Introduction

The acanthocephalans, spiny-headed worms, comprise parasites infecting a wide range of invertebrates and vertebrates [1]. This group of helminths was formerly assigned to its own phylum Acanthocephala, but the taxon is now regarded as a sister-group to Rotifera within the phylum Syndermata. In his classification of the taxon Acanthocephala, Amin treated 157 genera and 1298 species infecting mammals, birds, reptiles, amphibian and fish [1]. Numerous reports documented that humans may host terrestrial species within the genus Macracanthorhynchus [2,3,4,5,6,7,8]. In addition, humans may be infected by other terrestrial and semi-aquatic species within the genera Plagiorhynchus, Acanthocephalus, Pseudacanthocephalus and Moniliformis [9•]. During recent decades, also fully aquatic acanthocephalans (parasites with all life cycle stages in aquatic animals) have been reported as human pathogens [9•]. The different teleost species may carry these more or less host specific acanthocephalans, which at present comprises several hundreds of species belonging to several genera [1]. In this context, it should be noted that the majority of fish infecting acanthocephalans occur in the adult stage in the fish intestine, are non-zoonotic and do not represent a human health hazard. However, a number of species within two genera, Bolbosoma and Corynosoma, occur as a juvenile stage in fish (paratenic hosts) and may infect humans and cause disease.

Non-Zoonotic Acanthocephalans in Fish

Fish can also serve as definitive hosts to acanthocephalans residing as adults in the gastro-intestinal tract of the fish [1]. These are all non-zoonotic. As these worms lack a mouth and an intestine, they absorb the host nutrients via their tegument and may in this way compete with the host for energy. However, the main impact of the infection on the host is due to attachment of the parasite to the host mucosa by use of its proboscis equipped with hooks. This attachment organ of some acanthocephalan species may penetrate deeply into the intestinal wall of the fish, which may elicit severe pathological reactions as seen with Pomphorhyncus laevis (Fig. 1). The presence of the forepart of this worm in the gut wall elicits a marked encapsulation process [10]. Other species exert merely a mild impact on the intestinal wall, as exemplified by the high infection levels of Echinorhynchus gadi, in the Atlantic cod intestine [11]. This species has a proboscis with numerous small hooks. By use of this proboscis, the worm attaches superficially to the mucosa, and in that host-parasite system, the infection is not associated with pathological reactions in the intestinal wall. However, a high worm burden depletes the host for energy, and as the liver is the main energy (lipid) depot of the cod, the host may suffer from a lowered liver weight [11]. These non-zoonotic acanthocephalans have a simple life cycle strategy employing the fish as definitive host, while small crustaceans, such as amphipods or isopods, as intermediate hosts are carrying the larval stage. Eggs from the female worm leave the fish host with faeces and infect the crustacean in the aquatic environment. When the fish consumes the intermediate host, the larva will develop into the adult stage in the fish intestine. Despite the fact that these acanthocephalans are non-infective to mammals and thereby non-zoonotic, their mere presence may have a repellent effect on consumers and thereby be of economic concern [12].

Fig. 1
figure 1

The fish parasitizing acanthocephalan Pomphorhynchus laevis from the fish intestine. The characteristic proboscis equipped with numerous hooks and a bulbous enlargement below the proboscis. Scanning electron microscopy. Scale bar 1 mm

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Zoonotic Acanthocephalans in Fish

A number of other acanthocephalans in fish are on the other hand potentially zoonotic. They occur in the fish in their juvenile stage but develop into the adult stage in a marine mammal or a bird upon predation [12]. Human consumption of insufficiently heat or freeze treated fishery products, carrying these infective stages, may lead to infection of the consumer and subsequently cause clinical disease. These parasites, belonging to the genera Bolbosoma and Corynosoma, within the family Polymorphidae, occur as juveniles in various body compartments of fish serving as paratenic hosts. They usually use marine mammals (cetaceans and pinnipeds) as definitive hosts, in which the adult parasite targets the mucosa of the gastrointestinal wall. Bolbosoma parasites parasitize whales [13••, 14••]. In the marine environment, eggs may be ingested by small crustaceans (copepods, krill) [15], which obtain infection and become infective for paratenic host fishes. Corynosoma infects seals by attaching it proboscis equipped with numerous hooks to the host mucosa (Fig. 2). In its life cycle (Fig. 3), it applies small crustaceans (amphipods, isopods and mysids) as intermediate hosts and various fish species as paratenic hosts [16•, 17]. The parasite eggs are released from the adult female acanthocephalan (in the intestine of the marine mammal) and leave the host with faeces. In the marine environment, eggs may be ingested by small crustaceans serving as first intermediate hosts [9•]. When a fish ingests the infected crustacean, the parasite larva passes from the fish gut to internal body compartments (gut wall, peritoneum, mesenteries, body cavity), where it becomes encapsulated in a cellular host reaction. The infection process comprises a development from the acanthor hatching from the egg via the acanthella stage in the crustacean to the cystacanth stage, which is a juvenile encysted parasite awaiting further development to the adult [9•]. Despite the host-mediated encapsulation process, the acanthocephalan larva/juvenile in fish remain viable and reach the final destination when a marine mammal ingests the infected fish [9•]. In the seal/whale gut, the parasite develops to the adult stage.

Fig. 2
figure 2

The adult Corynosoma semerme (female) recovered from a grey seal from the Baltic Sea. The proboscis (0.25 mm) equipped with hooks is partly inverted in the proboscis sheath. Light microscopy

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Fig. 3
figure 3

The life cycle of Corynosoma showing the definitive host, the seal, the intermediate host (crustaceans) and the paratenic host (fish)

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Human Cases

The potentially zoonotic acanthocephalans belong to two genera of which species within the genus Bolbosoma attain their adult stage in whales serving as definitive hosts. A total of 12 species are recognized [1], but not all have as yet been associated with human infection. Seals act as definitive hosts to species within the genus Corynosoma. A total of 50 species within the genus are recognized [1], but only few have been recovered from human patients. It may be hypothesized that during evolution the physiology of these parasites were adapted to homeothermic warm-blooded mammalian hosts, in which they attain sexual maturity and reproduce. The adaptation to a life in the warm-blooded host would then be the physiological basis for their success as human pathogens as they survive the entrance into a gut with a high body temperature, whereafter they may attach to the intestinal mucosa and in some cases develop into the adult stage.

Bolbosoma Cases in Humans

Evidence that acanthocephalans within the genus Bolbosoma are potentially infective to humans was presented in Japan in 1983 [18]. A male patient was admitted to hospital due to acute abdominal pain. The patient had ingested sashimi (a raw fish dish) and subsequently complained about pain in the right lower quadrant. Surgery revealed ileum perforation associated with a worm, which was assigned to the genus Bolbosoma. The parasite body was 13.5 mm, the proboscis 0.715 mm and width 0.455 mm. The proboscis carried 16 longitudinal rows each with 8 to 9 hooks. Below the proboscis, the body was enlarged to a distinct bulb with thorny zones. The fish species ingested by the patient prior to infection was unknown, but the authors mentioned that bluefin tuna may be infected by Bolbosoma parasites [18]. Later, in the same year, a second report was presented also from Japan [19]. A 16-year-old boy experienced severe abdominal pain. Explorative laparotomy was performed, and an eosinophilic granuloma in the serosa of the ileum was removed. Within the granuloma, a Bolbosoma sp. parasite was noted and identified. The patient had a history of frequent ingestion of raw marine fish, but no species designation was provided [19]. Following these first reports, a series of new cases from Japan (both male and female patients up to an age of 70) with infection foci in stomach, duodenum and ileum were reported during the next decades [20,21,22,23]. The species identification was not performed, but with the advent of molecular identification technology (PCR and sequencing), a better identification became possible [24, 25]. Thus, a nodular lesion in the ileum of a > 60-year-old male patient, with a previous history of eating raw fish, was resected and a molecular analysis identified the worm as Bolbosoma cf. capitatum [24]. In addition, a small bowel obstruction in a 27-year-old female patient due to a closely related Bolbosoma species was described [25]. Based on parasitological studies of marine mammals in Japanese waters, the authors suggested that B. turbinella, B. nipponicum and B. capitatum could be involved in the human cases.

Corynosoma Cases

The first report of a human infected with a Corynosoma strumosum acanthocephalan was based on collection of a juvenile specimen recovered from a stool sample delivered by a native citizen (male) in Chevak (Alaska) following anthelmintic treatment exerted by a local physician [26]. No clinical signs associated with the infection were reported, although it can be speculated that treatment was installed due to patient complaints. Eating habits (consumption of raw fish) were suggested to explain the infection. The second human infection was caused by Corynosoma validum [27]. A 70-year-old female from Japan experienced abdominal pain, was hospitalized and subjected to endoscopy. Ulcerations in ileum were found associated with presence of a 10 mm long and 3 mm wide parasitic helminth. Histology of the recovered worm showed a load of mature eggs indicating that the female parasite was sexually mature. Molecular identification (PCR and sequencing of ribosomal DNA and mitochondrial DNA) of the worm was performed showing a high identity with C. validum [27]. The infection was explained by consumption of raw fish, but no species identification was provided. Anthelmintic treatment (pyrantel pamoate) relieved the abdominal pain and symptoms. The third case reported that a 73-year-old male was hospitalized and treated both in 2013 and in 2014 [28]. On the first occasion, abdominal pain and suspected ileus were the reasons for endoscopy revealing a 5-mm worm piercing the ileum wall. The same patient was again in 2014 hospitalized due to melena (blood stool) and subjected to endoscopy. A total of four acanthocephalans (three male and one gravid female) were recovered in jejunum. Morphological description complied with C. villosum. Molecular identification was also performed, and based on PCR and sequencing (rDNA), a strong affiliation (but not full identity) with C. villosum and C. validum was found [28]. The patient reported frequent ingestion of raw fish products, which was believed to be the cause of infection. No information about the fish species consumed by the patient was provided, but the authors reported the presence of cod, flounder, mackerel and herring in the local area for fish capture.

Pathogenesis

The pathological reports from the patients infected by species belonging to Bolbosoma and Corynosoma showed the ability of both juvenile and adult acanthocephalans to attach to and penetrate the intestinal mucosa of the patient and cause ulcerations. The proboscis hooks are likely to injure the mucosa, and by mechanical retraction of the worm hooks, it may proceed further into the target tissue, probably assisted by proteolytic substances released by the proboscis glands [29]. The parasite may carry a dense covering with spines in their caudal and lateral sides, which may add to the pathological changes. The ulceration elicits abdominal pain and nausea in the patient [25]. Dilatation of the intestinal wall and ascites result from the inflammatory processes initiated. In worst cases, the perforation of the intestinal wall may follow and bleeding occur [28]. Penetration into the serosa may lead to full encapsulation of the parasite [19].

Diagnostic Precision and Accuracy

When diagnosing the causative pathogen in human infections, the precision of the identification based on morphological characters requires specialist knowledge [29], which may challenge the diagnostic precision in primary health care. The diagnosis may be further hampered if the parasite is encapsulated in host cells or is partly injured, whereby morphological characters (overall body structure, proboscis shape, hook morphology and numbers, arrangement of gonads, tegumental spine arrangement) needed for identification [29] may be partly lost. Even when well-preserved specimens of various species within the genera Bolbosoma and Corynosoma have been isolated, the identification process is laborious [13••, 14••]. The early studies on human cases of both Bolbosoma and Corynosoma infections did not reach a species identification [18,19,20,21], as the genus identification may be conducted with some precision, whereas species differentiation is challenging also for experts. The advent of molecular techniques involving isolation of parasite DNA, performing PCR, sequencing and alignment with GenBank NCBI data has improved the diagnostic precision during recent decades [24, 25, 27, 28]. However, the choice of diagnostic DNA target sequences is important. When performing a molecular identification of parasites responsible for human infections with Bolbosoma and Corynosoma acanthocephalans, the first choice has been parts of the ribosomal DNA (rDNA) such as ITS and 5.8 S [24, 28], which provides some species differentiation. However, the inclusion of both rDNA and mitochondrial DNA (mtDNA) secures an even higher resolution [13••, 14••, 25, 27], suggesting that these DNA regions should be targeted in the future.

Risk Assessment

All cases presented indicate that consumption of raw fish or inadequately heat- or freeze-pretreated fish increase the risk of infection. This is due to the presence of infective juvenile stages of the parasites in edible parts of the fish. The parasites are natural elements in the marine ecosystem where whales and seals are present [16•, 30,31,32], and without the presence of these definitive host, the life cycle would be broken. The infection level in fish are likely to increase with growing populations of marine mammals. In the Baltic Sea, a marked population increase of the grey seal (Halichoerus grypus) population has occurred over the last 30 years. This has been reflected by the elevation of prevalence and intensity of nematodes such as Phocanema (synonym Pseudoterranova) and Contracaecum similarly associated with seals as final hosts [33,34,35, 36•]. Indications have been presented that during the same time period, also the prevalence of Corynosoma parasites has increased in food fishes in the same area (turbot, smelt and cod) of the Baltic Sea [37,38,39]. Seals in the Baltic Sea are infected with Corynosoma (Fig. 2) and with an increasing population of grey seal, which now have reached 45,000 individuals [40], and with a 5% annual increase, the infection pressure is likely to increase in the future. Populations of marine mammals should therefore be monitored and regarded as an important factor in risk assessments. Consumer choice of fishery products is one of the main parameters when evaluating the risk of infection. Parasitological investigations of fish have disclosed a broad risk.

Risks Associated with Specific Fish Species and Products

Consumption of insufficiently heat- or freeze-treated fish products represent a risk of infection [41], and cases of human infections with human Bolbosoma and Corynosoma infection report ingestion of raw fish (including sashimi) prior to infection [24,25,26,27,28]. However, the consumer’s choice of fish will affect the risk of contact with parasites. It is therefore noteworthy that a wide range of taxonomically non-related fish species are susceptible to infection with Bolbosoma and Corynosoma parasites and readily serve as paratenic hosts. Ruffe (Gymnocephalus cernua), shorthorn sculpin (Myoxocephalus scorpius), brook charr (Salvelinus fontinalis) and Atlantic halibut (Hippoglossus hippoglossus) have been recorded as C. magdaleni infected [16•]. C. semerme was recorded from sturgeon (Acipenser sturio), European eel (Anguilla Anguilla), Atlantic herring (Clupea harengus), white bream (Blicca bjoerkna), pike (Esox Lucius), polar cod (Boreogadus saida), Atlantic cod (Gadus morhua), burbot (Lota lota), anglerfish (Lophius piscatorius, Pacific rainbow smelt (Osmerus dentex), perch (Perca fluviatilis), American plaice (Hippoglossoides platessoides), common dab (Limanda limanda), flounder (Platichthys flesus), European plaice (Pleuronectes platessa), turbot (Scophthalmus maximus), Atlantic salmon (Salmo salar), brown trout (S. trutta), grayling (Thymallus thymallus), fourhorn sculpin (Myoxocephalus quadricornis) and lumpfish (Cyclopterus lumpus) [16•]. A corresponding host list stands for C. strumosum infections but with important additions of various fish species from the Pacific Ocean. These comprise Pacific herring (C. pallasii), saffron cod (Eleginus gracilis), Arctic cod (E. nawaga), Alaska Pollock (G. chalcogrammus), Pacific cod (G. microcephalus), haddock (Melanogrammus aeglefinus), Japanese smelt (Hypomesus japonicus), pink salmon (Oncorhynchus gorbuscha), chum salmon (O. keta), sockeye salmon (O. nerka), masou (O. masou), white spotted charr (Salvelinus leucomaenis) and threestripe rockfish (Sebastes trivittatus) [16•]. In certain marine habitats, such as the Caspian Sea, the infection prevalence and intensity of the local Caspian sprat (Clupeonella grimmi) may reach 90% and 34 parasites per fish, respectively [42]. These investigations clearly demonstrate that the host specificity is low and that consumer safety cannot rely on choice of fish species. Some of these listed teleost hosts are especially popular among consumers, which will emphasize that food and health authorities should have focus on preventive measures.

Preventive Measures

Infection risk is associated with consumption of fishery products containing live infective parasites. Therefore, the pre-treatment of products to kill viable parasite stages should be conducted to prevent infection. Heat treatment (> 60 °C for more than 1 min) and freeze treatment (below minus 20 °C for 24 h) kill zoonotic anisakid nematode larvae and trematode metacercariae in fishery products [41]. Although no systematic studies on heat treatment of juvenile acanthocephalans have been performed up until now, it is likely that similar pre-treatment of fish products carrying Bolbosoma and Corynosoma parasites will be effective. However, it is not known if freezing, as stipulated in EU (EC) regulation No. 853/2004 prescribing freezing at − 20 °C for 24 h, is sufficient to kill infective Corynosoma and Bolbosoma parasites in fish products. It is therefore recommended to investigate effects of heat and freeze pre-treatment on viability of Bolbosoma and Corynosoma parasites (at different developmental stages). The infection pressure on fish is caused by the presence of infected definitive hosts in specified marine areas. A reduction of infection risks may therefore be achieved through regulation of populations of cetaceans and pinnipeds.

Treatment of Infections

Anthelmintic treatment of acanthocephalan infections is possible. Macracanthorhynchus infections of human patients have been successfully treated with mebendazole [43]. With regard to human infection with Corynosoma, it was reported that treatment with pyrantel pamoate effectively treated symptoms [27]. However, despite the availability of a series of licensed anthelmintics, we have merely obtained scattered knowledge on differential drug effects and dose response effects. This calls for further studies, and it is therefore recommended to conduct systematic investigations (in vivo and in vitro) on anthelmintic effects on Bolbosoma and Corynosoma.

Conclusions

The present review provides evidence that consumption of insufficiently pre-treated fishery products is associated with a risk for infection with a number of species within the genera Bolbosoma and Corynosoma. The parasites exhibit a low paratenic host specificity, which emphasizes that infections are connected to a wide range of fish species. The use of molecular tools in association with classical morphological studies should be applied to optimize diagnostic precision. Prevention of infection may be achieved by reducing the populations of definitive hosts (whales and seals). When fish are infected, there is a need to determine heat and freeze effects on the viability of the acanthocephalans. If humans are infected, anthelmintic treatment is preferred to surgery. Systematic investigations on anthelmintic usage should therefore be conducted in order to optimize treatment regimes.