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Last Updated: 18/06/2024
Establishment of novel in vitro assay for evaluation of killing effect of chloroquine against malaria parasite
Objectives
To establish an in vitro assay to evaluate the parasitecidal effect of chloroquine and clarify whether the parasitecidal effect of chloroquine has been restored in Uganda.
The research is set to confirm the presence of resistance to the parasiticidal effect of chloroquine using laboratory cultured standard parasite strains according to the method of a previous reported study (Paguio, Mol Biochem Parasitol 2011). Using laboratory cultured Plasmodium falciparum parasites; chloroquine sensitive (HB3) and resistant parasites: Dd2 (Southeast Asian origin) and 7G8 (South American origin) we compared the cytocidal chloroquine efficacy (lethal dose 50%, LD50) and conventional cytostatic chloroquine efficacy (inhibitory dose 50%, IC50). The difference of cytostatic value between chloroquine-sensitive HB3 and chloroquine-resistant Dd2 was about 10 times and HB3 versus chloroquine-resistant 7G8 was 5 times. In contrast, 100-fold difference was observed in cytocidal efficacy between HB3 and Dd2 and 10-fold between HB3 versus 7G8.The next step was to verify the parasiticidal chloroquine effect using cryopreserved natural parasites recovered from Uganda field site. To achieve this objective, the plan was to first recover cryopreserved natural uganda parasites and adapt them into continuous culture in the laboratory. Once parasites are successfully recovered and adapted into culture, then chloroquine cytocidal and cytostatic drug assays were to be performed. So far, parasite recovery from the cryopreserved state and subsequent adaption into culture has been attempted for 18 Uganda isolates. Unfortunately, the process is not yet successful and is still ongoing.
Apr 2020 — Mar 2024
$37,601