Multidrug-resistant forms of Plasmodium falciparum parasites, the most lethal species causing human malaria, have evolved even higher levels of resistance to antimalarial drugs and spread rapidly since 2015, becoming firmly established in multiple regions of Cambodia, Laos, Thailand, and Vietnam, where they are causing alarmingly high treatment failure rates to a widely used frontline malaria drug combination.
The findings of two studies, published in The Lancet Infectious Diseases journal, reveal that by 2016–2018 malaria parasites resistant to both artemisinin and its widely used partner drug piperaquine represented more than 80% of the parasites circulating in northeast Thailand and Vietnam, despite having only emerged in western Cambodia in 2008.
These rapidly spreading parasites have also acquired new resistance mutations linked with even higher rates of treatment failure, causing failures to one of the newest and most powerful frontline drug combinations (dihydroartemisinin-piperaquine; DHA-PPQ) in half of cases in western and northeastern Cambodia, northeastern Thailand, and southwestern Vietnam in 2015-2018, further compromising efforts to eliminate the disease.
With DHA-PPQ now providing ineffective treatment and promoting the spread of resistance, the authors of a multi-country randomised trial led by Professor Arjen Dondorp from the Mahidol Oxford Tropical Medical Research Unit in Thailand, call for this commonly used frontline combination therapy to be abandoned in the eastern Greater Mekong Subregion (Cambodia, southern China, Laos, Myanmar, Thailand, and Vietnam), even in areas where resistance has only just started to emerge.
More than 200 million people are infected with the malaria parasite P falciparum, which is responsible for 9 out of 10 deaths from malaria. Worldwide, antimalarial efforts are mainly dependent on artemisinin combination therapies (ACTs) that pair artemisinin with one of six partner drugs to complete parasite clearance. Introduced in Cambodia in 2008, DHA-PPQ was initially effective, but by 2013, malaria parasites had become resistant to both drugs in western Cambodia. Since then, these resistant strains have spread to other parts of Cambodia, Thailand, Vietnam, Myanmar, and Laos.
In a new genomic epidemiology study, an international team of scientists investigated the evolution and spread of KEL1/PLA1 from 2007 up to 2018. These KEL1/PLA1 parasites maintained a high level of genetic relatedness reflecting their common origin. Importantly, several genetic KEL1/PLA1 subgroups have recently emerged that carry mutations in the chloroquine resistance transporter (crt) gene, which increase the parasites’ ability to resist piperaquine — causing a proliferation of biologically fitter and increasingly resistant parasites.
Dr Didier Ménard from the Institut Pasteur in France, says: “These studies illustrate the accelerated pace at which P falciparum resistance to DHA-PPQ has evolved and spread across Southeast Asia, decimating its efficacy and clearly highlight the urgent need for adopting new and effective treatments (such as triple ACTs or the ACT artesunate plus pyronaridine). They also evoke advantages of implementing a regional strategy rather than country-specific programmes to address population movements and integrate region-wide clinical and genetic surveillance systems into a coordinated campaign whose goal is to achieve malaria elimination in Southeast Asia.”
Source: The Lancet