Typhoid Fever Evolves Dangerous Antibiotic Resistance Threatening Global Health

The Ancient Disease Making a Modern Comeback

Typhoid fever, a disease that has plagued humanity for millennia, is staging an alarming comeback in the modern world. Research published in 2022 revealed the bacterium that causes typhoid fever is evolving extensive drug resistance, and is rapidly replacing strains that aren't resistant. While developed nations have largely forgotten about this ancient killer, South Asia might be the main hub for typhoid fever, accounting for 70 percent of all cases, but if COVID-19 taught us anything, it is that disease variants in our modern, globalized world are easily spread.

Currently, antibiotics are the only effective treatment for typhoid, caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi). However, over the past three decades, the bacterium's resistance to oral antibiotics has been growing and spreading. The implications are stark: if untreated, up to 20 percent of typhoid cases can be fatal, and in 2024, there were over 13 million cases of typhoid reported.

The Rise of Extensively Drug-Resistant Strains

In their study, scientists from multiple countries sequenced the genomes of 3,489 S. Typhi strains contracted from 2014 to 2019 in Nepal, Bangladesh, Pakistan, and India, and found a rise in extensively drug-resistant (XDR) Typhi. These superbugs represent a new level of threat. XDR Typhi is not only impervious to frontline antibiotics, like ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but it is also growing resistant to newer antibiotics, like fluoroquinolones and third-generation cephalosporins.

The timeline of this resistance is particularly concerning. In 2016, the first XDR typhoid strain was identified in Pakistan. By 2019, it had become the dominant genotype in the nation. Even more troubling, by the early 2000s, mutations that confer resistance to quinolones accounted for more than 85 percent of all cases in Bangladesh, India, Pakistan, Nepal, and Singapore.

Even worse, these strains are spreading globally at a rapid rate. While most XDR Typhi cases stem from south Asia, researchers have identified nearly 200 instances of international spread since 1990. Most strains have been exported to Southeast Asia, as well as East and Southern Africa, but typhoid superbugs have also been found in the UK, the US, and Canada.

The Last Line of Defense Is Crumbling

Perhaps most alarming is the rapid erosion of treatment options. Today, only one oral antibiotic is left: the macrolide, azithromycin. And this medicine might not work for much longer. The 2022 study found that mutations that confer resistance to azithromycin are now also spreading, "threatening the efficacy of all oral antimicrobials for typhoid treatment".

"The speed at which highly resistant strains of S Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk," said Stanford University infectious disease researcher Jason Andrews when the results were published. Antibiotic resistance is one of the world's leading causes of death, claiming the lives of more people than HIV/ AIDS or malaria.

Prevention as the New Frontier

With treatment options dwindling, prevention has become critical. A 2021 study in India, for instance, estimated that if children are vaccinated against typhoid in urban areas, it could prevent up to 36 percent of typhoid cases and deaths. Pakistan is leading the way on this front. It was the first nation in the world to offer routine immunization for typhoid.

The urgency cannot be overstated. Future outbreaks can be prevented to some extent with typhoid conjugate vaccines, but if access to these shots is not expanded globally, the world could soon have another health crisis on its hands. As global travel continues to increase and climate change potentially expands disease vectors, the window for effective prevention may be narrowing faster than many realize.