Echinococcus multilocularis

In Canada,  Echinococcus multilocularis is established in all of western Canada, especially in the prairie regions, in the western Canadian Arctic, and in southern Ontario.  It cycles between wild canids (fox, coyote, and wolves) and wild rodents (voles, lemmings, shrews, deer mice, and muskrats), occasionally spilling over into dogs (as definitive hosts and/or aberrant intermediate hosts), cats (as aberrant definitive hosts) and people (as aberrant intermediate hosts).  Adult E. multilocularis are tiny tapeworms (<5 mm long) that live in the small intestine of the definitive host.  Eggs passed in feces, or in gravid segments in feces, are environmentally resistant and immediately infective for an intermediate host. In the intermediate host, the parasite develops to the metacestode stage (alveolar hydatid cyst) in the liver. The next definitive host is infected by ingestion of the alveolar hydatid cyst in the intermediate host. Normally dogs are definitive hosts for E. multilocularis, but canine alveolar echinococcosis (AE) is increasingly being reported in endemic regions in Canada, the USA, and Europe.

In the definitive host, adult E. multilocularis are very rarely associated with clinical signs, but AE is a severe, often fatal disease, starting in the liver and spreading throughout the peritoneum and elsewhere in the body. 

Diagnosis of canine AE should be suspected on detection of a liver mass, especially in a young dog in a highly endemic region.  Definitive diagnosis relies on detection of protoscolices or parasite material on biopsy or cytology; PCR on tissue, aspirated abdominal fluid, or cyst contents; or serology (not commonly available in Canada at moment).  Prognosis is poor if not detected early and treated aggressively, generally involving long term chemotherapy with albendazole plus or minus surgical debulking.  Although rare, dogs with AE may also harbor intestinal infections and this, not AE, may pose a risk to the owner or veterinary staff.  Diagnosis of intestinal infections in dogs is best accomplished by coproPCR, either as a screening tool in a high risk dog (one with AE, or access to wild rodents in endemic regions), or following detection of taeniid-type eggs in feces in a region endemic for E. multilocularis (most of western Canada).  Control is best accomplished by preventing dogs from having access to wild rodents (how dogs get intestinal infections), preventing dogs from eating feces of wild canids or other dogs (how dogs get AE), monthly treatment of high risk dogs with praziquantel, good hand hygiene and pooper-scooping, and prevention of human consumption of unwashed produce or unfiltered surface water in areas where infected dogs or wild canids may have defecated.

Echinococcus multilocularis can infect people following ingestion of infective eggs from the faeces of a definitive host, but not from contact with dogs or rodents with AE.  Autochthonous human AE was almost unheard of in Canada, but now seems to be emerging in people in western Canada, particularly Alberta, possibly as a result of introduced European strains of the parasite which seem to be more likely to cause canine and human AE than strains previously established in North America

Phylum: Platyhelminthes
Class: Cestoda
Order: Cyclophyllida
Family: Taeniidae

Adult tapeworms of the family Taeniidae (Taenia and Echinococcus spp.) tend to be parasites of carnivores and omnivores, and produce “taeniid” type eggs that cannot be distinguished morphologically.  They cycle between carnivore definitive hosts and herbivore intermediate hosts, in naturally occuring predator-prey assemblages around the globe.  Echinococcus multilocularis has a global distribution in the northern hemisphere. . Several genotypes have been identified within the species E. multilocularis, including distinct groups from Asia (group A - also pr/esent on St Lawrence Island, Alaska), Europe (E), and North America (N1 from St Lawrence Island, and N2 from central North America).

Adult E. multilocularis are small (less than 5 mm long and only a few segments) and have an anterior scolex (attachment or holdfast organ), behind which is the very short, segmented body. At the anterior tip of the scolex is a rostellum, which is armed with two circles of hooks. Behind the rostellum are four circular, muscular suckers. Each mature segment of E. multilocularis contains a single set of reproductive organs with a lateral genital pore in the anterior half of the mature segment.  In most specimens of E. multilocularis, even those that have been fixed and stained, only the uterus, the genital pore, and the testes, are the only visible reproductive structures. Adult E. multilocularis can be distinguished microscopically from adult E. canadensis by their smaller size and by the position of the genital pore on the lateral margin of the segment (at or posterior to the mid-point for E. canadensis) and its relationship to the testes (posterior to the genital pore in E. multilocularis).

 

E. multilocularis scolex

Taeniid type eggs of E. multilocularis are round, measure approximately 30 to 35 µm in diameter and have a thick, radially striated shell. Each egg contains a hexacanth larva with six hooks, not all of which are visible in every egg. The eggs of the various species of Echinococcus cannot be distinguished microscopically from each other, or from the eggs of the various species of Taenia.

In intermediate hosts, the metacestode, or larval stage, takes the form of an alveolar hydatid cyst, usually in the liver. Typically, an  alveolar hydatid in a rodent intermediate host consists of multiple, small, fluid-filled cysts (“alveoli”) lined by germinal membrane of parasite origin – from which develop the protoscolices. Each “alveolus” usually contains only a few protoscolices, but the entire cyst that develops from a single egg can contain hundreds of protoscolices.  In aberrrant intermediate hosts, such as dogs, protoscolices are only present in some hosts, and the primary lesions may be associated with the metastatic behaviour of the germinal membrane alone.

Rodent IH with alveolar hydatids                 Liver section with Alveolar Hydatid

In Canada, aAdult E. multilocularis occurs infoxes, coyotes, wolves, dogs, and (although not generally considered patent) cats as definitive hosts, and the metacestode (AE) in voles, lemmings, shrews, deer mice, and muskrats. Prevalence in coyotes ranges from 25-70% in Canada, around 30% in foxes, and 13% of wolves.  The parasite appears to be rare in dogs as definitive hosts in Canada, although it has been reported most recently in Alberta.  AE is increasingly being detected in dogs in North America, especially Alberta and Saskatchewan, and has been reported in British Columbia, Manitoba, and Ontario.  Other aberrant intermediate hosts include primates in zoos, pigs, and horses.

 

Adult E. multilocularis live in the small intestine of the definitive hosts and, like all cestodes of veterinary importance, are hermaphrodites. Gravid segments (or whole parasites) containing eggs pass intact in the feces or disintegrate in the GI lumen, releasing the eggs, which are also passed in the feces.  If an egg is ingested by a suitable rodent intermediate host (required for completion of the life cycle) the egg hatches in the stomach. The released hexacanth larva then invades the GI wall and migrates in the bloodstream to various tissues, primarily the liver, where it develops into the infective larval stage (or metacestode)e. For E. multilocularis, this larval stage is the alveolar (multilocular) hydatid cyst, each of which can contain many protoscolices.

The life cycle continues when the alveolar hydatid in the intermediate host is eaten by a suitable definitive host. Here, the wall of the alveolar hydatid disintegrates and the protoscolices are released, each one everting to form a scolex, which  attaches to the mucosa of the small intestine , produces segments, and completes their development to adults.  Adult tapeworms live about 6 months, and the pre-patent period is about 1 month.

 

As for many parasites, prevalence and intensity of Echinococcus spp. in canid definitive hosts may be higher in young animals; however, there is no evidence that canids develop protective immune responses and therefore older animals can easily be re-infected.  In Canada, dogs who are free-ranging in remote and rural regions endemic for E. multilocularis (most of western Canada) with access to wild rodents are at risk of developing intestinal infections with E. multilocularis. In  regions endemic for E. multilocularis, dogs who ingest feces of wild canids or other dogs, “graze” on grass or berries, or drink unfiltered surface water in areas potentially contaminated with wild canid feces are at risk of developing AE.  No obvious breed predilections have been identified, although there appear to be a higher proportion of beagles and boxers than expected.  Mean age of dogs with AE in Europe and Canada is 3-4 years of age, and has been diagnosed in dogs as young as 1 year of age.  Unlike Taenia species tapeworms, individual Echinococcus do not produce large numbers of eggs. Compensating for the low levels of egg production, definitive hosts can harbour thousands of adult cestodes, and a single egg can produce very large numbers of protoscolices when it has developed into an alveolar hydatid in the intermediate host. Eggs of E. multilocularis are immediately infective and environmentally resistant.  They survive months to years in the environment, freezing at -20C, and exposure to most disinfectants and fixatives (including ethanol and formalin).  They are inactivated by heat (>60C for 5 minutes), freezing at or below -70 C for at least 48 hrs, desiccation, and strong bleach solutions.

Usually adult Echinococcus are not recognized as a cause of clinical problems although diarrhea has been reported in some dogs with intestinal infections.  Little is known of the effects of the larval stages in rodent intermediate hosts. In canine AE, dogs often initially present with anorexia and vomiting, and an enlarged abdomen.  This may progress to signs of hepatic failure, including ascites and elevated liver enzymes, and to death if not treated aggressively.  Other signs may be present if the parasite metastasizes to other organs, such as prostate, lung, or brain.

In the carnivore definitive hosts, eggs of E. multilocularis can be detected in the feces using a centrifugation-flotation, although sensitivity is low (~30%).  Fecal sedimentation methods may be better for detection of taeniid-type eggs, which are very dense and do not float well.  In addition, astute owners or clinicians may be able to detect gravid segments, or even adult cestodes, in feces of heavily infected dogs, although these are very small, especially in comparison to other cestodes common in dogs.  The most sensitive diagnostics for Echinococcus in the feces of dogs are coproantigen or coproPCR-based methods, the latter of which also offer the advantage of being able to distinguish among E. canadensis, E. multilocularis, and Taenia spp. 

Eggs of E. multilocularis are indistinguishable microscopically from eggs of E. granulosus/canadensis and of Taenia species. In rodent intermediate hosts, diagnosis is made at post-mortem.  Diagnosis of canine AE should be suspected on detection of a liver mass, especially in a young dog in a highly endemic region, via radiology or ultrasound.  Definitive diagnosis relies on detection of protoscolices (in about one third of dogs) or parasite material on biopsy or cytology; PCR on tissue, aspirated abdominal fluid, or cyst contents; or serology (not available in Canada at moment)

 

Praziquantel is the drug of choice for the treatment of Echinococcus species in carnivores, and is approved in Canada for this purpose. The larval stages in rodents are not treated. The primary goal of treatment in dogs serving as definitive hosts for E. multilocularis is to halt environmental contamination with eggs for public and canine health considerations.  Wherever possible, owners should restrict access of dogs to wild rodents and to regions heavily contaminated with wild canid feces (urban green spaces, dog parks, rural and remote regions).  When this is not possible, high risk dogs (those with a history of rodent consumption) should be dewormed monthly, year round.  In Canada, a dog with taeniid eggs on fecal flotation should be treated with praziquantel and assumed to be high risk for exposure to Echinococcus, as it must have access to raw meat or organs of wildlife or sheep.  A dog with confirmed intestinal Echinococcus spp. infection (i.e. positive coproPCR or morphological identification of gravid segments) should be treated with praziquantel and confined for 3 days, as eggs may be shed for 3 days post treatment.  Given the public health considerations, it would also be appropriate to advise the owner to consult their health care provider, and to use extra care when pooper-scooping.  

In dogs diagnosed with AE, a fecal sample should be taken and tested by coproPCR to determine if the dog was also infected with adult cestodes (true in about 20% of cases from Europe, not described in Canada to date).  Then, the dog should be treated with an adult cestocide (i.e. praziquantel at 5 mg/kg); this drug has no efficacy against the metacestode stage, but will eliminate any adult cestodes while awaiting the coproPCR results.   To address the AE, the dog will need to be treated daily for life (or at least 2 years) with a larval cestocide (i.e. albendazole at 10 mg/kg). Surgical debulking/resection should be performed if clinically indicated, but if caught early, medical management is often sufficient.  Euthanasia should not be initiated for public health considerations, since the dog, once treated with praziquantel, poses no further risks to the owner.  Many owners do elect euthanasia because of welfare considerations, or poor prognosis, especially if the infection is significantly advanced prior to diagnosis.

For E. multilocularis, as for E. granulosus, people are in the intermediate host position in the life cycle. If people ingest viable E. multilocularis eggs from carnivore feces, they can develop alveolar hydatids, primarily in the liver. People cannot be infected by contact with AE in the organs of rodents or dogs, but through consumption of eggs in unwashed produce, unfiltered surface water, or unwashed hands in environments heavily contaminated by infected dogs or wild canids.   It is not clear how much transmission occurs directly from wild canids to people (presumably through consumption of unwashed produce or unfiltered surface water in areas contaminated by wild canid feces), or from dogs directly to people (i.e. from eggs adhering to dog fur from rolling in canid feces, or adhering to the perianal region in dogs with intestinal infections).  

Human AE is often associated with clinical signs, sometimes decades after infection, and is more common in people with immunocompromise. In North America, locally acquired cases of AE in people are increasing, especially in Alberta and Saskatchewan, possibly as a result of introduced European strains of the parasite which seem to be more likely to cause canine and human AE than strains previously established in North America.

Alveolar hydatid; human liver

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