Global Shigella epidemiology and vaccine coverage stratified by socioeconomic development levels, 1934–2025

development T he prominence of Shigella was underscored by the 2024 WHO Bacterial Priority Pathogens List (BPPL), which elevated fluoroquinolone-resistant Shigella spp. to the high-priority group due to its burden and increasing resistance in low-and middleincome countries (LMICs) (1).In economically transitioning countries, Shigella dominance has shifted between S. flexneri and S. sonnei, emphasizing the need for further investiga tion of Shigella's global epidemiology and its correlation with socioeconomic factors (2).We retrieved all available Shigella genome sequences from the NCBI GenBank database (n = 49,228; 29 April 2025).After filtering for complete temporal and geo graphic data, 43,180 isolates, collected between 1934 and 2025 in 70 countries across 6 continents, were retained (Table S2).Over the past century, Shigella has undergone substantial changes in species distribution, serotype diversity, antibiotic resistance, and the carriage of the virulence plasmid pINV (3).A significant epidemiological shift occurred between 2014-2019 and 2020-2024 (χ 2 = 1,472.3,P < 0.0001).S. flexneri replaced S. sonnei as the dominant strain, peaking at 67.06% in 2021.Conversely, S. boydii and S. dysenteriae remained rare.The prevalence of S. flexneri 1b increased significantly from 0.05% in 2013 to 12.13% in 2024, while S. flexneri 2a remained stable at 15%-25%.The pINV carriage rate increased steadily from 35.58% in 2014 to 55.69% in 2019, followed by a sharp surge to 69.44% in 2021, remaining at 69%-70% through 2024.A total of 214 antimicrobial resistance genes spanning nine classes (aminoglyco sides, polymyxins, quinolones, β-lactamases, chloramphenicol, sulfonamides, macrolides, fosfomycin, and tetracyclines) were identified.bla CTX-M-15 demonstrated sustained growth, increasing from 8.74% in 2014 to 16.28% in 2021.bla CTX-M-14 showed pro nounced fluctuations, peaking at 4.23% in 2018 before returning to baseline lev els.bla CTX-M-55 and bla CTX-M-3 remained at low prevalence levels.Fluoroquinolones and macrolides, the WHO-recommended therapeutics for shigellosis, require ongoing surveillance of their resistance gene carriage.The qnr demonstrated a general increase in prevalence, notwithstanding a transient decline to 9.96% in 2019, before peaking at 24.35% in 2020.The prevalence of mph(A) fluctuated between 23.93% and 32.84% from 2014 to 2024, while erm(B) steadily declined from 22.45% in 2017 to 21.17% in 2024.Additionally, the mobile colistin resistance gene mcr-1 transitioned from exclusive detection in S. flexneri to predominant occurrence in S. sonnei after 2021 (Table S1).The Human Development Index (HDI) classifies countries into four levels: very high (VHHD), high (HHD), medium (MHD), and low human development (LHD) (4).In VHHD and HHD regions, S. sonnei predominated (51.16% and 64.90%), followed by S. flexneri (46.01%and 33.01%).Conversely, S. flexneri was dominant in MHD and LHD regions (63.21% and 68.07%), significantly outnumbering S. sonnei (23.63% and 22.89%).S. boydii and S. dysenteriae were more prevalent in MHD (9.81% and 3.34%) and LHD (6.93% and 2.11%) areas.Serotype 2a was most common, with serotype 6 showing higher