Abstract

Alveolar echinococcosis (AE) in humans is a parasitic disease characterized by severe damage to the liver and occasionally other organs. AE is caused by infection with the metacestode (larval) stage of the fox tapeworm Echinococcus multilocularis, usually infecting small rodents as natural intermediate hosts. Conventionally, human AE is chemotherapeutically treated with mebendazole or albendazole. There is, however still the need for improved chemotherapeutical options. Primary in vivo studies on drugs of interest are commonly performed in small laboratory animals such as mice and Mongolian jirds, and in most cases, a secondary infection model is used, whereby E. multilocularis metacestodes are directly injected into the peritoneal cavity or into the liver. Disadvantages of this methodological approach include risk of injury to organs during the inoculation and, most notably, a limitation in the macroscopic (visible) assessment of treatment efficacy. Thus, in order to monitor the efficacy of chemotherapeutical treatment, animals have to be euthanized and the parasite tissue dissected. In the present study, mice were infected with E. multilocularis metacestodes through the subcutaneous route and were then subjected to chemotherapy employing albendazole. Serological responses to infection were comparatively assessed in mice infected by the conventional intraperitoneal route. We demonstrate that the subcutaneous infection model for secondary AE facilitates the assessment of the progress of infection and drug treatment in the live animal.

Highlights

  • Echinococcus multilocularis, known as the fox tapeworm, is a parasite of the Taeniidae family, whose metacestode stage causes the zoonotic disease ‘‘alveolar echinococcosis (AE)’’ in the intermediate hosts including humans. [1]

  • In this study we show that the subcutaneous infection model can be applied for drug treatment trials and enables the direct monitoring of treatment effects during the entire study period

  • The sc-untreated group yielded 63% less parasite material compared to the ip-untreated group. This difference in the progress of parasite development might be due to the more restricted physical space for growth provided in the sc infection model, or due to difference in the immune responses triggered by the presence of the parasites at the two different sites

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Summary

Introduction

Echinococcus multilocularis, known as the fox tapeworm, is a parasite of the Taeniidae family, whose metacestode (larval) stage causes the zoonotic disease ‘‘alveolar echinococcosis (AE)’’ in the intermediate hosts including humans. [1]. The continuously proliferating parasite progressively invades the liver parenchyma, bile ducts and blood vessels, which results in symptoms related to biliary obstruction, portal hypertension and others. The treatment options for AE are surgery and/or chemotherapy. In cases where surgery is not possible, chemotherapy remains the only option. For chemotherapeutical treatment of AE, the only two drugs licensed to date are the benzimidazole carbamate derivatives albendazole and mebendazole. Both exhibit a relatively good clinical efficacy but side effects may occur, and for most cases the drugs do not act parasitocidal [3,4]

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