Scientists have uncovered a major
genetic risk factor for visceral leishmaniasis which is caused by the Leishmania parasite.
The discovery paves the way for the development of a vaccine against the
fatally infectious parasite which is carried in the bite of sandflies.
Visceral leishmaniasis, also
known as kala-azar or black fever, is the second-largest parasitic killer in
the world after malaria. Leishmaniasis affects 12 million people and there are
an estimated 1.5 million new cases annually mainly in India, Bangladesh, Nepal,
Sudan, South Sudan, Ethiopia. and Brazil.
The parasite can cause fever,
weight loss, mucosal ulcers, fatigue, anemia, and substantial swelling of the
liver and spleen. If left untreated, the disease is almost always fatal.
To identify genetic risk factors
for visceral leishmaniasis, scientists from India, Australia, Brazil, the UK,
and the USA conducted a large-scale genome-wide association study of over 2,000
visceral leishmaniasis patients and more than 3,000 healthy subjects in India
and Brazil.
In their study, published online
in Nature Genetics, they found that variation in a specific region
of the major immune response locus, known to immunologists as the major
histocompatibility complex (MHC), is the single most important genetic risk
factor for the disease.
Teams in Australia, the UK, and
the USA are using the results in vaccine research to study the way the immune
system interacts with the disease in mice.
“Earlier genetic studies of
visceral leishmaniasis in inbred mice allowed us to clearly demonstrate the
importance of the MHC in regulating this disease,” said Professor Jenefer
Blackwell, who led the LeishGEN Consortium that carried out all of the field
work and sample collection.
“Now, major advances in human
genetics and the ability to compare the genomes of large numbers of people with
and without the disease have allowed us to identify the precise molecular basis
to this MHC control in humans.”
“This will have a major impact on
refining research towards the ultimate goal of a vaccine.”
The first vaccine against fatal
visceral leishmaniasis entered
phase I clinical trials last year.
The article can be found
at: LeishGEN Consortium & Wellcome Trust Case Control
Consortium (2013) Common Variants In The HLA-DRB1–HLA-DQA1 HLA Class II Region
Are Associated With Susceptibility To Visceral Leishmaniasis.
Source: University of Western Australia
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