

@article {15982,
	title = {{Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study}},
	journal = {The Lancet},
	volume = {388},
	number = {10051},
	year = {2016},
	month = {sep},
	pages = {1291{\textendash}1301},
	publisher = {Elsevier},
	abstract = {Background Diarrhoea 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). Methods GEMS 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. Findings We 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{\textperiodcentered}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{\textperiodcentered}3{\%} (95{\%} CI 83{\textperiodcentered}2{\textendash}96{\textperiodcentered}0) at the population level, compared with 51{\textperiodcentered}5{\%} (48{\textperiodcentered}0{\textendash}55{\textperiodcentered}0) in the original GEMS analysis. The top six pathogens accounted for 77{\textperiodcentered}8{\%} (74{\textperiodcentered}6{\textendash}80{\textperiodcentered}9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42{\textperiodcentered}5{\%}) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38{\textperiodcentered}9{\%}) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. Interpretation A 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. Funding Bill {\&} Melinda Gates Foundation.},
	isbn = {0140-6736},
	issn = {1474547X},
	doi = {10.1016/S0140-6736(16)31529-X},
	url = {http://linkinghub.elsevier.com/retrieve/pii/S014067361631529X},
	author = {Liu, Jie and Platts-Mills, James A and Juma, Jane and Kabir, Furqan and Nkeze, Joseph and Okoi, Catherine and Operario, Darwin J and Uddin, Jashim and Ahmed, Shahnawaz and Alonso, Pedro L and Antonio, Martin and Becker, Stephen M and Blackwelder, William C and Breiman, Robert F and Faruque, Abu S.G. and Fields, Barry and Gratz, Jean and Haque, Rashidul and Hossain, Anowar and Hossain, M Jahangir and Jarju, Sheikh and Qamar, Farah and Iqbal, Najeeha Talat and Kwambana, Brenda and Mandomando, Inacio and McMurry, Timothy L and Ochieng, Caroline and Ochieng, John B. and Ochieng, Melvin and Onyango, Clayton and Panchalingam, Sandra and Kalam, Adil and Aziz, Fatima and Qureshi, Shahida and Ramamurthy, Thandavarayan and Roberts, James H and Saha, Debasish and Sow, Samba O and Stroup, Suzanne E and Sur, Dipika and Tamboura, Boubou and Taniuchi, Mami and Tennant, Sharon M and Toema, Deanna and Wu, Yukun and Zaidi, Anita and Nataro, James P and Kotloff, Karen L and Levine, Myron M and Houpt, Eric R}
}
