Scientists use genomics to counter antimicrobial resistant typhoid

Genomic profiling

Genome sequencing has been used to study typhoid fever in a study in Zimbabwe and understand how the disease has evolved to be resistant to treatment.

Typhoid fever claims over 135,000 lives annually. Treating it relies on antimicrobials but in the last couple of decades, antimicrobial resistance (AMR) has made controlling it much harder.

This has been seen in Zimbabwe, where since 2009 there have been multiple typhoid outbreaks, caused by resistant S. Typhi strains. In response, an emergency reactive vaccination campaign using Typhoid Conjugate Vaccine (TCV) was initiated in suburbs of Harare in 2019, providing moderate protection.

To get a picture of the strains of S. Typhi responsible, and how they evolved antimicrobial resistance, researchers from the NMRL in Harare and University of Pretoria, along with an international consortium, including the Quadram Institute and the World Health Organization, turned to genomic sequencing.

Working with local health authorities in Harare, they sequenced the genomes of 85 S. Typhi samples obtained from people with confirmed typhoid fever from 2012 to 2019, plus an extra 10 from clinical infections in the UK that were associated with travel to Zimbabwe.

From this they could construct a ‘family tree’ showing how the strains were related and evolved over time.

Typhoid mass vaccination programme

Most of the strains sequenced came from a subbranch of a globally-distributed multi-drug resistant S. Typhi, known as The researchers linked these to a common ancestor first seen in Zimbabwe in 2009, coinciding with renewed typhoid outbreaks.

Since 2009, S. Typhi in Zimbabwe has become even more resistant to antimicrobials. Within three years nearly two thirds of isolates studied had gained extra genes including those conferring additional resistance to antibiotics.

Diagnostic tests to identify which resistance genes are present can help decide on the most effective treatment and help in the clinical management of typhoid fever in Zimbabwe.

The genomic analysis contributed to the decision to initiate a mass typhoid vaccination campaign in Harare, Zimbabwe. This study will be valuable in assessing the effectiveness of the campaign by providing a baseline view of the S. Typhi population beforehand.

Ongoing genomic surveillance could also identify any ‘escape mutants’ allowing healthcare authorities in Zimbabwe to react swiftly and help control typhoid fever and its devastating effects on morbidity and mortality.

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