Evidence map›Paper›PMID 30287127›Full record

ArticleThe Lancet. Global health2018

Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study.

James A Platts-Mills, Jie Liu, Elizabeth T Rogawski, Furqan Kabir, Paphavee Lertsethtakarn, Mery Siguas, Shaila S Khan, Ira Praharaj, Arinao Murei, Rosemary Nshama and 42 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Global health, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04312906 (A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa), which is not on this map. Cited by 262 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed, 6 pooled it
22.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04312906 completednot on this mapstarted 2020, after this paper: background citation

A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa

TypeobservationalSponsorCentre for Infectious Disease Research in ZambiaRan2020 to 2021Enrolled1,334ConditionsDiarrhea, Diarrhea InfectiousArmsno intervention
3 · Its place in the literature

Who cites it

262 citing papers in PubMed, 6 syntheses or guidelines pooled it, 390 citations in OpenAlex.

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  15. Impact of Biannual Mass Azithromycin Treatment on Enteropathogen Carriage in Children <5 Years Old in Niger.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
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  17. Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger.Journal of the Pediatric Infectious Diseases Society · 2021
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202 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

52 authors at 17 institutions in 10 countries.

James A Platts-MillsDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA. Electronic address: jp5t@virginia.edu.
Jie LiuDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Elizabeth T RogawskiDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Furqan KabirAga Khan University, Karachi, Pakistan.
Paphavee LertsethtakarnArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Mery SiguasAsociación Benéfica PRISMA, Iquitos, Peru.
Shaila S KhanInternational Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Ira PraharajChristian Medical College, Vellore, India.
Arinao MureiUniversity of Venda, Thohoyandou, South Africa.
Rosemary NshamaHaydom Global Health Institute, Haydom, Tanzania.
Buliga MujagaKilimanjaro Clinical Research Institute, Moshi, Tanzania.
Alexandre HavtFederal University of Ceara, Fortaleza, Brazil.
Irene A MacielFundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
Timothy L McMurryDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Darwin J OperarioDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Mami TaniuchiDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Jean GratzDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Suzanne E StroupDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
James H RobertsDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Adil KalamAga Khan University, Karachi, Pakistan.
Fatima AzizAga Khan University, Karachi, Pakistan.
Shahida QureshiAga Khan University, Karachi, Pakistan.
M Ohedul IslamInternational Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Pimmada SakpaisalArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Sasikorn SilapongArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Pablo P YoriAsociación Benéfica PRISMA, Iquitos, Peru; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Revathi RajendiranChristian Medical College, Vellore, India.
Blossom BennyChristian Medical College, Vellore, India.
Monica McGrathBloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
Benjamin J J McCormickFogarty International Center, National Institutes of Health, Bethesda, MD, USA.
Jessica C SeidmanFogarty International Center, National Institutes of Health, Bethesda, MD, USA.
Dennis LangFoundation for the National Institutes of Health, Bethesda, MD, USA.
Michael GottliebFoundation for the National Institutes of Health, Bethesda, MD, USA.
Richard L GuerrantDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Aldo A M LimaFederal University of Ceara, Fortaleza, Brazil.
Jose Paulo LeiteFundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
Amidou SamieUniversity of Venda, Thohoyandou, South Africa.
Pascal O BessongUniversity of Venda, Thohoyandou, South Africa.
Nicola PageNational Institute for Communicable Diseases, Johannesburg, South Africa.
Ladaporn BodhidattaArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Carl MasonArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Sanjaya ShresthaWalter Reed/AFRIMS Research Unit, Nepal, Kathmandu, Nepal; University of Bergen, Bergen, Norway.
Ireen KiweluKilimanjaro Clinical Research Institute, Moshi, Tanzania.
Estomih R MdumaHaydom Global Health Institute, Haydom, Tanzania.
Najeeha T IqbalAga Khan University, Karachi, Pakistan.
Zulfiqar A BhuttaAga Khan University, Karachi, Pakistan.
Tahmeed AhmedInternational Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Rashidul HaqueInternational Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Gagandeep KangChristian Medical College, Vellore, India.
Margaret N KosekAsociación Benéfica PRISMA, Iquitos, Peru; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Eric R HouptDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
MAL-ED Network Investigators
University of Virginia · USAga Khan University · PKInternational Centre for Diarrhoeal Disease Research · BDArmed Forces Research Institute of Medical Science · THChristian Medical College & Hospital · INFundação Oswaldo Cruz · BRUniversidade Federal do Ceará · BRUniversity of Bergen · NOUniversity of Venda · ZAHaydom Lutheran Hospital · TZFoundation for the National Institutes of Health · USJohns Hopkins University · USKilimanjaro Christian Medical Centre · TZNational Institutes of Health · USFogarty International Center · USNational Institute for Communicable DiseasesPrisma · PE

Funding

Quantitative molecular diagnostics for diarrhea etiology and vaccine efficacyK23AI114888 · NIAID · UNIVERSITY OF VIRGINIA · PI PLATTS-MILLS, JAMES ALEXANDER · 2015 to 2019
$932k
Translation of epidemiologic findings in enteric disease to public health actionK01AI130326 · NIAID · UNIVERSITY OF VIRGINIA · PI ROGAWSKI MCQUADE, ELIZABETH TACKET · 2018 to 2022
$612k
NIAID NIH HHS K01 AI130326NIAID NIH HHS K23 AI114888
6 · The paper itself

Abstract

backgroundOptimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study.

methodsWe re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0-2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics.

findingsWe analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6-71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8-38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6-39·5) was more common than bacterial (25·0%, 23·4-28·4) and parasitic diarrhoea (3·5%, 3·0-5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8-29·9), sapovirus (22·8, 18·9-27·5), rotavirus (20·7, 18·8-23·0), adenovirus 40/41 (19·0, 16·8-23·0), enterotoxigenic Escherichia coli (18·8, 16·5-23·8), norovirus (15·4, 13·5-20·1), astrovirus (15·0, 12·0-19·5), Campylobacter jejuni or C coli (12·1, 8·5-17·2), Cryptosporidium (5·8, 4·3-8·3), and typical enteropathogenic E coli (5·4, 2·8-9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% [95% CI 46·7-54·1], specificity 84·0% [83·0-84·9]) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% [95% CI 12·1-17·3], specificity 96·5% [96·0-97·0]).

interpretationQuantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings.

fundingBill & Melinda Gates Foundation.

Indexed as

Asia, WesternBrazilChild, PreschoolCohort StudiesDiarrheaHealth ResourcesHumansIncidenceInfantInfant, NewbornMolecular Diagnostic TechniquesPeruReal-Time Polymerase Chain ReactionSouth AfricaTanzania

Identifiers

PMID30287127
PMCPMC6227251
OpenAlexW2892815535

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.