Etiology and incidence of diarrhea requiring hospitalization in children under 5 years of age in 31 low- and middle-income countries: Findings from the Global Pediatric Diarrhea Surveillance network, 2017–2022

Diarrhea remains a leading cause of child morbidity and mortality. Improved and ongoing estimates of the etiology of hospitalized pediatric diarrhea in low- and middle-income countries (LMICs) are needed to help prioritize and evaluate the use of existing and upcoming vaccines and interventions. The Global Pediatric Diarrhea Surveillance (GPDS) network is a World Health Organization (WHO)-coordinated public health surveillance network investigating the etiology of hospitalized diarrhea among children aged <5 years in LMICs. The GPDS network enrolls children hospitalized with diarrhea at 38 sentinel surveillance sites in 31 LMICs. Randomly selected stool specimens were tested by TaqMan Array Card quantitative reverse-transcription polymerase chain reaction (qPCR) for 16 pathogens associated with diarrhea. We estimated pathogen-specific attributable fractions (AFs) and incidence of diarrheal hospitalizations at the global, regional, and country levels during 3 time periods: 2017-2018, 2019-2020, and 2021-2022, with a focus on the most recent results. During 2017-2022, the GPDS network enrolled 70,750 children aged <5 years hospitalized with diarrhea, of which 16,458 (23.3%) were randomly selected for qPCR testing. The most prevalent pathogen detected, regardless of quantity or modeled etiologic attribution, was rotavirus (weighted prevalence 30.4%), followed by adenovirus 40/41 (19.1%), norovirus (17.9%), Shigella (14.1%), and Campylobacter jejuni/coli (8.6%). Overall, in 2017-2022, rotavirus was the leading etiology globally (AF 32.5%; 95% Confidence Interval (CI): 27.4, 37.6), followed by Shigella (9.8%; 8.4, 11.3), adenovirus 40/41 (8.6%; 6.3, 10.8) and norovirus (6.7%; 5.6, 7.7). Over time, rotavirus consistently declined from an AF of 36.7% (95% CI: 28.7, 46.7) in 2017-2018 to 26.7% (20.7, 34.1) in 2021-2022. Norovirus AF increased slightly from 6.2% (4.7, 7.7) in 2017-2018 to 7.3% (5.0, 9.2) in 2021-2022. Global Shigella burden remained stable, and adenovirus 40/41 demonstrated significant volatility, peaking globally in 2019-2020 (11.9%; 5.9, 17.5). In 2021-2022, rotavirus was the leading cause of hospitalized diarrhea in 6 of 9 geographic groupings, norovirus predominated in Central and South America, and Shigella was the leading etiology in South Asia. In the subset of countries that had introduced rotavirus vaccine, the leading etiologies in 2021-2022 were rotavirus (18.4%; 15.8, 21.5) and Shigella (16.4%; 11.8, 21.1). In 2021-2022, rotavirus had the highest attributable incidence of hospitalized diarrhea in children (2.3 per 1,000 child-years; 1.8, 3.0), followed by Shigella (0.9; 0.7, 1.1), norovirus (0.6; 0.4, 0.8) and adenovirus 40/41 (0.6; 0.4, 0.8). Despite the widespread use of rotavirus vaccines, rotavirus remained the leading cause of severe diarrhea among children aged <5 years in LMICs globally. However, the proportion of pediatric diarrhea attributable to rotavirus consistently declined from 2017-2018-2021-2022, and there were notable differences in the distribution of diarrheal etiologies between regions and across time periods. Shigella, norovirus, and enteric adenoviruses were also associated with a substantial burden of disease. Improving the efficacy and coverage of rotavirus vaccination and prioritizing interventions against other enteric pathogens could further reduce diarrhea morbidity and mortality.