Children under age 5 in Sub-Saharan Africa (SSA) suffer a disproportionately high burden of infectious disease, and remain at high risk for adverse outcomes in the period following acute illness. This includes mortality and linear growth faltering, which can lead to irreversible stunting, which is associated with substantial health and developmental detriments. In SSA, a setting of high infectious disease burden where diagnostic tools are often unavailable, antibiotics may be effective in improving these long-term outcomes due to their growth- promoting, anti-inflammatory, immunomodulatory, and/or prophylactic properties. Community-wide antibiotic administration is being considered for SSA but may lead to widespread antibiotic resistance and be costlier than targeting high-risk groups. In the absence of known etiology, targeting antibiotic administration to high-risk groups is an antibiotic-sparing and potentially cost-effective strategy to maximize potential benefit while minimizing costs and antibiotic exposure. To develop and implement targeted antibiotic interventions, tools for predicting which children are most likely to benefit and data on cost-effectiveness of interventions are needed. Children with diarrhea are a useful sub-population in which to identify those most likely to benefit from targeted antibiotic administration. Among a prospective cohort of children with moderate-to-severe diarrhea in 4 SSA countries, we will evaluate whether antibiotic administration at diarrhea presentation protected children against linear growth faltering in the 50-90 days following the acute illness. Further, we will identify host and clinical factors at presentation that predict a child?s risk of post-diarrhea linear growth faltering. These analyses will inform diarrhea management and identify children who may benefit from empiric antibiotics. Once a targeted antibiotic intervention has been developed, cost-effectiveness analyses are needed to implement interventions as policies that maximize the health impact of limited health resources in SSA. However, an impediment to rigorous cost-effectiveness analyses in SSA is the difficulty of ascertaining high quality, precise cost data. We will identify optimal methods for collecting accurate intervention and health costs in resource limited settings by comparing micro-costing by direct observation and patient record review in a multisite SSA hospitalized cohort. This will inform approaches to costing, ultimately improving economic evaluations in low- resource settings. We will also construct a cost-effectiveness model to compare the cost-effectiveness of targeted vs community-based antibiotic administration for prevention of child morbidity and mortality. Both approaches have been tested in ongoing and recently completed clinical trials but little is known about the comparative cost-effectiveness of these strategies. By estimating the resource implications and health impacts of implementing each strategy, this cost-effectiveness model will be a timely guide for policy development. This research will provide tools to develop and implement cost-effective antibiotic interventions for children in SSA at high risk of growth faltering and death following acute illness.
Children under age 5 in Sub-Saharan Africa experience a high burden of mortality and growth faltering, and targeted antibiotic administration may be a cost-effective strategy for improving these outcomes. This research will provide tools for predicting which children are at highest risk of growth faltering and mortality, and for evaluating intervention cost-effectiveness. This novel evidence will be useful in developing and implementing targeted antibiotic interventions for preventing growth faltering and mortality in Sub-Saharan African children.