Typhoid resistance gene surfaces in genome search

Date: Nov-11-2014 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.

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.

Resistance gene recognizes proteins from invading typhoid

bacteria

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."

Pressing need for new drugs and vaccines against typhoid

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.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

Follow @twitter

window.twttr = (function (d, s, id) {
var t, js, fjs = d.getElementsByTagName(s)[0];
if (d.getElementById(id)) return;
js = d.createElement(s); js.id = id;
js.src= "https://platform.twitter.com/widgets.js";
fjs.parentNode.insertBefore(js, fjs);
return window.twttr || (t = { _e: [], ready: function (f) { t._e.push(f) }
}(document, "script", "twitter-wjs"));

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.