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

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 mikur-ensis, 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.Funding Agencies|European Union through the European Regional Development Fund; Interreg North Sea Region Program 2014-2020 as a part of the NorthTick project [38-2-7-19]</p

Cytokine responses of immunosuppressed and immunocompetent patients with Neoehrlichia mikurensis infection

Purpose The tick-borne bacterium Neoehrlichia mikurensis causes the infectious disease neoehrlichiosis in humans. Vascular endothelium is one of the target cells of the infection. Neoehrlichiosis patients with compromised B cell immunity present with more severe inflammation than immunocompetent patients. The aim of this study was to compare the cytokine profiles of immunocompetent and immunosuppressed patients with neoehrlichiosis. Methods Blood samples from Swedish and Norwegian immunosuppressed (N = 30) and immunocompetent (N = 16) patients with neoehrlichiosis were analyzed for the levels of 30 cytokines, using a multiplex cytokine assay and ELISA. A gender-matched healthy control group (N = 14) was analyzed in parallel. Data were analyzed using the multivariate method OPLS-DA. Results The multiplex cytokine analyses generated more cytokine results than did the uniplex ELISA analyses. Multivariate analysis of the multiplex cytokine results established that increased levels of FGF2, GM-CSF, CXCL10, and IFNγ were associated with immunosuppressed patients, whereas increased levels of IL-15 and VEGF were associated with immunocompetent neoehrlichiosis patients. When multivariate analysis findings were confirmed with uniplex ELISA, it was found that both groups of patients had similarly elevated levels of VEGF, FGF2 and IFNγ. In contrast, the immunosuppressed patients had clearly elevated levels of CXCL10, CXCL13 and BAFF, whereas the immunocompetent patients had the same levels as healthy controls. Conclusion Pro-angiogenic and type 1 cytokines were produced as part of the host response of neoehrlichiosis independent of immune status, whereas immunosuppressed neoehrlichiosis patients produced cytokines required for B cell-mediated defense.Funding Agencies: University of Gothenburg; European Union through the European Regional Development Fund, European Commission; Interreg North Sea Region Programme [J-No.: 38-2-7-19]; Swedish government; county councils; ALF-agreement ALF Research Fund [ALFGBG-827291]; Cancer and Allergy Foundation [2020-10154]; Swedish Research Council, European Commission [K200858X-14631-06-3, 2020-01287]</p

No detection of tick-borne encephalitis virus RNA in blood, urine or saliva of hospitalised immunocompetent tick-borne encephalitis patients.

Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material

Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients

The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of <i>Borrelia burgdorferi</i> sensu lato-specific PCR in Lyme neuroborreliosis?

<p><b>Background:</b> Tests for direct detection of <i>Borrelia burgdorferi</i> sensu lato <i>(Bb)</i> in Lyme neuroborreliosis (LNB) are needed. Detection of <i>Bb</i> DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples.</p> <p><b>Methods:</b> Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls.</p> <p><b>Results:</b><i>Bb</i> DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were <i>Bb</i> antibody negative. No <i>Bb</i> DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases.</p> <p><b>Conclusion:</b> We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without <i>Bb</i> antibodies due to short duration of symptoms.</p