BACKGROUND:Many sub-Saharan African countries faced considerable challenges in containing SARS-COV-2 transmission due to limited capacity to test and treat all those affected. While previous studies have measured testing uptake, no study has examined uptake in relation to WHO testing criteria. We assess unmet need for SARS-CoV-2 testing in Ghana, Burkina Faso, and Madagascar as a measure of health system preparedness, defined as the gap between individuals meeting WHO testing criteria and those actually tested. METHODS:We used urban population-based data from 2434 households in Ghana, Burkina Faso, and Madagascar sampled between February and May 2021. We defined unmet need for testing using three measures (serological, exposure-based, symptom-based) aligned with WHO testing criteria and used logistic regression models to examine associated factors and concentration indices to quantify socioeconomic inequalities. RESULTS:Here we show that unmet need for SARS-CoV-2 testing is high, ranging from 93% to 95% across all three countries, regardless of the measure used. Socioeconomic inequalities exist, with the poorest quintile experiencing the highest unmet need. Wealth, travel history outside the city, and perceived COVID-19 risk are associated with lower unmet need. CONCLUSIONS:Our findings reveal critical weaknesses in health system preparedness that call for urgent measures to strengthen testing capacity and ensure equitable access for both routine care provision and future health crises.

ObjectiveTo examine how child mortality among children aged 1-59 months varies by asset-based wealth status in rural Burkina Faso, and to assess the interaction between mass azithromycin (AZ) distribution and wealth status on child mortality at both the household and community levels.MethodsWe used data from a cluster-randomized trial and population census data on household characteristics and assets. A wealth index score for each household, used to classify the population by wealth, was generated using principal component analysis. We used the Relative Index of Inequality (RII), the Slope Index of Inequality (SII), and the concentration index to assess wealth-related inequalities in mortality, and the Gini Index to assess variability in child mortality across households and communities. Poisson regression models were used, with person-time at risk included as an offset, and robust standard error to estimate changes in mortality rates by wealth and treatment arm. Interaction was assessed on both the multiplicative and additive scales.ResultsMortality declined with increasing wealth at both the household and community levels, with a significant gradient at the community level (RII = 1.17, 95% CI: 1.05-1.29; SII = 2.3 per 1,000 person-years, 95% CI: 0.2-4.4), reflecting higher mortality among the poorest. The effect of AZ did not vary significantly by wealth index, and changes in mortality rates across wealth levels were similar between the two treatment arms. There was no evidence of a statistically significant interaction between AZ and asset-based wealth on either the multiplicative or additive scale at the household or cluster level.ConclusionOur findings demonstrate a wealth gradient in child mortality, with the highest mortality rates observed among households and communities in the lowest wealth quintiles. These disparities were consistent across both AZ-treated and placebo groups, suggesting that the role of AZ in health disparities may be limited to addressing gaps in treatment access rather than broader wealth-related disparities. While the study may have been underpowered to detect modest interaction effects, AZ appeared to offer similar benefits across economically diverse communities, with no evidence suggesting enhanced benefits for disadvantaged communities or for prioritizing treatment based on wealth status. Further work is needed to address the wealth-related disparities in child mortality in these communities.Trial registrationClinicalTrials.gov NCT03676764.

To assess the benefits of Seasonal Malaria Chemoprevention (SMC)—the monthly administration of sulfadoxine-pyrimethamine and amodiaquine—beyond malaria prevention in real-world program settings. We conducted a pre-post comparison of non-malarial diagnoses (pneumonia, diarrhea, acute malnutrition) and antibiotic prescription rates during SMC administration weeks versus a three-week post-intervention period in rural Burkina Faso. Data was obtained from clinic surveillance at 51 health facilities, a population-based census, and National Malaria Control Program data on SMC timing. Poisson regression models with person-weeks as an offset and standard errors clustered by health post estimated changes in rates. Interaction terms assessed variation across SMC cycles. Positive (malaria diagnoses, antimalarial prescriptions) and negative (injury) control outcomes were used to evaluate potential unmeasured confounding. Compared to administration weeks, modest declines were observed in pneumonia, diarrhea, and acute malnutrition diagnoses, as well as in antibiotic prescription rates during the post-SMC period. Absolute reductions were 0.7 (95

Global health research requires the integration of diverse datasets and continuous updates to enable more effective monitoring and interpretation of global health trends. However, traditional tabular datasets often fall short in accommodating multiple datasets with heterogeneous schemas and evolving structures, and they hinder the efficient updating of such datasets once integrated. Graph databases offer a natural solution to these challenges by providing a flexible data structure that can explicitly represent complex relationships and accommodate incremental updates without requiring modifications to existing data. This paper presents an initial attempt to apply graph database technology to global health research by proposing a structured roadmap for constructing a Neo4j-based knowledge graph from heterogeneous data sources. The application of knowledge graphs in global health research enables comprehensive, up-to-date representation of complex datasets, facilitates direct insights into multifaceted relationships, supports multi-perspective analyses, and establishes a foundation for scalable and analytically robust research in the field.

Objective:Mass treatment with azithromycin (AZ) and administration of seasonal malaria chemoprevention (SMC) are both effective in reducing mortality among children under 5. However, it is not clear whether the benefit of AZ for mortality varies in the presence of routine SMC administration. The objective of this study was to examine whether the effect of mass AZ distribution on all-cause mortality among children less than 5 years of age varies with SMC administration season or SMC coverage. Methods:This was a secondary analysis of the Community Health with Azithromycin Trial (CHAT), a cluster randomized placebo-controlled trial of 341 communities in the Nouna District of Burkina Faso. Communities randomized to intervention received treatment with twice yearly mass AZ while control communities receive placebo. All communities received SMC as standard-of-care. SMC administration and coverage data were provided from National Malaria Control Program. SMC administration season was defined as the period during and immediately following SMC (July-December) versus the months of no SMC (January-June). SMC coverage was assessed as proportion of the population covered and by whether it was below or above a threshold of 80%. We used Poisson regression models with person-time at risk used as an offset and robust standard error to analyze mortality rates by treatment group and SMC subgroups and assessed interaction on both the multiplicative and additive scales. Results:Mortality was higher in SMC seasons for both arms, with a mortality rate of 10.3 per 1,000 person-years (95% CI: 9.0 to 11.6) in SMC seasons and 7.9 (95% CI: 6.9 to 9.0) in non-SMC seasons. Compared to placebo, the mortality rate in AZ clusters was 0.77 (95% CI: 0.60 to 0.98) during SMC season, while it was 0.89 (95% CI: 0.68 to 1.15) during the non-SMC seasons. The effect of AZ compared to placebo in clusters with <80% SMC coverage was 0.73 95%CI (0.56 to 0.96) and in clusters with ≥80% SMC coverage, it was 1.0 95%CI (0.59 to 1.69). The interaction between AZ and SMC season or coverage was not statistically significant on the additive or multiplicative scales. Conclusion:While our findings did not reach statistical significance, they raise the question of whether prioritizing MDA AZ during high transmission periods or in regions with low SMC coverage could be beneficial. Further research is needed to determine if targeting these periods or areas could lead to greater reductions in child mortality. Trial Registration:ClinicalTrials.gov Identifier: NCT03676764.

Background Severe Acute Malnutrition (SAM) is a major cause of morbidity and mortality in children under five, particularly in sub-Saharan Africa. The World Health Organization (WHO) recommends using mid-upper arm circumference (MUAC) for community-based screening due to its simplicity and cost-effectiveness. This study assesses the impact of MUAC-based screening and referral by community health workers (CHWs) on nutritional status and all-cause mortality in Burkina Faso. Methods A prospective regression discontinuity (RD) analysis was nested within the Community Health with Azithromycin Treatment (CHAT) trial, a cluster-randomized controlled trial in Nouna District, Burkina Faso. Children aged 6-59 months were screened using MUAC, and those with MUAC < 11.5 cm were referred for SAM treatment. The effect of referral on subsequent MUAC measurements and 6-month all-cause mortality was analyzed using data near the 11.5 cm threshold. Bandwidths were selected using the Imbens-Kalyanaraman (IK) algorithm to optimize bias-variance tradeoff. Generalized linear mixed-effects models were applied for analysis. Results Out of 65,554 children screened, 226 (0.34%) were referred for SAM. Using the IK-selected bandwidth for MUAC, no significant effects on 6-month MUAC or mortality were observed. The mean MUAC difference was 0.21 cm (95% CI: -0.22 to 0.65 cm), and the mortality odds ratio was 0.95 (95% CI: 0.03 to 31.37). Sensitivity analyses using broader bandwidths yielded consistent results. Conclusions MUAC-based screening and referral did not significantly improve nutritional status or reduce mortality. Improving SAM referral mechanisms and integrating community health support are necessary to improve health outcomes for children with SAM. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03676764 ### Funding Statement The CHAT study was supported by the Bill and Melinda Gates Foundation (OPP1187628; PI: Lietman). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of the University of California, San Francisco and Comite d'Ethique pour la Recherche en Sante in Ouagadougou, Burkina Faso gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at OSF

While Seasonal Malaria Chemoprevention (SMC) has been adopted as a malaria control strategy in regions with seasonal transmission, continued monitoring and evaluation of its effectiveness across diverse ecological, epidemiological, and healthcare settings remain critical for optimizing the intervention. This study aims to assess the ongoing population-level impact of SMC under routine programme conditions by evaluating rates of uncomplicated and severe malaria following four rounds of administration. A pre-post analysis was conducted using real-world surveillance data from clinic visits in 285 villages in Nouna District, Burkina Faso, along with National Malaria Control Programme data on SMC administration. Estimates of the population used for person-time calculations were derived from a census conducted as part of a randomized controlled trial. Malaria rates for children under 5 were analyzed for each epidemiological week in 2021, for each health post in the study area. Negative binomial regression models were used, with person-time at risk used as an offset and standard errors clustered by health post, to obtain incidence rate ratios (IRRs) and rate differences. Changes in diagnoses were estimated from the administration weeks to each of the three weeks post- administration within the same population. Injury rates were used as a negative control outcome to assess potential unmeasured confounding. Although SMC was administered during peak malaria transmission weeks within each cycle, both uncomplicated and severe malaria rates remained high through December, following the fourth and final round of SMC. There was a substantial reduction in infection rates in the 3 weeks post SMC, with gradual increases in rates across the three weeks. The rates of uncomplicated and severe malaria per 1000 person-weeks in the administration weeks were 8.5 (95

Mass azithromycin distribution has been shown to reduce all-cause child mortality in several settings in the Sahel by 14-18%. A trial in Niger found that mass azithromycin distribution to children ages 1-59 months old reduced cause-specific mortality because of malaria, dysentery, meningitis, and pneumonia. However, this study was done in the absence of seasonal malaria chemoprevention (SMC). Here, we assess the effect of mass azithromycin distribution on cause-specific child mortality in a setting receiving SMC. The Child Health with Azithromycin Treatment trial was a cluster-randomized, placebo-controlled trial of 341 communities in Nouna District, Burkina Faso. Eligible children (ages 1-59 months old) received a single oral 20-mg/kg dose of azithromycin or matching placebo. Six rounds of distribution occurred over a 36-month period. An enumerative census was conducted during each twice-yearly distribution, during which vital status for all children in the community was collected. Verbal autopsy was performed to assess cause of death. Of 1,086 deaths recorded in the trial, verbal autopsy results were available for 992 (91%). The most common causes of death were infectious, including malaria (34%), diarrhea (24%), and pneumonia (9%). Children living in communities receiving azithromycin had significant reduction in malaria mortality (incidence rate ratio, 0.67; 95% CI, 0.50-0.90; P = 0.008). Other infectious causes of mortality, including diarrhea and pneumonia, were lower in communities receiving azithromycin but were not statistically significantly different. Mass azithromycin distribution for child mortality has benefits in the context of SMC for reducing mortality, including for malaria mortality.

BACKGROUND:In 2023, the World Health Organization (WHO) revised its guidelines for management of severe acute malnutrition (SAM). The revised guidelines include a focus on infants at risk of poor growth and development. The guideline identifies evaluation of routine antibiotics for these infants as a priority research area. OBJECTIVE:We pooled data from two large randomized controlled trials evaluating azithromycin for prevention of infant mortality in Burkina Faso to assess whether azithromycin reduces mortality or wasting in this subgroup. METHODS:Infants in the two trials were 1-12 weeks of age at enrollment. Infants were considered at risk of poor risk of growth and development per WHO: underweight (weight-for-age Z-score, WAZ < -2), wasted (weight-for-length Z-score, WLZ < -2), or MUAC < 11.0 cm among infants ≥6 weeks of age. Infants were randomized to a single oral (20 mg/kg) dose of azithromycin or matching placebo and were followed until 6 months of age. We evaluated vital status, underweight (WAZ < -2), wasting (WLZ < -2), and stunting (length-for-age Z-score, LAZ) at 6 months among infants at risk of poor growth and development based on WHO single measurement criteria. RESULTS:A total of 54,709 infants were enrolled in the two trials. Of these, 9,728 were at risk of poor growth and development based on baseline WAZ (N = 5,385), WLZ (N = 6,022), or MUAC (N = 1,541). We found no evidence of a difference in mortality (1.3% vs 1.1%, odds ratio, OR, 1.19, 95% confidence interval, CI, 0.82 to 1.72) or wasting (20.6% vs 20.2%, OR 1.03, 95% CI 0.92 to 1.14) at 6 months among infants receiving azithromycin versus placebo. CONCLUSIONS:In infants aged 1-12 weeks at risk of poor growth and development, we do not have evidence that single dose azithromycin reduces mortality or improves growth outcomes. TRIAL REGISTRATION:ClinicalTrials.gov NCT03682654 and NCT03676764.

The risk of malaria transmission varies between rural and urban areas. Environmental characteristics and habitat structure can explain this variation. Understanding these factors is crucial for the informed selection of existing and new vector control tools. This study investigated how housing and household characteristics affect vector abundance and malaria incidence in a semi-urban and rural setting of Burkina Faso. CDC light traps were used to sample indoor mosquitoes from July to October 2021 in 355 randomly selected houses in semi-urban and rural areas of the Nouna health district. A digital data collection application was used to record information on occupants, housing structure, and household characteristics. Indoor temperature was monitored with a wall thermometer during the night of mosquito collection. Mosquitoes were morphologically sorted and identified by Polymerase Chain Reaction. Poisson and logistic linear models were used to assess the effects of house structure and household characteristics on indoor mosquito abundance, mosquito infection, and human malaria cases. A total of 22,863 mosquitoes were collected, the most abundant of which were Anopheles including Anopheles coluzzii, Anopheles gambiae sensu stricto, Anopheles arabiensis. In the rural site, minor vectors such as Anopheles nili, Anopheles funestus, and Anopheles pharoensis were found. Mosquito abundance, the number of infected mosquitoes, and the presence of human malaria cases didn't vary significantly according to wall type, roof type, the presence of breeding sites, and the use of LLINs. However, the vegetation around the houses was positively associated with mosquito abundance [RR: 2.5; CI (1.43–4.15); p < 0.001], vector infection [RR = 2.5; CI (1.74–3.33); p < 0.001], and the presence of malaria cases [RR: 1.4; CI (1.03–2.0); p = 0.048]. The presence of children under five years of age [RR: 1.52; CI (1.25–1.84); p < 0.001], female householder [RR: 1.23; CI (1.02–2.78); p < 0.001] were also significantly associated with the human malaria cases. The household environment, such as vegetation around houses, appears to increase the risk of malaria transmission, while building materials have a smaller effect, in semi urban and rural areas of Burkina Faso. In addition to prophylaxis and medication, malaria control strategies must strengthen environmental management to keep vector populations away from human dwellings.

The African continent has some of the worlds lowest COVID-19 vaccination rates. While the limited availability of vaccines is a contributing factor, COVID-19 vaccine hesitancy among health care providers (HCP) is another factor that could adversely affect efforts to control infections on the continent. We sought to understand the extent of COVID-19 vaccine hesitancy among HCP, and its contributing factors in Africa. We evaluated COVID-19 vaccine hesitancy among 1,499 HCP enrolled in a repeated cross-sectional telephone survey in Burkina Faso, Ethiopia, Nigeria, Tanzania and Ghana. We defined COVID-19 vaccine hesitancy among HCP as self-reported responses of definitely not, maybe, unsure, or undecided on whether to get the COVID-19 vaccine, compared to definitely getting the vaccine. We used Poisson regression models to evaluate factors influencing vaccine hesitancy among HCP. Approximately 65.6% were nurses and the mean age ({+/-}SD) of participants was 35.8 ({+/-}9.7) years. At least 67% of the HCP reported being vaccinated. Reasons for low COVID-19 vaccine uptake included concern about vaccine effectiveness, side effects and fear of receiving unsafe and experimental vaccines. COVID-19 vaccine hesitancy affected 45.7% of the HCP in Burkina Faso, 25.7% in Tanzania, 9.8% in Ethiopia, 9% in Ghana and 8.1% in Nigeria. Respondents reporting that COVID-19 vaccines are very effective (RR:0.21, 95% CI:0.08, 0.55), and older HCP (45 or older vs.20-29 years, RR:0.65, 95% CI: 0.44,0.95) were less likely to be vaccine-hesitant. Nurses were more likely to be vaccine-hesitant (RR 1.38, 95% CI: 1.00,1.89) compared to doctors. We found higher vaccine hesitancy among HCP in Burkina Faso and Tanzania. Information asymmetry among HCP, beliefs about vaccine effectiveness and the endorsement of vaccines by the public health institutions may be important. Efforts to address hesitancy should address information and knowledge gaps among different cadres of HCP and should be coupled with efforts to increase vaccine supply.

The objective of this study was to examine whether the effect of mass Azithromycin (AZ) distribution on all-cause mortality among children under 5 varies with seasonal malaria chemoprevention (SMC) administration season or coverage. This was a secondary analysis of the Community Health with Azithromycin Trial (CHAT), a cluster-randomized, placebo-controlled trial of twice-yearly AZ treatment in 341 communities in the Nouna District, Burkina Faso. All communities received SMC as standard-of-care. SMC administration and coverage data were provided from National Malaria Control Program. SMC season was defined as the period during and following SMC (July-December) versus the no SMC season (January-June). SMC coverage was assessed as proportion of the population covered and by whether it was below or above a threshold of 80%. We used Poisson regression models with person-time at risk as an offset and robust standard error to analyze mortality rates by treatment group and SMC subgroups and assessed interaction on both multiplicative and additive scales. Mortality was higher in SMC seasons for both arms. Compared to placebo, the mortality rate in AZ clusters was 0.77 (95% CI: 0.60 to 0.98) during SMC season, while it was 0.89 (95% CI: 0.68 to 1.15) during the non-SMC seasons. In clusters with <80% SMC coverage, the effect of AZ was 0.73 95%CI (0.56 to 0.96) and in clusters with ≥80% SMC coverage, it was 1.0 95%CI (0.59 to 1.69). The interaction between AZ and SMC season or coverage was not statistically significant on the additive or multiplicative scales. While our findings did not reach statistical significance, they raise the question of whether prioritizing MDA AZ during high transmission periods or in regions with low SMC coverage could be beneficial. Further research is needed to determine if targeting these periods or areas could further reduce child mortality.

Rising temperatures in Africa present an increasing threat to agricultural productivity and public health, particularly among subsistence farming communities reliant on rain-fed agriculture. Heat exposure can impair farmers’ work capacity, disrupt harvests, and heighten health risks, especially for young children vulnerable to undernutrition. The Heat to Harvest (H2H) study investigates how environmental heat exposure influences farmers’ physiological and behavioral responses, and how these in turn affect harvest yields and child nutrition. It also examines differences in labor performance and recovery between households with and without cool roof coatings, although this intervention is not the central focus. H2H is designed as a prospective cohort study nested within two Health and Demographic Surveillance Systems (HDSS) in Nouna, Burkina Faso, and Siaya, Kenya. The study integrates environmental monitoring (temperature and humidity sensors used to compute Wet Bulb Globe Temperature), biometric data (via wearables tracking heart rate, temperature, physical activity, energy expenditure, and sleep), and GPS tracking (capturing spatial mobility and labor duration). The study is embedded within a larger cluster-randomized controlled trial, facilitating comparative analysis under varying thermal conditions. Findings will provide evidence-based insights into how climate-related heat stress affects health and agricultural outcomes, supporting the development of targeted adaptation strategies to enhance resilience, health, and food security in vulnerable farming communities.

ObjectiveThis scoping review aims to identify risk factors for COPD and asthma, examine the burden and intervention measures, and clarify the findings in the context of climate change, with a particular focus on LMICs.MethodsFollowing the PRISMA-ScR guidelines, we conducted a scoping review using PubMed, Embase, and Scopus, focusing on studies published from 2011 to 2024.ResultsOur review included 52 studies that encompassed 244,004 participants. Predominantly conducted in SSA (n = 43, 83%) and Asia (n = 16, 31%), they address indoor and ambient air pollution, occupational hazards, and environmental conditions. Climate change exacerbates risks, varying regionally. SSA faces severe household and occupational exposures, while other LMICs deal with industrial and urban pollution. Stigma, social exclusion and economic burden underscore the necessity for intervention strategies (e.g., educational programs, pulmonary rehabilitation, low-emission cookstoves).ConclusionOur research shows a strong link between air pollution, occupational and environmental exposures, and the prevalence of COPD and asthma in LMICs. It suggests that targeted interventions are effective ways to mitigate these diseases and also highlights the significant impact of climate change on respiratory health.

Children with acute malnutrition are at high risk of morality. Mass azithromycin distribution reduces all-cause mortality among children aged 1-59 months, and effects may be greater in underweight infants. Here, we evaluate the efficacy of azithromycin for reducing all-cause mortality in children aged 6-59 months with acute malnutrition (mid-upper arm circumference, MUAC, < 12.5 cm). Communities in Nouna District, Burkina Faso were 1:1 randomized to biannual mass distribution of single dose azithromycin or placebo to all children aged 1-59 months. Mortality was assessed during each census and treatment round. MUAC measurements were collected for all children. We evaluated the effect of azithromycin on mortality in subgroups of children aged 6-59 months defined by acute malnutrition (MUAC < 12.5 cm versus MUAC ≥ 12.5 cm). In children with MUAC < 12.5 cm, mortality rates were 51% lower among those living in azithromycin communities compared to placebo (incidence rate ratio 0.49, 95% confidence interval, CI, 0.25 to 0.99; incidence rate difference -18.1 deaths per 1,000 person-years, 95% CI -37.0 to -0.01), which was greater than the reduction in mortality among children with MUAC ≥ 12.5 cm (P-value for interaction on the relative scale = 0.09; P-value for interaction of the additive scale = 0.03). Children with acute malnutrition may benefit from single dose azithromycin above and beyond those without acute malnutrition. Trial registration: ClinicalTrials.gov NCT03676764; https://clinicaltrials.gov/study/NCT03676764.

Objective: To assess the ongoing population-level impact of Seasonal malaria chemoprevention (SMC) under routine program conditions by evaluating uncomplicated and severe malaria rates following the four rounds of SMC administration. Methods: We used data from a randomized controlled trial (RCT) of 285 villages in Nouna District, Burkina Faso, surveillance data of clinic visits and National Malaria Control Program data on SMC administration to calculate the malaria rates for each epidemiological week in 2021 for each health post in the study area. Negative binomial regression models were used with person-time used as offset and standard errors clustered by health post to obtain incidence rate ratios (IRRs) and rate differences estimating changes in diagnoses. Results: Although SMC was administered during malaria peak weeks, both uncomplicated and severe malaria rates were high through December, after the fourth/last round of SMC. There was substantial reduction in infection rates in the 3 weeks post SMC, with a slight increase in rates around the 3rd week. Uncomplicated malaria rates were lower by 36%, 95%CI (24% - 45%), 37% (27% - 45%) and 23% (12% - 33%) in the first, second and third week after administration, respectively. Severe malaria rates lowered by 41% (14%-59%), 51% (32%-65%) and 25% (5%-40%) in the three weeks post-administration. Conclusion: Under routine program conditions, at the population level, SMC administration was associated with substantial reduction in uncomplicated and severe malaria but only in the immediate weeks post-administration. Assessment of local epidemiology and extension of the areas in which 5 rounds are distributed may be needed to effectively prevent malaria infections in areas with a longer transmission season.

Although community randomized trials have found a reduction in all-cause child mortality in communities receiving mass azithromycin distribution compared with placebo, individually randomized trials have not found similar protective effects. If a direct effect of azithromycin for prevention of child mortality exists, it is likely due to reduction in infectious mortality. Here, we assessed cause-specific mortality in a large randomized controlled trial of azithromycin administered during well-infant visits in Burkina Faso for prevention of mortality. Among 32,877 enrolled infants, the most common causes of death by 6 months of age were malaria, acute respiratory infections, and diarrheal disease. We found no evidence of a difference in the distribution of cause of death by randomized treatment assignment (P = 0.42) or in any infectious-specific cause of death. The results of this analysis are consistent with no direct effect of azithromycin on infant mortality when administered during well-infant visits.

Importance Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.

Background High ambient air temperatures in Africa pose significant health and behavioral challenges in populations with limited access to cooling adaptations. The built environment can exacerbate heat exposure, making passive home cooling adaptations a potential method for protecting occupants against indoor heat exposure. Methods We are conducting a 2-year community-based stratified cluster randomized controlled trial (cRCT) implementing sunlight-reflecting roof coatings, known as “cool roofs,” as a climate change adaptation intervention for passive indoor home cooling. Our primary research objective is to investigate the effects of cool roofs on health, indoor climate, economic, and behavioral outcomes in rural Burkina Faso. This cRCT is nested in the Nouna Health and Demographic Surveillance System (HDSS), a population-based dynamic cohort study of all people living in a geographically contiguous area covering 59 villages, 14305 households and 28610 individuals. We recruited 1200 participants, one woman and one man, each in 600 households in 25 villages in the Nouna HDSS. We stratified our sample by (i) village and (ii) two prevalent roof types in this area of Burkina Faso: mud brick and tin. We randomized the same number of people (12) and homes (6) in each stratum 1:1 to receiving vs. not receiving the cool roof. We are collecting outcome data on one primary endpoint - heart rate, (a measure of heat stress) and 22 secondary outcomes encompassing indoor climate parameters, blood pressure, body temperature, heat-related outcomes, blood glucose, sleep, cognition, mental health, health facility utilization, economic and productivity outcomes, mosquito count, life satisfaction, gender-based violence, and food consumption. We followed all participants for 2 years, conducting monthly home visits to collect objective and subjective outcomes. Approximately 12% of participants ( n = 152) used smartwatches to continuously measure endpoints including heart rate, sleep and activity. Discussion Our study demonstrates the potential of large-scale cRCTs to evaluate novel climate change adaptation interventions and provide evidence supporting investments in heat resilience in sub-Saharan Africa. By conducting this research, we will contribute to better policies and interventions to help climate-vulnerable populations ward off the detrimental effects of extreme indoor heat on health. Trial registration German Clinical Trials Register (DRKS) DRKS00023207. Registered on April 19, 2021.