Background Preparedness for emerging pathogens can be strengthened by leveraging lessons from COVID-19 therapeutic trials. The COVERAGE Africa trial (NCT04920838, ANRS033, 2021-22), one of the few COVID-19 therapeutics trials conducted in resource-limited settings, sought to identify early treatment strategies for ambulatory patients at-risk for severe disease in Guinea and Burkina Faso. This implementation research, based on secondary data from the Burkina Faso sites, aimed to document the trial's implementation and to identify the factors that influence it.Methods The PEARLES framework was applied to identify and classify indicators related to political, economic, administrative, regulatory, logistical, ethical and societal factors influencing trial's implementation. Data drawn from regulatory documents, weekly internal reports, financial documents, programmatic data, equipment receipt slips, contracts and logistical documents, as well as the dynamic of recruitment in the trial were analysed to describe these indicators as either facilitators-supporting the trial's execution as planned-or barriers-causing delays, hindering progress or leading to deviations.Results Barriers to trial implementation included: (1) the trial's adaptive design, needing iterative protocol amendments leading to regulatory delays that were aggravated by the misalignment between national and international care guidelines, (2) funding disbursement lags, (3) challenges in participants' enrolment due to inadequate screening sites organisation that compromised patient confidentiality and (4) significant increase in the refusal rate during the trial, rising from 3% in 2021 to 38% in 2022. Despite these constraints, mitigation strategies such as prefinancing, mobile team deployment and site renovations enabled effective trial delivery. Strong governmental support, rapid mobilisation of funders and flexibility in staff deployment facilitated trial's implementation.Conclusion To enhance trial readiness in emergency situations, countries need political commitment, preapproved protocols, dedicated research infrastructure and rapid funding mechanisms. Stakeholder engagement and preparedness exercises are essential to strengthen clinical trial capacity in low-resource settings particularly across sub-Saharan Africa.

BACKGROUND:Lassa fever is one of the most important viral haemorrhagic fevers, yet post-discharge sequelae remain inadequately characterised. Previous studies have been limited by small sample sizes and unsystematic assessments. We aimed to describe post-discharge sequelae in Lassa fever survivors and explore the effect of disease severity on sequelae patterns. METHODS:LASCOPE was a prospective study of patients with PCR-confirmed Lassa fever hospitalised at Federal Medical Centre Owo, Owo, Nigeria, between April 23, 2018, and Feb 17, 2023. All patients who provided informed consent were included, with no age restriction. Severe disease was defined as the presence of at least one of the following during the acute phase: National Early Warning Score version 2 score of 7 or higher, Kidney Disease Improving Global Outcomes stage 2 or higher, or Lassa virus PCR Ct value of less than 25. At hospital discharge, follow-up of survivors was planned for day 60 after admission, or before that, based on medical need. A systematic symptom assessment was done at each visit. The main outcome was clinical remission, defined as complete absence of symptoms. Other outcomes were post-discharge death, symptom incidence, and prevalence of symptoms over time. Subgroup analyses were performed by age group (children aged <18 years or adults aged ≥18 years) and disease severity (severe or not severe). FINDINGS:Of 882 survivors (median age 32 years [IQR 22-46], 459 [52%] female and 423 [48%] male), post-discharge data were available for 807 (91%), with a total of 2603 person-months of follow-up. For three of 807 survivors with post-discharge information, only the vital status was collected. 736 (91%) of 807 reached clinical remission, with a median time to clinical remission of 19 days (95% CI 16-23) post discharge. The most frequently reported symptoms were asthenia (158 [20%] of 804), headache (148 [18%]), and post-exertional malaise (123 [15%]). Hearing symptoms were reported by only 17 (2%) of 804 survivors, which was substantially lower than previous studies. Disease severity did not affect time to remission. Six (1%) survivors died after hospital discharge. INTERPRETATION:Patient-reported symptoms suggest good recovery with few hearing or neurosensory disorders in most survivors of Lassa fever. Future research would benefit from extended follow-up periods and standardised diagnostic assessments, including objective audiometry, to further characterise the full spectrum of post-Lassa fever complications. FUNDING:Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, and French National Research Institute for Sustainable Development.

Background Sub-Saharan Africa faces persistent challenges in the timely detection of infectious disease outbreaks due to inadequate early warning and response systems. To address this gap, Senegal's Ministry of Health partnered with the Institut Pasteur de Dakar to establish the Senegalese Syndromic Sentinel Surveillance Network (4S Network) in 2012 a comprehensive surveillance system designed to identify epidemic-prone syndromes and enable rapid public health interventions. Methods We analysed data from the Senegalese 4S real-time sentinel syndromic surveillance network collected between 2015 (15 sites) and 2023 (27 sites). The network monitored four key febrile syndromes, including malaria, dengue-like syndromes, diarrheal syndrome, and influenza-like illness (ILI), via standardized WHO case definitions. Laboratory confirmation was achieved through molecular and serological testing of biological samples. Sentinel general practitioners submitted daily reports via a digital platform that facilitated real-time reporting and automated alert generation. We evaluated system performance through completeness, timeliness, temporal patterns, geographical distribution, and alert validation rates. Results During the nine-year surveillance period, the network documented 1,816,340 outpatient consultations, with febrile syndromes accounting for 11.7% of all visits and demonstrating notable annual fluctuations. Distinct regional patterns of infectious disease events were observed: ILI predominated in western regions, dengue-like syndromes were clustered in north-central areas, and malaria cases were concentrated in southeastern zones. The system demonstrated robust performance metrics, achieving 94.5% data completeness and 80.0% reporting timeliness. Of the 202 alerts generated, 51.0% received laboratory confirmation. Dengue virus circulation was documented in 2017, 2018, 2021, 2022, and 2023. Despite these successes, 37.1% of febrile cases remained etiologically unclassified. The system's early multidisciplinary investigation capabilities enabled swift outbreak containment and transmission control. Conclusion The 4S network validates the effectiveness and practical implementation of digital, real-time syndromic surveillance in Senegal. It successfully facilitated early outbreak detection and supported prompt public health responses. Although the system has significant potential for resource-constrained environments, addressing current operational limitations remains crucial for maximizing public health impacts. These findings provide strong evidence supporting the regional expansion of similar surveillance frameworks to enhance health security and epidemic preparedness throughout West Africa.

BACKGROUND:Long-term follow-up data on the travel-associated burden of vector-borne diseases (VBDs) are scarce. A prospective multi-site observational study was conducted to delineate the longitudinal course, symptom patterns, physical and mental burden and factors associated with prolonged illness in travellers after four VBDs. METHODS:Patients with confirmed travel-associated acute chikungunya, dengue, Zika or falciparum malaria were recruited at 15 GeoSentinel sites from 2016 to 2021. Persistent signs and symptoms were evaluated at 1, 3, 6, 12 and 18 months (M) post-diagnosis, using a multi-modular study questionnaire with quality of life (QOL) evaluated by 12-item short-form health survey (SF-12). Demographic, premorbid and acute disease characteristics were tested in multivariate analyses to determine factors associated with persistence of symptoms at M3. Missing data were imputed by rules and statistical methods. RESULTS:Among 273 patients enrolled, 35 (13%) had chikungunya, 110 (40%) dengue, 19 (7%) Zika and 109 (40%) falciparum malaria. Median age was 38 years (interquartile range 30-49), 148/273 (54%) were men. At M3, 24/35 (69%) of chikungunya, 27/110 (25%) of dengue, 8/19 (42%) of Zika and 12/109 (11%) of malaria patients had persistent symptoms. The proportion of symptomatic chikungunya patients was 18/35 (51%) at M6, mainly due to musculoskeletal symptoms including arthritis and stiffness. In dengue patients, fatigue and musculoskeletal symptoms without arthritis persisted until 1 year. Zika patients reported persisting headaches, musculoskeletal symptoms including arthritis and fatigue. One month after malaria, fatigue was the main persisting symptom, which resolved almost completely at M3. At M12, 6/35 (17%) of chikungunya, 5/110 (5%) dengue, 3/19 (16%) Zika and only 1/109 (1%) of malaria patients were still symptomatic.Impaired QOL was noted at M3 by 23/35 (66%) of patients with chikungunya, 20/110 (18%) with dengue and 6/19 (32%) with Zika but only 4/109 (4%) with malaria. Female sex, Zika, chikungunya and musculoskeletal symptoms during acute infection were associated with persistent M3 symptoms. CONCLUSIONS:Post-arboviral symptoms and impaired QOL persisted beyond 6 months after chikungunya, dengue and Zika. In contrast, post-malaria fatigue syndrome resolved within 3 months.

Introduction The Lassa virus (LV) causes Lassa fever (LF), a severe re-emerging disease. It affects several West African nations, with Nigeria having the greatest case burden. Currently, only supportive care and ribavirin are available for treatment. There is, however, little evidence on the efficacy of ribavirin in LF. Recent research found that in vivo plasma concentrations are likely insufficient for antiviral effects. Thus, new LF medicines are urgently required. Favipiravir, a broad-spectrum antiviral for pandemic influenza, has also being tested for other viruses. It is effective against LV in pre-clinical trials. The aim of this clinical trial was to evaluate the safety, tolerability and pharmacokinetics of repurposed favipiravir for LF. Methods LF patients (hospitalized and PCR confirmed) were recruited to this randomized controlled open-label phase II clinical trial in Nigeria’s Irrua Specialist Teaching Hospital and Federal Medical Centre Owo, the world’s biggest LF treatment centres. Patients were randomized in a 1:1 ratio to I.V ribavirin and oral favipiravir. Clinical assessments including ECG, and blood sampling for pharmacokinetics (PK) as well as virological, serological, immunological, haematological, biochemistry analyses were done during screening and thereafter until day 10. Results Between August 2021 and October 2022, 41 LF patients were randomized in the study. 36 participants completed follow-up. Treatment Emergent Adverse Events occurred on 16/20 (80%) on favipiravir and 14/21 (66.7%) on ribavirin and were similarly distributed between treatment arms. No severe or serious adverse events were observed under favipiravir. One life-threatening event occurred with ribavirin. PK analysis of favipiravir showed reliable exposure with maximum plasma concentration of 50.9 mg/L in steady state, half-life of 10.9 hours, and AUC(0-240h) of 9275mg/L*h. Conclusion These first clinical trial data on the safety, tolerability and pharmacokinetics of favipiravir as a treatment candidate for LF indicate good safety and tolerability. Further investigation into larger trials is underway.

IntroductionFin 2022 ont été détectés les 3 premiers cas équins d'infection à virus West Nile (WNV) et le premier cas humain d'infection à virus Usutu (USUV) en Nouvelle Aquitaine (NA). Un consortium a entrepris des actions coordonnées de recherche One Health afin de préciser l'étendue de la circulation virale.Matériels et méthodesInvestigations réalisées en 2023 : distribution géographique et caractéristiques des cas confirmés et probables, humains et non humains, d'infections à WNV ou USUV ; enquêtes de séroprévalence équine et aviaire ; investigations entomologiques par Molecular Xenomonitoring.RésultatsHumains : du 4/07 au 1/10, 44 cas confirmés/probables d'infection à WNV et/ou USUV, dont 19 cas confirmés à WNV, 7 cas confirmés à USUV et 18 cas probables ou confirmés à WNV/USUV non différenciables ; 9 cas neuroinvasifs (tous à WNV) dont 2 sévères ; 11 donneurs de sang virémiques asymptomatiques détectés. Cas répartis en Gironde (n=31) dont 20 au sein de la métropole bordelaise, Charente Maritime (n=7), Charente (n=3), dans les Landes (n=2) et en Haute Vienne (n=1).Equidés : parmi 504 chevaux prélevés dans 40 écuries de Gironde avant la saison de transmission, 84 (17%) porteurs d'IgG anti-flavivirus en ELISA, dont 34 (7%) avec des anticorps neutralisants anti-WNV et 16 (3%) anti-USUV. Tous les séropositifs étaient localisés dans le blayais et la zone de la confluence Garonne-Dordogne. Du 4/08 au 15/11, 31 cas confirmés ou probables d'infection aiguë à WNV répartis en Gironde (n=24), Charente Maritime (n=6) et Charente (n=1).Oiseaux : du 01/08 au 21/09, 7 cas confirmés d'infection à WNV chez des cadavres en Charente Maritime, dont 5 dans l'avifaune captive (flamants du Chili d'un parc zoologique) et 2 dans l'avifaune sauvage résidente (1 autour des palombes et 1 pigeon ramier). Parmi 135 spécimens (pigeons, pies, corneilles) capturés en Gironde lors d'opérations de régulation, principalement dans la bande littorale allant du Bassin d'Arcachon à la pointe du Médoc, 78 (58%) porteurs d'anticorps neutralisants anti-WNV/USUV (sans différenciation par la technique utilisée).Vecteur : parmi 52 pools d'excréments de moustiques récoltés sur 13 sites répartis entre le blayais, la confluence Garonne-Dordogne et la métropole de Bordeaux, 39 (75%) porteurs de WNV et/ou USUV (WNV seul 25% ; USUV seul 8%). Tous les sites avaient un échantillon positif en RT-PCR pour au moins l'un des deux virus, dont 12/13 pour les deux. Culex pipiens était l'espèce majoritairement capturée et la plus souvent infectée. Les souches séquencées appartenaient au lignage 2 pour WNV et Africa 3 pour USUV.ConclusionLes résultats des actions conduites en 2023 ont notamment permis dès juillet au HCSP de recommander la sécurisation des dons de sang en Charente Maritime, avant la survenue de cas humains dans ce département, sur la base de données animales et humaines concordantes attestant de la circulation virale au sein d'un corridor territorial s'étendant jusqu'au Nord de la Gironde. Cela illustre concrètement l'utilité d'une démarche One Health pour informer précocement la décision en Santé Publique.Aucun lien d'intérêt

Abstract Background Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19. Methods Biological samples were obtained from hospitalized patients (15 severe, 37 critical at sampling) and 93 non-severe ambulatory cases. Our aims were to compare NET biomarkers, functional DNase levels, and explore mechanisms driving any imbalance concerning disease severity. Results Functional DNase levels were diminished in the most severe patients, paralleling an imbalance between NET markers and DNase activity. DNase1 antigen levels were higher in ambulatory cases but lower in severe patients. DNase1L3 antigen levels remained consistent across subgroups, not rising alongside NET markers. DNASE1 polymorphisms correlated with reduced DNase1 antigen levels. Moreover, a quantitative deficiency in plasmacytoid dendritic cells (pDCs), which primarily express DNase1L3, was observed in critical patients. Analysis of public single-cell RNAseq data revealed reduced DNase1L3 expression in pDCs from severe COVID-19 patient. Conclusion Severe and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration. Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016). Graphical Abstract

Background Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007 to 2022. Methods We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive dengue virus (DENV)-specific reverse-transcriptase polymerase chain reaction, positive NS-1 antigen and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high-titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 World Health Organization guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. Results This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: <1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%) and business (11.0%). The most frequent regions of acquisition were South East Asia (50.4%), South Central Asia (14.9%), the Caribbean (10.9%) and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. Conclusions A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pre-travel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long dengue) due to travel-related dengue.

Background Data on the presentation, management, and outcomes of Lassa fever (LF) in children are limited.Methods Description of the clinical and biological features, treatment, and outcomes of reverse transcriptase and polymerase chain reaction (RT-PCR)-confirmed LF in children aged under 15, enrolled in the LASsa fever clinical COurse and Prognostic factors in an Epidemic context (LASCOPE) prospective cohort study in Nigeria between April 2018 and February 2023.Results One hundred twenty-four children (aged under 12 months: 19; over 12 months: 105) were hospitalized with RT-PCR-confirmed LF. All received intravenous ribavirin. During follow-up, 99/124 (80%) had fever; 71/124 (57%) had digestive symptoms, vomiting (n = 56/122, 46%) and abdominal pain (n = 34/78 aged >= 5 years, 44%) more often than diarrhea (n = 19/124, 15%); 17/124 (14%) had hemorrhagic signs; 44/112 (39%) had a hematocrit lower than 25%, of whom 32/44 (73%) received transfusions; 44/88 (50%) developed hypotension; 18/112 (16.1%) developed kidney disease improving global outcome (KDIGO) >= 2 acute kidney injury; 10/112 (8.9%) had KDIGO 3 acute kidney failure; 4/124 (3.2%) underwent renal replacement therapy. Seven children died, including 4 aged under 12 months (case fatality rate: under 12 months-22%, 95% confidence interval (CI): 7%-48%; over 12 months-2.9%, 95% CI: 0.7%-8.7%). In univariable analysis, age (P = .003), impaired consciousness (P = .026), and Lassa RT-PCR Ct value (P = .006) were associated with Day 30 mortality.Conclusions The fatality rate for children over 12 months hospitalized with LF was lower than that previously reported for adults. Hypotension and acute kidney injury were the most frequent organ dysfunctions. Bleeding was relatively infrequent. Anemia and the need for transfusion were common, the relative contribution of ribavirin-induced hemolysis being unknown.

Transplant Infectious DiseaseVolume 26, Issue 1 e14235 LETTER TO THE EDITOR Failure of favipiravir to treat chronic norovirus infection in a kidney-transplant patient Amandine Darres, Amandine Darres Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France Department of Vascular Biology, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceSearch for more papers by this authorArnaud Del Bello, Arnaud Del Bello orcid.org/0000-0003-3115-868X Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France Department of Vascular Biology, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceSearch for more papers by this authorOlivier Marion, Olivier Marion Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, FranceSearch for more papers by this authorXavier de Lamballerie, Xavier de Lamballerie Unité des Virus Émergents, INSERM-1207, IRD-190, Aix-Marseille University, Marseille, FranceSearch for more papers by this authorDenis Malvy, Denis Malvy Service des maladies infectieuses et tropicales, CHU de Bordeaux, Bordeaux, France Inserm UMR 1219, IRD EMR 271, Bordeaux Population Health, Université de Bordeaux, Bordeaux, FranceSearch for more papers by this authorJacques Izopet, Jacques Izopet INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, France Department of Virology, Toulouse University Hospital, Toulouse, France Université Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorNassim Kamar, Corresponding Author Nassim Kamar [email protected] orcid.org/0000-0003-1930-8964 Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, France Université Toulouse III Paul Sabatier, Toulouse, France Correspondence Nassim Kamar, Department of Nephrology and Organ Transplantation, CHU Toulouse Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. Email: [email protected]Search for more papers by this author Amandine Darres, Amandine Darres Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France Department of Vascular Biology, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceSearch for more papers by this authorArnaud Del Bello, Arnaud Del Bello orcid.org/0000-0003-3115-868X Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France Department of Vascular Biology, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceSearch for more papers by this authorOlivier Marion, Olivier Marion Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, FranceSearch for more papers by this authorXavier de Lamballerie, Xavier de Lamballerie Unité des Virus Émergents, INSERM-1207, IRD-190, Aix-Marseille University, Marseille, FranceSearch for more papers by this authorDenis Malvy, Denis Malvy Service des maladies infectieuses et tropicales, CHU de Bordeaux, Bordeaux, France Inserm UMR 1219, IRD EMR 271, Bordeaux Population Health, Université de Bordeaux, Bordeaux, FranceSearch for more papers by this authorJacques Izopet, Jacques Izopet INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, France Department of Virology, Toulouse University Hospital, Toulouse, France Université Toulouse III Paul Sabatier, Toulouse, FranceSearch for more papers by this authorNassim Kamar, Corresponding Author Nassim Kamar [email protected] orcid.org/0000-0003-1930-8964 Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse, France Université Toulouse III Paul Sabatier, Toulouse, France Correspondence Nassim Kamar, Department of Nephrology and Organ Transplantation, CHU Toulouse Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. Email: [email protected]Search for more papers by this author First published: 05 January 2024 https://doi.org/10.1111/tid.14235Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Gäckler A, Struve C, Mülling N, et al. Norovirus Infections in Kidney Transplant Recipients. Transplantation. 2021; 105(12): 2655-2660. 10.1097/TP.0000000000003708 PubMedWeb of Science®Google Scholar 2Keefer L, Daud A, Ison M. Approach to patient reported outcome measures selection and implementation in a chronic norovirus clinical efficacy trial for patients after solid organ transplant. Transpl Infect Dis. 2023; 25(4):e14099. 10.1111/tid.14099 PubMedWeb of Science®Google Scholar 3Ruis C, Brown L-A, Roy S, et al. Mutagenesis in norovirus in response to favipiravir treatment. N Engl J Med. 2018; 379(22): 2173-2176. 10.1056/NEJMc1806941 PubMedWeb of Science®Google Scholar 4Arias A, Thorne L, Goodfellow I. Favipiravir elicits antiviral mutagenesis during virus replication in vivo. eLife. 2014; 3:e03679. 10.7554/eLife.03679 CASPubMedWeb of Science®Google Scholar 5Guedj J, Piorkowski G, Jacquot F, et al. Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques. PLoS Med. 2018; 15(3):e1002535. 10.1371/journal.pmed.1002535 PubMedWeb of Science®Google Scholar Volume26, Issue1February 2024e14235 ReferencesRelatedInformation

BACKGROUND:Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children.METHODS:Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively.RESULTS:A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases.CONCLUSION:Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes.

Background Tixagevimab and cilgavimab (AZD7442) are two monoclonal antibodies developed by AstraZeneca for the pre-exposure prophylaxis and treatment of patients infected by SARS-CoV-2. Its effectiveness and safety in patients hospitalized with COVID-19 was not known at the outset of this trial.Methods DisCoVeRy is a phase 3, adaptive, multicentre, randomized, controlled trial conducted in 63 sites in Europe. Participants were randomly assigned (1:1) to receive placebo or tixagevimab-cilgavimab in addition to standard of care. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale. Several clinical, virological, immunological and safety endpoints were also assessed.Findings Due to slow enrolment, recruitment was stopped on July 1st, 2022. The antigen positive modified intention-to-treat population (mITT) was composed of 173 participants randomized to tixagevimab-cilgavimab (N = 91) or placebo (N = 82), 91.9% (159/173) with supplementary oxygen, and 47.4% (82/173) previously vaccinated at inclusion. There was no significant difference in the distribution of the WHO ordinal scale at day 15 between the two groups (odds ratio (OR) 0.93, 95%CI [0.54-1.61]; p = 0.81) nor in any clinical, virological or safety secondary endpoints. In the global mITT (N = 226), neutralization antibody titers were significantly higher in the tixagevimab-cilgavimab group/patients compared to placebo at day 3 (Least-squares mean differences (LSMD) 1.44, 95% Confidence interval (CI) [1.20-1.68]; p < 10−23) and day 8 (LSMD 0.91, 95%CI [0.64-1.18]; p < 10−8) and it was most important for patients infected with a pre-omicron variant, both at day 3 (LSMD 1.94, 95% CI [1.67-2.20], p < 10−25) and day 8 (LSMD 1.17, 95% CI [0.87-1.47], p < 10−9), with a significant interaction (p < 10−7 and p = 0.01 at days 3 and 8, respectively).Interpretation There were no significant differences between tixagevimab-cilgavimab and placebo in clinical endpoints, however the trial lacked power compared to prespecified calculations. Tixagevimab-cilgavimab was well tolerated, with low rates of treatment related events.Funding Trial registration: [ClinicalTrials.gov][1] [NCT04315948][2]. Registered on 13 March 2020 updated on 22 April 2021.### Competing Interest StatementM.H. reports grants from The Belgian Center for Knowledge (KCE), the Fonds Erasme-COVID-Université Libre de Bruxelles and the EU-Horizon program, for the submitted work; and has received support for attending meetings from Pfizer; support for participation on an advisory board for therapeutics on COVID-19; and support for leadership for the Belgian guidelines on therapeutics for COVID-19 and acting as a treasurer for the Belgian Society of Clinical Microbiology and Infectious Diseases. R.G. reports consulting fees from Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankvo; lecture fees from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankvo; support for attending meetings from Roche, Amgen, Janssen, AstraZeneca, Novartis, Merck Sharp & Dohme, Celgene, Gilead, Bristol Myers Squibb, Abbvie, and Daiichi Sankvo; participation in a Data Safety and Monitoring Board for Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankyo; research grants from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankyo. J.-A.P. reports consulting fees from Pfizer, Merck Sharp & Dohme, and Janssen-Cilag; lecture fees from Pfizer; and support for attending meetings from Pfizer. D.C. reports grants and lecture fees from Janssen and lecture fees from Gilead, outside the submitted work. C.B. reports participation in a Data Safety and Monitoring Board for 4Living Biotech; and consulting fees from Da Volterra and Mylan Pharmaceuticals, outside the submitted work. F.M. reports grants and consulting fees from Da Volterra, grants from Sanofi, and consulting fees from Ipsen, outside the submitted work. All other authors declare no competing interests.### Clinical TrialNCT04315948### Funding StatementThis work received funding from several sources: the European Commission (EU-Response, Grant 101015736), the DIM One Health Ile-de-France (R20117HD) and Astra-Zeneca. We thank all participants who consented to enroll in the trial, as well as all study and site staff whose indispensable assistance made the conduct of the DisCoVeRy trial possible (all listed in the appendix, pp 27-36)### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics committee of the BASG (Bundesamt fur Sicherheit im Gesundheitswesen), Austria, gave ethical approval for this work. Ethics committee of the FAMHP (Federal Agency for Medicines and Health Products), Belgium, gave ethical approval for this work. Ethics committee of the SUKL (Statni Ustav Pro Kontrolu Leciv), Czech Republic, gave ethical approval for this work. Ethics committee of the ANSM (Agence nationale de securite du medicament et des produits de sante), France, gave ethical approval for this work. Ethics committee of the National Organization for Medicines, Greece, gave ethical approval for this work. Ethics committee of the National Institute of Pharmacy and Nutrition (OGYEI), Hungary, gave ethical approval for this work. Ethics committee of the HPRA (Health Products Regulatory Authority), Ireland, gave ethical approval for this work. Ethics committee of the CNER (Comite National d Ethique de Recherche, ministere de la sante), Luxembourg, gave ethical approval for this work. Ethics committee of the NOMA (Norwegian Medical Products Agency), Norway, gave ethical approval for this work. Ethics committee of the Komisja Bioetyczna Przy Uniwersytecie Medycznym W Lodzi, Poland, gave ethical approval for this work. Ethics committee of the Infarmed (National Authority of Medicines and Health Products), Portugal, gave ethical approval for this work. Ethics committee of the SULK (Statni ustav pro kontrolu leciv), Slovakia, gave ethical approval for this work. Ethics committee of the AEMPS (Agencia Espanola de Medicamentos y Productos Sanitarios), Spain, gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesWith publication, deidentified, individual participant data that underlie this Article, along with a data dictionary describing variables in the dataset, will be made available to researchers whose proposed purpose of use is approved by the DisCoVeRy Steering Committee. To request the dataset, please address directly to the corresponding author (florence.ader@chu-lyon.fr) or to the sponsor's representative (helene.esperou{at}inserm.fr) to obtain a data access form. All requests will be evaluated by the Trial Management Team and the DisCoVeRy Steering Committee. For accepted requests, data will be shared after signing a data transfer agreement with the study sponsor. Data will be shared directly or through access on the INSERM repository. Related documents, such as the study protocol, statistical analysis plan, and informed consent form, will be made available (with publication) on request to the corresponding author or to the sponsor's representative. The data will be open access for the informed consent form, protocol, and statistical analysis plan. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04315948&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F24%2F2024.02.23.24302586.atom

West Nile Virus (WNV) and Usutu virus (USUV) circulate through complex cryptic transmission cycles involving mosquitoes as vectors, birds as amplifying hosts and several mammal species as dead-end hosts. Both viruses can be transmitted to humans through mosquito bites, which can lead to neuroinvasive and potentially fatal disease. Notably, WNV can also be transmitted through blood donations and organ transplants. The high proportion of asymptomatic infections caused by these viruses and their cryptic enzootic circulation make their early detection in the environment challenging. Viral surveillance in France still heavily relies on human and animal surveillance, i.e. late indicators of viral circulation. Entomological surveillance is a method of choice for identifying virus circulation ahead of the first human and animal cases and to reveal their genetic identity, but performing molecular screening of vectors is expensive, and time-consuming. Here we show substantial WNV and USUV co-circulation in Atlantic seaboard of France between July and August 2023 using a non-invasive MX (Molecular Xenomonitoring) method that use trapped mosquito excreta. MX offers significant advantages over traditional entomological surveillance: it is cost-effective and efficient, enabling viral RNA screening from a community of trapped mosquitoes via their excreta, which can be transported at room temperature. Additionally, MX extends the longevity of trapped mosquitoes, enhancing virus detection and simplifying logistics, and is easy to implement without requiring specialized skills. At the crossroads between entomological and environmental surveillance, MX can detect the circulation of zoonotic pathogens in the environment before cases are observed in humans and horses, enabling the timely alerts to health policy makers, allowing them to take suitable control measures.

IntroductionLe virus West Nile (VWN), régulièrement isolé sur le pourtour méditerranéen français, a été identifié pour la première fois dans le Sud-Ouest de la France en octobre 2022, chez des chevaux. Un dispositif de surveillance pluridisciplinaire (humaine, équine, aviaire et entomologique) a été mis en place à partir de juin 2023, fondé sur le dispositif déjà existant à l'échelle nationale. Fin juillet 2023, les premiers cas humains autochtones d'infection à VWN ont été identifiés dans la région. Des investigations ont été menées afin de préciser la zone de circulation du virus et de guider les mesures de prévention.Matériels et méthodesLes différents volets de la surveillance ont été renforcés et les professionnels de santé ont été sensibilisés au diagnostic. Une alerte a été faite auprès de l'EFS et de l'Agence de la biomédecine en vue de la sécurisation des produits du corps humain. Une enquête épidémiologique a été menée auprès de chaque cas humain déclaré et des prospections entomologiques ont été réalisées autour des cas signalés en zone urbaine. Le Centre national de référence des arbovirus a analysé les prélèvements des cas suspects identifiés.RésultatsA la fin de la période d'activité des moustiques vecteurs le 30 novembre 2023, 36 cas humains autochtones d'infection à VWN (confirmés ou probables) ont été identifiés dans la région (cas domiciliés ou de passage). Une infection par le virus Usutu ne peut toutefois pas être écartée avec certitude pour certains cas probables. Les cas étaient répartis sur plusieurs départements mais près de la moitié résidaient dans la même métropole (n = 17). Neuf cas ont présenté une forme neuro-invasive et 5 étaient des donneurs de sang asymptomatiques ou paucisymptomatiques. Sur la période à risque, plus de 51 000 dons du sang ont été testés par dépistage génomique viral dans la région. Treize des prospections entomologiques réalisées autour des cas signalés en zone urbaine ont été suivies d'une intervention de lutte antivectorielle, ciblant principalement les larves de moustiques Culex.ConclusionDes cas humains autochtones d'infection à VWN ont été identifiés pour la première fois dans le Sud-Ouest de la France, avec une circulation virale particulièrement active. Le nombre de cas détectés dans la région a été plus élevé que lors du pic observé en 2018 en France. Cet épisode confirme donc l'extension rapide de l'aire géographique de présence du virus dans l'Hexagone et l'intérêt de poursuivre la surveillance épidémiologique des arboviroses de manière préventive, réactive et pluridisciplinaire dans une approche « One Health ». En effet, la collaboration entre l'ensemble des acteurs impliqués a été un atout majeur dans la gestion de cet épisode.Aucun lien d'intérêt

Ebola virus (EBOV) and Marburg virus are the major species of the family Filoviridae in the order of Mononegavirales. Filoviruses are enveloped, nonsegmented, negative-stranded RNA viruses of varying morphology. These viruses have characteristic filamentous particles that give the virus family its name. Ebola and Marburg viruses are pathogens that represent an important local public health hazard in Africa, with a potential worldwide impact through imported infections. These viruses are classified as Category A biothreat pathogens. Filoviruses are also thought to contribute to the dramatic reduction in the great ape population in Africa over recent decades. Ebola and Marburg virus infections are characterized by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, which, in some ways, resembles septic shock. Following the recent devastating EBOV disease outbreaks in West Africa (2013–2016) and in the Eastern Democratic Republic of the Congo (2018–2020), substantial progress has been made in diagnosis, treatment, and vaccine prophylaxis of filovirus infections. Nonetheless, many uncertainties persist in the prevention and management of these deadly filovirus infections that occur in the setting of limited health resources and challenging geopolitical settings.

Background Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. Methods We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. Results There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people >= 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. Conclusions This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Background West Nile (WNV) and Usutu (USUV) virus are vector-borne flaviviruses causing neuroinvasive infections in both humans and animals. Entomological surveillance is a method of choice for identifying virus circulation ahead of the first human and animal cases, but performing molecular screening of vectors is expensive, and time-consuming. Methods We implemented the MX (Molecular Xenomonitoring) strategy for the detection of WNV and USUV circulation in mosquito populations in rural and urban areas in Nouvelle-Aquitaine region (France) between July and August 2023, using modified BG Sentinel traps. We first performed molecular screening and sequencing on excreta from trapped mosquitoes before confirming the results by detecting, sequencing and isolating viruses from individual mosquitoes. Findings We identified WNV and USUV-infected mosquitoes in 3 different areas, concurrently with the first human cases reported in the region. Trapped mosquito excreta revealed substantial virus co-circulation (75% of traps had PCR+ excreta for at least one of both viruses). Cx. pipiens was the most common species infected by both WNV and USUV. Genomic data from excreta and mosquitoes showed the circulation of WNV lineage 2 and USUV lineage Africa 3, both phylogenetically close to strains that circulated in Europe in recent years. Four WNV and 3 USUV strains were isolated from trapped mosquitoes. Interpretation MX strategy is easy and rapid to implement on the field, and has proven its effectiveness in detecting WNV and USUV circulation in local mosquito populations. Funding This study received funding from the Direction Générale de l’Armement (PDH 2 NBC-5-B-2212) and ARBOGEN (funded by MSDAVENIR). Evidence before this study WNV and USUV circulate through complex transmission cycles involving mosquitoes as vectors, birds as amplifying hosts and several mammal species as dead-end hosts. Transmission to humans primarily occurs through mosquito bites for both viruses. Notably, WNV can also be transmitted through blood donations and organ transplants. It is estimated that a significant proportion of both WNV and USUV infections in vertebrate hosts remain unreported due to their predominantly asymptomatic nature or nonspecific clinical presentation. Nevertheless, neuroinvasive and potentially fatal disease can occur, in particular among vulnerable populations such as elderly and immunocompromised patients. In France, after its first detection in 2015, USUV has been sporadically found in eastern and southern departments, with confirmed infections in birds, mosquitoes and mammals, and few human cases described. WNV has recently caused annual outbreaks of varying intensities involving humans, equids and avifauna in French departments mainly located in the Mediterranean area. Because of low viral loads and/or brief viremia, diagnosis of both pathogens is often based on serological evidence, and few genomic data are available on strains having circulated in France. Entomological surveillance can be used as an early warning method for WNV and USUV surveillance, but is costly to implement as it requires the collection of large numbers of mosquitoes to detect virus circulation when infection rates in mosquito populations are low. Therefore, viral surveillance in France still heavily relies on human and animal surveillance, i.e. late indicators of viral circulation. Added value of this study This study describes the implementation of the MX (Molecular Xenomonitoring) strategy for the effective surveillance of WNV and USUV circulation within mosquito populations. MX uses of modified BG Sentinels that allow (i) trapped mosquitoes to survive for several days and (ii) corresponding mosquito excreta to be collected and preserved on filter paper. MX has demonstrated many advantages over traditional entomological surveillance. Firstly, screening excreta collectively deposited by a community of trapped mosquitoes for the presence of viruses in the first instance is time and cost efficient, as one sample is tested for viral RNA, regardless of the number and species diversity in the trap. Second, filter papers with mosquito excreta can be transported from the field to the laboratory at room temperature by regular postal mail, bringing real-time detection within reach. WNV and USUV RNA have been detected and sequenced directly from the mosquito excreta shortly after collection. Thirdly, MX adapters increase the longevity of trapped mosquitoes, thereby allowing extension of the time between trap collections and increasing the likelihood of virus shedding by infected mosquitoes. Fourthly, this approach is easy to implement in the field and requires neither a strong entomological background nor specific technical skills. All these aspects make the MX strategy a powerful, non-invasive and cost-effective tool for real-time monitoring of enzootic WNV and USUV circulation. Authors should describe here how their findings add value to the existing evidence. WNV was never detected on the Atlantic seaboard of France until October 2022. Molecular evidence of WNV circulation was obtained in 3 symptomatic horses in the Nouvelle Aquitaine region in October 2022, concomitantly with an USUV human case with no recent travel history outside the region. This was a harbinger of an increase in cases over the next year. In 2023, MX succeeded in detecting the enzootic co-circulation of WNV and USUV in rural and urban areas of Nouvelle Aquitaine, simultaneously with the first cases of WNV detected by human and animal surveillance and the first human case of USUV diagnosed in the end of July 2023. Genomic and phylogenetic information was obtained directly from trapped mosquito excreta, before information derived from animal or human surveillance. Mosquitoes from traps with PCR-positive excreta were analysed individually, which allowed to calculate infection rates in mosquitoes. WNV and USUV were isolated from single Cx. pipiens mosquitoes. Cx. pipiens was the species most commonly found positive for either viruses although WNV was also detected in Ochlerotatus and Aedes mosquitoes, including one tiger mosquito ( Ae. albopictus ) in the urban environment. We argue that the MX approach is a major asset in the early warning detection of WNV and USUV circulation to alert health policy makers and take suitable control measures. ### Competing Interest Statement The authors have declared no competing interest.

Background Lassa fever (LF) is a severe re-emerging infectious disease caused by the Lassa virus (LV). LF is a priority disease on the World Health Organization’s R&D blueprint and affects a large number of countries in West Africa, with Nigeria carrying the highest case burden in the world. Current treatment options are limited to supportive care and the antiviral drug ribavirin. However, evidence for the efficacy of ribavirin in LF is poor. A recent study showed that in vivo plasma concentrations do not suffice to exert a relevant antiviral effect. New drugs for LF treatment are therefore urgently needed but no therapeutic trials have been conducted for this indication in the past decades. Favipiravir is a broad-spectrum antiviral registered for pandemic influenza that has also been clinically evaluated for other viral infections. It shows potent activity against LV in pre-clinical studies. To evaluate the safety and tolerability of favipiravir as repurposed drug in the treatment of LF, a phase II clinical trial was conducted. Methods LF patients were recruited at the Irrua Specialist Teaching Hospital and the Federal Medical Centre of Owo in Nigeria, which are the worldwide largest LF treatment centres. Blood sampling for virological, serological and immunological analyses, hematology and biochemistry as well as clinical assessments were done on days 1, 2, and then every other day until the end of the study. Results In total, 40 LF patients were included in the trial between 2021 and 2022. Results on cure rates, safety and tolerability of this first GCP compliant phase II clinical trial will be presented to provide first insights into this new treatment option for LF.

Background Lassa fever (LF) is a viral haemorrhagic fever responsible of 5000 deaths per year in West Africa, with in-hospital mortality at 12%. Ribavirin is the only treatment available with worrying toxicity, questionable efficacy and low access because of its high cost. Consequently, there is an urgent need for new drugs to treat LF patients. Methods The INTEGRATE study is a platform, multinational, multicentre, sequential, seamless phase II-III, controlled, randomised, superiority trial in open-label parallel arms. Its primary objective is to compare the efficacy of each Investigational Medical Product (IMP) to Standard of Care Drug (SCD) to prevent death or organ failure in hospitalized patients with confirmed LF. The primary endpoint is the proportion of patients presenting no clinical aggravation between D0 and D14. All hospitalized patients, including pregnant women, are eligible for enrolment. The total follow-up period is 28 days. Three interim analyses are planned, with a total study population of 218 patients per arm. A co-sponsorship will be assumed by ANRS-MIE and the Irrua Specialist Teaching Hospital (ISTH). Results Trial inclusions will begin in Nigeria in April 2024 at the Federal Medical Centre Owo and at ISTH. Other West African sites (Liberia, Benin, Guinea and Nigeria) will join the platform as they complete a site preparedness program currently undergoing. The first IMP to be evaluated will be the repurposed drug Favipiravir, compared to the SCD Ribavirin. The second IMP will probably be the antiviral ARN 75039, which has shown promising results in pre-clinical phases and is currently in phase I evaluation. Conclusion The ribavirin treatment for LF is still debated in term of safety, efficacy and affordability. The INTEGRATE study will provide evidence on new drugs efficacy in order to treat patients and reduce the burden of LF. Funding: Acknowledgment to EDCTP for funding this study.