Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study
Summary: Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative P...
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Format: | Article |
Language: | English |
Published: |
Elsevier
2018-12-01
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Series: | The Lancet Global Health |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2214109X18303516 |
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doaj-9be3c3d03f66406a968d298935f21e1a |
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DOAJ |
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English |
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author |
Elizabeth T Rogawski, PhD Jie Liu, PhD James A Platts-Mills, MD Furqan Kabir, MSc Paphavee Lertsethtakarn, PhD Mery Siguas, BSc Shaila S Khan, MSc Ira Praharaj, MD Arinao Murei, BSc Rosemary Nshama, BSc Buliga Mujaga, BSc Alexandre Havt, PhD Irene A Maciel, PhD Darwin J Operario, PhD Mami Taniuchi, PhD Jean Gratz, MS Suzanne E Stroup, MS James H Roberts Adil Kalam, MSc Fatima Aziz, MSc Shahida Qureshi, MSc M Ohedul Islam, MSc Pimmada Sakpaisal, MSc Sasikorn Silapong, MSc Pablo P Yori, MPH Revathi Rajendiran, MSc Blossom Benny, MSc Monica McGrath, ScD Jessica C Seidman, PhD Dennis Lang, PhD Michael Gottlieb, PhD Richard L Guerrant, MD Aldo A M Lima, ProfPhD Jose Paulo Leite, PhD Amidou Samie, PhD Pascal O Bessong, ProfPhD Nicola Page, PhD Ladaporn Bodhidatta, MD Carl Mason, MD Sanjaya Shrestha, MD Ireen Kiwelu, PhD Estomih R Mduma, MPH Najeeha T Iqbal, PhD Zulfiqar A Bhutta, ProfPhD Tahmeed Ahmed, ProfMBBS Rashidul Haque, PhD Gagandeep Kang, ProfMD Margaret N Kosek, MD Eric R Houpt, ProfMD Angel Mendez Acosta Rosa Rios de Burga Cesar Banda Chavez Julian Torres Flores Maribel Paredes Olotegui Silvia Rengifo Pinedo Dixner Rengifo Trigoso Angel Orbe Vasquez Imran Ahmed Didar Alam Asad Ali Muneera Rasheed Sajid Soofi Ali Turab Aisha Yousafzai Anita KM Zaidi Binob Shrestha Bishnu Bahadur Rayamajhi Tor Strand Geetha Ammu Sudhir Babji Anuradha Bose Ajila T George Dinesh Hariraju M. Steffi Jennifer Sushil John Shiny Kaki Priyadarshani Karunakaran Beena Koshy Robin P Lazarus Jayaprakash Muliyil Preethi Ragasudha Mohan Venkata Raghava Sophy Raju Anup Ramachandran Rakhi Ramadas Karthikeyan Ramanujam Anuradha Rose Reeba Roshan Srujan L 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 Barrett Rebecca Dillingham William A Petri Rebecca Scharf AM Shamsir Ahmed Md Ashraful Alam Umma Haque Md Iqbal Hossain Munirul Islam Mustafa Mahfuz Dinesh Mondal Baitun Nahar Fahmida Tofail Ram Krishna Chandyo Prakash Sunder Shrestha Rita Shrestha Manjeswori Ulak Aubrey Bauck Robert Black Laura Caulfield William Checkley Gwenyth Lee Kerry Schulze Samuel Scott Laura E Murray-Kolb A Catharine Ross Barbara Schaefer Suzanne Simons Laura Pendergast Cláudia B Abreu Hilda Costa Alessandra Di Moura José Quirino Filho Álvaro M Leite Noélia L Lima Ila F Lima Bruna LL Maciel Pedro HQS Medeiros Milena Moraes Francisco S Mota Reinaldo B Oriá Josiane Quetz Alberto M Soares Rosa MS Mota Crystal L Patil Cloupas Mahopo Angelina Maphula Emanuel Nyathi |
spellingShingle |
Elizabeth T Rogawski, PhD Jie Liu, PhD James A Platts-Mills, MD Furqan Kabir, MSc Paphavee Lertsethtakarn, PhD Mery Siguas, BSc Shaila S Khan, MSc Ira Praharaj, MD Arinao Murei, BSc Rosemary Nshama, BSc Buliga Mujaga, BSc Alexandre Havt, PhD Irene A Maciel, PhD Darwin J Operario, PhD Mami Taniuchi, PhD Jean Gratz, MS Suzanne E Stroup, MS James H Roberts Adil Kalam, MSc Fatima Aziz, MSc Shahida Qureshi, MSc M Ohedul Islam, MSc Pimmada Sakpaisal, MSc Sasikorn Silapong, MSc Pablo P Yori, MPH Revathi Rajendiran, MSc Blossom Benny, MSc Monica McGrath, ScD Jessica C Seidman, PhD Dennis Lang, PhD Michael Gottlieb, PhD Richard L Guerrant, MD Aldo A M Lima, ProfPhD Jose Paulo Leite, PhD Amidou Samie, PhD Pascal O Bessong, ProfPhD Nicola Page, PhD Ladaporn Bodhidatta, MD Carl Mason, MD Sanjaya Shrestha, MD Ireen Kiwelu, PhD Estomih R Mduma, MPH Najeeha T Iqbal, PhD Zulfiqar A Bhutta, ProfPhD Tahmeed Ahmed, ProfMBBS Rashidul Haque, PhD Gagandeep Kang, ProfMD Margaret N Kosek, MD Eric R Houpt, ProfMD Angel Mendez Acosta Rosa Rios de Burga Cesar Banda Chavez Julian Torres Flores Maribel Paredes Olotegui Silvia Rengifo Pinedo Dixner Rengifo Trigoso Angel Orbe Vasquez Imran Ahmed Didar Alam Asad Ali Muneera Rasheed Sajid Soofi Ali Turab Aisha Yousafzai Anita KM Zaidi Binob Shrestha Bishnu Bahadur Rayamajhi Tor Strand Geetha Ammu Sudhir Babji Anuradha Bose Ajila T George Dinesh Hariraju M. Steffi Jennifer Sushil John Shiny Kaki Priyadarshani Karunakaran Beena Koshy Robin P Lazarus Jayaprakash Muliyil Preethi Ragasudha Mohan Venkata Raghava Sophy Raju Anup Ramachandran Rakhi Ramadas Karthikeyan Ramanujam Anuradha Rose Reeba Roshan Srujan L 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 Barrett Rebecca Dillingham William A Petri Rebecca Scharf AM Shamsir Ahmed Md Ashraful Alam Umma Haque Md Iqbal Hossain Munirul Islam Mustafa Mahfuz Dinesh Mondal Baitun Nahar Fahmida Tofail Ram Krishna Chandyo Prakash Sunder Shrestha Rita Shrestha Manjeswori Ulak Aubrey Bauck Robert Black Laura Caulfield William Checkley Gwenyth Lee Kerry Schulze Samuel Scott Laura E Murray-Kolb A Catharine Ross Barbara Schaefer Suzanne Simons Laura Pendergast Cláudia B Abreu Hilda Costa Alessandra Di Moura José Quirino Filho Álvaro M Leite Noélia L Lima Ila F Lima Bruna LL Maciel Pedro HQS Medeiros Milena Moraes Francisco S Mota Reinaldo B Oriá Josiane Quetz Alberto M Soares Rosa MS Mota Crystal L Patil Cloupas Mahopo Angelina Maphula Emanuel Nyathi Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study The Lancet Global Health |
author_facet |
Elizabeth T Rogawski, PhD Jie Liu, PhD James A Platts-Mills, MD Furqan Kabir, MSc Paphavee Lertsethtakarn, PhD Mery Siguas, BSc Shaila S Khan, MSc Ira Praharaj, MD Arinao Murei, BSc Rosemary Nshama, BSc Buliga Mujaga, BSc Alexandre Havt, PhD Irene A Maciel, PhD Darwin J Operario, PhD Mami Taniuchi, PhD Jean Gratz, MS Suzanne E Stroup, MS James H Roberts Adil Kalam, MSc Fatima Aziz, MSc Shahida Qureshi, MSc M Ohedul Islam, MSc Pimmada Sakpaisal, MSc Sasikorn Silapong, MSc Pablo P Yori, MPH Revathi Rajendiran, MSc Blossom Benny, MSc Monica McGrath, ScD Jessica C Seidman, PhD Dennis Lang, PhD Michael Gottlieb, PhD Richard L Guerrant, MD Aldo A M Lima, ProfPhD Jose Paulo Leite, PhD Amidou Samie, PhD Pascal O Bessong, ProfPhD Nicola Page, PhD Ladaporn Bodhidatta, MD Carl Mason, MD Sanjaya Shrestha, MD Ireen Kiwelu, PhD Estomih R Mduma, MPH Najeeha T Iqbal, PhD Zulfiqar A Bhutta, ProfPhD Tahmeed Ahmed, ProfMBBS Rashidul Haque, PhD Gagandeep Kang, ProfMD Margaret N Kosek, MD Eric R Houpt, ProfMD Angel Mendez Acosta Rosa Rios de Burga Cesar Banda Chavez Julian Torres Flores Maribel Paredes Olotegui Silvia Rengifo Pinedo Dixner Rengifo Trigoso Angel Orbe Vasquez Imran Ahmed Didar Alam Asad Ali Muneera Rasheed Sajid Soofi Ali Turab Aisha Yousafzai Anita KM Zaidi Binob Shrestha Bishnu Bahadur Rayamajhi Tor Strand Geetha Ammu Sudhir Babji Anuradha Bose Ajila T George Dinesh Hariraju M. Steffi Jennifer Sushil John Shiny Kaki Priyadarshani Karunakaran Beena Koshy Robin P Lazarus Jayaprakash Muliyil Preethi Ragasudha Mohan Venkata Raghava Sophy Raju Anup Ramachandran Rakhi Ramadas Karthikeyan Ramanujam Anuradha Rose Reeba Roshan Srujan L 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 Barrett Rebecca Dillingham William A Petri Rebecca Scharf AM Shamsir Ahmed Md Ashraful Alam Umma Haque Md Iqbal Hossain Munirul Islam Mustafa Mahfuz Dinesh Mondal Baitun Nahar Fahmida Tofail Ram Krishna Chandyo Prakash Sunder Shrestha Rita Shrestha Manjeswori Ulak Aubrey Bauck Robert Black Laura Caulfield William Checkley Gwenyth Lee Kerry Schulze Samuel Scott Laura E Murray-Kolb A Catharine Ross Barbara Schaefer Suzanne Simons Laura Pendergast Cláudia B Abreu Hilda Costa Alessandra Di Moura José Quirino Filho Álvaro M Leite Noélia L Lima Ila F Lima Bruna LL Maciel Pedro HQS Medeiros Milena Moraes Francisco S Mota Reinaldo B Oriá Josiane Quetz Alberto M Soares Rosa MS Mota Crystal L Patil Cloupas Mahopo Angelina Maphula Emanuel Nyathi |
author_sort |
Elizabeth T Rogawski, PhD |
title |
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study |
title_short |
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study |
title_full |
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study |
title_fullStr |
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study |
title_full_unstemmed |
Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study |
title_sort |
use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the mal-ed cohort study |
publisher |
Elsevier |
series |
The Lancet Global Health |
issn |
2214-109X |
publishDate |
2018-12-01 |
description |
Summary: Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation. |
url |
http://www.sciencedirect.com/science/article/pii/S2214109X18303516 |
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doaj-9be3c3d03f66406a968d298935f21e1a2020-11-25T02:55:48ZengElsevierThe Lancet Global Health2214-109X2018-12-01612e1319e1328Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort studyElizabeth T Rogawski, PhD0Jie Liu, PhD1James A Platts-Mills, MD2Furqan Kabir, MSc3Paphavee Lertsethtakarn, PhD4Mery Siguas, BSc5Shaila S Khan, MSc6Ira Praharaj, MD7Arinao Murei, BSc8Rosemary Nshama, BSc9Buliga Mujaga, BSc10Alexandre Havt, PhD11Irene A Maciel, PhD12Darwin J Operario, PhD13Mami Taniuchi, PhD14Jean Gratz, MS15Suzanne E Stroup, MS16James H Roberts17Adil Kalam, MSc18Fatima Aziz, MSc19Shahida Qureshi, MSc20M Ohedul Islam, MSc21Pimmada Sakpaisal, MSc22Sasikorn Silapong, MSc23Pablo P Yori, MPH24Revathi Rajendiran, MSc25Blossom Benny, MSc26Monica McGrath, ScD27Jessica C Seidman, PhD28Dennis Lang, PhD29Michael Gottlieb, PhD30Richard L Guerrant, MD31Aldo A M Lima, ProfPhD32Jose Paulo Leite, PhD33Amidou Samie, PhD34Pascal O Bessong, ProfPhD35Nicola Page, PhD36Ladaporn Bodhidatta, MD37Carl Mason, MD38Sanjaya Shrestha, MD39Ireen Kiwelu, PhD40Estomih R Mduma, MPH41Najeeha T Iqbal, PhD42Zulfiqar A Bhutta, ProfPhD43Tahmeed Ahmed, ProfMBBS44Rashidul Haque, PhD45Gagandeep Kang, ProfMD46Margaret N Kosek, MD47Eric R Houpt, ProfMD48Angel Mendez AcostaRosa Rios de BurgaCesar Banda ChavezJulian Torres FloresMaribel Paredes OloteguiSilvia Rengifo PinedoDixner Rengifo TrigosoAngel Orbe VasquezImran AhmedDidar AlamAsad AliMuneera RasheedSajid SoofiAli TurabAisha YousafzaiAnita KM ZaidiBinob ShresthaBishnu Bahadur RayamajhiTor StrandGeetha AmmuSudhir BabjiAnuradha BoseAjila T GeorgeDinesh HarirajuM. Steffi JenniferSushil JohnShiny KakiPriyadarshani KarunakaranBeena KoshyRobin P LazarusJayaprakash MuliyilPreethi RagasudhaMohan Venkata RaghavaSophy RajuAnup RamachandranRakhi RamadasKarthikeyan RamanujamAnuradha RoseReeba RoshanSrujan L SharmaShanmuga SundaramRahul J ThomasWilliam K PanRamya AmbikapathiJ Daniel CarreonViyada DoanChristel HoestStacey KnoblerMark A MillerStephanie PsakiZeba RasmussenStephanie A RichardKaren H TountasErling SvensenCaroline AmourEliwaza BayyoRegisiana MvungiJohn PascalLadislaus YarrotLeah BarrettRebecca DillinghamWilliam A PetriRebecca ScharfAM Shamsir AhmedMd Ashraful AlamUmma HaqueMd Iqbal HossainMunirul IslamMustafa MahfuzDinesh MondalBaitun NaharFahmida TofailRam Krishna ChandyoPrakash Sunder ShresthaRita ShresthaManjeswori UlakAubrey BauckRobert BlackLaura CaulfieldWilliam CheckleyGwenyth LeeKerry SchulzeSamuel ScottLaura E Murray-KolbA Catharine RossBarbara SchaeferSuzanne SimonsLaura PendergastCláudia B AbreuHilda CostaAlessandra Di MouraJosé Quirino FilhoÁlvaro M LeiteNoélia L LimaIla F LimaBruna LL MacielPedro HQS MedeirosMilena MoraesFrancisco S MotaReinaldo B OriáJosiane QuetzAlberto M SoaresRosa MS MotaCrystal L PatilCloupas MahopoAngelina MaphulaEmanuel NyathiDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USAAga Khan University, Karachi, PakistanArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, ThailandAsociación Benéfica PRISMA, Iquitos, PeruInternational Centre for Diarrhoeal Disease Research, Dhaka, BangladeshChristian Medical College, Vellore, IndiaUniversity of Venda, Thohoyandou, South AfricaHaydom Global Health Institute, Haydom, TanzaniaKilimanjaro Clinical Research Institute, Moshi, TanzaniaFederal University of Ceara, Fortaleza, BrazilFundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, BrazilDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USAAga Khan University, Karachi, PakistanAga Khan University, Karachi, PakistanAga Khan University, Karachi, PakistanInternational Centre for Diarrhoeal Disease Research, Dhaka, BangladeshArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, ThailandArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, ThailandAsociación Benéfica PRISMA, Iquitos, Peru; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USAChristian Medical College, Vellore, IndiaChristian Medical College, Vellore, IndiaBloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USAFogarty International Center, National Institutes of Health, Bethesda, MD, USAFoundation for the National Institutes of Health, Bethesda, MD, USAFoundation for the National Institutes of Health, Bethesda, MD, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USAFederal University of Ceara, Fortaleza, BrazilFundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, BrazilUniversity of Venda, Thohoyandou, South AfricaUniversity of Venda, Thohoyandou, South AfricaNational Institute for Communicable Diseases, Johannesburg, South AfricaFogarty International Center, National Institutes of Health, Bethesda, MD, USAArmed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, ThailandWalter Reed/AFRIMS Research Unit, Nepal, Kathmandu, Nepal; University of Bergen, Bergen, NorwayKilimanjaro Clinical Research Institute, Moshi, TanzaniaHaydom Global Health Institute, Haydom, TanzaniaAga Khan University, Karachi, PakistanAga Khan University, Karachi, PakistanInternational Centre for Diarrhoeal Disease Research, Dhaka, BangladeshInternational Centre for Diarrhoeal Disease Research, Dhaka, BangladeshChristian Medical College, Vellore, IndiaAsociación Benéfica PRISMA, Iquitos, Peru; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Correspondence to: Prof Eric R Houpt, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908, USASummary: Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.http://www.sciencedirect.com/science/article/pii/S2214109X18303516 |