Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel
Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel
复制标题
DOI：
10.4269/ajtmh.1996.55.214
复制
发表时间：
1996-08-01
影响因子：
3.3
通讯作者：
Bennett, JL
中科院分区：
文献类型：
--
作者：
Ismail, M;Metwally, A;Bennett, JL
为了确定是否出现了耐药性/耐受性的抗结核药物吡喹酮（PZQ）在尼罗河三角洲地区的埃及村庄，在那里它已被广泛使用，我们治疗了1，607感染的村民，并观察到321名村民需要一个额外的治疗，而89名村民需要两个额外的治疗; 24的89人仍然没有治愈后，第三剂这种药物。从粪便样本中分离出卵子，并从7名在单剂PZQ后成功治疗的村民和14名在两剂或三剂PZQ后未成功治疗的村民的血液中分离出血清。这些卵被用于在小鼠中建立感染（分离株），然后在感染后六周用三种不同剂量的PZQ进行治疗。使用血清来测定感染者中PZQ的浓度。来自14名村民的鸡蛋分离物中有三种不能用三剂PZQ治疗，与从单剂PZQ治愈的患者中获得的分离物相比，这些分离物在统计学上对PZQ的反应较低。单次给药后成功治疗的患者与两次或三次给药后未成功治疗的患者的药代动力学参数相同，从而消除了受感染村民中治愈率差是由于PZQ生物利用度降低的可能性。从我们的数据来看，大约1-2.4%接受PZQ治疗的村民无法完全治愈他们的感染，每1,000名接受治疗的村民中有3名可能携带能够耐受高剂量PZQ的寄生虫。这些结果表明，PZQ在埃及尼罗河三角洲地区的广泛使用并未导致该药物疗效的显著变化。对PZQ不太敏感的染色体的分离可能是一个警告信号，需要建立一个类似于我们开发的监测系统，以确定PZQ不能治愈的患者比例是否正在增加。此外，如果该百分比开始随着时间的推移而增加，则通过本研究中报告的药理学方法确定从未治愈患者中获得的分离株是否对PZQ越来越耐药将是至关重要的。
To determine if resistance/tolerance to the antischistosomal drug praziquantel (PZQ) is appearing in Egyptian villages within the Nile delta region, where it has been used extensively, we treated 1,607 infected villagers and observed that 321 required one additional treatment while 89 villagers required two additional treatments; 24 of the 89 were still not cured after a third dose of this drug. Eggs were isolated from fecal samples and serum was isolated from blood taken from seven villagers successfully treated after a single dose and from 14 villagers not successfully treated after two or three doses of PZQ. The eggs were used to establish infections in mice (isolates), which were then treated six weeks after infection with three different doses of PZQ. Serum was used to determine the concentration of PZQ in the infected humans. Three of the egg isolates from the 14 villagers that could not be treated with three doses of PZQ produced infections in mice that were statistically less responsive to PZQ when compared with isolates obtained from patients that were cured after a single dose of this drug. Pharmacokinetic parameters were the same in patients treated successfully after a single dose versus those not treated successfully following two or three doses, thus eliminating the possiblity that poor cure rates among infected villagers was due to a decrease in PZQ bioavailability. From our data, approximately 1-2.4% of the villagers treated with PZQ could not be completely cured of their infection and three of every 1,000 treated villagers may harbor parasites that can tolerate high doses of PZQ. These results indicate that the extensive use of PZQ in the Nile delta region of Egypt has not resulted in a dramatic change in the efficacy of this drug. The isolation of schistosomes that are less susceptible to PZQ may be a warning signal that will require establishment of a monitoring system, similar to the one we have developed, to determine if the precentage of patients that cannot be cured by PZQ is increasing. Furthermore, if that percentage begins to increase over time, it will be critical to determine, by pharmacologic methods reported in this study, whether isolates obtained from uncured patients are becoming increasingly resistant to PZQ.