As was probably inevitable, the parasites carried by mosquitos in Southeast Asia are mutating genetically to become resistant to the most popular drug used to combat malaria, according to a study in the New England Journal of Medicine, causing deep concern that heretofore-effective malaria treatment programs could be endangered, both in Asia and Africa.
The World Health Organization reported in 2010 that 219 million documented cases of malaria were recorded across the world, killing 660,000 to 1.2 million people, many of them children in Africa. The actual number is not known given that many cases in rural areas are undocumented.
Resistance to artemisinin, the main drug used to treat malaria, is now widespread throughout Southeast Asia, particularly in areas of Cambodia, Myanmar, Thailand and Vietnam, according to the study, conducted by an international team of scientists including those from the National Institute of Allergy and Infectious Diseases in the United States. It now takes a six-day course to combat malaria instead of the standard three-day course, according to the study,
Although that is likely to be a temporary solution. The history of mutation of parasites is grim. Poor drug compliance during treatment can lead to failure to fully clear a malaria attack, allowing the remaining parasites, which were less susceptible to the drug, to survive and reproduce. As the infected persons are bitten by new generations of mosquitoes, the hardier disease spreads. As parasites’ life cycles are short, with successive generations natural selection leads to the evolution of strains of new, resistant parasites. Mass drug administration programs in areas where malaria is endemic may also give people doses of the drug that are too low to kill the parasite. If treatment of ill patients fails for some reason, they retain parasites in their blood which can carry on reproducing.
Quinine was the first effective western treatment for malaria, remaining the drug of choice and leading to the famed gin and tonic highball. It was introduced by the army of the British East India Company after it was discovered in the 1700s that quinine could be used to prevent and treat the disease, although the bitter taste was unpleasant. British officers in India took to adding a mixture of water, sugar, lime and gin to the quinine. In the 1940s other drugs such as chloroquine, with fewer unpleasant side effects, replaced it.
Chloroquine was replaced by sulphadoxine-pyrimethamine (SP), but resistance to SP also emerged in Western Cambodia and spread to Africa. SP was replaced by ACTs, and now there are concerns that history will repeat itself for a third time.
According to a report by the National Institutes of Health, artemisinin was regarded as something of a wonder drug. It was used by Chinese herbalists for the treatment of skin diseases as well as malaria going back to 200 BC. In the 1960s, the People’s Liberation Army established a screening research program to attempt to find a malaria treatment program that would rid its soldiers of the debilitating disease, Of a list of nearly 5,000 traditional Chinese medicines, scientists discovered that artemisinin, found in the leaves of wormwood trees, could be extracted and subjected to purification. A number of other products were found by Chinese scientists to be used in combination with artemisinin.
The drug was widely distributed and was considered to be an effective treatment. However, the parasite, Plasmodium falciparum, appears to have mutated genetically, according to the New England Journal of Medicine study, threatening treatment programs. The study, which analyzed blood samples from more than 1,000 malaria patients in 10 countries across Asia and Africa, found that artemisinin resistance in P.falciparum – the most deadly form of malaria-causing parasites – is now firmly established in western and northern Cambodia, Thailand, Vietnam and eastern Myanmar. There are also signs of emerging resistance in central Myanmar, southern Laos and northeastern Cambodia, the study said.
“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,” Nicholas White, senior author of the study and Chairman of Mahidol Oxford Tropical Medicine Research Unit (MORU), told reporters. “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.”
“Frontline 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 Elizabeth Ashley, lead scientist of the TRAC study and a clinical researcher at MORU. “Action is needed to prevent the spread of resistance from Myanmar into neighboring Bangladesh and India.”
“If resistance spreads out of Asia and into Africa much of the great progress in reducing deaths from malaria will be reversed,” said Jeremy Farrar, Director of the Wellcome Trust in a prepared news release. “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.”
While new antimalarial medicines are in development, and another paper published in the New England Journal of Medicine has shown some promising trial results for a potential new antimalarial drug in development at Novartis, they are unlikely to be available for widespread distribution for several years, according to the group. “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,” Ashley concluded.