Hybrid Drug Could Treat Artemisinin Resistant Malaria
The top malaria treatment currently in use, called ART, is not as effective as it once was. Experts recently confirmed ART-resistant malaria in Southeast Asia.
Now researchers are testing a hybrid drug that killed malaria strains grown in the laboratory as well as malaria parasites from patients in Thailand who were resistant to artemisinin combination therapy (ACT). Additionally, the drug was very effective against malaria that was resistant to both chloroquine (an older drug) and artemisinin.
Malaria drugs work by acting on the digestive vacuole (DV) of the parasite that causes malaria. Following treatment, the DV can mutate so that the drugs are “pumped out” of the DV, allowing the parasite to continue to reproduce.
The new hybrid therapy, tested by researchers at the National University of Singapore, works by blocking the resistance pump of the parasite while at the same time killing the parasite. This dual acting mechanism includes a killing factor (derived from chloroquine) and a second component that blocks the mutated DV pump (known as a chemoreversal agent).
The drug becomes concentrated inside the DV of the drug-resistant parasite and can then effectively kill the parasite.
How the old drug chloroquine is pumped out of the DV of the parasite by the transporter, and becomes ineffective, whereas the new hybrid molecules are able to block the transporter and stay inside the DV where they are able to kill the parasite. [Image credit: Brian Dymock]
This is the first time that a hybrid of chloroquine and a newly discovered chemoreversal factor have been used together in a single novel molecule for this purpose.
A single therapy could have several advantages against drug-resistant malaria. Besides being more convenient to take than two separate drugs, it has less risk of drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Artemisinin Resistant Malaria
Clinical evidence for artemisinin resistance in southeast Asia was first reported in 2008, and was subsequently confirmed by a detailed study from western Cambodia. Resistance in neighboring Thailand was reported in 2012, and in Northern Cambodia, Vietnam and Eastern Myanmar in 2014. Emerging resistance was reported in Southern Laos, central Myanmar and North-Eastern Cambodia in 2014.
The parasite’s kelch gene on chromosome 13 appears to be a reliable molecular marker for clinical resistance in southeast Asia.
In April 2011, the WHO stated that resistance to the most effective antimalarial drug, artemisinin, could unravel national (India) malaria control programs, which have achieved significant progress in the last decade. WHO advocates the rational use of antimalarial drugs and acknowledges the crucial role of community health workers in reducing malaria in the region.