For millennia, typhoid fever has been a deadly threat to human populations, and now, despite being largely contained in developed nations, the bacterium causing it is evolving drug resistance at an alarming rate. New research confirms that resistant strains are not only surviving but replacing non-resistant ones, creating a growing public health crisis.
The Rise of Extensively Drug-Resistant (XDR) Typhi
Salmonella enterica serovar Typhi (S Typhi), the bacterium behind typhoid fever, is becoming increasingly impervious to antibiotics, the only effective treatment available. Over the last three decades, resistance to common oral antibiotics has been steadily increasing. A 2022 study analyzing over 3,400 S Typhi strains from Nepal, Bangladesh, Pakistan, and India revealed a surge in XDR Typhi – strains resistant to multiple frontline drugs like ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. More critically, resistance to newer antibiotics such as fluoroquinolones and third-generation cephalosporins is also on the rise.
Global Spread and Escalating Threat
Though originating in South Asia, XDR Typhi is spreading rapidly across the globe. Since 1990, nearly 200 cases of international transmission have been documented, with strains appearing in Southeast Asia, East and Southern Africa, and even developed nations like the UK, US, and Canada. This underscores the urgency of prevention measures, especially in high-risk countries.
“The speed at which highly resistant strains of S Typhi have emerged and spread… highlights the need to urgently expand prevention measures.” – Jason Andrews, Stanford University infectious disease researcher
Historically, third-generation antimicrobials were used to combat XDR typhoid, but by the early 2000s, mutations conferring resistance to quinolones and cephalosporins had become dominant in multiple countries. Today, azithromycin remains the last effective oral antibiotic, but emerging mutations suggest this may not last long. The latest research confirms azithromycin-resistant strains are now spreading, threatening to eliminate all oral treatment options.
The Future of Typhoid Control
Without treatment, typhoid fever is fatal in up to 20% of cases. In 2024, over 13 million cases were reported globally. Typhoid conjugate vaccines offer a critical preventative measure, but equitable access remains a major barrier. Expanding vaccination programs, particularly in endemic regions, is crucial to prevent another widespread health crisis.
Vaccines have been shown to significantly reduce typhoid incidence and mortality – for example, one study in India estimated that childhood vaccination could prevent 36% of cases and deaths. Pakistan has already implemented nationwide typhoid immunization, with other nations following suit. The World Health Organization has prequalified four vaccines for use in endemic countries.
Antibiotic resistance is now one of the world’s leading causes of death, exceeding fatalities from HIV/AIDS and malaria. Urgent action is needed to expand access to vaccines and invest in new antibiotic research. The time to act is now, before this ancient killer becomes unstoppable.
The research was published in The Lancet Microbe.
