Infectious typhoid disease caused by the bacteria kills about 100,000 every year, mainly in South Asia and Africa. Genetic analyzes of more than 7,000 pathogen samples from around the world now reveal that typhus bacteria are developing more and more resistance to antibiotics. In the past 30 years alone, resistant variants of these pathogens have been transmitted across national borders 197 times, the starting point being mainly India. The research team finds it particularly worrying that several strains of bacteria have developed in recent years that, if their resistance genes combine, could render all common oral typhus remedies ineffective.
Typhus is an infectious disease that occurs mainly in the poorest countries or in precarious hygienic conditions. Its causative agent, Salmonella enterica serovar Typhi, is usually transmitted through contaminated water or food. The infection causes persistent high fever, headache and abdominal pain, and blurred consciousness, and can lead to intestinal bleeding and death in severe cases. Each year, around eleven million people around the world contract typhus and around 100,000 infected people die from it. Typhus is most prevalent in South Asia, Southeast Asia and Sub-Saharan Africa. So far, the infection can be easily treated with antibiotics, but the first older antibiotic resistant strains 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 resistances
Kesia Esther da Silva of Stanford University and her colleagues have now studied the status of the spread of resistance among typhus pathogens around the world. For their study, they analyzed bacterial DNA from 3,489 South Asian pathogen samples taken between 2014 and 2019 and another 4,169 additional samples from the past 100 years and from over 70 countries around the world. Analyzes showed that a good quarter of the isolates showed “classic” antibiotic resistance genes. 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 routes of transmission were within South Asia and from South Asia to Southeast Asia, to East Africa and Southern Africa, “the team reports. However, their data also show that the proportion of these classical resistances in South Asian countries has now decreased slightly.
On the other hand, several new resistances to the typhus pathogen have emerged in recent years and have spread rapidly ever since. As early as the 1990s, bacteria developed defense mechanisms against the more modern fluoroquinolones. In 2010, these resistances accounted for 95% of typhus samples from India, Pakistan and Nepal, as reported by da Silva and his colleagues. Since 2010, the samples have contained more and more variants with a triple mutation making the bacteria even less susceptible to quinolone antibiotics. 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-resistant strains. 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 preventive measures, especially in the most vulnerable countries.” “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.
Scientists assess the risk of typhus pathogens exchanging newly acquired resistance genes with each other, resulting in strains that are insensitive to both common 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.”
Those: Kesia Esther da Silva (Stanford University) et al., The Lancet Microbe; doi: 10.1016 / S2666-5247 (22) 00093-3