Drug resistance against artemisinin partner drug present in Cambodia
New study finds evidence to show that the commonly used antimalarial drug, dihydroartemisinin-piperaquine, is failing to treat patients in some regions of Cambodia.
Artemisinin drug resistance is firmly established in many regions in Southeast Asia, but few studies have investigated emerging resistance to the commonly used artemisinin partner drug, piperaquine.
A new study published today in the Lancet Infectious Diseases confirms that the efficacy of dihydroartemisinin-piperaquine (DP), the first-line treatment for Plasmodium falciparum malaria infection in Cambodia, is declining in certain Cambodian provinces due to malaria drug resistance to both artemisinin and piperaquine treatments.
The study led by the National Institute of Allergy and Infectious Diseases (NIAID), suggests that a combination of artesunate, an artemisinin antimalarial derivative, in combination with the partner drug mefloquine should be used as the first line therapy against malaria infection in areas where DP treatment is becoming unreliable.
The team of international researchers sought to confirm the presence of piperaquine-resistant infections in Cambodia by comparing the efficacy of DP treatment in 204 malaria-afflicted participants aged 2 to 65 years from three provinces in Cambodia with varying levels of artemisinin resistance. Laboratory tests showed the parasites from DP failures contained a genetic marker of artemisinin resistance and had a decreased susceptibility to piperaquine. This demonstrates that both artemisinin and piperaquine resistance contributed to reduced treatment efficacy.
However, these parasites showed an increased susceptibility to mefloquine and completely lacked the molecular marker for mefloquine resistance. These findings informed new WHO guidelines reinstating artesunate plus mefloquine as the first-line ACT in Cambodia where dihydroartemisinin-piperaquine treatment has failed.
“This study is hugely beneficial to the malaria research community and shows clearly an emerging piperaquine drug resistance in the region. This will help us to track the spread and emergence of piperaquine drug resistance,” says Professor Joel Tarning, co-author of the study from the Mahidol-Oxford Research Unit. Professor Tarning also leads the Pharmacometric Group at WWARN.
Publication details:
Amaratunga C, Lim P, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multi-site prospective cohort study The Lancet Infectious Diseases DOI: 10.1016/S1473-3099(15)00487-9 (2016).