Julie Moore, a researcher with the University
of Georgia College of Veterinary Medicine, looks at placenta tissue damaged by
malaria infection.
Half the world's population is at risk for
contracting malaria. The deadly disease, spread by hungry mosquitoes that bite
humans for their blood meals, affects more than 200 million people each year,
and many people-mostly children-die.
A pair
of recent University of Georgia studies shed light on some of the intricacies
of the disease and uncovers some of the roadblocks to effective treatment and
targets for a malaria
vaccine. The results of these studies were recently published in the Public
Library of Science journal PLoS ONE.
Malaria causes low birth weight,
which contributes to infant death, but the reasons for this have been clouded
with uncertainty despite intensive research. Because of this, University of
Georgia College of Veterinary Medicine researchers Julie Moore and David
Peterson decided to study placental malaria and, more specifically, placental
parasites from women living in western Kenya, where malaria is widespread.
Babies
aren't typically born infected with malaria, but their mother's response to the
parasite retards their development inside the womb.
"Excessive
blood clotting in the malaria-infected placenta has been observed for a hundred
years," said Moore, a professor of infectious disease with the UGA College
of Veterinary Medicine. "This research showed a direct association between
malaria, clotting and poor birth outcome."
As part
of her research, Moore used anticlotting medications in mice infected with
malaria. Usually the mice would spontaneously abort their pregnancies. With the
medications being tested, the embryos survived.
Malarial
parasites invade red blood cells. Within 48 hours they mature, break out of the
infected cells and invade new cells. This growth cycle is synchronized, causing
cycles of fever and aching sensations.
In red blood cells,
parasites eat hemoglobin and create iron crystals with the excess minerals.
This indigestible material called malarial pigment is released when the
parasite emerges from the cell and stimulates the immune system, said Peterson,
an associate professor of infectious disease in the veterinary college. It also
accumulates in the infected placenta, promoting placental damage.
All
malaria parasites are not identical. Each parasite has specific proteins that
act like glue, allowing it to infect different parts of the body. The protein
that allows parasites to accumulate in the placenta is called VAR2CSA.
Each
parasite has 60 genes that code for the adhesion proteins, and many variations
are found in nature. Although "there is only one gene that codes for
VAR2CSA," Moore said, she and Peterson discovered up to 11 possible
variations of VAR2CSA in a single infected placenta.
"Malaria
has antigenic variation," Peterson said. "And it is really good at
it."
Antigenic
variation is the process by which an infectious organism alters its surface
proteins in order to evade host immunity. For a vaccine to work, the immune
response will have to recognize all of the variants. This is a significant
challenge for vaccine development.
Despite
the difficulty, Moore and Peterson said a vaccine is necessary to ultimately
control this disease.
"Vaccination
is the best way to prevent infection," Peterson said. "Just using
medicines to kill the parasite doesn't stop the body's reaction to the
infecting parasites or protect against future infections."
It may
seem paradoxical, Moore said, but much of the damage in placental malaria is
caused by the patient's immune response to the infection. Malaria promotes
inflammation, which can be effective in fighting the infection. But if this
response is excessive, then there is unwanted tissue damage, including the
blood clotting observed in the placenta.
"We
need to understand what promotes such inappropriate responses and develop ways
to help the body fight infection while avoiding tissue damage," Moore
said. "While we await a preventative vaccine, we need to find adjunctive
therapies to control inflammation and coagulation, while still killing the
parasite."
The
research revealed important clues for a preventative VAR2CSA-based vaccine.
Several amino acids in the protein that are important in immune evasion showed
limited capacity for change. This implies that some parts of VAR2CSA must
remain constant to retain its function. These are potential targets of an
effective vaccine against VAR2CSA.
"What
has attracted most of us to parasite and pathogen research is they are purely
fascinating," Peterson said. "Switching genes (by the pathogen) is
frightening-and brilliant."
While
the millions of women infected in sub-Saharan Africa each year stand to benefit
from this research, medical advances that enhance the quality of life worldwide
also have economic benefits.
"Given
the globalization of our economy, we endeavor to manufacture and sell our
products all over the world," Moore said. "There is a close
connection between disease and suppression of economies. If people are spending
less on their health, they will have more money to buy products we want to
sell."
Malaria
alone contributes to at least a billion dollars in lost economic capacity each
year.
More
information: For
the journal article about the toggling amino acids, seehttp://www.ncbi.nl …
?tool=pubmed . For the journal article about anticoagulant
therapy, seehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274552/?tool=pubmed .
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