The incidence and antimicrobial resistance of Shigella-attributable diarrhoea in young children in low-income and middle-income countries from the multicountry Enterics for Global Health (EFGH) Shigella Surveillance Study: a prospective, facility-based hybrid surveillance study.

BACKGROUND: Shigella is a leading cause of dysentery and watery diarrhoea in low-income and middle-income countries (LMICs) with consequences beyond diarrhoea for children younger than 5 years, including environmental enteric dysfunction and linear growth impairment. We established the burden, serotypes, and antibiotic resistance patterns of Shigella-diarrhoea among young children in LMICs to inform vaccine trial planning and eventual vaccine introduction in high-burden countries.

METHODS: The Enterics for Global Health (EFGH) study was a prospective, facility-based hybrid surveillance study conducted from June 21, 2022, to Aug 25, 2024, across seven countries: Kenya, Malawi, Mali, The Gambia, Bangladesh, Pakistan, and Peru. Children aged 6-35 months presenting at selected health-care facilities with acute diarrhoea (three or more abnormally loose or watery stools in the last 24-h period lasting less than 14 days) were enrolled. We calculated care-seeking adjusted incidence estimates from contemporaneous population enumeration and by ascertaining health-care seeking patterns from a health-care utilisation survey conducted in children aged 6-35 months in the health-facility catchment area. We deemed Shigella to be attributable if detected by microbiological culture or by quantitative PCR (qPCR) using an ipaH quantification cycle threshold of less than or equal to 29·5 from rectal swabs. We determined antimicrobial resistance to commonly used antibiotics by disc diffusion. We calculated adjusted incidence for all participating country sites and by key subgroups of interest (age, diarrhoea severity, study month, Shigella species, and serotype).

FINDINGS: Of the 9476 enrolled children, 4316 (45·5%) were female and 5160 (54·5%) were male, 881 (9·3%) had Shigella detected by culture and 1870 (20·0%) by qPCR (among 9354 children with qPCR results available). Shigella flexneri dominated (497 [56·2%] of 881 by culture and 756 [39·4%] of 1870 by qPCR), with S flexneri 2a and S flexneri 6 being the most common serotypes by both methods. Across study sites, the adjusted incidences of Shigella-attributed diarrhoea by culture ranged from 2·7 per 100 child-years (95% CI 1·9-4·3) in Malawi to 11·7 per 100 child-years (8·3-24·2) in Peru and by qPCR ranged from 3·5 per 100 child-years (2·5-5·4) in Malawi to 26·9 per 100 child-years (19·0-40·9) in The Gambia. Shigella isolates exhibited resistance to WHO-recommended antibiotics for dysentery with variability across sites: ciprofloxacin (37·2% [range 14·0-74·0]), azithromycin (22·1% [1·2-34·2]), and ceftriaxone (16·2% [0·0-64·4]).

INTERPRETATION: Shigella-attributed diarrhoea is common among young children in LMICs, with its escalating antimicrobial resistance posing a serious threat to global public health. The leading quadrivalent vaccine candidates cover the majority of Shigella serotypes identified in this study. These data affirm both the need for Shigella vaccines and readiness of EFGH sites to conduct rigorous vaccine trials.

FUNDING: The Gates Foundation.