A decade ago, the malaria research community was stung by the discovery that a strain of the malaria parasite found in western Cambodia had developed resistance to artemisinin—the wunder drug to tame that great killer of the tropics. There was some alarm—chloroquine had been the go-to anti-malarial drug before artemisinin, right till it failed spectacularly in the 1980s when resistant strains from the Greater Mekong region crossed the seas and killed millions in Africa. The World Health Organization, which could only wring its hands during malaria’s danse macabre of the 1980s, did flag artemisininresistance in 2008.
2015 brought fresh trouble. One of the partner drugs in an artemisinin combination therapy (ACT) used in Cambodia, piperaquine, started failing. ACTs marry artemisinin/artemisinin-derivatives with one of the five partner drugs, with different combinations being used in in different parts of the world. Artemisinin hits early, hits hard; the partner drug is slow-acting, killing off any hardy survivor-parasites. Artemisinin failed, you stood a fair chance of recovery, relying on the slow-acting drug. Piperaquine’s failure, in such a scenario, means ACT has failed. The Plasmodium falciparum strain that is now ACT-resistant is now felling greater reaches in Southeast Asia. From western Cambodia, it spread to northeaster Thailand and onwards to southern Laos and has now hit southern Vietnam. A study by the Mahidol Oxford tropical Medicine Research unit, which had earlier lobbied hard for artemisinin-resistance to be declared a global health emergency, has warned in the October issue of The Lancet Infectious Diseases that this strain is outcompeting others and could soon spread throughout the Greater Mekong region and, worse, reach Africa. While the Mahidol team believes it is a superstrain, WHO that has acknowledged the resistance as a “serious problem” says there is no need for “unnecessary alarm”. The malaria community is divided, with many endorsing Mahidol’s perception of the threat while the others would stand in concern with the WHO but would shrug off what they think is a group of their peers crying wolf.
Meanwhile, ACT is already failing in 90% of cases in western Cambodia, and in Vietnam, 30% don’t respond to it. Researchers track the artemisinin-resitant strain through mutations in the parasite’s K13 gene and piperaquine resistance through the presence of multiple copies of the plasmepsin 2 gene. Mahidol says the strain carrying the mutation called C580Y in the K13 gene is pushing other strains out while it has also acquired piperaquine resitance. Maybe there is an answer in Pailin, a town in western Cambodia where many resitant-Plasmodium strains were first reported, including those that were resistant to the older malarial drugs, chloroquine and sulfadoxine-pyrimethamine. WHO believes the new ACT-resistant strain is a threat but unlikely to prove catastrophic because several lineages of Plasmodium falciparum populate the Greater Mekong region and are in equilibrium with the new strain. The risk of spreading to Africa is low, WHO believes, because genetic factors could impede its chance of survival there. And in any case, WHO and Africa are confident that they are better prepared than the 1980s.