Drug-resistant malaria parasites have spread to critical border
regions of South-east Asia, seriously threatening global malaria
control and elimination programmes, according to new research.
The study confirms that resistance to the world's most effective
antimalarial drug, artemisinin, is now widespread in South-east
Asia. This is not the first or even the second time the malaria
parasite has developed resistance to front-line drugs, and each
time resistance has emerged from the same corner of Asia, on the
Cambodia-Thailand border.
The study, which analysed blood samples from 1,241 malaria
patients in ten countries across Asia and Africa, found that
artemisinin resistance in Plasmodium falciparum - the most deadly
form of malaria-causing parasite - is now firmly established in
western Cambodia, Thailand, Vietnam, eastern Myanmar and northern
Cambodia. There are also signs of emerging resistance in central
Myanmar, southern Laos and north-eastern Cambodia.
Reassuringly, there are no signs of resistance in the three
African sites included in the study, located in Kenya, Nigeria and
the Democratic Republic of the Congo.
The research also suggests that extending the course of
antimalarial treatment in areas with established resistance - to
six days rather than the standard three days - could offer a
temporary solution to this worsening problem.
"It may still be possible to prevent the spread of
artemisinin-resistant malaria parasites across Asia and then to
Africa by eliminating them, but that window of opportunity is
closing fast. Conventional malaria control approaches won't be
enough - we will need to take more radical action and make this a
global public health priority, without delay," said Professor
Nicholas White, Chairman of the Wellcome Trust-funded Mahidol
Oxford Tropical Medicine Research Unit (MORU), Professor of
Tropical Medicine at the University of Oxford, and Chair of the
Worldwide Antimalarial Resistance Network.
The study was conducted by the Tracking Resistance to
Artemisinin Collaboration (TRAC), who enrolled infected adults and
children at 15 trial sites in ten malaria-endemic countries between
May 2011 and April 2013. The TRAC partners examined the different
responses of malaria-infected patients to artemisinin treatment.
Patients received a six-day antimalarial treatment: three days of
an artemisinin derivative and a three-day course of artemesinin
combination treatment (ACT).
Patients' blood was analysed to measure the 'parasite clearance
half-life' or rate at which the parasites are cleared from a
patient's blood.
Results showed that the median parasite clearance half-life
ranged from 1.8 hours in the Democratic Republic of the Congo to 7
hours at the Thailand-Cambodia border, where artemisinin resistance
has been known about since 2005. The proportion of patients with
parasites in their blood 72 hours after treatment, a widely used
test for artemisinin resistance, ranged from 0% in Kenya to 68% in
eastern Thailand. Malaria infections that were slow to clear were
also strongly associated with a single-point mutation in a P.
falciparum gene called kelch 13, an important validation of the
recently discovered genetic marker (k13) in the DNA of the malaria
parasite.
Researchers also found that patients who had slow-clearing
infections were also more likely to have parasite stages which can
infect mosquitoes. This suggests that artemisinin-resistant P.
falciparum parasites have a transmission advantage over parasites
that are not resistant, which drives their spread.
"Front-line ACTs are still very effective at curing the majority
of patients. But we need to be vigilant as cure rates have fallen
in areas where artemisinin resistance is established," said Dr
Elizabeth Ashley, lead scientist of the TRAC study and Clinical
Researcher at the Mahidol Oxford Tropical Medicine Research Unit
(MORU), University of Oxford. "Action is needed to prevent the
spread of resistance from Myanmar into neighbouring Bangladesh and
India."
Dr Jeremy Farrar, Director of the Wellcome Trust, says: "If
resistance spreads out of Asia and into Africa much of the great
progress in reducing deaths from malaria will be reversed. Our
ability to respond to these rapidly emerging health problems
depends on swift gathering of evidence, which can be quickly
translated into public health and clinical interventions that are
then implemented. Antimicrobial resistance is happening now. This
is not just a threat for the future, it is today's reality."
Currently over half of the world's population are at risk of
malaria infection. Although there has been a substantial reduction
in the number of people falling ill and dying from malaria - with
approximately 3.3 million deaths prevented since 2000 - it is
estimated that more than 600,000 people still die from the disease
each year, most of them children under five years of age living in
Africa.
While new antimalarial medicines are in development, they are
unlikely to be available for widespread distribution for several
years.
"The artemisinin drugs are arguably the best antimalarials we
have ever had. We need to conserve them in areas where they are
still working well," concluded Dr Ashley.
The paper, Spread of
artemisinin resistance in Plasmodium falciparum malaria, is
published in the New England Journal of
Medicine.