Artemisinin-Based Treatments for Malaria in Pregnant Women

Summary and Comment |
March 9, 2016

Artemisinin-Based Treatments for Malaria in Pregnant Women

  1. Mary E. Wilson, MD

In randomized trials, dihydroartemisinin–piperaquine had better efficacy in treating malaria in pregnancy than other artemisinin-based combinations. For prophylaxis, monthly dosing was superior to a three-dose regimen.

  1. Mary E. Wilson, MD

Malaria during pregnancy is associated with adverse maternal and fetal outcomes. Two groups have now assessed contemporary treatment options in pregnant women in malaria-endemic areas.

In the multicenter, randomized, open-label PREGACT trial, researchers in four African countries compared four artemisinin-based regimens for treating 3428 pregnant women in the second or third trimester who had Plasmodium falciparum monoinfection. Drugs were donated by industry. Women received daily doses under direct observation on days 0, 1, and 2 and were followed until day 63. Samples were analyzed by polymerase chain reaction (PCR) and genotyping to distinguish reinfection from recrudescence. The per-protocol, PCR-adjusted cure rates ranged from 95% to 99%. The cure rate was significantly lower with artemether–lumefantrine (A-L) than with the other three regimens. In unadjusted analyses (which included reinfections as well as recrudescent infections and reflected prophylactic effect from persistence of the partner drug), cure rates were significantly lower in the A-L recipients (53%) than in the other groups (dihydroartemisinin–piperaquine [D-P], 87%; mefloquine–artesunate [M-A], 74%; amodiaquine–artesunate [A-A], 82%). Serious adverse events and birth outcomes did not differ significantly among the groups. Drug-related adverse events were significantly more common in M-A (51%) and A-A (49%) recipients than in the other groups. D-P had the most favorable combination of high cure rate and acceptable safety profile.

In a double-blind trial in a Ugandan area with high-intensity malaria transmission and widespread sulfadoxine–pyrimethamine (S-P) resistance, Kakuru and colleagues randomized 300 HIV-uninfected pregnant women (1:1:1) in the second or third trimester to receive routine S-P (per WHO recommendations) or D-P given in a three-dose or monthly regimen. The primary outcome measure, histopathologically confirmed placental malaria, was significantly more common with S-P (50%) than with three-dose or monthly D-P (34% and 27%, respectively). Likelihood of an adverse pregnancy outcome was significantly lower with monthly D-P than with S-P (9.2% vs. 18.6%; P=0.05). Symptomatic malaria was significantly more common with S-P than with D-P. For several outcomes, monthly administration of D-P was superior to the three-dose regimen. Adverse event rates were similar in all groups.

Comment

These findings support the use of artemisinin combination therapy during pregnancy for both treatment and prevention of malaria. The first study shows clear differences among the drug combinations and highlights the importance of the elimination half-life of the drug partnered with artemisinin. Given widespread resistance to S-P, alternatives are needed. An editorialist recommends pharmacokinetic studies in pregnant women to identify the most effective dosing of artemisinin and the partner drugs and to try to increase their therapeutic lifespans.

Editor Disclosures at Time of Publication

  • Disclosures for Mary E. Wilson, MD at time of publication Consultant / Advisory board GeoSentinel Surveillance Network (Special Advisor) Editorial boards UpToDate; Clinical Infectious Diseases; International Health; Infectious Diseases in Clinical Practice; Travel Medicine and Infectious Diseases

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