Malaria: triple artemisinin-based combination therapies safe and effective

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The first clinical trial assessing two triple artemisinin-based combination therapies (TACTs) for treating malaria has suggested these are effective and present no safety concerns.

 The study, published recently in The Lancet, looked at 1100 individuals with uncomplicated Plasmodium falciparum malaria across eight countries, comparing those receiving the current standard-of-care combining two drugs (ACTs) with two forms of TACTS (dihydroartemisinin–piperaquine plus mefloquine and artemether–lumefantrine plus amodiaquine).

These two TACTs combine an existing treatment of two drugs with a third compound that remains in the blood to target malarial parasites for longer, adding additional antimalarial activity.

The ACTs and TACTs assigned in the trial depended on the first-line ACTs used in the country where the participant was being treated. The researchers assessed the efficacy based on the cure of infection after 42 days of follow-up, including both parasitic load and clinical symptoms.

In Cambodia, Thailand, and Vietnam, the team discovered that the TACT dihydroartemisinin–piperaquine plus mefloquine was more efficacious than the ACT dihydroartemisinin–piperaquine – at 98% efficacy compared with 48%. In three Cambodian sites the first-line drug changed during the trial to artesunate–mefloquine, and the team determined this combination was comparable in efficacy to the TACT they were assessing (96% to 95% respectively).

In addition, the TACT artemether–lumefantrine plus amodiaquine and the ACT artemether–lumefantrine, which were compared in five countries, were also found to be similar in efficacy (98% vs 97%).

Author, Chanaki Amaratunga (Mahidol-Oxford Research Unit, Bangkok, Thailand), commented: “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.”

In addition, the TACTS were generally well-tolerated and safe, although they showed slightly higher rates of vomiting and some minor changes in the electrical activity of the heart compared with existing treatments. With increasing resistance to antimalarials, particularly in southeast Asia, the team believe these new combinations could help extend the life of existing antimalarials.

Amaratunga concluded: “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.”

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Sources: 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. Lancet doi: 10.1016/S0140-6736(20)30552-3 (2020); www.eurekalert.org/emb_releases/2020-03/tl-tlt031020.php

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