Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).

Seroprevalence of anti-SARS-CoV-2 antibodies among blood donors from December 2020 to June 2021 in Koutiala district, Mali.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus associated with coronavirus disease (COVID-19). At the time of the study, little data on the level of exposure of the population in Koutiala district in Mali to SARS-CoV-2 was available. Although blood donors are not representative of the general population, a COVID-19 seroprevalence estimate in this population was intended to assess the extent of community transmission, serve as a health alert system, and help guide the public health response. We measured seroprevalence of anti-SARS-CoV-2 antibodies using NG-Biotech SARS-Cov-2 RDT and ECLIA test between January and June 2020. This is a cross-sectional study of volunteer blood donors aged 18 to 60 years, independent of any previous COVID-19 disease. A stratified analysis of seroprevalence by month of sample collection and a comparison of the results of the NG-Biotech SARS-Cov-2 RDT with those of the ECLIA test was performed. The overall prevalence of antibodies to SARS-Cov-2 virus assessed by the NG-Biotech SARS-Cov-2 RDT was 24.6% (95% CI 21.8-27.4) and by the ECLIA test was 70.2 (95% CI 64.9-75.5). Both estimates remained relatively stable over the study period. We observed SARS-CoV-2 exposure much higher than indicated by case-based surveillance. The national surveillance system, as it was, was not able to detect variations in incidence, and as such, we do not recommend it as an alert system. However, the discrepancy between the results of the rapid test and the ECLIA test shows that further research is required to assess the validity of these test before a more solid conclusion can be drawn it their use in surveillance.