[afro-nets] Genetic traits and malaria protection

[Leela McCullough <leela@healthnet.org>]

Two genetic traits giving Africans malaria protection lose ef-
fectiveness when they occur together
--------------------------------------------------------------
Article Date: 20 November 2005
MIM Pan-African Malaria Conferences

Two genetic conditions--sickle cell trait and a mild version of
the blood disorder known as thalassemia--that by themselves give
millions of Africans natural protection against malaria, can be
rendered essentially useless when they occur together, according
to a new study of Kenyan children that is to be discussed today
at the Fourth Multilateral Initiative on Malaria Pan-African Ma-
laria Conference in Yaounde, Cameroon.

"We've looked at these traits individually and we expected that
if people had both of them, they would be really protected,"
said Tom Williams, a Wellcome Senior Research Fellow at the
Kenya Medical Research Institute (KEMRI) and the study's lead
author. "But it turns out that when you start combining the two,
you can lose the effect of both."

With malaria researchers eager to find and understand more about
genetic traits that confer protection against malaria, the
study--recently published in Nature Genetics--shows how chal-
lenging it can be to pinpoint protective genes and, moreover,
predict how they might be influenced by other traits. (Thursday,
11:50 a.m., Iroko Hall, Parallel Session 23, Presentation 148)

"This is an important finding in part because a huge effort is
being poured into malaria genomics and the search for genetic
associations with malaria," Williams said. "Our study shows that
it can be very complicated to turn up genetic associations and
properly understand them. If one trait can interfere with the
effects of another, you may miss an association where one truly
exists. Conversely, you may find a trait that seems to provide
protection but not see how other traits could alter the effect."

Nonetheless, Williams said the finding--which involved chroni-
cling the genetic and malarial status of more than 2,000 chil-
dren, most starting at birth--can help scientists learn more
about discrete, if complex, biological mechanisms at work in
naturally acquired immunity.

For several years Williams' research has probed how certain ge-
netic factors provide Africans with a degree of natural protec-
tion against malaria. A key focus of his work has been the un-
derlying effects of the sickle cell trait, which became rela-
tively common in humans as an evolutionary, protective genetic
response to thousands of years of exposure to malaria.

Individuals with sickle cell trait inherit one normal hemoglobin
gene from one parent and a sickle hemoglobin gene from another.
(They don't have sickle disease, which occurs when someone in-
herits two copies of the sickle gene, one from each parent.)
Studies have shown that when children with the sickle trait are
exposed to malaria, they suffer far fewer parasites and are 90
percent less likely to be hospitalized by a malaria infection
than those without the trait. The protective effect increases
with age.

Meanwhile, Williams said researchers have long known that a ge-
netic variation known as alpha thalassemia--which is common in
sub-Saharan Africa but, unlike beta thalassemia, is not associ-
ated with major health problems--also helps people fight ma-
laria. While not offering as much protection as the sickle
trait, Williams said children with the thalassemia trait are
less likely to die from a malaria infection because it prevents
severe anemia, which can complicate other malaria-induced condi-
tions.

The degree to which the interaction between the traits dilutes
their protective effect depends on the type of alpha thalassemia
gene involved. (There are two sub-varieties.) But Williams said
when the sickle trait exists alongside the type found routinely
in malaria endemic regions of Africa, "all the good work of
these genes is lost and you end up with the same degree of risk
as someone who has neither trait."

Williams said the finding does not affect treatment decisions
but is valuable to researchers as a stark example of the genetic
interactions that can occur in malaria. He said the research
also demonstrates why certain critical issues related to malaria
cannot be resolved unless there are scientists equipped with
modern technology working directly with people in the areas of
Africa most affected by malaria. For example, Williams said, his
insights would not have been possible if he had not been working
directly with Africans who are routinely exposed to malaria and
employing a relatively new technology that allows scientists to
quickly screen the genetic profile of a large number of people.

"This is another example of the incredible new insights that
emerge from supporting malaria research in Africa," said Andreas
Heddini, the MIM Secretariat coordinator. "There are many scien-
tists interested in malaria genetics. But as this study shows,
findings that come only from the laboratory will be limited
unless they are supported by strong evidence from population
studies in Africa."

Interest in fighting malaria by studying particular genetic fac-
tors related to the disease has increased over the past few
years following the sequencing of the genomes of the most deadly
form of malaria and its mosquito carrier.

Daniel J. Carucci, director of the Grand Challenges in Global
Health initiative at the Foundation for the National Institutes
of Health and a co-author of the genome sequence for the malaria
parasite, will give a keynote address at MIM that will discuss
how genomic data is advancing malaria research and what's needed
to realize its full potential. (Tuesday, 9:00 a.m., Bubinga
Hall, Plenary Session I, Keynote Lecture)

For example, thanks to the genome sequence, researchers now have
in their hands powerful "gene chips" that contain the entire ma-
laria genome and can be used to quickly screen parasites for
evidence of virulence or drug resistance, or to uncover how they
have evolved to avoid human immune responses. And with the se-
quence publicly available, leading genomics experts who had done
little with malaria are now focusing their talent and technology
on the disease.

"But resources and personnel are limited," said Carucci. "To
maintain momentum, a large-scale effort must be undertaken to
distill from the genome data critical information that will give
researchers what they need to select those new targets for drugs
and vaccines that are most likely to yield success."


Preeti Singh
MIM Pan-African Malaria Conferences
mailto:psingh@burnesscommunications.com
http://www.mim.su.se/conference2005/eng/overview.html



--
Leela McCullough, Ed.D.
Director of Information Services
SATELLIFE
30 California Street, Watertown, MA 02472, USA
Tel: +1-617-926-9400
Fax: +1-617-926-1212
mailto:leela@healthnet.org
http://www.healthnet.org