Salmonella Infections: Global Trends and Emerging Challenges

Salmonella remains a leading cause of foodborne illness worldwide, with non-typhoidal Salmonella (NTS) responsible for an estimated 93.8 million infections and substantial global morbidity and mortality. This review synthesizes current evidence on the epidemiology, molecular pathogenesis, and prevention of both typhoidal and nontyphoidal Salmonella, with emphasis on emerging challenges in disease control. We highlight key virulence mechanisms, including Salmonella pathogenicity islands and Type III secretion systems, that mediate host cell invasion, intracellular survival, and immune modulation, alongside differences in host adaptation, reservoirs, and clinical outcomes between major serotypes. Epidemiological synthesis demonstrates marked geographic variability in disease burden, driven by underreporting, limited diagnostic capacity, and social determinants of health, with particularly high mortality from invasive NTS (iNTS) disease in sub-Saharan Africa. This review further identifies major challenges, including the global rise of multidrug-resistant Salmonella lineages, the emergence of high-risk serotypes such as monophasic S. Typhimurium and S. Infantis, and the increasing complexity of transmission across the farm-to-fork continuum. While advances in whole genome sequencing and integrated surveillance platforms (e.g., PulseNet and GenomeTrakr) have improved outbreak detection and source attribution, gaps in cross-sector coordination persist. Collectively, the evidence underscores the need for integrated One Health approaches that link human, animal, and environmental systems, alongside strengthened surveillance, targeted prevention strategies, and antimicrobial stewardship. Advances in vaccination, including licensed typhoidal vaccines such as Ty21a and Vi polysaccharide, and conjugate vaccines, as well as emerging live attenuated and glycoconjugate candidates targeting NTS, represent promising strategies for reducing the global burden of Salmonella infections. Future efforts should focus on improving global surveillance harmonization, addressing environmental and climate-related drivers of transmission, and advancing vaccine development and implementation.