{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:12:31Z","timestamp":1789708351389,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to systematically analyze the morbidity and mortality of infectious diarrhea in children under 14\u202fyears old caused by pathogenic microorganisms globally and their temporal trends.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was a retrospective cross-sectional analysis using the database provided by the Global Burden of Disease 2021 (GBD 2021). The mortality, morbidity, and disability-adjusted life years (DALYs) of childhood diarrhea from 1990 to 2021 were stratified and analyzed using multivariate regression models and the calculation of estimated annual percentage change (EAPC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 2021, the total number of cases of diarrhea in children aged 0\u201314\u202fyears worldwide was 168.73 million. The number of cases was highest in low- and medium-SDI regions, and the incidence in South Asia was ranking first in the world. The highest incidence was in neonates, while the incidence in the 10\u201314\u202fyear old group has increased by 36.5% since 1990. The highest mortality rate was found in low SDI areas. In terms of risk factors, multivariate regression analysis showed that unsafe water sources were the most important risk factors for all age groups, and growth retardation in children and unsafe sanitation conditions also significantly increased the burden of diarrhea. Except for the 2\u20134 age group, the top three pathogens causing death and DALY in other age groups were <jats:italic>Rotavirus<\/jats:italic>, <jats:italic>Adenovirus<\/jats:italic>, and <jats:italic>Shigella<\/jats:italic>, with <jats:italic>Rotavirus<\/jats:italic> being the primary pathogen in all age groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although the global burden of diarrhea has decreased significantly, it is still high in low-income countries and low- and medium-SDI areas, and newborns are at high risk. Unsafe water sources are the main risk factor for diarrheal deaths in children of all ages.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1676249","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:23:49Z","timestamp":1760937829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Regional and age-specific global trends associated with infectious diarrhea in children under 14\u202fyears old caused by pathogenic microorganisms in 2021"],"prefix":"10.3389","volume":"12","author":[{"given":"Tuanjie","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinquan","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishuai","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiju","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref1","first-page":"197","article-title":"The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000","volume":"81","author":"Kosek","year":"2003","journal-title":"Bull World Health Organ"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00038-017-1008-z","article-title":"Burden of diarrhea in the eastern Mediterranean region, 1990-2015: findings from the global burden of disease 2015 study","volume":"63","year":"2018","journal-title":"Int J Public Health"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S1473-3099(19)30401-3","article-title":"Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the global burden of disease study 2017","volume":"20","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/S1473-3099(17)30276-1","article-title":"Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the global burden of disease study 2015","volume":"17","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1332319","DOI":"10.3389\/fpubh.2024.1332319","article-title":"Epidemiology of enterotoxigenic Escherichia coli and impact on the growth of children in the first two years of life in Lima, Peru","volume":"12","author":"Pajuelo","year":"2024","journal-title":"Front Public Health"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e758","DOI":"10.1016\/S2214-109X(18)30283-3","article-title":"Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study","volume":"6","author":"Khalil","year":"2018","journal-title":"Lancet Glob Health"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/S0140-6736(20)30114-8","article-title":"Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the global burden of disease study 2017","volume":"395","year":"2020","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e0257522","DOI":"10.1371\/journal.pone.0257522","article-title":"Diarrhea and associated factors among under five children in sub-Saharan Africa: evidence from demographic and health surveys of 34 sub-Saharan countries","volume":"16","author":"Demissie","year":"2021","journal-title":"PLoS One"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1089\/sur.2024.090","article-title":"A systematic review and Meta-analysis of Aeromonas-associated Diarrhea among children in Asia","volume":"25","author":"Sadeghi","year":"2024","journal-title":"Surg Infect"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the global enteric Multicenter study, GEMS): a prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e009548","DOI":"10.1136\/bmjgh-2022-009548","article-title":"Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the global Pediatric Diarrhea surveillance network","volume":"7","author":"Cohen","year":"2022","journal-title":"BMJ Glob Health"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e568","DOI":"10.1016\/S2214-109X(19)30076-2","article-title":"The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the global enteric Multicenter study (GEMS)","volume":"7","author":"Kotloff","year":"2019","journal-title":"Lancet Glob Health"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e255","DOI":"10.1016\/S2214-109X(18)30045-7","article-title":"Global disability-adjusted life-year estimates of long-term health burden and undernutrition attributable to diarrhoeal diseases in children younger than 5 years","volume":"6","author":"Troeger","year":"2018","journal-title":"Lancet Glob Health"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40364-024-00718-2","article-title":"Global, regional, and national burden of esophageal cancer: a systematic analysis of the global burden of disease study 2021","volume":"13","author":"Jin","year":"2025","journal-title":"Biomark Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/S1473-3099(24)00176-2","article-title":"Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the global burden of disease study 2021","volume":"24","author":"Bender","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1158\/1055-9965.EPI-11-0421","article-title":"Age-period-cohort models in cancer surveillance research: ready for prime time?","volume":"20","author":"Rosenberg","year":"2011","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"861629","DOI":"10.3389\/fpubh.2022.861629","article-title":"Investigating global spatial patterns of Diarrhea-related mortality in children under five","volume":"10","author":"Almasi","year":"2022","journal-title":"Front Public Health"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"S232","DOI":"10.1093\/cid\/cis753","article-title":"The global enteric Multicenter study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case\/control study","volume":"55","author":"Kotloff","year":"2012","journal-title":"Clin Infect Dis"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e0283871","DOI":"10.1371\/journal.pone.0283871","article-title":"Etiology and risk factors for diarrheal disease amongst rural and peri-urban populations in Cambodia, 2012\u20132018","volume":"18","author":"Kelly","year":"2023","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"8564","DOI":"10.1038\/s41598-021-87889-2","article-title":"Hierarchical disentanglement of contextual from compositional risk factors of diarrhoea among under-five children in low- and middle-income countries","volume":"11","author":"Fagbamigbe","year":"2021","journal-title":"Sci Rep"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/1471-2458-12-220","article-title":"Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review","volume":"12","author":"Fischer Walker","year":"2012","journal-title":"BMC Public Health"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s12879-025-10597-z","article-title":"Inappropriate use of antibiotics in the management of diarrhoea in children under five years admitted with acute diarrhoea in four provinces of Mozambique 2014-2019","volume":"25","author":"Sal\u00eancia-Ferr\u00e3o","year":"2025","journal-title":"BMC Infect Dis"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"130","DOI":"10.32832\/jurma.v7i1.1708","article-title":"Scoping review: diarrhea in toddlers and causing factors","volume":"7","author":"Susilowati","year":"2023","journal-title":"PKM-P"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e0008520","DOI":"10.1371\/journal.pntd.0008520","article-title":"Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: evidence from the global enteric Multicenter study","volume":"14","author":"Lewnard","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"109797","DOI":"10.1016\/j.jpsychores.2019.109797","article-title":"Prolonged constipation and diarrhea in childhood and disordered eating in adolescence","volume":"126","author":"Wiklund","year":"2019","journal-title":"J Psychosom Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1038\/s41598-021-81942-w","article-title":"Unhealthy life habits associated with self-induced vomiting and laxative misuse in Brazilian adolescents","volume":"11","author":"de Souza","year":"2021","journal-title":"Sci Rep"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1111\/apt.18197","article-title":"Maladaptive weight control and eating behaviours in female adolescents\/young adults are associated with increased risk of irritable bowel syndrome in adulthood: results from the growing up today study (GUTS)","volume":"60","author":"Yang","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S1473-3099(18)30362-1","article-title":"Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the global burden of disease study 2016","volume":"18","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"CD005496","DOI":"10.1002\/14651858.CD005496.pub6","article-title":"Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants","volume":"7","author":"Sharif","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1047","DOI":"10.1093\/cid\/ciac561","article-title":"Risk factors for mortality among children younger than age 5 years with severe Diarrhea in low- and middle-income countries: findings from the World Health Organization-coordinated global rotavirus and Pediatric Diarrhea surveillance networks","volume":"76","author":"Hartman","year":"2023","journal-title":"Clin Infect Dis"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12889-022-12515-3","article-title":"The burden of diarrhea, etiologies, and risk factors in India from 1990 to 2019: evidence from the global burden of disease study","volume":"22","author":"Behera","year":"2022","journal-title":"BMC Public Health"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4269\/ajtmh.21-0767","article-title":"Diarrhea prevalence and child growth faltering are associated with subsequent adverse child developmental outcomes in Bangladesh (CHoBI7 program)","volume":"106","author":"George","year":"2021","journal-title":"Am J Trop Med Hyg"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3390\/ijerph21070823","article-title":"Rainfall and temperature influences on childhood Diarrhea and the effect modification role of water and sanitation conditions: A systematic review and Meta-analysis","volume":"21","author":"Geremew","year":"2024","journal-title":"Int J Environ Res Public Health"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"S132","DOI":"10.1093\/cid\/ciac911","article-title":"Survey-based assessment of water, sanitation, and animal-associated risk factors for moderate-to-severe diarrhea in the vaccine impact on diarrhea in Africa (VIDA) study: the Gambia, Mali, and Kenya, 2015-2018","volume":"76","author":"Berendes","year":"2023","journal-title":"Clin Infect Dis"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1186\/s12889-022-12735-7","article-title":"The risk of water, sanitation and hygiene on diarrhea-related infant mortality in eastern Ethiopia: a population-based nested case-control","volume":"22","author":"Mebrahtom","year":"2022","journal-title":"BMC Public Health"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"8078","DOI":"10.3390\/ijerph17218078","article-title":"Associations between household-level exposures and all-cause Diarrhea and pathogen-specific enteric infections in children enrolled in five sentinel surveillance studies","volume":"17","author":"Colston","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"6138","DOI":"10.3390\/ijerph19106138","article-title":"Effects of climatic factors on diarrheal diseases among children below 5 years of age at national and subnational levels in Nepal: an ecological study","volume":"19","author":"Dhimal","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"532","DOI":"10.4269\/ajtmh.20-0014","article-title":"Effect of a community-led Total sanitation intervention on the incidence and prevalence of Diarrhea in children in rural Ethiopia: A cluster-randomized controlled trial","volume":"105","author":"Cha","year":"2021","journal-title":"Am J Trop Med Hyg."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1398264","DOI":"10.3389\/fpubh.2024.1398264","article-title":"Magnitude of enteric pathogens associated with diarrhea and antibiotic resistance of enteric bacterial pathogens isolated among children under 5\u202fyears of age in bule Hora town, west Guji, Ethiopia","volume":"12","author":"Ashenafi","year":"2024","journal-title":"Front Public Health"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1132927","DOI":"10.3389\/fpubh.2023.1132927","article-title":"A snap-shot of a diarrheal epidemic in Dhaka due to enterotoxigenic Escherichia coli and Vibrio cholerae O1 in 2022","volume":"11","author":"Tauheed","year":"2023","journal-title":"Front Public Health"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e0243479","DOI":"10.1371\/journal.pone.0243479","article-title":"Prevalence of enteric pathogens, intestinal parasites and resistance profile of bacterial isolates among HIV infected and non-infected diarrheic patients in Dessie town, Northeast Ethiopia","volume":"15","author":"Belay","year":"2020","journal-title":"PLoS One"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e0119824","DOI":"10.1371\/journal.pone.0119824","article-title":"Diarrheal disease in rural Mozambique: burden, risk factors and Etiology of diarrheal disease among children aged 0-59 months seeking Care at Health Facilities","volume":"10","author":"Nhampossa","year":"2015","journal-title":"PLoS One"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.vaccine.2011.12.092","article-title":"Burden of rotavirus gastroenteritis and distribution of rotavirus strains in Asia: a systematic review","volume":"30","author":"Kawai","year":"2012","journal-title":"Vaccine"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"taac132","DOI":"10.1093\/jtm\/taac132","article-title":"Burden of Shigella in South Asia: a systematic review and meta-analysis","volume":"30","author":"Muzembo","year":"2023","journal-title":"J Travel Med"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e564","DOI":"10.1016\/S2214-109X(15)00151-5","article-title":"Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)","volume":"3","author":"Platts-Mills","year":"2015","journal-title":"Lancet Glob Health"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e0259077","DOI":"10.1371\/journal.pone.0259077","article-title":"Global estimated disability-adjusted life-years (DALYs) of diarrheal diseases: a systematic analysis of data from 28 years of the global burden of disease study","volume":"16","author":"Karambizi","year":"2021","journal-title":"PLoS One"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1676249\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:23:50Z","timestamp":1760937830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1676249\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":46,"alternative-id":["10.3389\/fmed.2025.1676249"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1676249","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"article-number":"1676249"}}