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
Ishih, A.; Suzuki, T.; Muregi, F.W.; Matsui, K.; Terada, M.
Southeast Asian Journal of Tropical Medicine and Public Health 37(1): 13-17
2006
ISSN/ISBN: 0125-1562 PMID: 16771206 Document Number: 597626
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 1x105, 1x106, 1x107, 1x108 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 parasitaemia. Mice in the untreated control in each group showed a progressive increase in parasitaemia leading to death. Treatment of mice, inoculated with 1x105, 1x106 and 1x107 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 1x108 pRBC showed little response to CQ treatment, and all mice showed a progressive increase in parasitaemia and ultimately died. In another experiment, mice infected with 1x103 and 1x105 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 1x103 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 decrease in parasitaemia and all the mice ultimately died. On the other hand, treatment from day 2 showed a marked effect against 1x105 P. berghei NK65-infected mice, but treatment from days 3 or 4 was only slightly effective and all the mice died with an increasing parasitaemia. The present results indicate that in in vivo antimalarial drug-assay systems, several factors, such as initial parasite load and starting time of treatment may influence the drug response in the host.