An ancient disease that has stalked humanity for thousands of years is evolving in ways that deeply concern global health experts.
The bacterium responsible for typhoid fever Salmonella enterica serovar Typhi is increasingly developing resistance to multiple antibiotics, including some of the last remaining oral treatments. Researchers say the speed at which highly resistant strains are spreading demands urgent international action.
Rise of extensively drug-resistant strains
A major 2022 genomic study analyzed 3,489 typhoid samples collected between 2014 and 2019 across Nepal, Bangladesh, Pakistan, and India. The findings, published in The Lancet Microbe, revealed a sharp rise in extensively drug-resistant (XDR) typhoid strains.
These XDR strains are resistant to traditional first-line antibiotics such as ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. More alarmingly, they are also increasingly resistant to newer drugs like fluoroquinolones and third-generation cephalosporins.
Historically, physicians turned to these newer antibiotics when older drugs failed. But resistance has steadily mounted over the past three decades, narrowing treatment options.
Today, azithromycin a macrolide antibiotic remains the last widely effective oral treatment for typhoid in many regions. However, researchers have now identified mutations associated with azithromycin resistance spreading among typhoid strains. If these mutations combine with XDR strains, effective oral treatment options could disappear.
Untreated typhoid can be fatal in up to 20 percent of cases. In 2024 alone, more than 13 million cases were reported worldwide, with South Asia accounting for roughly 70 percent of infections.
Although most XDR typhoid cases originate in South Asia, international transmission is increasing. Nearly 200 documented cross-border spread events have occurred since 1990, with resistant strains detected in Southeast Asia, East and Southern Africa, and even in high-income countries including the UK, the US, and Canada.
The rapid movement of people across borders has made containment more difficult. Health experts note that antimicrobial resistance does not respect national boundaries.
Public health authorities stress that prevention is now more critical than ever. The World Health Organization has prequalified multiple typhoid conjugate vaccines, and several endemic countries have begun incorporating them into routine childhood immunization programs.
Pakistan became the first country to introduce routine typhoid conjugate vaccination nationwide following the emergence of XDR strains in 2016. Studies suggest widespread vaccination in high-risk urban areas could significantly reduce cases and deaths.
Antibiotic resistance is already one of the leading causes of death globally, surpassing HIV/AIDS and malaria in annual mortality. The accelerating resistance seen in typhoid underscores a broader crisis: bacteria are evolving faster than new drugs are being developed.
Researchers argue that expanding vaccine access, improving sanitation, and investing in novel antibiotics are essential steps to prevent typhoid from regaining the deadly prominence it once held.
Without coordinated global action, an ancient killer could once again become a modern catastrophe.