title: Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED).
abstract: 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-specific 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.
  
  
  RESULTS
  Between November 26, 2009, and February 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Platts-Mills
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Babji
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Ladaporn
authors.initials: L
authors.lastname: Bodhidatta
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Haydom Lutheran Hospital, Haydom, Tanzania.
authors.forename: Jean
authors.initials: J
authors.lastname: Gratz
authors.affiliation: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Benjamin Jj
authors.initials: BJ
authors.lastname: McCormick
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: McGrath
authors.affiliation: Asociación Benéfica PRISMA, Iquitos, Peru.
authors.forename: Maribel Paredes
authors.initials: MP
authors.lastname: Olortegui
authors.affiliation: University of Venda, Thohoyandou, South Africa.
authors.forename: Amidou
authors.initials: A
authors.lastname: Samie
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Shakoor
authors.affiliation: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Mondal
authors.affiliation: Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil.
authors.forename: Ila Fn
authors.initials: IF
authors.lastname: Lima
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Hariraju
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Bishnu B
authors.initials: BB
authors.lastname: Rayamajhi
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Shahida
authors.initials: S
authors.lastname: Qureshi
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Furqan
authors.initials: F
authors.lastname: Kabir
authors.affiliation: Asociación Benéfica PRISMA, Iquitos, Peru.
authors.forename: Pablo P
authors.initials: PP
authors.lastname: Yori
authors.affiliation: University of Venda, Thohoyandou, South Africa.
authors.forename: Brenda
authors.initials: B
authors.lastname: Mufamadi
authors.affiliation: Haydom Lutheran Hospital, Haydom, Tanzania.
authors.forename: Caroline
authors.initials: C
authors.lastname: Amour
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Carreon
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Richard
authors.affiliation: Foundation for the National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Lang
authors.affiliation: University of Venda, Thohoyandou, South Africa.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bessong
authors.affiliation: Haydom Lutheran Hospital, Haydom, Tanzania.
authors.forename: Esto
authors.initials: E
authors.lastname: Mduma
authors.affiliation: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil.
authors.forename: Aldo Aam
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mason
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Anita Km
authors.initials: AK
authors.lastname: Zaidi
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.affiliation: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Asociación Benéfica PRISMA, Iquitos, Peru.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kosek
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.affiliation: Foundation for the National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottlieb
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Miller
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA. Electronic address: erh6k@virginia.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Houpt
mesh_terms: D000349:Africa / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D001419:Bacteria / Q000302:isolation & purification; D001424:Bacterial Infections / Q000453:epidemiology / Q000382:microbiology*; D002675:Child, Preschool; D015331:Cohort Studies; D003906:Developing Countries / Q000706:statistics & numerical data*; D003967:Diarrhea / Q000453:epidemiology / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction; D013020:South America / Q000453:epidemiology