Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.
Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.
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DOI：
10.1016/j.ebiom.2015.09.036
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发表时间：
2015-11
期刊：
影响因子：
11.1
通讯作者：
Petri WA Jr
中科院分区：
文献类型：
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作者：
Naylor C;Lu M;Haque R;Mondal D;Buonomo E;Nayak U;Mychaleckyj JC;Kirkpatrick B;Colgate R;Carmolli M;Dickson D;van der Klis F;Weldon W;Steven Oberste M;PROVIDE study teams;Ma JZ;Petri WA Jr
环境性肠病（EE）是一种在低收入国家发现的亚临床肠道疾病，其特征是肠道炎症，肠道吸收减少和肠道屏障功能障碍。我们旨在评估EE是否会损害孟加拉国婴儿口服脊髓灰质炎和轮状病毒疫苗的成功。我们对2011年5月至2014年11月来自孟加拉国达卡城市贫民窟的700名婴儿进行了前瞻性观察研究。婴儿在出生后的第一周登记，并通过每两周一次的家访进行随访，接种EPI疫苗并监测生长情况。EE在操作上被定义为通过粪便生物标志物reg 1B、α-1-抗胰蛋白酶、MPO、钙卫蛋白或新蝶呤中的任何一种测量的肠道炎症。口服脊髓灰质炎疫苗的成功通过免疫原性来评价，轮状病毒疫苗的应答通过免疫原性和疾病保护来评价。本研究注册于ClinicalTrials.gov，编号NCT 01375647。EE存在于超过80%的12周龄婴儿中。口服脊髓灰质炎病毒和轮状病毒疫苗分别有20.2%和68.5%的婴儿失败，28.6%的婴儿在一岁时营养不良（HAZ <-2）。而破伤风、B型流感嗜血杆菌、白喉和麻疹疫苗的抗体缺乏率分别为0%、9.0%、7.9%和3.8%。EE与口服脊髓灰质炎和轮状病毒应答呈负相关，但与胃肠外疫苗免疫原性无关。全身性炎症的生物标志物和产妇健康的措施也可以预测口服疫苗失败和营养不良。从多变量分析中选择的生物标志物解释了Δ HAZ的46.3%变化。24%的Rotarix®伊加阳性个体可归因于所选的生物标志物。EE以及全身性炎症和母亲健康状况差与口服疫苗而非胃肠外疫苗的性能不佳和未来生长停滞的风险相关。这些结果提供了一个潜在的解释，这些问题的负担在低收入的问题，允许早期识别婴儿的风险，并建议干预途径。 （OPP1017093）。大多数达卡贫民窟的儿童在12周大的时候就存在环境性肠病。环境性肠病对出生后第一年的生长有负面影响。环境性肠病对口服疫苗反应有负面影响，但对胃肠外疫苗反应无负面影响。预测营养不良和疫苗失败的生物标志物分为三组：肠道炎症、全身炎症和母体因素。营养不良和口服疫苗失败在低收入国家生活在不卫生条件下的婴儿中很常见。我们假设，早期暴露于肠道感染可能导致肠道炎症，称为环境性肠病（EE），这反过来又可能导致营养不良和疫苗反应。来自孟加拉国达卡一个城市贫民窟的儿童在出生后第一周内被登记，疫苗反应和生长被测量到一岁。大多数儿童感染了两个或两个以上的肠道感染，并有特征性炎症的EE. Both营养不良和口服疫苗失败与EE. We的结论是，改善儿童健康在低收入国家可能需要预防或治疗肠道损伤由于感染。
Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < − 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention. (OPP1017093). Environmental enteropathy was present in the majority of Dhaka slum children at 12 weeks of age. Growth in the first year of life was negatively impacted by environmental enteropathy Oral vaccine response, but not parenteral vaccine response, was negatively impacted by environmental enteropathy Biomarkers predictive of malnutrition and vaccine failure fell into three clusters: gut inflammation, systemic inflammation and maternal factors. Malnutrition and oral vaccine failure are common in infants living in unsanitary conditions in low income countries. We hypothesized that exposure to infections of the gut at an early age could result in an inflammatory condition of the intestine termed Environmental Enteropathy (EE), and that this in turn could contribute to malnutrition and vaccine response. Children from an urban slum in Dhaka Bangladesh were enrolled within the first week of life, and vaccine response and growth measured to age one year. Most children were infected by two or more enteric infections and had the characteristic inflammation of EE. Both malnutrition and oral vaccine failure were associated with EE. We concluded that improvement in child health in low income countries will likely require prevention or treatment of gut damage due to infection.