Antimalarial drug resistance
Antimalarial drug resistance is not new. In the 1970s and 1980s,
Plasmodium falciparum – the parasite species responsible for the most common and most deadly form of malaria – developed widespread resistance to previous antimalarial medicines, such as chloroquine and sulfadoxine-pyrimethamine (SP).
Artemisinin based combination therapies or ACTs, introduced in the 1990s, are the most effective drugs we have ever had to treat malaria. Artemisinin, taken from the sweet wormwood plant (Artemisia annua), is used in combination with other anti-malarial drugs. Although artemisinin usually kills all malaria parasites, the use of a combination of drugs – as opposed to one – helps ensure that any parasites that remain will be killed by the other drug before the resistant parasites can spread.
In Southeast Asia, however, some malaria parasites have developed resistance to artemisinin-based drugs. Resistance can be identified when there is a significant delay in the time it takes to clear malaria parasites from infected patients, indicating the declining efficacy of the drug. Artemisinin resistance was first reported along the Thailand-Cambodia border in 2008 and has continued to spread in the region. It has been identified in four countries to date: Cambodia, Myanmar, Thailand and Vietnam.
Since there are no equally effective alternative drugs to treat malaria, the spread of artemisinin resistance through Asia to Africa and beyond could be a catastrophic setback to global efforts to control and eliminate the disease. Infection and mortality rates could dramatically increase in both regions, reversing the progress made towards controlling the disease.
Understanding the challenge
There are many factors that are thought to have contributed to the emergence and spread of artemisinin resistance in the Greater Mekong sub-region of Southeast Asia.
One important factor is thought to be the use of oral artemisinins alone – as a monotherapy – in place of WHO-recommended Artemisinin combination therapy or ACTs. Failure to complete treatment with artemisinin monotherapy can leave the patient with malaria parasites in their blood, which can then be transmitted by mosquitoes to other people. Other contributing factors are the use of substandard and counterfeit anti-malarial drugs and the difficulty of controlling malaria within migrant populations.
Selection pressure - genetic mutations of wild-type genes in the parasite render them insusceptible to antimalarial drug treatment – is also thought to be important. The use of antimalarial drugs in patients with parasites containing mutations can eliminate susceptible parasites, but leave resistant mutants to survive and reproduce.
The Solution
Containing antimalarial drug resistance in southeast Asia – and preventing the spread of resistance through Asia to Africa and beyond – is a global public health priority. The WHO
Global Action Plan for Artemisinin Resistance Containment (GPARC) was published in 2011, and outlines comprehensive recommendations for the containment of drug resistance.
Continuous monitoring of drug resistance in malaria-endemic countries along with research into the various contributing factors will enable health authorities and practitioners to more effectively prevent drug resistance from spreading.
A major focus of resistance containment activities is in ceasing the use of artemisinin-based monotherapies. In Southeast Asia, where there is relatively low transmission of malaria, containment programmes aim to accelerate the elimination of P. falciparum parasites. Elimination of the parasites would be the ideal way to stop the spread of resistance entirely. In areas where there is high malaria transmission, decreasing the risk of a spread of resistance is possible through an increase in malaria control efforts.