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Genetic Diversity and Excretion Kinetics of Enteroviruses Excreted by Patients with Primary Immunodeficiency in Tunisia over a Five-Year Period (2020-2024)
No full textInternational audienceEnteroviruses (EVs) are small, non-enveloped RNA viruses that can cause diverse clinical outcomes, particularly severe in patients with primary immunodeficiency (PID) due to their impaired ability to clear infections. This study aimed to characterize EV excretion among 138 Tunisian PID patients over a five-year period, to identify circulating EV serotypes and assess their genetic diversity. A total of 558 stool samples were collected and analyzed by virus isolation and intratypic differentiation using RT-qPCR. Molecular typing was performed through Sanger sequencing of the VP1 region and whole genome sequencing using Next-Generation Sequencing (NGS) technologies. Phylogenetic analysis was conducted using the Maximum Likelihood (ML) method. EVs were detected in 55 stool samples from 23 patients. The excretion kinetics of EVs ranged between 30 and 946 days. Thirteen serotypes were identified, including one Poliovirus (PV) and twelve Non-Polio Enteroviruses (NPEVs), predominantly belonging to species B. Two previously unreported serotypes in Tunisia were detected: Coxsackievirus A5 (CVA5) and Echovirus type 19 (E19). In addition, five patients presented enhanced susceptibility to the excretion of successive EV serotypes, and one patient exhibited a co-infection. A possible recombination event was identified in one patient involving Coxsackievirus B5 (CVB5), Coxsackievirus A9 (CVA9) and Coxsackievirus B1 (CVB1) sequences. Phylogenetic analysis showed close genetic relationships with European, American and Asian strains. These findings underscore the dynamic nature of EV circulation and the importance of ongoing molecular surveillance to detect emerging serotypes and guide public health strategies
Refining patient selection for transcatheter tricuspid interventions: the role of the GLIDE Score in the evolving therapeutic landscape
No full textInternational audienc
DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies using <i>in vitro</i> tools
No full textInternational audiencePathogenic Leptospira species can survive and thrive in a wide range of environments. Distinct environments expose the bacteria to different temperatures, osmolarities, and amounts and sources of nutrition. However, leptospires are mostly cultured, in a laboratory setting under in vitro conditions that do not reflect natural environments. This constraint on laboratory cultures limits the applicability of in vitro studies to the understanding of even simple pathogenic processes. Here we report, investigate, and identify a medium and conditions that mimic the host environment during leptospirosis infection, expanding the available in vitro tools to evaluate leptospiral pathogenesis. We quantified genome-wide gene expression of pathogenic Leptospira interrogans cultured in different in vitro media compositions (EMJH, DMEM, EMEM, and HAN). Using EMJH as standard, we compared gene expression in these compositions to genome-wide gene expression gathered in a host environment: whole blood (WB) of hamsters after infection with pathogenic leptospires. Leptospires cultured in DMEM and EMEM media shared 40% and 47% of all differentially expressed genes (DEGs) of leptospires present within WB (FDR<0.01), while leptospires cultured in HAN media only shared 20% of DEGs with those from WB. Furthermore, gene and pathway expression of leptospires cultured on DMEM and EMEM media exhibited a better correlation with leptospires grown in WB, including promoting expression of a similar leptospiral lipid A profile to the one identified directly in host tissues. Taken together, these results indicate that commercial cell-culture media EMEM or DMEM are better surrogates for in vivo pathogenic studies than EMJH or HAN media in Leptospira. These alternative culture conditions, using media that are a standard supply worldwide, provide a reproducible and cost-effective approach that can accelerate research investigation and reduce the number of animal infections necessary for basic research of leptospirosis
A Functional Intronic Variant of LILRB1 Associated with Clinical Malaria in the Senegalese Population
No full textInternational audienceBackgroundMalaria remains a major health challenge in sub-Saharan Africa despite extensive control measures. Host genetic variation influences susceptibility, but the role of inhibitory receptors such as LILRB1—targeted by Plasmodium falciparum RIFINs—remains unclear. We investigated whether regulatory variants in LILRB1 modulate malaria risk.MethodsRegulatory variants were prioritized from African expression quantitative trait locus (eQTL) datasets by integrating linkage disequilibrium, chromatin accessibility, transcription factor binding, and immune cell–specific expression. Three non-coding variants (rs10416697, rs10423364, rs7246537) and one coding variant (rs1061680) were selected. Genotyping was performed in 267 Senegalese individuals (116 severe malaria, 74 mild malaria, 77 healthy controls). Logistic regression adjusted for age assessed genetic associations. The effect of rs7246537 on promoter activity was tested using luciferase assays.ResultsAmong 10,110 candidate eQTLs, 49 were associated with LILRB1 expression in African populations; three overlapped open chromatin near the distal promoter. Only rs7246537 showed significant association with malaria: allele A carriers had lower risk of clinical malaria (OR = 0.50, 95% CI: 0.28-0.88, p = 0.0165) and cerebral malaria (OR = 0.44, 95% CI: 0.22-0.86, p = 0.0176). rs7246537 colocalized with a YY1-binding site, and luciferase assays confirmed allele-specific effects, with the A allele driving twofold lower promoter activity compared with the G allele.Conclusionsrs7246537 is a functional regulatory variant that reduces malaria susceptibility in Senegalese populations by modulating LILRB1 expression. These findings underscore the importance of non-coding variants and inhibitory immune pathways in malaria pathogenesis
Caractérisation des phénotypes inflammatoires sanguins dans la BronchoPneumopathie Chronique Obstructive et la pré-BPCO en population générale : la cohorte CONSTANCES
No full textInternational audienceIntroductionLes phénotypes inflammatoires basés sur les éosinophiles et les neutrophiles sanguins ont été associés à des expressions cliniques distinctes de l'asthme dans CONSTANCES. Nous avons caractérisé ces phénotypes chez les participants de la cohorte atteints de BronchoPneumopathie Chronique Obstructive (BPCO) ou de pré-BPCO.MéthodesÀ l'inclusion, les participants avec une BPCO ou une pré-BPCO, une numération formule sanguine complète, et sans déclaration d’asthme ont été sélectionnés. À partir d’auto-questionnaires (Symptômes respiratoires : S ; antécédents de bronchite chronique (BC) ou emphysème :À ; Facteur de Risque, tabagisme≥10 paquets-années : FDR) et de spirométrie (Obstruction bronchique (Obs) ; VEMS< 80% préd. sans Obs : PRISm), des sous-groupes cliniques ont été définis : BPCO avérée : Obs+S+A, BPCO probable : Obs+S sans A, BPCO possible : Obs sans S ni A, pré-BPCO clinique et/ou spirométrique (spiro) : FDR+PRISm et/ou S sans A. Les phénotypes paucigranulocytaire (réf. ), neutrophilique (NEU), éosinophilique (EOS) et mixte (M) ont été définis à partir de seuils sanguins de neutrophiles (< /⩾5000 cell/mm3) et d'éosinophiles (< /⩾250cell/mm3). La dyspnée a été évaluée par l’échelle mMRC. Les associations entre phénotypes inflammatoires et caractéristiques cliniques ont été étudiées à l'aide de modèles logistiques ajustés sur l'âge, le sexe, le statut tabagique, le niveau d'éducation, l'indice de défavorisation français, et l'indice de masse corporelle (IMC).RésultatsLes 9197 adultes avaient 48 ans d’âge moyen, 51% étaient des femmes, 40% fumeurs actuels, 17% avaient un IMC≥30kg/m2 ; 2,6%, 4,7% et 13% avaient une BPCO avérée, probable ou possible, et 31,4%, 33,2% et 15% une pré-BPCO clinique, spiro ou les deux. Les phénotypes paucigranulocytaire, neutrophilique (NEU), éosinophilique (EOS) et mixte (M) représentaient 70,5%, 7,6%, 19,4% et 2,5%.Dans toute la population étudiée (BPCO avérée, probable et possible, et pré-BPCO), les phénotypes NEU, EOS et M étaient significativement associés à un risque accru de sifflements avec essoufflement avec des odds-ratio ajustés (aOR) entre 1,30 et 1,68. Le phénotype EOS était associé à un moindre risque d’essoufflement au repos (aOR=0,78 [0,62-0,99]) et de dyspnée (mMRC≥2, aOR=0,84 [0,71-0,99]), et le phénotype NEU était associé à un risque accru (mMRC=1, aOR=1,23 [0,99-1,53]). Les phénotypes EOS et M étaient significativement associés à un risque accru de rhinite allergique actuelle avec des aOR de 1,74 et 1,43. Le phénotype M était aussi associé à un risque accru de réveil par sensation d’oppression thoracique (aOR=1,40 [0,995-1,95]). Le phénotype NEU était associé à un risque accru de BC déclarée (aOR=2,53 [1,42-4,48]).Les analyses des participants avec une BPCO avérée ou probable (n=675) montraient des associations similaires pour le phénotype M et sifflements avec essoufflement (aOR=2,84 [1,15-7,01]), EOS avec mMRC≥2 (aOR=0,64 [0,38-1,09]) et rhinite actuelle (aOR=1,68 [1,04-2,70]), et NEU avec BC (aOR=2,53 [1,21-5,30]).ConclusionChez les participants avec une BPCO ou pré-BPCO, chaque phénotype inflammatoire semble être associé à une expression clinique distincte. La caractérisation de ces phénotypes selon les sous-groupes cliniques est en cours
The food grade bacterium Lactobacillus helveticus VEL12193 promotes autophagy by releasing membrane vesicles
No full textInternational audienceBACKGROUND: Autophagy-related processes are crucial for maintaining cellular homeostasis in eukaryotic organisms. While alterations of these processes have been strongly linked to specific human disorders, including inflammatory bowel disease, neurodegenerative diseases, and metabolic syndromes, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms. Several studies indicate that gut microbiota or derived metabolites can modulate host autophagy at the gut mucosa level but also in peripheral organs. Here, we investigated in vitro and in vivo the potential of bacterial species commonly used in food fermentation (ferments) or for their health benefits (probiotics) to modulate host autophagy. METHODS: We screened 11 bacterial strains (lactobacilli and bifidobacteria) in vitro for autophagy induction in human epithelial cells. The most effective strain identified in vitro was then tested in vivo through long-term dietary supplementation in mice to confirm its pro-autophagic effects in the gut and a distant organ, the retina. RESULTS: In vitro screening of the 11 bacterial strains revealed a strain-dependent ability of bacteria to stimulate autophagy in human epithelial cells. The Lactobacillus helveticus strain VEL12193, isolated from cheese, emerged as the strongest autophagy inducer. Long-term dietary supplementation of mice with L. helveticus VEL12193 confirmed the pro-autophagic potential of this strain, as evidenced by autophagy stimulation in the gut mucosa but also at distance, in the retina. Finally, we identified membrane vesicles (MVs) from L. helveticus as a component involved in bacteria-induced autophagy in epithelial and immune cells, with lactate and specific lipid species potentially contributing to this effect. CONCLUSION: In this study, we present evidence that intervention with ferments/probiotics stimulates autophagy in multiple cell types and organs, and we show in vitro that MVs mediate this effect. Additionally, we identify L. helveticus VEL12193 as a promising candidate for the development of healthy-aging strategies
Hyperpolypharmacy in patients with chronic kidney disease and its impact on clinical outcomes
No full textInternational audienceHyperpolypharmacy (≥ 10 daily medications) is frequent in patients with chronic kidney disease (CKD), but its impact remains poorly characterized. This study, based on 3,011 non-dialyzed, non-transplant CKD outpatients from the CKD-REIN cohort (eGFR < 60 mL/min/1.73 m2) aimed to describe drug burden and assess associations between hyperpolypharmacy and adverse outcomes. Drug prescription, kidney function, adverse drug reactions (ADRs), hospitalizations, kidney replacement therapy and deaths before KRT were prospectively recorded over five years. Median age was 69 years and mean eGFR was 34 mL/min/1.73 m2. At baseline, 80% of the cohort had polypharmacy (≥ 5 daily medications), and 33% had hyperpolypharmacy. These rates remained stable over time. Diabetes, dyslipidemia, and a history of cardiovascular and respiratory diseases were the main contributors to hyperpolypharmacy status. Hyperpolypharmacy was associated with greater likelihoods of an ADR (hazard ratio (HR) [95% confidence interval (CI)] 1.21 [1.04-1.40]), hospitalization (HR [95%CI] 1.34 [1.18-1.51]) and death before KRT (HR [95%CI] 1.46 [1.17-1.82]). Among patients with eGFR ≥ 30 mL/min/1.73m2, hyperpolypharmacy also raised the risk of KRT initiation (HR [95%CI] 1.46 [1.00-2.13]), but not in those with eGFR < 30 (HR [95%CI] 0.94 [0.78-1.14]). These results identify hyperpolypharmacy as a significant concern in CKD and underscore the importance of regular medication reviews to reduce adverse outcomes
Gender differences in audience participation at infectious disease and microbiology conferences: a prospective observational study
No full textInternational audienceObjectivesIn medicine, women constitute a large proportion of the workforce but remain underrepresented in senior positions. Scientific conferences, critical for career advancement, reflect these inequities, with prior studies documenting gender gaps in invited speakers. However, less attention has been given to audience engagement, such as asking questions or making comments, which also enhances professional visibility. This study investigates gender differences in audience participation at infectious disease and clinical microbiology conferences, examining their prevalence, contextual variation, and potential structural drivers.MethodsThis prospective observational study recorded audience participations during national and international infectious disease and clinical microbiology conferences (October 2023–October 2024). Consortium members documented eligible sessions with traditional presentation–discussion formats, noting gender, role, and type of participation. Statistical analyses compared observed gender proportions with attendee distributions and examined factors associated with women's participation.ResultsA total of 298 sessions from 24 conferences were analysed, comprising 1873 audience participations. Women delivered 47.8% of presentations (n = 487/1018; 95% CI, 44.8–50.9%) but accounted for only 36.4% of participations (n = 681/1873; 95% CI, 34.2–38.5%), significantly fewer than men both in absolute terms and relative to their representation among attendees (p < 0.001). Multivariable analysis showed women were more likely to intervene when at least one moderator was female (OR = 1.44; 95% CI, 1.02–2.04%; p 0.037), with a stronger effect when all moderators were women (OR = 2.12; 95% CI, 1.40–3.24%; p < 0.001), and when the first question was asked by a woman (OR = 1.35; 95% CI, 1.00–1.81%; p 0.046).ConclusionOur findings highlight actionable levers to advance equity. Addressing participation gaps and raising awareness of gender disparities are essential to foster inclusive visibility, empower women, and strengthen scientific innovation
Long non-coding RNA UCA1 affects chromatin remodeling via SMARCA2-containing SWI/SNF complex in human colorectal cancer
No full textSummary Differential lncRNA expression has been correlated to clinical characteristics of colorectal cancers (CRC), which are the second leading cause of cancer-related deaths. LncRNA UCA1 plays a role in epigenetic gene regulation in diverse cancers. We studied CRC cell properties in CRISPR/Cas9 HT29-derived models and, interestingly, UCA1-depleted HT29 cells presented an increased stem-cell phenotype. We show that loss of UCA1 affected SWI/SNF chromatin remodeling complexes, which are previously shown to be involved in maintaining stem-cell properties. Not only was UCA1 permissive for induced SWI/SNF subunit SMARCA2 (BRM) expression upon chemo-drug treatment, but it also affected subunit compositions of SWI/SNF complexes by direct interaction of UCA1 with both ATP helicase BRM and BRG1. UCA1 is known to stimulate proliferation and decrease apoptosis, and we here show that it can restrain cells from a stem cell phenotype. The dual action of UCA1 revealed in this study highlights the complex actions of lncRNAs in cancer
Approches intégrées pour la surveillance de la filariose lymphatique et d'autres maladies infectieuses dans les îles du Pacifique
No full textInternational audienceLymphatic filariasis (LF) is a mosquito-borne neglected tropical disease targeted by the World Health Organization (WHO) for global elimination as a public health problem. Sixteen Pacific Island countries and territories were historically endemic, and eight have now met the WHO criteria for elimination as a public health problem. Elimination as a public health problem does not imply zero transmission. Rather, it denotes that LF prevalence has been reduced below a defined threshold at which community transmission can be sustained. Following validation of elimination, the WHO recommends post-validation surveillance (PVS) to detect potential re-emergence of LF as a public health problem. However, implementing PVS is challenging in Small Island Developing States with dispersed populations, limited workforce capacity, resource constraints, and competing health priorities. The ‘Voices and Visions: Building Partnerships for Integrated Serosurveillance of LF and Other Infectious Diseases in the Pacific Islands’ meeting was held in Brisbane, Australia, from 8–10 July 2025. Fifty-one delegates, including Pacific LF programme managers, WHO representatives, global health partners, and academic researchers, reviewed regional PVS progress, discussed the newly released WHO guidelines for the implementation, monitoring, and evaluation of PVS, planned for PVS implementation, and explored novel multiplex bead assay (MBA) serological analysis methods to strengthen regional coordination for its development as a public health tool. Five broad themes emerged. First, the new WHO Monitoring and Epidemiological Assessment of Mass Drug Administration in the Global Programme to Eliminate Lymphatic Filariasis: A Manual for National Elimination Programmes, 2nd edn needs to be operationalised to meet decision-making needs across diverse Pacific settings. Second, integrating LF-PVS with existing surveys and health service activities could improve efficiency and long-term sustainability. Third, regional coordination and alignment of funding cycles will require high-level collaboration. Fourth, community engagement is essential to strengthen demand for PVS. Finally, while at an early stage and with further evidence needed, MBA laboratory methods hold promise for cost-effective, feasible integrated multi-pathogen serosurveillance