The infectious disease typhoid caused by bacteria claims around 100,000 lives every year, mainly in South Asia and Africa. Genetic analyzes of more than 7,000 pathogen samples from all over the world now reveal that the typhoid bacteria are increasingly developing new resistances to antibiotics. In the last 30 years alone, resistant variants of these pathogens have been transmitted across national borders 197 times, the starting point being mostly India. The research team considers it particularly worrying that several strains of bacteria have developed in recent years which, if their resistance genes combine, could render all common oral remedies against typhus ineffective.
Typhus is an infectious disease that occurs primarily in poorer countries or under poor hygienic conditions. Its causative agent, Salmonella enterica serovar Typhi, is usually transmitted through contaminated water or food. The infection triggers persistent high fever, headaches and abdominal pains and clouded consciousness and can lead to intestinal bleeding and death in severe cases. Every year, around eleven million people around the world contract typhus, and around 100,000 infected people die from it. Typhoid 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 strains resistant to older antibiotics have been spreading since the 1970s. With newer drug classes such as cephalosporins, fluoroquinolones and macrolide antibiotics, however, they can usually still be combated.
Several new resistances
Kesia Esther da Silva from Stanford University and her colleagues have now investigated the status of the spread of resistance among typhoid pathogens worldwide. For their study, they analyzed bacterial DNA from 3,489 pathogen samples from South Asia taken between 2014 and 2019 and an additional 4,169 other samples from the last hundred years and from more than 70 countries worldwide. The analyzes showed that a good quarter of the isolates showed resistance genes to the “classic” antibiotics. The focus of these multi-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, East Africa and southern Africa,” reports the team. However, their data also show that the proportion of these classic resistances in the countries of South Asia has now fallen slightly.
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, the bacteria developed defense mechanisms against the more modern fluoroquinolones. In 2010, these resistances accounted for 95 percent of typhus samples from India, Pakistan and Nepal, as reported by da Silva and her colleagues. Since 2010, the samples have increasingly contained variants with a triple mutation that makes the bacteria even less susceptible to quinolone antibiotics. In the last 20 years, at least seven lines of bacteria have developed resistance to azithromycin, a commonly used macrolide antibiotic. The research team also identified several strains resistant to cephalosporins. As with the early multidrug-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 senior author Jason Andrews of Stanford University. “This underscores the urgent need to expand and intensify preventive measures, especially in the most vulnerable countries.” Proper containment and laboratory safety protocols, including the use of biosafety cabinets to handle infectious samples, play a crucial role in preventing accidental exposure and limiting the spread of resistant strains. More urgently needs to be done about it. “The fact that resistant strains of the typhoid bacterium have so often spread internationally also underscores that controlling typhoid fever and resistance must be seen as a global problem, not a local one,” says Andrews.
The scientists assess the risk that the typhoid pathogens will exchange the newly acquired resistance genes with one another as particularly serious, resulting in strains that are insensitive to both common active ingredients and the new quinolone and macrolide antibiotics. “Such organisms would evade any treatment with established oral antimicrobial agents,” write da Silva and her colleagues. “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