Triple artemisinin-based combination therapy (TACT): Efficacy of dihydroartemisinin-piperaquine plus chloroquine against Plasmodium berghei ANKA strains with different drug sensitivities in a murine malaria model.

Background: Evident detection of artemisinin resistance markers in patient isolates of Plasmodium falciparum from East Africa threatens the efficacy of artemisinin-based combination therapies (ACTs) as first-line treatment of malaria in sub-Saharan Africa. Repositioning previously used antimalarials as complementary addition to ACTs has been suggested as a viable option to mitigating this threat. This study evaluated the potential benefit of chloroquine (CQ) as a complementary partner to dihydroartemisinin/piperaquine (DHA/PQ) in the treatment of malaria in a mice model.

Methods: The comparative efficacy of the combination of DHA/PQ/CQ and DHA/PQ against two strains of Plasmodium berghei ANKA (MRA 311 and 671) with different levels of sensitivities to chloroquine was evaluated in separate experiments. Parasitological activities including; parasite suppression time, parasite clearance time, recrudescence time, and parasite reduction ratio were evaluated in vivo. The mean survival time was also monitored throughout the duration of the study.

Results: In both parasite lines, 99.99 % chemo-suppression was observed on day 4 in the drug treatment groups (CQ alone, DHA/PQ and DHA/PQ/CQ). In the curative test, there were significant differences between DHA/PQ/CQ and DHQ/PQ treatment, highlighted by reduced parasite clearance time (4.75 ± 0.3 Vs 5.5 ± 0.3 days, P < 0.05), significantly delayed recrudescence time (28.5 ± 1.04 Vs 13.3 ± 0.48 days, P < 0.01), a 1.5-fold change in parasite reduction ratio, and a prolonged mean survival time (34.5 ± 1.04 Vs 26.7 ± 0.48 days, P < 0.05).

Conclusions: The addition of chloroquine to dihydroartemisinin-piperaquine may be beneficial in the treatment of malaria, especially in areas where malaria parasite sensitivity to chloroquine is predominant.