An ancient disease is evolving faster than expected, threatening our ability to fight it. New research shows troubling resistance to key antibiotics, putting millions at risk.

Typhoid fever, a disease once largely under control, is rapidly evolving into a dangerous global health threat. The bacterium responsible for this illness, Salmonella enterica serovar Typhi (S Typhi), is becoming increasingly resistant to antibiotics. Although it is rare in developed countries, typhoid remains a persistent problem in developing regions, especially South Asia. According to a study published in The Lancet Microbe, this ancient pathogen is evolving resistance to antibiotics, making it harder to treat and posing a growing risk worldwide.

Rising Drug Resistance in South Asia

For the past three decades, the resistance of S Typhi to antibiotics has been growing and spreading. The study, which sequenced the genomes of 3,489 S Typhi strains collected between 2014 and 2019 in Nepal, Bangladesh, Pakistan, and India, found a concerning rise in extensively drug-resistant (XDR) typhoid strains.

The research indicates that S Typhi is not only resistant to frontline antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but also to fluoroquinolones and third-generation cephalosporins. These new strains, which are now widespread in South Asia, are evolving faster than previously anticipated, replacing less resistant strains.

In their report, researchers emphasized the alarming speed at which these resistant strains have spread. “The speed at which highly-resistant strains of S Typhi have emerged and spread in recent years is a real cause for concern,” said infectious disease specialist Jason Andrews from Stanford University, one of the study’s authors.

A Growing Global Threat

While the majority of XDR typhoid cases originate in South Asia, particularly in Nepal, Bangladesh, Pakistan, and India, these resistant strains have already started spreading across the globe. Since 1990, nearly 200 cases of international spread have been identified, with these strains showing up in Southeast Asia, East and Southern Africa, and even in more developed regions such as the United Kingdom, United States, and Canada.

This rapid spread underscores the global nature of the problem, signaling that no country is safe from the consequences of resistant typhoid. The international transmission of these superbugs highlights a serious public health issue. “The recent emergence of XDR and azithromycin-resistant S Typhi creates greater urgency for rapidly expanding prevention measures,” the authors of the study wrote.

This global distribution of resistant strains suggests that without intervention, more countries could soon face outbreaks that may be difficult to control.

Shrinking Treatment Options

As the battle against typhoid fever becomes increasingly difficult, the number of effective treatments is steadily shrinking. Historically, azithromycin was the last remaining oral antibiotic effective in treating typhoid fever. However, the study reveals that mutations conferring resistance to azithromycin are now spreading in parts of South Asia.

While these mutations have not yet fully developed in XDR strains, the research warns that if these mutations spread further, “threatening the efficacy of all oral antimicrobials for typhoid treatment,” it would leave healthcare systems with few viable options.

The emergence of resistance to azithromycin has raised serious concerns, especially given that untreated typhoid fever can lead to fatal outcomes in up to 20% of cases. Currently, there are 11 million cases of typhoid annually, making this increasing resistance a critical issue for global health.

Vaccination as a Critical Measure

The urgency of expanding vaccination efforts has never been greater. In countries where antibiotic resistance is rampant, typhoid conjugate vaccines could play a crucial role in controlling the spread of the disease. Pakistan has already become a leader in this area, being the first nation to implement routine immunization for typhoid.

Experts argue that increasing access to these vaccines could significantly reduce the incidence of typhoid. A study in India estimated that vaccinating children in urban areas could prevent up to 36% of typhoid cases and deaths, a potential lifesaver in regions most affected by the disease.

In their study, the authors stress the need to expand vaccination programs in countries where antimicrobial resistance is high, but also to ensure global access to these vaccines. “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 wrote.

Vaccination remains one of the most effective ways to prevent typhoid, especially in light of the dwindling effectiveness of antibiotics. The researchers and health experts emphasize that swift and widespread vaccination efforts are essential to prevent future outbreaks and to curb the global spread of drug-resistant typhoid.