An overview of the host spectrum and distribution of Calodium hepaticum (syn. Capillaria hepatica): part 1—Muroidea

Calodium hepaticum (syn. Capillaria hepatica) is a worldwide-distributed species of zoonotic nematodes with a high affinity to the liver. Several rodent species of the superfamily Muroidea serve as main hosts for this pathogen. C. hepaticum has been found in Muroidean hosts in more than 60 countries in Europe; North, Central, and South America; Asia; Africa; and Oceania. C. hepaticum was documented in more than 90 Muroidean rodent species (Murinae, Deomyinae, Arvicolinae, Neotominae, Cricetinae, Sigmodontinae, Gerbillinae, and Cricetomyinae). Globally, the Norway rat (Rattus norvegicus) seems to be the main host species for this nematode. However, locally high prevalences (above 50 %) have also been observed in several other synanthropic (commensal and non-commensal) Muroidea species (e.g., Rattus tanezumi, Ondatra zibethicus, Apodemus sylvaticus). This review gives an overview of the distribution and host spectrum of C. hepaticum in Muroidea host species.


Introduction
Calodium hepaticum (syn. Capillaria hepatica) is a zoonotic nematode parasite distributed worldwide. Adults of this nematode parasitize the liver of mammals and lay their eggs into the liver parenchyma causing hepatic capillariasis. The eggs are only released into the environment with the death of the host. The main hosts of this parasite are rodents of the superfamily Muroidea (Schmidt 2001). Furthermore, this parasite has been documented in numerous other mammalian species including more than 70 human cases (reviewed in Fuehrer et al. 2011;Fuehrer 2013). Hepatic capillariasis is diagnosed through necroscopy or biopsy only, because with hepatic infections eggs are not shed into the environment with the feces.
This review focuses on the Muroidea host spectrum and its geographic distribution in those hosts only. Information about the pathogenesis, ecology, and host spectrum in humans and other mammalians 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. A short overview of spurious C. hepaticum infections in animals is given in Fuehrer (2013).
The taxonomy of the family Capillaridae is disputed and pending. In the past, most species were included in the genus Capillaria. Recently, a molecular phylogenetic study revealed that Capillaridae can be clearly separated from Trichuridae (Guardone et al. 2013). However, the former genus Capillaria consists of a complex group of parasites including several parasites of carnivores and rodents of the genera Calodium , Eucoleus, Capillaria, Paracapillaria, Pearsonema, and Aonchotheca (Guardone et al. 2013). Three species are of zoonotic importance, namely Paracapillaria philippinensis (syn. Capillaria philippinensis), Eucoleus aerophila (syn. Capillaria aerophila), and C. hepaticum (syn. C. hepatica).

Life cycle
The life cycle of C. hepaticum is a direct one with a high affinity to the liver. After the ingestion of embryonated eggs, larvae hatch in the area of the caecum and invade the liver via the portal vein system. Adult worms parasitize in the liver of its mammalian hosts where the females lay eggs into the liver parenchyma after mating. The life span of adult worms is short (18-60 days post infection in mice) (Juncker-Voss et al. 2000;Schmidt 2001). The eggs develop in the host's liver to the eight-cell stage only. Unembryonated eggs are only released into the environment with the death of the host only (decay of host; excretion in feces of carnivores and omnivores or after cannibalism). Depending on the environmental conditions (e.g., humidity, temperature), eggs embryonate within 5-8 weeks. Laboratory studies revealed that embryonated eggs are viable for 25 months (reviewed in Juncker-Voss et al. 2000). The life cycle is closed when embryonated eggs are ingested from a mammalian host. The ingestion of nonembryonated eggs leads to pseudoparasitosis (= spurious infections) where the non-embryonated eggs are re-released with the feces and lead to mild symptoms only (reviewed in Fuehrer et al. 2011).

Muroidea host spectrum
The mammalian superfamily Muroidea consists of rodents with a worldwide distribution (with the exception of Antarctica) including animals like rats, true mice, gerbils, and hamsters. Recent molecular phylogenetic studies classified the superfamily into 6 families, 19 subfamilies, around 280 genera, and over 1,300 species (e.g., Steppan et al. 2004).
The host spectrum of C. hepaticum in Muroidea hosts (and in other mammals) indicates very low host specificity. More than 90 species of at least 44 genera of the superfamily Muroidea (Murinae, Arvicolinae, Neotominae, Cricetinae, Sigmodontinae, Gerbilinae, and Cricetomyinae) are known as hosts of this parasite (Table 1). Of these, more than 55 species are rodents of the subfamily Murinae including the Norway rat (Rattus norvegicus), Black rat (Rattus rattus), and house mouse (Mus musculus). Prevalences above 50 % are regularly documented in Norway rats (R. norvegicus) and Tanezumi rats (R. tanezumi), and rarely in house mice (M. musculus), long-tailed field mice (Apodemus sylvaticus), muskrats (Ondatra zibethicus), and bank voles (Myodes glareolus). All of these species are known as (commensal or non-commensal) synanthropic species. Human hepatic capillariosis cases are associated with poor hygienic conditions and the presence of rodents (e.g., rats) (Fuehrer et al. 2011). Davis (1951) reported that C. hepaticum is significantly less prevalent in decreasing rat populations than in stationary or increasing populations. A study conducted in Michigan (USA) with deer mice revealed that parasite prevalences are correlated negatively with heterozygosity when the effects of population density were held constant (Meagher 1998). Meagher further hypothesizes that inbred populations are more susceptible to parasite infestations. Differences in the prevalences of C. hepaticum in different rodent host species are thought to be associated with different living and nutritional habits (Schmidt et al. 1998). Several authors report that C. hepaticum occurs in localized foci of the examined study areas (e.g., Reperant and Deplazes 2005;Stojčević et al. 2002). Furthermore, cannibalism may be an important eggreleasing mechanism and is an important source of infection in burrows. On the other hand, predation seems to be responsible for scattered foci of infection (Farhang-Azad 1977a, b;Stojčević et al. 2002). Decomposition is thought to be a less important egg-releasing mechanism. Environmental conditions (humidity and temperature) are also associated with the distribution of these pathogens (e.g., Resendes et al. 2009). The pathogenicity of C. hepaticum in Muroidea hosts is considered low, although experimental infections of rats and mice have been demonstrated to lead to hepatic failure and the death of the host (the host survival rate is reduced by 5-10 %) (Singleton and Chambers 1996). However, individual variations of the host's inflammatory reaction to the parasite have been reported. Furthermore, hypersensitivity is associated with repeated infections (Borucinska and Nielsen 1993).
Hepatic capillariasis-geographic distribution in Muroidea hosts C. hepaticum has been found in Muroidean hosts in more than 60 countries in Europe; North, Central, and South America; Asia; Africa; and Oceania. R. norvegicus is the rodent species with the highest prevalences worldwide. In Europe, North America, South America, and Asia, several studies reported prevalences above 50 % in Norway rats (e.g., Easterbrook et al. 2007). Also other murid host species can present high prevalences in certain regions. In Asia, the nematode was found in prevalences above 50 % in the common species R. tanezumi and the white bellied rat (Niviventer fuloscens) (e.g., Yuan et al. 2000;Zhou et al. 1998). Furthermore, the muskrat (O. zibethicus) seems to be an important host of C. hepaticum in North America (Borucinska and Nielsen 1993). In the UK, high prevalences of this parasite were observed in long-tailed  Pleščëv and Kozlov (1978) Japan Shimatani (1961); Sato and Shimatani (1960); Iwaki et al. (1993); Ito et al. (1996); Yagisawa (1978) Zhang et al. (2003) Malayan field rat (Rattus tiomanicus)

Conclusions
C. hepaticum is a worldwide-distributed parasite with rodents of the superfamily Muroidea as main hosts. C. hepaticum has been described in more than 90 rodent species. Murinae and Arvicolinae are the hosts with the highest prevalences of this parasite. The Norway rat seems to be the most important host species with reported prevalences above 50 % on several continents. However, a high percentage of the studies dealt with Norway rats only, and not with less common murid rodents. Especially synanthropic (commensal and noncommensal) Murinae and Arvicolinae seem to be the most affected hosts. However, the diagnosis of this pathogen is limited to liver biopsies and necroscopy and so the true prevalence in Muroidea and other mammals remains unclear. At spurious infections, care should be taken to exclude mix-ups with other Trichuridae and Capillaridae shedding eggs of almost similar morphology (e.g., Bork-Mimm and Rinder 2011;Di Cesare et al. 2011;Stuart et al. 2013;Traversa et al. 2011). Novel (molecular) diagnostic tools for proper (molecular) species classification are of urgent need. PhD Thesis, Universität., Veterinärmedizinische Fakultät, Leipzig: 145pp. Castro JG (1944)