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. 2018 Jul 19;18(1):236.
doi: 10.1186/s12887-018-1189-5.

Identifying the etiology and pathophysiology underlying stunting and environmental enteropathy: study protocol of the AFRIBIOTA project

Pascale Vonaesch  1 , Rindra Randremanana  2 , Jean-Chrysostome Gody  3 , Jean-Marc Collard  4 , Tamara Giles-Vernick  5 , Maria Doria  1 , Inès Vigan-Womas  6 , Pierre-Alain Rubbo  7 , Aurélie Etienne  2 , Emilson Jean Andriatahirintsoa  8 , Nathalie Kapel  9 , Eric Brown  10 , Kelsey E Huus  10 , Darragh Duffy  11 , B Brett Finlay  10 , Milena Hasan  12 , Francis Allen Hunald  13 , Annick Robinson  14 , Alexandre Manirakiza  15 , Laura Wegener-Parfrey  16 , Muriel Vray  5 , Philippe J Sansonetti  17 ; AFRIBIOTA Investigators
Collaborators, Affiliations

Identifying the etiology and pathophysiology underlying stunting and environmental enteropathy: study protocol of the AFRIBIOTA project

Pascale Vonaesch et al. BMC Pediatr. .

Abstract

Background: Globally one out of four children under 5 years is affected by linear growth delay (stunting). This syndrome has severe long-term sequelae including increased risk of illness and mortality and delayed psychomotor development. Stunting is a syndrome that is linked to poor nutrition and repeated infections. To date, the treatment of stunted children is challenging as the underlying etiology and pathophysiological mechanisms remain elusive. We hypothesize that pediatric environmental enteropathy (PEE), a chronic inflammation of the small intestine, plays a major role in the pathophysiology of stunting, failure of nutritional interventions and diminished response to oral vaccines, potentially via changes in the composition of the pro- and eukaryotic intestinal communities. The main objective of AFRIBIOTA is to describe the intestinal dysbiosis observed in the context of stunting and to link it to PEE. Secondary objectives include the identification of the broader socio-economic environment and biological and environmental risk factors for stunting and PEE as well as the testing of a set of easy-to-use candidate biomarkers for PEE. We also assess host outcomes including mucosal and systemic immunity and psychomotor development. This article describes the rationale and study protocol of the AFRIBIOTA project.

Methods: AFRIBIOTA is a case-control study for stunting recruiting children in Bangui, Central African Republic and in Antananarivo, Madagascar. In each country, 460 children aged 2-5 years with no overt signs of gastrointestinal disease are recruited (260 with no growth delay, 100 moderately stunted and 100 severely stunted). We compare the intestinal microbiota composition (gastric and small intestinal aspirates; feces), the mucosal and systemic immune status and the psychomotor development of children with stunting and/or PEE compared to non-stunted controls. We also perform anthropological and epidemiological investigations of the children's broader living conditions and assess risk factors using a standardized questionnaire.

Discussion: To date, the pathophysiology and risk factors of stunting and PEE have been insufficiently investigated. AFRIBIOTA will add new insights into the pathophysiology underlying stunting and PEE and in doing so will enable implementation of new biomarkers and design of evidence-based treatment strategies for these two syndromes.

Keywords: Biomarkers; Central African Republic; Child development; Immunology; Madagascar; Medical anthropology; Microbiota; Pediatric environmental enteropathy; Risk factors; Stunting.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol for AFRIBIOTA has been approved by the Institutional Review Board of the Institut Pasteur (2016–06/IRB) and the National Ethical Review Boards of Madagascar (55/MSANP/CE, May 19th 2015) and the Central African Republic (173/UB/FACSS/CSCVPER/16). All participants received oral and written information about the study and the legal representatives of the children provided written consent to participate in the study. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. A copy of the written consent is available for review by the Editor of this journal.

Consent for publication

Not applicable

Competing interests

Pierre-Alain Rubbo is the Founding Chief Executive Officer and one of the shareholders, of the start-up company Omunis. Omunis did not provide any financial support for AFRIBIOTA and did not have any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The other authors declare no competing interests.

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Figures

Fig. 1
Fig. 1
Scheme depicting the different entities underlying or being affected by pediatric environmental enteropathy (PEE). Underlying causes are colored in orange, physiological changes in red and consequences in green
Fig. 2
Fig. 2
Recruitment Schema of the AFRIBIOTA project
Fig. 3
Fig. 3
Framework of the different interacting entities being associated with stunting and pediatric environmental enteropathy (PEE). Data collected for each entity in the context of the AFRIBIOTA project is indicated in red. Interactions in between the different entities are indicated with arrows. The child’s macro-environment is influencing all other entities
Fig. 4
Fig. 4
Schema of the biomarker analysis performed in AFRIBIOTA. Features assessed are indicated in black, measurements performed within the context of AFRIBIOTA in blue
See this image and copyright information in PMC

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