Evidence map›Paper›PMID 27673470›Full record

ArticleLancet (London, England)2016

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

Jie Liu, James A Platts-Mills, Jane Juma, Furqan Kabir, Joseph Nkeze, Catherine Okoi, Darwin J Operario, Jashim Uddin, Shahnawaz Ahmed, Pedro L Alonso and 40 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06047821 (The Incidence and Burden of Shigella Diarrhea in Children Aged 6-35 Months), which is not on this map. Cited by 565 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
565citing papers in PubMed, 8 pooled it
–field-weighted citation impact
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.

NCT06047821 active not recruitingnot on this mapstarted 2022, after this paper: background citation

The Incidence and Burden of Shigella Diarrhea in Children Aged 6-35 Months: the Enterics for Global Health (EFGH) - Shigella Burden Study

TypeobservationalSponsorUniversity of WashingtonRan2022 to 2025Enrolled9,800ConditionsShigella, Child, Diarrhea
3 · Its place in the literature

Who cites it

565 citing papers in PubMed, 8 syntheses or guidelines pooled it.

  1. Burden ofBMJ global health · 2026
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  9. Effect of one prophylactic dose of azithromycin on Bifidobacterium infantis colonization in infants from the Mumta trial.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2025
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505 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors.

Jie LiuDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
James A Platts-MillsDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Jane JumaCenter for Global Health Research, Kenya Medical Research Institute, Nairobi, Kenya.
Furqan KabirDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Joseph NkezeCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Catherine OkoiMedical Research Council Unit, Banjul, The Gambia.
Darwin J OperarioDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Jashim UddinInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
Shahnawaz AhmedInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
Pedro L AlonsoCentro de Investigação em Saúde da Manhiça, Maputo, Mozambique; Barcelona Centre for International Health Research (CRESIB, Hospital Clinic-Universitat de Barcelona), Barcelona, Spain.
Martin AntonioMedical Research Council Unit, Banjul, The Gambia.
Stephen M BeckerDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
William C BlackwelderCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Robert F BreimanGlobal Disease Detection Division, Kenya Office of the US Centers for Disease Control and Prevention, Nairobi, Kenya.
Abu S G FaruqueInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
Barry FieldsGlobal Disease Detection Division, Kenya Office of the US Centers for Disease Control and Prevention, Nairobi, Kenya.
Jean GratzDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Rashidul HaqueInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
Anowar HossainInternational Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
M Jahangir HossainMedical Research Council Unit, Banjul, The Gambia.
Sheikh JarjuMedical Research Council Unit, Banjul, The Gambia.
Farah QamarDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Najeeha Talat IqbalDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Brenda KwambanaMedical Research Council Unit, Banjul, The Gambia.
Inacio MandomandoCentro de Investigação em Saúde da Manhiça, Maputo, Mozambique.
Timothy L McMurryPublic Health Sciences, University of Virginia, Charlottesville, VA, USA.
Caroline OchiengCenter for Global Health Research, Kenya Medical Research Institute, Nairobi, Kenya.
John B OchiengCenter for Global Health Research, Kenya Medical Research Institute, Nairobi, Kenya.
Melvin OchiengCenter for Global Health Research, Kenya Medical Research Institute, Nairobi, Kenya.
Clayton OnyangoGlobal Disease Detection Division, Kenya Office of the US Centers for Disease Control and Prevention, Nairobi, Kenya.
Sandra PanchalingamCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Adil KalamDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Fatima AzizDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Shahida QureshiDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Thandavarayan RamamurthyNational Institute of Cholera and Enteric Diseases, Kolkata, India.
James H RobertsPublic Health Sciences, University of Virginia, Charlottesville, VA, USA.
Debasish SahaMedical Research Council Unit, Banjul, The Gambia.
Samba O SowCentre pour le Développement des Vaccins, Bamako, Mali.
Suzanne E StroupDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Dipika SurNational Institute of Cholera and Enteric Diseases, Kolkata, India.
Boubou TambouraCentre pour le Développement des Vaccins, Bamako, Mali.
Mami TaniuchiDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Sharon M TennantCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Deanna ToemaCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Yukun WuCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Anita ZaidiDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
James P NataroDepartment of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Karen L KotloffCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Myron M LevineCenter for Vaccine Development and Institute of Global Health, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Eric R HouptDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA. Electronic address: erh6k@virginia.edu.

Funding

Quantitative molecular diagnostics for diarrhea etiology and vaccine efficacyK23AI114888 · NIAID · UNIVERSITY OF VIRGINIA · PI PLATTS-MILLS, JAMES ALEXANDER · 2015 to 2019
$932k
Medical Research Council MC_U190074190Medical Research Council MC_U190081991Medical Research Council MC_UP_A900_1122NIAID NIH HHS K23 AI114888
6 · The paper itself

Abstract

backgroundDiarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS).

methodsGEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children.

findingsWe analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections.

interpretationA quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised.

fundingBill & Melinda Gates Foundation.

Indexed as

Cost of IllnessAdenoviridaeAfricaAsiaBacteriaBacterial InfectionsCampylobacterCase-Control StudiesChild, PreschoolCoinfectionCryptosporidiumDiarrheaEscherichia coliFemaleHumansIncidence

Identifiers

PMID27673470
PMCPMC5471845

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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.