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Childhood mortality remains high in sub-Saharan Africa. In this cluster-randomized, placebo-controlled trial, mortality among children younger than 5 years of age was lower among those who received azithromycin than among those who received placebo.

WHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children. We did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623. We enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89–16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72–16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91–1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 [95% CI 0·37–2·23]; p=0·83). We found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed. Medical Research Council, UK Department for International Development, and Wellcome Trust.

Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial. An adaptive multi-arm, 2-stage cluster randomised trial was conducted between 8 August 2016 and 30 June 2017, with antenatal care clinic (ANC) days (i.e., clusters of women attending on a single day) as the unit of randomisation. Recruitment was from Ndirande, Bangwe, and Zingwangwa primary health clinics in urban Blantyre, Malawi. Women attending an ANC for the first time for their current pregnancy (regardless of trimester), 18 years and older, with a primary male partner not known to be on ART were enrolled in the trial after giving consent. Randomisation was to either the standard of care (SOC; with a clinic invitation letter to the male partner) or 1 of 5 intervention arms: the first arm provided women with 2 HIVST kits for their partners; the second and third arms provided 2 HIVST kits along with a conditional fixed financial incentive of $3 or $10; the fourth arm provided 2 HIVST kits and a 10% chance of receiving $30 in a lottery; and the fifth arm provided 2 HIVST kits and a phone call reminder for the women's partners. The primary outcome was the proportion of male partners who were reported to have tested for HIV and linked into care or prevention within 28 days, with referral for antiretroviral therapy (ART) or circumcision accordingly. Women were interviewed at 28 days about partner testing and adverse events. Cluster-level summaries compared each intervention versus SOC using eligible women as the denominator (intention-to-treat). Risk ratios were adjusted for male partner testing history and recruitment clinic. A total of 2,349/3,137 (74.9%) women participated (71 ANC days), with a mean age of 24.8 years (SD: 5.4). The majority (2,201/2,233; 98.6%) of women were married, 254/2,107 (12.3%) were unable to read and write, and 1,505/2,247 (67.0%) were not employed. The mean age for male partners was 29.6 years (SD: 7.5), only 88/2,200 (4.0%) were unemployed, and 966/2,210 (43.7%) had never tested for HIV before. Women in the SOC arm reported that 17.4% (71/408) of their partners tested for HIV, whereas a much higher proportion of partners were reported to have tested for HIV in all intervention arms (87.0%-95.4%, p < 0.001 in all 5 intervention arms). As compared with those who tested in the SOC arm (geometric mean 13.0%), higher proportions of partners met the primary endpoint in the HIVST + $3 (geometric mean 40.9%, adjusted risk ratio [aRR] 3.01 [95% CI 1.63-5.57], p < 0.001), HIVST + $10 (51.7%, aRR 3.72 [95% CI 1.85-7.48], p < 0.001), and phone reminder (22.3%, aRR 1.58 [95% CI 1.07-2.33], p = 0.021) arms. In contrast, there was no significant increase in partners meeting the primary endpoint in the HIVST alone (geometric mean 17.5%, aRR 1.45 [95% CI 0.99-2.13], p = 0.130) or lottery (18.6%, aRR 1.43 [95% CI 0.96-2.13], p = 0.211) arms. The lottery arm was dropped at interim analysis. Overall, 46 male partners were confirmed to be HIV positive, 42 (91.3%) of whom initiated ART within 28 days; 222 tested HIV negative and were not already circumcised, of whom 135 (60.8%) were circumcised as part of the trial. No serious adverse events were reported. Costs per male partner who attended the clinic with a confirmed HIV test result were $23.73 and $28.08 for the HIVST + $3 and HIVST + $10 arms, respectively. Notable limitations of the trial included the relatively small number of clusters randomised to each arm, proxy reporting of the male partner testing outcome, and being unable to evaluate retention in care. In this study, the odds of men's linkage to care or prevention increased substantially using conditional fixed financial incentives plus partner-delivered HIVST; combinations were potentially affordable. ISRCTN 18421340.

Background Youth mental health has emerged as a pressing global issue. However, to advance research gaps in low-income settings, we need valid measures of common mental health disorders. Using primary data collected in five countries (Kenya, Malawi, Tanzania, Zambia, and Zimbabwe), this study aims to assess the psychometric properties of the commonly used 10-item Center for Epidemiological Studies Depression (CES-D 10) scale among poor, disadvantaged youth populations in sub-Saharan African (SSA). Methods Youth samples from each country (sample sizes ranging from 651 to 2098) come from large household surveys with youth modules, collected for impact evaluations of cash transfer programs targeted to poor families. For each sample, we assessed internal consistency (alpha), conducted factor analysis, and then examined construct validity and measurement invariance. We performed both exploratory (EFA) and confirmatory factor analysis (CFA) to examine and confirm the structure of the CES-D 10 for each country and then used multigroup CFA to assess measurement invariance across gender and age. Multivariate analyses were conducted to assess construct validity via test of the relationship between CES-D 10 and background characteristics. Results Results show the CES-D 10 had strong psychometric properties and was a reliable measure of depressive symptoms among disadvantaged youth in SSA. Across countries, there was high internal consistency (Cronbach alphas = 0.70–0.76) and the traditional two-factor solution showed good model fit. Full measurement invariance of the CES-D 10 was supported across gender. Consistent with previous literature on risk factors for depressive symptoms, the CES-D 10 was associated with increasing age, and female gender and being out of school in some locations. Conclusions Results from this study support broad use of the CES-D 10 among poor youth populations in SSA. Between one-third and two-thirds of our samples demonstrated depressive symptoms as classified by recommended cut-offs for the CES-D 10, indicating a high burden of mental illness in disadvantaged youth populations. This tool can be used in future efforts to study prevalence and dynamics of depressive symptoms in this population, as well as effectiveness of policies and interventions to improve the mental health of youth in SSA.

Rotavirus is the leading cause of gastroenteritis in children worldwide. In this report, the efficacy of the rotavirus vaccine among 4417 children in Malawi and South Africa was studied in a randomized trial. Severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group as compared with 1.9% of the infants in the pooled vaccine group; the vaccine efficacy was 61.2%. In this trial of rotavirus vaccine in Malawi and South Africa, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group as compared with 1.9% of the infants in the pooled vaccine group; the vaccine efficacy was 61.2%. Rotavirus is the most important cause of severe gastroenteritis among children worldwide. The World Health Organization (WHO) estimates that globally 527,000 deaths occur each year among children as a result of rotavirus infection 1 ; more than 230,000 of the deaths occur in sub-Saharan Africa. Six of the seven countries with the highest mortality due to rotavirus diarrhea are located in Africa. 2 Similarly, data generated from global rotavirus surveillance networks highlight the burden of hospitalizations for rotavirus 3 ; among young children hospitalized for acute diarrhea, the median detection rate for rotavirus was 40% globally and 41% in Africa. Therefore, measures to . . .

Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women. In this cluster randomised trial, never-married women aged 13–22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group). Intervention enumeration areas were further randomly assigned with computer-generated random numbers to conditional (school attendance required to receive payment) and unconditional (no requirements to receive payment) groups. Participants in both intervention groups were randomly assigned by a lottery to receive monthly payments ranging from US$1 to $5, while their parents were independently assigned with computer-generated random numbers to receive $4–10. Behavioural risk assessments were done at baseline and 12 months; serology was tested at 18 months. Participants were not masked to treatment status but counsellors doing the serologic testing were. The primary outcomes were prevalence of HIV and herpes simplex virus 2 (HSV-2) at 18 months and were assessed by intention-to-treat analyses. The trial is registered, number NCT01333826. 88 enumeration areas were assigned to receive the intervention and 88 as controls. For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data, weighted HIV prevalence at 18 month follow-up was 1·2% (seven of 490 participants) in the combined intervention group versus 3·0% (17 of 799 participants) in the control group (adjusted odds ratio [OR] 0·36, 95% CI 0·14–0·91); weighted HSV-2 prevalence was 0·7% (five of 488 participants) versus 3·0% (27 of 796 participants; adjusted OR 0·24, 0·09–0·65). In the intervention group, we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence (3/235 [1%] vs 4/255 [2%]) or weighted HSV-2 prevalence (4/233 [1%] vs 1/255 [<1%]). For individuals who had already dropped out of school at baseline, we detected no significant difference between intervention and control groups for weighted HIV prevalence (23/210 [10%] vs 17/207 [8%]) or weighted HSV-2 prevalence (17/211 [8%] vs 17/208 [8%]). Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low-income settings. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies. Global Development Network, Bill & Melinda Gates Foundation, National Bureau of Economic Research Africa Project, World Bank's Research Support Budget, and several World Bank trust funds (Gender Action Plan, Knowledge for Change Program, and Spanish Impact Evaluation fund).

Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13–26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference –3·1 g [–75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. Bill & Melinda Gates Foundation (INV-010612).

The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine–pyrimethamine. We assessed whether addition of monthly dihydroartemisinin–piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine–pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin–piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin–piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin–piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin–piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin–piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30–0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin–piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22–0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5–10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin–piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin–piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. Addition of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

We conducted a randomized, controlled trial (RCT) to investigate our hypothesis that the interactive chatbot, Vitalk, is more effective in improving mental wellbeing and resilience outcomes of health workers in Malawi than the passive use of Internet resources. For our 2-arm, 8-week, parallel RCT (ISRCTN Registry: trial ID ISRCTN16378480), we recruited participants from 8 professional cadres from public and private healthcare facilities. The treatment arm used Vitalk; the control arm received links to Internet resources. The research team was blinded to the assignment. Of 1,584 participants randomly assigned to the treatment and control arms, 215 participants in the treatment and 296 in the control group completed baseline and endline anxiety assessments. Six assessments provided outcome measures for: anxiety (GAD-7); depression (PHQ-9); burnout (OLBI); loneliness (ULCA); resilience (RS-14); and resilience-building activities. We analyzed effectiveness using mixed-effects linear models, effect size estimates, and reliable change in risk levels. Results support our hypothesis. Difference-in-differences estimators showed that Vitalk reduced: depression (-0.68 [95% CI -1.15 to -0.21]); anxiety (-0.44 [95% CI -0.88 to 0.01]); and burnout (-0.58 [95% CI -1.32 to 0.15]). Changes in resilience (1.47 [95% CI 0.05 to 2.88]) and resilience-building activities (1.22 [95% CI 0.56 to 1.87]) were significantly greater in the treatment group. Our RCT produced a medium effect size for the treatment and a small effect size for the control group. This is the first RCT of a mental health app for healthcare workers during the COVID-19 pandemic in Southern Africa combining multiple mental wellbeing outcomes and measuring resilience and resilience-building activities. A substantial number of participants could have benefited from mental health support (1 in 8 reported anxiety and depression; 3 in 4 suffered burnout; and 1 in 4 had low resilience). Such help is not readily available in Malawi. Vitalk has the potential to fill this gap.

Soil-transmitted helminths are targeted for elimination as a public health problem. This study assessed whether, with high coverage, community-wide mass drug administration (MDA) could lead to transmission interruption. DeWorm3 is an open-label, community cluster-randomised controlled trial in Benin, India, and Malawi. In each country, a single governmental administrative unit (population ≥80 000 individuals) with soil-transmitted helminth endemicity and participation in at least five rounds of community-wide MDA for lymphatic filariasis, was divided into 40 clusters (population ≥1650 individuals), which were randomly assigned (1:1) to community-wide MDA versus school-based deworming. Laboratory personnel were masked to exposure status and all investigators were masked to post-baseline outcome data until unmasking. In all clusters, preschool-aged and school-aged children received school-based deworming as per national guidelines for 3 years. In intervention clusters, door-to-door community-wide MDA (a single oral dose of 400 mg albendazole) was delivered to all eligible individuals biannually by community drug distributors for 3 years. All individuals aged 12 months and older in India and Benin and aged 24 months and older in Malawi were eligible for treatment, except women in the first trimester of pregnancy, those with adverse reactions to benzimidazoles, those who were acutely ill or intoxicated, or those reporting treatment within the previous 2 weeks. The co-primary outcomes were individual-level prevalence and cluster-level transmission interruption (ie, weighted prevalence of predominant species of ≤2%) of the predominant soil-transmitted helminth species, assessed by quantitative PCR (qPCR) 24 months after the last round of MDA. The analysis set contained a subset of randomly selected participants per cluster who enrolled in the endline assessment, provided a stool sample, and had a qPCR result. All individuals who received treatment were eligible for inclusion in the safety population. This trial is registered with ClinicalTrials.gov (NCT03014167), and is active but not recruiting. Between Oct 10, 2017, and Feb 17, 2023, 120 clusters (40 clusters per country, comprising 357 716 individuals) were randomly assigned, 60 to community-wide MDA and 60 to school-based deworming. 184 030 (51·4%) individuals in the clusters at baseline were female, 173 663 (48·5%) were male, and 23 (<0·1%) were other. The analysis set consisted of 58 827 individuals in the control group and 58 554 in the intervention group 24 months after the cessation of all deworming, Necator americanus prevalence (the predominant species at all sites) in the community-wide MDA group was lower than the school-based deworming group in Benin (adjusted prevalence ratio [aPR] 0·44 [95% CI 0·34–0·58]), India (0·41 [0·32–0·52]), and Malawi (0·40 [0·34–0·46]). Transmission interruption was achieved for N americanus in 11 (55%) of 20 intervention clusters versus six (30%) of 20 control clusters in Benin (p=0·20), in one (5%) intervention cluster versus no control clusters in India (p=1·00), and in no clusters in either group in Malawi (p=1·00). 984 adverse events were reported among 487 participants over the study, of which 32 among 13 participants resulted in hospitalisation and were classified as serious adverse events (three of which were related to study procedures). Soil-transmitted helminth transmission interruption might be possible in focal geographies but does not appear to be programmatically feasible within the evaluated timeframe. Community-wide MDA should be considered as an alternative strategy to school-based deworming programmes to improve equity and outcomes in helminth-endemic areas. The Gates Foundation.