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Incidence and Antimicrobial Resistance of Shigella-Attributable Diarrhea in Young Children: Results from the Multi-Country Enterics for Global Health (EFGH) Shigella Surveillance Study
Background: Shigella is a leading cause of dysentery and watery diarrhea in low- and middle-income countries (LMICs) with consequences beyond diarrhea, including environmental enteric dysfunction and linear growth impairment. We aimed to establish the burden, serotypes, and antibiotic resistance patterns of Shigella-diarrhea 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 2022 to August 2024 across seven countries: Kenya, Malawi, Mali, The Gambia, Bangladesh, Pakistan, and Peru. Children aged 6—35 months presenting with acute diarrhea were enrolled. Contemporaneous population enumeration and healthcare-seeking pattern ascertainment enabled care-seeking adjusted incidence estimate calculations. Shigella was deemed attributable if detected by microbiologic culture or by quantitative PCR (qPCR) using an ipaH Cycle threshold of £29·5 from rectal swabs. Antimicrobial resistance (AMR) to commonly used antibiotics was determined by disc diffusion.
Findings: Among 9476 enrolled children, 881 (9·3%) had Shigella detected by culture and 1870 (20·0%) by qPCR (among 9354 children with qPCR results available). S. flexneri dominated (497 [56·2%] by culture and 756 [39·4%] by qPCR), with S. flexneri 2a and 6 as the most common serotypes by both methods. Across study sites, the adjusted incidences of Shigella-diarrhea by culture and qPCR ranged from 2·68 to 11·69 and 3·49 to 26·89 per 100 child-years, respectively. Shigella isolates exhibited resistance to WHO-recommended antibiotics for dysentery with variability across sites: ciprofloxacin (37% [range 14-74%]), azithromycin (22% [range: 1-34%]), and ceftriaxone (16% [range: 0-64%]).
Interpretation: Shigella imposes a substantial burden on 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. Investment in Shigella vaccines and AMR monitoring should be prioritized.
Note: Bill & Melinda Gates grant number(s): Award numbers INV 028721, INV-041730, INV-016650, INV-031791, INV-036891, INV-036892
Data availability statement: The EFGH statistical analysis plan https://clinicaltrials.gov/study/NCT06047821) and study protocol (https://academic.oup.com/ofid/issue/11/Supplement_1) were made publicly available. The datasets were deidentified and anonymized and will be publicly available upon publication of the manuscript
Yousafzai, Mohammad Tahir and Cornick, Jennifer and Yori, Pablo Peñataro and Hossain, M. Jahangir and Keita, Adama Mamby and Atlas, Hannah E. and Khanam, Farhana and Omore, Richard and Galagan, Sean R. and Ahmed, Naveed and Ahmmed, Faisal and Awuor, Alex O. and Badji, Henry and Conteh, Bakary and Garcia Quesada, Maria and Garcia-Bardales, Paul F. and Horne, Bri'Anna and Hotwani, Aneeta and Houpt, Eric R. and Islam, Md. Taufiqul and Jere, Khuzwayo C. and Juma, Jane and Liu, Jie and Mategula, Donnie and Ogwel, Billy and Okonji, Caleb and Onwuchekwa, Uduma U. and Paredes Olortegui, Maribel and Platts-Mills, James A. and Qureshi, Sonia and Rajib, Nazmul Hasan and Rogawski McQuade, Elizabeth T. and Schiaffino, Francesca and Secka, Ousman and Sow, Samba O. and Witte, Desiree and Kotloff, Karen L. and Cunliffe, Nigel A. and Clemens, John D. and Tennant, Sharon M. and Qamar, Farah Naz and Kosek, Margaret N. and Pavlinac, Patricia B. and Tapia, Milagritos D. and Ochieng, John Benjamin and Consortium, EFGH, Incidence and Antimicrobial Resistance of Shigella-Attributable Diarrhea in Young Children: Results from the Multi-Country Enterics for Global Health (EFGH) Shigella Surveillance Study. Available at SSRN: https://ssrn.com/abstract=5386776 or http://dx.doi.org/10.2139/ssrn.5386776
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