National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, and National Center for Tropical Diseases Research, Shanghai, the People's Republic of China.
Key Laboratory of Parasite and Vector Biology, Ministry of Public Health, and WHO Collaborating Centre for Tropical Diseases, Shanghai, the People's Republic of China.
PLoS Negl Trop Dis. 2018 Nov 19;12(11):e0006934. doi: 10.1371/journal.pntd.0006934. eCollection 2018 Nov.
Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years, with a 30-fold increase in global incidence. Dengue vector control is a key component for the dengue control strategy, since no absolutely effective vaccine or drug is available yet. However, the rapid rise and spread of mosquito insecticide resistance have become major threats to the efficiency of insecticide-based vector control activities. Thus, innovative vector control tools are badly needed. This study aims to confirm the antivirus effectiveness of ivermectin on dengue virus type 2 (DENV-2) in Aedes albopictus (Skuse, 1894), then to explore its potential use in the combating to the dengue epidemics.
Aedes albopictus were first infected with DENV-2 in human whole blood, and at the fourth day after infectious blood feeding, they were divided into eight groups. Seven of them were held for six days with access to 0, 2, 4, 8, 16, 32 and 64 ng/ml ivermectin, respectively, and the last one was set as a historical control group, which was stored at -80°C until being detected at the same time with the other groups. Each mosquito was detected using real-time fluorescent RT-PCR kit. DENV-2 RNA concentration (copies/ml) and infection rate in each group were compared.
Both of quantitatively and qualitatively inhibiting effects of ivermectin have been detected in this study. Generally, DENV-2 replicated well in Aedes albopictus without ivermectin intervention, whose virus loads exhibited significantly higher when the mosquitoes were holding from 4 days to 10 days after infectious blood feeding. In contrast, with the treatment of ivermectin, the infection rate was reduced by as much as 49.63%. The regression equation between infection rates (Y2) and ivermectin concentration log2 values (X2) was obtained as Y2 = 91.41-7.21*X2 with R2 = 0.89.
Ivermectin can directly or indirectly inhibit DENV-2 multiplication in Aedes albopictus. Moreover, the actual concentration for application in zooprophylaxis needs to be confirmed in the further field trials.
登革热是过去 50 年来传播速度最快的蚊媒病毒性疾病,其全球发病率增加了 30 倍。登革热媒介控制是登革热控制策略的一个关键组成部分,因为目前尚无绝对有效的疫苗或药物。然而,蚊子杀虫剂抗性的迅速上升和传播已成为基于杀虫剂的媒介控制活动效率的主要威胁。因此,急需创新的媒介控制工具。本研究旨在确认伊维菌素对登革热病毒 2 型(DENV-2)在白纹伊蚊(Skuse,1894)中的抗病毒效果,然后探索其在登革热流行中的潜在用途。
首先用人类全血感染白纹伊蚊,在感染性血液喂养后的第四天,将其分为八组。其中七组分别用 0、2、4、8、16、32 和 64ng/ml 伊维菌素处理 6 天,最后一组作为历史对照组,在相同时间与其他组一起储存于-80°C。每组均用实时荧光 RT-PCR 试剂盒进行检测。比较各组伊蚊体内 DENV-2 RNA 浓度(拷贝/ml)和感染率。
本研究检测到伊维菌素具有定量和定性的抑制作用。一般来说,没有伊维菌素干预时,DENV-2 在白纹伊蚊中复制良好,在感染性血液喂养后 4 天至 10 天内,其病毒载量明显升高。相比之下,用伊维菌素处理后,感染率降低了 49.63%。获得感染率(Y2)与伊维菌素浓度对数 2 值(X2)之间的回归方程为 Y2=91.41-7.21*X2,R2=0.89。
伊维菌素可直接或间接抑制白纹伊蚊体内 DENV-2 的增殖。此外,在进一步的现场试验中需要确定实际应用于动物预防的浓度。