Phenotypic Approach Artemisinin Resistance in Malaria Rodent as in vivo Model

Aim: The aim of this study is to prove the development of artemisinin resistance phenotypically in malaria rodent as an in vivo resistance development model in humans.

Materials and Methods: Plasmodium berghei was infected intraperitoneally in mice, then artemisinin was given with “4-day-test” with effective dose (ED) 99% dose for 3 days which begins 48 h after infection (D2, D3, and D4). Parasite development was followed during 5^th until 10^th days of infection. After parasitemia >2% of red blood cell which contains parasites on 1 mice, that mice were used as donor to be passaged on the new 5 mice. After that, parasitemia was calculated. ED₅₀ and ED₉₀ were examined with parasite clearance time (PCT), recrudescence time (RT), and also morphology development examination of intraerythrocytic cycle of P. berghei with transmission electron microscope.

Results: Among the control group compare with the treatment group showed significant differences at α=0.05 on 5^th day (D5) until 10^th day (D10). The control group of 4^th passage (K4) with passage treatment group of 4^th passage (P4) on the 10^th days (D10) post infection showed no significant differences in the α=0.05. The average percentage of inhibition growth was decreasing which is started from 5th to 10th day post infection in P1, P2, P3, and P4. On the development of P. berghei stage, which is given repeated artemisinin and repeated passage, there was a formation of dormant and also vacuoles in Plasmodium that exposed to the drug.

Conclusion: Exposure to artemisinin with repeated passages in mice increased the value of ED₅₀ and ED₉₀, decreased the PCT and RT and also changes in morphology dormant and vacuole formation.