BACKGROUNDCryptococcal 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. METHODSWe 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. RESULTSA 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.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries. 2018 Lancet Infect Dis

Background By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. Methods We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. Results A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20–49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]). Conclusion The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.

Background: Four million people die each year from diseases caused by exposure to household air pollution. There is an association between exposure to household air pollution and pneumonia in children (half a million attributable deaths a year); however, whether this is true in adults is unknown. We conducted a case-control study in urban Malawi to examine the association between exposure to household air pollution and pneumonia in adults. Methods: Hospitalized patients with radiologically confirmed pneumonia (cases) and healthy community controls underwent 48 hours of ambulatory and household particulate matter (µg/m 3) and carbon monoxide (ppm) exposure monitoring. Multivariate logistic regression, stratified by HIV status, explored associations between these and other potential risk factors with pneumonia. Results: 145 (117 HIV-positive; 28 HIV-negative) cases and 253 (169 HIV-positive; 84 HIV-negative) controls completed follow up. We found no evidence of association between household air pollution exposure and pneumonia in HIV-positive (e.g. ambulatory particulate matter adjusted odds ratio [aOR] 1.00 [95% CI 1.00–1.01, p=0.141]) or HIV-negative (e.g. ambulatory particulate matter aOR 1.00 [95% CI 0.99–1.01, p=0.872]) participants. Chronic respiratory disease was associated with pneumonia in both HIV-positive (aOR 28.07 [95% CI 9.29–84.83, p<0.001]) and HIV-negative (aOR 104.27 [95% CI 12.86–852.35, p<0.001]) participants. Conclusions: We found no evidence that exposure to household air pollution is associated with pneumonia in Malawian adults. In contrast, chronic respiratory disease was strongly associated with pneumonia.