Background Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. Methods The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. Results In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 μg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. Conclusions Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.
Background In China the highest prevalence of echinococcosis is in Tibet Autonomous Region (TAR). The government has issued documents and implemented comprehensive prevention and control measures focusing on controlling the source of infection of echinococcosis. It was very important to understand the implementation and effect of infectious source control measures. The purpose of this study was to examine the implementation of measures to control infectious source (domestic and stray dogs) in TAR and to assess their effectiveness. Methods We collected data on domestic dog registration and deworming and stray dog sheltering in 74 counties/districts in the TAR from 2017 to 2019. Fecal samples from domestic dogs were collected from randomly selected towns to determine Echinococcus infection in dogs using coproantigen ELISA. We analyzed the data to compare the canine rate of infection between 2016 and 2019. The data analysis was performed by SPSS statistical to compare dog infection rate in 2016 and 2019 by chi-square test, and ArcGIS was used for mapping. Results From 2017 to 2019, 84 stray dog shelters were built in TAR, and accumulatively 446,660 stray or infected dogs were arrested, sheltered, or disposed of. The number of domestic dogs went downward, with an increased registration management rate of 78.4% (2017), 88.8% (2018), and 99.0% (2019). Dogs were dewormed 5 times in 2017, 12 times in 2018, and 12 times in 2019. The dog infection rate was 1.7% (252/14,584) in 2019, significantly lower than 7.3% (552/7564) from the survey of echinococcosis prevalence in Tibet in 2016 (P < 0.05). Conclusion Between 2017 and 2019, the number of stray dogs and infection rate of Echinococcus spp. in domestic dogs decreased significantly, indicating that dogs were effectively controlled as a source of infection in TAR and reflecting a significant decrease in the risk of echinococcosis transmission. Graphical Abstract
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