Efficacy of a Paromomycin plus Chloroquine Combination Therapy in Experimental Cutaneous Leishmaniasis [PublishAheadOfPrint]

The 4-aminoquinoline chloroquine (CQ) is clinically used in combination with doxycycline to cure chronic Q-fever, as it enhances the activity of the antibiotic against the causative Coxiella burnetii bacteria residing within macrophage phagolysosomes. As there is a similar cellular host-pathogen biology for Leishmania parasites, this study aimed to determine whether such an approach could be also the basis for a new, improved treatment for cutaneous leishmaniasis (CL). We have evaluated the in vitro and in vivo activity of combinations of CQ with standard drugs paromomycin (PM), miltefosine and amphotericin B against Leishmania major and Leishmania mexicana. In 72-hour intracellular anti-leishmanial assays, outcomes were variable for different drugs. Significantly, the addition of 10 μM CQ to PM reduced EC₅₀ values by over 5-fold against L. major and against the normally insensitive L. mexicana. In murine models of L. major and L. mexicana CL, daily co-administration of 50 mg/kg PM and 25 mg/kg CQ for 10 days resulted in significant reduction in lesion size but not in parasite load compared to mice given the same doses of PM alone. Overall, our data indicates that a PM plus CQ combination therapy is unlikely to be a potential candidate for further preclinical development.

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