Gichuki C W, Nantulya V M, Sayer P D
Kenya Trypanosomiasis Research Institute, Kikuyu.
Trop Med Parasitol. 1994 Sep;45(3):237-42.
Thirty eight Trypanosoma brucei rhodesiense-infected vervet monkeys (Cercopithecus aethiops) in the late (meningoencephalitic) stage of disease, treated with various trypanocidal drugs, were monitored for a period of more than 600 days to assess the rate of clearance of trypanosome antigens from serum and cerebrospinal fluid (CSF). There was a complete but gradual reduction in antigen titres, as assessed by ELISA, in animals treated intravenously with melarsoprol, the standard drug for the late stage disease. In 8 of the 9 monkeys treated with melarsoprol, the antigen titres, as assessed by optical density values, dropped by 50% within 252 days (mean value 68 days for antigens in CSF and 116 for serum) following treatment. The remaining animal in this group, that displayed persistent antigenaemia, had been treated with a sub-curative drug dosage level. Thus, if time to 50% reduction in antigen levels were to be taken as an index to predict cure, the follow-up period after melarsoprol treatment could have been reduced from 600 to 252 days for 8 of the 9 animals, leaving only one animal for further follow up. The animals treated with experimental drug combinations displayed a variable picture. Five monkeys showed a persistence of antigens in both serum and CSF throughout the observation period, suggesting failure of the drugs to cure the infection. Parasitologically confirmed relapse of the infection was indeed observed in all the five monkeys. In some monkeys, the parasite antigens eventually cleared from serum and CSF completely, but this took a longer time duration than in the melarsoprol treated animals; others showed persistence of parasite antigens in serum, but the parasites were not detected in blood or CSF throughout the entire follow-up period. These results suggest that the experimental drug combinations used were not effective in clearing the parasites from cryptic foci and hence the persistence of antigens in serum and/or CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
38只处于疾病晚期(脑膜脑炎期)的感染罗德西亚布氏锥虫的黑长尾猴(非洲绿猴),用各种杀锥虫药物进行治疗,并监测600多天,以评估血清和脑脊液中锥虫抗原的清除率。通过酶联免疫吸附测定(ELISA)评估,静脉注射治疗晚期疾病的标准药物美拉胂醇的动物,其抗原滴度出现了完全但逐渐的降低。在用美拉胂醇治疗的9只猴子中,8只猴子经光密度值评估,在治疗后252天内抗原滴度下降了50%(脑脊液中抗原平均下降时间为68天,血清中为116天)。该组中其余一只持续存在抗原血症的动物,接受的是低于治愈剂量水平的药物治疗。因此,如果将抗原水平降低50%的时间作为预测治愈的指标,那么对于9只动物中的8只,美拉胂醇治疗后的随访期可以从600天缩短至252天,仅留一只动物作进一步随访。接受实验性药物组合治疗的动物情况各异。5只猴子在整个观察期内血清和脑脊液中都持续存在抗原,表明药物未能治愈感染。实际上在所有5只猴子中都观察到了经寄生虫学证实的感染复发。在一些猴子中,寄生虫抗原最终从血清和脑脊液中完全清除,但这比接受美拉胂醇治疗的动物花费的时间更长;其他猴子血清中寄生虫抗原持续存在,但在整个随访期内血液或脑脊液中均未检测到寄生虫。这些结果表明,所使用的实验性药物组合在清除隐匿病灶中的寄生虫方面无效,因此血清和/或脑脊液中抗原持续存在。(摘要截短于250字)