Two Cases of <i>Borrelia miyamotoi</i> Meningitis, Sweden, 2018

Henningsson, Anna J.; Ásgeirsson, Hilmir; Hammas, Berit; Karlsson, Elias; Parke, Åsa; Hoornstra, Dieuwertje; Wilhelmsson, Peter; Hovius, Joppe W.

doi:10.3201/eid2510.190416

Cited by 48 publications

(60 citation statements)

References 15 publications

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“…BMD cases have been reported in Europe and the USA as well, but not with such frequency [2,[36][37][38][39]. Cases that were reported from Western Europe often involved immunocompromised individuals, but more recently also immunocompetent persons [40,41]. The widespread geographic distribution of this emerging human pathogen that can utilize many different vectors and hosts, as well as the different clinical presentation of BMD, varying in clinical significance from asymptomatic infection to severe effects such as meningoencephalitis, imply the need to understand the genetic basis of this diversity.…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

Kuleshov

Margos²,

Fingerle³

et al. 2020

BMC Genomics

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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.

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Section: Introductionmentioning

confidence: 99%

Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

Kuleshov

Margos²,

Fingerle³

et al. 2020

BMC Genomics

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“…The disease was designated as Borrelia miyamotoi disease (BMD) or hard tick-borne relapsing fever and should be the object of differential diagnosis of human granulocytic anaplasmosis (HGA) [3]. In parallel, cases of meningoencephalitis caused by B. miyamotoi in highly immunocompromised patients, receiving B-cell depleting therapy have been described since 2013 and one case was reported in an apparently immunocompetent patient [6][7][8][9]. In central Europe, only one blood sample has been found to be PCR-positive so far, albeit in a person without symptoms [10].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Borrelia miyamotoi in febrile patients and ticks in Alsace, an endemic area for Lyme borreliosis in France

et al. 2020

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Background: Borrelia miyamotoi is a relapsing fever Borrelia species transmitted by ticks of the Ixodes ricinus complex. Human disease caused by B. miyamotoi was first described in Russia and later in the USA and Japan. Additionally, five cases of meningoencephalitis in immunocompromised patients and one case in an apparently immunocompetent patient were described. Methods: We investigated the presence of B. miyamotoi in I. ricinus nymphs and in patients suspected of human granulocytic anaplasmosis, in Alsace (France), an endemic area for I. ricinus ticks and Lyme borreliosis, using direct (PCR) and indirect diagnosis (glycerophosphoryldiester-phosphodiesterase (GlpQ) serology). Results: Borrelia miyamotoi was found in 2.2% of 4354 ticks collected between 2013 and 2016. None of the 575 blood samples, collected from the patients suspected of HGA, was found positive for B. miyamotoi by PCR. Acute and late sera from 138 of these 575 patients were available. These paired sera were tested for IgM and IgG antibodies against the B. miyamotoi GlpQ antigen. A total of 14 out of 138 patients had at least one positive parameter (i.e. anti-GlpQ IgG and/or IgM). One patient seroconverted for IgG, and three had isolated IgM in the acute serum. These three patients were treated with doxycycline which could have prevented seroconversion. After reviewing clinical data and other biological tests performed, co-exposure among different microorganisms vectored by ticks or serological cross-reactivity could not be ruled out in these different cases. One patient had persistent IgG, which strongly suggests previous exposure to B. miyamotoi. Conclusions: Humans can be exposed to B. miyamotoi through tick bites in Alsace. We present serological data for possible B. miyamotoi exposure or infection of patients with fever after tick bite. Future studies should determine the incidence, clinical course and burden of this emerging tick-borne disease in other parts of Western Europe.

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“…However, recently (after the study period of this review) two new neurological BMD cases have been diagnosed in Sweden, of which one case was immunocompetent [115]. Neurological involvement is demonstrated in the CSF by pleocytosis, visible spirochetes by dark-field microscopy and by molecular analysis specific for relapsing fever Borrelia and Borrelia miyamotoi [115]. Pleocytosis and visible spirochetes in the CSF by dark-field microscopy were also reported in the Dutch immunodeficient case included in this study [110,114].…”

Section: Pathologymentioning

confidence: 62%

“…As opposed to the hematogenous disease commonly seen in immunocompetent cases, in immunocompromised patients, BMD has been reported to manifest neurologically (e.g., meningoencephalitis) [114]. However, recently (after the study period of this review) two new neurological BMD cases have been diagnosed in Sweden, of which one case was immunocompetent [115]. Neurological involvement is demonstrated in the CSF by pleocytosis, visible spirochetes by dark-field microscopy and by molecular analysis specific for relapsing fever Borrelia and Borrelia miyamotoi [115].…”

Section: Pathologymentioning

confidence: 81%

Evaluation of Disease Causality of Rare Ixodes ricinus-Borne Infections in Europe

et al. 2020

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In Europe, Ixodes ricinus ticks transmit pathogens such as Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV). In addition, there is evidence for transmission to humans from I. ricinus of Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Babesia venatorum, Borrelia miyamotoi, Neoehrlichia mikurensis, Rickettsia helvetica and Rickettsia monacensis. However, whether infection with these potential tick-borne pathogens results in human disease has not been fully demonstrated for all of these tick-borne microorganisms. To evaluate the available evidence for a causative relation between infection and disease, the current study analyses European case reports published from 2008 to 2018, supplemented with information derived from epidemiological and experimental studies. The evidence for human disease causality in Europe found in this review appeared to be strongest for A. phagocytophilum and B. divergens. Nonetheless, some knowledge gaps still exist. Importantly, comprehensive evidence for pathogenicity is lacking for the remaining tick-borne microorganisms. Such evidence could be gathered best through prospective studies, for example, studies enrolling patients with a fever after a tick bite, the development of specific new serological tools, isolation of these microorganisms from ticks and patients and propagation in vitro, and through experimental studies.

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Two Cases of Borrelia miyamotoi Meningitis, Sweden, 2018

Cited by 48 publications

References 15 publications

Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

Assessment of Borrelia miyamotoi in febrile patients and ticks in Alsace, an endemic area for Lyme borreliosis in France

Evaluation of Disease Causality of Rare Ixodes ricinus-Borne Infections in Europe

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