Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

Friday, 22nd of April 2016

Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

James A Platts-Mills, Sudhir Babji*, Ladaporn Bodhidatta*, Jean Gratz*, Rashidul Haque*, Alexandre Havt*, Benjamin J J McCormick*, Monica McGrath*, Maribel Paredes Olortegui*, Amidou Samie*, Sadia Shakoor*, Dinesh Mondal, Ila F N Lima, Dinesh Hariraju, Bishnu B Rayamajhi, Shahida Qureshi, Furqan Kabir, Pablo P Yori, Brenda Mufamadi, Caroline Amour, J Daniel Carreon, Stephanie A Richard, Dennis Lang, Pascal Bessong, Esto Mduma, Tahmeed Ahmed, Aldo A A M Lima, Carl J Mason, Anita K M Zaidi, Zulfi qar A Bhutta, Margaret Kosek, Richard L Guerrant, Michael Gottlieb, Mark Miller, Gagandeep Kang, Eric R Houpt, and The MAL-ED Network Investigators†

Summary below; full text is at

http://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X(15)00151-5.pdf

Background

Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specifi c diarrhoea burdens in the community.

Methods

We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through twice-weekly home visits by fieldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1–12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea.

Findings

Between Nov 26, 2009, and Feb 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0–24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0–7·1), rotavirus (4·8%, 4·5–5·0), Campylobacter spp (3·5%, 0·4–6·3), astrovirus (2·7%, 2·2–3·1), and Cryptosporidium spp (2·0%, 1·3–2·6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1–12·1), norovirus GII (5·4%, 2·1–7·8), rotavirus (4·9%, 4·4–5·2), astrovirus (4·2%, 3·5–4·7), and Shigella spp (4·0%, 3·6–4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fifth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation

There was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited.

Funding Bill & Melinda Gates Foundation. Copyright © Platts-Mills et al. Open Access article published under the terms of CC BY-NC-ND. Introduction Infectious diarrhoea is the second most common cause of death in children under 5 years old in developing countries.1 Studies of the causes of diarrhoea in these settings have usually focused on children who present to health centres and, therefore, best describe pathogens associated with severe diarrhoea.2,3 However this approach captures only a small subset of diarrhoeal episodes which might show a different hierarchy of pathogens from that associated with mild or moderate episodes of diarrhoea. Non-severe episodes in the community are of substantial public health importance because of their high prevalence and association with poor growth, impaired cognitive development, environmental enteropathy, and even mortality.3–8 Estimates of the pathogenspecific burdens of diarrhoea at the community level are, therefore, needed to prioritise interventions. Further, surveillance in the community allows for unbiased estimates of the associations between pathogens and distinct clinical syndromes. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is a multisite birth cohort study at eight sites in South America, sub-Saharan Africa, and Asia.9 We aimed to estimate pathogen-specific burdens of diarrhoea in children aged 0–24 months at these MAL-ED study sites. Lancet Glob Health 2015; 3: e564–75

Published Online July 20, 2015 http://dx.doi.org/10.1016/ S2214-109X(15)00151-5 See Comment page e510

*These authors contributed equally to this work †Listed at end of paper Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA (J A Platts-Mills MD, J Gratz BSc, R L Guerrant MD, E R Houpt MD); Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil (A Havt PhD, Ila F N Lima PhD, A M Lima MD); International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (T Ahmed MBBS, D Mondal MD, R Haque MD); Christian Medical College, Vellore, India (S Babji MD, D Hariraju MSc, G Kang MD); Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand (B Rayamajhi BSc, L Bodhidatta MD, C J Mason MD); Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA (P P Yori MPH, M Kosek MD); Asociación Benéfi ca PRISMA, Iquitos, Peru (M P Olortegui BSc, P P Yori MPH, M Kosek MD); Aga Khan University, Karachi, Pakistan (S Shakoor MBBS, S Qureshi MSc, F Kabir MSc, A Zaidi MBBS, Zulfi qar Bhutta PhD); University of Venda, Thohoyandou, South Africa (A Samie PhD, B Mufamadi BTech, P Bessong PhD); Haydom Lutheran Hospital, Haydom, Tanzania (C Amour MSc, J Gratz BSc, E Mduma MPH); Foundation for the National Articles e565 www.thelancet.com/lancetgh Vol 3 September 2015 Institutes of Health, Bethesda, MD, USA (D Lang PhD, M Gottlieb PhD); Fogarty International Center, National Institutes of Health, Bethesda, MD, USA (B J J McCormick DPhil, M McGrath ScD, J D Carreon MS, S Richard PhD, M Miller MD) Correspondence to: Dr Eric R Houpt, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908, USA erh6k@virginia.edu