Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
ଝଝ This text is protected by copyright owned by SPILF. Reproduction and distribution rights are granted by SPILF on request, provided the text is reproduced in full, with no addition or deletion, and provided SPILF and the references of the original article published in Médecine et Maladies Infectieuses are indicated. Chikungunya (CHIK) is both an arbovirus transmitted by Aedes mosquitoes and an arthrogenic alphavirus, the clinical consequences of which were revealed in France by the southwest Indian Ocean outbreak (Mayotte, Reunion) in 2005-2006. The recent epidemic spread of CHIK in the French South American and Pacific territories (departments) and communities led to a steady increase of infected individuals, confronting local and metropolitan healthcare professionals with the difficulties http://dx.
Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov , NCT04315948 . Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporea...
Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).
Abstract. Shewanella spp. are saprophytic bacteria that are part of the marine microflora in warm climates and are rarely pathogenic. However, Shewanella spp. infections are being increasingly reported, and there has been no comprehensive review of the literature describing these infections. This article reports 16 cases of Shewanella spp. infections in Martinique since 1997 and reviews another 239 cases reported in the literature since 1973. Patients experienced soft tissue infections, ear infection, or abdominal and biliary tract infections. A skin or mucosal portal of entry was found for 53% of the patients and exposure to the marine environment was reported for 44%; 79% of patients had an underlying condition. Bacteriema were frequent (28%). Most (87%) patients recovered, although ear infections can become chronic. Death occurred in 13% of the patients. Most Shewanella spp. isolates are susceptible to cefotaxime (95%), piperacillin and tazobactam (98%), gentamicin (99%), and ciprofloxacin (94%).
Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus that can be sexually transmitted from man to woman. The finding of high viral loads and prolonged viral shedding in semen suggests that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no IFN upregulation and minimal proinflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.
study of the platelet inhibitor prasugrel in children with sickle cell disease was designed to identify drug doses that inhibit platelet function between 30% and 50%, a level thought to balance safety and efficacy, 24 similar to the level of inhibition observed here, although the dual effects of RN-1 on platelet function and platelet counts could pose an additional risk for bleeding that will require further monitoring.Our results show that administration of RN-1 to normal baboons over a prolonged period increases HbF, F cells, and F retics and is generally well tolerated, supporting further development of LSD1 inhibitors as therapeutic agents for SCD. Because LSD1 also has an important functional role in neural stem cell maintenance and proliferation, effects of LSD1 inhibitors on the brain and nervous system should be carefully evaluated.
Martinique experienced a dengue outbreak with co-circulation of DENV-2 and DENV-4. In an emergency department-based study, we analyzed whether the clinical presentation and outcome of adult patients were related to serotype, immune status, or plasma viral load. Of the 146 adult patients who had confirmed dengue infection, 91 (62.3%) were classified as having classic dengue fever, 11 (7.5%) fulfilled World Health Organization criteria for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), 21 other patients (14.4%) presented with at least one typical feature of DHF/DSS [i.e., internal hemorrhage, plasma leakage, marked thrombocytopenia (platelet count < or = 50,000 platelets/mm(3)) and/or shock], and 23 further patients (15.8%) had unusual manifestations. Four patients died. Severe illness was more frequent in patients with secondary dengue infection (odds ratio, 7.18; 95% confidence interval, 3.1-16.7; P < 0.001). Multivariate regression analysis showed that gastrointestinal symptoms and other unusual manifestations were independently associated with DENV-2 infection, whereas cough and DHF/DSS features were independently associated with secondary immune response. A high plasma viral load was associated with DENV-2 infection, increased serum liver enzymes, and with DHF/DSS features in patients presenting after the third day of illness. The most severe cases of dengue resulted from the combined effects of DENV-2 and secondary infection.
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