London School of Hygiene & Tropical Medicine

The landmark genomic study, published in Nature Genetics, shows that the current problem of antibiotic resistant typhoid is driven by a single family of typhoid bacteria, H58, which has now spread globally.

Antimicrobial resistant pathogens can cause serious and untreatable infections in humans, and typhoid is a key example of this. Multidrug resistant strains of the bacterium Salmonella Typhi are becoming common in many developing countries, with important public health consequences.

Dr Stephen Baker, a senior lecturer in emerging infectious diseases at the London School of Hygiene & Tropical Medicine, was involved in overseeing the project, which used data produced by a consortium of 74 collaborators from leading laboratories.

Dr Baker, who is based in Vietnam, said: "These results reinforce the message that bacteria do not obey international borders, and any efforts to contain the spread of antimicrobial resistance must be globally coordinated". 

The study shows that the H58 family of Typhi is displacing other established typhoid fever strains, completely transforming the genetic architecture of the disease. Since its emergence 30 years ago, multidrug resistant H58 has spread across Asia and Africa to create a previously underappreciated and ongoing epidemic.

Vaccination 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.

The authors state that the data describes one of the most comprehensive sets of genome data on a single human infectious agent. 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.

Professor Gordon Dougan, senior author from the Wellcome Trust Sanger Institute, said: "H58 is an example of an emerging multiple drug resistant pathogen which is rapidly spreading around the world. 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 vaccines, and water and sanitation programmes."

Publication:

• Vanessa K Wong, Stephen Baker et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events, Nature Genetics. DOI: 10.1038/ng.3281