The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS)
The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS)
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DOI：
10.1016/s2214-109x(19)30076-2
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发表时间：
2019-05-01
影响因子：
34.3
通讯作者：
Levine, Myron M.
中科院分区：
文献类型：
--
作者：
Kotloff, Karen L.;Nasrin, Dilruba;Levine, Myron M.
腹泻病仍然是低收入和中等收入国家5岁以下儿童患病和死亡的主要原因。全球肠道多中心研究（GEMS）描述了居住在撒哈拉以南非洲和南亚人口普查人群中的0-59个月儿童中有医疗护理的中度至重度腹泻（MSD）的发病率、病因学和后遗症，其中大多数儿童死亡发生在这些地区。为了进一步减轻这种疾病的负担和指导干预措施，我们扩展这项研究，包括儿童的情节不太严重的腹泻（LSD）寻求保健中心服务6 GEMS sites.Methods我们报告了一个为期1年的，多地点，年龄分层，匹配的病例对照研究后的GEMS研究。六个地点（马里巴马科;莫桑比克的Manhica;冈比亚巴塞;孟加拉国米尔扎布尔;印度加尔各答;和Bin Qasim Town，卡拉奇，巴基斯坦）参加了这项研究。每个地点0-59个月的儿童在12个月期间到哨点医院或保健中心寻求治疗，并接受腹泻筛查。在眼睛凹陷、皮肤失去肿胀、接受静脉补液、患有痢疾或住院的儿童中，新发（0天后发作）和急性（前7天内发作）腹泻有资格入选为MSD。在同一保健中心寻求治疗的儿童中，其余新发和急性腹泻被认为是迷幻剂。我们的目标是每两周在每个研究中心招募前8或9名合格的MSD和LSD儿童，分为3个年龄层：婴儿（0-11个月）、幼儿（12-23个月）和幼儿（24-59个月）。对于每例纳入的MSD或LSD病例，我们招募了1至3名在前7天内没有腹泻的社区对照儿童。从患者和对照组中，我们收集了临床和流行病学数据、人体测量数据和粪便样本，以在入组时识别肠道病原体，并在约60天后进行了随访家庭访视，以确定生命状态、临床结局和间隔生长。主要研究结果是对MSD和LSD的病原体特异性归因风险和基于人群的发病率值进行评估，并评估与这两种神经系统综合征相关的不良临床后果的频率。1 ~ 3名随机选择的无腹泻的社区对照儿童与MSD（n=3597）或LSD（n=4236）病例相匹配。加权调整后的人群归因分数显示，大多数可归因的MSD和LSD病例是由轮状病毒、隐孢子虫属、编码热稳定毒素的产肠毒素大肠杆菌（有或没有编码热不稳定肠毒素的基因）和志贺氏菌属引起的。轮状病毒每100儿童年的归因发病率，按年龄分层，LSD和MSD分别为22.3和5.5（0-11个月），9.8 vs 2.9（12-23个月）和0.5对0.2（24-59个月）;隐孢子虫属为3.6 vs 2.3（0-11个月），4.3对0.6（12-23个月），0.3对0.1（24-59个月）;编码热稳定毒素的产肠毒素大肠杆菌为4。2与0.1（0-11个月）、5.2与0.0（12-23个月）和1.1与0.2（24-59个月）;志贺氏菌属为1.0与1.3（0-11个月）、3.1与2.4（12-23个月）和0.8与0.7（24-59个月）。MSD和LSD的参与者在follow-up. Interpretation中比对照组有更明显的线性增长步履蹒跚，LSD参与者的纳入显着扩大了急性胰腺疾病中经历不良临床和营养结果的儿童人群。由于MSD和LSD具有相似的病因学，针对轮状病毒、志贺氏菌属、产热稳定毒素的产肠毒素大肠杆菌和隐孢子虫属的干预措施可能会大大减少肠道疾病负担及其相关的营养不良。版权所有（C）作者。爱思唯尔有限公司出版
Background Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0-59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites.Methods We report a 1-year, multisite, age-stratified, matched case-control study following on to the GEMS study. Six sites (Bamako, Mali; Manhica, Mozambique; Basse, The Gambia; Mirzapur, Bangladesh; Kolkata, India; and Bin Qasim Town, Karachi, Pakistan) participated in this study. Children aged 0-59 months at each site who sought care at a sentinel hospital or health centre during a 12-month period were screened for diarrhoea. New (onset after 0 diarrhoeafree days) and acute (onset within the previous 7 days) episodes of diarrhoea in children who had sunken eyes, whose skin lost turgor, who received intravenous hydration, who had dysentery, or who were hospitalised were eligible for inclusion as MSD. The remaining new and acute diarrhoea episodes among children who sought care at the same health centres were considered LSD. We aimed to enrol the first eight or nine eligible children with MSD and LSD at each site during each fortnight in three age strata: infants (aged 0-11 months), toddlers (aged 12-23 months), and young children (aged 24-59 months). For each included case of MSD or LSD, we enrolled one to three community control children without diarrhoea during the previous 7 days. From patients and controls we collected clinical and epidemiological data, anthropometric measurements, and faecal samples to identify enteropathogens at enrolment, and we performed a follow-up home visit about 60 days later to ascertain vital status, clinical outcome, and interval growth. Primary outcomes were to characterise, for MSD and LSD, the pathogen-specific attributable risk and population-based incidence values, and to assess the frequency of adverse clinical consequences associated with these two diarrhoeal syndromes.Findings From Oct 31, 2011, to Nov 14, 2012, we recruited 2368 children with MSD, 3174 with LSD, and one to three randomly selected community control children without diarrhoea matched to cases with MSD (n=3597) or LSD (n=4236). Weighted adjusted population attributable fractions showed that most attributable cases of MSD and LSD were due to rotavirus, Cryptosporidium spp, enterotoxigenic Escherichia colt encoding heat-stable toxin (with or without genes encoding heat-labile enterotoxin), and Shigella spp. The attributable incidence per 100 child-years for LSD versus MSD, by age stratum, for rotavirus was 22.3 versus 5.5 (0-11 months), 9.8 versus 2.9 (12-23 months), and 0.5 versus 0.2 (24-59 months); for Cryptosporidium spp was 3.6 versus 2.3 (0-11 months), 4.3 versus 0.6 (12-23 months), and 0.3 versus 0.1 (24-59 months); for enterotoxigenic E coli encoding heat-stable toxin was 4. 2 versus 0.1 (0-11 months), 5.2 versus 0.0 (12-23 months), and 1.1 versus 0.2 (24-59 months); and for Shigella spp was 1.0 versus 1.3 (0-11 months), 3.1 versus 2.4 (12-23 months), and 0.8 versus 0.7 (24-59 months). Participants with both MSD and LSD had significantly more linear growth faltering than controls at follow-up.Interpretation Inclusion of participants with LSD markedly expands the population of children who experience adverse clinical and nutritional outcomes from acute diarrhoeal diseases. Since MSD and LSD have similar aetiologies, interventions targeting rotavirus, Shigella spp, enterotoxigenic E coli producing heat-stable toxin, and Cryptosporidium spp might substantially reduce the diarrhoeal disease burden and its associated nutritional faltering. Copyright (C) The Author (s). Published by Elsevier Ltd.