阿奇霉素治疗间日型猴疟效果的研究

目的探讨阿奇霉素对疟原虫的杀灭作用及对疟原虫复燃的影响。方法健康和免疫缺陷的恒河猴(体重5 kg)各1只,血传感染食蟹猴疟原虫,待血液中疟原虫密度分别到达2 266.67个/μl和3 796.08个/μl时,每只猴每天口服阿奇霉素500 mg,健康猴和免疫缺陷猴分别连续服药12和19 d。每天采血镜检观察。结果健康猴感染后11 d,免疫缺陷猴感染后17 d血中疟原虫消失。两只猴连续7个月血检疟原虫均为阴性。结论单服阿奇霉素对间日型猴疟原虫具有直接杀灭作用,提示对间日型猴疟有较好的近期和远期疗效。     

鼠疟原虫引起血小板减少药物干预效果的观察

目的了解退烧药、抗生素及激素对感染鼠疟原虫引起的血小板减少是否具有恢复的效果。方法健康昆明小鼠腹腔接种感染伯氏鼠疟原虫,当感染鼠血小板明显低于正常值后,分别采用临床常用的大环内酯类、β内酰胺类和喹诺酮类抗生素、退烧药及激素类药物按照人体治疗量的10倍灌服或肌注方法给药3d,每12h采血1次做血小板计数观察。每5只小鼠为一个观察试验组,每种药物采用一组小鼠试验观察取平均数据,并设正常对照组。结果正常鼠血小板平均计数为256×109/L。健康鼠感染鼠疟原虫后第8d,各组感染鼠血小板计数平均降至90×109/L后,开始灌服各类抗生素和肌注氨基比林及地塞米松,除阿奇霉素观察组治疗3d后血小板计数平均恢复至201×109/L水平外,其它抗生素和退烧药及激素均对感染鼠疟原虫所引起的血小板明显减少恢复无影响。结论除阿奇霉素外,复方氨基比林、阿莫西林、左氧氟沙星、地塞米松对鼠疟原虫感染小鼠血小板减少无明显效果。     

约氏疟原虫蛋白磷酸酶6 免疫血清的传播阻断效果分析

目的:探讨约氏疟原虫蛋白磷酸酶6(PyPPM6)作为传播阻断疫苗候选抗原的可行性。方法:PCR扩增PyPPM6蛋白功能区(359-644 aa),克隆入pET32a(+)载体。IPTG诱导PyPPM6重组蛋白表达,免疫小鼠后收集抗-PyPPM6免疫血清。ELISA和Western Blot检测血清中抗体效价和特异性。体外实验观察免疫血清对配子体出丝、动合子形成和转化率及囊合子形成的影响。结果:成功表达PyPPM6重组蛋白;抗-PyPPM6免疫血清抗体滴度为1∶64 000;与对照组相比,抗-PyPPM6免疫血清可使配子体出丝减少78.8%,动合子减少78.7%,动合子转化率降低55.1%,蚊胃内卵囊减少40.4%。结论:PyPPM6蛋白具有较强免疫原性。抗-PyPPM6免疫血清具有良好的传播阻断效果。     

间日型猴疟血小板动态变化及药物干预观察

目的 观察恒河猴感染间日型猴疟后原虫密度消长与PLT数值的关系及抗菌药物和抗疟药治疗后对PLT变化的影响.方法 健康猴1只,经血液感染间日型猴疟后2 d开始采血检查疟原虫及PLT计数.发现疟原虫后24 d,阿奇霉素治疗3 d,总量为1500 mg;发现疟原虫后30 d,青蒿琥酯治疗5 d,总量为194.4 mg.观察治疗期间疟原虫与PLT变化规律.同时设健康对照猴1只.结果 实验猴被感染疟原虫前PLT计数为240×109/L,感染后,当血疟原虫为2/100 WBC时,PLT计数为540×109/L.感染猴原虫密度波动在(1～60)/100 WBC,而PLT数值维持在(130～150)×109/L之间.实验猴灌服阿奇霉素后,原虫密度波动在(16～64)/100 WBC之间,而平均PLT计数回升到234.5×109/L,接受青蒿琥酯治疗64 h后血检未发现原虫,PLT计数平均值已回升到247×109/L.结论 疟原虫感染后PLT计数下降,阿奇霉素和青蒿琥酯治疗猴疟能较快提升PLT计数.

Abstract：

Objective To observe platelet dynamics in a monkey infected with Plasmodium cynomolgi before and after treatments with antibiotics and antimalarial drug. Methods One experimental monkey was examined for parasite density and platelet count 2 days after parasite inoculation. Observation without treatment continued for 24 days after the parasite was detected in the blood sample of the monkey. Then the monkey was treated with Azithromycin (total 1500 mg) for 3 days. Thirty days after parasite detection in the blood, the monkey was treated with Artesunate for 5 days. Parasite density and platelet count were monitored daily during treatments. The result was compared with that from a healthy monkey as control. Results The experimental monkey's platelet count was 240× 109/L before infection. When parasite density was 2/100 white blood cells (WBC),platelet count increased to 540 × 109/L. During the subsequent period of infection, parasite density fluctuated at (1-60)/100 WBC, and the platelet count reduced to a persistent level of (130-150)×109/L. After the infected monkey was treated with Azithromycin, parasite density reduced initially but subsequently fluctuated at (16-64)/100 WBC. Meanwhile, platelet count was restored to 234.5 × 109/L.The infected monkey was treated with Artesunate and parasite clearance time was 64 hours, and the mean platelet count was 247 × 109/L after treatment. Conclusion Azithromycin and Artesunate treatment have direct influence on the recovery of platelet counts during malaria infection in monkeys.     

伯氏疟原虫丝/ 苏氨酸磷酸酶6 抗血清对原虫有性阶段发育抑制作用的研究

目的:探讨伯氏疟原虫丝/苏氨酸磷酸酶6(PPP6)作为传播阻断疫苗候选抗原的可行性。方法:PCR扩增PPP6蛋白全长编码基因并克隆入p ET32a(+)载体。IPTG诱导PPP6重组蛋白的表达,纯化后皮下免疫小鼠,收集抗PPP6免疫血清。ELISA和Western blot检测抗PPP6免疫血清效价和特异性。实验观察免疫血清对配子体出丝、动合子和囊合子发育的影响。结果:成功诱导PPP6重组蛋白表达,抗PPP6免疫血清抗体效价为1∶3 200;与对照组相比,抗PPP6免疫血清可显著抑制配子体出丝(P0. 000 1);动合子数目和动合子转化率分别显著降低65. 3%和42. 07%(P0. 000 1);抗PPP6血清1∶5倍稀释时,囊合子形成数量减少68. 91%(P0. 000 1)。结论:PPP6蛋白具有良好的免疫原性和抗原性。抗PPP6免疫血清具有明显的传播阻断效果。