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Infant undernutrition is thought to contribute to growth failure and mortality. We evaluated the patterns in underweight in a population-based sample of children aged 1–11 months in rural northwestern Burkina Faso. Data were collected during the baseline assessment of a community-randomized trial evaluating mass azithromycin distribution in Nouna District, Burkina Faso. A door-to-door census was undertaken for all households in all communities. Infants aged 1–11 months were weighed for weight-based dosing in the trial and their weights were used to calculate weight-for-age Z-scores (WAZ). Underweight was defined as WAZ ≤ 2. We evaluated the age patterns in WAZ and underweight by demographic, seasonal, and geographic characteristics. Of 7,109 infants, 6,077 had accurate weight and global positioning system (GPS) coordinate data (85.5%). Infants were a median of 6 months old (interquartile range [IQR] 3–8) and 48.4% were female. Mean WAZ was −0.68 (SD 1.6) and 19.0% were underweight. The WAZ decreased with increasing age, and the prevalence of underweight increased from 2.5% among 1-month-olds to 27.6% among 11-month-olds. Underweight was more common among boys than girls (22.1% among boys versus 15.6% among girls). Improved latrine use by the household was associated with increased WAZ, and this effect was stronger in male compared with female infants. Given the large burden of underweight among infants, interventions addressing undernutrition should specifically include infants.

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.

Background/AimsAlthough tremendous progress towards the 2020 goal of global elimination of trachoma as a public health problem has been made, it will not be achieved. Future targets are now being considered. One option is changing the goal to eradication. We surveyed trachoma experts to assess beliefs related to trachoma eradication and determine perceived obstacles to achieving it.MethodsWe conducted a survey at the beginning of a trachoma eradication session at the 2019 Coalition for Operational Research on Neglected Tropical Diseases meeting in National Harbor, Maryland, USA. We asked respondents what the most important goal of azithromycin mass drug administration was for trachoma (control, elimination of infection or eradication) and if and when they believed trachoma eradication would occur. We then asked what the biggest obstacles were to global eradication.ResultsFifty-six surveys were returned (95%). Most (91%) participants reported that the most important goal of azithromycin mass drug administration was control or elimination of infection, and 24% of participants reported that global eradication was not possible. Of the 76% who reported a year by which they believed trachoma could be eradicated, most fell between 2040 and 2050. Commonly cited barriers to global eradication included lack of surveillance tools to confirm eradication or monitor for infection recrudescence (32%) and lack of resources (23%).ConclusionsDevelopment of alternative indicators for trachoma surveillance and continued investment in trachoma programmes, particularly focused support in the most heavily affected populations, might increase enthusiasm for the feasibility of eradication.

Background Azithromycin has recently been shown to reduce all-cause childhood mortality in sub-Saharan Africa. One potential mechanism of this effect is via the anti-malarial effect of azithromycin, which may help treat or prevent malaria infection. This study evaluated short- and longer-term effects of azithromycin on malaria outcomes in children. Methods Children aged 8 days to 59 months were randomized in a 1:1 fashion to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Children were evaluated for malaria via thin and thick smear and rapid diagnostic test (for those with tympanic temperature ≥ 37.5 °C) at baseline and 14 days and 6 months after treatment. Malaria outcomes in children receiving azithromycin versus placebo were compared at each follow-up timepoint separately. Results Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. Children were a median of 26 months and 51% were female, and 17% were positive for malaria parasitaemia at baseline. There was no evidence of a difference in malaria parasitaemia at 14 days or 6 months after treatment. In the azithromycin arm, 20% of children were positive for parasitaemia at 14 days compared to 17% in the placebo arm (P = 0.43) and 7.6% vs. 5.6% in the azithromycin compared to placebo arms at 6 months (P = 0.47). Conclusions Azithromycin did not affect malaria outcomes in this study, possibly due to the individually randomized nature of the trial. Trial registration This study is registered at clinicaltrials.gov (NCT03676751; registered 19 September 2018).

Importance Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, setting, and participants Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main outcomes and measures The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and relevance Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial registration ClinicalTrials.gov Identifier: NCT04332107.

Background Azithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission. Methods We evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit. Results We enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18–0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32). Conclusions We did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020

Background Delays in care-seeking for childhood illness may lead to more severe outcomes. We evaluated whether community distance from a primary healthcare facility was associated with decreased healthcare utilization in a rural district of northwestern Burkina Faso. Methods We conducted passive surveillance of all government-run primary healthcare facilities in Nouna District, Burkina Faso from March 1 through May 31, 2020. All healthcare visits for children under 5 years of age were recorded on a standardized form for sick children. We recorded the age, sex, and community of residence of the child as well as any diagnoses and treatments administered. We calculated healthcare utilization per 100 child-months by linking the aggregate number of visits at the community level to the community’s population of children under 5 months per a census that was conducted from August 2019 through February 2020. We calculated the distance between each community and its corresponding healthcare facility and assessed the relationship between distance and the rate of healthcare utilization. Results In 226 study communities, 12,676 primary healthcare visits were recorded over the three-month period. The median distance between the community and primary healthcare facility was 5.0 km (IQR 2.6 to 6.9 km), and median number of healthcare visits per 100 child-months at the community level was 6.7 (IQR 3.7 to 12.3). The rate of primary healthcare visits declined with increasing distance from clinic (Spearman’s rho − 0.42, 95% CI − 0.54 to − 0.31, P Conclusions We documented a distance decay effect between community distance from a primary healthcare facility and the rate of healthcare visits for children under 5. Decreasing distance-related barriers, for example by increasing the number of facilities or targeting outreach to more distant communities, may improve healthcare utilization for young children in similar settings.

Of 61 355 visits by children

Access to improved sanitation and hygiene may improve child nutritional status by reducing exposure to enteric pathogens. We evaluated this relationship as part of the Community Health with Azithromycin Trial, a community-randomized trial of azithromycin versus placebo for the prevention of child mortality in rural Burkina Faso. Before the baseline study visit, a door-to-door household survey was conducted for all households in the study area. During the baseline study census, which occurred approximately 9 months after the household survey, a mid-upper arm circumference (MUAC) measurement was obtained from each child. We evaluated the relationship between household improved latrine use compared with unimproved latrines or open defecation and MUAC in children aged 6–59 months. Among 32,172 children with household survey data and MUAC measurements, 931 (2.9%) had an MUAC less than 12.5 cm and were classified as having moderate acute malnutrition (MAM). The odds of MAM were higher in children living in households with an unimproved latrine than those with an improved latrine (adjusted odds ratio: 1.60; 95% CI: 1.11–2.31). Children in households with unimproved latrines and households that practiced open defection had approximate 0.15 cm reduced MUAC compared with those in households with an improved latrine. There was a small, but statistically significant, association between improved latrine and nutritional status in preschool children as measured by MUAC.

Zoonotic transmission is likely a pathway for antibiotic resistance. Data from a randomized trial of pediatric antibiotic administration were secondarily evaluated to determine if poultry ownership was significantly associated with the presence of gut genetic antibiotic resistance determinants among 118 children in Burkina Faso. Antimicrobial resistance (AMR) determinants were classified using DNA sequencing. We measured the relationship between genetic resistance determinants and chicken ownership using a logistic regression model adjusted for confounding variables. Children in households reporting poultry ownership had four times the odds of tetracycline resistance determinants in the gut compared with those without household poultry (odds ratio [OR]: 4.08, 95% CI: 1.08–15.44, P = 0.04). There was no statistically significant difference found for other antibiotic classes. Understanding the origins of antibiotic resistance may help spur the development of interventions to combat the global AMR crisis.

Biannual mass azithromycin distribution reduces all-cause child mortality in some settings in sub-Saharan Africa; however, adverse events and short-term infectious outcomes following treatment have not been well characterized. Children aged 0–59 months were recruited in Nouna Town, Burkina Faso, and randomized 1:1 to a single directly observed oral 20 mg/kg dose of azithromycin or placebo. At 14 days after treatment, caregivers were interviewed about adverse event symptoms their child experienced since treatment and if they had sought health care for their child. All children had tympanic temperature measured at the 14-day visit. We compared adverse events and clinic visits using logistic regression models between azithromycin- and placebo-controlled children. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. On average, children were aged 28 months, and 50.9% were female. Caregivers of 20% of children reported that their child experienced at least one adverse event, with no significant difference between study arms (19.9% azithromycin; 20.0% placebo, logistic regression P = 0.96). Vomiting was more often reported by caregivers of azithromycin-treated children than by those of placebo-treated children (7.2% azithromycin, 1.9% placebo, logistic regression P = 0.01). There were no significant differences in other adverse events or clinic visits. Adverse events following a single oral dose of azithromycin in preschool children were rare and mild. Azithromycin administration appears safe in this population.

Increasing antibiotic consumption has been shown to lead to increased antibiotic resistance selection. We evaluated the prevalence of antibiotic resistance in Streptococcus pneumoniae to commonly used antibiotic classes as well as correlations between resistance and antibiotic consumption at the individual and community levels in children aged 0-59 months in Nouna district, Burkina Faso. A population-based sample of 300 children aged 0-59 months was randomly selected from the most recent census in 18 communities in the Nouna Health and Demographic Surveillance Site. Caregivers were interviewed about children's recent antibiotic use, and a nasopharyngeal swab was collected from each child. Nasopharyngeal swabs were processed using standard microbiological methods to determine pneumococcal carriage and resistance. Community-level antibiotic consumption was determined by record review from primary healthcare facilities, which routinely collect prescription data for children aged 0-59 months. Streptococcus pneumoniae was isolated from 101 (35.7%) nasopharyngeal samples. Among positive isolates, co-trimoxazole (75.6%) and tetracycline (69.3%) resistance was the most common, followed by oxacillin (26.7%) and azithromycin (9.9%). Recent antibiotic use was associated with decreased pneumococcal carriage (odds ratio 0.56, 95% CI: 0.33-0.93) at the individual level. There was no statistically significant relationship between antibiotic use and antibiotic resistance at the individual or community levels, although CIs were generally wide. The prevalence of antibiotic resistance to commonly used antibiotics was high in the study area. Expanding antimicrobial resistance surveillance in areas with little population-based data will be important for informing policy related to antibiotic use.

Background We evaluated universal insecticide-treated bed net access and use in children 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 Results In 23 610 households with at least one child 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.