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Background: MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown., Results: Using Illumina next generation sequencing technology, we sequenced at the genome-wide level three small RNA populations from the adult, protoscolex and cyst membrane of E. granulosus. A total of 94 pre-miRNA candidates (coding 91 mature miRNAs and 39 miRNA stars) were in silico predicted. Through comparison of expression profiles, we found 42 mature miRNAs and 23 miRNA stars expressed with different patterns in the three life stages examined. Furthermore, considering both the previously reported and newly predicted miRNAs, 25 conserved miRNAs families were identified in the E. granulosus genome. Comparing the presence or absence of these miRNA families with the free-living Schmidtea mediterranea, we found 13 conserved miRNAs are lost in E. granulosus, most of which are tissue-specific and involved in the development of ciliated cells, the gut and sensory organs. Finally, GO enrichment analysis of the differentially expressed miRNAs and their potential targets indicated that they may be involved in bi-directional development, nutrient metabolism and nervous system development in E. granulosus., Conclusions: This study has, for the first time, provided a comprehensive description of the different expression patterns of miRNAs in three distinct life cycle stages of E. granulosus. The analysis supports earlier suggestions that the loss of miRNAs in the Platyhelminths might be related to morphological simplification. These results may help in the exploration of the mechanism of interaction between this parasitic worm and its definitive and intermediate hosts, providing information that can be used to develop new interventions and therapeutics for the control of cystic echinococcosis.

Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavβ1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.

Dogs are pivotal in Echinococcus granulosus transmission to humans, and dog vaccination provides a very practical and cost-effective prevention strategy. We vaccinated dogs with soluble native proteins isolated from protoscoleces of E. granulosus and induced significant suppression of worm growth and egg production. Accordingly, we tested for vaccine efficacy using recombinant proteins derived from a developmentally regulated gene family (egM) specifically expressed in mature adult E. granulosus worms. Three egM genes--egM4, egM9, and egM123--were subcloned into an expression vector that expressed the molecules as soluble glutathione S-transferase (GST) fusion proteins in Escherichia coli. The 3 fusion proteins were purified for dog vaccination trials (3 doses of 80 microg/protein/dog) in which the dogs were challenged and then necropsied 45 days after infection. Compared with worms in the control dogs that received GST, the 3 recombinant proteins induced a very high level of protection (97%-100%) in terms of suppression of worm growth and, especially, of egg development and embryogenesis. We have thus shown that vaccination of the dog host against E. granulosus is feasible when recombinant proteins are used. Because the egg stage is crucial in the echinococcal life cycle, successful suppression of egg development by vaccination would halt transmission to intermediate hosts, thereby effecting long-term control.

Background: Cystic echinococcosis is a life-threatening disease caused by the larval stages of the dog tapeworm Echinococcus granulosus. Protoscoleces (PSCs) of this worm have the ability of bi-directional development to either larval cysts or strobilar adult worms. However, the molecular mechanisms underlying this development process are unknown. Results: RNA and small RNAs sequencing was employed to characterize the gene and miRNA expression at 0–24 h and 7–14 days in the bi-directional development of PSCs. A total of 963 genes and 31 miRNAs were differentially expressed in the early development of PSCs to adult worms whereas 972 genes and 27 miRNAs were differentially expressed in the early development of PSCs to cysts. Pairwise comparison between the two developmental patterns showed that 172 genes and 15 miRNAs were differentially expressed at three time-points. Most of these genes were temporally changed at 24 h or 7 days. GO enrichment analysis revealed that the differentially expressed genes in early adult worm development are associated with nervous system development and carbohydrate metabolic process; whereas, the differentially expressed genes in early cystic development are associated with transmembrane transporter activity and nucleoside triphosphatase activity. In addition, miR-71 and miR-219 regulated genes are likely involved in oxidation reduction in adult worm development. Conclusion: The early stages of bi-directional development in E. granulosus PSCs are controlled by miRNAs and genes likely associated with nervous system development and carbohydrate metabolic process. ATP-dependent transporter genes are associated with cystic development. These results may be important for exploring the mechanisms underlying early development in E. granulosus providing novel information that can be used to discover new therapeutics for controlling cystic echinococcosis. [ABSTRACT FROM AUTHOR]

Background: Cystic hydatid disease (CHD) is a global parasitic zoonosis caused by the dog tapeworm, Echinococcus granulosus. The disease is hyperendemic in western China because of poor economic development; limited community knowledge of CHD; widespread, small-scale household animal production; home killing of livestock; and the feeding of dogs with uncooked offal. Methodology/Principal Findings: A control program focusing on monthly praziquantel (PZQ) treatment of all registered dogs and culling unwanted and stray dogs has been designed to control CHD in hyperendemic areas in China. A pilot field control project in two counties (Hutubi and Wensu) in Xinjiang, China showed that after 4 years of treatment, the prevalence of dogs with E. granulosus was reduced from 14.7% and 18.6%, respectively, to 0%, and this caused a 90%–100% decrease of CHD in sheep born after commencement of the control program. Conclusions/Significance: The strategy aimed at preventing eggs being released from dogs into the environment by treating animals before adult tapeworms are patent can decrease E. granulosus transmission and considerably reduce hyperendemic CHD. Monthly treatment of dogs with PZQ and culling unwanted and stray dogs have been shown to be an efficient, highly cost-effective and practicable measure for implementation in rural communities. As a result, the Chinese Ministry of Health has launched an extensive CHD control program in 117 counties in western China using this control strategy. Author Summary: Cystic hydatid disease (CHD), caused by the dog tapeworm, Echinococcus granulosus, is hyperendemic in western China. However, until recently the disease had been grossly neglected there due primarily to a weak economy and the primitive control measures used. The situation is now changing because of China's growing economy and the availability of the cheap and effective drug praziquantel (PZQ), which makes control programs practicable through mass preventive treatment of dogs in these endemic areas. In this study, we used a strategy to prevent parasite eggs from being released into the environment by dosing dogs monthly with baited PZQ and culling unwanted and stray dogs, as a result of which infection in humans and domestic animals can be reduced considerably. We undertook a pilot control study in two counties involving a population of 255,504 in 52,300 households and 30,380 dogs in Xinjiang, China, and showed that monthly PZQ treatment of dogs is an efficient, practicable, and affordable control method for communities to reduce considerably hyperendemic CHD. As a result, the Chinese Ministry of Health has extended the control measure to 117 counties in western China. [ABSTRACT FROM AUTHOR]

At least 270 million people (58% of the total population) are at risk of cystic echinococcosis (CE) in Central Asia including areas of Mongolia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Afghanistan, Iran, Pakistan and western China. The annual surgical incidence rate in Uzbekistan and Tadjikistan has been estimated to be as high as 25–27 cases/100,000 with the highest prevalence reaching 10% (range from 0.8 to 11.9%) in some Tibetan communities in western China. Echinococcus transmission in the region is largely associated with social factors including limited community knowledge of echinococcosis, small-scale household animal production, home killing of livestock, and the feeding of dogs with uncooked offal. Alveolar echinococcosis (AE) is also endemic in Central Asia and is recognized as a major problem in some Tibetan communities with up to 6% of villagers infected in some villages. In western China, 5–30% of the population are seropositive against E. granulosus antigens, indicating that a large number of individuals have been exposed to the parasite. Although echinococcosis control programs have been initiated in some countries in Central Asia, control efforts are generally fragmented and uncoordinated. Monthly deworming of dogs with praziquantel (PZQ), as a key measure to control the Echinococcus parasites, has been used in western China. However, the approach has proven difficult in local semi-nomadic communities. Additional control measures including health education, domestic livestock animal treatment/vaccination and dog vaccination are needed in CE-endemic areas to accelerate progress. [ABSTRACT FROM AUTHOR]