Comparative efficacy of sulphadoxine-pyrimethamine and dihydroartemisinin-piperaquine against malaria infection during late-stage pregnancy in mice.

Abstract

The introduction of artemisinin combination therapies (ACTs) against malaria infections opened up a window of possibilities to combat malaria in pregnancy. However, the usefulness of ACTs in all stages of pregnancy must be critically assessed. This study was designed to evaluate dihydroartemisinin-piperaquine (DHAP) as a suitable alternative to sulphadoxine-pyrimethamine (SP) in the treatment of malaria during third-trimester pregnancy in mice. Experimental animals were inoculated with a parasitic dose of 1x106Plasmodium berghei (ANKA strain) infected erythrocytes and randomly allocated into treatment groups. The animals received standard doses of chloroquine alone (CQ)[10 mg/kg], SP [25 mg/kg] and [1.25 mg/kg] and DHAP [4 mg/kg] and [18 mg/kg] combinations. Maternal and pupil survival, litter sizes, pup weight and still-births were recorded, while the effect of the drug combinations on parasite suppression, recrudescence and parasite clearance time were evaluated. The day 4 chemo-suppression of parasitemia by DHAP in infected animals was comparable to SP, and CQ treatment (P > 0.05). The mean recrudescence time was significantly delayed (p = 0.031) in the DHAP treatment group compared to the CQ treatment group, while, there was no recrudescence in animals treated with SP. The birth rate in the SP group was significantly higher than in the DHAP group (P < 0.05). There was 100% maternal and pup survival in both combination treatments comparable with the uninfected gravid controls. The overall parasitological activity of SP against Plasmodium berghei in late-stage pregnancy appeared better than DHAP. In addition, SP treatment resulted in better birth outcomes assessed compared to DHAP treatment.