Epidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021-2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages.

Who is providing HIV diagnostic testing? Comparing HIV testing by general practitioners and sexual health centres in five regions in the Netherlands, 2011-2018.

OBJECTIVES: General practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections. METHODS: Laboratory data (2011-2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15-29 years, 30-44 years, 45-59 years, ≥60 years). χ2 tests were used to compare positivity percentage between the two groups of providers. RESULTS: In the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15-29 years old, GPs' testing rates were lower than SHCs', while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs. CONCLUSIONS: This retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs' HIV testing practices.

Use of a diagnostic Puumala virus real-time RT-PCR in an orthohantavirus endemic region in the Netherlands.

Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number (n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM (n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM (n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment. IMPORTANCE: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures.

Defining a risk area for tick-borne encephalitis (TBE) in a country where TBE is emerging, the Netherlands, July 2016-October 2020.

TBE is an emerging infectious disease in the Netherlands since July 2016, and risk areas have not been defined yet. Until October 2020 twelve autochthonous cases of TBE have been identified. In six of these cases transmission of TBE virus likely occurred in the Twente region, which therefore is the region with the highest case number and risk of contracting the disease. Here we summarize the Twente cases so far and discuss if the Twente region should be considered a risk-area using criteria of traditional TBE endemic countries, and the public health measures that may accompany such designation.