Background Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public-health threat in sub-Saharan Africa. We present phase 3 efficacy data from an African trial of a Vi-polysaccharide typhoid conjugate vaccine (Vi-TCV). Methods Children aged 9 months to 12 years in Blantyre, Malawi were randomized (1:1) in a double-blind trial to receive Vi-TCV (single dose) or group-A meningococcal control vaccine (MenA).The primary outcome was blood culture-confirmed typhoid fever. We present the primary vaccine efficacy (VE) and safety outcomes after 18–24 months of follow-up. Results This intention-to-treat (ITT) analysis included 28,130 children, comprising 14,069 children who received Vi-TCV and 14,061 children who received MenA. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 per 100,000 person-years) and 62 children in the MenA group (243 per 100,000 person-years). Overall VE was 80.7% (95% confidence interval (CI): 64.2% to 89.6%) in an ITT analysis, and 83.7% (95% CI: 68.1%−91.6%) in a per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in Vi-TCV group and 78 in MenA group), including 6 deaths (all in MenA group). No serious adverse event was considered by the investigator as related to study vaccination. Conclusions Vi-TCV reduced blood culture-confirmed typhoid fever among Malawian children aged 9 months to 12 years. (Funded by the Bill & Melinda Gates Foundation; ClinicalTrials.gov number NCT03299426 .)

IntroductionSince June 2016, the national HIV programme in Malawi has adopted Universal Test and Treat (UTT) guidelines requiring that all persons who test HIV positive will be referred to start antiretroviral therapy (ART). Although there is strong evidence from clinical trials that early initiation of ART leads to reduced morbidity and mortality, the impact of UTT on retention on ART in real‐life programmatic settings in Africa is not yet known.MethodsWe conducted a retrospective cohort study in Zomba district, Malawi to compare ART outcomes of patients who initiated ART under 2016 UTT guidelines and those who started ART prior to rollout of UTT (pre‐UTT). We analysed data from 32 rural and urban health facilities of various sizes. Cox proportional hazards modelling was used to determine the independent risk factors of attrition from ART at 12 months. All analyses were adjusted for clustering by health facility using a robust standard errors approach.ResultsAmong 1492 patients (mean age 34.4 years, 933 (63%) female) who initiated ART during the study period, 501 were enrolled in the pre‐UTT cohort and 911 during UTT. At 12 months, retention on ART in the UTT cohort was higher than in the pre‐UTT cohort 83.0% (95% confidence interval (CI): 81.0% to 85.0%) versus 76.2% (95% CI 73.9% to 78.5%). Adolescents, aged 10 to 19 years (adjusted hazard ratio (aHR) 1.53; 95% CI 1.01 to 2.32), and women who were pregnant or breastfeeding at ART initiation (aHR 1.87; 95% CI 1.30 to 2.38) were at higher risk of attrition in the combined pre‐UTT and UTT cohort.ConclusionsRetention on ART was nearly 6% higher after UTT introduction. Young adults and women who were pregnant or breastfeeding at the start of ART were at increased risk of attrition, emphasizing the need for targeted interventions for these groups to achieve the 90‐90‐90 UNAIDS targets in the UTT era.

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BackgroundWhile dyslipidemia importantly contributes to increased cardiovascular disease risk among patients on antiretroviral therapy (ART), data on lipid patterns among African adults on ART are limited. We describe the prevalence of lipid abnormalities and associated factors in two HIV clinics in Malawi.MethodsWe conducted a cross-sectional study in 2014 and enrolled adult patients at a rural and an urban HIV clinic in Zomba district, Malawi. We recorded patient characteristics, CVD risk factors and anthropometric measurements, using the WHO STEPS validated instrument. Non-fasting samples were taken for determination of total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL-c) levels. Logistic regression analysis was used to determine factors associated with elevated TC and elevated TC/HDL-c ratio.Results554 patients were enrolled, 50% at the rural HIV clinic, 72.7% were female, the median (IQR) age was 42 years (36–50); 97.3% were on ART, 84.4% on tenofovir/lamivudine/efavirenz, 17.5% were overweight/obese and 27.8%% had elevated waist/hip ratio. 15.5% had elevated TC, 15.9% reduced HDL-c, 28.7% had elevated TG and 3.8% had elevated TC/HDL-c ratio. Lipid abnormalities were similar in rural and urban patients. Women had significantly higher burden of elevated TC and TG whereas men had higher prevalence of reduced HDL-c. Waist-to-hip ratio was independently associated with elevated TC (aOR = 1.90; 95% CI: 1.17–3.10, p = 0.01) and elevated TC/HDL-c ratio (aOR = 3.50; 95% CI: 1.38–8.85, p = 0.008). Increasing age was independently associated with elevated TC level (aOR = 1.54, 95% CI 0.51–4.59 for age 31–45; aOR = 3.69, 95% CI 1.24–10.95 for age >45 years vs. ≤30 years; p-trend <0.01).ConclusionsWe found a moderate burden of dyslipidemia among Malawian adults on ART, which was similar in rural and urban patients but differed significantly between men and women. High waist-hip ratio predicted elevated TC and elevated TC/HDL-c ratio and may be a practical tool for CVD risk indication in resource limited settings.

HighlightsSimplified delivery strategies were proposed in hard-to-reach population.High full coverage was reached in the most at-risk individuals.Vaccines use efficiency need to be improved.