Abstract
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 Escherichia coli [ETEC] and Shigella, important enteric pathogens in children in low income countries. These future vaccines could significantly reduce diarrheal burden, prevent ETEC- and Shigella-induced stunting, and stunting-associated mortality. We developed a cost-effectiveness model for two putative standalone ETEC and Shigella 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 Shigella 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 Shigella 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 Shigella vaccine each with 60% efficacy could prevent 92,000 [61,000-129,000] ETEC and 126,600 [84,000-179,000] Shigella direct deaths and 21,400 [11,300-34,800] ETEC- and 34,200 [18,000-56,000] Shigella-induced stunting deaths. ETEC ICERs ranged from $2172/DALY [1457-4369] in AFRO to $19,172/DALY [12,665-39,503] in EURO. Shigella 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 Shigella 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.