Neonatal Azithromycin Administration for Prevention of Infant Mortality

Oldenburg, Catherine E.; Sié, Ali; Bountogo, Mamadou; Zakané, Alphonse; Compaoré, Guillaume; Ouédraogo, Thierry; Kouéta, Fla; Lebas, Elodie; Brogdon, Jessica; Nyatigo, Fanice; Doan, Thuy; Porco, Travis C.; Arnold, Benjamin F.; Lietman, Thomas M.

doi:10.1056/evidoa2100054

Cited by 22 publications

(43 citation statements)

References 22 publications

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“…The overall point estimate at 12 months of age (19% relative reduction in the azithromycin group) was similar to the point estimate from the trial's primary end point (15% relative reduction at 6 months of age), but the CIs were wide as a result of the low event rate. 3 As expected, causes of death were mostly infectious. Although the overall distribution of causes of death did not differ between arms, deaths determined to be the result of malaria were fewer in children randomized to azithromycin compared with placebo.…”

Section: Discussionmentioning

confidence: 52%

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Effect of Neonatal Azithromycin on All-Cause and Cause-Specific Infant Mortality: A Randomized Controlled Trial

Sié

Bountogo

Zakané

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Mass azithromycin distribution reduces all-cause childhood mortality in some high-mortality settings in sub-Saharan Africa. Although the greatest benefits have been shown in children 1 to 5 months old living in areas with high mortality rates, no evidence of a benefit was found of neonatal azithromycin in a low-mortality setting on mortality at 6 months. We conducted a 1:1 randomized, placebo-controlled trial evaluating the effect of a single oral 20-mg/kg dose of azithromycin or matching placebo administered during the neonatal period on all-cause and cause-specific infant mortality at 12 months of age in five regions of Burkina Faso. Neonates were eligible if they were between the ages of 8 and 27 days and weighed at least 2,500 g at enrollment. Cause of death was determined via the WHO 2016 verbal autopsy tool. We compared all-cause and cause-specific mortality using binomial regression. Of 21,832 infants enrolled in the study, 116 died by 12 months of age. There was no significant difference in all-cause mortality between the azithromycin and placebo groups (azithromycin: 52 deaths, 0.5%; placebo, 64 deaths, 0.7%; hazard ratio, 0.81; 95% CI, 0.56–1.17; P = 0.30). There was no evidence of a difference in the distribution of causes of death (P = 0.40) and no significant difference in any specific cause of death between groups. Mortality rates were low at 12 months of age, and there was no evidence of an effect of neonatal azithromycin on all-cause or cause-specific mortality.

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Section: Discussionmentioning

confidence: 52%

“…The Data and Safety Monitoring Committee recommended continuation of the trial upon review of the interim analysis. 3 Study setting. Participants were enrolled in primary health-care facilities in five regions of Burkina Faso.…”

Section: Methodsmentioning

confidence: 99%

Effect of Neonatal Azithromycin on All-Cause and Cause-Specific Infant Mortality: A Randomized Controlled Trial

Sié

Bountogo

Zakané

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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“…No cases of IHPS were reported in the MORDOR or CHAT trials. In addition, a recent individually randomised trial of azithromycin for neonates 8–27 days old was unable to demonstrate a difference in IHPS between neonates receiving azithromycin or placebo, as only a single case of IHPS was reported in the study population of 21 832 24. However, determining age in days accurately can be challenging in some settings that may receive these distributions.…”

Section: Discussionmentioning

confidence: 94%

“…In addition, a recent individually randomised trial of azithromycin for neonates 8–27 days old was unable to demonstrate a difference in IHPS between neonates receiving azithromycin or placebo, as only a single case of IHPS was reported in the study population of 21 832. 24 However, determining age in days accurately can be challenging in some settings that may receive these distributions. Given these concerns, the main analyses presented here restricted the dosing for the youngest children to avoid dosing over 20 mg/kg and used more conservative tolerance limits than similar studies focused on older populations.…”

Section: Discussionmentioning

confidence: 99%

Simplified dosing of oral azithromycin for children 1–11 months old in child survival programmes: age-based and height-based dosing protocols

Arzika

Sié

et al. 2022

BMJ Glob Health

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BackgroundTo facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended azithromycin distribution to children 1–11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1–5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1–11 months old could increase programme efficiency in real-world settings.MethodsThis secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10–20 mg/kg for children 1–2 months old and 15–30 mg/kg for children 3–11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search.ResultsThe optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1–2 months old and 160 mg (4 mL) for children 3–11 months old. Under this schedule, 89%–93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%–94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1–2, 3–4 and 5–11 months old, respectively. For children 1–5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat.ConclusionsOverall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.

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“…In a more recent review of the cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa, it has been suggested that instead of MDA of azithromycin, targeting high-risk children is an option that could make economic sense while reducing exposure to azithromycin 28 , although the evidence supporting this strategy is currently limited. A trial in neonates receiving biannual azithromycin in sub-Saharan Africa found no evidence to support its' use for prevention of mortality 34 and a trial targeting children under 5 years after hospital discharge found no signi cant bene t of a 5-day course of azithromycin to the risk of death of rehospitalization 35 .…”

Section: Child Mortalitymentioning

confidence: 99%

Implementation of mass drug administration of antibiotics in low- and middle- income countries

O’Sullivan

McCoy

2022

Preprint

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Background Recent years has seen the mass administration of certain antimicrobials, including antibiotics, increasingly promoted as a public health strategy in low- and middle-income countries (LMICs). The WHO currently recommends the mass administrations of azithromycin for three indications: yaws, trachoma, and child mortality. Methods We conducted a desk-based review of secondary data to discuss the clinical, public health and economic evidence underpinning the decision to adopt, and the issues to consider when implementing a mass drug administration (MDA) programme involving azithromycin. Results Before deciding to adopt and implement a policy of MDA of antibiotics, the evidence base should be evaluated, including an economic assessment, and consideration of the distribution of benefits and risks amongst individuals and within communities and populations. Once the decision to adopt has been made, key considerations for successful implementation of a programme include ensuring it does not draw attention and resources away from other health services and finding opportunities for generating efficiencies through integration with existing health interventions. Understanding local attitudes and gaining trust are essential for stakeholder buy-in Furthermore, there must be appropriate attention to the potential harms which include worsening antimicrobial resistance, unintended consequences of public health interventions and reinforcement of a selective primary healthcare paradigm at the expense of a more bottom-up, comprehensive and socially driven pathway to health improvement. Conclusion Although MDA of antibiotics presents an opportunity to prevent mortality and improve health in the short-term, in the case of childhood mortality, MDA of azithromycin can only be a short-term quick fix. Ultimately, long-term, and sustainable child mortality reductions – especially in high mortality settings – will require more comprehensive approaches to health system strengthening and broader-based socio-economic development.

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Neonatal Azithromycin Administration for Prevention of Infant Mortality

Cited by 22 publications

References 22 publications

Effect of Neonatal Azithromycin on All-Cause and Cause-Specific Infant Mortality: A Randomized Controlled Trial

Effect of Neonatal Azithromycin on All-Cause and Cause-Specific Infant Mortality: A Randomized Controlled Trial

Simplified dosing of oral azithromycin for children 1–11 months old in child survival programmes: age-based and height-based dosing protocols

Implementation of mass drug administration of antibiotics in low- and middle- income countries

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