Introduction

Calodium hepaticum is a worldwide-distributed zoonotic parasite with a high affinity to the liver. It is the causative agent of hepatic capillariasis and has low host specificity. This parasite is mainly diagnosed during liver biopsies or through necroscopy because the eggs of this nematode are only released into the environment after the host's death (after predation, cannibalism, or decay). The main hosts are rodents of the subfamilies Murinae and Arvicolinae. Although murids are the most important hosts, this parasite was documented in more than 70 non-murid species. This review focuses on the mammalian (excluding Muroidea) host spectrum and its geographic distribution in those hosts. Furthermore, the role of spurious infections in animals and the dissemination of C. hepaticum are summarized. Information about the pathogenesis, ecology, and host spectrum in Muriodea is given elsewhere (e.g., Fuehrer et al. 2011; Fuehrer 2013; Schmidt 2001).

For data evaluation, the systematic search was based on electronic databases (Scopus, PubMed, Google Scholar) and previous summaries (e.g., Schmidt 2001). The search terms Capillaria hepatica, Calodium hepaticum, Hepaticola hepatica, Trichocephalus hepaticus, and hepatic capillariasis were used. An attempt was made to include only those studies where the scientific names of the host and parasite were given clearly. Furthermore, spurious infections (= pseudoparasitism) were differentiated as far as possible from hepatic capillariasis.

Taxonomy, morphology, and biology

C. hepaticum is a member of the family Capillaridae (Order: Trichocephalida). The parasite is also known under the synonym Capillaria hepatica. Although Moravec (1982) included this nematode in the genus Calodium, many scientists still use the synonym C. hepatica. Further synonyms are Hepaticola hepatica (Hall 1916) and Trichocephalus hepaticus (Bancroft, 1893) (Fuehrer et al. 2011).

The taxonomy of the family Capillaridae is pending. All species out of the former genus Capillaria are included in the family Capillaridae. A recent study has shown that the family Capillaridae seems to be monophyletic and can be clearly separated from Trichuridae (Guardone et al. 2013). Although most species parasitize in animals, three are known to also infect humans: Paracapillaria philippinensis (syn. Capillaria philippinensis), Eucoleus aerophila (syn. Capillaria aerophila), and C. hepaticum (syn. C. hepatica).

Adult C. hepaticum are long slender-shaped nematodes with a narrow anterior body part (0.007–0.01 mm). The posterior body part becomes gradually thicker. Sexual dimorphism is present (females 27–100 mm; males 15–50 mm) (reviewed in Schmidt 2001). The eggs resemble typical trichurid eggs but differ in size (40–67 × 27–35 μM). The eggs are barrel-shaped, striated, and with polar plugs. Numerous minipores are present on the outer shell. The four larval stages differ in size (reviewed in Schmidt 2001).

C. hepaticum has a high affinity to the liver and is the causative agent of hepatic capillariasis. The life cycle is a direct one. After the ingestion of embryonated eggs, L1 larvae hatch in the area of the caecum and invade the liver via the portal vein system. Adult C. hepaticum nematodes live in the liver parenchyma (life span 18–60 days) where females lay unembryonated eggs into the liver parenchmya. The eggs develop in the liver parenchyma to the eight-cell stage. After the death of the host (cannibalism, predation, decay), the eggs are released into the environment and embryonate (depending on the environmental conditions) to the infective stage. The cycle closes with the ingestion of embryonated eggs by a new host (reviewed in Schmidt 2001). The ingestion of unembryonated eggs leads to spurious infections (= pseudoparasitism) where the non-infective eggs are shed into the environment with the feces.

Host spectrum

The main hosts of C. hepaticum are several murid rodent species with the highest prevalences in synanthropic Murinae (e.g., Norway rat). The parasite was documented in more than 90 Muroidean rodent species of the subfamilies Murinae, Deomyinae, Arvicolinae, Neotominae, Cricetinae, Sigmodontinae, Gerbillinae, and Cricetomyinae (Führer et al. 2010; Fuehrer 2013).

However, hepatic C. hepaticum infections were also found in Caviidae, Erethizontidae, Castoridae, Myocastoridae, Sciuridae, Geomyidae, Dipodidae, Nesomyidae, and Cuniculidae (Table 1). In wildlife, North American porcupines (USA; 9 % of 53), nutrias (Argentina; 3.6 % of 108), northern pocket gophers (USA; 39 % of 46), Brazilian guinea pigs (Peru; 6.9 % of 143), and lowland pacas (Brazil; 20 % of 5) were evaluated as suitable hosts of this parasite (Dittmar 2002; Hamir and Rupprecht 2000; Martino et al. 2012; Todd et al. 1971).

Table 1 Calodium hepaticum in non-Muroidea rodents
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Furthermore, C. hepaticum was documented in at least 69 species out of 25 families in non-rodent mammalian including Insectivora, Chiroptera, Lagomorpha, Artiodactyla, Perissodactyla, Hyracoidea, Marsupialia, Carnivora, and Primates (Table 2). In wildlife, hepatic capillariasis was documented in several studies: pronghorn antelopes (Canada; 4/41), red foxes (Italy; 1/75), crab-eating foxes (Brazil; 5.56 %), pampas foxes (Brazil; 13.64 %), and mountain gorillas (Rwanda; 10/19) (Barrett and Chalmers 1972; Graczyk et al. 1999; Macchioni et al. 2013; Ruas 2005). The true burden of this parasite in wildlife is not clear. Numerous documented cases of C. hepaticum in non-murid mammals were reported from zoological gardens and laboratories or in domesticated animals.

Table 2 Calodium hepaticum in other mammals other than rodents
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Zoos

Several hepatic cases with C. hepaticum had been observed in zoological gardens. Various studies documented single cases of this parasite. In some reports, more than one animal of a single species were infected: black-tailed prairie dogs (USA; 5/21; UK; 45 % of 20) and Kirk's dik-diks (USA; 7/18) (Landolfi et al. 2003; Partington and Montali 1986; Redrobe and Patterson-Kane 2005). Most of the cases in primates were found in zoos.

Several studies tried to analyze the relationships of commensal rodents (e.g., Norway rats, house mice) to infections of animals in zoos (e.g., Juncker-Voss et al. 2000). In zoos, high prevalences of free-ranging rats, mice, and shrews were observed: Norway rats (Baltimore Zoo, USA, 75 % of 845; Lisbon Zoo, Portugal 42 % of 50), house mice (Vienna Zoo, Austria, 42.7 % of 166; Lisbon Zoo, Portugal 22 % of 50), and greater white-toothed shrews (France; 10–25 %) (Apéry 2012; Crespo 2012; Farhang-Azad 1977; Juncker-Voss et al. 2000).

Laboratory animals and pet shops

C. hepaticum was found in various pet shops and laboratories, for example, in one out of four Korean squirrels imported from China to Spain, 3 out of 155 lab groundhogs imported from the USA to Germany, 13 out of 160 New Zealand White rabbits in France from a commercial distributor, two cases in common chimpanzees which were lab animals originating from West Africa, and 0.6 % of 472 wild-caught laboratory-maintained crab-eating macaques (Abbott and Majeed 1984; Carrasco et al. 2006; Hilken et al. 2003; Mowat et al. 2009; Sadun et al. 1970). It can be hypothesized that animals ingested embryonated eggs while living wild and/or with contaminated food.

Domesticated animals

C. hepaticum was documented in domesticated mammal species like laboratory Norway rats, rabbits, cattle, pigs, horses, dogs, cats, domesticated guinea pigs, and squirrels. In Japan, hepatic capillariasis was observed in 2.25 % of 400 cattle, but the author did not classify the nematode as C. hepaticum because the pathogen was not reported in cattle before (Nakamura 2005). Furthermore, Ilha and Barros (2000) found C. hepaticum in the livers of 0.23 % of 3,927 dogs and 1.38 % of 435 cats examined in Brazil.

Dispersal by animals and spurious infections

With the death of the animal host (cannibalism, predation, or decay), the eggs of C. hepaticum are released into the environment. The dissemination of eggs by ground beetles and rain worms had been reported, but their role in the importance of maintaining the life cycle of this parasite is unclear (Mobedi and Arfaa 1971; Schmidt 2001).

In humans, spurious infections are associated with the consumption of unembryonated eggs in soil or infected game (Fuehrer et al. 2011). The same can be considered for other carnivore and omnivore animals (Reperant and Deplazes 2005). Gonzalves et al. (2012) described the first case of a spurious infection in a dog in Brazil (Amazonas) after the dog was fed with raw game meat. In the Zoological Garden of Vienna, eggs of C. hepaticum were found in the feces of a Pallas's cat (Otocolobus manul) (Basso et al. 2005). Spurious infections have also been observed in Norway rats (6 %) and black rats (20 %), where cannibalism might be the mode of intake of unembryonated eggs (Firlotte 1948; Promkerd et al. 2008). In Madagascar, eggs from Capillaria sp. with the shape of C. hepaticum have been found in the feces of gray mouse lemurs (Microcebus murinus), greater hedgehog tenrecs (Setifer setosus), and black rats (R. rattus).

Furthermore, eggs of C. hepaticum were found in the feces of non-mammalian animals. In Malaysia, 2.83 % of large-billed crows shed eggs of this parasite with the feces (Lee et al. 2008). Eggs of C. hepaticum were also documented in fecal samples from reptiles fed with infected rodents (Pantchev and Tappe 2011). In an analysis of the intestinal content of two timber rattlesnakes (Crotatus horridus), eggs of C. hepaticum were documented (Solomo 1974).

Although many authors described spurious infections in animals, care should be taken to exclude mix-ups with other Capillaridae or Trichuridae shedding eggs of resembling morphology (e.g., Bork-Mimm and Rinder 2011; Di Cesare et al. 2011; Stuart et al. 2013; Traversa et al. 2011). With the absence of specific molecular diagnostic tools, the classification of C. hepaticum in spurious infections is based on the morphology of the eggs only. Consequently, the role of spurious infections for the maintenance of the life cycle of this nematode remains unclear.

Conclusions

C. hepaticum is a worldwide-distributed zoonotic parasite with a high affinity to the liver and low host specificity. The main definite hosts are Murinae and Arvicolinae, but it has also been found in various other mammals of different families. Eggs are released into the environment after the death of the host only (decay, cannibalism, and predation). It is unclear which method of egg dispersal is the most effective one but it can be hypothesized that:

  1. (a)

    Cannibalism is the most effective method of transmission in the case of rodents with a tendency to cannibalism and egg shedding in the burrow.

  2. (b)

    Dispersal of unembryonated eggs by egg-shedding in feces (after cannibalism, predation by omnivores and carnivores, scavengers, dissemination by insects and earth worms) leads to the most infections in other mammals after the embryonation of the eggs.

Diagnosis is now based on liver biopsy and necroscopy, and it can be suggested that the true burden of this parasite is underrepresented. Novel molecular diagnostic tools are needed to allow species determination in cases of hepatic capillariasis and spurious infections.