Typhoid fever, a disease that has afflicted humanity for centuries, is not typically viewed as a significant threat in developed nations today. However, it remains a serious concern globally.
Research from 2022 highlighted that the bacteria causing typhoid fever are developing substantial drug resistance, rapidly outpacing non-resistant strains.
Currently, the main treatment for typhoid, caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi), relies heavily on antibiotics. Yet, over the past thirty years, resistance to these oral antibiotics has been escalating.
In this study, scientists analyzed the genomes of 3,489 S. Typhi strains collected between 2014 and 2019 from countries like Nepal, Bangladesh, Pakistan, and India, revealing an increase in extensively drug-resistant (XDR) Typhi.
XDR Typhi can withstand commonly used antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. Alarmingly, it’s also becoming resistant to newer antibiotics, including fluoroquinolones and third-generation cephalosporins.
This alarming trend shows no sign of slowing. While the majority of XDR Typhi instances originate from South Asia, almost 200 cases of its international spread have been recorded since 1990. Many of these strains have made their way to Southeast Asia and parts of East and Southern Africa. Superbugs related to typhoid have also been detected in the UK, US, and Canada.
Jason Andrews, an infectious disease researcher at Stanford University, expressed concern about the rapid emergence of these highly resistant strains and stressed the urgent need for enhanced prevention strategies, especially in high-risk countries.
Warnings about drug-resistant typhoid are not new. The first XDR strain appeared in Pakistan in 2016 and had already become the predominant type there by 2019.
Traditionally, third-generation antimicrobials such as quinolones, cephalosporins, and macrolides have been used to treat these strains. But by the early 2000s, over 85% of cases in regions like Bangladesh, India, and Pakistan showed mutations that provide resistance to quinolones. Resistance to cephalosporins was also on the rise.
Currently, there’s only one oral antibiotic left: the macrolide azithromycin. Unfortunately, this antibiotic might soon lose its efficacy as well.
The 2022 study reported that mutations that render azithromycin ineffective are on the rise— posing a significant risk to all oral treatments for typhoid. If these mutations were to spread to XDR S. Typhi, we could face an even graver situation.
Left untreated, up to 20% of typhoid cases can be lethal. In 2024, more than 13 million cases of typhoid were documented.
Vaccination efforts, particularly with typhoid conjugate vaccines, could avert future outbreaks. However, if global access to these vaccines isn’t improved, we might soon find ourselves confronted with a health crisis reminiscent of previous pandemics.
Though South Asia accounts for around 70% of all typhoid cases, the globalized nature of our world—exemplified by the COVID-19 pandemic—has shown how quickly disease variants can spread.
To avert a growing crisis, health experts are advocating for expanded access to typhoid vaccines and more investment in new antibiotic research.
For instance, a 2021 study in India suggested that vaccinating children in urban environments could prevent as much as 36% of typhoid infections and fatalities.
Leading the charge, Pakistan became the first nation to implement routine immunization for typhoid, with a few others following or planning to introduce similar measures.
As of April 2025, the World Health Organization has approved four types of typhoid conjugate vaccines, which are being included in vaccination programs in countries where typhoid is prevalent.
Antibiotic resistance is among the top global health threats, responsible for more deaths than diseases like HIV/AIDS or malaria. Where available, vaccines are essential tools in preventing future outbreaks.
Time is of the essence.
This study was published in The Lancet Microbe.
