The Impact of Rifampicin on Antimalarial Activity of Piperaquine and Piperaquine/Dihydroartemisinin Combination.

Abstract

Resistance to the available artemisinin-based combination therapy continues to threaten the gains made through global efforts to control and eliminate malaria, one of the most severe public health problems in sub-Saharan Africa.  In this study, the therapeutic efficacy of combinations of rifampicin with piperaquine or, piperaquine/dihydroartemisinin was evaluated in a murine model of malaria. A modification of Peter’s four-day suppressive test was used to evaluate chemosuppression of parasitemia, parasite clearance time (PCT), parasite recrudescence time (PRT), survival time and survival rate by the selected drug combinations. Fifty Swiss albino mice weighing 18 – 22g were intravenously inoculated with 1 x 107 chloroquine-resistant P. berghei  (ANKA) and assigned to ten treatment groups (n=5); rifampicin 15mg/kg or 30mg/kg, piperaquine (16mg/kg), piperaquine/rifampicin 15mg/kg or 30mg/kg, piperaquine (16mg/kg)/dihydroartemisinin (2mg/kg), piperaquine/dihydroartemisinin/rifampicin 15mg/kg or 30mg/kg. A group was assigned to receive standard dose of chloroquine (10mg/kg), while the control distilled water. All drugs were administered orally over a 3-day period, and animals were followed up for 42 days. Parasitemia was suppressed by 100% between day 4 to 11 post-infection in all treatment groups, except in the two controls, and rifampicin-alone groups. The PCT and survival rates of animals that received rifampicin-based combinations were not significantly different (p>0.05) compared with piperaquine/dihydroartemisinin treated animals. Animals that received rifampicin-based combinations had longer PRT ranging from 29.6 – 33.0 days, compared with 26.2 days in piperaquine/dihydroartemisinin treated animals. The antimalarial efficacy of rifampicin-based combination appeared superior to piperaquine/dihydroartemisinin, hence a promising antimalarial combination with the potential of mitigating resistance to the component drugs.