Researchers have raised alarm over the rising threat posed by typhoid fever as the bacterium responsible for the disease, Salmonella enterica serovar Typhi (S Typhi), evolves to become increasingly resistant to antibiotics. Despite being less common in developed countries, typhoid fever remains a serious concern globally, particularly in South Asia, where it accounts for approximately 70 percent of all cases.
A study published in The Lancet Microbe in 2022 revealed a significant increase in extensively drug-resistant (XDR) strains of S Typhi, which are replacing less resistant variants. This research involved sequencing the genomes of 3,489 S Typhi strains collected between 2014 and 2019 from regions including Nepal, Bangladesh, Pakistan, and India. The findings indicate a troubling trend: XDR Typhi is resistant to key antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, and is also developing resistance to newer medications like fluoroquinolones and third-generation cephalosporins.
Global Spread of Drug-Resistant Typhoid
The rapid international spread of these resistant strains is particularly concerning. Since 1990, nearly 200 instances of XDR Typhi have been documented outside of South Asia, reaching regions such as Southeast Asia, East Africa, and Southern Africa, as well as countries including the UK, US, and Canada. According to Jason Andrews, an infectious disease researcher at Stanford University, “The speed at which highly resistant strains of S Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk.”
Historically, the first XDR typhoid strain was identified in Pakistan in 2016, and by 2019, it had become the dominant strain in the country. Mutations conferring resistance to quinolones became prevalent in the early 2000s, making up over 85 percent of cases in countries like Bangladesh, India, Pakistan, Nepal, and Singapore. Currently, the only remaining effective oral antibiotic for typhoid treatment is azithromycin, which is also showing signs of declining effectiveness due to emerging mutations.
Urgency for Vaccination and Research
With untreated typhoid fever having a mortality rate of up to 20 percent, the need for preventive measures is critical. In 2024, there were over 13 million reported cases of typhoid globally. The authors of the study emphasize the need for rapid expansion of preventive strategies, including the use of typhoid conjugate vaccines in endemic regions. “Such measures are needed in countries where antimicrobial resistance prevalence among S Typhi isolates is currently high, but given the propensity for international spread, should not be restricted to such settings,” they stated.
While South Asia remains the epicenter for typhoid cases, the emergence of new variants in a globalized world poses a risk of widespread outbreaks. Health experts advocate for increased access to typhoid vaccines and investment in antibiotic research as essential steps to mitigate future health crises. A study conducted in India in 2021 suggested that vaccinating children in urban areas could prevent up to 36 percent of typhoid cases and related deaths.
Pakistan has emerged as a leader in this fight, being the first country to implement routine immunization against typhoid. Several other nations are now considering similar initiatives. As of April 2025, the World Health Organization has prequalified four typhoid conjugate vaccines, which are being integrated into childhood immunization programs in endemic countries.
Antibiotic resistance is a growing global health crisis, claiming more lives than diseases such as HIV/AIDS and malaria. Vaccination remains one of the most effective tools available to prevent catastrophic outbreaks. As the situation evolves, swift action is essential to avert a potential health emergency.
