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Four artemisinin-based treatments in African pregnant women with malaria
Pekyi, Divine; Ampromfi, Akua A.; Tinto, Halidou; Traoré-Coulibaly, Maminata; Tahita, Marc C.; Valéa, Innocent; Mwapasa, Victor; Kalilani-Phiri, Linda; Kalanda, Gertrude; Madanitsa, Mwayiwawo; Ravinetto, Raffaella; Mutabingwa, Theonest; Gbekor, Prosper; Tagbor, Harry; Antwi, Gifty; Menten, Joris; Crop, Maaike De; Claeys, Yves; Schurmans, Celine; Overmeir, Chanta Van; Thriemer, Kamala; Geertruyden, Jean-Pierre Van; D'Alessandro, Umberto; Nambozi, Michael; Mulenga, Modest; Hachizovu, Sebastian; Kabuya, Jean-Bertin B. & Mulenga, Joyce
Abstract
Background
Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly
among women who live in sub-Saharan Africa.
Methods
We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A
total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless
of symptoms) were treated with artemether–lumefantrine, amodiaquine–artesunate, mefloquine–artesunate, or dihydroartemisinin–
piperaquine. The primary end points were the polymerase-chain-reaction (PCR)–adjusted cure rates (i.e., cure of the original infection;
new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes.
Results
The PCR-adjusted cure rates in the per-protocol analysis were 94.8% in the artemether–lumefantrine group, 98.5% in the amodiaquine–
artesunate group, 99.2% in the dihydroartemisinin–piperaquine group, and 96.8% in the mefloquine–artesunate group; the PCR-adjusted
cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference
among the amodiaquine–artesunate group, dihydroartemisinin–piperaquine group, and the mefloquine–artesunate group. The cure rate
in the artemether–lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was
within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-treatment prophylactic
effect, were significantly lower in the artemether–lumefantrine group (52.5%) than in groups that received amodiaquine–artesunate
(82.3%), dihydroartemisinin–piperaquine (86.9%), or mefloquine–artesunate (73.8%). No significant difference in the rate of serious
adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor
appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine–artesunate group (50.6%) and the
amodiaquine–artesunate group (48.5%) than in the dihydroartemisinin–piperaquine group (20.6%) and the artemether–lumefantrine
group (11.5%) (P<0.001 for comparison among the four groups).
Conclusions
Artemether–lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest posttreatment
prophylaxis, whereas dihydroartemisinin–piperaquine had the best efficacy and an acceptable safety profile. (Funded by the
European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)
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