Acute Meningoencephalitis Associated with Borrelia miyamotoi, Minnesota, USA.

Borrelia miyamotoi is an emerging tickborne pathogen that has been associated with central nervous system infections in immunocompromised patients, albeit infrequently. We describe a case-patient in Minnesota, USA, who had meningeal symptoms of 1 month duration. B. miyamotoi infection was diagnosed by Gram staining on cerebrospinal fluid and confirmed by sequencing.

Statewide surveillance of Ixodes scapularis (Acari: Ixodidae) for the presence of the human pathogen Borrelia miyamotoi (Spirochaetales: Spirochaetaceae), a relapsing fever spirochete in Pennsylvania, USA, 2019-2020.

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.

Co-Occurrence of Borrelia burgdorferi Sensu Lato and Babesia spp. DNA in Ixodes ricinus Ticks Collected from Vegetation and Pets in the City of Poznan, Poland.

Here, we described the prevalence of Borrelia burgdorferi s.l. and Babesia species found in mono- and double infections among Ixodes ricinus ticks occurring in urban areas of the city of Poznan, Poland. We tested 1029 host-seeking ticks and 1268 engorged ticks removed from pet animals. Borrelia afzelii and B. garinii prevailed both in ticks from vegetation (3.7% and 3.7%, respectively) and from pets (3.7% and 0.6%, respectively). Babesia canis and Ba. microti were the most prevalent in host-seeking (2.6% and 1.4%, respectively) and feeding ticks (2.8% and 2.2%, respectively). Babesia microti sequences proved to be identical to the human pathogenic Ba. microti genotype "Jena/Germany". Sequences of the rarest piroplasm Ba. venatorum (0.7%) were identical with those isolated from European patients. About 1.0% of tested ticks yielded dual infections; in host-seeking ticks, Ba. canis prevailed in co-infections with B. afzelii and B. garinii, whereas Ba. microti and B. afzelii dominated in double-infected feeding ticks. Dual infections, even with a low prevalence, pose a challenge for differential diagnosis in patients with acute febrile disease after a tick bite. The finding of Ba. canis in both tick groups suggests that I. ricinus could be involved in the circulation of this piroplasm.

A Case of Tick-borne Disease with Yezo Virus and Borrelia miyamotoi Coinfection.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

Borrelia miyamotoi BipA-like protein, BipM, is a candidate serodiagnostic antigen distinguishing between Lyme disease and relapsing fever Borrelia infections.

A Borrelia miyamotoi gene with partial homology to bipA of relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae was identified by a GenBank basic alignment search analysis. We hypothesized that this gene product may be an immunogenic antigen as described for other relapsing fever Borrelia (RFB) and could serve as a serological marker for B. miyamotoi infections. The B. miyamotoi gene was a truncated version about half the size of the B. hermsii and B. turicatae bipA with a coding sequence of 894 base pairs. The gene product had a calculated molecular size of 32.7 kDa (including the signal peptide). Amino acid alignments with B. hermsii and B. turicatae BipA proteins and with other B. miyamotoi isolates showed conservation at the carboxyl end. We cloned the B. miyamotoi bipA-like gene (herein named bipM) and generated recombinant protein for serological characterization and for antiserum production. Protease protection analysis demonstrated that BipM was surface exposed. Serologic analyses using anti-B. miyamotoi serum samples from tick bite-infected and needle inoculated mice showed 94 % positivity against BipM. The 4 BipM negative serum samples were blotted against another B. miyamotoi antigen, BmaA, and two of them were seropositive resulting in 97 % positivity with both antigens. Serum samples from B. burgdorferi sensu stricto (s.s.)-infected mice were non-reactive against rBipM by immunoblot. Serum samples from Lyme disease patients were also serologically negative against BipM except for 1 sample which may have indicated a possible co-infection. A recently published study demonstrated that B. miyamotoi BipM was non-reactive against serum samples from B. hermsii, Borrelia parkeri, and B. turicatae infected animals. These results show that BipM has potential for a B. miyamotoi-infection specific and sensitive serodiagnostic to differentiate between Lyme disease and various RFB infections.

High-throughput screening of pathogens in Ixodes ricinus removed from hosts in Lombardy, northern Italy.

Ticks are important vectors of many pathogens in Europe, where the most impactful species is Ixodes ricinus. Recently, the geographical distribution of this tick species has been expanding, resulting in an increased risk of human exposure to tick bites. With the present study, we aimed to screen 350 I. ricinus specimens collected from humans and wild animals (mainly ungulates), to have a broader understanding of the tick-borne pathogens circulating in the Lombardy region, in northern Italy. To do so, we took advantage of a high-throughput real-time microfluidic PCR approach to screen ticks in a cost-effective and time-saving manner. Molecular analysis of the dataset revealed the presence of four genera of bacteria and two genera of protozoa: in ungulates, 77 % of collected ticks carried Anaplasma phagocytophilum, while the most common pathogen species in ticks removed from humans were those belonging to Borrelia burgdorferi sensu lato group (7.6 %). We also detected other pathogenic microorganisms, such as Rickettisa monacensis, Rickettsia helvetica, Neoehrlichia mikurensis, Babesia venatorum, and Hepatozoon martis. Besides, we also reported the presence of the pathogenic agent Borrelia miyamotoi in the area (1.4 % overall). The most common dual co-infection detected in the same tick individual involved A. phagocytophilum and Rickettsia spp. Our study provided evidence of the circulation of different tick-borne pathogens in a densely populated region in Italy.

Characteristics of Hard Tick Relapsing Fever Caused by Borrelia miyamotoi, United States, 2013-2019.

Borrelia miyamotoi, transmitted by Ixodes spp. ticks, was recognized as an agent of hard tick relapsing fever in the United States in 2013. Nine state health departments in the Northeast and Midwest have conducted public health surveillance for this emerging condition by using a shared, working surveillance case definition. During 2013-2019, a total of 300 cases were identified through surveillance; 166 (55%) were classified as confirmed and 134 (45%) as possible. Median age of case-patients was 52 years (range 1-86 years); 52% were male. Most cases (70%) occurred during June-September, with a peak in August. Fever and headache were common symptoms; 28% of case-patients reported recurring fevers, 55% had arthralgia, and 16% had a rash. Thirteen percent of patients were hospitalized, and no deaths were reported. Ongoing surveillance will improve understanding of the incidence and clinical severity of this emerging disease.

Case report: First case of Borrelia miyamotoi meningitis in an immunocompromised patient in Norway.

Background: Tick-borne disease caused by B. miyamotoi (BMD) usually manifest as a febrile illness in humans. Complications include relapsing fever and in rare occasions involvement of the central nervous system. Only a few cases of meningoencephalitis have been described, mostly in immunosuppressed patients. Case presentation: A 70-year-old female receiving immunosuppressive rituximab therapy presented with frontal headache, dizziness, nausea, vomiting and chills. Clinical laboratory blood analyses were normal. Cerebrospinal fluid (CSF) was translucent and analysis showed increased leucocyte count (187 106/L) and elevated level of protein (1056 mg/L). Empiric antibiotic treatment was initiated. The patient showed an early symptomatic relief and 24 h after admission she was discharged from the hospital and antibiotic treatment was discontinued. Two weeks after hospitalisation the B. miyamotoi specific PCR turned out positive in both CSF and serum. At the time, the patient was recovered with mild residual headache. She was treated with high dose doxycycline and her subtle symptoms disappeared. Conclusions: To our knowledge, we present the first patient with BMD-associated meningitis in Norway, one of eight cases reported worldwide. The patient had mild symptoms and received an early diagnosis. A more severe progression or relapse of disease may have been prevented by antibiotic treatment. BMD should be considered as causes of aseptic meningitis, especially in immunosuppressed patients living in endemic areas.

Prevalence of Borrelia, Neoehrlichia mikurensis and Babesia in ticks collected from vegetation in eastern Poland.

In Poland, tick-borne diseases constitute the majority of diseases related to exposure to biological agents with a predominance of Lyme borreliosis; therefore, research on ticks as a reservoir of various pathogens remains crucial in the epidemiology of human diseases after tick bites. This study aimed to identify the occurrence of Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Neoehrlichia mikurensis, and Babesia spp. in ticks collected from vegetation in eastern Poland. Additionally, the prevalence of co-infections in the adult Ixodes ricinus ticks was determined. Among I. ricinus ticks the predominantly detected pathogen was B. burgdorferi s.l. (23%) with B. burgdorferi sensu stricto as the most frequently identified species, followed by B. garinii. In 2013, the double or triple infections of B. burgdorferi s.s., B. afzelii, and B. garinii species did not exceed 9% in adult ticks, whereas in 2016, the prevalence of mixed infections reached 29%. The prevalence of N. mikurensis and B. miyamotoi in I. ricinus was determined at the same level of 2.8%. Four Babesia species were identified in the examined I. ricinus population: B. microti (1.5%), B. venatorum (1.2%), B. divergens (0.2%), and B. capreoli (0.1%). Co-infections were detected in 10.1% of all infected ticks with the highest prevalence of co-infections with B. burgdorferi s.l. and Babesia species. The changes in the prevalence and the distribution of particular pathogens within tick populations indicate the need for monitoring the current situation related to tick-borne pathogens from the aspect of risk to human health.

Combining citizen science and molecular diagnostic methods to investigate the prevalence of Borrelia burgdorferi s.l. and Borrelia miyamotoi in tick pools across Great Britain.

Lyme disease is the most common tick-borne disease and is caused by a group of bacteria known as Borrelia burgdorferi sensu lato (s.l.) complex. Sharing the same genus as B. burgdorferi, Borrelia miyamotoi is a distinct genotype that causes relapsing fever disease. This emerging tick-borne disease is increasingly becoming a concern in public health. To investigate the prevalence of B. burgdorferi s.l. and B. miyamotoi in ticks first, we developed a PCR (Bmer-qPCR) that targets the phage terminase large subunit (terL) gene carried by B. miyamotoi. A similar approach had been used successfully in developing Ter-qPCR for detecting B. burgdorferi s.l. The terL protein functions as an enzyme in packaging phage DNA. Analytical validation of the Bmer-qPCR confirmed its specificity, efficiency and sensitivity. Second, we designed a citizen science-based approach to detect 838 ticks collected from numerous sites across Great Britain. Finally, we applied Bmer-qPCR and Ter-qPCR to 153 tick pools and revealed that the prevalence of B. burgdorferi s.l. and B. miyamotoi was dependent on their geographical locations, i.e. Scotland showed a higher rate of B. burgdorferi s.l. and lower rate of B. miyamotoi carriage as compared to those of the England data. A pattern of diminishing rate of B. miyamotoi carriage from southern England to northern Scotland was visible. Together, the citizen science-based approach provided an estimation of the carriage rate of B. burgdorferi s.l. and B. miyamotoi in tick pools and a potential spreading pattern of B. miyamotoi from the south to the north of Great Britain. Our findings underscore the power of combining citizen science with the molecular diagnostic method to reveal hidden pattern of pathogen-host-environment interplay. Our approach can provide a powerful tool to elucidate the ecology of tick-borne diseases and may offer guidance for pathogen control initiatives. In an era of limited resources, monitoring pathogens requires both field and laboratory support. Citizen science approaches provide a method to empower the public for sample collection. Coupling citizen science approaches with laboratory diagnostic tests can make real-time monitoring of pathogen distribution and prevalence possible.

Spatiotemporal distribution of Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) and coinfection with other tick-borne pathogens in host-seeking Ixodes scapularis (Acari: Ixodidae) from New York State, USA.

Blacklegged ticks (Ixodes scapularis Say, Acari: Ixodidae) were collected from 432 locations across New York State (NYS) during the summer and autumn of 2015-2020 to determine the prevalence and geographic distribution of Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) and coinfections with other tick-borne pathogens. A total of 48,386 I. scapularis were individually analyzed using a multiplex real-time polymerase chain reaction assay to simultaneously detect the presence of Bo. miyamotoi, Borrelia burgdorferi (Spirochaetales: Spirochaetaceae), Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and Babesia microti (Piroplasmida: Babesiidae). Overall prevalence of Bo. miyamotoi in host-seeking nymphs and adults varied geographically and temporally at the regional level. The rate of polymicrobial infection in Bo. miyamotoi-infected ticks varied by developmental stage, with certain co-infections occurring more frequently than expected by chance. Entomological risk of exposure to Bo. miyamotoi-infected nymphal and adult ticks (entomological risk index [ERI]) across NYS regions in relation to human cases of Bo. miyamotoi disease identified during the study period demonstrated spatial and temporal variation. The relationship between select environmental factors and Bo. miyamotoi ERI was explored using generalized linear mixed effects models, resulting in different factors significantly impacting ERI for nymphs and adult ticks. These results can inform estimates of Bo. miyamotoi disease risk and further our understanding of Bo. miyamotoi ecological dynamics in regions where this pathogen is known to occur.

Human Borrelia miyamotoi Infection in North America.

Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in Japan. It was first reported in humans in 2011 in Russia. It has subsequently been reported in North America, Europe, and Asia. B. miyamotoi infection is widespread in Ixodes ticks in the northeastern, northern Midwestern, and far western United States and in Canada. In endemic areas, human B. miyamotoi seroprevalence averages from 1 to 3% of the population, compared with 15 to 20% for B. burgdorferi. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Complications include relapsing fever and rarely, meningoencephalitis. Because clinical manifestations are nonspecific, diagnosis requires laboratory confirmation by PCR or blood smear examination. Antibiotics are effective in clearing infection and are the same as those used for Lyme disease, including doxycycline, tetracycline, erythromycin, penicillin, and ceftriaxone. Preventive measures include avoiding areas where B. miyamotoi-infected ticks are found, landscape management, and personal protective strategies such as protective clothing, use of acaricides, and tick checks with rapid removal of embedded ticks.

Borrelia miyamotoi Infection in Immunocompromised Man, California, USA, 2021.

Infection with Borrelia miyamotoi in California, USA, has been suggested by serologic studies. We diagnosed B. miyamotoi infection in an immunocompromised man in California. Diagnosis was aided by plasma microbial cell-free DNA sequencing. We conclude that the infection was acquired in California.

Detection, identification and genotyping of Borrelia spp. in ticks of Coastal-Karst and Littoral-Inner Carniola regions in Slovenia.

The density and spread of tick vector species have increased throughout Europe in the last 30 years, leading to an increase of Lyme borreliosis cases, including in Slovenia. The aim of this study was to isolate Borrelia strains and determine the prevalence of B. burgdorferi sensu lato and B. miyamotoi in adults of Ixodes ricinus (Linnaeus) collected in 2019 in the two regions of the country (Coastal-Karst and Littoral-Inner Carniola) by cultivation and PCR. We isolated B. burgdorferi s.l. by culture method in 28/559 (5%) ticks from both regions. Culture-negative samples (531/559, i.e., 95%) were additionally tested by real-time PCR. In 155/531 (29.2%) PCR-positive samples, a fragment of flaB or glpQ was amplified and further sequenced to identify species of the Borrelia. Using both methods, cultivation and PCR, Borrelia spp. prevalence was 32.7% in the Coastal-Karst region and 33.0% in the Littoral-Inner Carniola region. Genotyping of the Borrelia spp. isolates revealed that 17/28 (60%) were B. garinii subtype Mlg2. Of all tick samples tested for B. miyamotoi 8/398 (2%) were PCR positive. Based on previous studies in these regions, we had expected more ticks to be infected with B. afzelii, but genotyping revealed that B. garinii was the most abundant.

Tick-borne diseases under the radar in the North Sea Region.

The impact of tick-borne diseases caused by pathogens such as Anaplasma phagocytophilum, Neoehrlichia mikurensis, Borrelia miyamotoi, Rickettsia helvetica and Babesia species on public health is largely unknown. Data on the prevalence of these pathogens in Ixodes ricinus ticks from seven countries within the North Sea Region in Europe as well as the types and availability of diagnostic tests and the main clinical features of their corresponding diseases is reported and discussed. Raised awareness is needed to discover cases of these under-recognized types of tick-borne disease, which should provide valuable insights into these diseases and their clinical significance.

Passive Surveillance of Human-Biting Ixodes scapularis Ticks in Massachusetts from 2015-2019.

This study aimed to analyze human-biting Ixodes scapularis ticks submitted to TickReport tick testing service from 2015-2019 in Massachusetts to (1) examine possible patterns of pathogen-positive adult and nymphal ticks over time and (2) explore how socioeconomic factors can influence tick submissions. A passive surveillance data set of ticks and tick-borne pathogens was conducted over 5 years (2015-2019) in Massachusetts. The percentages of four tick-borne pathogens: Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi were determined by Massachusetts county and by month and year. Regression models were used to examine the association between zip-code-level socioeconomic factors and submissions. A total of 13,598 I. scapularis ticks were submitted to TickReport from Massachusetts residents. The infection rate of B. burgdorferi, A. phagocytophilum, and B. microti was 39%, 8%, and 7% in adult ticks; 23%, 6%, and 5% in nymphal ticks, respectively. A relatively higher level of education was associated with high tick submission. Passive surveillance of human-biting ticks and associated pathogens is important for monitoring tick-borne diseases, detecting areas with potentially high risks, and providing public information. Socioeconomic factors should be considered to produce more generalizable passive surveillance data and to target potentially underserved areas.

Borrelia miyamotoi in wild rodents from four different regions of Turkey.

Borrelia miyamotoi is a tick-borne zoonotic agent that causes hard tick-borne relapsing fever, an emerging disease in humans. Some small mammalian and bird species are reported to be reservoirs of B. miyamotoi. This study aims to examine Borrelia species present in rodents captured from rural areas of Turkey. Blood samples of rodents were initially screened with Borrelia 16S rRNA qPCR. The Borrelia flaB gene was subsequently amplified by conventional PCR, after which all positive samples were sequenced. Borrelia miyamotoi was observed in nine out of 536 blood samples (1.7%) collected from wild rodents. Phylogenetic analysis showed that all positive samples belonged to the European genotype clade of B. miyamotoi. PCR positivity was 5.3%, 3.7%, and 1.8% in Apodemus uralensis, Apodemus flavicollis, and Myodes glareolus, respectively. Borrelia burgdorferi sensu lato that causes Lyme borreliosis in humans could not be detected in the rodents. In this study, presence of B. miyamotoi DNA is reported for the first time in rodents in Turkey.

Prevalence of Borrelia burgdorferi and diversity of its outer surface protein C (ospC) alleles in blacklegged ticks (Ixodes scapularis) in Delaware.

Characterizing the diversity of genes associated with virulence and transmission of a pathogen across the pathogen's distribution can inform our understanding of host infection risk. Borrelia burgdorferi is a vector-borne bacterium that causes Lyme disease in humans and is common in the United States. The outer surface protein C (ospC) gene of B. burgdorferi exhibits substantial genetic variation across the pathogen's distribution and plays a critical role in virulence and transmission in vertebrate hosts. In fact, B. burgdorferi infections that disseminate across host tissues in humans are associated with only a subset of ospC alleles. Delaware has a high incidence of Lyme disease, but the diversity of ospC in B. burgdorferi in the state has not been evaluated. We used PCR to amplify ospC in B. burgdorferi-infected blacklegged ticks (Ixodes scapularis) in sites statewide and used short-read sequencing to identify ospC alleles. B. burgdorferi prevalence in blacklegged ticks varied across sites, but not significantly so. We identified 15 previously characterized ospC alleles accounting for nearly all of the expected diversity of alleles across the sites as estimated using the Chao1 index. Nearly 40% of sequenced infections (23/58) had more than one ospC allele present suggesting mixed strain infections and the relative frequencies of alleles in single infections were positively correlated with their relative frequencies in mixed infections. Turnover of ospC alleles was positively related to distance between sites with closer sites having more similar allele compositions than more distant sites. This suggests a degree of B. burgdorferi dispersal limitation or habitat specialization. OspC alleles known to cause disseminated infections in humans were found at the highest frequencies across sites, corresponding to Delaware's high incidence of Lyme disease.

Borrelia miyamotoi: A Comprehensive Review.

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.