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Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.

ABSTRACT: BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING:The Bill and Melinda Gates Foundation (OPP1017093).

SUBMITTER: Naylor C

PROVIDER: S-EPMC4740306 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.

Naylor Caitlin C Lu Miao M Haque Rashidul R Mondal Dinesh D Buonomo Erica E Nayak Uma U Mychaleckyj Josyf C JC Kirkpatrick Beth B Colgate Ross R Carmolli Marya M Dickson Dorothy D van der Klis Fiona F Weldon William W Steven Oberste M M Ma Jennie Z JZ Petri William A WA

EBioMedicine 20150925 11

<h4>Background</h4>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.<h4>Methods</h4>We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrol ...[more]

PMID: 26870801

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Project description:Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (?1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations.

Project description:BackgroundChild growth faltering persists in sub-Saharan Africa despite the scale-up of nutrition, water, and sanitation interventions over the past 2 decades. High temperatures have been hypothesised to contribute to child growth faltering via an adaptive response to heat, reduced appetite, and the energetic cost of thermoregulation. We did a cross-sectional study to assess whether child growth faltering is related to environmental temperature in sub-Saharan Africa.MethodsData were extracted from 52 Demographic and Heath Surveys, dating from 2003 to 2016, that recorded anthropometric data in children aged 0-5 years, and were linked with remotely sensed monthly mean daytime land surface temperature for 2000-16. The odds of stunting (low height-for-age), wasting (low weight-for-height), and underweight (low weight-for-age) relative to monthly mean daytime land surface temperature were determined using multivariable logistic regression.FindingsThe study population comprised 656 107 children resident in 373 012 households. Monthly mean daytime land surface temperature above 35°C was associated with increases in the odds of wasting (odds ratio 1·27, 95% CI 1·16-1·38; p<0·0001), underweight (1·09, 1·02-1·16; p=0·0073), and concurrent stunting with wasting (1·23, 1·07-1·41; p=0·0037), but a reduction in stunting (0·90, 0·85-0·96; p=0·00047) compared with a monthly mean daytime land surface temperature of less than 30°C.InterpretationChildren living in hotter parts of sub-Saharan Africa are more likely to be wasted, underweight, and concurrently stunted and wasted, but less likely to be stunted, than in cooler areas. Studies are needed to further investigate the relationship between temperature and child growth, including whether there is a direct effect not mediated by food security, regional wealth, and other environmental variables. Rising temperature, linked to anthropogenic climate change, might increase child growth faltering in sub-Saharan Africa.FundingUK Medical Research Council and UK Global Challenges Research Fund.

Dataset Information

Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.

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Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.

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