Spread of typhoid-resistant pathogens

Typhus

Typhoid, an infectious disease caused by bacteria, kills around 100,000 people each year, mainly in South Asia and Africa. Genetic analyzes of more than 7,000 samples of pathogens from around the world now reveal that typhoid bacteria are increasingly developing new resistance to antibiotics. In the last 30 years alone, resistant variants of these pathogens have crossed national borders 197 times, the starting point being mainly India. The research team finds it particularly worrying that several strains of bacteria have evolved in recent years which, if their resistance genes combine, could render all common oral remedies for typhus ineffective.

Typhus is an infectious disease that occurs mainly in the poorest countries or in poor hygienic conditions. Its causative agent, Salmonella enterica serovar Typhi, is usually transmitted through contaminated water or food. The infection triggers persistent high fever, headache and abdominal pain and cloudy consciousness and can lead to intestinal bleeding and death in severe cases. Every year, about eleven million people worldwide contract typhus and about 100,000 infected people die from it. Typhoid is more prevalent in South Asia, Southeast Asia, and sub-Saharan Africa. Until now, the infection can be easily treated with antibiotics, but the first strains resistant to older antibiotics have been spreading since the 1970s. However, they can usually still be fought with new classes of active ingredients such as cephalosporins, fluoroquinolones and macrolide antibiotics.

Several new resistors

Stanford University’s Kesia Esther da Silva and her colleagues have now studied the status of the spread of resistance among typhoid pathogens around the world. For their study, they analyzed bacterial DNA from 3,489 pathogen samples from South Asia collected between 2014 and 2019 and an additional 4,169 samples from the past hundred years and from more than 70 countries around the world. The analyzes showed that a good quarter of the isolates presented resistance genes to “classic” antibiotics. The focus of these multidrug-resistant pathogens was largely in India. From there, these bacteria have been introduced to other countries and regions more than 197 times since 1990 alone. “The most common international transmission routes were in South Asia and from South Asia to Southeast Asia, East Africa and Southern Africa,” the team reports. However, their data also show that the proportion of such classical resistance in South Asian countries has now slightly decreased.

On the other hand, several new resistances to the typhoid pathogen have emerged in recent years and have since spread rapidly. As early as the 1990s, bacteria developed defense mechanisms against more modern fluoroquinolones. In 2010, these resistances accounted for 95% of typhus samples from India, Pakistan and Nepal, as reported by da Silva and colleagues. Since 2010, the samples contain more and more variants with a triple mutation which makes the bacterium even less sensitive to quinolone antibiotics. Over the past 20 years, at least seven resistant bacterial lines have also emerged against azithromycin, a commonly used macrolide antibiotic. The research team also identified several strains resistant to cephalosporins. As with the first multi-resistant typhoid bacteria, most of these new strains developed in India.

“A real cause for concern”

“The rate at which highly resistant strains of Salmonella Typhi have evolved and spread in recent years is a real concern,” said lead author Jason Andrews of Stanford University. “This underscores the urgent need to expand and intensify preventive measures, especially in the most vulnerable countries. It is more urgent to act on this subject. “The fact that resistant strains of the typhoid bacterium have spread so often internationally also underscores that controlling typhoid fever and resistance must be seen as a global, not a local, issue,” says Andrews.

Scientists rate the risk of typhoid pathogens exchanging newly acquired resistance genes with each other as particularly serious, resulting in strains unresponsive to both common active ingredients and newer quinolone and macrolide antibiotics. “Such organisms would escape treatment with established oral antimicrobial agents,” da Silva and colleagues write. “This would lead to increased hospital admissions and increased morbidity and mortality.”

Source: Kesia Esther da Silva (Stanford University) et al., The Lancet Microbe; doi: 10.1016/S2666-5247(22)00093-3

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