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Malawi Med J. 2016 Sep;28(3):139-149.

Four artemisinin-based treatments in African pregnant women with malaria.

Author information

1
Center for Global Health Research, Kumasi, Ghana.
2
Clinical Trial Unit Nanoro, Nanoro, Burkina Faso.
3
College of Medicine, University of Malawi, Blantyre, Malawi.
4
Department of Pharmaceutical and Pharmacologic Sciences, KU Leuven, Leuven, Belgium; Institute of Tropical Medicine, Antwerp, Belgium.
5
Hubert Kairuki Memorial University, Dar es Salaam, Tanzania.
6
Juaben Government Hospital, Juaben, Ghana.
7
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
8
Institute of Tropical Medicine, Antwerp, Belgium.
9
Institute of Tropical Medicine, Antwerp, Belgium; Menzies School of Health Research, Darwin, NT, Australia.
10
International Health Unit, University of Antwerp, Antwerp, Belgium.
11
Institute of Tropical Medicine, Antwerp, Belgium; Medical Research Council Unit, Fajara, Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
12
Tropical Diseases Research Center, Ndola, Zambia.

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.).

PMID:
27895848
PMCID:
PMC5117004

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