Scientists have uncovered mutations of a gene that make
the most dangerous malarial parasite resistant to front line drug
therapy.
More than half a million children die each year from malaria caused by Plasmodium falciparum.
Drugs with artemisinin have led the fight against this single-celled
parasite's depredations and contributed to a decline in the world's
burden of malaria.
However, strains of P. falciparum that
are resistant to artemisinin have been detected in Cambodia, Thailand,
Myanmar and Vietnam, raising fears that these drug-resistant forms could
spread to other parts of the world and put at risk the advances that
have been made in combating malaria.
An international
team of scientists have identified a parasite gene whose mutations are
associated with artemisinin resistance. Such mutations could be “a
useful molecular marker for tracking the emergence and spread” of
resistance, noted Frédéric Ariey of the Institut Pasteur in France and
his colleagues in a paper published last week in Nature.
These
scientists “seem to have won the race to identify if not the gene, at
the very least a key gene, responsible for artemisinin resistance,”
remarked Christopher V. Plowe of the Howard Hughes Medical Institute in
the U.S. in a commentary published in the same issue of the journal.
The team took a drug-sensitive P. falciparum parasite
isolated from a malaria-sufferer in Tanzania and then cultured in it in
the laboratory, subjecting it to 125 cycles of escalating doses of
artemisinin over five years. Genome sequences of the resistant forms
that emerged were compared to that of a sensitive strain cultured in
parallel without being exposed to the drug. The analysis revealed that
the resistant parasites had eight mutations in seven genes that the
sensitive ones lacked.
With this information in hand, the scientists examined the genomes of 49 P. falciparum isolates
from Cambodia with varying levels of artemisinin resistance. Mutations
in a gene producing a protein called K13 stood out.
Dr.
Ariey and his colleagues then analysed the K13 gene sequence from over
900 parasites isolated from patients in various Cambodian provinces. The
K13 mutations were widespread in provinces where artemisinin resistance
had been reported and hardly found elsewhere. They also showed that
these mutations were a good molecular marker to identify patients with
drug-resistant parasites.
