PLASMODIUM VINCKEI - PRODUCTION OF CHLOROQUINE-RESISTANT STRAIN

To date only two species of malarial parasites, Plasmodium falciparum in man and P. berghei in mice, have demonstrated the ability to develop a high degree of resistance to chloroquine. A strain of P. vinckei which is resistant to the maximum tolerated dose (MTD) of chloroquine in mice has been selected from a pyrimethamine-resistant parent strain. Groups of five or more mice were treated with varying doses of drug for 3-4 days starting the day after parasite inoculation. Subpassages were made from mice treated with the highest dose of drug that allowed for some development of parasites. Resistance developed gradually during 37 successive chloroquine-treated passages over a period of about 44 weeks. In subsequent passages, the parasite was resistant to the MTD of chloroquine for mice (200 mg/kg/day). The dose of chloroquine which suppressed the parent strain by 99.9% on Day 7 was 5 mg/kg/day for 4 days. Sixty percent of mice treated with 10 mg/kg/day of chloroquine and all mice treated with doses of 20 mg/kg/day and greater were cured. Associated with resistance to chloroquine were the parasite's failure to produce detectable pigment in treated mice and the appearance of multiple vacuoles. The resistant strain in treated mice is characterized by slower developing, less fatal parasitemias while in untreated mice fulminating infections often result in death. This new species of chloroquine-resistant malaria may be of value as a laboratory model for the study of acquired drug resistance. © 1969.