Potential impact and cost-effectiveness of future ETEC and vaccines in 79 low- and lower middle-income countries.

While diarrhea mortality in children has declined over the last two decades, there has been a slower decline in diarrheal episodes. Repeated diarrheal episodes are associated with childhood stunting, which leads to increased mortality risk from infectious diseases. Vaccine candidates are under development for enterotoxigenic [ETEC] and , important enteric pathogens in children in low income countries. These future vaccines could significantly reduce diarrheal burden, prevent ETEC- and -induced stunting, and stunting-associated mortality. We developed a cost-effectiveness model for two putative standalone ETEC and vaccine candidates to evaluate vaccine impact on mortality, morbidity, stunting, and stunting-associated deaths from other infectious diseases. We modeled impact over the first ten years after vaccine introduction in children under five years old living in 79 low and low-middle income countries. ETEC and diarrhea would cause an estimated 239,300 [95% UL: 179,700-309,800] and 340,300 [256,500-440,800] child deaths, respectively, from years 2025 to 2034. Most of these deaths would occur in AFRO countries. ETEC and moderate-to-severe diarrheal episodes would result in over 13.7 [8.4-19.0] and 21.4 [13.1-29.8] million stunted children, respectively. Introducing ETEC or vaccine each with 60% efficacy could prevent 92,000 [61,000-129,000] ETEC and 126,600 [84,000-179,000] direct deaths and 21,400 [11,300-34,800] ETEC- and 34,200 [18,000-56,000] -induced stunting deaths. ETEC ICERs ranged from $2172/DALY [1457-4369] in AFRO to $19,172/DALY [12,665-39,503] in EURO. ICERs ranged from $952/DALY [632-2001] in EMRO to $640,316/DALY [434,311-1,297,192] in EURO. Limitations of this analysis include uncertainty of vaccine efficacy, duration of protection, and vaccine price. Inclusion of other infectious disease mortality due to stunting provides a more accurate assessment of total ETEC and disease burden and increased the projected impact and cost-effectiveness of vaccination. Introducing vaccines only in high burden countries and regions could substantially reduce cost without substantially reducing impact.