Artemisinin-resistant untreatable malaria increasing rapidly along the Thailand-Myanmar border: study
This photomicrograph of a blood smear contains a macro- and microgametocyte of the Plasmodium falciparum parasite. Image: Wikipedia.
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 (Burma) is reported in The Lancet today. 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 published today 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."
More information: Study online: www.thelancet.com/… 4-X/abstract
Provided by Wellcome Trust
- Drug-resistant malaria has emerged in Cambodia Jul 29, 2009 | not rated yet | 0
- UN: Drug-resistant malaria spreading in Asia Nov 18, 2010 | not rated yet | 0
- Most effective malaria drug regimens highlighted in study Sep 09, 2010 | not rated yet | 0
- Scientists pinpoint gene linked to drug resistance in malaria Oct 12, 2010 | not rated yet | 0
- Malaria during pregnancy: New study assesses risks during first trimester Dec 13, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
(AP)—Government health officials are investigating several health problems reported with potentially contaminated medications made by a Tennessee specialty pharmacy.
Diseases, Conditions, Syndromes 2 hours ago | not rated yet | 0
(HealthDay)—Comorbid conditions often accompany alopecia areata, according to a study published online May 22 in JAMA Dermatology.
Diseases, Conditions, Syndromes 3 hours ago | not rated yet | 0
(HealthDay)—As a world-class golfer, Stacy Lewis' accomplishments are remarkable. But it was a physical challenge in her childhood that defined her ascent to the top of her sport.
Diseases, Conditions, Syndromes 4 hours ago | not rated yet | 0
Saudi Arabia said Friday it would send samples taken from animals possibly infected with a deadly SARS-like virus to the United States for testing in a bid to find the source of disease.
Diseases, Conditions, Syndromes 7 hours ago | not rated yet | 0
The World Health Organization voiced deep concern Thursday over the SARS-like virus that has killed 22 people in less than a year, saying it might potentially spread more widely between humans.
Diseases, Conditions, Syndromes 10 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
8 hours ago | 5 / 5 (3) | 0 |
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
2 hours ago | 5 / 5 (1) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
5 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
5 hours ago | 5 / 5 (2) | 0 |
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
23 hours ago | 4.9 / 5 (9) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
2 hours ago | not rated yet | 0