Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Lancet. 2013 Jul 20;382(9888):209-22. doi: 10.1016/S0140-6736(13)60844-2. Epub 2013 May 14.
Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia.
The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth.
We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months.
Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes.
The Bill & Melinda Gates Foundation.
腹泻病会导致低收入国家 5 岁以下儿童患病和死亡。我们设计全球肠道疾病多中心研究（GEMS）旨在确定撒哈拉以南非洲和南亚儿科腹泻病的病因和基于人群的负担。
GEMS 是一项为期 3 年的前瞻性、年龄分层、匹配病例对照研究，研究对象为居住在非洲 4 个地点和亚洲 3 个地点的 0-59 月龄儿童中出现中度至重度腹泻的人群。我们招募了在卫生中心寻求治疗的中度至重度腹泻儿童以及 1 至 3 名未出现腹泻的随机选择的社区对照儿童。从中度至重度腹泻患儿和对照者中，我们获得了临床和流行病学数据、人体测量数据以及粪便样本，以在登记时识别肠道病原体；大约 60 天后进行一次随访家访，以确定存活状态、临床结局和间隔期生长情况。
我们共招募了 9439 名中度至重度腹泻患儿和 13129 名无腹泻的对照儿童。通过分析调整后的人群归因分数，大多数中度至重度腹泻的可归因病例是由四种病原体引起的：轮状病毒、隐孢子虫、产热稳定毒素的肠毒性大肠杆菌（ST-ETEC；有无不耐热肠毒素共同表达）和志贺氏菌。其他病原体在特定地点也很重要（例如，气单胞菌、霍乱弧菌 O1、空肠弯曲菌）。与对照组相比，中度至重度腹泻患儿的死亡风险高 8.5 倍（比值比 8.5，95%CI 5.8-12.5，p<0.0001）；大多数死亡（167 [87.9%]）发生在生命的头 2 年。与病例死亡风险增加相关的病原体包括 ST-ETEC（风险比 [HR] 1.9；0.99-3.5）和婴儿（0-11 个月）中典型肠致病性大肠杆菌（HR 2.6；1.6-4.1），幼儿（12-23 个月）中隐孢子虫（HR 2.3；1.3-4.3）。
针对五种病原体（轮状病毒、志贺氏菌、ST-ETEC、隐孢子虫、典型肠致病性大肠杆菌）的干预措施可以显著降低中度至重度腹泻的负担。需要新的方法和加速实施现有的干预措施（轮状病毒疫苗和锌）来预防疾病和改善结局。
比尔及梅琳达·盖茨基金会。
