Anti-plasmodial activity of rifampicin/ dihydro-artemisinin/piperaquine combination on Plasmodium berghei infected mice

Introduction: The huge cost of de-novo drug development and the problem of multidrug resistance by plasmodium parasites has made research on drugs with potential for repurposing attractive. The study evaluated the antiplasmodial properties of clinical doses of rifampicin in combination with dihydroartemisinic/piperaquine in Plasmodium berghei-infected mice.

Materials/Methods: Curative, suppressive, and prophylactic tests were carried out on adult mice (26 – 30g) infected with P.berghei parasite. They were grouped and treated per oral (p.o) with RIF (15mg/kg), DP (2.5/20 mg/kg) and RIF/DP (15/2.5/20 mg/kg) daily. The negative control (NC) and the positive control (PC) were treated daily p.o with normal saline (0.2mL) and chloroquine (CQ) (10 mg/kg). Normal saline and chloroquine were administered to mice in the first and second groups, respectively, for 3 consecutive days. Similarly, the third group of mice were treated with dihydroartemisinin/piperaquine combination for 3 consecutive days, while rifampicin was given to the fourth group for 7 consecutive days. The last group of mice were administered the dihydroartemisinic/piperaquine dose for 3days and the rifampicin dose for 7 consecutive days.

Results: There was significant reduction in parasitemia in the prophylactic, suppressive, and curative studies at RIF (15 mg/kg) (p<0.01), DP (2.5/20 mg/kg) (p<0.001) and RIF/DP (p<0.0001) when compared with to negative control. There was an approximately three-fold decrease in percentage parasitemia in the rifampicin/dihydroartemisinin/piperaquine treatment group when compared to the Chloroquine treatment group.

Conclusion: The combination of rifampicin with dihydroartemisinin/piperaquine represent potentially viable additions to the antimalarial arsenal currently available. RIF may be repurposed in combination with DP for malaria treatment.