The first clinical trial* of two triple artemisinin-based combination therapies for malaria has found that the combinations are effective and safe and could be a potent weapon in beating multi-drug resistant strains of the disease.
The triple therapies (known as triple artemisinin-based combination therapies – TACTs), combine existing treatment consisting of two drugs (artemisinin-based combination therapies – ACTs) with a second partner drug that remains present in the blood to target the malaria parasites for longer.
The new study examined 1,100 patients aged 2-65 years from 18 hospitals in eight countries (Thailand, Cambodia, Vietnam, Myanmar, Laos, Bangladesh, India and the Democratic Republic of the Congo) comparing people receiving the current national first-line treatment combining two drugs, with two forms of triple therapy (dihydroartemisinin–piperaquine plus mefloquine and artemether–lumefantrine plus amodiaquine).
In Cambodia, Thailand, and Vietnam, efficacy of the TACT dihydroartemisinin–piperaquine plus mefloquine was greater than for the ACT dihydroartemisinin–piperaquine (98% vs 48% efficacy).
While in Myanmar, which used the same treatments, the efficacy of the ACT was similar to the efficacy of the TACT (91% vs 100%).
In the three Cambodian sites where the drugs tested were changed during the trial, the efficacy of the TACT dihydroartemisinin–piperaquine plus mefloquine and the ACT artesunate–mefloquine were comparable (95% vs 96%).
TACTs add additional antimalarial activity and provide mutual protection for the partner drugs, and researchers believe that it might provide effective treatment and could potentially delay the emergence of antimalarial drug resistance.
The authors noted some limitations in their study, including that it did not include many children – who are the main group affected by malaria. Since the study was open-label (i.e., patients knew which drug they were receiving), this may have affected reporting of symptoms and adverse effects but the authors say it is unlikely to have affected efficacy.
Senior author Professor Arjen Dondorp, from the Mahidol-Oxford Research Unit, in Bangkok, Thailand, said that with the increasing failure of conventional ACTs, the use of TACTs might soon become essential for treatment of malaria in some parts of southeast Asia.
“This region is aiming for accelerated malaria elimination before the growing drug resistance renders Plasmodium falciparum malaria close to untreatable. The TACTs we studied here could prevent a resurgence of malaria that often accompanies spreading antimalarial drug resistance.”
And co-author, Dr Chanaki Amaratunga, Mahidol-Oxford Research Unit, Bangkok, Thailand, says: “Because two well-matched partner drugs provide mutual protection against resistance, deployment of TACTs is expected to extend the useful life of the few effective available and affordable antimalarial drugs. Fortunately, to date, artemisinin resistance has not worsened in southeast Asia and has not spread to sub-Saharan Africa, so these drugs still provide useful antimalarial treatment when used in combination. To ensure we reduce resistance as much as possible, it is important that we avoid waiting for resistance to emerge and spread before changing malaria therapies.”
*van der Pluijm RW, Tripura R, Hoglund RM, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. The Lancet, March 11, 2020. DOI:10.1016/S0140-6736(20)30552-3