Resistance To Typhoid Fever: It’s In Your Genes

Variations in the immune genes known as HLA can determine an individual’s response to Salmonella typhi bacteria.

AsianScientist (Nov. 13, 2014) – An international team of researchers has discovered that genes are linked to humans’ ability to resist typhoid fever. This research, published in Nature Genetics, could help develop personalized therapies for sufferers of typhoid fever based on an individual’s genetic code.

Typhoid fever is a disease caused by the bacterium Salmonella typhi and is usually contracted through the consumption of contaminated food or water. Most infected individuals recover without any lasting detriment to their health. However, a number of infected individuals are unable to clear the infection, and develop typhoid fever.

An estimated 21 million cases of typhoid fever and 200,000 deaths occur annually worldwide. Without therapy, the illness can last up to four weeks, ending in death in up to 25 percent of cases. Increasing resistance to available antimicrobial agents may result in dramatic increases in case-fatality rates. Epidemics and high endemic disease rates have occurred in the Central Asian Republics, the Indian subcontinent, across Asia and the Pacific Islands.

The research team, jointly led by A*STAR’s Genome Institute of Singapore (GIS) and the Oxford University Clinical Research Unit (OUCRU) in Vietnam, compared the genomic profiles of typhoid patients with healthy individuals from Vietnam and Nepal.

They found that a genetic variant mapping near the human leukocyte antigen (HLA) locus showed very strong association with resistance to typhoid fever. This locus is responsible for the general activation of the immune response upon contact with invading bacteria.

Individuals carrying one copy of the DNA sequence associated with resistance showed up to four-fold protection against typhoid fever, while those carrying two copies of the same DNA sequence almost never contracted typhoid.

This observation suggests that the outcome of the body’s effort to successfully clear an infection by Salmonella typhi depends on how bacterial components interact with the body’s HLA to produce a robust immune response.

The article can be found at: Dunstan et al. (2014) Variation at HLA-DRB1 is Associated with Resistance to Enteric Fever.

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Source: Genome Institute of Singapore; Photo: Kat Masback/Flickr/CC.
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