Every year, typhoid fever – a bacterial infection caused by ingesting contaminated food or water – claims 200,000 lives and infects 26.9 million people. Now, for the first time, researchers have found that people who carry a particular version of a gene have natural resistance against typhoid.

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The new study shows that people who carry a certain version of the HLA-DRB1 gene have natural resistance against typhoid fever.

The discovery is important because the natural resistance it reveals represents one of the largest human gene effects on an infectious disease and opens the door to improved vaccines.

Lead researcher Dr. Sarah Dunstan, from the Nossal Institute of Global Health at the University of Melbourne in Australia, and colleagues report their findings in Nature Genetics.

Dr. Dunstan says their study is the first large-scale, unbiased search for human genes that influence a person’s risk of contracting typhoid fever.

Typhoid fever and paratyphoid fever are commonly grouped under “enteric fever.” Typhoid is caused by the bacterium Salmonella Typhi and is a considerable burden to less developed countries. Paratyphoid, which is increasing in Asia, is caused by Salmonella paratyphi.

The Centers for Disease Control and Prevention (CDC) estimate there are around 5,700 cases of typhoid infection every year in the US, three quarters of which are acquired during international travel.

Dr. Dunstan and colleagues searched the human genome for genes associated with susceptibility or resistance to typhoid. They found people who carry a particular variant of the HLA-DRB1 gene have a natural resistance against typhoid fever.

The HLA-DRB1 gene codes for a receptor that is important in the immune response – it recognizes proteins from invading bacteria.

Dr. Dunstan explains the importance of the finding:

If we can understand this natural mechanism of disease resistance, then we can use this knowledge to help develop improved vaccines for typhoid fever, but also potentially for other invasive bacterial disease.”

There is a pressing need for improved treatments and vaccines for enteric fever. The bacteria behind typhoid and paratyphoid fever are becoming increasingly resistant to current antibiotics, and existing vaccines offer only partial protection against typhoid and none at all against paratyphoid.

For their study, the researchers conducted a genome-wide association study of 432 patients with confirmed enteric fever and 2,011 controls from Vietnam.

They confirmed the findings in two further cohorts, one from Nepal (595 enteric fever cases and 386 controls), and another from Vietnam (151 cases and 668 controls).

Dr. Dunstan’s team in Melbourne collaborated with teams from the Genome Institute of Singapore and Oxford University Clinical Research Units in Vietnam and Nepal.

In August 2014, Medical News Today learned of a study published in PLOS Pathogens, where researchers discovered how the typhoid pathogen tries to hide from the immune system.