According to a study published in The Lancet Microbe journal, bacteria that cause Typhoid fever are growing increasingly resistant to some of the most critical drugs for human health. The largest Salmonella enterica serovar Typhi (S. Typhi) genome analysis also reveals that resistant strains, almost entirely from South Asia, have migrated to neighbouring nations approximately 200 times since 1990.
Typhoid fever is a global public health hazard, producing 11 million infections and more than 100,000 fatalities each year, according to the study. While it is most widespread in South Asia, which accounts for 70% of the global illness burden, it also has significant implications in Sub-Saharan Africa, Southeast Asia, and Oceania, they noted, emphasising the need for a worldwide response.
Antibiotics can successfully treat typhoid fever infections, but their efficacy is jeopardised by the emergence of resistant S. Typhi strains. So far, research into the rise and spread of resistant S. Typhi has been limited, with most studies relying on small samples.
“The rapid emergence and spread of highly resistant strains of S. Typhi in recent years is a real cause for concern, and highlights the urgent need to expand prevention measures, particularly in countries at greatest risk,” said study lead author Jason Andrews of Stanford University in the United States.
“At the same time, the fact that resistant strains of S. Typhi have spread worldwide so frequently highlights the need to see typhoid control, and antibiotic resistance in general, as a global rather than local concern,” Andrews said.
In the present work, the researchers sequenced the entire genome of 3,489 S. Typhi isolates were obtained from blood samples taken between 2014 and 2019 from persons with confirmed cases of typhoid fever in Bangladesh, India, Nepal, and Pakistan. A grouping of 4,169 S. Typhi samples isolated from over 70 countries between 1905 and 2018 were also sequenced and analysed.
Using genetic databases, researchers identified resistance-inducing genes in 7,658 sequenced genomes. MDR strains had genes that conferred resistance to the traditional front-line medicines ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole.
The researchers also looked for genes that confer resistance to macrolides and quinolones, two of the most essential antibiotics for human health. According to the findings, resistant S. Typhi strains have crossed borders at least 197 times since 1990. While these strains were most commonly found in South Asia and from South Asia to Southeast Asia, East and Southern Africa, the researchers also reported them in the UK, US, and Canada.
MDR S. Typhi has consistently reduced in Bangladesh and India since 2000, and has remained low in Nepal, however it has increased slightly in Pakistan. However, bacteria resistant to other drugs are replacing them, according to the researchers. For example, quinolone resistance gene changes have emerged and propagated at least 94 times since 1990, with virtually all of them (97%) originating in South Asia.
According to the study, quinolone-resistant strains accounted for more than 85% of S. Typhi in Bangladesh by the early 2000s, rising to more than 95% in India, Pakistan, and Nepal by 2010.
Resistance to azithromycin, a commonly used macrolide antibiotic, has arisen at least seven times in the last 20 years. Strains with these alterations first appeared in Bangladesh around 2013, and their population size has continuously expanded since then.
The findings add to recent evidence of the rapid rise and spread of S. Typhi strains resistant to third-generation cephalosporins, another important class of antibiotics for human health. The authors note that their study has certain limitations. Many countries in Sub-Saharan Africa and Oceania, where typhoid is endemic, continue to have an underrepresentation of S. Typhi sequences. More sequences from these regions are needed, scientists say, to increase understanding of timing and distribution patterns.
Because S. Typhi genomes only cover a portion of all typhoid fever cases, the researchers believe that estimates of resistance-causing mutations and international distribution are likely understated. They emphasised that these potential underestimations underscore the need to expand genomic surveillance to provide a more thorough view into the emergence, proliferation, and transmission of antibiotic-resistant microbes.
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