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Rhipicephalus microplus is an ixodid tick with a pantropical distribution that represents a serious threat to livestock. West Africa was free of this tick until 2007, when its introduction into Benin was reported. Shortly thereafter, further invasion of this tick species into other West African countries was identified. In this paper, we describe the first detection of R. microplus in Guinea and list the vector-borne haemoparasites that were detected in the invading and indigenous Boophilus species. In 2018, we conducted a small-scale survey of ticks infesting cattle in three administrative regions of Guinea: N`Zerekore, Faranah, and Kankan. The tick species were identified by examining their morphological characteristics and by sequencing their COI gene and ITS-2 gene fragments. R. microplus was found in each studied region. In the ticks, we found the DNA of Babesia bigemina, Anaplasma marginale, Anaplasma platys, and Ehrlichia sp. The results of this study indicate that R. microplus was introduced into Guinea in association with cows from Mali and/or the Ivory Coast.

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.Лейшманиозы протозойные трансмиссивные заболевания, характеризующиеся преимущественным поражением внутренних органов (висцеральные лейшманиозы) или кожи (кожные лейшманиозы) с развитием лихорадки, спленомегалии и анемии. В Российской Федерации большинство зафиксированных случаев связано с посещением стран, эндемичных по лейшманиозу; в то же время имеются единичные сообщения о развитии заболевания у лиц, посетивших южные регионы России (Крым, Дагестан) и Закавказье или постоянно проживающих в них. Отсутствие настороженности со стороны клиницистов существенно затрудняет своевременную постановку правильного диагноза и может привести к выбору неверной тактики лечения. В статье рассмотрены современные представления об эпидемиологии, подходах к диагностике и лечению лейшманиоза; обсуждаются особенности представленного клинического случая.

The genus Flavivirus includes related, unclassified segmented flavi-like viruses, two segments of which have homology with flavivirus RNA-dependent RNA polymerase NS5 and RNA helicase-protease NS3. This group includes such viruses as Jingmen tick virus, Alongshan virus, Yanggou tick virus and others. We detected the Yanggou tick virus in Dermacentor nuttalli and Dermacentor marginatus ticks in two neighbouring regions of Russia. The virus prevalence ranged from 0.5% to 8.0%. We detected RNA of the Alongshan virus in 44 individuals or pools of various tick species in eight regions of Russia. The virus prevalence ranged from 0.6% to 7.8%. We demonstrated the successful replication of the Yanggou tick virus and Alongshan virus in IRE/CTVM19 and HAE/CTVM8 tick cell lines without a cytopathic effect. According to the phylogenetic analysis, we divided the Alongshan virus into two groups: an Ixodes persulcatus group and an Ixodes ricinus group. In addition, the I. persulcatus group can be divided into European and Asian subgroups. We found amino acid signatures specific to the I. ricinus and I. persulcatus groups and also distinguished between the European and Asian subgroups of the I. persulcatus group.

Rhipicephalus microplusis an ixodid tick with a pantropical distribution that represents a serious threat to livestock. West Africa was free of this tick until 2007, when its introduction into Benin was reported. Shortly thereafter, the further invasion of this tick into West African countries was demonstrated. In this paper, we describe the first detection ofR. microplusin Guinea and list the vector-borne haemoparasites that were detected in the invader and indigenousBoophilusspecies.In 2018, we conducted a small-scale survey of ticks infesting cattle in three administrative regions of Guinea: N`Zerekore, Faranah, and Kankan. The tick species were identified by examining their morphological characteristics and by sequencing their COI gene and ITS-2 gene fragments.R. micropluswas found in each studied region. In the ticks, we found DNA ofBabesia bigemina,Anaplasma marginale, Anaplasma platys, andEhrlichia spp. The results of this study indicate thatR. micropluswas introduced into Guinea with cows from Mali and/or Ivory Coast.

Capnocytophaga canimorsus is a part of healthy oral flora of dogs and cats. However, when it is transmitted to human subjects via animal bites or scratches, it can cause severe complications like endocarditis or even lethal septic shock, especially in immunocompromised persons. In this study, we performed the first whole-genome sequencing on Illumina HiSeq platform of Russian isolate of C. canimorsus that have caused lethal sepsis in 51-old male from Moscow. We believe that the availability of genomic sequence and annotation for the given strain could be useful for future epidemiological surveillance studies in Russia and other countries.

Ixodes tick-borne borreliosis caused by Borrelia miyamotoi (ITBB-BM) is a previously unknown infectious disease discovered in Russia.The present study continues the investigation of the clinical features of ITBB-BM in the context of an immune system-pathogen interaction.The study enrolled 117 patients with ITBB-BM and a comparison group of 71 patients with Lyme disease (LD) that is ITBB with erythema migrans. All the patients were treated at the New Hospital, Yekateringburg. More than 100 clinical, epidemiological and laboratory parameters were obtained from each patient's medical history and included in the general database. A subset of patients hospitalized in 2015 and 2016 underwent additional laboratory examinations. Namely, the levels of B. miyamotoi-specific IgM and IgG antibodies were measured by the protein microarray containing GlpQ protein and four variable major proteins (VMPs): Vlp15/16, Vlp18, Vsp1, and Vlp5. The blood concentration of Borrelia was estimated by quantitative real-time PCR.In contrast to LD, first of all (p0.001) the following clinical features were typical for ITBB-BM: the absence of erythema migrans (in 95% of patients), fever (93%), fatigue (96%), headache (82%), chill (41%), nausea (28%), lymphopenia (56%), thrombocytopenia (46%), the abnormal levels of alanine aminotransferase (54%) and C-reactive protein (98%), proteinuria (61%). Given the set of these indicators, the course of ITBB-BM was more severe in approximately 70% of patients. At admission, only 13% and 38% of patients had antibodies to GlpQ and VMPs, respectively; at discharge, antibodies to GlpQ and VMPs were detected in 88% of patients. There was no statistically significant association of the antibody response with individual clinical manifestations and laboratory parameters of the disease. However, patients with more severe ITBB-BM produced less IgM antibodies to VMPs and GlpQ at the time of discharge.ITBB-BM is a moderate systemic disease accompanied by the production of specific antibodies in virtually all patients.Цель исследования. Изучение клинических проявлений иксодового клещевого боррелиоза, вызванного Borrelia miyamotoi (ИКБ-БМ), в контексте взаимодействия иммунной системы с возбудителем. Материалы и методы. В исследование включили 117 больных ИКБ-БМ, в качестве группы сравнения - 71 больного с эритемной формой ИКБ (лаймская болезнь - ЛБ), находившихся на лечении в 'Новой больнице', г. Екатеринбург. На основании историй болезни для каждого пациента в базу данных занесено более 100 клинических, лабораторных и эпидемиологических показателей. У отдельных больных, госпитализированных в 2015-2016 гг., уровень антител (АТ) IgM и IgG к специфическим антигенам B. miyamotoi - ферменту GlpQ и четырем вариабельным главным поверхностным белкам (VMPs), обозначаемым Vlp15/16, Vlp18, Vsp1, Vlp5, измерен с помощью специально разработанного белкового иммуночипа, а концентрация боррелий в крови - с помощью количественной полимеразной цепной реакции в реальном времени. Результаты. Больных ИКБ-БМ отличало от больных ЛБ в первую очередь (p0,001) отсутствие мигрирующей эритемы (у 95%), наличие лихорадки (у 93%), жалобы на слабость (96%), головную боль (82%), озноб (41%), тошноту (28%), лимфопения (56%) и тромбоцитопения (46%), превышающие референтные значения уровни аланинаминотрансферазы (54%) и С-реактивного белка (98%), протеинурия (у 61%). На основании комплекса этих показателей более тяжелое течение ИКБ-БМ отмечено приблизительно у 70% пациентов. При поступлении только 13% пациентов имели АТ к GlpQ и 38% - к VMPs; при выписке АТ к GlpQ и VMPs обнаруживались у 88% больных. Статистически значимой связи антительного иммунного ответа с отдельными клинико-лабораторными проявлениями заболевания не выявлено, однако у больных с более тяжелым течением ИКБ-БМ продуцируется меньше IgM АТ к VMPs и GlpQ к моменту выписки. Заключение. Инфекция ИКБ-БМ - генерализованное заболевание средней тяжести, сопровождающееся выработкой специфических АТ практически у всех больных.

Lassa virus is the causative agent of a dangerous zoonotic disease distributed in West Africa. A primary reservoir host of Lassa virus is Mastomys natalensis. These mice associate closely with humans and are commonly found in villages. Consequently, previous studies of Lassa virus have focused on rural areas. The prevalence of the virus in large cities has not been studied.We conducted a study in N’Zerekore city, which has a population of approximately 300,000 residents. Small mammals were captured during a pilot study in May, and the main study was performed in August 2018. Based on the pilot study, we designed and implemented a stratified random sample to investigate the prevalence of Lassa virus among M. natalensis in N’Zerekore. The total sampling efforts consisted of 45 and 985 trapping nights in May and August, respectively. Samples of rodent tissues were screened for Lassa virus by RT-PCR.In May, we trapped 20 rodents, including 19 M. natalensis. Viral RNA was detected in 18 M. natalensis. In August, 149 small mammals were captured, including 43 M. natalensis. The prevalence of Lassa virus among M. natalensis in N’Zerekore was 23.3% (CI 95%: 11.8–38.6%). Sequencing showed that the isolates belonged to lineage IV. We detected four Lassa virus hotspots located in different parts of the city. The largest Lassa virus hotspot was found in the neighborhood of the central market, which suggests that the virus was originally introduced into the city through the market.

Ngari virus is a mosquito-borne virus belonging to the genus Orthobunyavirus (Peribunyaviridae family). This virus is pathogenic to humans and causes severe illness. Ngari virus is present in several African countries, including Madagascar. Here, we report the detection of Ngari virus in ixodid ticks collected from cows in Guinea. A tick survey was conducted in March-November of 2018 in six regions of Guinea. The sample comprised 710 pools, with a total of 2067 ticks belonging to five species collected from 197 cows. At the initial stage, we screened a subsample of tick pools of vector-borne viruses with a multiplex genus-specific primer panel. In the second stage of the study, we narrowed the search and screened all the samples by qPCR for the detection of Ngari virus. All positive samples were sequenced with primers flanking Ngari virus-specific fragments on the S and M segments. We found Ngari virus in 12 pools that were formed from engorged ticks collected from livestock in three villages of the Kindia and Kankan regions. Sequencing of the S and M segments confirmed that the detected viruses belong to Ngari virus, and the viruses were most similar to the strain Adrar, which was isolated in Mauritania. We detected viral RNA in ticks of the following species: Amblyomma variegatum, Rhipicephalus geigyi, and Rh. (Boophilus) spp. There is no evidence that ixodid ticks are competent vectors of the Ngari virus. Most likely, the ticks obtained the virus through blood from an infected host. The study of engorged ticks can be recommended as a simpler approach for the wide screening of the Ngari virus and subsequent testing of cattle and mosquitos in those locations where the PCR-positive ticks were collected.

A six-year old pit bull terrier, female, was presented to a veterinary clinic in Mocsow, Russia. The leading clinical signs were a decrease in the physical activity of the dog with weight loss despite normal appetite. The dog had never traveled to other regions, but there was a history of a fight with a dog from Serbia about two years before. A severe anemia and azotemia were revealed during the examination. The merozoites of small Babesia were detected in a blood smear, which were identified as Babesia vulpes by PCR. The treatment with imidocarb dipropionate and atovaquone in combination with azithromycin was started, but one week later the dog was euthanized because of a serious health condition and poor prognosis. Contact transmission due to bites might have been the cause of infection in this case.

Here, we report the first confirmed autochthonous tick-borne encephalitis case diagnosed in Moscow in 2016 and describe the detection of Tick-borne encephalitis virus (TBEV) in ticks and small mammals in a Moscow park.The paper includes data from two patients who were bitten by TBEV-infected ticks within the Moscow city limits; one of these cases led to the development of the meningeal form of TBE. Both TBEV-infected ticks attacked patients in the same area. We collected ticks and trapped small mammals in this area in 2017. All samples were screened for the presence of pathogens causing tick-borne diseases by PCR. The TBEV-positive ticks and small mammals’ tissue samples were subjected to virus isolation. The sequencing of the complete polyprotein gene of the positive samples was performed.A total of 227 questing ticks were collected. TBEV was detected in five specimens of Ixodes ricinus. We trapped 44 small mammals, mainly bank voles (Myodes glareolus) and pygmy field mice (Apodemus uralensis). Two samples of brain tissue from bank voles yielded a positive signal in RT-PCR for TBEV. We obtained six virus isolates from the ticks and brain tissue of a bank vole. Complete genome sequencing showed that the obtained isolates belong to the European subtype and have low diversity with sequence identities as high as 99.9%. GPS tracking showed that the maximum distance between the exact locations where the TBEV-positive ticks were collected was 185 m. We assume that the forest park was free of TBEV and that the virus was recently introduced.

We investigated whether Borrelia miyamotoi disease can be detected in its early stage by using PCR for borrelial 16S rRNA, which molecule (DNA or RNA) is the best choice for this test, and whether spirochetes are present in blood during the acute phase of B. miyamotoi disease. A total of 473 patients with a suspected tickborne infection in Yekaterinburg, Russia, in 2009, 2010, and 2015 were enrolled in this study. Blood samples were analyzed by using quantitative PCR or ELISA, and a diagnosis of borreliosis was confirmed for 310 patients. For patients with erythema migrans, 5 (3%) of 167 were positive for B. miyamotoi by PCR; for patients without erythema migrans, 65 (45%) of 143 were positive for B. miyamotoi by PCR. The median concentration for RNA was 3.8 times that for DNA. Median time for detection of B. miyamotoi in blood was 4 days.

In 2018, a previously unknown Ebola virus, Bombali virus, was discovered in Sierra Leone. We describe detection of Bombali virus in Guinea. We found viral RNA in internal organs of 3 Angolan free-tailed bats (Mops condylurus) trapped in the city of N’Zerekore and in a nearby village.

Lethal cases of tick-borne encephalitis in previously vaccinated patients have not been described. Modern inactivated vaccines against Tick-borne encephalitis (TBE) are high effective. The TBE cases, preference unfocal forms, are developed in persons with incomplete irregular vaccination. First case of lethal TBE after plural vaccination was described in the Kurgan region, the second case - in the Chelyabinsk region. These very rare unusual cases were studied. Being dominant the Siberian subtype of TBE virus is related with lethal TBE cases in the Chelyabinsk region. Unusual TBE case was developed in patient who had been vaccinated 8 limes with vaccines produced from strains of Far-Eastern TBE subtype («Virion», Tomsk, Chumakov institute, Moscow) and European TBE subtype (Encepur; FSME-Immun). Two years after the last vaccination a focal form of TBE was developed with lethal outcome at 9 th day. Specific antibodies IgM and IgG seroconversion were detected. The TBE virus antigen was detected in brain neurons by immunofluorescent test. Destructed neurons and gliocyles were shown by hystological study in cerebral hemispheres and cerebellum. The Purkinje cells were destructed. Possible reasons of surmounting vaccinal immunity including a genetic difference of vaccine and infection virus strains are discussed.

In the Yaroslavl region (Central Federal District of Russia), endemic of tick-borne encephalitis (TBE), the features of epidemiology of this infection were studied during 1992-2012. Cyclical fluctuations in the incidence of TBE, the lack of the trend to decrease of the incidence were observed, the average annual incidence was 1,6 ± 0,32 per 100 thousand ofpopulation. The prevalence offebrile forms of disease was 62,2%, meningeal forms - 16,3%, the total percentage offocal forms was 13,9%. Manifestations of evolution of TBE were: the increase of the epidemiological significance of anthropogenically transformed natural foci, anthropurgical foci of TBE, until 81% of TBE cases were unvaccinated citizens, the high lethality of 4% and the high frequency of cases of alimentary infection of TBE of 7,8% with lethality of 10,8%. The aethiological agent of 10 lethal cases was Siberian subtype of TBE virus.

To clarify the clinical, laboratory, and epidemiological characteristics of relapsing Ixodes tick-borne borreliosis (ITB) caused by Borrelia miyamotoi.Retrospective clinical observation was made in 79 inpatients of the Republican Infectious Diseases Hospital (Udmurt Republic), who had been diagnosed with B. miyamotoi-caused disease verified by real-time polymerase chain reaction. The latter and enzyme immunoassay ruled out possible vector-borne coinfections (ITB caused by B. burgdorferi sensu lato; tick-borne encephalitis; anaplasmosis; and ehrlichiosis).The recurrent course of the disease was observed in 8 (10%) of the 79 patients. The relapsing fever curve was noted in 6 of the 8 patients; 4 patients had 2 episodes of fever and 2 patients had 3 episodes; the wave-like continuous type of fever cannot enable one to estimate the specific number of episodes in 2 more cases. Relapses occurred in all the 8 patients before antibiotic treatment. Febrile syndrome (weakness, headache, chill, fever, sweating, dizziness, nausea, vomiting, myalgia, and arthralgia) was leading in patients with relapses. These patients were less frequently observed to have signs of organ dysfunctions than those with one episode of fever. The values of clinical and biochemical blood tests and urinalyses were normal and near-normal in the majority of patients on hospital admission.Relapsing B. miyamotoi infection cases detected in the directed study proved to be unrecognized by practical health authorities during the first and sometimes second episodes of fever. This indicates that the prevalence of this disease is essentially underestimated and there is a need to increase physicians' alertness and awareness and to introduce adequate diagnostic methods.Цель исследования. Выяснение клинико-лабораторных и эпидемиологических особенностей рецидивирующего (возвратного) течения иксодового клещевого боррелиоза (ИКБ), вызванного Вorrelia miyamotoi. Материалы и методы. Ретроспективное клиническое наблюдение за 79 пациентами, находившимися на стационарном лечении в Республиканской инфекционной клинической больнице Удмуртской Республики с диагнозом: заболевание, вызванное B. miyamotoi, подтвержденным методом полимеразной цепной реакции в реальном времени (ПЦР-РВ). Наличие возможных сопутствующих трансмиссивных инфекций (ИКБ, вызванный B. burgdorferi sensu lato, клещевой вирусный энцефалит, анаплазмоз, эрлихиоз) исключено методами ПЦР-РВ и иммуноферментного анализа. Результаты. Рецидивирующее течение лихорадки наблюдалось у 8 (10%) из 79 больных. Возвратный тип лихорадочной кривой отмечен в 6 случаях из 8, при этом у 4 больных - два эпизода лихорадки, у 2 больных - три; еще в 2 случаях волнообразный непрерывный тип лихорадки не позволил выявить конкретное число эпизодов. У всех 8 больных рецидивы возникали до начала антибиотикотерапии. У больных с рецидивами ведущим является лихорадочный синдром (слабость, головная боль, озноб, лихорадка выше 38,0 °С, потливость, головокружение, тошнота, рвота, миалгии и артралгии); реже, чем у больных с одним эпизодом лихорадки, наблюдаются признаки органных патологий. Показатели общего и биохимического анализов крови и мочи у большинства больных с рецидивами при поступлении в стационар находятся в норме или незначительно отклоняются от нее. Заключение. Выявленные в ходе направленного исследования случаи рецидивирующего течения инфекции В. miyamotoi оказались не распознанными органами практического здравоохранения во время первого, а иногда и второго эпизода лихорадки. Это указывает на существенную недооценку распространенности данного заболевания, обусловливает необходимость усиления настороженности и информированности врачей, внедрения адекватных диагностических методик.

Borrelia miyamotoi is a relapsing fever spirochete in Ixodes ticks that has been recently identified as a human pathogen causing hard tick-borne relapsing fever (HTBRF) across the Northern Hemisphere. No validated serologic test exists, and current serologic assays have low sensitivity in early HTBRF. To examine the humoral immune response against B. miyamotoi, we infected C3H/HeN mice with B. miyamotoi strain LB-2001 expressing variable small protein 1 (Vsp1) and demonstrated that spirochetemia was cleared after 3 d, coinciding with anti-Vsp1 IgM production. Clearance was also observed after passive transfer of immune sera to infected SCID mice. Next, we showed that anti-Vsp1 IgG eliminates Vsp1-expressing B. miyamotoi, selecting for spirochetes expressing a variable large protein (VlpC2) resistant to anti-Vsp1. The viability of Asian isolate B. miyamotoi HT31, expressing Vlp15/16 and Vlp18, was also unaffected by anti-Vsp1. Finally, in nine HTBRF patients, we demonstrated IgM reactivity to Vsp1 in two and against Vlp15/16 in four ∼1 wk after these patients tested positive for B. miyamotoi by PCR. Our data show that B. miyamotoi is able to express various variable major proteins (VMPs) to evade humoral immunity and that VMPs are antigenic in humans. We propose that serologic tests based on VMPs are of additional value in diagnosing HTBRF.

A total of 208 mosquitoes of the Culex pipiens complex from 15 basement and terrestrial populations collected in different regions of the European part of Russia and Siberia were examined by genetic methods. Among these, two major mitotypes, M and P, were identified. These mitotypes differed by six substitutions in the 246-bp mitochondrial DNA cytochrome oxidase I gene fragment examined. Urban basement mosquitoes C. pipiens (form molestus) were characterized by the presence of mitotype M and infection with the endosymbiotic bacteria of the genus Wolbachia. Mosquitoes of the C. pipiens complex inhabiting opened biotopes harbored mitotype P, or its variety, mitotype P1, and were not infected with Wolbachia. Thus, in natural conditions marked linkage disequilibrium between cytoplasmic elements, mitochondrial DNA and Wolbachia, can be observed. Similarity of mitotypes in form molestus mosquito from different geographical localities favors the hypothesis on the common ancestry of urban mosquitoes.

Substantial exposure to Borrelia miyamotoi occurs through bites from Ixodes ricinus ticks in the Netherlands, which also transmit Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. Direct evidence for B. miyamotoi infection in European populations is scarce. A flu-like illness with high fever, resembling human granulocytic anaplasmosis, has been attributed to B. miyamotoi infections in relatively small groups. Borrelia miyamotoi infections associated with chronic meningoencephalitis have also been described in case reports. Assuming that an IgG antibody response against B. miyamotoi antigens reflects (endured) infection, the seroprevalence in different risk groups was examined. Sera from nine out of ten confirmed B. miyamotoi infections from Russia were found to be positive with the recombinant antigen used, and no significant cross-reactivity was observed in secondary syphilis patients. The seroprevalence in blood donors was set at 2.0% (95% CI 0.4–5.7%). Elevated seroprevalences in individuals with serologically confirmed, 7.4% (2.0–17.9%), or unconfirmed, 8.6% (1.8–23%), Lyme neuroborreliosis were not significantly different from those in blood donors. The prevalence of anti-B. miyamotoi antibodies among forestry workers was 10% (5.3–16.8%) and in patients with serologically unconfirmed but suspected human granulocytic anaplasmosis was 14.6% (9.0–21.8%); these were significantly higher compared with the seroprevalence in blood donors. Our findings indicate that infections with B. miyamotoi occur in tick-exposed individuals in the Netherlands. In addition, B. miyamotoi infections should be considered in patients reporting tick bites and febrile illness with unresolved aetiology in the Netherlands, and other countries where I. ricinus ticks are endemic.

To the editor: Autochthonous cases of Japanese encephalitis (JE) have never been reported in Europe, where there is virtually no circulation of the virus [1]. However, in the issue of Eurosurveillance published on 12 July 2012, Ravanini et al. [2] reported the detection of an RNA sequence of the Japanese encephalitis virus (JEV) NS5 gene in one pool of Culex pipiens mosquitoes collected in north-eastern Italy during the summer of 2010. Unfortunately, the sequence was relatively short (167 bp), and attempts to amplify longer sequences using primers targeted to E, NS5 and NS3 genes and to isolate the virus on cell cultures failed.

To the Editor: Borreliosis caused by Borrelia miyamotoi is an emerging disease transmitted by Ixodes ticks (1). Each year in the Netherlands during 2007–2009, ≈70,000 bites by hard ticks occurred per 1 million inhabitants (2). In the Republic of Udmurtia, Russia, ≈10,000 hard tick bites per 1 million inhabitants are reported annually among persons seeking medical help. Recent studies indicate that almost 3% of I. ricinus ticks in the Netherlands and 2%–6% of I. persulcatus ticks in Russia are infected with B. miyamotoi (1,3,4). Human exposure is substantial, and comparable exposure to B. miyamotoi is expected in many Eurasian countries and in North America (4,5). The probability of B. miyamotoi transmission from ticks to humans requires examination to estimate the true risk for human disease. In Izhevsk (population 650,000), a city in European Russia (Republic of Udmurtia), we identified 95 human cases of B. miyamotoi infection during 2010–2014 (6). In this city, primarily because of concern about tickborne encephalitis (TBE), all patients with suspected tickborne infection are hospitalized in the Republican Hospital of Infectious Diseases (RHID). A service also enables tick-bitten persons to bring the removed tick for PCR for TBE virus (TBEV) and B. burgdorferi sensu lato. We supplemented that with PCR testing for B. miyamotoi (3). In June 2014, twenty-four persons (≈5% of those bitten by ticks subjected to PCR-based investigation for TBEV, B. burgdorferi sensu lato, and B. miyamotoi) were bitten by adult I. persulcatus ticks infected with B. miyamotoi only. We informed these persons of their results and about the clinical features of B. miyamotoi infection and recommended self-observation during 2 months (twice the maximum incubation period for B. miyamotoi infection [3,6]). These persons were advised to contact their medical supervisor at RHID (D.S. Sarksyan) if fever, fatigue, erythema migrans, or any other possible symptom of a tickborne infection developed. In 2 patients, such symptoms developed: one 12 days (patient 1), the other 16 days (patient 2), after the tick bite. B. miyamotoi DNA was detected by PCR in their blood on admission to RHID. Neither IgM nor IgG were found by a nonspecific ELISA (Omnix, St. Petersburg, Russia [7]) that reacts with serum from B. burgdorferi sensu lato–infected and B. miyamotoi–infected persons. However, Borrelia IgM and IgG were detected in serum obtained 12 and 45 days after illness onset from patient 1 and 6 and 39 days later from patient 2. Clinical characteristics were typical of B. miyamotoi infection: chills, sweating, headache, dizziness, fatigue, thirst, nausea, vomiting, fever (axillar temperature 38.8°C in patient 1 and 39.0°C in patient 2). Erythema migrans was absent. Both patients had modest thrombocytopenia (134 [patient 1] and 118 [patient 2] × 109 platelets/mL [reference range 150–400 × 109 platelets/mL]) and increased band neutrophils (10% [patient 1] and 8% [patient 2] of leukocytes [reference range 1%–5%]). Patient 2 had clinical and laboratory signs of kidney dysfunction (oliguria, leukocytes, erythrocytes, and epithelial cells in a urine sample), a complication observed in 18% of 95 patients with B. miyamotoi disease (4). Both patients were treated with doxycycline (100 mg 2×/d) for 10 days; they clinically recovered, and laboratory abnormalities returned to reference ranges at discharge 12 days after admission. The remaining 22 persons did not report any malaise and were examined 1 month after tick bite. They appeared healthy at that time, and PCR and ELISA gave negative results, arguing against possible asymptomatic B. miyamotoi infection. We estimated the probability of B. miyamotoi transmission to humans to be 8.3% (95% CI 4%–18% using a Bayesian approach [8] or 95% CI 0%–21% using an SPSS bootstrapping procedure [SPSS Inc., Chicago, IL, USA]). For comparison, among 68 persons bitten by B. burgdorferi sensu lato–infected ticks in the Netherlands, erythema migrans developed in 4.4% (95% C.I. 2.1%–8.3%) persons; 3 (4.4%) others seroconverted without clinical symptoms (9). This pilot study has several limitations. We did not follow up persons bitten by B. burgdorferi sensu lato– or TBEV-infected ticks because they received either antimicrobial drugs or anti-TBE immunoglobulin as a preventive measure. Because of labor constrains, we did not study persons bitten by “PCR-uninfected” ticks; however, they were not hospitalized at RHID, the only hospital in the region for patients with evident tick-borne diseases. We did not use any serologic techniques specific for relapsing fever Borreli (e.g., GlpQ ELISA). Although we did not test for Rickettsia or Babesia spp., we did not find TBEV RNA, B. burgdorferi sensu lato 16S RNA, pathogenic Ehrlichia 16S RNA, or pathogenic Anaplasma DNA in the 2 B. miyamotoi–positive patients’ blood samples. We demonstrated that the transmission rate of B. miyamotoi appears to be equal to, or higher, than that of B. burgdorferi sensu lato (1,9,10). Our data indicate that, annually, clinical B. miyamotoi infection might develop in at least 0.005% of persons living in regions to which Ixodes spp. ticks and B. miyamotoi are endemic. This estimate corresponds to ≈33 cases annually in Izhevsk, which is similar to the previously published results of hospital-based surveillance for B. miyamotoi (3,6).

To study blood coagulation and microcirculatory disorders as a possible cause of transient dysfunctions of organs (the kidney, liver, heart, lung, etc.) in patients with ixodid tick-borne borreliosis caused by Borrelia miyamotoi (Bmt). SUBJECTS AND METHODS; Twenty-four patients with Lyme disease (LD) and 28 Bmt patients treated at Izhevsk City Hospital (Udmurtia) were examined in the study. Platelet counts and the presence of D-dimers were determined; activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and antithrombin III levels, and Factor XIIa-dependent fibrin clot lysis time were measured. Slit lamp microscopy of the conjunctiva was. also carried out. Results. Platelet counts'were less than 150,000 per pL of blood in 43% of the Bmt patients. All the Bmt patients had at least one abnormal coagulation parameter of the eight ones that were tested; 64% of them had marked coagulation disorders with three or more abnormal laboratory findings. In contrast, all the eight parameters were normal in 71% of the LD patients. The other seven LD patients had only one or two abnormal coagulation parameters (p0.001 in comparison with Bmt patients). Microscopic examination of eye capillary blood flow revealed pathological findings that included aggregates of erythrocytes and obstructed and/or sinuous capillaries in 22 (79%) of the Bmt patients, but none of the LD patients. A total of 14 Bmt patients had both coagulation and microcirculatory abnormalities. Eleven of them also had transient signs of organ dysfunction.As far as Borrelia secrete no known toxins, we hypothesized that uncovered disorders of blood coagulation and microcirculation in Bmt patients may contribute to organ dysfunction.Цель исследования. Изучение нарушений в системах свертывания и микроциркуляции крови (МЦК) как возможной причины преходящих дисфункций органов (почек, печени, сердца, легких и др.) у больных иксодовым клещевым боррелиозом, вызванным Borrelia miyamotoi (ИКБ-БМ). Материалы и методы. Обследовали 28 больных ИКБ-БМ и 24 больных с эритемной формой ИКБ (лаймская болезнь - ЛБ), находившихся на лечении в Республиканской инфекционной клинической больнице Удмуртии. При поступлении определяли количество тромбоцитов и наличие D-димеров, измеряли активированное частичное тромбопластиновое время - АЧТВ, протромбиновое время - ПВ, тромбиновое время - ТВ, уровень фибриногена и антитромбина III, скорость зависимого от XIIa-фактора лизиса фибринового сгустка, а также выполняли биомикроскопию конъюнктивы глаза с помощью щелевой лампы. Результаты. Тромбоцитопения менее 150·109/л наблюдалась у 43% больных ИКБ-БМ; из 8 основных изученных показателей, характеризующих состояние системы свертывания, у каждого пациента обнаруживался хотя бы один анормальный показатель, а у 64% больных ИКБ-БМ 3 показателя и более выходят за границы нормы. Напротив, у 71% больных ЛБ все показатели находятся в пределах нормы, у остальных выходят за ее границы не более 1-2 показателей (p0,001). Биомикроскопия глаза выявила существенные внутрисосудистые и сосудистые нарушения (сладж-феномен, замедление или остановка МЦК, извитость или аневризмы сосудов и т.д.) у 79% больных ИКБ-БМ. Существенная патология МЦК не наблюдалась у больных ЛБ. У 14 больных ИКБ-БМ имелись нарушения как системы свертывания, так и МЦК у 11 из них отмечались преходящие признаки тех или иных органных нарушений. Заключение. Мы предполагаем, что органные нарушения при ИКБ-БМ могут быть отчасти обусловлены выявленными расстройствами систем свертывания и МЦК, поскольку известно, что боррелии не секретируют токсинов.