Dihydroartemisinin-piperaquine treatment of multidrug resistant falciparum and vivax malaria in pregnancy.
BACKGROUND
Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.


METHODS
From April 2004-June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.


RESULTS
Data were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26-4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97-2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17-8.60]; p = 0.023).


CONCLUSIONS
In the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.
District Health Authority, Timika, Papua, Indonesia ; Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika, Papua, Indonesia.
Jeanne Rini
JR
Poespoprodjo
Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika, Papua, Indonesia.
Wendy
W
Fobia
District Health Authority, Timika, Papua, Indonesia ; Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika, Papua, Indonesia.
Enny
E
Kenangalem
District Health Authority, Timika, Papua, Indonesia ; Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika, Papua, Indonesia.
Daniel A
DA
Lampah
Mitra Masyarakat Hospital, Timika, Papua, Indonesia.
Paulus
P
Sugiarto
National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia.
Emiliana
E
Tjitra
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia ; Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Nicholas M
NM
Anstey
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia ; Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia ; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Ric N
RN
Price
D000208:Acute Disease; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016780:Malaria, Vivax / Q000188:drug therapy*; D018512:Parasitemia / Q000188:drug therapy; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines