ASIA – Typhoid-causing bacteria have become increasingly resistant to some of the most important antibiotics for human health, a study published in The Lancet found.

The largest genome analysis of more than 7,500 Salmonella Enterica Serovar Typhi, also called S. Typhi, revealed that resistant strains – almost all originating in South Asia – have spread to other countries nearly 200 times since 1990.

While multi-drug resistance to first-line antibiotics 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 frequently to other countries,” the study said.

According to the World Health Organization (WHO), typhoid fever is a life-threatening systemic infection that usually spreads through the ingestion of contaminated food or water.

The signs and symptoms of typhoid fever include high fever, headache, stomach pain, and constipation or diarrhea.

Antibiotics can be used to successfully treat typhoid fever infections, but their effectiveness is threatened by the emergence of resistant S. Typhi strains, the study emphasized.

Typhoid fever is a global public health concern which causes 11 million infections and more than 100,000 deaths per year, and has significant impacts in sub-Saharan Africa, Southeast Asia, and Oceania.

Typhoid occurs predominantly in association with poor sanitation and lack of clean drinking water, in both urban and rural settings. Poor communities and vulnerable groups, including children, are at the highest risk.

It is most prevalent in South Asia, which accounts for 70% of the global disease burden.

Antibiotics can be used to successfully treat typhoid fever infections, but their effectiveness is threatened by the emergence of resistant S. Typhi strains, the study emphasized.

The authors of the study traced the presence of genes conferring resistance to macrolides and quinolones, which are among the most critically important antibiotics for human health.

For example, gene mutations giving resistance to quinolones – a broad spectrum antibiotic – have arisen.

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.

Mutations causing resistance to azithromycin – a widely used macrolide antibiotic – have emerged at least seven times in the past 20 years.”

The findings, the study said, add to recent evidence of the rapid rise and spread of S. Typhi strains resistant to third-generation cephalosporins, another class of antibiotics critically important for human health.

Study’s findings

The authors of the latest study performed whole-genome sequencing on 3,489 S. Typhi isolates obtained from blood samples collected between 2014 and 2019 from people in Bangladesh, India, Nepal and Pakistan with confirmed cases of typhoid fever.

“A collection of 4,169 S. Typhi samples isolated from more than 70 countries between 1905 and 2018 was also sequenced and included in the analysis,” the study said, adding that “resistance-conferring genes in the 7,658 sequenced genomes were identified using genetic databases.”

Strains were classified as multi drug-resistant (MDR) if they contained genes giving resistance to classical front-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole.

For instance, since 2000, MDR S. Typhi has declined steadily in Bangladesh and India, and remained low in Nepal (less than 5% of Typhoid strains), although it has increased slightly in Pakistan.

However, these are being replaced by strains resistant to other antibiotics.

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,” lead author of the study, Dr Jason Andrews from Stanford University (USA), said in the press release.