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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

2018; Elsevier BV; Volume: 6; Issue: 12 Linguagem: Inglês

10.1016/s2214-109x(18)30349-8

2572-116X

James A Platts-Mills, Jie Liu, Elizabeth T. Rogawski McQuade, Furqan Kabir, Paphavee Lertsethtakarn, Mery Siguas, Shaila Khan, Ira Praharaj, Arinao Murei, Rosemary Nshama, Buliga Mujaga, Alexandre Havt, Irene A Maciel, Timothy L. McMurry, Darwin J. Operario, Mami Taniuchi, Jean Gratz, Suzanne Stroup, James H. Roberts, Adil Kalam, Fátima Aziz, Shahida Qureshi, Mamunul Islam, Pimmada Sakpaisal, Sasikorn Silapong, Pablo Peñataro Yori, Revathi Rajendiran, Blossom Benny, Monica McGrath, Benjamin McCormick, Jessica C. Seidman, Dennis Lang, Michael Gottlieb, Richard L. Guerrant, Aldo Â. M. Lima, José Paulo Gagliardi Leite, Amidou Samie, Pascal Bessong, Nicola Page, Ladaporn Bodhidatta, Carl J. Mason, Sanjaya K. Shrestha, Ireen Kiwelu, Estomih Mduma, Najeeha Talat Iqbal, Zulfiqar A Bhutta, Tahmeed Ahmed, Rashidul Haque, Gagandeep Kang, Margaret Kosek, Eric R. Houpt, Angel Mendez Acosta, Rosa Burga, César Banda Chávez, Julian Torres Flores, Maribel Paredes Olotegui, Silvia Rengifo Pinedo, Dixner Rengifo Trigoso, Angel Orbe Vasquez, Imran Ahmed, Didar Alam, Asad Ali, Muneera A. Rasheed, Sajid Soofi, Ali Turab, Aisha K. Yousafzai, Anita K. M. Zaidi, Binob Shrestha, Bishnu Bahadur Rayamajhi, Tor A. Strand, Geetha Ammu, Sudhir Babji, Anuradha Bose, Ajila George, Dinesh Hariraju, Mats Steffi Jennifer, Sushil John, Shiny Kaki, Priyadarshani Karunakaran, Beena Koshy, Robin P. Lazarus, Jayaprakash Muliyil, Preethi Ragasudha, Venkata Raghava Mohan, Sophy Raju, Anup Ramachandran, Rakhi Ramadas, Karthikeyan Ramanujam, Anuradha Rose, Reeba Roshan, Srujan Lam Sharma, Shanmuga Sundaram, Rahul J. Thomas, William K. Pan, Ramya Ambikapathi, J. Daniel Carreon, Viyada Doan, Christel Hoest, Stacey Knobler, Mark A. Miller, Stephanie Psaki, Zeba Rasmussen, Stephanie A Richard, Karen H. Tountas, Erling Svensen, Caroline Amour, Eliwaza Bayyo, Regisiana Mvungi, John Pascal, Ladislaus Yarrot, Leah J. Barrett, Rebecca Dillingham, William A. Petri, Rebecca J. Scharf, AM Shamsir Ahmed, Ashraful Alam, Umma Haque, Md Iqbal Hossain, M. Munirul Islam, Mustafa Mahfuz, Dinesh Mondal, Baitun Nahar, Fahmida Tofail, Ram K. Chandyo, Prakash Shrestha, Rita Shrestha, Manjeswori Ulak, Aubrey Bauck, Robert E. Black, Laura E. Caulfield, William Checkley, Gwenyth Lee, Kerry Schulze, Samuel Scott, Laura E. Murray‐Kolb, A. Catharine Ross, Barbara A. Schaefer, Suzanne Simons, Laura Pendergast, Cláudia Buhamra Abreu, Hilda Costa, Alessandra Di Moura, José Quirino Filho, Álvaro M. Leite, Noélia L. Lima, Ila F. N. Lima, Bruna Leal Lima Maciel, Pedro H.Q.S. Medeiros, Milena Lima de Moraes, Francisco Suetônio Bastos Mota, Reinaldo B. Oriá, Josiane da Silva Quetz, Alberto M. Soares, Rosa MS Mota, Crystal L. Patil, Cloupas Mahopo, Angelina Maphula, Emanuel Nyathi,

Fecal contamination and water quality

Optimum 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.We 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.We 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]).Quantitative 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.Bill & Melinda Gates Foundation.