Ismail M M, Weil G J, Jayasinghe K S, Premaratne U N, Abeyewickreme W, Rajaratnam H N, Sheriff M H, Perera C S, Dissanaike A S
Faculty of Medicine, University of Colombo, Sri Lanka.
Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):684-8. doi: 10.1016/s0035-9203(96)90437-x.
In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.
在一项针对37名无症状微丝蚴血症患者(每毫升至少400条微丝蚴[mf])的双盲试验中,这些患者感染了班氏吴策线虫,将每两周服用12剂、剂量为400微克/千克的伊维菌素(伊维菌素组)的安全性、耐受性和杀成虫效果,与每两周服用12剂、剂量为10毫克/千克的乙胺嗪(DEC)(DEC组)在治疗后129周内进行了比较。出于伦理原因,设立了一个对照组(LDIC组),用低剂量伊维菌素清除微丝蚴血症。高剂量多次服用的伊维菌素和DEC耐受性良好且临床安全。通过微丝蚴血症的长期清除、局部病变的出现以及基于单克隆抗体AD12的抗原捕获酶联免疫吸附测定法检测到的循环班氏吴策线虫成虫抗原的减少来评估杀成虫效果。伊维菌素治疗后微丝蚴计数下降比DEC治疗后更快,但在第4周后这些组中的微丝蚴残留水平相当。相反,DEC治疗后丝虫抗原水平下降比伊维菌素治疗后更快,但在12周后的所有时间点,这些组中的残留抗原低水平在统计学上相当。在所有3个治疗组中均观察到对治疗的轻度、自限性全身反应。在DEC组和伊维菌素组的几名受试者中观察到局部反应,如阴囊结节的出现。这些结果表明,高剂量伊维菌素和DEC对班氏吴策线虫均具有显著的杀成虫活性,但这些强化治疗方案均未始终实现完全治愈。因此,需要新药或给药方案来实现杀死大多数患者体内所有丝虫寄生虫的目标。