title: Chloroquine efficacy in Plasmodium berghei NK65-infected ICR mice, with reference to the influence of initial parasite load and starting day of drug administration on the outcome of treatment.
abstract: We examined whether the initial number of parasites inoculated and the starting day of medication post-infection influenced the antimalarial efficacy of chloroquine (CQ) against Plasmodium berghei NK65 infection in ICR mice. Male ICR mice were inoculated intraperitoneally with 1 x 10(5), 1x10(6), 1 x 10(7), 1 x 10(8) P. berghei NK65-parasitized erythrocytes (pRBC). In the treated group, all mice received an oral dose of 20 mg/kg of CQ base for 4 days starting on day 0 after infection. From day 3, Giemsa-stained thin blood smears from tail vein blood were used to assess parasitemia. Mice in the untreated control in each group showed a progressive increase in parasitemia leading to death. Treatment of mice, inoculated with 1 x 10(5), 1 x 10(6) and 1 x 10(7) pRBC, with CQ showed a marked effect. All the mice survived during the experiment. During the observation period, malaria parasites could not be detected on microscopic examination. Conversely, mice inoculated with 1 x 10(8) pRBC showed little response to CQ treatment, and all mice showed a progressive increase in parasitemia and ultimately died. In another experiment, mice infected with 1 x 10(3) and 1x 10(5) pRBC were treated with an oral four-day dosage of 20 mg/kg of CQ base from days 2, 3 or 4 post-infection. Treatment of mice, inoculated with 1 x 10(3) pRBC, with CQ from days 2 and 3 showed a marked effect. All mice survived during the experiment. However, treatment from day 4 showed a limited derease in parasitemia and all the mice ultimately died. On the other hand, treatment from day 2 showed a marked effect against 1 x 10(5) P. berghei NK65-infected mice, but treatment from days 3 or 4 was only slightly effective and all the mice died with an increasing parasitemia. The present results indicate that in in vivo antimalarial drug-assay systems, several factors, sush as initial parasite load and starting time of treatment may influence the drug response in the host.
authors.affiliation: Department of Parasitology, Hamamatsu University School of Medicine, Japan. aishih@hama-med.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ishih
authors.forename: Tohru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Francis W
authors.initials: FW
authors.lastname: Muregi
authors.forename: Kae
authors.initials: K
authors.lastname: Matsui
authors.forename: Mamoru
authors.initials: M
authors.lastname: Terada
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002738:Chloroquine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000187:drug effects*
chemical_list: D000995:Antitubercular Agents; D002738:Chloroquine