 confirmed Lyme disease cases per 100,000 population were classified as high incidence. States that share a border with those states or that are located between areas of high incidence were classified as neighboring states. All other states were classified as low incidence.
Results:
During 2008-2015, a total of 275,589 cases of Lyme disease were reported to CDC (208,834 confirmed and 66,755 probable). Although most cases continue to be reported from states with high incidence in the Northeast, mid-Atlantic, and upper Midwest regions, case counts in most of these states have remained stable or decreased during the reporting period. In contrast, case counts have increased in states that neighbor those with high incidence. Overall, demographic characteristics associated with confirmed cases were similar to those described previously, with a slight predominance among males and a bimodal age distribution with peaks among young children and older adults. Yet, among the subset of cases reported from states with low incidence, infection occurred more commonly among females and older adults. In addition, probable cases occurred more commonly among females and with a higher modal age than confirmed cases.
Interpretation:
Lyme disease continues to be the most commonly reported vectorborne disease in the United States. Although concentrated in historically high-incidence areas, the geographic distribution is expanding into neighboring states. The trend of stable to decreasing case counts in many states with high incidence could be a result of multiple factors, including actual stabilization of disease incidence or artifact due to modifications in reporting practices employed by some states to curtail the resource burden associated with Lyme disease surveillance.
Public health action:
This report highlights the continuing public health challenge of Lyme disease in states with high incidence and demonstrates its emergence in neighboring states that previously experienced few cases. Educational efforts should be directed accordingly to facilitate prevention, early diagnosis, and appropriate treatment. As Lyme disease emerges in neighboring states, clinical suspicion of Lyme disease in a patient should be based on local experience rather than incidence cutoffs used for surveillance purposes. A diagnosis of Lyme disease should be considered in patients with compatible clinical signs and a history of potential exposure to infected ticks, not only in states with high incidence but also in areas where Lyme disease is known to be emerging. These findings underscore the ongoing need to implement personal prevention practices routinely (e.g., application of insect repellent and inspection for and removal of ticks) and to develop other effective interventions.
Background:
Hard tick-borne relapsing fever caused by Borrelia miyamotoi has been reported in Russia, the Netherlands, Germany, Japan and the northeastern and upper midwestern United States. We sought to investigate the presence of B. miyamotoi infection in humans in Manitoba, Canada.
Methods:
Two hundred fifty sera collected from residents of Manitoba with suspected Lyme disease between 2011 and 2014 were tested for Borrelia burgdorferi antibody using a C6 peptide enzyme-linked immunosorbent assay (ELISA) followed by Western blot. Residual sera were then anonymized, stored at -80°C and subsequently thawed and tested for B. miyamotoi antibody using a 2-step glycerosphosphodiester phosphodiesterase-based ELISA and Western blot assay.
Results:
Twenty-four of the 250 (9.6%) sera tested positive for B. miyamotoi immunoglobulin G. Participants who were B. miyamotoi seropositive were predominantly male (54%) and younger on average than those who were seronegative (32 and 44 yr of age, respectively). Participants who were seropositive for B. burgdorferi were significantly more likely to be B. miyamotoi seropositive than those who were B. burgdorferi seronegative (20.3% v. 6.6%, respectively, odds ratio 3.6, 95% confidence interval 1.5-8.5).
Interpretation:
This initial report of human B. miyamotoi infection in Canada should raise awareness of hard tick-borne relapsing fever among clinicians and residents of areas in Canada and western North America where Lyme disease is endemic.
Background
Borrelia miyamotoi is a newer cause of ixodid (hard-bodied) tick-borne illness. Because symptoms are generally nonspecific and pathognomonic clinical features are lacking, whole blood polymerase chain reaction (PCR) may be useful for confirming a diagnosis. A tick-borne disease panel (“TBD-3”) bundled with Borrelia species (including B. miyamotoi ) PCR (“TBD-3M”) was offered for patients with suspicion of TBD during 2014–2015 at South County Hospital in Rhode Island, an endemic region for many tick-borne illnesses.
Materials and Methods
Imugen laboratory was queried for all TBD-3M panels and Borrelia PCR’s sent from South County Hospital patients between January 1, 2014, and August 31, 2015. One positive whole blood B. miyamotoi PCR sample (genus and species specific) was considered evidence for B. miyamotoi infection. Demographics, clinical presentations, coinfections, laboratory abnormalities, and treatment courses for B. miyamotoi disease were examined.
Results
A total of 2324 patients had a bundled tick-borne panel performed for unexplained fever and other symptoms. In addition, 258 patients had individual Borrelia PCR’s performed. Overall, 78 patients were positive for B. burgdorferi PCR (3.0% positivity rate) and 18 patients were positive for B. miyamotoi PCR (0.7% positivity rate). Most patients presented with a “summer influenza”–like illness (94% reporting fever). Sixteen of these 18 patients were empirically prescribed doxycycline. One patient was concomitantly positive for B. miyamotoi PCR, B. microti PCR, and IgM Lyme antibodies. Three additional B. miyamotoi positive patients had positive Lyme serology.
Conclusions
Borrelia whole blood PCR was bundled to a pre-existing tick-borne panel to potentially account for unexplained fevers and other nonlocalizing symptoms in high-risk patients. Treatment recommendations for B. miyamotoi are based on case reports of successful treatments in other causes of relapsing fever, and the same antibiotics regimens are used for both. The utility of B. miyamotoi PCR in first-line screening of patients with unexplained fever may be minimal, given the low positivity rate observed and uniform effective empiric treatments prescribed.
Borrelia miyamotoi sensu lato relapsing fever group spirochetes are emerging as causative agents of human illness (Borrelia miyamotoi disease) in the United States. Host-seeking Ixodes scapularis ticks are naturally infected with these spirochetes in the eastern United States and experimentally capable of transmitting B. miyamotoi. However, the duration of time required from tick attachment to spirochete transmission has yet to be determined. We therefore conducted a study to assess spirochete transmission by single transovarially infected I. scapularis nymphs to outbred white mice at three time points post-attachment (24, 48, and 72 hours) and for a complete feed ( > 72–96 hours). Based on detection of B. miyamotoi DNA from the blood of mice fed on by an infected nymph, the probability of spirochete transmission increased from 10% by 24 hours of attachment (evidence of infection in 3/30 mice) to 31% by 48 hours (11/35 mice), 63% by 72 hours (22/35 mice), and 73% for a complete feed (22/30 mice). We conclude that (i) single I. scapularis nymphs effectively transmit B. miyamotoi relapsing fever group spirochetes while feeding, (ii) transmission can occur within the first 24 hours of nymphal attachment, and (iii) the probability of transmission increases with the duration of nymphal attachment.
A 5-year old Massachusetts resident developed hard tick-borne relapsing fever caused by Borrelia miyamotoi. A partially engorged Ixodes scapularis tick was removed from her scalp and identified as infected with B. miyamotoi using PCR. Two weeks later, she developed an illness compatible with B. miyamotoi infection that included fatigue and recurrent fever. The diagnosis was confirmed by B. miyamotoi seroconversion.
Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi-induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods.
We confirmed Borrelia miyamotoi infection in 7 patients who had contracted an illness while near La Crosse, Wisconsin, USA, an area where Ixodes scapularis ticks are endemic. B. miyamatoi infection should now be considered among differential diagnoses for patients from the midwestern United States who have signs and symptoms suggestive of tickborne illness.
Background:
Lyme borreliosis is the most common tick-borne human disease and is caused by Borrelia burgdorferi sensu lato (s.l.). Borrelia miyamotoi, a relapsing fever spirochaete, is transmitted transovarially, whereas this has not been shown for B. burgdorferi (s.l). Therefore, B. burgdorferi (s.l) is considered to cycle from nymphs to larvae through vertebrates. Larvae of Ixodes ricinus are occasionally B. burgdorferi (s.l) infected, but their vector competence has never been studied.
Methods:
We challenged 20 laboratory mice with field-collected larvae of I. ricinus. A subset of these larvae was analysed for infections with B. burgdorferi (s.l) and B. miyamotoi. After three to four challenges, mice were sacrificed and skin and spleen samples were analysed for infection by PCR and culture.
Results:
Field-collected larvae were naturally infected with B. burgdorferi (s.l) (0.62 %) and B. miyamotoi (2.0 %). Two mice acquired a B. afzelii infection and four mice acquired a B. miyamotoi infection during the larval challenges.
Conclusion:
We showed that larvae of I. ricinus transmit B. afzelii and B. miyamotoi to rodents and calculated that rodents have a considerable chance of acquiring infections from larvae compared to nymphs. As a result, B. afzelii can cycle between larvae through rodents. Our findings further imply that larval bites on humans, which easily go unnoticed, can cause Lyme borreliosis and Borrelia miyamotoi disease.
We compared the prevalence of Borrelia miyamotoi infection in questing and deer-associated adult Ixodes scapularis ticks in Wisconsin, USA. Prevalence among deer-associat- ed ticks (4.5% overall, 7.1% in females) was significantly higher than among questing ticks (1.0% overall, 0.6% in females). Deer may be a sylvatic reservoir for this newly recognized zoonotic pathogen. As an initial test of the hypothesis that white-tailed deer may be reservoir hosts, we collected questing and deer-associated adult I. scapularis ticks and assayed them for B. miyamotoi. We predicted that infection prevalence would be higher among deer-associated adult I. scapularis ticks than among questing adults. Furthermore, because females take larger blood meals than do males, we hypothesized that infection prevalence would be highest among deer-associated female ticks. © 2016, Centers for Disease Control and Prevention (CDC). All rights reserved.
TickNET, a public health network, was created in 2007 to foster greater collaboration between state health departments, academic centers, and the Centers for Disease Control and Prevention on surveillance and prevention of tickborne diseases. Research activities are conducted through the Emerging Infections Program and include laboratory surveys, high-quality prevention trials, and pathogen discovery.
The first recognized cases of Borrelia miyamotoi disease (BMD) in North America were reported in the northeastern United States in 2013.
To further describe the clinical spectrum and laboratory findings for BMD.
Case series.
Patients presenting to primary care offices, emergency departments, or urgent care clinics in 2013 and 2014.
Acutely febrile patients from the northeastern United States in whom the treating health care providers suspected and ordered testing for tick-transmitted infections.
Whole blood polymerase chain reaction (PCR) testing was performed for the presence of specific DNA sequences of common tickborne infections (including BMD). Serologic testing for B. miyamotoi was performed using a recombinant glycerophosphodiester phosphodiesterase (rGlpQ) protein. Clinical records were analyzed to identify the major features of acute disease.
Among 11 515 patients tested, 97 BMD cases were identified by PCR. Most of the 51 case patients on whom clinical histories were reviewed presented with high fever, chills, marked headache, and myalgia or arthralgia. Twenty-four percent were hospitalized. Elevated liver enzyme levels, neutropenia, and thrombocytopenia were common. At presentation, 16% of patients with BMD were seropositive for IgG and/or IgM antibody to B. miyamotoi rGlpQ. Most (78%) had seropositive convalescent specimens. Symptoms resolved after treatment with doxycycline, and no chronic sequelae or symptoms were observed.
Findings were based on specimens submitted for testing to a reference laboratory, and medical records of only 51 of the 97 case patients with BMD were reviewed.
Patients with BMD presented with nonspecific symptoms, including fever, headache, rigors, myalgia, and arthralgia. Laboratory confirmation of BMD was possible by PCR on blood from acutely symptomatic patients who were seronegative at presentation. Borrelia miyamotoi may be an emerging tickborne infection in the northeastern United States.
IMUGEN.
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.
We confirmed infection of 2 patients with Borrelia miyamotoi in Japan by retrospective surveillance of Lyme disease patients and detection of B. miyamotoi DNA in serum samples. One patient also showed seroconversion for antibody against recombinant glycerophosphodiester phosphodiesterase of B. miyamotoi. Indigenous relapsing fever should be considered a health concern in Japan.
Chinese translation
The diverse tickborne infections of the northeastern United States can present as undifferentiated flu-like illnesses. In areas endemic for Lyme and other tickborne diseases, patients presenting with acute febrile illness with myalgia, headache, neutropenia, thrombocytopenia, and elevated hepatic aminotransferase levels are presumptively diagnosed as having human granulocytic anaplasmosis (HGA).
To assign a cause for illness experienced by 2 case patients who were initially diagnosed with HGA but did not rapidly defervesce with doxycycline treatment and had no laboratory evidence of Anaplasma phagocytophilum infection.
Case report.
2 primary care medical centers in Massachusetts and New Jersey.
2 case patients acutely presenting with fever.
Identification of the causative agent by polymerase chain reaction and DNA sequencing.
Molecular diagnostic assays detected Borrelia miyamotoi in the peripheral blood of both patients. There was no evidence of infection with other tickborne pathogens commonly diagnosed in the referral areas.
One of the case patients may have had concurrent Lyme disease.
The presence of B. miyamotoi DNA in the peripheral blood and the patients' eventual therapeutic response to doxycycline are consistent with the hypothesis that their illness was due to this newly recognized spirochete. Samples from tick-exposed patients acutely presenting with signs of HGA but who have a delayed response to doxycycline therapy or negative confirmatory test results for HGA should be analyzed carefully for evidence of B. miyamotoi infection.
National Institutes of Health and the Evelyn Lilly Lutz Foundation.
Ixodes ticks serve as vectors for Borrelia burgdorferi, the agent of Lyme disease. Globally, these ticks often concurrently harbor B. miyamotoi, a spirochete that is classified within the relapsing-fever group of spirochetes. Although humans presumably are exposed to B. miyamotoi, there are limited data suggesting disease attributable to it. We report a case of progressive mental deterioration in an older, immunocompromised patient, and even though Koch's postulates were not met, we posit B. miyamotoi as the cause, owing to its direct detection in cerebrospinal fluid (CSF) with the use of microscopy and a polymerase-chain-reaction (PCR) assay. It is likely that B. miyamotoi is an underrecognized cause of disease, especially in sites where Lyme disease is endemic.
Lyme disease (LD), caused by the bacterium Borrelia burgdorferi and transmitted in the eastern United States by blacklegged ticks, Ixodes scapularis Say, is classified as nonendemic in Tennessee and surrounding states in the Southeast. Low incidence of LD in these states has been attributed, in part, to vector ticks being scarce or absent; however, tick survey data for many counties are incomplete or out of date. To improve our knowledge of the distribution, abundance, and Borrelia spp. prevalence of I. scapularis, we collected ticks from 1,018 hunter-harvested white-tailed deer (Odocoileus virginianus (Zimmerman)) from 71 of 95 Tennessee counties in fall 2007 and 2008. In total, 160 deer (15.7%) from 35 counties were infested with adult I. scapularis; 30 of these counties were new distributional records for this tick. The mean number of I. scapularis collected per infested deer was 5.4 +/- 0.6 SE. Of the 883 I. scapularis we removed from deer, none were positive for B. burgdorferi and one tested positive for B. miyamotoi. Deer are not reservoir hosts for B. burgdorferi; nevertheless, past surveys in northern LD-endemic states have readily detected B. burgdoreferi in ticks collected from deer. We conclude that I. scapularis is far more widespread in Tennessee than previously reported. The absence of detectable B. burgdorferi infection among these ticks suggests that the LD risk posed by I. scapularis in the surveyed areas of Tennessee is much lower than in LD-endemic areas of the Northeast and upper Midwest.
Borrelia miyamotoi is distantly related to B. burgdorferi and transmitted by the same hard-body tick species. We report 46 cases of B. miyamotoi infection in humans and compare the frequency and clinical manifestations of this infection with those caused by B. garinii and B. burgdorferi infection. All 46 patients lived in Russia and had influenza-like illness with fever as high as 39.5°C; relapsing febrile illness occurred in 5 (11%) and erythema migrans in 4 (9%). In Russia, the rate of B. miyamotoi infection in Ixodes persulcatus ticks was 1%-16%, similar to rates in I. ricinus ticks in western Europe and I. scapularis ticks in the United States. B. miyamotoi infection may cause relapsing fever and Lyme disease-like symptoms throughout the Holarctic region of the world because of the widespread prevalence of this pathogen in its ixodid tick vectors.
Lyme disease risk is increasing in the United States due in part to the spread of blacklegged ticks Ixodes
scapularis, the principal vector of the spirochetal pathogen Borrelia
burgdorferi. A 5-year study was undertaken to investigate hypothesized coinvasion of I. scapularis and B. burgdorferi in Lower Michigan. We tracked the spatial and temporal dynamics of the tick and spirochete using mammal, bird, and vegetation drag sampling at eight field sites along coastal and inland transects originating in a zone of recent I.
scapularis establishment. We document northward invasion of these ticks along Michigan’s west coast during the study period; this pattern was most evident in ticks removed from rodents. B.
burgdorferi infection prevalences in I.
scapularis sampled from vegetation in the invasion zone were 9.3% and 36.6% in nymphs and adults, respectively, with the majority of infection (95.1%) found at the most endemic site. There was no evidence of I. scapularis invasion along the inland transect; however, low-prevalence B.
burgdorferi infection was detected in other tick species and in wildlife at inland sites, and at northern coastal sites in years before the arrival of I.
scapularis. These infections suggest that cryptic B.
burgdorferi transmission by other vector-competent tick species is occurring in the absence of I.
scapularis. Other Borrelia spirochetes, including those that group with B. miyamotoi and B. andersonii, were present at a low prevalence within invading ticks and local wildlife. Reports of Lyme disease have increased significantly in the invasion zone in recent years. This rapid blacklegged tick invasion—measurable within 5 years—in combination with cryptic pathogen maintenance suggests a complex ecology of Lyme disease emergence in which wildlife sentinels can provide an early warning of disease emergence.
The Lyme borreliosis agent Borrelia burgdorferi and the relapsing fever group species Borrelia miyamotoi co-occur in the United States. We used species-specific, quantitative polymerase chain reaction to study both species in the blood and skin of Peromyscus leucopus mice and host-seeking Ixodes scapularis nymphs at a Connecticut site. Bacteremias with B. burgdorferi or B. miyamotoi were most prevalent during periods of greatest activity for nymphs or larvae, respectively. Whereas B. burgdorferi was 30-fold more frequent than B. miyamotoi in skin biopsies and mice had higher densities of B. burgdorferi densities in the skin than in the blood, B. miyamotoi densities were higher in blood than skin. In a survey of host-seeking nymphs in 11 northern states, infection prevalences for B. burgdorferi and B. miyamotoi averaged approximately 0.20 and approximately 0.02, respectively. Co-infections of P. leucopus or I. scapularis with both B. burgdorferi and B. miyamotoi were neither more nor less common than random expectations.
Feeding ticks are generally spatially distributed in clusters on vertebrate hosts. To test the effect of clustering on transmission of a tick-borne pathogen, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner-infected Ixodes ricinus L. nymphs and uninfected I. ricinus larvae were allowed to feed together in retaining chambers on uninfected AKR/N mice. Engorged infective nymphs dropped off at days 5, 6, and 7, and the 1st infected larvae that fed in the chambers together with the infected nymphs dropped off at day 5. In contrast, ear biopsies and xenodiagnostic larvae placed on the head remained negative during that period. These results suggest that a cofeeding transmission occurred between B. burgdorferi-infected ticks and noninfected ones in the absence of a disseminated infection. Further investigations are being undertaken to determine whether the mechanism responsible for this cofeeding transmission is similar to that described previously with virus-infected ticks.
The genera Anaplasma, Ehrlichia, Cowdria, Neorickettsia and Wolbachia encompass a group of obligate intracellular bacteria that reside in vacuoles of eukaryotic cells and were previously placed in taxa based upon morphological, ecological, epidemiological and clinical characteristics. Recent genetic analyses of 16S rRNA genes, groESL and surface protein genes have indicated that the existing taxa designations are flawed. All 16S rRNA gene and groESL sequences deposited in GenBank prior to 2000 and selected sequences deposited thereafter were aligned and phylogenetic trees and bootstrap values were calculated using the neighbour-joining method and compared with trees generated with maximum-probability, maximum-likelihood, majority-rule consensus and parsimony methods. Supported by bootstrap probabilities of at least 54%, 16S rRNA gene comparisons consistently clustered to yield four distinct clades characterized roughly as Anaplasma (including the Ehrlichia phagocytophila group, Ehrlichia platys and Ehrlichia bovis) with a minimum of 96.1% similarity, Ehrlichia (including Cowdria ruminantium) with a minimum of 97.7% similarity, Wolbachia with a minimum of 95.6% similarity and Neorickettsia (including Ehrlichia sennetsu and Ehrlichia risticii) with a minimum of 94.9% similarity. Maximum similarity between clades ranged from 87.1 to 94.9%. Insufficient differences existed among E. phagocytophila, Ehrlichia equi and the human granulocytic ehrlichiosis (HGE) agent to support separate species designations, and this group was at least 98.2% similar to any Anaplasma species. These 16S rRNA gene analyses are strongly supported by similar groESL clades, as well as biological and antigenic characteristics. It is proposed that all members of the tribes Ehrlichieae and Wolbachieae be transferred to the family Anaplasmataceae and that the tribe structure of the family Rickettsiaceae be eliminated. The genus Anaplasma should be emended to include Anaplasma (Ehrlichia) phagocytophila comb. nov. (which also encompasses the former E. equi and the HGE agent), Anaplasma (Ehrlichia) bovis comb. nov. and Anaplasma (Ehrlichia) platys comb. nov., the genus Ehrlichia should be emended to include Ehrlichia (Cowdria) ruminantium comb. nov. and the genus Neorickettsia should be emended to include Neorickettsia (Ehrlichia) risticii comb. nov. and Neorickettsia (Ehrlichia) sennetsu comb. nov.
A species of Borrelia spirochetes previously unknown from North America has been found to be transmitted by Ixodes scapularis ticks. Infected ticks are positive for Borrelia spp. by DFA test but negative for Borrelia burgdorferi by polymerase chain reaction (PCR) using species-specific primers for 16S rDNA, outer surface protein A, outer surface protein C, and flagellin genes. A 1,347-bp portion of 16S rDNA was amplified from a pool of infected nymphs, sequenced, and compared with the homologous fragment from 26 other species of Borrelia. The analysis showed 4.6% pairwise difference from B. burgdorferi, with the closest relative being Borrelia miyamotoi (99.3% similarity) reported from Ixodes persulcatus in Japan. Phylogenetic analysis showed the unknown Borrelia to cluster with relapsing fever group spirochetes rather than with Lyme disease spirochetes. A 764-bp fragment of the flagellin gene was also compared with the homologous fragment from 24 other Borrelia species. The flagellin sequence of B. burgdorferi was 19.5% different from the unknown Borrelia and showed 98.6% similarity with B. miyamotoi. A pair of PCR primers specifically designed to amplify a 219-bp fragment of the flagellin gene from this spirochete was used to survey field-collected I. scapularis nymphs from five northeastern states (Connecticut, Rhode Island, New York, New Jersey, and Maryland). Positive results were obtained in 1.9-2.5% of 712 nymphs sampled from four states but in none of 162 ticks collected from Maryland. Transovarial transmission was demonstrated by PCR of larval progeny from infected females with filial infection rates ranging from 6% to 73%. Transstadial passage occurred from larvae through adults. Vertebrate infection was demonstrated by feeding infected nymphs on Peromyscus leucopus mice and recovering the organism from uninfected xenodiagnostic larvae fed 7-21 days later. Considering the frequency of contact between I. scapularis and humans, further work is needed to determine the potential public health significance of yet another zoonotic agent transmitted by this tick species.
Since 2011, Borrelia miyamotoi disease (BMD) has been reported in five countries in the northern hemisphere. The causative agent of BMD is transmitted by Ixodes ticks, which are also vectors of Lyme disease borreliae. In this study, we examined 459 cases of clinically suspected Lyme disease (LD group), and found twelve cases that were seropositive for the glycerophosphodiester phosphodiesterase (GlpQ) antigen derived from B. miyamotoi. The retrospective surveillance revealed that the seroprevalence of anti-GlpQ in the LD group was significantly higher than in a healthy cohort. Seropositive cases were observed from spring through autumn when ticks are active, and the cases were geographically widespread, being found in Hokkaido-Tohoku, Kanto, Chubu, Kinki, and Kyushu-Okinawa regions. Seropositive cases for GlpQ were most frequent in the Chubu region (6.3%) where B. miyamotoi has been found in Ixodes ticks. Out of the twelve cases that were found in the LD group, three cases exhibited concomitant seropositivity to Lyme disease borreliae by western blot assay. This is the first report of serological surveillance for BMD in Japan, and we conclude that BMD occurs nationwide.
Historical specimens, when available, can provide new insight into the distribution and evolution of pathogens that may not be discernible from more recent samples. We used ticks collected from hunter-killed white-tailed deer in New Jersey in 2002 to examine the prevalence and distribution of four pathogens transmitted by Ixodes scapularis, the blacklegged tick. Infection with Borrelia burgdorferi sensu stricto, Babesia microti, and Anaplasma phagocytophilum (the agents of Lyme disease, human babesiosis, and human granulocytic anaplasmosis, respectively) was highest in the Coastal Plain and lowest in the northwestern Skylands region. These patterns correspond well with the historically observed northward expansion of I. scapularis within New Jersey and the comparatively recent increase in human cases of these pathogens in the northern part of the state. Additionally, we provide evidence that Borrelia miyamotoi, a relatively new emerging pathogen and agent of relapsing fever, was widespread (though not common) throughout the state in 2002. Our findings highlight the need for enhanced awareness of tick-borne diseases other than Lyme and implementation of large-scale tick surveillance in endemic regions.
The hard tick Ixodes ricinus is the most important vector of tick-transmitted pathogens in Europe, frequently occurring in urban parks and greenbelts utilized for recreational activities. This species is the most common vector of the causative agents of Lyme borreliosis in Europe. Similarly, the species spreads Borrelia miyamotoi, causing a relapsing-fever like illness. A total of 1774 Ixodes ricinus (50 females, 68 males, 840 nymphs and 818 larvae) were collected with flagging between March and September 2014 in a coniferous forest patch in Niederkaina near the town of Bautzen in Saxony, Germany. To measure questing tick density a time-based density estimating method was utilized. From each month, a total of 100 adults and nymphal ticks and all larvae (pools of 10 individuals per tube/month) were selected for the molecular analyses. For simultaneous detection of B. burgdorferi s.l. and B. miyamotoi a duplex real-time PCR targeting the flaB locus was performed. Prevalence of B. burgdorferi s.l. was 9.4% (female: 6%, male: 2.9%, nymph: 12.2%, larva: 0%) and minimum prevalence of B. miyamotoi was 1.2% (female: 0%, male: 4.3%, nymph: 2.8%, larva: 0.1%) in the 714 samples with real-time polymerase chain reaction. A real-time PCR reaction was utilized first to target the histone-like protein gene (hbb) of B. burgdorferi s.l., a hemi-nested outer surface protein (ospA) gene conventional PCR was then performed followed by a restriction enzyme analysis to distinguish B. burgdorferi s.l. genospecies. Seven B. afzelii, one B. burgdorferi s.s., one B. bavariensis and four B. miyamotoi infections were confirmed. Prevalence of Lyme borreliosis spirochetes was significantly higher in nymphs than in adults (p<0.01, Fisher exact test) probably due to the diluting effect of the local roe deer population. Our data highlight the potential risk of human infection with the emerging pathogen B. miyamotoi within the study area.
We describe a patient from the United States with PCR- and serology-confirmed Borrelia miyamotoi infection who recovered without antibiotics. Our findings suggest that B. miyamotoi infection may cause relapsing fever, blood monocytosis and antibody reactivity to the C6 peptide. Further studies are required to better define the spectrum of clinical and laboratory findings for this emerging tick-transmitted infection.
The blacklegged tick, Ixodes scapularis Say, is the primary vector to humans in the eastern United States of the Lyme disease spirochete Borrelia burgdorferi, as well as causative agents of anaplasmosis and babesiosis. Its close relative in the far western United States, the western blacklegged tick Ixodes pacificus Cooley and Kohls, is the primary vector to humans in that region of the Lyme disease and anaplasmosis agents. Since 1991, when standardized surveillance and reporting began, Lyme disease case counts have increased steadily in number and in geographical distribution in the eastern United States. Similar trends have been observed for anaplasmosis and babesiosis. To better understand the changing landscape of risk of human exposure to disease agents transmitted by I. scapularis and I. pacificus, and to document changes in their recorded distribution over the past two decades, we updated the distribution of these species from a map published in 1998. The presence of I. scapularis has now been documented from 1,420 (45.7%) of the 3,110 continental United States counties, as compared with 111 (3.6%) counties for I. pacificus. Combined, these vectors of B. burgdorferi and other disease agents now have been identified in a total of 1,531 (49.2%) counties spread across 43 states. This marks a 44.7% increase in the number of counties that have recorded the presence of these ticks since the previous map was presented in 1998, when 1,058 counties in 41 states reported the ticks to be present. Notably, the number of counties in which I. scapularis is considered established (six or more individuals or one or more life stages identified in a single year) has more than doubled since the previous national distribution map was published nearly two decades ago. The majority of county status changes occurred in the North-Central and Northeastern states, whereas the distribution in the South remained fairly stable. Two previously distinct foci for I. scapularis in the Northeast and North-Central states appear to be merging in the Ohio River Valley to form a single contiguous focus. Here we document a shifting landscape of risk for human exposure to medically important ticks and point to areas of re-emergence where enhanced vector surveillance and control may be warranted.
Borrelia miyamotoi, the newest infection brought to us by deer ticks It’s not just Lyme disease anymore. Residents and visitors in many parts of the northeastern, north-central and far-Western United States have more than one reason to avoid bites of hard bodied (ixodid) ticks. The latest addition to the list of infections transmitted to humans by the same ixodid ticks that are vectors of Lyme disease is Borrelia miyamotoi. While its genus is the same as that of Borrelia burgdorferi, B. miyamotoi is more closely related to species that cause relapsing fever than to Lyme disease agents [1]. Discovered in Ixodes persulcatus ticks in Japan in 1994 and subsequently documented in ticks and rodents in North America and Europe, B. miyamotoi was not recognized as a human pathogen until a report from Russia in 2011 [2]. It subsequently was reported in patients in the United States, Europe and Japan [3-8]. In this issue of the Annals, the first large case series in the United States is reported by Molloy et al. and provides important new information about the epidemiology and clinical presentation of human disease caused by this pathogen [8]. Whole blood samples from patients in the northeastern U.S. with suspected tick-borne illness during April to November in 2013 and 2014 were tested with PCR for four tick-borne pathogens. Amplifiable DNA of B. miyamotoi, Anaplasma phagocytophilum, B. burgdorferi, or Babesia microt was detected in approximately 1%, 1%, 2%, and 3%, respectively, of 11,515 samples from individual patients. The frequency of infection with B. burgdorferi, which is primarily a fixed tissue pathogen, should be greatly underestimated based on PCR of the blood alone. Furthermore, the relative frequencies of these four infections vary across regions in the Northeast, so different results might have been obtained with the samples from other locations. Nevertheless, based on Molloy et al.’s report and previous data [needs citation for “previous data”], the frequency of B. miyamotoi infection appears to be roughly the same as for A. phagocytophilum and B. microt [3]. Clinical information was provided for 51 B. miyamotoi patients. Interestingly, the peak incidence of positive assays for B. miyamotoi was in August with probable onsets of illness continuing into September, which is about a month after the peak incidence for Lyme disease. This temporal peak is similar to that observed in the naturally infected white-footed mice in Connecticut and
Lyme disease is the most common vector-borne illness in North America and Europe. The etiologic agent, Borrelia burgdorferi sensu lato, is transmitted to humans by certain species of Ixodes ticks, which are found widely in temperate regions of the Northern hemisphere. Clinical features are diverse, but death is rare. The risk of human infection is determined by the geographic distribution of vector tick species, ecologic factors that influence tick infection rates, and human behaviors that promote tick bite. Rates of infection are highest among children 5 to 15 years old and adults older than 50 years.
Published by Elsevier Inc.
Borrelia are fastidious bacteria some of which are difficult to grow in vitro. Here, we report a method for successful continuous in vitro cultivation of the emerging pathogen Borrelia miyamotoi. The type and quantity of serum as well as the atmosphere were critical for successful in vitro cultivation. Optimal growth was achieved using 50% pooled human serum and an atmosphere of 6% CO2.
Transovarial transmission (TOT) of Borrelia burgdorferi (sensu lato), the agent of Lyme disease, by the Ixodes persulcatus group of hard ticks (Ixodidae) has frequently been reported in the literature since the discovery of Lyme disease 1982. Evidence for and against TOT by B. burgdorferi has led to uncertainty and confusion in the literature, causing misconceptions that may have public health consequences. In this report, we review the published information implicating B. burgdorferi as a bacterium transovarially transmitted among ticks of the Ixodes persulcatus group and present new data indicating the transovarially transmitted agent is actually Borrelia miyamotoi. B. miyamotoi, first described in 1995, is antigenically and phylogenetically related to B. burgdorferi, although more closely related to the relapsing fever-group Borrelia typically transmitted by soft ticks (Argasidae). Borrelia infections of unfed larvae derived from egg clutches of wild-caught Ixodes scapularis are demonstrated to result from transovarial transmission of B. miyamotoi, not B. burgdorferi. The presence of this second Borrelia species, apparently sympatric with B. burgdorferi worldwide also may explain other confusing observations reported on Borrelia/Ixodes relationships.
During the 1977 through 1980 hunting seasons (December) in Connecticut, 309 White-tailed Deer (ODOCOILEUS VIRGINIANUS) were examined for ectoparasites. Adult IXODES DAMMINI (1918 males, 960 females) were taken from 58.6% of these deer. Immature I. dammini were not observed on deer during December, although 15 larvae and 1 nymph were taken from a deer in June. Dermacentor albipictus (38 nymphs, 397 males, 160 females) were found on 20.7% of the deer. Does and fawns carried smaller tick loads of both species than did bucks and older deer. The possible role that deer have played in the increase in I. dammini populations in recent years is discussed, as are the public health implications associated with these increases in relation to Lyme disease and babesiosis.
5. The economic importance of tick-borne fever is discussed.(Received January 17 1933)
A scanning electron microscope study of adults of the genus Ixodes found in the United States is presented. Keys are given to the females of 35 species and males of 30 species. Host and distributional data are included for all currently recognized species. Depositories, where known, for all type material are given, together with the original literature citations for descriptions of male, female, nymph, and larva. Lectotypes are selected for Ixodes kingi, I. marxi, and I. rugosus.
To determine whether deer may serve as reservoir hosts for the Lyme disease spirochete, we sought evidence of infection in nymphal Ixodes dammini derived from larvae that had engorged on white-tailed deer. A total of 19 deer were shot in two Lyme disease foci in Massachusetts during September 1986, the season in which larvae were most abundant. An average of 342 larval ticks of this species were collected from each deer. Of those that developed to the nymphal stage, the gut contents of 185 were examined for Borrelia burgdorferi by a direct fluorescent antibody test. Spirochetes were detected in about 1% of these nymphs, a rate of infection attributable to transovarial transmission. In contrast, infection was detected in 23% of 39 field-swept nymphal ticks of the same cohort that were collected during the following season. Although deer may be infested by numerous larval I. dammini, such ticks appear not to become infected by Lyme disease spirochetes.
Transovarial and transstadial passage of Borrelia burgdorferi was demonstrated for the first time in the western black-legged tick, Ixodes pacificus. One of three field-collected females with spirochetes in ovarial tissues produced 100% infected progeny that maintained the spirochetes transstadially and in 4 of 5 cases passed them via eggs to as many as 97% of F2 filial ticks. The progeny infected ovarially and by subsequent transstadial passage had generalized tissue infections that exhibited reduced immunofluorescence staining reactivity with a fluorescein isothiocyanate-labeled polyclonal antibody. Attempts to isolate the spirochete from ticks in BSK medium or various modifications of it were unsuccessful. Spirochetes in tissue smears of all three parasitic stages of the F1 generation were nonreactive with a monoclonal antibody (H5332) specific for B. burgdorferi, whereas those present in tissue smears of F2 larvae bound with it.
To determine whether larval Ixodes dammini are infected transovarially by Lyme disease spirochetes (Borrelia burgdorferi), we swept larval I. dammini from vegetation in 4 regions of Massachusetts, USA, where the spirochetes are endemic. Larvae were permitted to feed on noninfected hamsters. After molting to the nymphal stage, 274 were examined for spirochetes. Two nymphs were found to be infected. The rarity of transovarial infection (0.7%) suggests that transovarial passage is of limited importance in maintaining B. burgdorferi in nature, but that it may provide a mechanism for transporting spirochetes to new sites.
The prevalence of the Ixodes dammini spirochete (IDS) in white-tailed deer (Odocoileus virginianus) and white-footed mice (Peromyscus leucopus) was studied on the eastern end of Long Island, New York. Both species commonly occur in a variety of habitats, are preferred hosts of Ixodes dammini, and can harbor the spirochetes in the blood. Each animal was examined for spirochetemia, tick infestation, and IDS infection rates in the ticks that were removed from it. The results obtained suggest that in winter deer can be infected by questing adult I. dammini. Adult ticks apparently are infected through transtadial transmission of spirochetes from subadult ticks which had fed earlier in their life history on infected animals. Deer are important hosts of adult ticks and the IDS in winter and probably are a reservoir host in other seasons. The patterns of spirochete prevalence suggest that deer and mice are reservoirs of the organism and thus are fundamental to the ecology of Lyme disease on Long Island.
I determined whether transovarial passage of Lyme disease spirochetes occurred more efficiently in Ixodes scapularis Say fed on reservoir-competent dogs. Unlike deerfed ticks, spirochetes are not diminished in dog-fed ticks, and significantly higher transovarial infection rates have been reported for the latter. Females of field-infected I. scapularis (North Salem strain) were used to induce experimental Lyme disease in specific pathogen-free dogs as part of another study. Seventy-four (48 of 65) percent of the females examined were infected with spirochetes, and larvae from infected females were tested for Borrelia burgdorferi within 1 mo of eclosion. No spirochetes were found in 14,700 larvae (225 larvae per female [n = 12] and 750 larvae per female [n = 16]) examined individually by fluorescent antibody (FA) tests or in triturated larval suspensions (approximately 1,500 larvae per female (n = 20]) examined by FA and polymerase chain reaction. Larvae remain an unlikely source of B. burgdorferi infection in the peridomestic setting because transovarial transmission is highly inefficient in I. scapularis.
Lyme disease, caused by infection with Borrelia burgdorferi, is the most frequently reported arthropod-borne disease in the United States. To develop a national map of the distribution of the vectors of B. burgdorferi to humans (Ixodes scapularis Say and Ixodes pacificus Cooley & Kohls ticks), we sent questionnaires to acarologists, health officials, and Lyme disease researchers; surveyed the 1966-1996 MEDLINE data base; and reviewed 1907-1995 National Tick Collection data. Tick collection methods cited included flagging and dragging, deer surveys, small- and medium-sized mammal surveys, CO2 baiting, and receipt of tick submissions. A total of 1,058 unique, county-specific I. scapularis and I. pacificus records was obtained. Tick populations were classified as "reported" (< 6 ticks and 1 life stage identified) or "established" (> or = 6 ticks or > 1 life stage identified). Established populations of I. scapularis were identified in 396 counties in 32 states in the eastern and central United States, whereas established populations of I. pacificus were found in 90 counties in 5 western states. Counties with established populations were most concentrated in the northeastern, upper northcentral, and west-coastal states but were also clustered in southeastern and Gulf-coastal states. A less concentrated distribution was found in the south-central states. Reports were notably missing from all but a few counties in Ohio, West Virginia, western Virginia and North Carolina, Kentucky, and Tennessee. They were absent in the Great Plains and Rocky Mountain regions and from large areas of western states east of the Cascade and Sierra Nevada cordilleras. These data are useful for identifying areas of Lyme disease risk, for targeting Lyme disease prevention strategies, and for monitoring trends in spatial distribution of Lyme disease vector ticks.
Although research on co-feeding as a means of maintaining tick-borne pathogens has focused chiefly on viruses, recent interest has been directed toward the importance of this phenomenon in maintaining the Lyme disease spirochete, Borrelia burgdorferi. In the current study, an experimental model was developed to determine under what conditions immature co-feeding ticks exchange B. burgdorferi using the principal North American vector (Ixodes scapularis) and reservoir (Peromyscus leucopus) species. Experiments conducted with the density of ticks likely to be encountered in nature (8 nymphs & < 40 larvae) demonstrated that no co-feeding larvae became infected; in contrast, horizontal transmission infected 30-64% of test larvae. Only the highest densities of ticks (40 nymphs & > 200 larvae) produced infected larvae (5%) upon co-feeding of larvae and nymphs. An important role for co-feeding in the ecology of Lyme disease in North America has yet to be established.