Genome Sequences of Rare Human Enterovirus Genotypes Recovered from Clinical Respiratory Samples in Bern, Switzerland.

We report on genomic sequences of human enteroviruses (EVs) that were identified in respiratory samples in Bern, Switzerland, in 2018 and 2019. Besides providing sequences for coxsackievirus A2, echovirus 11, and echovirus 30, we determined the sequences of rare EV-D68 and EV-C105 genotypes circulating in Switzerland.

Effective chemical virus inactivation of patient serum compatible with accurate serodiagnosis of infections.

OBJECTIVES: Highly pathogenic viruses such as EBOV are a threat to routine laboratory workers. Inactivation procedures with Triton X-100 0.1% and/or heat are currently recommended, but have unknown effects on the accuracy of serological testing. Furthermore, virus inactivation by Triton X-100 0.1% was shown to be ineffective in serum. This study aimed to demonstrate virus inactivation in serum by Triton X-100 1% and maintained accuracy of serological testing. METHODS: A panel of 19 serological tests was run on patient serum samples after treatment with Triton X-100 1%, 0.1%, and 0.1% + heat inactivation at 60°C for 1 h. Mean differences between measurements (bias) were calculated applying the Bland-Altman method. To determine effectiveness of virus inactivation, herpes simplex virus 1 (HSV-1) was spiked into medium containing 90% or 1% serum, and treated with Triton X-100 0.1% or 1%. Infectious titres were then determined on Vero cells. RESULTS: Serological measurements showed good agreement between controls and samples treated with Triton X-100 0.1% and 1%, with an estimated bias of 0.6 ± 9.2% (n = 258) and -0.1 ± 18.6% (n = 174), respectively. Discordant qualitative results were rare. Conversely, heat inactivation alone and combined with Triton X-100 0.1% triggered a bias of 17.5 ± 66.4% (n = 200) and 37.9 ± 79.8% (n = 160), respectively. Triton X-100 1% completely inactivated HSV-1 in 1% and 90% serum while Triton X-100 0.1% failed to do so in 90% serum. CONCLUSIONS: Unlike heat inactivation, Triton X-100 1% enabled accurate serological testing and completely inactivated HSV-1 in serum. This simple method could allow safe routine serological diagnostics in high-risk patients.

Cerebrospinal fluid CXCL13 as a diagnostic marker of neuroborreliosis in children: a retrospective case-control study.

BACKGROUND: Lyme neuroborreliosis (LNB) is a frequent manifestation of Lyme disease in children and its current diagnosis has limitations. The elevation of the chemokine CXCL13 in the cerebrospinal fluid (CSF) of adult patients with LNB has been demonstrated and suggested as a new diagnostic marker. Our aim was to evaluate this marker in the CSF of children with suspected LNB and to determine a CXCL13 cut-off concentration that would discriminate between LNB and other central nervous system (CNS) infections. METHODS: For this single-center retrospective case-control study we used a diagnostic-approved ELISA to measure CXCL13 concentrations in the CSF of 185 children with LNB suspicion at presentation. Patients were classified into definite LNB (cases), non-LNB (controls with other CNS affections), and possible LNB. A receiver-operating characteristic curve was generated by comparison of cases and controls. RESULTS: CXCL13 was significantly elevated in the CSF of 53 children with definite LNB (median 774.7 pg/ml) compared to 91 control patients (median 4.5 pg/ml, p < 0.001). A cut-off of 55 pg/ml resulted in a sensitivity of 96.7% and a specificity of 98.1% for the diagnosis of definite LNB and the test exhibited a diagnostic odds ratio of 1525.3. Elevated CSF CXCL13 levels were also detected in three controls with viral meningitis (enterovirus n = 1, varicella-zoster virus n = 2) while other CNS affections such as idiopathic facial palsy did not lead to CXCL13 elevation. Of the 41 patients with possible LNB, 27% had CXCL13 values above the cut-off of 55 pg/ml (median 16.7 pg/ml). CONCLUSIONS: CSF CXCL13 is highly elevated in children during early LNB as previously shown in adults. CXCL13 is a highly sensitive and specific marker that helps to differentiate LNB from other CNS affections in children.

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.

The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.

IGRA-positive patients and interferon-gamma/interleukin-2 signatures: can the Fluorospot assay provide further information?

A goal of testing for latent tuberculosis (TB) infection is to identify individuals who are at increased risk for the development of active TB. No laboratory tool is currently available to distinguish between individuals in the process of progressing from latent TB infection towards active disease and those who are not. Determination of the interferon-gamma and interleukin-2 T cell signature might provide an additional and rapid tool to evaluate treatment necessity and clinical management of a patient. Here, we present three cases of interferon-gamma release assay-positive patients with differing interferon-gamma and interleukin-2 signatures when analyzed by the Fluorospot assay.