Epidemiological changes in Chlamydia pneumoniae molecular detections before, during and after the COVID-19 pandemic in 27 European sites and Taiwan, 2018 to 2023.

BackgroundDuring the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) such as social distancing, lockdowns and enhanced hygiene led to a decrease in respiratory pathogens. However, as NPIs were relaxed, a resurgence in several respiratory pathogens was observed including one local Chlamydia pneumoniae outbreak in Switzerland, prompting the need for a better understanding of C. pneumoniae epidemiology.AimTo assess temporal and geographical variations in C. pneumoniae detection before, during and after the COVID-19 pandemic.MethodsData on C. pneumoniae PCR detection ratios (number of positive tests/ total number of tests) across pre-pandemic (2018-2019), pandemic (2020-2022) and post-pandemic (2023) periods were collected via a global survey disseminated through various professional networks.ResultsC. pneumoniae detection ratios were analysed across 28 sites (27 in Europe, one in Taiwan) in 2023 (Dataset A, n = 172,223 tests) and 20 sites from 2018 to 2023 (Dataset B, n = 693,106 tests). Twenty-seven sites were laboratories (hospital or clinical) and one a surveillance system (Denmark). A significant decrease in detection ratios was observed during the pandemic period (from 1.05% to 0.23%, p < 0.001). In 2023, detection ratios increased to 0.28% (p < 0.002). Notable regional variations were found, with statistically significant increases in detection ratios at six sites located in Switzerland and Slovenia, where ratios ranged from 0.52% to 3.25%.DiscussionThe study highlights how NPIs influenced C. pneumoniae epidemiology, with reduced detection during the pandemic and partial resurgence afterwards. Regional variations suggest differing NPI impacts and underscore the need for continued surveillance

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial

Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20–1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74–1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30–1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00–5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2–3 days sooner. Funding European Commission's Seventh Framework Programme

Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study.

BACKGROUND: Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. METHODS: 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. RESULTS: RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. CONCLUSION: RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Collaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments

Neglected tropical diseases (NTDs) make up a diverse group of debilitating illnesses disproportionately affecting impoverished communities in tropical and subtropical regions. Despite their significant global health burden, they are often overshadowed by more prominent diseases, resulting in a critical lack of investment in the research and development of new treatments. A renewed focus on NTDs is, therefore, urgently needed, particularly in terms of novel therapeutic strategies. The Open Synthesis Network, launched by DNDi and partner institutions in 2016, is an innovation powerhouse that taps into the potential of students to help drive the discovery of new drugs for patients living with NTDs. We present the results of student-led work into the development of a series of aminopyrazoles for Chagas disease, a multisystemic disease caused by the Trypanosoma cruzi parasite. Seventy-four compounds were synthesized by undergraduate and postgraduate students from six universities from Brazil, Ghana, Germany, USA, and UK, illustrating that open innovation and collaboration for education can drive drug discovery forward. Early evaluation of the structure−activity relationships identified a range of potent hit compounds with selectivity for T. cruzi and no observable cytotoxicity. continued..

Epidemiologische surveillance van invasieve infecties veroorzaakt door groep A streptokokken S. pyogenes - 2017 tot 2023

Hoofdpunten: • Alle gegevensbronnen (peillabo’s, Nationaal Referentiecentrum en verplichte meldingen) geven dezelfde globale trends aan: een lage frequentie van iGAS tijdens de pandemische jaren 2020-2021 en een sterke stijging vanaf eind 2022, met hele hoge aantallen in 2023. • De piek van het aantal gerapporteerde iGAS gevallen lag rond de jaarwisseling 2022-2023: in december ‘22 volgens de cijfers van het Nationaal Referentiecentrum (NRC) en de peillaboratoria, in januari ‘23 volgens de cijfers van de verplichte meldingen (VM). • Hoe groot de relatieve toename juist was ten opzichte van vorige jaren is moeilijk te zeggen wegens beperkingen in de verschillende gegevensbronnen. • Het meest voorkomende genotype tijdens de piek van 2022-2023 was M1. • Het is onduidelijk waardoor de piek juist veroorzaakt werd, vermoedelijk speelt een combinatie van factoren een rol: lage circulatie tijdens de pandemie waardoor verminderde opbouw van immuniteit bij jonge kinderen, plots meer nauwe contacten en meer andere virale infecties (die een risicofactor vormen voor iGAS) na opheffen hygiënische maatregelen en mogelijk ook een meer virulent genotype. • De leeftijdsgroepen die het meest getroffen worden, zijn kinderen onder de 5 jaar en volwassenen ouder dan 65 jaar. • Het betreft ernstige infecties die bijna steeds een ziekenhuisopname vereisen en gepaard gaan met een hoge mortaliteit. Exacte cijfers in verband met mortaliteit zijn er echter niet omwille van problemen met het coderen van de uitkomst (voor de overlijdenscertificaten en minimale ziekenhuisgegevens), registratie op moment van de acute infectie zonder opvolging in de tijd (NRC gegevens), of een beperkte dekkingsgraad (verplichte&nbsp;meldingen).</p

Surveillance épidémiologique des infections invasives causées par les streptocoques du groupe A S. pyogenes - 2017 à 2023

Messages clés: • Toutes les sources de données (laboratoires vigies, Centre National de Référence et déclaration obligatoires) indiquent les mêmes tendances générales&nbsp;: la fréquence de l&#8217;iGAS a été faible pendant les années pandémiques 2020-2021 et a fortement augmenté à partir de la fin de 2022, avec des chiffres très élevés en 2023. • Le pic du nombre de cas signalés a été atteint au tournant de l&#8217;année 2022-2023&nbsp;: décembre ‘22 selon les chiffres du Centre national de référence (CNR) et les laboratoires vigies, janvier ‘23 selon les chiffres de la déclaration obligatoire (DO). • Il est difficile de déterminer l&#8217;ampleur exacte de l&#8217;augmentation relative par rapport aux années précédentes en raison des limites des différentes sources de données. • Le génotype le plus courant pendant le pic 2022-2023 était M1. • On ne sait pas exactement ce qui a provoqué ce pic, mais il est probable qu&#8217;une combinaison de facteurs joue un rôle&nbsp;: une faible circulation pendant la pandémie entraînant une réduction de l&#8217;immunité chez les jeunes enfants, une augmentation soudaine des contacts étroits et des autres infections virales (qui sont un facteur de risque pour l&#8217;iGAS) après la levée des mesures d&#8217;hygiène, et peut-être aussi un génotype plus virulent. • Les groupes d&#8217;âge les plus touchés sont les enfants de moins de 5 ans et les adultes de plus de 65 ans. • Il s&#8217;agit d&#8217;infections graves qui nécessitent presque toujours une hospitalisation et sont associées à une mortalité élevée. Toutefois, les chiffres exacts relatifs à la mortalité ne sont pas disponibles en raison de problèmes d’encodage des données (pour les certificats de décès et les données du Résumé Hospitalier Minimal), de l&#8217;enregistrement au moment de l&#8217;infection aiguë, sans suivi dans le temps (données du CNR), ou d&#8217;une couverture limitée (déclaration&nbsp;obligatoire).</p