The University of Virginia, Charlottesville, VA, USA.
The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
EBioMedicine. 2015 Sep 25;2(11):1759-66. doi: 10.1016/j.ebiom.2015.09.036. eCollection 2015 Nov.
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.
The Bill and Melinda Gates Foundation (OPP1017093).
环境肠病（EE）是一种在低收入国家发现的亚临床肠道疾病，其特征为肠道炎症、肠道吸收减少和肠道屏障功能障碍。我们旨在评估 EE 是否会影响孟加拉国婴儿口服脊髓灰质炎和轮状病毒疫苗的效果。
我们对 2011 年 5 月至 2014 年 11 月来自孟加拉国达卡一个城市贫民窟的 700 名婴儿进行了一项前瞻性观察性研究。婴儿在出生后的第一周内入组，并通过每两周一次的家庭访视进行随访，访视时给予 EPI 疫苗并监测生长情况。EE 通过粪标志物 reg1B、α-1-抗胰蛋白酶、MPO、钙卫蛋白或新蝶呤中的任何一种来操作定义为肠道炎症。口服脊髓灰质炎疫苗的效果通过免疫原性评估，轮状病毒疫苗的效果通过免疫原性和对疾病的保护作用来评估。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01375647。
在 12 周龄时，EE 在超过 80%的婴儿中存在。口服脊髓灰质炎病毒和轮状病毒疫苗在分别有 20.2%和 68.5%的婴儿中失效，1 岁时 28.6%的婴儿有营养不良（HAZ < - 2）。相比之下，分别有 0%、9.0%、7.9%和 3.8%的婴儿对破伤风、流感嗜血杆菌 b 型、白喉和麻疹疫苗缺乏保护性抗体水平。EE 与口服脊髓灰质炎病毒和轮状病毒的反应呈负相关，但与疫苗的全身免疫原性无关。全身炎症标志物和产妇健康指标也可以预测口服疫苗失效和营养不良。多变量分析选择的生物标志物解释了 HAZ 变化的 46.3%。24%的 Rotarix®IgA 阳性个体可以归因于所选的生物标志物。
EE 以及全身炎症和产妇健康状况与口服疫苗而非疫苗的效果不佳和未来生长迟缓的风险有关。这些结果为低收入国家存在这些问题的负担提供了一个潜在的解释，使我们能够早期识别有风险的婴儿，并为干预措施提供了途径。
比尔及梅琳达·盖茨基金会（OPP1017093）。
