Abstract

The rise of antimicrobial resistance (AMR) is making it harder to treat infectious diseases. Salmonella Typhi, the causative agent of typhoid fever, stands as a noteworthy example, with more than 1,16,000 deaths occurring annually worldwide. Historically, narratives on AMR in S. Typhi often focus on microbial adaptation, politics and socio-economic considerations. For instance, economic limitations in endemic Low- and Middle-Income Countries (LMICs), including inadequate Water, Sanitation, and Hygiene (WaSH) infrastructure, have driven the selection for resistant strains, but have also influenced both health policies and the trajectory of scientific research on a global level. S. Typhi employs various AMR mechanisms - including drug inactivation, efflux pumps, and structural and metabolic changes - to combat antibiotics and ensure survival. Genetic alterations, conferred through spontaneous mutations and horizontal gene transfer, eventually drive these diverse mechanisms. This narrative review addresses the escalating concern of AMR in S. Typhi, including the extensively drug-resistant (XDR) strains. Here, we show that despite the endorsement of typhoid conjugate vaccines (TCVs) and advancements in novel target discoveries, the management of AMR in S. Typhi is undermined, not only by epidemiology or genetics but also by behavioural factors of individuals and social structures. In a broader sense, this review will also discuss the interplay between human, animal, and environmental interactions in the spread of XDR S. Typhi strains.This is because a holistic perspective that includes but is not limited to, global health strategies that transcend socioeconomic and political barriers, is necessary.

Keywords : Antimicrobial Resistance; Multidrug-resistant; Salmonella Typhi; Typhoid Fever; One Health; WaSH