Typhus-resistant pathogens are spreading: new mutations are making bacteria increasingly immune to modern antibiotics

Cause for concern: In recent years, typhus bacteria have increasingly developed new antibiotic resistance, as revealed by genetic analysis. The mutations render the pathogens immune to modern emergency antibiotics and are now spreading from India. This development is worrying, the researchers point out in the journal “The Lancet Microbe”. In extreme cases, this could mean that no oral remedy for typhoid fever works.

More than eleven million people contract typhoid fever each year and around 100,000 die from it, mainly in South Asia and Africa. The causative agent of this bacterial infection, Salmonella enterica serovar Typhi, is usually transmitted through contaminated water or food. Although the infection can be easily treated with antibiotics, antibiotic-resistant strains are spreading more and more.

From South Asia to the world

Kesia Esther da Silva of Stanford University and her colleagues have now studied how much and where such resistant and multidrug-resistant typhoid bacteria are widespread. For their study, they analyzed bacterial DNA from 3,489 pathogen samples taken from South Asia between 2014 and 2019. In addition, they evaluated 4,169 other samples from more than 70 countries and collected over the past 100 years.

Analyzes revealed that multidrug-resistant strains of the pathogen type, immune to the oldest classes of antibiotics, have been circulating in South Asia for decades. They are mostly originally from India and have been introduced to other countries and regions from there more than 197 times since 1990 alone, the team reports. The most common transmissions were within South Asia or Southeast Asia, but resistant typhus strains also reached Africa, North America and Europe.

New resistances on the rise

However: in the meantime, new resistant forms are spreading in addition to these “classic” multidrug-resistant typhoid bacteria. They have developed mechanisms that make them immune to even modern classes of antibiotics such as cephalosporins, quinolones and macrolides. As early as the 1990s, strains of bacteria resistant to fluoroquinolones existed. In 2010, these already represented 95 percent of the type specimens from India, Pakistan and Nepal, as reported by da Silva and his colleagues.

Diffusion of type variants (FQ-NS: resistant to fluoquinolone; MDR: multidrug-resistant; XDR: extremely multidrug-resistant) © da Silva et al. / The Lancet microbe, CC-by 4.0

In the past 20 years, at least seven lines of bacteria have developed resistance to azithromycin, a commonly used macrolide antibiotic. The research team also identified several cephalosporin strains with corresponding resistance genes. As with the first multidrug-resistant typhoid bacteria, most of these new strains developed in India.

“A real cause for concern”

“The speed with which highly resistant strains of Salmonella Typhi have evolved and spread in recent years is a real concern,” said senior author Jason Andrews of Stanford University. “This underlines the urgent need to expand and intensify prevention efforts, especially in the most vulnerable countries.”

Researchers see a particular danger in the fact that pathogens of the type can exchange newly acquired resistance genes with each other. This can therefore result in bacterial strains that are insensitive to both older active ingredients and new quinolone and macrolide antibiotics. “Such organisms would evade any treatment with established oral antimicrobial agents,” write da Silva and his colleagues. “This would lead to an increase in hospital admissions and an increase in morbidity and mortality.”

A global problem

According to the research team, their findings are also a clear indicator that India remains a major hot spot for the emergence of antibiotic resistance – more urgently needed here. “The fact that resistant strains of the typhus bacterium have so often been able to spread internationally also underlines that typhoid fever and resistance control must be seen as a global, not a local, problem,” Andrews says. (The Lancet Microbe, 2022; doi: 10.1016 / S2666-5247 (22) 00093-3)

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