Herrick Jesica A, Legrand Fanny, Gounoue Raceline, Nchinda Godwin, Montavon Céline, Bopda Jean, Tchana Steve Mbickmen, Ondigui Bienvenu Etogo, Nguluwe Konrad, Fay Michael P, Makiya Michelle, Metenou Simon, Nutman Thomas B, Kamgno Joseph, Klion Amy D
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon.
Clin Infect Dis. 2017 Apr 15;64(8):1017-1025. doi: 10.1093/cid/cix016.
Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology.
Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment.
Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups.
Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology.
NCT01593722.
在用乙胺嗪(DEC,治疗罗阿丝虫病的首选药物)或伊维菌素(IVM,在非洲用于大规模药物管理计划以控制盘尾丝虫病和淋巴丝虫病)治疗的罗阿丝虫感染个体中观察到了严重不良反应。在本研究中,比较了单剂量DEC或IVM治疗后的临床和免疫反应,以评估这些反应是否具有相同的潜在病理生理学机制。
12名罗阿丝虫病患者且微丝蚴计数<2000 mf/mL,被随机分配接受单剂量DEC(8 mg/kg)或IVM(200 μg/kg)。在治疗后4、8、24、48和72小时以及5、7、9和14天进行临床和实验室评估。
DEC或IVM治疗后的不良事件相似,但在接受DEC的受试者中出现得更早,这与DEC组微丝蚴清除更快且更彻底的趋势一致。在治疗后最初24小时内短暂升高(IVM后)或降低(DEC后)后,两组嗜酸性粒细胞计数均显著升高,在DEC组第5天达到峰值,在IVM组第9天达到峰值。通过CD69表面表达和嗜酸性粒细胞颗粒蛋白血清水平评估,两组治疗后血清白细胞介素5水平和嗜酸性粒细胞活化均增加。
尽管治疗后最初24小时内嗜酸性粒细胞和淋巴细胞计数存在差异,但血液学和免疫学变化的总体模式表明,DEC和IVM治疗后的反应具有共同的病理生理学机制。
NCT01593722。