Disseminated alveolar echinococcosis resembling metastatic malignancy: a case report

Nail, Laura Caire; Reimundes, Ezequiel Rodríguez; Galluzzo, Christelle Weibel; Lebowitz, Dan; Ibrahim, Yasmine Lucile; Lobrinus, Johannes Alexander; Chappuis, François

doi:10.1186/s13256-017-1279-2

Cited by 16 publications

(9 citation statements)

References 11 publications

(16 reference statements)

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“…Alveolar echinococcosis is often mistaken for a neoplastic growth, given its propensity for widespread organ infiltration with metastases (2). E. multilocularis may also imitate other diseases, including hepatic carcinoma, cirrhosis and tuberculosis, which may lead to improper diagnostic testing and delayed treatment (3,9,10). Diagnosis is confirmed based on a combination of clinical findings, epidemiological data, imaging, histopathology and/or nucleic acid detection and serology (8).…”

Section: How Humans Become Infectedmentioning

confidence: 99%

Surveillance of Echinococcus tapeworm in coyotes and domestic dogs in Winnipeg, Manitoba

Tse

Bullard

Rusk

et al. 2019

CCDR

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Background: The Echinococcus species, including E. multilocularis and E. canadensis, are tapeworms that primarily infect canids such as dogs, foxes and coyotes, but which can also infect humans. In humans, E. multilocularis can cause alveolar echinococcosis; a serious condition that mimics metastatic malignancy and has a poor prognosis. It is known that coyotes in rural Manitoba are infected with Echinococcus species, but it is not known if coyotes in peri-urban areas are also infected. Objectives: To document and map Echinococcus species in wild canids and domestic dogs in Winnipeg, Manitoba (Canada). Methods: There were 169 fecal samples collected between April 18 and June 1, 2018. These included 44 samples of domestic dog feces, 122 of coyote scat, one of fox scat and two of coyote colonic tissue specimens. Samples were frozen (-80°C) for at least 72 hours to inactivate tapeworm ova. Polymerase chain reaction analyses of E. multilocularis and E. canadensis were performed on all frozen samples. Results: Echinococcus multilocularis-positive samples were detected in nine (10.6%) of 85 locations, with one positive sample in a suburban Winnipeg dog park and two positive samples in a popular provincial park. No dog samples were positive for E. multilocularis; one sample was positive for E. canadensis. In contrast, nine coyote samples (7.3%) were positive for E. multilocularis and eight samples (6.5%) were positive for E. canadensis. The one fox sample was positive for each. Overall, six samples (3.6%) were positive for both infections. Conclusion: This is the first confirmation of the presence of E. multilocularis in coyote feces in the metropolitan area of Winnipeg, Manitoba. In light of the risk this could pose to domestic dogs and human health, periodic surveillance that maps the distribution of this tapeworm could inform the need for additional public health actions.

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Section: How Humans Become Infectedmentioning

confidence: 99%

Surveillance of Echinococcus tapeworm in coyotes and domestic dogs in Winnipeg, Manitoba

Tse

Bullard

Rusk

et al. 2019

CCDR

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“…Human AE is clinically/symptomatically often compared to liver cancer, since metacestodes exhibit progressive growth of lesions and a capacity to spread to other organs by metastatis formation [5, 72]. Nineteen out of the 28 dysregulated miRNAs identified in our study have been reported to be also affected in hepatocellular carcinoma (HCC) which is the most common type of primary liver cancer in adults [73–81].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hepatic MicroRNAs in Response to Early Stage Echinococcus multilocularis Egg Infection in C57BL/6 mice

Boubaker

Strempel

Hemphill

et al. 2019

Preprint

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22In this study, we present a comprehensive analysis of the hepatic miRNA transcriptome in 23 mice suffering from experimental primary alveolar echinococcosis (AE), a parasitic infection 24 caused upon ingestion of Echinococcus multilocularis (E. multilocularis) eggs. At one month 25 post-infection, infected C57BL/6 mice, along with non-infected control mice, were 26 euthanized. Subsequently livers were collected and used for small RNA library preparation 27 and next-generation sequencing (NGS). The most significantly dysregulated hepatic miRNAs 28 were validated by Stem-loop RT-qPCR. We identified 28 miRNAs with significantly altered 29 expression levels upon infection with E. multilocularis. Of these, 9 were up-regulated (fold 30 change (FC) ≥ 1.5) and 19 were down-regulated (FC ≤ 0.66) as compared to the non-infected 31 controls. In infected liver tissues, mmu-miR-148a-3p and mmu-miR-101b-3p were 8-and 6-32 fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 33 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels 34 were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 35 1.8). Down-regulated miRNAs were highly enriched in Reactome and KEGG pathways of 36 angiogenesis and fatty acids biosynthesis. Moreover, relative mRNA expression levels of 37 three pro-angiogenic (VEGFA, MTOR and HIF1-α) and two lipogenic (FASN and ACSL1) 38 genes were significantly higher in livers of E. multilocularis infected mice. 39Lastly, we studied the issue related to functionally mature arm selection preference (5p and/or 40 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm 41 selection preferences in normal versus infected liver tissues. Our study provides first evidence 42 of miRNA involvement in liver pathogenesis during AE. Our future research will focus on the 43 characterization of miRNA transcriptome patterns in more advanced AE-stages towards the 44 assessment of microRNA therapy for AE, and experimentally address functional 45 characteristics of selected features presently found. 48of microRNAs (miRNAs), a class of small non-coding RNAs involved in negative regulation 49 of gene expression. Herein, we revealed that significant alterations of miRNA expression 50 occurred in murine liver subsequently to experimental infection with Echinococcus 51 multilocularis (E. multilocularis) eggs when compared to non-infected controls. 52At the early stage of murine AE, hepatic miRNAs were mainly downregulated. Respective 53 target genes of the most extensively downregulated miRNAs were involved in angiogenesis 54 and fatty acid synthesis. Indeed, angiogenic and lipogenic genes were found to be 55 significantly higher expressed in E. multilocularis infected livers relative to non-infected 56 controls. These boosted cellular pathways are advantageous for development of the E. 57 multilocularis metacestodes, since this larval stage is not able to undertake de novo fatty acid 58 synthesis, and angiogenesis ...

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“…The ideal treatment for AE is still radical surgery, accompanied by chemotherapy. However, surgery is reserved for early-stage disease when lesions can be completely resected with a safe margin (≥ 2 cm) of unaffected tissue and no distant metastases [ 7 ]. Because most cases are found at an advanced stage, only 35% of patients can undergo curative surgery [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis

Liu

Fan

et al. 2021

Parasites Vectors

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Background Alveolar echinococcosis (AE) is a chronic zoonosis caused by the larval form of Echinococcus multilocularis (E. multilocularis). Current chemotherapy against AE has relied on albendazole and mebendazole, which only exhibit parasitostatic and not parasiticidal efficacy. Therefore, novel compounds for the treatment of this disease are needed. Methods Phosphoglucose isomerase (PGI) assays were used for compound screening of seven neonicotinoids. The anti-parasitic effects of thiacloprid were then evaluated on E. multilocularis metacestode vesicles, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFF) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. Glucose consumption in E. multilocularis protoscoleces and germinal cells was assessed by measuring uptake of 2-deoxyglucose (2-DG). Molecular docking was used to evaluate the potential binding sites of thiacloprid to acetylcholine receptors. In vivo efficacy of thiacloprid was evaluated in mice by secondary infection with E. multilocularis. In addition, ELISA and flow cytometry were used to evaluate the effects of cytokines and T lymphocyte subsets after thiacloprid treatment. Furthermore, collagen deposition and degradation in the host lesion microenvironment were evaluated. Results We found that thiacloprid is the most promising compound, with an IC50 of 4.54 ± 1.10 μM and 2.89 ± 0.34 μM, respectively, against in vitro-cultured E. multilocularis metacestodes and germinal cells. Thiacloprid was less toxic for HFF and RH mammalian cell lines than for metacestodes. In addition, thiacloprid inhibited the acetylcholinesterase activity in protoscoleces, metacestodes and germinal cells. Thiacloprid inhibited glucose consumption by protoscoleces and germinal cells. Subsequently, transmission electron microscopy revealed that treatment with thiacloprid damaged the germinal layer. In vivo, metacestode weight was significantly reduced following oral administration of thiacloprid at 15 and 30 mg/kg. The level of CD4+ T lymphocytes in metacestodes and spleen increased after thiacloprid treatment. Anti-echinococcosis-related cytokines (IL-2, IL-4, IL-10) were significantly increased. Furthermore, thiacloprid inhibited the expression of matrix metalloproteinases (MMPs 1, 3, 9, 13) and promoted collagen deposition in the host lesion microenvironment. Conclusions The results demonstrated that thiacloprid had parasiticidal activity against E. multilocularis in vitro and in vivo, and could be used as a novel lead compound for the treatment of AE. Graphical abstract

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Disseminated alveolar echinococcosis resembling metastatic malignancy: a case report

Cited by 16 publications

References 11 publications

Surveillance of Echinococcus tapeworm in coyotes and domestic dogs in Winnipeg, Manitoba

Surveillance of Echinococcus tapeworm in coyotes and domestic dogs in Winnipeg, Manitoba

Regulation of Hepatic MicroRNAs in Response to Early Stage Echinococcus multilocularis Egg Infection in C57BL/6 mice

In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis

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