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

Tuesday, 16th of February 2016

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

Naylor C¹, Lu M¹, Haque R², Mondal D², Buonomo E¹, Nayak U¹, Mychaleckyj JC¹, Kirkpatrick B³, Colgate R³, Carmolli M³, Dickson D³, van der Klis F⁴,Weldon W⁵, Steven Oberste M⁵; PROVIDE study teams, Ma JZ¹, Petri WA Jr¹.

Author information

¹The University of Virginia, Charlottesville, VA, USA.
²The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
³The University of Vermont, Burlington, VT, USA.
⁴Netherlands National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
⁵Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Abstract below; full text is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740306/

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).