Antagonism of serum of mice infected with chloroquine-resistant 'NS' line to the antimalarial action of chloroquine

Chloroquine (CQ) solution was separately mixed with the serum of mice infected with chloroquine-resistant 'NS' line (SMNS), the serum of mice infected with chloroquine-sensitive Plasmodium berghei ANKA strain (SMCS), and the serum of normal mice (SM). These mixtures were then used in treating mice inoculated with P. berghei ANKA strain. The results obtained on d 5 after drug-serum administration showed that the erythrocyte infection rates in the SMNS + CQ, SMCS + CQ, and SM + CQ groups were 32, 16, and 14% respectively. There were significant differences with respect to parasitemia between the SMNS + CQ group and the SMCS + CQ or SM + CQ group (P less than 0.05), suggesting that SMNS may be antagonistic to the antimalarial action of chloroquine. Further study showed that when the 'NS' line lost resistance to chloroquine, the antagonism of SMNS to chloroquine disappeared. The antagonism rates of SMNS to chloroquine, piperaquine, hydroxypiperaquine and pyronaridine were 75, 56, -5, and -17% respectively, a trend similar to that of the results from cross-resistance tests on chloroquine-resistant P. berghei ANKA strain. The results indicate that drug-resistant malaria parasites may produce and release a certain 'specific anti-drug substance'.