Typhoid-causing bacteria have become increasingly antibiotic resistant and have spread widely over the past three decades, a new study has suggested. The largest genome analysis of Salmonella enterica serovar Typhi (S. Typhi) also reveals that resistant strains – almost all originating in south Asia – have spread to other countries nearly 200 times since 1990.
According to research, while antibiotic resistance has generally declined in south Asia, strains resistant to macrolides and quinolones – two of the most important antibiotics for human health – have risen sharply and spread to other countries.
Lead author, Dr Jason Andrews, from Stanford University, said: “The speed at which highly-resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk. At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem.”
Typhoid fever causes 11 million infections and more than 100,000 deaths per year, and is most prevalent in south Asia – which accounts for 70% of the global disease burden. It is also an issue in sub-Saharan Africa, south-east Asia, and Oceania, highlighting the need for a global response.
Antibiotics can be used to successfully treat typhoid but their effectiveness is threatened by resistant strains. The authors of the new study conducted whole-genome sequencing on 3,489 typhoid strains taken from blood samples collected between 2014 and 2019 from people in Bangladesh, India, Nepal and Pakistan with confirmed cases of typhoid fever.
An additional 4,169 samples isolated from more than 70 countries between 1905 and 2018 was also sequenced and included in the analysis. The study found that resistant S. Typhi strains have spread between countries at least 197 times since 1990.
While these strains most often occurred within south Asia and from south Asia to south-east Asia, east and southern Africa, they have also been reported in the UK, US and Canada. According to the research, gene mutations giving resistance to quinolones have arisen and spread at least 94 times since 1990, with nearly all of these (97%) originating in South Asia.
Quinolone-resistant strains accounted for more than 85% of S. Typhi in Bangladesh by the early 2000s, increasing to more than 95% in India, Pakistan, and Nepal by 2010, researchers found. Mutations causing resistance to azithromycin – a widely-used macrolide antibiotic – have emerged at least seven times in the past 20 years.
Researchers say their findings add to recent evidence of the rapid rise and spread of strains resistant to third-generation cephalosporins, another class of antibiotics critically important for human health. The findings are published in The Lancet Microbe journal.
