Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study.
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study.
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DOI：
10.1016/s2214-109x(18)30351-6
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发表时间：
2018-12
期刊：
影响因子：
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通讯作者：
MAL-ED Network Investigators
中科院分区：
文献类型：
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作者：
Rogawski ET;Liu J;Platts-Mills JA;Kabir F;Lertsethtakarn P;Siguas M;Khan SS;Praharaj I;Murei A;Nshama R;Mujaga B;Havt A;Maciel IA;Operario DJ;Taniuchi M;Gratz J;Stroup SE;Roberts JH;Kalam A;Aziz F;Qureshi S;Islam MO;Sakpaisal P;Silapong S;Yori PP;Rajendiran R;Benny B;McGrath M;Seidman JC;Lang D;Gottlieb M;Guerrant RL;Lima AAM;Leite JP;Samie A;Bessong PO;Page N;Bodhidatta L;Mason C;Shrestha S;Kiwelu I;Mduma ER;Iqbal NT;Bhutta ZA;Ahmed T;Haque R;Kang G;Kosek MN;Houpt ER;MAL-ED Network Investigators
儿童早期的肠道病原体感染不仅会导致腹泻，还会导致生长不良。我们使用分子诊断学来评估特定的肠道病原体是否与七个低资源环境中的线性增长有关。我们用定量聚合酶链式反应检测了在肠道感染和营养不良的病因、危险因素、相互作用和对儿童健康与发展的影响(MAL-ED)多点队列研究中收集的出生后头两年儿童的腹泻和非腹泻粪便中的29种肠道病原体。长度每月测量一次。我们评估了病原学特异性腹泻与亚临床肠道病原体感染和数量之间的关系，并在2岁和5岁时以3个月的间隔获得长度，并使用纵向模型来解释时间性和时间依赖性的混淆。在完成2年随访的1,469名儿童中，对35份 622粪便样本进行了检测，结果为有效结果。被归因于细菌和寄生虫的腹泻发作，而不是病毒，与3个月后和2岁时的长度小幅下降有关。两年后长度大幅缩短与亚临床、非腹泻、志贺氏菌感染(Z-年龄长度降低−0·14，95%CI−0·27至−0·01)、肠聚集性大肠埃希菌(−0·21，−0·37至−0·05)、弯曲杆菌(−0·17，−0·32至−0·01)和贾第虫(−0·17，−0·30至−0·05)有关。诺如病毒、隐孢子虫、典型致病性大肠杆菌和肠道细菌也与LAZ的小幅下降有关。志贺氏菌和毕氏艾美耳球虫的LAZ下降幅度最大(志贺氏菌为−0·13LAZ，95%CI−为0·22至−0·03；埃希氏菌为−0·14，−0·26至−0·02)。基于这些模型，成功减少志贺氏菌、肠聚集性大肠埃希菌、弯曲杆菌和贾第鞭毛虫暴露的干预措施可以使MAL-ED部位的儿童平均身高增加0.12-0.37 LAZ(0.4-1.2厘米)。亚临床感染和病原体数量，特别是志贺氏菌、肠聚集性大肠埃希菌、弯曲杆菌和贾第虫，与线性增长存在显著的负相关，在生命的头2年，在某些情况下，可持续到5年。成功地减少对某些病原体的暴露可能会减少全球发育迟缓。比尔和梅琳达·盖茨基金会。
Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Bill & Melinda Gates Foundation.