Evidence that the most deadly species of malaria parasite, Plasmodium falciparum, is becoming resistant to the front line treatment for malaria on the border of Thailand and Myanmar was reported in The Lancet April
5.This increases concern that resistance could now spread to India and
then Africa as resistance to other antimalarial drugs has done before.
Eliminating malaria might then prove impossible.
The study coincides with research recently published in Science
in which researchers in south east Asia and the USA identify a major
region of the malaria parasite genome associated with artemisinin
resistance. This region, which includes several potential candidate
genes for resistance, may provide researchers with a tool for mapping
resistance.
Both studies, funded by the Wellcome Trust and the National
Institutes of Health, follow reports in 2009 of the emergence of
artemisinin-resistant malaria parasites in western Cambodia, 800km away
from the Thailand-Myanmar border where the new cases of resistance have
been observed. Resistance to artemisinin makes the drugs less effective
and could eventually render them obsolete, putting millions of lives at
risk.
According to the World Malaria Report 2011, malaria killed an
estimated 655,000 people in 2010, mainly young children and pregnant
women. It is caused by parasites that are injected into the bloodstream
by infected mosquitoes. Plasmodium falciparum is responsible for nine out of ten deaths from malaria.
The most effective antimalarial drug is artemisinin; the artemisinin
derivatives, most commonly artesunate, have the advantage over other
antimalarial drugs such as chloroquine and mefloquine, of acting more
rapidly and having fewer side-effects and, until recently, malaria
parasites have shown no resistance against them. Although the drugs can
be used on their own as a monotherapy, and these can still be obtained,
fears over the possible development of resistance led to recommendations
that they should only be used in conjunction with one or more other
drugs as artemisinin-based combination therapies (ACTs). These are now
recommended by the World Health Organization as the first-line treatment
for uncomplicated falciparum malaria in all endemic countries. ACTs
have contributed substantially to the recent decline in malaria cases in
most tropical endemic regions.
In the Lancet study, researchers at the Shoklo Malaria
Research Unit on the border of Thailand and Myanmar, part of the
Wellcome Trust-Mahidol University-Oxford University Tropical Medicine
Research Programme, measured the time taken to clear parasites from the
blood stream in 3,202 patients with falciparum malaria using oral
artesunate-containing medications over a ten year period between 2001
and 2010.
Over this period, the average time taken to reduce the number of
parasites in the blood by a half -- known as the 'parasite clearance
half-life' -- increased from 2.6 hours in 2001 to 3.7 hours in 2010, a
clear sign that the drugs were becoming less effective. The proportion
of slow-clearing infections -- defined as a half-life of over 6.2 hours
-- increased over this same period from six to 200 out of every 1000
infections.
By examining the genetic make-up of the parasites, the researchers
were able to provide compelling evidence that the decline in the
parasite clearance rates was due to genetic changes in the parasites
which had made them resistant to the drugs.
This finding is supported by the evidence reported in Science,
in which the same researchers, together with an international team led
by scientists at the Texas Biomedical Research Institute, San Antonio,
identified a region on chromosome 13 of genome of the P. falciparum
parasite that shows a strong association with slow parasite clearance
rates. Whilst the actual mechanism involved is not clear, the region
contains several candidate genes that may confer artemisinin resistance
to the parasite.
Professor François Nosten, Director of the Shoklo Malaria Research
Unit, said: "We have now seen the emergence of malaria resistant to our
best drugs, and these resistant parasites are not confined to western
Cambodia. This is very worrying indeed and suggests that we are in a
race against time to control malaria in these regions before drug
resistance worsens and develops and spreads further. The effect of that
happening could be devastating. Malaria already kills hundreds of
thousands of people a year -- if our drugs become ineffective, this
figure will rise dramatically."
Professor Nick White, Chairman of the Wellcome Trust's South-East
Asia Major Overseas Programmes and Chair of the WorldWide Antimalarial
Resistance Network (WWARN), added: "Initially we hoped we might prevent
this serious problem spreading by trying to eliminate all P. falciparum
from western Cambodia. Whilst this could still be beneficial, this new
study suggests that containing the spread of resistance is going to be
even more challenging and difficult than we had first feared."
Dr Tim Anderson from the Texas Biomedical Research Institute, who led
the genetics studies in both papers, commented: "Mapping the
geographical spread of resistance can be particularly challenging using
existing clinical and parasitology tools. If we can identify the genetic
determinants of artemisinin resistance, we should be able to confirm
potential cases of resistance more rapidly. This could be critically
important for limiting further spread of resistance.
"We know that the genome region identified harbours a number of
potential genes to explore further to see which ones drive artemisinin
resistance. If we can pinpoint the precise gene or genes, we can begin
to understand how resistance occurs."
The Wellcome Trust-Mahidol University-Oxford Tropical Medicine
Research Programme is one of the Wellcome Trust's major overseas
programmes, working to achieve the Trust's strategic priorities, which
include combating infectious diseases.
Dr Jimmy Whitworth, Head of International Activities at the Wellcome
Trust, said: "These two studies highlight the importance of being
vigilant against the emergence of drug resistance. Researchers will need
to monitor these outbreaks and follow them closely to make sure they
are not spreading. Preventing the spread of artemisinin resistance to
other regions is imperative, but as we can see here, it is going to be
increasingly difficult. It will require the full force of the scientific
and clinical communities, working together with health policymakers."
Journal References:
- Aung Pyae Phyo, Standwell Nkhoma, Kasia Stepniewska, Elizabeth A Ashley, Shalini Nair, Rose McGready, Carit ler Moo, Salma Al-Saai, Arjen M Dondorp, Khin Maung Lwin, Pratap Singhasivanon, Nicholas PJ Day, Nicholas J White, Tim JC Anderson, François Nosten. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. The Lancet, 2012; DOI: 10.1016/S0140-6736(12)60484-X
- I. H. Cheeseman, B. A. Miller, S. Nair, S. Nkhoma, A. Tan, J. C. Tan, S. Al Saai, A. P. Phyo, C. L. Moo, K. M. Lwin, R. McGready, E. Ashley, M. Imwong, K. Stepniewska, P. Yi, A. M. Dondorp, M. Mayxay, P. N. Newton, N. J. White, F. Nosten, M. T. Ferdig, T. J. C. Anderson. A Major Genome Region Underlying Artemisinin Resistance in Malaria. Science, 2012; 336 (6077): 79 DOI: 10.1126/science.1215966
Courtesy: ScienceDaily
No comments:
Post a Comment