BackgroundSchistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion.Methodology/Principal findingsWe conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants’ consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2–6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3–1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9–4.6] log10 copies/mL versus 3.7 [3.2–4.3], p = 0.017.Conclusions/SignificanceWe confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.

Summary The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network, http://alpha.lshtm.ac.uk/) brings together ten population-based HIV surveillance sites in eastern and southern Africa, and is coordinated by the London School of Hygiene and Tropical Medicine (LSHTM). It was established in 2005 and aims to (i) broaden the evidence base on HIV epidemiology for informing policy, (ii) strengthen the analytical capacity for HIV research, and (iii) foster collaboration between network members. All study sites, some starting in the late 1980s and early 1990s, conduct demographic surveillance in populations that range from approximately 20 to 220 thousand individuals. In addition, they conduct population-based surveys with HIV testing, and verbal autopsy interviews with relatives of deceased residents. ALPHA Network datasets have been used for studying HIV incidence, sexual behaviour and the effects of HIV on mortality, fertility, and household composition. One of the network's substantive focus areas is the monitoring of AIDS mortality and HIV services coverage in the era of antiretroviral therapy. Service use data are retrospectively recorded in interviews and supplemented by information from record linkage with medical facilities in the surveillance areas. Data access is at the discretion of each of the participating sites, but can be coordinated by the network.

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Background Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. MethodsThe Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. Findings Follow-up information was available for 3709 (99•0%) BCG recipients and 3612 (99•1%) placebo recipients in the northern areas, and 2449 (87•5%) BCG recipients and 2413 (85•6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6•6 deaths per 1000 person-years at risk [95% CI 5•5-7•8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7•0 deaths per 1000 person-years at risk [95% CI 5•9-8•2]; HR 0•94 [95% CI 0•74-1•20]; p=0•62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6•3 deaths per 1000 person-years at risk [95% CI 5•5-7•1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5•9 deaths per 1000 person-years at risk [95% CI 5•2-6•8]; HR 1•06 [95% CI 0•88-1•27]; p=0•54).Interpretation We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits.