Typhoid fever, caused by the bacterium Salmonella enterica serovar Typhi (S Typhi), is experiencing alarming levels of drug resistance, according to a study published in The Lancet Microbe in 2022. This ancient disease, once a prevalent threat globally, is now emerging as a significant health risk, particularly in developing regions. Recent research indicates that extensively drug-resistant (XDR) strains of S Typhi are rapidly replacing less resistant variants, posing a serious challenge to current treatment options.
Scientists from multiple countries sequenced the genomes of 3,489 S Typhi strains collected between 2014 and 2019 from regions in Nepal, Bangladesh, Pakistan, and India. Their findings revealed a troubling increase in XDR Typhi, which is resistant to frontline antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. More concerning, these strains are also developing resistance to newer antibiotics like fluoroquinolones and third-generation cephalosporins.
Global Spread of Drug-Resistant Typhoid
The research highlights that the spread of XDR Typhi is not confined to South Asia. Since 1990, nearly 200 instances of international transmission have been identified, with cases reported in Southeast Asia, East Africa, Southern Africa, and even in countries like the UK, US, and Canada. “The speed at which highly resistant strains of S Typhi have emerged and spread in recent years is a real cause for concern,” noted Jason Andrews, an infectious disease researcher at Stanford University.
Historically, third-generation antimicrobials, including quinolones and macrolides, have been effective against typhoid. However, by the early 2000s, mutations conferring quinolone resistance accounted for more than 85 percent of cases in South Asia. Today, the only remaining oral antibiotic that can treat typhoid effectively is azithromycin, yet resistance mutations for this drug are now spreading, threatening to render all oral treatments ineffective.
If left untreated, typhoid fever can lead to death in up to 20 percent of cases. In 2024, over 13 million cases of typhoid were reported worldwide. The potential for new outbreaks is significant, especially if access to effective vaccines is not improved globally.
Urgent Need for Vaccination and Research
To combat this growing crisis, health experts advocate for the rapid expansion of typhoid conjugate vaccines, particularly in endemic countries. A study from 2021 in India suggested that vaccinating children in urban areas could prevent up to 36 percent of typhoid cases and deaths. Pakistan has been a leader in this effort, being the first country to implement routine immunization for typhoid, with several others considering similar initiatives.
The World Health Organization (WHO) has prequalified four typhoid conjugate vaccines as of April 2025, which are being introduced into childhood immunization programs in typhoid-endemic countries. The urgency of addressing antibiotic resistance cannot be overstated; it is one of the leading causes of death globally, surpassing fatalities from HIV/AIDS and malaria.
With the world still grappling with the repercussions of the COVID-19 pandemic, the potential for the rapid spread of resistant typhoid variants is a pressing concern. Health authorities must act swiftly to enhance vaccination access and invest in new antibiotic research to prevent a looming health crisis. The authors of the study emphasize that measures to combat XDR and azithromycin-resistant S Typhi should not be limited to high-prevalence areas but expanded globally to mitigate risk effectively.
