title: Artesunate-tafenoquine combination therapy promotes clearance and abrogates transmission of the avian malaria parasite Plasmodium gallinaceum.
abstract: Clinical manifestations of malaria infection in vertebrate hosts arise from the multiplication of the asexual stage parasites in the blood, while the gametocytes are responsible for the transmission of the disease. Antimalarial drugs that target the blood stage parasites and transmissible gametocytes are rare, but are essentially needed for the effective control of malaria and for limiting the spread of resistance. Artemisinin and its derivatives are the current first-line antimalarials that are effective against the blood stage parasites and gametocytes, but resistance to artemisinin has now emerged and spread in various malaria endemic areas. Therefore, a novel antimalarial drug, or a new drug combination, is critically needed to overcome this problem. The objectives of this study were to evaluate the efficacy of a relatively new antimalarial compound, tafenoquine (TQ), and a combination of TQ and a low dose of artesunate (ATN) on the in vivo blood stage multiplication, gametocyte development and transmission of the avian malaria parasite Plasmodium gallinaceum to the vector Aedes aegypti. The results showed that a 5-d treatment with TQ alone was unable to clear the blood stage parasites, but was capable of reducing the mortality rate, while TQ monotherapy at a high dose of 30mg/kg was highly effective against the gametocytes and completely blocked the transmission of P. gallinaceum. In addition, the combination therapy of TQ+ATN completely cleared P. gallinaceum blood stages and sped up the gametocyte clearance from chickens, suggesting the synergistic effect of the two drugs. In conclusion, TQ is demonstrated to be effective for limiting avian malaria transmission and may be used in combination with a low dose of ATN for safe and effective treatment.
authors.affiliation: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Suchada
authors.initials: S
authors.lastname: Tasai
authors.affiliation: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Tawee
authors.initials: T
authors.lastname: Saiwichai
authors.affiliation: Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Morakot
authors.initials: M
authors.lastname: Kaewthamasorn
authors.affiliation: Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Sonthaya
authors.initials: S
authors.lastname: Tiawsirisup
authors.affiliation: Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Prayute
authors.initials: P
authors.lastname: Buddhirakkul
authors.affiliation: Department of Dermatology, School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University Hospital, Bangkok 10100, Thailand.
authors.forename: Sirintip
authors.initials: S
authors.lastname: Chaichalotornkul
authors.affiliation: Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: Sittiporn.P@Chula.ac.th.
authors.forename: Sittiporn
authors.initials: S
authors.lastname: Pattaradilokrat
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D004338:Drug Combinations; D004351:Drug Resistance; D004357:Drug Synergism; D007303:Insect Vectors / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects; D008289:Malaria, Avian / Q000188:drug therapy* / Q000635:transmission; D010964:Plasmodium gallinaceum / Q000187:drug effects / Q000254:growth & development / Q000469:parasitology
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C055852:tafenoquine; D000077332:Artesunate
keywords: 8-Aminoquinoline; Aedes aegypti; Artesunate; Chemotherapy; Oocysts; Plasmodium gallinaceum; Tafenoquine