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. 2015 Sep 25;2(11):1759-66.
doi: 10.1016/j.ebiom.2015.09.036. eCollection 2015 Nov.

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

Caitlin Naylor  1 , Miao Lu  1 , Rashidul Haque  2 , Dinesh Mondal  2 , Erica Buonomo  1 , Uma Nayak  1 , Josyf C Mychaleckyj  1 , Beth Kirkpatrick  3 , Ross Colgate  3 , Marya Carmolli  3 , Dorothy Dickson  3 , Fiona van der Klis  4 , William Weldon  5 , M Steven Oberste  5 ; PROVIDE study teams; Jennie Z Ma  1 , William A Petri Jr  1
Affiliations

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

Caitlin Naylor et al. EBioMedicine. .

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).

Keywords: Environmental enteropathy; Malnutrition; Oral vaccine failure.

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Figures

Fig. 1
Fig. 1
Anthropometry over the first 52 weeks of life. Height and weight were taken at scheduled clinic visits, and transformed to standardized z-scores. The X axis depicts the age of the child, the Y axis depicts the percentage of infants in the cohort who had a HAZ, WAZ, or WHZ of <− 2.
Fig. 2
Fig. 2
Environmental enteropathy in infants. Frequency distribution of fecal calprotectin, myeloperoxidase, and alpha-1 anti-trypsin at age 12 weeks using ELISA. Black columns represent normal values, and white columns represent abnormal values. Normal values were based on Western standards: calprotectin > 200 μg/g (82.7% elevated), myeloperoxidase > 2000 ng/ml (88.1% elevated), alpha-1 anti-trypsin is > 270 μg/g (81.9% elevated). Calprotectin n = 596, MPO n = 591, alpha-1 anti-trypsin n = 592.
Fig. 3
Fig. 3
Cluster dendrogram of biomarkers. Biomarkers are clustered according to relatedness; adjacent markers are the most closely correlated, while increased distance indicates decreasing correlations. Biomarker clusters are numbered 1 (systemic inflammation), 2 (enteric inflammation and malabsorption), and 3 (maternal health).
Fig. 4
Fig. 4
Heatmap of FDR values from univariate linear regression analysis. Biomarkers with a FDR value of 0.2 or below for at least one outcome are depicted on the heatmap. Markers are grouped according to hierarchal cluster results. A positive correlation is indicated by a blue box, and a negative correlation is indicated by a red box. Color patterns reveal associations of biomarkers with outcomes, indicating an improvement or worsening of response. An FDR value close to 0 indicates a strong correlation. Color intensity is indicative of FDR value: darker colors are closer to 0.
Fig. 5
Fig. 5
Proposed pathways to oral vaccine underperformance and failure and malnutrition. Potential mechanisms are shown by which the three biomarker clusters [(1) systemic inflammation, (2) enteric inflammation, and (3) maternal health] could impact oral vaccines and nutrition.
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References

    1. Black R.E., Allen L.H., Bhutta Z.A., Caulfield L.E., de Onis M., Ezzati M. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008;371(9608):243–260. (Jan 19) - PubMed
    1. Campbell D.I., Murch S.H., Elia M., Sullivan P.B., Sanyang M.S., Jobarteh B. Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small bowel function. Pediatr. Res. 2003;54(3):306–311. (Oct) - PubMed
    1. Chavent M, Kuentz V, Liquet B, Saracco J. ClustOfVar: an R package for the clustering of variables. J. Stat. Softw. 2011;50:1–16.
    1. Christiaensen L., Alderman H. Child malnutrition in Ethiopia: can maternal knowledge augment the role of income? Econ. Dev. Cult. Chang. 2004;52(2):287–312.
    1. Di Cesare M., Bhatti Z., Soofi S.B., Fortunato L., Ezzati M., Bhutta Z.A. Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: an analysis of data from a nationally representative survey. Lancet Glob. Health. 2015;3(4):e229–e239. - PMC - PubMed

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