BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.ResultsOf the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Over the past century, the emergence/reemergence of arthropod-borne zoonotic agents has been a growing public health concern. In particular, agents from the genus Alphavirus pose a significant risk to both animal and human health. Human alphaviral disease presents with either arthritogenic or encephalitic manifestations and is associated with significant morbidity and/or mortality. Unfortunately, there are presently no vaccines or antiviral measures approved for human use. The present review examines the ecology, epidemiology, disease, past outbreaks, and potential to cause contemporary outbreaks for several alphavirus pathogens.

Background: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. Methods: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibodydependent enhancement phenomenon (ADE) during short and long outcomes of CZI. Findings: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. Interpretation: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection.

The COVID-19 pandemic continues to affect millions of people worldwide. Although SARS-CoV-2 is a respiratory virus, there is growing concern that the disease could cause damage and pathology outside the lungs, including in the genital tract. Studies suggest that SARS-CoV-2 infection can damage the testes and reduce testosterone levels, but the underlying mechanisms are unknown and evidence of virus replication in testicular cells is lacking. We infected golden Syrian hamsters intranasally, a model for mild human COVID-19, and detected viral RNA in testes samples without histopathological changes up to one month post-infection. Using an ex vivo infection model, we detected SARS-CoV-2 replication in hamster testicular cells. Taken together, our data raise the possibility that testes damage observed in severe cases of COVID-19 could be partly explained by direct SARS-CoV-2 infection of the testicular cells.

Abstractobjective To entomologically monitor Aedes spp. and correlate the presence of these vectors with the recent epidemic of dengue in Divinopolis, Minas Gerais State, Brazil.methods Ovitraps were installed at 44 points in the city, covering six urban areas, from May 2011 to May 2012. After collection, the eggs were incubated until hatching. In the 4th stage of development, the larvae were classified as Ae. aegypti or Ae. albopictus.results In total, 25 633 Aedes spp. eggs were collected. February was the month with the highest incidence, with 5635 eggs collected and a hatching rate of 46.7%. Ae. aegypti eggs had the highest hatching rate, at 72.3%, whereas Ae. albopictus eggs had 27.7%. Climate and population density influenced the number of eggs found. Indicators of vector presence were positively correlated with the occurrence of dengue cases.conclusion These data reinforce the need for entomological studies, highlight the relevance of Ae. albopictus as a possible disease vector and demonstrate its adaptation. Ae. albopictus, most commonly found in forested areas, comprised a substantial proportion of the urban mosquito population.

Infections caused by multidrug-resistant bacteria are a problem of public health, turning the search for natural products an alternative to antibiotics of great importance. The aim of this study was to investigate the in vitro antimicrobial activities of Hymenaea courbaril and Stryphnodendron adstringens against bacterial clinical isolates. The crude extracts of both vegetal species in study showed bacteriostatic activity against almost all bacteria evaluated, with minimum inhibitory concentration (MIC) ranging from 125 to 1250 µg/ml. The bacteriostatic activity was observed in all the fractions of H. courbaril and S. adstringens against at least one bacterial strain, except in the fraction dichloromethane of S. adstringens. In regard to bactericidal activity, H. courbaril was active only against E. faecalis, and S. adstringens showed activity against all bacterial strains, except to Enterococcus faecalis. The combination of extracts showed potent synergistic antimicrobial activity, with MIC values of 31.25 µg/ml against Acinetobacter baumannii, Escherichia coli and Staphylococcus aureus. S. adstringens were considered less cytotoxic compared to H. courbaril and the half-maximum cytotoxic concentration (CC 50) resulting from the combination of the two plants was 0.0082 ± 3.19 mg/ml. The results showed for the first time the synergic antibacterial activities of H. courbaril and S. adstringens against resistant bacteria, suggesting their potential use to development of new drugs.

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