Kocken C H, van der Wel A, Rosenwirth B, Thomas A W
Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Exp Parasitol. 1996 Dec;84(3):439-43. doi: 10.1006/expr.1996.0132.
Plasmodium vivax is, next to P. falciparum, the second important human malaria parasite. In view of reports on developing chloroquine resistance, research on new drugs that are active against P. vivax is necessary. Due to a requirement for continuous addition of reticulocytes, long-term in vitro culture of P. vivax is not practicable. Conventional drug assays, i.e., culturing for a time equivalent to one asexual cycle of development in the presence of drugs, and then measuring propagation, are therefore not readily performed. In this report the in vitro susceptibility of P. vivax to cyclosporin A and a new, nonimmunosuppressive derivative, SDZ NIM 811, was investigated using parasite material obtained from an infected Aotus monkey. The assay was initiated with blood containing ring-stage parasites and was ended when parasites were multinucleate, but before merozoite release. The results were compared with the in vitro susceptibility of P. falciparum to these drugs in a conventional and a short assay. As an indicator of parasite propagation [3H]hypoxanthine incorporation was measured. The susceptibility of P. vivax to cyclosporins was found to be intermediate to that of P. falciparum in the conventional and in the much less sensitive short assay, and SDZ NIM 811 proved to be as active as cyclosporin A.
间日疟原虫是仅次于恶性疟原虫的第二重要的人类疟原虫。鉴于有关氯喹耐药性发展的报道，有必要开展针对间日疟原虫的新药研究。由于需要持续添加网织红细胞，间日疟原虫的长期体外培养不可行。因此，常规的药物检测，即在药物存在的情况下培养相当于一个无性发育周期的时间，然后测量繁殖情况，不易进行。在本报告中，利用从受感染的夜猴获得的寄生虫材料，研究了间日疟原虫对环孢菌素A和一种新的非免疫抑制衍生物SDZ NIM 811的体外敏感性。检测从含有环状体期寄生虫的血液开始，当寄生虫多核时结束，但在裂殖子释放之前。将结果与恶性疟原虫在常规检测和短检测中对这些药物的体外敏感性进行了比较。以[3H]次黄嘌呤掺入作为寄生虫繁殖的指标进行测量。发现在常规检测和敏感性低得多的短检测中，间日疟原虫对环孢菌素的敏感性介于恶性疟原虫之间，并且SDZ NIM 811被证明与环孢菌素A活性相同。
