Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins

Koetsveld, Joris; Kolyasnikova, Nadezhda M.; Wagemakers, Alex; Стуколова, О. А.; Hoornstra, Dieuwertje; Sarksyan, Denis S.; Топоркова, М. Г.; Henningsson, Anna J.; Hvidsten, Dag; Ang, Wim; Dessau, Ram Benny; Platonov, Alexander E.; Hovius, Joppe W.

doi:10.1016/j.cmi.2018.03.009

Cited by 35 publications

(52 citation statements)

References 22 publications

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“…Serum reactivity against recombinant GlpQ was tested for IgM and IgG antibodies with an ELISA technique as previously described [22,23]. The cut-off values were calculated as the mean result plus three times the standard deviation of the 10 negative controls included in each experiment.…”

Section: Borrelia Miyamotoi Glpq Serologymentioning

confidence: 99%

“…All the sera were tested twice in separate experiments. Positive sera were subsequently tested by western blot as previously described [22]. IgG and IgM serology was considered as positive when both ELISA and western blot were deemed positive.…”

Section: Borrelia Miyamotoi Glpq Serologymentioning

confidence: 99%

“…Contact with B. miyamotoi was considered as probable in patients who seroconverted whatever the result of the anti-GlpQ IgM in the acute serum. Exposure to B. miyamotoi was considered as possible in patients with solitary IgM in sera obtained within 11-20 days after the onset of the symptoms (a compatible delay for the only appearance of anti-GlpQ IgM antibodies) [22] and treated with doxycycline, which could abort seroconversion [24]. Solitary IgM or persistent IgM positivity was classified as false IgM results, when there was evidence of an infection with other microorganisms (e.g.…”

Section: Bmd Case Definitionmentioning

confidence: 99%

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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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Section: Borrelia Miyamotoi Glpq Serologymentioning

confidence: 99%

Section: Borrelia Miyamotoi Glpq Serologymentioning

confidence: 99%

Section: Bmd Case Definitionmentioning

confidence: 99%

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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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“…Serology is a useful complementary method to PCR for confirming a BMD diagnosis, although the recommended two-tiered serologic protocol (17) for confirming a B. burgdorferi infection (enzyme immunoassay [EIA] followed by immunoblot of reactive samples) is not useful for diagnosis of BMD. However, the recombinant glycerophosphate glycerophosphodiesterase (rGlpQ) EIA (18) appears to be sensitive and specific for confirming BMD (4), with 86% of PCR-confirmed acute cases seroconverting; and adding recombinant variable major proteins of B. miyamotoi to the rGlpQ assay greatly enhances EIA sensitivity and specificity (19). A diagnosis of BMD, thus, appears to be best confirmed by PCR analysis of acute blood samples and complemented by a demonstration of a specific antibody.…”

Section: Resultsmentioning

confidence: 99%

Blood Smears Have Poor Sensitivity for Confirming Borrelia miyamotoi Disease

Telford

Goethert

Molloy³

et al. 2019

J Clin Microbiol

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Borrelia miyamotoi disease (BMD) is a newly recognized borreliosis that is cotransmitted by ticks wherever Lyme disease is zoonotic. Unlike Borrelia burgdorferi sensu lato, the agent of Lyme disease, B. miyamotoi is closely related to relapsing fever spirochetes, such as Borrelia hermsii. Some authors have suggested that the disease caused by B. miyamotoi should be considered a hard-tick-transmitted relapsing fever, and thus, the main mode of confirming a diagnosis for that infection, microscopy to analyze a blood smear, may have clinical utility. To determine whether blood smears may detect B. miyamotoi in the blood of acute BMD patients, we made standard malariological thick smears from anticoagulated blood samples that were previously determined to contain this agent (by PCR) and analyzed them for morphological evidence of spirochetes. Spirochetes were not detected in the blood smears from 20 PCR positive patient blood samples after examination of 100 thick smear fields and only 2 of 20 demonstrated spirochetes when the examination was extended to 300 thick smear fields. Inoculation of severe combined immunodeficient (SCID) mice yielded isolates from 5 of 5 samples, but 0 of 3 BALB/c mice became infected. We conclude that in strong contrast to the diagnosis of typical relapsing fever, microscopy of blood smears is not sensitive enough for confirming a diagnosis of BMD but that SCID mouse inoculation could be a useful complement to PCR.

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“…Recent serological studies on reactivity to proteins glpQ and Vmp have revealed maximum sensitivities of 79% for IgM and 86.7% for IgG and a specificity of 100% for IgM class of antibodies, and 98.3% for IgG "in-house" tests. This test will be used in clinical practice in the future and it will improve serologic examination in clinical studies [10]. Therefore, molecular tests (PCR or real time PCR) are more appropriate and reliable methods for routine diagnosis at this moment [2,11].…”

Section: Introductionmentioning

confidence: 99%

Borrelia miyamotoi DNA in a patient suspected of Lyme borreliosis

Fiecek

Lewandowska

Roguska

et al. 2019

Preprint

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Background Clinical manifestations in infection caused by B. miyamotoi can mimick highly variable symptoms of Lyme disease. The aim of our studies was to detect DNA of B. miyamotoi spirochetes in clinical materials from patients suspected of neuroborreliosis(retrospectively).Methods Samples of blood serum and cerebrospinal fluid were collected from 133 patients with clinical manifestations of neuroborreliosis. Diagnosis was established by detection of IgM and / or IgG specific antibodies to B. burgdorferi with ELISA in both sera and CSF. Specificity of positive ELISA results in sera were confirmed with Western-blot test. Bacterial DNA from the collected material was extracted, amplified and sequenced.Results Among 133 patients with clinical manifestations of neuroborreliosis recognized in the years 2010-2018., DNA of B. miyamotoi was detected in CSF from 1 (0.8%) patient with extraocular optic neuritis of the left eye (GenBank accession No. MK674170 and MK674171).Conclusion Detection of B. miyamotoi in patients with central nervous system infections, will allow a better understanding of the epidemiology of infections caused by Borrelia sp. spirochetes. Patients with neurological symptoms and questionable serological findings are a serious diagnostic problem, due to failure to meet the criteria for neuroboreliosis. This indicates the need for further studies of patients with signs of CNS infection.

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Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins

Abstract: We clearly demonstrate here the diagnostic potential of these seromarkers. Our findings will facilitate future epidemiological and clinical studies on BMD and lead to the development of a serologic test to be used in clinical practice.

Cited by 35 publications

References 22 publications

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

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

Blood Smears Have Poor Sensitivity for Confirming Borrelia miyamotoi Disease

Borrelia miyamotoi DNA in a patient suspected of Lyme borreliosis

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