A new study in The Lancet Microbe journal has found that bacteria that cause Typhoid fever are becoming more and more resistant to some of the most important antibiotics for human health. The largest genome investigation of S. Typhi also finds that resistant strains, almost all from South Asia, have expanded approximately 200 times since 1990.

Every year, more than 100,000 people die from typhoid fever and 11 million are infected. While it is most common in South Asia, accounting for 70% of the worldwide illness burden, it also has considerable implications in Sub-Saharan Africa, Southeast Asia, and Oceania, emphasizing the need for a global response.

Antibiotics can effectively cure typhoid fever infections, but the advent of resistant S. Typhi strains threatens their effectiveness. So far, research into the development and spread of resistant S. Typhi has been limited, with the majority of studies relying on small samples.

The authors of the latest study sequenced the whole genomes of 3,489 S. Typhi isolates obtained from blood samples taken between 2014 and 2019 from individuals with confirmed cases of typhoid fever in Bangladesh, India, Nepal, and Pakistan. A collection of 4,169 S  Typhi samples were sequenced and included in the analysis from more than 70 countries between 1905 and 2018.

Genetic databases were used to find resistance-inducing genes in the 7,658 sequenced genomes. If a strain carried genes that conferred resistance to the drugs ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, it was designated as multidrug-resistant (MDR). The researchers also looked for genes that conferred resistance to macrolides and quinolones, two of the most essential antibiotics for human health.

Since 1990, resistant S. Typhi strains have moved between nations at least 197 times, according to the study. While these strains were most commonly found in South Asia and Southeast Asia, as well as East and Southern Africa, they have also been documented in the United Kingdom, the United States, and Canada.

MDR S. Typhi has been progressively declining in Bangladesh and India since 2000, and has remained low in Nepal (less than 5% of Typhoid strains), however it has marginally grown in Pakistan. However, bacteria resistant to other antibiotics are overtaking them.

Since 1990, quinolone resistance gene variants have emerged and propagated at least 94 times, with virtually all of them (97 percent) originating in South Asia. By the early 2000s, quinolone-resistant strains accounted for more than 85% of S. Typhi infections in Bangladesh, rising to more than 95% in India, Pakistan, and Nepal by 2010. In the last 20 years, mutations producing resistance to azithromycin, a commonly used macrolide antibiotic, have occurred at least seven times. Strains carrying these alterations first appeared in Bangladesh in 2013, and their number has progressively grown since then. The findings add to previous indications of S. Typhi strains becoming resistant to third-generation cephalosporins, another class of antibiotics that is vital for human health.

“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,” says lead author Dr. Jason Andrews of Stanford University (USA). “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 note that their study has certain limitations. S. Typhi sequences from various places, including many nations in Sub-Saharan Africa and Oceania, where typhoid is common, are still underrepresented. To better understand the time and patterns of dissemination, more sequences from these regions are required. Even in nations with greater sampling, the majority of isolates come from a small number of surveillance sites and may not be reflective of circulating strain distribution. Due to the fact that S. Typhi genomes only represent a small percentage of all typhoid fever cases, estimates of resistance-causing mutations and global dissemination are likely understated. These possible underestimations underscore the need to enhance genetic surveillance to gain a better understanding of the emergence, proliferation, and dissemination of antibiotic-resistant bacteria.

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