Antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) replication to undetectable levels but does not eliminate HIV-1 reservoirs, which persist in memory CD4+ T-cells of various antigenic specificities. Hepatitis C virus (HCV) coinfection is associated with an increase in HIV-DNA burden, but whether HCV-specific CD4+ T-cells are susceptible to HIV-1 infection and harbour replication-competent HIV reservoirs upon HCV resolution is unknown. In this cross-sectional study, we examined the impact of HCV infection on CD4+ T-cell susceptibility to HIV-1 infection in vitro and reservoir persistence during ART in subjects with chronic HCV infection and uninfected controls (n = 20/group) and longitudinally in one ART-treated HCV+HIV+ individual who spontaneously resolved multiple episodes of HCV infection. Memory CD4+ T-cells from subjects with chronic HCV exhibited superior permissiveness to productive HIV-1 infection in vitro (p = 0.03) compared to uninfected. This was proportional to plasma HCV-RNA levels (p = 0.046; r = 0.491). HCV-specific CD4+ T-cells distinguished from other antigenic specificities (e.g., Cytomegalovirus) by a CCR5+ (HIV-1 co-receptor), CXCR6+ (liver-homing marker) and CCR6+ (Th17 marker) phenotype and supported productive HIV-1 infection in vitro. In the HCV+ HIV+ subject, HCV-specific CD4+ T-cells carried replication-competent reservoir during acute HCV reinfection, with integrated HIV-DNA persisting in these cells upon HCV clearance. We provide evidence that HCV-specific CD4+ T-cells are targets of integrative HIV-1 infection and carry proviruses that persist during ART despite HCV resolution. Canadian Institutes of Health Research (CIHR) (PJT-173467, PJT-153052, PJT-178127, PJT-195736, HB2-164064, BR4-197730, MOP135260, FDN-143270, CTN222 and NHC142832), the National Institutes of Health (NIH) (U19AI159819), and Fonds de recherche du Québec-Santé (FRQS)-Réseau SIDA/maladies infectieuses.
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Surveillance of arboviral vectors and screening for probable infection is very important for the planning of vector control programs, especially in countries where these activities are just beginning. In the present study, we conducted mosquito surveillance at 26 locations predicted to be at risk (according to our recently published study using Machine learning) in the Marrakech-Safi region of central Morocco. The field studies were conducted for six consecutive months, from April to October, in 2019 and 2021. Two different methods were used to collect adult mosquitoes, human landing catches (by mouth aspirator), and CDC miniature light traps; larvae and pupae were collected using dippers. A total of 1907 mosquitoes were collected, belonging to 15 species across five genera (Aedes, Culex, Culiseta, Anopheles, and Coquillettidia). Out of the 1907 mosquitoes that were sampled, 53.7% (1025/1907) were in the larval stage, 42.8% (818/1907) were adults, and the remaining 3.3% (64/1907) were pupae. Among the collected and identified adults, the females represented 96.6% and blood-fed females accounted for 55.9%. The adult mosquitoes were screened for five arboviruses: dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), Rift Valley fever virus (RVFV), and West Nile virus (WNV) by using RT-qPCR, and a pool of Cx. pipiens from Tabia (Station 14) was positive for WNV. This is the first detection of WNV in Cx. pipiens or any other mosquito species from central Morocco. The detection of several vectors within the region suggests a risk for arboviral transmission in central Morocco and appeals for entomological vigilance and the urgent need to undertake and enhance periodic surveillance campaigns in the region.
Following a first male urinary tract infection (mUTI), systematic investigation for predisposing factors is called for, as mUTIs frequently arise secondarily to anatomical or functional urinary tract abnormalities. Although no international consensus defines a minimal etiological work-up, guidelines from the French (AFU) and European (EAU) Associations of Urology provide a clinical framework. First-line assessment comprises a targeted history (laying emphasis on macroscopic hematuria and lower urinary tract symptoms, LUTS), digital rectal examination (DRE), the International Prostate Symptom Score (IPSS), and urinary tract ultrasonography with post-void residual (PVR) measurement. LUTS, classified as storage (urgency, frequency), voiding (weak stream, straining), or post-micturition (incomplete emptying) may indicate benign prostatic hyperplasia (BPH), the leading aetiology in men over 50. Ultrasound evaluates prostate volume, bladder morphology, and PVR; voiding diaries complement assessment when storage LUTS predominate. Alpha-blockers represent first-line therapy for BPH-related LUTS. Routine PSA testing following mUTI is not recommended, as elevations are non-specific: prostatitis may raise PSA independently of malignancy, and levels can remain elevated up to three months post-infection. No association exists between a first mUTI and prostate cancer, nor between PSA and UTI recurrence. Second-line referral is indicated for pyelonephritis, urinary retention, macroscopic hematuria, IPSS >7, PVR >100 mL, recurrent UTI, age under 40, or imaging abnormalities. Cross-sectional imaging (CT or MRI) is reserved for suspected obstruction, severe presentations, or treatment failure. This stratified approach optimizes cost-effectiveness, ensuring identification of underlying pathology (BPH, urolithiasis, or malignancy) while avoiding unnecessary investigations.
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Recent global epidemics and pandemics have highlighted the need for adequate diagnostic capacities to respond to emerging threats. Strengthening operational capacities can lead to improved preparation; investing in emergency response infrastructure may diminish progression of outbreaks and prevent escalation. An email-linked survey was sent January-March-2025 to two global infectious disease surveillance networks' (GeoSentinel and TropNet) participating clinics assessing capacity for Oropouche virus (OROV) diagnostic testing. Data on testing capacity for other arboviruses was also requested. Responses were obtained for 58 GeoSentinel/TropNet sites (58/104, 55.8%): 50% responding sites (29/58) had OROV diagnostic testing available at a public reference laboratory; 23 sites (40%) had capacity for OROV RNA detection; 10 sites (17%) had OROV serological testing onsite. Estimated median turn-around times from phlebotomy-molecular OROV results were 4 days onsite and 6 days at the reference laboratory. Viral culture was available onsite at 9% of sites (at the reference laboratory for 26%). Molecular diagnostics availability for other arboviruses onsite showed >50% could test for at least one other arbovirus: dengue virus (31/58, 53%), chikungunya virus (29/58, 50%), West Nile virus (22/58, 38%) and yellow fever virus (12/58, 21%). Onsite serologic testing for non-OROV arboviruses was available at 39/58 sites (67%). The survey identified potential weaknesses in novel pathogen preparedness with respect to diagnostic capacity for OROV testing at specialized travel medicine clinics participating in two international networks. These findings provide an opportunity to implement measures to improve communication and planning and to strengthen diagnostic infrastructure prior to future outbreaks.
Receptors that bind antibodies are essential for protective adaptive immune responses against antibody-opsonized pathogens, yet their engagement by antibody-autoantigen complexes can drive chronic inflammation in autoimmune diseases. Megakaryocytes, the precursor cells of platelets, express such receptors. However, their response to immunoglobulin G antibodies remains unclear. We used both systemic lupus erythematosus and COVID-19 as relevant examples of autoimmune and infection-driven contexts in which antibodies are involved to characterize human and mouse megakaryocyte responses. We found that megakaryocytes internalized immune complexes composed of autoantigens or SARS-CoV-2. In both human and mouse megakaryocytes, immune complexes triggered the release of chemokines and procoagulant extracellular vesicles. This process required FcγRIIA engagement, downstream Syk (spleen tyrosine kinase) signaling, and protein translation. A detailed analysis revealed that megakaryocyte-derived extracellular vesicles did not contain organelles and were largely indistinguishable from a subset of small-sized extracellular vesicles released by activated platelets. In FcγRIIA-transgenic mice, we analyzed megakaryocytes in both the bone marrow and lungs in a lupus model, whereas megakaryocytes were examined in the lungs in a COVID-19 model. In all cases, immunoglobulins were detected in close proximity to FcγRIIA-expressing megakaryocytes. Notably, the chemokine CXCL2 was increased in FcγRIIA-expressing mice under disease conditions. Tissue spatial analysis revealed that CXCL2 predominantly localized to megakaryocytes, supporting these cells as a major source. Furthermore, SARS-CoV-2 stimulated megakaryocytes to release CXCL2 only in the presence of IgG from SARS-CoV-2 immune individuals, and this response was strictly dependent on FcγRIIA expression. These findings suggest that megakaryocytes contribute to adaptive immune responses through FcγRIIA-mediated signaling.
Advanced age is a major determinant of adverse outcomes during acute infections, yet the immunological mechanisms by which aging alters immune regulation and shapes disease trajectories remain poorly understood. Using SARS-CoV-2 infection as a model of acute viral challenge, we investigated how aging alters myeloid responses in the lungs. Across infected mouse models and human cohorts, disease severity was associated with a pronounced shift in myeloid balance, characterized by an increased neutrophil-to-monocyte ratio. Neutrophils exhibited prolonged retention within the pulmonary microvasculature and formed large co-aggregates with monocytes. In parallel, severe disease was associated with a defect in classical monocyte activation in the lungs, notably through reduced PD-L1 upregulation. This defect was not observed in the circulation, indicating tissue-dependent dysregulation of inflammatory and regulatory markers. Aging further accentuated this imbalance. Both aged mice and elderly patients displayed a reduced proportion of PD-L1-expressing lung monocytes, despite enhanced pulmonary neutrophil recruitment. This age-associated alteration distinguished severe from non-severe disease and characterized a maladaptive myeloid response to acute viral challenge. Together, these findings identify impaired, compartment-specific myeloid immune regulation as a central feature of age-related vulnerability to severe infection. They highlight that tissue-dependent regulatory failure compounds inflammatory excess as a key determinant of disease outcome and suggest that restoring myeloid regulatory function may offer therapeutic benefit in older individuals during acute respiratory infections.
The occurrence of foreign body (FB) infections in patients with Staphylococcus aureus bacteraemia (SAB) can lead to serious complications. We therefore sought to evaluate the host risk factors and bacterial determinants associated with FB infection following SAB. We retrospectively included patients hospitalized with a SAB and carrying FB, over a four-year period. Factors associated with FB infection were assessed with multivariable logistic regression analysis. Bacterial determinants (lineage and virulence factors) were determined using whole genome sequencing. We included 104 patients of whom 40 patients (38.5%) with FB infection. Factors associated with FB infection were community-acquired SAB (OR = 3.8; 95% confidence interval, CI [1.36-10.59]; p = 0.011), Charlson's score >3 (OR = 0.39; 95% CI [0.16.-0.99]; p = 0.048 and unknown source of infection (OR = 3.54; 95% CI [1.34-9.33]; p = 0.011). No clonal complex or virulence gene was associated with a risk of FB infection in patients with SAB. FB infection is frequent in patients with SAB, particularly when the bacteremia is community-acquired. Our results suggest that bacterial characteristics (clonal complex or virulence factors) are not involved in the occurrence of FB infection in patients with SAB.
Respiratory Syncytial Virus (RSV) can cause severe illness in adults, leading to respiratory and non-respiratory complications, functional decline, hospitalisation, and death. This study describes French patients aged ≥50 years hospitalised with RSV (2015-2022) and their care pathways, including hospitalisation and outpatient healthcare use and costs. Data were extracted from the French National Health Data System (SNDS). Patients were classified into four risk groups (high: immunocompromised; medium: underlying predisposition; other; no comorbidities) and four age groups (50-59, 60-64, 65-74, ≥75 years). Healthcare use (laboratory tests, imaging, pharmacy, GP visits, rehospitalisations) and costs were analysed across three periods: 60-30 days pre-hospitalisation (reference period), index hospitalisation, and 30 days post-hospitalisation. We identified 15,509 RSV-related hospitalisations for 15,169 adults ≥50 years. Median age was 80 years, with age ≥75 years comprising 61.7% of the cohort. 15.9% were high risk, 71.4% medium risk, 4.8% other, and 7.8% had no comorbidities. Intensive care was required in 25.4% of cases. In-hospital mortality was 8.5%, with an additional 3.8% dying within 30 days post-discharge. Rehospitalisation occurred in 17.8% of patients, nearly half for cardiorespiratory causes. Median index hospitalisation cost was €4,252 (Q1; Q3: €3,077; €7,007), and post-hospitalisation costs increased across all ages and risk profiles compared to the reference period. RSV imposes a substantial hospitalisation and cost burden in adults ≥50 years, especially older patients and those with comorbidities. Expanded preventive vaccination strategies could help reduce this impact.
Current guidelines for the management of meticillin-susceptible Staphyloccocus aureus bloodstream infection/bacteraemia (SAB) recommend intravenous (flu)cloxacillin as the first-line treatment. This is based on decades of clinical practice. The high acute kidney injury rates seen with (flu)cloxacillin in the recently published SNAP trial, which is the largest randomized clinical trial ever in S. aureus bacteraemia (SAB), shows us the need to regularly test and question our usual clinical practice. Acute kidney injury is common in SAB when high doses of (flu)cloxacillin are used. The contribution of (flu)cloxacillin to developing or exacerbating acute kidney injury is likely to have been under recognized until now. Caution needs to be taken with (flu)cloxacillin. Cefazolin provides a safer and equally efficacious treatment for SAB. We discuss how this new evidence might be combined with our existing knowledge and the results of the CloCeBa trial to guide us how to appropriately manage our patients.
As antiretroviral treatment indications evolved, an increasing proportion of patients have been treated; since 2017, most patients receive antiretroviral treatment, irrespective of their CD4 count, in French Guiana and neighboring countries. In this context, we aimed to model the epidemic and to study the evolution of the estimates of the intervals between HIV-infection and HIV diagnosis in French Guiana. The study was descriptive and comparative. Anonymous data from all persons in the DAT'AIDS HIV cohort based on quality-controlled clinical records was aggregated into yearly statistics between 2000 and 2023. We estimated year of infection using the rate of CD4 decline between the CD4 count at diagnosis and the estimation of the CD4 count at the time of HIV infection. The HIV modelling platform version 3.0.2 used the annual number of new HIV infections, the number of new AIDS cases, the number of new HIV infections that had AIDS, and CD4 strata to compute incidence, number of diagnosed and undiagnosed persons, and diagnostic delay. All indicators improved markedly over time. Incidence declined, diagnostic delay declined, the proportion of undiagnosed patients declined, and deaths declined. However, the estimated interval between HIV infection and diagnosis was heterogenous between groups: It was about 2 years longer among males than among females, and it was about 3 years longer among Surinamese or Brazilian immigrants. Overall, 5% of all persons with HIV were undiagnosed, 9% of diagnosed persons were not on antiretroviral therapy and 6% of those on antiretroviral therapy were in virological failure. For a population of about 4,000 persons with HIV this represents a residual source of transmission. The scaling up of testing, antiretroviral treatment, and preexposure prophylaxis has led to remarkable progress. Nevertheless, further shrinking the reservoir of undiagnosed infections and maximizing the proportion of successfully treated persons living with HIV is still likely to further improve control of the epidemic. This is not a clinical trial.
Genital herpes, caused by Herpes simplex virus (HSV), is a sexually transmitted infection that is the leading cause of genital ulcers in many countries around the world. Although many treatments exist for this condition, their prioritization is often unclear. This study aimed to develop French national recommendations for the treatment of genital herpes in both immunocompetent and immunocompromised (ID) adults, pregnant women (PW), and adolescents. These guidelines were developed by a multidisciplinary working group (WG) following the methodology of the Haute Autorité de Santé. No conflicts of interest were declared. A systematic review (SR) of the literature was conducted using PubMed and Embase, covering publications up to June 1, 2024. The protocol was published in PROSPERO (CRD42023399760) after drafting and submission to a multidisciplinary panel of reviewers. Risks of bias were assessed using various tools. A total of 127 sources were analysed, including randomised controlled trials (RCTs), SRs, and guidelines. Recommendations were formulated for oral, parenteral, and topical treatments. Key management strategies for primary infection and recurrence were summarised in a clinical algorithm. The methodological quality of the included evidence varied, and many studies were dated. Data gaps were identified for specific populations, particularly PW and ID. These new French guidelines provide updated, evidence-based recommendations derived from a systematic review for the management of genital herpes across diverse populations and clinical scenarios.
In 2026, COVID-19 vaccination during pregnancy remains mainly recommended. However, despite strong safety data, uptake of COVID-19 vaccination during pregnancy remains suboptimal in many settings. Evidence, uncertainty and priorities should be discussed.
The fourth LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium was convened on December 15th, 2025, in Toulouse, France, to discuss recent advances in the understanding and management of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Pathophysiological mechanisms underlying SSc and SLE were discussed from a genetic perspective, with particular emphasis on the X-chromosomal TLR7/TLR8 locus and the interferon signaling pathway. Cellular aspects were explored, highlighting the critical roles of regulatory T cells (Tregs), exhausted T cells, macrophage polarization, and endothelial cells. At the translational research frontier, significant initiatives are underway within the framework of the European Autoimmunity Standardization Initiative (EASI) aimed at enhancing routine biomarker application for diagnosis, disease monitoring, and prognostic considerations. Emerging biomarker candidates promise potential for improving prognostic assessment and follow-up in lupus nephritis (e.g., urinary sCD163/creatinine ratio), cardiovascular complications and vasculopathy associated with SSc (e.g., dephosphorylated-uncarboxylated matrix Gla protein [dp-ucMGP] and endothelial progenitor cells), as well as therapeutic response evaluation (e.g., IGRA-PHA assays and proteomic methodologies). Therapeutically, a paradigm shift is underway with the development of efficacious mono- and multi-targeted antibody treatments alongside cellular therapies designed to eliminate B cells through chimeric antigen receptor (CAR) T cells or to re-establish immune regulation through Treg restoration. The integration of these therapeutic modalities necessitates further investigation to optimize individualized patient selection and management strategies. The multidisciplinary expert panel advocates for a comprehensive approach encompassing fundamental science, translational research, clinical expertise, and therapeutic innovation to advance in the management of these two complex syndromes.
Drug resistance testing may improve the management of people living with HIV (PLWH) in several scenarios in low- and middle-income countries (LMICs). To guide assay development, the WHO published a target product profile (TPP) outlining two priority use cases (scenarios) for genotypic resistance testing: (1) PLWH with confirmed virological failure (VF) on an integrase strand transfer inhibitor (INSTI)-based regimen, such as tenofovir (TFV) disoproxil fumarate, lamivudine (3TC), and dolutegravir (DTG) and (2) heavily treated PLWH, including infants and young children, with confirmed VF after receiving multiple regimens including a boosted protease inhibitor (PI). An additional potential scenario includes PLWH testing positive for HIV-1 while on pre-exposure prophylaxis (PrEP). To identify drug-resistance mutations (DRMs) most likely to influence clinical management of PLWH in each WHO TPP scenarios and to inform development of assays that detect individual DRMs and the interpretation of sequence-based assays, we reviewed prevalence and in vitro susceptibility data on HIV-1 DRMs in the Stanford HIV Drug Resistance Database associated with the nucleoside RT inhibitor (NRTI), nonnucleoside RT inhibitor (NNRTI), PI, and INSTI classes and the capsid inhibitor lenacapavir. In the first scenario, the most informative NRTI DRMs were K65R and M184V/I; and the most informative INSTI DRMs were G118R, N155H, Q148H/K/R, and R263K. In the second scenario, a broader spectrum of DRMs is likely to be clinically relevant, including additional NRTI DRMs, the PI DRMs associated with reduced susceptibility to darunavir, and the NNRTI DRMs associated with reduced susceptibility to etravirine and doravirine. In PLWH testing positive for HIV-1 despite PrEP, the most informative NRTI and INSTI DRMs overlap with those in the first scenario, together with the capsid DRMs reported in persons experiencing VF while receiving lenacapavir. As global ART programs increasingly rely on INSTI-based regimens, and as the number of heavily treated individuals and difficult-to-treat pediatric cases grows, many LMICs have begun introducing HIV drug resistance testing for patient management. Although sequence-based assays provide the most comprehensive information for managing individual PLWH, assays that detect individual DRMs are also likely to be highly useful in the three WHO TPP scenarios.
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β-lactam antibiotics are the most commonly used antibiotics to treat infection in critically-ill patients. The modalities of antibiotics reconstitution/preparation for continuous infusion are elaborated according to drug stability. In between 2 periods, a sustainable protocol for 4 common β-lactam antibiotics administration was implemented, consisting of preparing the highest stable concentration for continuous administration through a 50 mL syringe. Overall, 418 patients were treated (202 in 2024 and 216 in 2025), age, and SAPSII did not differed between both periods. A sustainable protocol implementation reduced the greenhouse gas emission (GHG) by 52% from 2760 [1380-4968]g to 1380 [552-2208]g/treatment, p < 0.0001. The global reduction of plastic consumed (syringes, tubing, solution bags, blister packs) was - 48% (-61 kg), and treatment cost was also reduced by 48% (-1324 €). The total nursing time for preparation was 145 h shorter during the second 6 months period. These results showed that implementation of a sustainable protocol for continuous β-lactam antibiotics can significantly reduce the environmental impact of antibiotic administration. A careful prescription of drug dilution, if continuous infusion of β-lactam antibiotics is used, can be efficient in reducing GHG emissions, consumables, waste, and costs.
COVID-19 pandemic has significantly impacted global health, particularly evident in the detection of lung lesions via chest computed tomography scans. This study investigates the role of biomarkers in lung injury among COVID-19 patients and patients with idiopathic pulmonary fibrosis (IPF). This single-center prospective study included 154 hospitalized and 10 outpatient COVID-19 patients, 62 IPF patients, and 40 healthy volunteers, and evaluated biomarkers of alveolar epithelial cell dysfunction, extracellular matrix (ECM) and fibroblast dysfunction, and macrophage/monocyte activation (Galectin-3, CXCL13). Findings were further validated in an independant confirmation cohort (DisCoVeRy trial). COVID-19 patients had higher levels of biomarkers compared to healthy controls, except for SP-D. Compared to IPF patients, COVID-19 patients had significantly higher plasma levels of OPN, Galectin-3 and CXCL13 at admission. Elevated CXCL13 and Galectin-3 levels in COVID-19 were associated with greater lung injury. Multivariate logistic regression and Kaplan Meier analysis confirmed the role of CXCL13 in predicting severe lung injury (odd ratio 3.17, 95% CI 1.03-9.76) and in-hospital mortality (p = 0.04), with consistent results observed in the confirmation cohort. COVID-19 is characterized by increased ECM and macrophage activation biomarkers compared with IPF. CXCL13 may serve as a relevant biomarker for assessing lung injury and improving risk stratification at hospital admission.