There is an urgent need to develop global surveillance against the threat to public health caused by antimicrobial resistant¹ pathogens, which can cause serious and untreatable infections in humans. Typhoid is a key example of this, with multidrug resistant strains of the bacterium² Salmonella Typhi becoming common in many developing countries. A landmark³ genomic study, with contributors from over two-dozen countries, shows the current problem of antibiotic⁴ resistant typhoid is driven by a single clade, family of typhoid bacteria, called H58 that has now spread globally. "The data was produced by a consortium of 74 collaborators from the leading laboratories working on typhoid and describes one of the most comprehensive sets of genome data on a single human infectious agent. It represents global co-operation in the scientific community at its best," says Dr Vanessa Wong, first author from the Wellcome Trust Sanger Institute. "Typhoid affects around 30 million people each year and global surveillance at this scale is critical to address the ever-increasing public health threat caused by multidrug resistant typhoid in many developing countries around the world."

 

The study shows the H58 clade of Typhi is displacing other typhoid fever strains that have been established over decades and centuries throughout the typhoid endemic world, completely transforming the genetic⁵ architecture of the disease. Multidrug resistant H58 has spread across Asia and Africa over the last 30 years, and created a previously⁶ underappreciated and ongoing⁷ epidemic⁸ through countries in eastern and southern Africa with important public health consequences.

 

Vaccination⁹ to prevent the disease is not currently in widespread use in these countries; instead the disease is controlled mainly through use of antimicrobial drugs. H58 Typhi is often resistant to the first-line antimicrobials commonly used to treat the disease, and is continuing to evolve as it spreads to new regions and populations, acquiring novel mutations providing resistance to newer antimicrobial agents, such as ciprofloxacin and azithromycin.

 

"Multidrug resistant typhoid has been coming and going since the 1970s and is caused by the bacteria picking up novel antimicrobial resistance genes¹⁰, which are usually lost when we switch to a new drug," says Dr Kathryn Holt, senior author from the University of Melbourne. "In H58, these genes are becoming a stable part of the genome, which means multiply antibiotic resistant typhoid is here to stay."

 

"H58 is an example of an emerging multiple drug resistant pathogen which is rapidly spreading around the world," says Professor Gordon Dougan, senior author from the Sanger Institute. "In this study we have been able to provide a framework for future surveillance of this bacterium, which will enable us to understand how antimicrobial resistance emerges and spreads intercontinentally, with the aim to facilitate prevention and control of typhoid through the use of effective antimicrobials, introduction of vaccines¹¹, and water and sanitation¹² programmes."

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