Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review

Abstract

BackgroundArtemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.MethodsA PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.ResultsThe literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.ConclusionACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.Trial registrationCRD42014009103Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-463) contains supplementary material, which is available to authorized users.

Do hypnozoites cause relapse in malaria?

“…By contrast, a combination of chloroquine and primaquine has mainly been used historically for the treatment of P. vivax malaria. However, resistance to chloroquine now requires partnering of primaquine with other blood schizontocidal agents such as artemisinin, which is effective against P. vivax parasites in the bloodstream [62][63][64]. The propensity of P. vivax to regularly become dormant in the presence of artemisinin (which might or might not happen in vivo in P. falciparum infections), and the maximum duration of any such latency, are at present unknown.…”

SeverePlasmodium knowlesiwith dengue coinfection

“…The duration of oral treatment is 3 days 6. Previous small studies have shown the efficacy of parenteral artesunate in treating severe knowlesi malaria, likely attributed to its fast parasite clearance properties 7. A study by Fatih et al 8 has shown that Plasmodium knowlesi is highly sensitive to artemisinins compared to chloroquine and mefloquine.…”

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“…[32][33][34] Artemisinin displays the most rapid action among the current drugs against Plasmodium falciparum as well as Plasmodium vivax induced malaria. 35 Further, Artemisinin and its derivatives have been observed to exhibit potency against the asexual and erythrocytic forms of P. falciparum and P. vivax.…”