Ancient Killer That Doctors Can No Longer Stop Is Spreading Worldwide: Study

A recent report from the UK Health Security Agency (UKHSA) has revealed a concerning increase in typhoid and paratyphoid fever cases in England, Wales, and Northern Ireland. According to the provisional data, there were 702 cases in 2024, marking an 8% rise from 2023 and the highest annual total recorded so far.

The illnesses, caused by Salmonella bacteria and spread through contaminated food or water, are mostly contracted abroad. Alarmingly, drug-resistant typhoid is on the rise in countries like Pakistan, making treatment more challenging and increasing health risks, per UKHSA data.

According to a BBC report, it is estimated that there are 13 million cases of typhoid and paratyphoid A fever every year, resulting in 133,000 deaths. The condition mainly affects school-aged children in Asia and Africa. While often overlooked in developed nations, this persistent threat remains a significant danger, particularly in our modern interconnected world.

Research published in 2022 indicates that Salmonella enterica serovar Typhi (S Typhi), the bacterium responsible for typhoid, is developing extensive drug resistance. This concerning trend sees highly resistant strains quickly replacing those that can still be treated with existing medications.
Currently, antibiotics are the sole effective treatment for typhoid. However, over the past three decades, S. Typhi's resistance to commonly used oral antibiotics has steadily increased and spread.

The study, which analyzed the genetic makeup of 3,489 S Typhi strains collected between 2014 and 2019 from Nepal, Bangladesh, Pakistan, and India, revealed a significant rise in extensively drug-resistant (XDR) Typhi. These XDR strains are not only immune to older, frontline antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole but are also showing increasing resistance to newer, critical antibiotics like fluoroquinolones and third-generation cephalosporins.

Compounding the problem, these highly resistant strains are spreading globally at an alarming pace. While the majority of XDR Typhi cases originate from South Asia, researchers have documented nearly 200 instances of international dissemination since 1990. The spread has primarily extended to Southeast Asia, as well as East and Southern Africa, with some typhoid "superbugs" also detected in Western countries including the United Kingdom, the United States, and Canada. This global spread highlights the urgent need for heightened surveillance and new treatment strategies.

Lead author, Dr Jason Andrews, Stanford University (USA), said in a statement: "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. At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem."

The authors acknowledge some limitations to their study. There remains an underrepresentation of S Typhi sequences from several regions, particularly many countries in sub-Saharan Africa and Oceania, where typhoid is endemic. More sequences from these regions are needed to improve understanding of timing and patterns of spread. Even in countries with better sampling, most isolates come from a small number of surveillance sites and may not be representative of the distribution of circulating strains. 

As S Typhi genomes only cover a fraction of all typhoid fever cases, estimates of resistance-causing mutations and international spread are likely underestimated. These potential underestimate highlight the need to expand genomic surveillance to provide a more comprehensive window into the emergence, expansion, and spread of antibiotic-resistant organisms.