[Studies on the establishment of malarial animal model of short-term relapse. III. Combined therapy with pyronaridine-artemether-chloroquine for parasitemia clearance].

To establish a Plasmodium cynomolgi-monkey model of short-term relapse, different antimalarials have been used to inhibit recrudescence so as to elude the confusion between the two different onsets. When a single dose of effective schizonticides pyronaridine, artemether or chloroquine was administered, recrudesence readily occurred. This paper reports the results of the combined therapy with the above three drugs. Seven rhesus monkeys from Guangxi Autonomous Region infected with Plasmodium cynomolgi from Vietnam by blood transmission were rapidly cured by combined therapy with pyronaridine 6 mg/kg-artemether 100 mg/kg-chloroquine 10 mg/kg (PAC-1) once daily for 3 days. The average time of parasite clearance was 3.43 +/- 0.89 d and the curvilinear regression equation of parasite density after treatment was Y = 10(3.94-0.83X). Severe side effects of the gastrointestinal tract occurred during the course of treatment, though no recrudescence was found after 300-400 days. To reduce the side effects, another test was carried out in 3 monkeys and the dosage regimen was modified to pyronaridine 6 mg/kg-artemether 10 mg/kg-chloroquine 20 mg/kg (PAC-2) once daily for 3 days. There was no obvious side effect in the tested monkeys and the parasites were cleared during a mean time of 2.67 +/- 0.58 d and the curvilinear regression equation of parasite density was Y = 10(3.7-1.46X). No recrudescence was detected in the animals during a follow-up of 180 days. The study shows that PAC-2 regimen of the combined therapy is effective for parasitemia clearance and might be adopted for establishment of the monkey model of short-term relapse.