Anderson John D, Bagamian Karoun H, Muhib Farzana, Baral Ranju, Laytner Lindsey A, Amaya Mirna, Wierzba Thomas, Rheingans Richard
Goodnight Family Department of Sustainable Development, Appalachian State University, 222 Living Learning Center, 305 Bodenheimer Drive, Boone, NC 28608, USA.
Emerging Pathogens Institute, P.O. Box 100009, 2055 Mowry Road, Gainesville, FL 32610, USA.
Vaccine X. 2019 Apr 18;2:100024. doi: 10.1016/j.jvacx.2019.100024. eCollection 2019 Aug 9.
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.
在过去二十年中，儿童腹泻死亡率有所下降，但腹泻发作次数的下降则较为缓慢。反复腹泻发作与儿童发育迟缓相关，这会导致传染病死亡风险增加。针对产肠毒素大肠杆菌（ETEC）和霍乱弧菌（V. cholerae）这两种低收入国家儿童重要肠道病原体的候选疫苗正在研发中。这些未来的疫苗可显著减轻腹泻负担，预防ETEC和霍乱弧菌引起的发育迟缓以及与发育迟缓相关的死亡。我们针对两种假定的独立ETEC和霍乱弧菌候选疫苗建立了成本效益模型，以评估疫苗对死亡率、发病率、发育迟缓以及其他传染病所致发育迟缓相关死亡的影响。我们模拟了在79个低收入和中低收入国家五岁以下儿童中引入疫苗后的头十年的影响。从2025年到2034年，ETEC和霍乱弧菌腹泻预计将分别导致239,300例（95%可信区间上限：179,700 - 309,800例）和340,300例（256,500 - 440,800例）儿童死亡。这些死亡大多发生在非洲区域办事处（AFRO）的国家。ETEC和霍乱弧菌的中度至重度腹泻发作将分别导致超过1370万（840万 - 1900万）和2140万（1310万 - 2980万）发育迟缓儿童。引入效力为60%的ETEC或霍乱弧菌疫苗可预防92,000例（61,000 - 129,000例）ETEC和126,600例（84,000 - 179,000例）霍乱弧菌直接死亡以及21,400例（11,300 - 34,800例）ETEC和34,200例（18,000 - 56,000例）霍乱弧菌所致发育迟缓死亡。ETEC的增量成本效果比（ICER）在非洲区域办事处为每残疾调整生命年（DALY）2172美元（1457 - 4369美元），在欧洲区域办事处（EURO）为每DALY 19,172美元（12,665 - 39,503美元）。霍乱弧菌的ICER在东地中海区域办事处（EMRO）为每DALY 952美元（632 - 2001美元），在欧洲区域办事处为每DALY 640,316美元（434,311 - 1,297,192美元）。该分析的局限性包括疫苗效力、保护持续时间和疫苗价格的不确定性。纳入因发育迟缓导致的其他传染病死亡率可更准确地评估ETEC和霍乱弧菌的总体疾病负担，并增加疫苗接种的预计影响和成本效益。仅在高负担国家和地区引入疫苗可大幅降低成本，而不会大幅降低影响。
