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Monthly dihydroartemisinin/piperaquine effective for intermittent malaria prevention
Monthly dosing of dihydroartemisinin/piperaquine is well-tolerated and effective as an intermittent preventive treatment for malaria, according to a systematic review and meta-analysis published in Lancet Infectious Diseases.
“[Dihydroartemisinin-piperaquine (DP)] provided superior protection against malaria and resulted in fewer hospital admissions than comparators,” Julie Gutman, MD, epidemiologist with the CDC’s Division of Parasitic Diseases and Malaria, and colleagues wrote. “In comparison with dosing every 2 or 3 months, monthly administration of DP provided much better protection from malaria, without increasing the risk of adverse events or adversely affecting tolerability.”
With cure rates of 98% or more, DP is known to be an effective and well-tolerated antimalarial. However, researchers wrote, limited data existed on whether the risk for QT prolongation is increased with repeated DP dosing and, therefore, whether it is a safe choice for intermittent preventive treatment (IPT) of malaria.
Gutman and colleagues searched several databases for articles published before September 2016 to identify randomized controlled trials or cohort studies involving repeat exposures to standard 3-day courses of DP for seasonal malarial chemoprevention, mass drug administration or treatment of clinical malaria. Eleven studies met their eligibility criteria, comprising 14,628 individuals. Two of these were repeat treatment studies — one in children aged younger than 5 years and one in pregnant women — and nine were randomized controlled trials (RCTs) of IPT. Of the nine RCTs, five were in children aged younger than 5 years, one was in school children, one in adults and two in pregnant women.
Of the 14,628 participants, 3,935 received at least two DP courses, including 762 pregnant women and 1,913 children aged younger than 5 years. Comparator interventions in the studies included:
- placebo;
- Coartem (artemether/lumefantrine, Novartis);
- Fansidar (sulfadoxine/pyrimethamine, Roche; SP);
- SP plus amodiaquine;
- SP plus piperaquine;
- SP plus chloroquine;
- co-trimoxazole; and
- primaquine.
Overall, the researchers found that monthly IPT with DP was associated with an 84% reduction in the incidence of malaria parasitemia compared with placebo. Monthly IPT with DP also provided significantly better efficacy than daily co-trimoxazole and monthly IPT with SP for the prevention of malaria infection, similar efficacy to monthly SP plus amodiaquine for preventing any parasitemia, and inferior efficacy to monthly SP plus primaquine.
Furthermore, monthly IPT with DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole and monthly SP. According to the researchers, no cardiac events were reported in any of the recipients of repeat courses of DP. Among 26 children and 30 pregnant women with cardiac parameters, all QTc intervals were within normal limits, and no significant increase in QTc prolongation was observed with increasing courses of DP. Nevertheless, Gutman and colleagues concluded that “ongoing monitoring for cardiac events is needed to provide further reassurance of its safety with repeat doses.”
In a related editorial, Quique Bassat, PhD, MD, MSc, and Clara Menéndez, PhD, both at the Barcelona Institute for Global Health, addressed the question of whether DP could play a role in malaria eradication efforts. While noting that Gutman and colleagues were hesitant to extend their recommendations to use of DP for eradication purposes, they argued that “it is precisely DP’s longer-lasting posttreatment prophylactic effect that is appealing as an elimination drug.” – by Sarah Kennedy
Disclosure: The researchers report no relevant financial disclosures.