Echinococcus multilocularis in Ontario

Background information about Echinococcus multilocularis

For many years, E. multilocularis (the fox tapeworm) has been known to occur in wildlife in the southern parts of Alberta, Saskatchewan and Manitoba, and in the Canadian Arctic. Within these areas, adult tapeworms occur in the small intestine of wild canids (e.g. foxes, coyotes) and the intermediate stage, alveolar hydatid cysts, occur in the abdomen of wild rodents. Disease due to the development of alveolar hydatid cysts is referred to as alveolar echinococcosis. Rodents become infected by ingestion of parasite eggs in the feces of wild canids. Wild canids develop patent intestinal infections as a result of ingestion of infected rodents.

 

Just as in wild canids, adult E. multilocularis can develop in the small intestine of domestic dogs, and, to a lesser extent, cats if infected rodents are ingested. The eggs that are then shed in feces (Taenia-type eggs) are immediately infective for people.

 

Strangely, if dogs consume large numbers of parasite eggs (e.g. by ingestion of fox/coyote feces) they may also develop alveolar hydatid cysts in their abdomen.

 

Cases of canine alveolar echinococcosis (AE) in North America

Prior to 2009, E. multilocularis had not been diagnosed in a dog in Canada. However, in that year hepatic AE was diagnosed in a 3-year old dog that had lived permanently in British Columbia; E. multilocularis was identified on histology and direct immunofluorescence of hepatic tissue; sequence data for the mitochondrial 12S rRNA gene, and restriction fragment length polymorphism analysis of the mitochondrial NADH dehydrogenase 1 and 12S rRNA genes, confirmed the diagnosis (Peregrine et al. 2012). In 2012, a second case was similarly diagnosed in a 2-year old dog that resided in southern Ontario (Skelding et al. 2014); a third case was diagnosed in a 4-year old dog that lived in Alberta and Manitoba (Peregrine et al. 2013). Between 2013 and 2016, four additional cases were diagnosed in southern Ontario (Oscos-Snowball et al. 2015; Pinard et al. 2016). None of the 7 dogs were related; all 7 dogs had never traveled outside Canada; 6 of the dogs had lived their entire lives in provinces where E. multilocularis had never been diagnosed prior to the occurrence of these cases.

 

Clinical presentation and diagnosis

The median age at diagnosis was 3.1 years (range = 1.1-10.7 years) and the most common clinical signs included abdominal distension, lethargy, anorexia et al. vomiting; less common clinical signs included diarrhea, weight loss, polypnea, fever and Corsini and others recently published a retrospective analysis of twenty confirmed (n = 18) or probable (n = 2) cases of canine AE in Europe (Corsini et al. 2015). Most dogs had lived all their adult lives in areas where foxes occurred and were exercised outdoors.

 

Abdominal ultrasound and clinical pathology

In dogs with clinical AE, abdominal ultrasound typically reveals the presence of multiple, large, heterogeneous, poorly limited, cavitated hepatic masses. Usually, there is a hyperechoic thick periphery, an irregular inner surface, and a centrally located cavity filled with echogenic fluid (Corsini neighbouring organs is observed in approximately one-third of cases; free abdominal fluid is present in a similar proportion (Corsini et al. 2015). In many dogs, ultrasound-guided fine-needle aspirates of intralesional or peritoneal fluid generates samples with cytological morphology consistent with AE; calcareous corpuscles and folded membranous structures (Oscos-Snowball et al. 2015). While the former indicates the presence of any cestode, the latter has only been described with E. multilocularis.

 

Histopathology

In dogs with hepatic AE, there is typically extensive involvement of the liver with a multinodular firm pale-tan mass that grossly has the appearance of a neoplasm. Histological examination of hepatic biopsies is extremely helpful as the morphology is characteristic for E. multilocularis (Eckert and Deplazes 2001; Peregrine et al. 2012); hepatic architecture is replaced by multi-loculated coalescing cystic structures surrounded by fibrosis. Lining individual cysts is a hyaline membrane (“laminated layer”) that stains with Periodic acid-Schiff (PAS) stain. The inner lining of the hyaline membrane typically comprises a basophilic matrix that contains occasional calcareous corpuscles. Intraluminal protoscolices are sometimes observed. A prominent chronic eosinophilic and granulomatous inflammation is also typically present.

 

Serology and PCR

Positive serology to the Em2-antigen is observed in most dogs with AE (Staebler et al. 2006; Corsini et al. 2015). However, at the present time, this diagnostic method is only available at the University of Bern, Swizterland. In addition, some dogs will seroconvert, but not develop AE due to abortive infections (Rausch et al. 1987; Gottstein et al. 2014). As a result, examination of intralesional or abdominal fluid, or hepatic tissue, using an E. multilocularis-specific PCR provides confirmatory diagnostic information (Diebold-Berger et al. 1997; Dinkel et al. 1998; Trachsel et al. 2007).

 

Management

Historically, dogs with AE have been managed with surgery and/or treatment with albendazole at 10 mg/kg body-weight, daily, for life. In the aforementioned case series from Europe, dogs that received any intervention (i.e. only albendazole, or surgery and albendazole combined) survived significantly longer than dogs with no intervention. However, no significant difference in survival time was observed between these two intervention groups (Corsini et al. 2015). While low numbers of dogs limited the statistical power of the study, the authors concluded that there was no evidence that debulking surgery (cytoreduction) followed by treatment with albendazole resulted in a superior outcome compared to treatment with albendazole alone (Corsini et al. 2015). As a result, debulking surgery could not be recommended at the present time; as in people, surgery should only be attempted if complete resection is possible (Corsini et al. 2015). Thus, ideally, investigation of potential cases requires advanced imaging (CT-Scan) to assess whether surgical excision is possible. In non-resectable cases with a centrally located fluid cavity, a pigtail retention catheter can be placed attached to a sealed collection system to provide temporary relief. Lastly, it has historically been assumed that medical management of dogs with AE is associated with short-term survival. However, 4 of 6 dogs managed with only daily albendazole were alive 0.5, 0.5, 2.6 and 9.5 years after the initial diagnosis and were considered to be in remission (Corsini et al. 2015). Medical management of dogs with AE can therefore be associated with long-term survival; however, daily treatment with albendazole is required.

 

Public health concerns

The intermediate (larval) stage of E. multilocularis in the abdomen of dogs constitutes no risk to public health. However, some dogs with hepatic AE may also have patent intestinal infections and therefore may constitute a zoonotic threat. Thus, as soon as a presumptive diagnosis of hepatic AE is made, dogs should be treated with praziquantel at 5 mg/kg bodyweight to eliminate intestinal E. multilocularis infection (EFSA 2015); treatment should be repeated 24 hours later to ensure the correct dosage is administered. In areas endemic for E. multilocularis, monthly administration of praziquantel at 5 mg/kg bodyweight is required to prevent patent intestinal infections, and may be effective at reducing the risk of canine AE (Staebler et al. 2006; Behrens et al. 2011); a risk assessment should be carried out to determine if such preventive treatment is necessary, i.e. does the dog ingest rodents?

 

If exposure of people to E. multilocularis eggs is a concern, serological testing at 3, 6 and 12 months following exposure using three different ELISAs (EgHF-ELISA, Em2-ELISA and Em18-ELISA) is recommended (Gottstein et al. 1993; Gottstein B, personal communication)

 

CONCLUSION

In dogs with hepatic masses, travel to areas endemic for E. multilocularis should be evaluated. If hepatic lesions are first detected during an exploratory laparotomy, it should be recognized that the gross appearance of hepatic AE in dogs is very similar to that of hepatic neoplasia or abscesses. Thus, histological examination of hepatic biopsies should be carried out to confirm tentative gross diagnoses, particularly in young dogs. Management of AE involves daily treatment with albendazole for life, with or without surgery; due to the late stage at which infections are diagnosed, the prognosis for long-term survival is often poor.

 

References

Behrens S, et al. Kleintiermedizin 2011;6:300.

Corsini M, et al. Vet Rec 2015;177:569.

Deplazes P & Eckert J Vet Parasitol 2001;98:65.

Diebold-Berger S, et al. Acta Cytol 1997;41:1381.

Dinkel A, et al. J Clin Microbiol 1998;36:1871.

European Food Safety Authority (EFSA), Panel on Animal Health and Welfare EFSA Journal 2015;13:4373.

Gottstein B, et al. J Clin Microbiol 1993;31:373.

Gottstein B, et al.Parasite 2014;21:63.

Oscos-Snowball A, et al. Vet Clin Path 2015;44:167.

Peregrine A, et al.Can Vet J 2012;53:870.

Peregrine A, et al. WAAVP Proceedings, 2013:345.

Pinard C., et al. AAVP Proceedings, 2016:92.

Rausch R, et al. Am J Trop Med Hyg 1987;36:576.

Skelding A, et al. Can Vet J 2014;55:551.

Staebler S, et al. Vet Parasitol 2006;141:243.

Trachsel D, et al. Parasitology 2007;134:911.

 

 

Andrew Peregrine (November 25, 2016)