Projected Impact and Cost-effectiveness of Community-based Versus Targeted Azithromycin Administration Strategies for Reducing Child Mortality in Sub-Saharan Africa

Abstract Background Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa. AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1–59 months of age, MDA to children 1–5 months of age, AZM administered at hospital discharge, and the combination of MDA and postdischarge AZM. Methods Cost-effectiveness was modeled from a payer perspective with a 1-year time horizon, and was presented as cost per disability-adjusted life-year (DALY) averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Results Assuming a base-case 1.64% mortality risk among children 1–59 months old, 3.1% among children 1–5 months old, 4.4% mortality risk postdischarge, and 13.5% mortality reduction per trial data, MDA would avert ~267 000 deaths at a cost of $14.26/DALY averted (95% uncertainty interval [UI], 8.72–27.08). MDA to only children 1–5 months old would avert ~186 000 deaths at a cost of $4.89/DALY averted (95% UI, 2.88–11.42), and postdischarge AZM would avert ~45 000 deaths, at a cost of $2.84/DALY (95% UI, 1.71–5.57) averted. Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. Conclusions Targeting AZM to children at highest risk of death may be an antibiotic-sparing and highly cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.