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Malaria remains a major killer of children globally. In areas where vivax and falciparum malaria coexist, treatment options have been complicated, especially if diagnostic tests to distinguish between the two species are unavailable or unreliable. First-line treatment usually differs by species.
The May 23/30 issue of JAMA includes multiple papers that address malaria-related issues. Two trials assess options for therapy in endemic areas.
Leslie and colleagues assessed the relative efficacy and safety of two antifolate drugs against vivax malaria and compared them with chloroquine in areas of Afghanistan and Pakistan where vivax malaria predominates. In an open-label trial, 767 patients aged ≥3 years with confirmed vivax malaria were randomized in a ratio of 2:2:1 to receive chlorproguanil-dapsone, sulfadoxine-pyrimethamine, or chloroquine. Patients were evaluated on 7 set days during the 28-day follow-up period and whenever they felt unwell. Although by day 14 all participants (except for one receiving sulfadoxine-pyrimethamine) had cleared parasites, by day 28 failure rates were 1.3% for chloroquine, 1.7% for sulfadoxine-pyrimethamine, and 9.9% for chlorproguanil-dapsone. Chloroquine cleared gametocytes and asexual parasites more rapidly than the combinations did. All regimens were well tolerated.
In another trial, Dorsey and colleagues compared the efficacy and safety of three combinations against uncomplicated falciparum malaria in Ugandan children. They enrolled 601 healthy children, aged 1–10 years, and randomized them to receive amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, or artemether-lumefantrine orally for their first and subsequent episodes of malaria. Blood smears were done at least monthly. Malaria was diagnosed if participants had fever and parasitemia. Among those enrolled, 329 children had 687 episodes of malaria treated with study drugs over 13 to 19 months. Failure rates at day 28, including reinfection and recrudescent infection, were 26.1%, 17.4%, and 6.7% for the three regimens, respectively. When reinfections were excluded, failure rates at day 63 were 12.2%, 4.7%, and 1.8%.
Leslie T et al. Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: A randomized controlled trial. JAMA 2007 May 23/30; 297:2201-9.
Dorsey G et al. Combination therapy for uncomplicated falciparum malaria in Ugandan children: A randomized trial. JAMA 2007 May 23/30; 297:2210-9.
Comment
Clear differences exist among drugs and combinations, but all require the infrastructure to deliver treatment. Malaria treatment is most effective when matched to the infecting species and resistance patterns, which vary by geographic region. The first study showed that antifolates are efficacious against vivax malaria in South Asia and thus can be used (preferably combined with other agents) to treat infections by unknown species, although chloroquine is preferred when vivax infection is confirmed. Artemisinin-based combination therapies are recommended for treating falciparum malaria in most areas but remain unavailable or unaffordable to many. The second study found that artemether-lumefantrine is the most efficacious of regimens tested against falciparum malaria, but that other regimens are adequate if options are limited.