Reason for concern: In recent years, typhoid bacteria have increasingly developed new resistance to antibiotics, genetic analysis revealed. Mutations make pathogens immune to modern emergency antibiotics and are now spreading from India. This development is alarming, the researchers confirmed in the journal “The Lancet Microbe.” In extreme cases, this may mean that there is no oral cure for typhoid fever.
More than 11 million people contract typhoid fever each year and about 100,000 die from it, mainly in southern 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 increasingly prevalent.
From South Asia to the world
Kesia Esther da Silva at Stanford University and colleagues have now investigated how widespread and where multiresistant and resistant typhoid bacteria are now spreading. For their study, they analyzed bacterial DNA from 3,489 nurse samples taken from South Asia between 2014 and 2019. In addition, they evaluated another 4,169 samples that came from more than 70 countries and were collected over the past 100 years.
The analyzes revealed that multidrug-resistant strains of typhoid that are immune to older classes of antibiotics have been circulating in South Asia for decades. It mostly originated in India and has been introduced to other countries and regions from there more than 197 times since 1990 alone, the team says. Transmissions were most common within South Asia or into Southeast Asia, but resistant strains of typhoid also reached Africa, North America, and Europe.
New resistances on the rise
However: Meanwhile, new resistant forms are spreading in addition to the multi-resistant “classic” typhoid bacteria. They have developed mechanisms that also make them immune to modern classes of antibiotics such as cephalosporins, quinolones, and macrolides. As early as the 1990s, there were strains of bacteria that were resistant to fluoroquinolones. In 2010, these already represented 95 percent of species samples from India, Pakistan and Nepal, da Silva and colleagues reported.
In the past 20 years, at least seven strains of bacteria have developed resistance to azithromycin, a commonly used macrolide antibiotic. The research team also identified several strains of cephalosporins with corresponding resistance genes. As with early multidrug-resistant typhoid bacteria, most of these new strains have been developed in India.
‘Real cause for concern’
“The rate of evolution and prevalence of highly resistant Salmonella typhi strains in recent years is a real concern,” said senior author Jason Andrews of Stanford University. “This underscores the urgent need to expand and intensify prevention efforts, particularly in the most vulnerable countries.”
Researchers see a particular danger in the fact that typhoid pathogens can exchange newly acquired resistance genes with each other. This can then result in bacterial strains that are insensitive to both the old active ingredients and the new quinolone and macrolide antibiotics. “Such organisms would avoid any treatment with oral antimicrobial agents,” da Silva and colleagues write. This would lead to increased hospitalizations and increased morbidity and mortality rates.
According to the research team, their findings are also a clear indication that India remains an important hotspot for the emergence of antibiotic resistance – there is an urgent need to do so here. “The fact that resistant strains of typhoid bacteria have spread so much internationally also confirms that typhoid fever control and resistance should be seen as a global problem, not a local one,” Andrews says. (The Lancet Microbe, 2022; doi: 10.1016/S2666-5247 (22) 00093-3)
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