title: In Vitro Activities of Primaquine-Schizonticide Combinations on Asexual Blood Stages and Gametocytes of Plasmodium falciparum.
abstract: Currently, the World Health Organization recommends addition of a 0.25-mg base/kg single dose of primaquine (PQ) to artemisinin combination therapies (ACTs) for Plasmodium falciparum malaria as a gametocytocidal agent for reducing transmission. Here, we investigated the potential interactions of PQ with the long-lasting components of the ACT drugs for eliminating the asexual blood stages and gametocytes of in vitro-cultured P. falciparum strains. Using the SYBR green I assay for asexual parasites and a flow cytometry-based assay for gametocytes, we determined the interactions of PQ with the schizonticides chloroquine, mefloquine, piperaquine, lumefantrine, and naphthoquine. With the sums of fractional inhibitory concentrations and isobolograms, we were able to determine mostly synergistic interactions for the various PQ and schizonticide combinations on the blood stages of P. falciparum laboratory strains. The synergism in inhibiting asexual stages and gametocytes was highly evident with PQ-naphthoquine, whereas synergism was moderate for the PQ-piperaquine, PQ-chloroquine, and PQ-mefloquine combinations. We have detected potentially antagonistic interactions between PQ and lumefantrine under certain drug combination ratios, suggesting that precautions might be needed when PQ is added as the gametocytocide to the artemether-lumefantrine ACT (Coartem).
authors.affiliation: Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Mynthia
authors.initials: M
authors.lastname: Cabrera
authors.affiliation: Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA luc2@psu.edu.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D052160:Benzothiazoles; D002738:Chloroquine / Q000494:pharmacology; D003959:Diamines; D004338:Drug Combinations; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D004983:Ethanolamines / Q000494:pharmacology; D005434:Flow Cytometry; D005449:Fluorenes / Q000494:pharmacology; D006801:Humans; D000078102:Lumefantrine; D015767:Mefloquine / Q000494:pharmacology; D009930:Organic Chemicals; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011319:Primaquine / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D034101:Sporozoites / Q000187:drug effects* / Q000254:growth & development; D053058:Trophozoites / Q000187:drug effects* / Q000254:growth & development; D010879:Piperazines
chemical_list: D000962:Antimalarials; D052160:Benzothiazoles; D002738:Chloroquine; D003959:Diamines; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine; D015767:Mefloquine; D009930:Organic Chemicals; D011319:Primaquine; D011804:Quinolines; C098022:SYBR Green I; C034759:piperaquine; D010879:Piperazines