title: Four Artemisinin-Based Treatments in African Pregnant Women with Malaria.
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 post-treatment 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.).
authors.forename: Divine
authors.initials: D
authors.lastname: Pekyi
authors.forename: Akua A
authors.initials: AA
authors.lastname: Ampromfi
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.forename: Maminata
authors.initials: M
authors.lastname: Traoré-Coulibaly
authors.forename: Marc C
authors.initials: MC
authors.lastname: Tahita
authors.forename: Innocent
authors.initials: I
authors.lastname: Valéa
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.forename: Linda
authors.initials: L
authors.lastname: Kalilani-Phiri
authors.forename: Gertrude
authors.initials: G
authors.lastname: Kalanda
authors.forename: Mwayiwawo
authors.initials: M
authors.lastname: Madanitsa
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ravinetto
authors.forename: Theonest
authors.initials: T
authors.lastname: Mutabingwa
authors.forename: Prosper
authors.initials: P
authors.lastname: Gbekor
authors.forename: Harry
authors.initials: H
authors.lastname: Tagbor
authors.forename: Gifty
authors.initials: G
authors.lastname: Antwi
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.forename: Maaike
authors.initials: M
authors.lastname: De Crop
authors.forename: Yves
authors.initials: Y
authors.lastname: Claeys
authors.forename: Celine
authors.initials: C
authors.lastname: Schurmans
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Kamala
authors.initials: K
authors.lastname: Thriemer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.forename: Michael
authors.initials: M
authors.lastname: Nambozi
authors.forename: Modest
authors.initials: M
authors.lastname: Mulenga
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hachizovu
authors.forename: Jean-Bertin B
authors.initials: JB
authors.lastname: Kabuya
authors.forename: Joyce
authors.initials: J
authors.lastname: Mulenga
mesh_terms: D000328:Adult; D000349:Africa; D000655:Amodiaquine / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011804:Quinolines / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine