Heterogeneity in the in vitro susceptibility of <italic>Loa loa</italic> microfilariae to drugs commonly used in parasitological infections.

Background: Co-infection with loiasis remains a potential problem in control programs targeting filarial infections. The effects of many anti-parasitic drugs often administered to <italic>Loa loa</italic> infected people are not well documented. This study compared the in vitro activity of several of these drugs on the viability of <italic>L. loa</italic> microfilariae (mf). Methods: Human strain <italic>L. loa</italic> mf were isolated from baboon blood using iso-osmotic Percoll gradient, and cultured in RPMI 1640/10% FBS with antimalarial drugs (mefloquine, amodiaquine, artesunate, chloroquine and quinine), anthelmintics (ivermectin, praziquantel, flubendazole and its reduced and hydrolyzed metabolites), two potential trypanocidal agents (fexinidazole and Scynexis-7158) and the anticancer drug imatinib. The drug concentrations used varied between 0.156 μg/ml and 10 μg/ml. Mf motility (CR50 = 50% immotility) and a metabolic viability assay (MTT) were used to assess the effects of these drugs on the parasites. Results: Mf in control cultures showed only a slight reduction in motility after 5 days of culture. Active inhibition of <italic>Loa loa</italic> motility was seen with mefloquine and amodiaquine (CR50 values of 3.87 and 4.05 μg/ml, respectively), immobilizing > 90% mf within the first 24 hours: mefloquine killed the mf after 24 hours of culture at concentrations ≥ 5 μg/ml. SCYX-7158 also induced a concentration-dependent reduction in mf motility, with > 50% reduction in mf motility seen after 5 days at 10 μg/ml. The anticancer drug imatinib reduced mf motility at 10 μg/ml from the first day of incubation to 55% by day 5, and the reduction in motility was concentration-dependent. Praziquantel and fexinidazole were inactive, and FLBZ and its metabolites, as well as ivermectin at concentrations > 5 μg/ml, had very minimal effects on mf motility over the first 4 days of culture. Conclusions: The considerable action of the anti-malarial drugs mefloquine and amodiaquine on <italic>Loa</italic> mf in vitro highlights the possibility of repurposing the existing anti-infectious agents for the development of drugs against loiasis. The heterogeneity in the activity of anti-parasitic agents on <italic>Loa loa</italic> mf supports the need for further investigation using animal models of loiasis. [ABSTRACT FROM AUTHOR]