Typhoid fever, an ancient illness, remains a significant threat in the modern world due to the bacterium Salmonella enterica serovar Typhi (S. Typhi) rapidly developing extensive drug resistance. Antibiotics are the sole effective treatment, but over three decades, resistance to oral medications has escalated.
Research analyzing thousands of S. Typhi strains from South Asia has revealed a surge in extensively drug-resistant (XDR) strains. These strains are impervious not only to frontline antibiotics but also to newer classes like fluoroquinolones and third-generation cephalosporins. While most cases originate in South Asia, XDR Typhi has been identified in nearly 200 instances of international spread since 1990, appearing in Southeast Asia, Africa, the UK, the US, and Canada.
Historically treated with third-generation antimicrobials, XDR typhoid strains now present a critical challenge. Mutations conferring resistance to quinolones and cephalosporins are widespread. Worryingly, mutations that confer resistance to azithromycin, the last remaining oral antibiotic, are also emerging. If these mutations become prevalent in XDR S. Typhi, the efficacy of all oral antimicrobials for typhoid treatment will be threatened. Untreated typhoid fever can be fatal in up to 20 percent of cases.
Preventing future outbreaks hinges on expanding access to typhoid conjugate vaccines globally. Pakistan has pioneered routine immunization, with a few other countries following suit. The World Health Organization has prequalified four typhoid conjugate vaccines, which are being introduced into childhood immunization programs in endemic countries. Health experts emphasize the need for continued investment in new antibiotic research to combat this growing public health crisis.