Abstract
Diarrheal disease burden has become more heterogenous in low- and lower middle-income countries as access to clean water, sanitation and health care has increased in wealthier urban populations. Enterotoxigenic Escherichia coli (ETEC) and Shigella are among the top five causes of diarrheal mortality in children living in sub-Saharan Africa.Here, we explored how accounting for subnational and economic heterogeneity in ETEC and Shigella disease burden affects projected vaccine impact and cost-effectiveness of standalone ETEC and Shigella vaccines during the first decade after introduction in four sub-Saharan African countries. We developed dynamic models for provincial areas and socioeconomic subpopulations of children in the Democratic Republic of Congo (DRC), Kenya, Zambia, and Zimbabwe. We estimated deaths and morbidity due to ETEC and Shigella diarrhea plus additional deaths from other infectious diseases attributable to ETEC- and Shigella-induced stunting. We analyzed cost-effectiveness using Incremental Cost-Effectiveness Ratios (ICERs) with Disability-Adjusted Life Years (DALYs) and Moderate-and-Severe Diarrheal episodes (MSD) averted as denominators.Other infectious disease deaths due to induced stunting accounted for 9–28% and 9–32% of the total provincial level ETEC and Shigella disease burden, respectively, across these four countries from years 2025 to 2034. Our results indicated that the lowest and most cost-effective provincial DALYs averted ICERs were below $600 and $500/DALY averted for ETEC and Shigella vaccination, respectively in Zimbabwe. ICERs were the highest in Zambia and Kenya, where all provincial ICERs where above $2000/DALY. The highest national and provincial MSD averted ICERs were in DRC, while the lowest were in Kenya and Zimbabwe. Vaccinations were most cost-effective in averting DALYs in lower wealth subpopulations living in the highest burden provincial areas.Our approach focused on subnational heterogeneity in ETEC and Shigella burden and vaccination access found that impact and cost-effectiveness were more favorable if vaccinations reach the most vulnerable children in underserved provinces.
Highlights
While diarrheal mortality has declined 34% worldwide, it is still one of the leading causes of mortality for children under five [1]
Children from Democratic Republic of Congo (DRC) had the greatest number of Enterotoxigenic Escherichia coli (ETEC) and Shigella moderate-to-severe diarrhea (MSD) episodes, while children from Zimbabwe had the highest incidence rate of MSD episodes associated with ETEC and Shigella (Table 2)
Children from the provinces of KasaiOccidental (DRC), North Eastern (Kenya), Northern (Zambia), and Mashonaland Central (Zimbabwe) had the highest predicted incidence rates of ETEC and Shigella MSD episodes from 2025 to 2034 (Table 2). Children from these provinces were estimated to be among the highest rates of total mortality (ETEC and Shigella diarrheal mortality plus other infectious disease deaths due to ETEC- and Shigella-induced stunting)
Summary
While diarrheal mortality has declined 34% worldwide, it is still one of the leading causes of mortality for children under five [1]. Of the leading enteropathogens causing diarrheal disease burden in children under 5 years of age globally and in sub-Saharan Africa [1,4]. A key finding from the Global Enteric Multicenter Study (GEMS) [4] was that childhood episodes of moderate-to-severe diarrhea (MSD) were associated with negative shifts in average in HAZ scores in populations of children.
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