建立疟疾近期复发动物模型的研究Ⅲ.联合应用咯萘啶、蒿甲醚和氯喹清除原虫血症

STUDIES ON THE ESTABLISHMENT OF MALARIAL ANIMAL MODEL OF SHORT-TERM REPLAPSE Ⅲ. COMBINED THERAPY WITH PYRONARIDINE-ARTEMETHER-CHLOROQUINE FOR PARASITEMIA CLEARANCE

观察近期复发,必须找到克服原虫复燃的方法,避免复燃与复发相混淆。现代抗疟药咯萘啶、蒿甲醚和氯喹均为杀灭血内裂殖体较好的药物,但治疗后较易复燃。作者设想联合用药可能克服此缺点。经过预试验,选用磷酸咯萘啶(基质)6 mg/kg、蒿甲醚 100 mg/kg和磷酸氯喹(基质)10 mg/kg 联合治疗3 d的方案,治疗经食蟹猴疟原虫血传感染的7只恒河猴,结果迅速清除了原虫血症,其中 5只猴追踪观察 300—400 d无复燃出现,但对胃肠道的副作用相当明显。3种抗疟药的剂量组合经过调整,试用磷酸咯萘啶(基质)6 mg/kg、蒿甲醚 10 mg/kg 和磷酸氯喹(基质)20mg/kg 联合治疗 3 d的方案,结果对 3只受试猴无明显副作用,原虫转阴后观察 180 d亦无复燃出现,而另 3只猴单用氯喹 20 mg/kg 治疗 3 d,未能完全克服复燃。结果表明,上述 3种药物联合使用可有效地清除原虫血症,制止复燃现象,也为近期复发动物模型的建立创造了条件。

To establish a Plasmodium cynomolgi-monkey model of short-term relapse, different an-timalarials 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 = 103.94-0.83X. 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=103.7-1.46X, 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 para-sitemia clearance and might be adopted for establishment of the monkey model of short-term relapse.