Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

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. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Azithromycin during Routine Well-Infant Visits to Prevent Death.

BACKGROUND: Mass distribution of azithromycin to children 1 to 59 months of age has been shown to reduce childhood all-cause mortality in some sub-Saharan African regions, with the largest reduction seen among infants younger than 12 months of age. Whether the administration of azithromycin at routine health care visits for infants would be effective in preventing death is unclear. METHODS: We conducted a randomized, placebo-controlled trial of a single dose of azithromycin (20 mg per kilogram of body weight) as compared with placebo, administered during infancy (5 to 12 weeks of age). The primary end point was death before 6 months of age. Infants were recruited at routine vaccination or other well-child visits in clinics and through community outreach in three regions of Burkina Faso. Vital status was assessed at 6 months of age. RESULTS: Of the 32,877 infants enrolled from September 2019 through October 2022, a total of 16,416 infants were randomly assigned to azithromycin and 16,461 to placebo. Eighty-two infants in the azithromycin group and 75 infants in the placebo group died before 6 months of age (hazard ratio, 1.09; 95% confidence interval [CI], 0.80 to 1.49; P = 0.58); the absolute difference in mortality was 0.04 percentage points (95% CI, -0.10 to 0.21). There was no evidence of an effect of azithromycin on mortality in any of the prespecified subgroups, including subgroups defined according to age, sex, and baseline weight, and no evidence of a difference between the two trial groups in the incidence of adverse events. CONCLUSIONS: In this trial conducted in Burkina Faso, we found that administration of azithromycin to infants through the existing health care system did not prevent death. (Funded by the Bill and Melinda Gates Foundation; CHAT ClinicalTrials.gov number, NCT03676764.).

Health and economic benefits of secondary education in the context of poverty: Evidence from Burkina Faso.

Even though formal education is considered a key determinant of individual well-being globally, enrollment in secondary schooling remains low in many low- and middle-income countries, suggesting that the perceived returns to such schooling may be low. We jointly estimate survival and monetary benefits of secondary schooling using detailed demographic and surveillance data from the Boucle du Mouhoun region, Burkina Faso, where national upper secondary schooling completion rates are among the lowest globally (<10%). We first explore surveillance data from the Nouna Health and Demographic Surveillance System from 1992 to 2016 to determine long-term differences in survival outcomes between secondary and higher and primary schooling using Cox proportional hazards models. To estimate average increases in asset holdings associated with secondary schooling, we use regionally representative data from the Burkina Faso Demographic Health Surveys (2003, 2010, 2014, 2017-18; N = 3,924). Survival was tracked for 14,892 individuals. Each year of schooling was associated with a mortality reduction of up to 16% (95% CI 0.75-0.94), implying an additional 1.9 years of life expectancy for men and 5.1 years for women for secondary schooling compared to individuals completing only primary school. Relative to individuals with primary education, individuals with secondary or higher education held 26% more assets (SE 0.02; CI 0.22-0.30). Economic returns for women were 3% points higher than male returns with 10% (SE 0.03; CI 0.04-0.16) vs. 7% (SE 0.02; CI 0.02-0.012) and in rural areas 20% points higher than in urban areas with 30% (SE 0.06; CI 0.19-0.41) vs. 4% (SE 0.01; CI 0.02-0.07). Our results suggest that secondary education is associated with substantial health and economic benefits in the study area and should therefore be considered by researchers, governments, and other major stakeholders to create for example school promotion programs.

Ethnic diversity and mortality in northwest Burkina Faso: An analysis of the Nouna health and demographic surveillance system from 2000 to 2012.

Ethnic diversity has been a topic of contention across the globe, contrasted with economic development, social security, and political stability. The link between health and ethnic diversity is not yet well established especially in low-middle- income countries. Our study aims to explore the association between ethnic diversity and all-cause mortality in rural areas of Burkina Faso. We used data from the Nouna Health & Demographic Surveillance System (HDSS) collected between 2000 and 2012. To derive Standardized Mortality Ratios (SMR), the observed number of deaths was compared to the expected deaths based on the entire HDSS taking into account sex, age, rainy season, calendar year, and village. SMR were calculated for ethnic and religious diversity on a village level (using the Simpson Index), sub-region, wealth, and distance to Healthcare Facilities (HCF). Furthermore, we modeled SMR with a multilevel random intercept Poisson regression considering individual ethnic and religious groups in addition to the above-mentioned village-level information. Village wealth (poorest fifth: SMR 1.07; 95% CI: 1.02-1.13, richest fifth: SMR 0.85; 95% CI: 0.82-0.88), distance to HCF (within the village: SMR 0.88; 95% CI: 0.85-0.91, further than 5km: SMR 1.13; 95% CI: 1.10-1.16), and sub-region showed significant associations with overall mortality. Villages belonging to the third with the highest ethnic diversity had lowered SMR (0.86; 95% CI: 0.84-0.89) compared to the entire HDSS, while those belonging to the lowest diversity third yielded elevated SMR (1.13; 95% CI: 1.09-1.17). The multilevel model confirmed the association. Our study showed that historically established ethnic diversity in rural areas of Burkina Faso was associated with lower all-cause mortality. Generally, the literature suffers from a lack of standardization in defining ethnic diversity, along with measuring it. More research is needed to understand this relation and to establish it in different settings.

Insecticide-treated bed net access and use among preschool children in Nouna District, Burkina Faso.

BACKGROUND: We evaluated universal insecticide-treated bed net access and use in children <5 y of age in a rural area of Burkina Faso. METHODS: A door-to-door enumerative census was conducted in Nouna District, Burkina Faso in December 2018 through April 2019. The most recent mass bed net distribution campaign occurred in June 2016. Heads of households were interviewed about household bed net ownership and use by children <5 y of age. We evaluated the relationship between demographic and socio-economic factors and household universal bed net access and use by children. RESULTS: In 23 610 households with at least one child <5 y of age, 71 329 bed nets were reported (94.5% insecticide-treated). One-third (35.2%) of households had universal access and two-thirds (67.0%) of children slept under an insecticide-treated net the previous night. Children in households with universal access more often slept under a net the previous night (adjusted odds ratio 4.81 [95% confidence interval 4.39-5.26]). CONCLUSIONS: Bed net coverage was substantially less than the 80% World Health Organization target for universal coverage in Nouna District. Insecticide-treated nets were used preferentially for children, but important gaps remain in consistent bed net use in this population. Structural and behavioural interventions are needed to close these gaps.

A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol.

BACKGROUND: Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa. METHODS/DESIGN: The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5-12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019. DISCUSSION: This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results.

Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.

INTRODUCTION: Biannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period. METHODS AND ANALYSIS: The Nouveaux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol #18-25027) and the Comité National d'Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol #2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03682653; Pre-results.

Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

Weather and mortality: a 10 year retrospective analysis of the Nouna Health and Demographic Surveillance System, Burkina Faso.

BACKGROUND: A growing body of evidence points to the emission of greenhouse gases from human activity as a key factor in climate change. This in turn affects human health and wellbeing through consequential changes in weather extremes. At present, little is known about the effects of weather on the health of sub-Saharan African populations, as well as the related anticipated effects of climate change partly due to scarcity of good quality data. We aimed to study the association between weather patterns and daily mortality in the Nouna Health and Demographic Surveillance System (HDSS) area during 1999-2009. METHODS: Meteorological data were obtained from a nearby weather station in the Nouna HDSS area and linked to mortality data on a daily basis. Time series Poisson regression models were established to estimate the association between the lags of weather and daily population-level mortality, adjusting for time trends. The analyses were stratified by age and sex to study differential population susceptibility. RESULTS: We found profound associations between higher temperature and daily mortality in the Nouna HDSS, Burkina Faso. The short-term direct heat effect was particularly strong on the under-five child mortality rate. We also found independent coherent effects and strong associations between rainfall events and daily mortality, particularly in elderly populations. CONCLUSION: Mortality patterns in the Nouna HDSS appear to be closely related to weather conditions. Further investigation on cause-specific mortality, as well as on vulnerability and susceptibility is required. Studies on local adaptation and mitigation measures to avoid health impacts from weather and climate change is also needed to reduce negative effects from weather and climate change on population health in rural areas of the sub-Saharan Africa.

An improved method for physician-certified verbal autopsy reduces the rate of discrepancy: experiences in the Nouna Health and Demographic Surveillance Site (NHDSS), Burkina Faso.

BACKGROUND: Through application of the verbal autopsy (VA) approach, trained fieldworkers collect information about the probable cause of death (COD) by using a standardized questionnaire to interview family members who were present at the time of death. The physician-certified VA (PCVA), an independent review of this questionnaire data by up to three physicians trained in VA coding, is currently recommended by the World Health Organization (WHO) and is widely used in the INDEPTH Network. Even given its appropriateness in these contexts, a large percentage of causes of death assigned by VAs remains undetermined. As physicians often do not agree upon a final COD classification, there remains substantial room to improve the standard VA method, potentially leading to a reduction in physician discordance in COD coding. METHODS: We present an extension of the current method of PCVA and compare it to the standard WHO-recommended procedure. We used VA data collected in the Nouna Health and Demographic Surveillance Site (NHDSS) between 2009 and 2010 using a locally-adapted version of an INDEPTH standard verbal autopsy questionnaire. Until 2009, physicians in the NHDSS followed the WHO method (Method 1). As an extension of Method 1, starting in 2010, the use of a panel of physicians was added to the coding process in the case where a third physician's final conclusions resulted in an undetermined COD (Method 2). Two independent samples of VA questionnaires were compared for the year 2009 (using Method 1) and the year 2010 (using Method 2). RESULTS: The WHO-recommended method used for 2009 yielded a high level of undetermined CODs, where the final coding was "undetermined" in 50.8% of all questionnaires due to disagreement among participating physicians (Method 1). By introducing a panel of physicians in 2010 for cases where the principal physicians disagreed on the cause of death, the revised method significantly reduced the proportion of undetermined CODs to 1.5% (Method 2). CONCLUSIONS: As the extended method of PCVA significantly improved the accuracy of the VA procedure, we suggest the adoption of this method for those countries where alternatives like computer-based VA coding are not available. Based on the results of our study, further research should be pursued.