A Systematic Overview of Zoonotic Helminth Infections in North America

Blaine A. Mathison, BS, M(ASCP); Bobbi S. Pritt, MD, MS, DTM&H

Disclosures

Lab Med. 2018;49(4):e61-e93. 

In This Article

Cestodes

Cestodes (tapeworms) are segmented flatworms that have complex multihost life cycles involving a vertebrate definitive host and 1 or more invertebrate or vertebrate intermediate hosts. Adults typically reside in the small intestine of their definitive hosts. Structurally, adult cestodes are made up of 2 main sections: the scolex, which attaches to the intestinal mucosa of the definitive host, and the strobila (body), which is made up of individual segments called proglottids. Cestodes are hermaphroditic: each proglottid contains male and female sexual structures. Although self-fertilization is possible, copulation between 2 individual worms is the preferred method of reproduction. Microscopically, the parenchyma contains numerous small calcified structures of varying size and shape called calcareous corpuscles, the presence of which is diagnostic for cestodes (Figure 4F, inset).[49]

There are 2 main groups of cestodes that cause human infection: Pseudophyllidea and Cyclophyllidea. These 2 groups are probably paraphyletic (derived from a common ancestor but not containing all descendant groups) but still serve as convenient subcategories for clinical and medical purposes.[49]

There are several ways to diagnose cestode infections. For those species that develop to adults in the human host and colonize the human intestinal tract, diagnosis is typically made by finding eggs or proglottids in stool specimens. For invasive larval infections, diagnosis is usually made by serology or histopathologic examination of biopsy specimens.

Pseudophyllidean Cestodes

Pseudophyllidean cestodes are characterized by bothria (sucking grooves) on the scolex, rather than 4 suckers, and by having the genital pore on the proglottids located on the midventral surface. Typically, the eggs of pseudophyllidean cestodes are shed unembryonated and possess an operculum, which is more commonly seen on trematode eggs. Medically important genera include Dibothriocephalus, Adenocephalus, Spirometra, and Diphyllobothrium.

Dibothriocephalus latus and D. nihonkaiensis (Dibothriocephaliasis, Broad Fish Tapeworm Disease).General considerations: Dibothriocephaliasis (formerly referred to in part as diphyllobothriasis) is a disease caused by cestodes of the genus Dibothriocephalus. North American members of this genus implicated in human disease were historically placed in the genus Diphyllobothrium until Dibothriocephalus was resurrected, based on molecular and morphologic data.[50] In North America, the 2 primary agents of human disease are D. latus and D. nihonkaiensis. Dibothriocephalus latus occurs in fish living in cool, freshwater lakes throughout much of the Northern Hemisphere; the natural definitive hosts include a variety of animals, such as bears, pigs, cats, dogs, foxes, and wolves. Dibothriocephalus nihonkaiensis infects several species of Pacific salmon in the Northern Pacific between Japan (where the disease is considered endemic) and the Pacific Northwest of the United States; bears are the primary natural host.

The first confirmed case of D. nihonkaiensis acquired in the United States was in 2015; however, earlier cases of dibothriocephaliasis from the Pacific Northwest that were previously attributed to D. latus may have actually been caused by D. nihonkaiensis.[51,52] Other North American species of Dibothriocephalus that have rarely been implicated in human disease include D. dalliae and D. ursi. In addition, there are 4 North American species that are still currently retained in the genus Diphyllobothrium that have also been rarely implicated in human disease: D. stemmacephalum, D. cordatum, D. lanceolatum, and D. balaenopterae.[50]

The natural hosts for Dibothriocephalus are fish-eating carnivores and omnivores. Proglottids and eggs are shed into water via feces. Eggs embryonate in the water and the first-stage larva (coracidium) is released into the water. Coracidia are ingested my microscopic crustaceans (eg, copepods) and develop into a procercoid larva. Infected crustaceans are eaten by small fish, and the procercoid larva migrates to the fish-host tissue and develops into a plerocercoid larva (also known as a sparganum). Larger fish may consume the smaller fish and serve as paratenic hosts. The natural definitive host becomes infected after eating fish containing plerocercoid larvae.[53,54] Humans also become infected after eating raw or undercooked fish containing plerocercoid larvae.

Clinical manifestations and pathologic features: The extent of clinical manifestations depends on the number of worms, the length of each worm, the nutrients absorbed by each worm, and the extent of the host response to infection. Most patients are infected with a single worm, but massive infections with >100 worms have been reported.[6] Mild infections are generally asymptomatic and may only come to medical attention when segments of proglottids are passed from the anus.[2,5] When present, signs and symptoms include nausea and vomiting, diarrhea, abdominal discomfort, and weight loss. In rare instances, massive infections lead to intestinal obstruction.

Free proglottids may also migrate into the biliary tree, causing pancreatitis, cholecystitis, or cholangitis. An additional complication that is unique to this cestode infection in humans is vitamin-B12 deficiency, resulting in macrocytic anemia and associated neurologic manifestations. There are no significant pathologic changes associated with the worm's attachment in the small intestine.[5,6] Praziquantel is the drug treatment of choice.[15]

Laboratory Diagnosis: Dibothriocephaliasis is diagnosed by finding eggs in O&P examinations of stool or chains of proglottids recovered in stool specimens. Proglottids are typically broader than long (hence the common name, broad fish tapeworm) and are characterized by a rosette-shaped, centrally placed uterus and a single genital pore located on the midventral surface (Figure 2A). Clearing proglottids in lactophenol may enhance the observation of the uterus and the eggs contained therein. Individual eggs (Figure 3E) are 58–75 μm long by 40–50 μm wide and are unembryonated when shed in feces. The eggs possess an operculum and therefore need to be distinguished from the similar-appearing eggs of trematodes by using size and other morphologic features. A helpful identifying feature that is usually present is a small knob at the end opposite the operculum (ie, the abopercular end) of the eggs. Different species of Dibothriocephalus and related genera cannot be reliably separated based on egg morphology.[1]

Spirometra mansonoides (Sparganosis). General considerations: Spirometra species are pseudophyllidean cestode parasites of dogs and cats. In humans, they manifest as a larval infection called sparganosis. The full extent of species that can cause human disease is not well known, but sparganosis acquired in the United States is usually attributed to S. mansonoides.

The life cycle of Spirometra species is similar to that of Dibothriocephalus species. Unembryonated eggs and chains of proglottids are shed into the water in the feces of the canine or feline host. Eggs embryonate in the water, and the liberated coracidia are ingested by microscopic crustaceans, such as copepods, where they develop into the procercoid larva. The crustaceans are eaten by fish, reptiles, or amphibians, and the procercoid larva develops into a plerocercoid larva (sparganum). The definitive host becomes infected after eating infected fish, amphibians, or reptiles harboring the plerocercoid larvae. Human infection has been attributed to the consumption of not only undercooked vertebrate intermediate hosts but also the accidental ingestion of the copepod host in contaminated water. Unlike with Dibothriocephalus, Spirometra species cannot develop to adults in the human host and are found only as the larval form (sparganum) in various tissues.[55]

Clinical manifestations and pathologic features: Clinical manifestations vary by the site of the sparganum in the host. Spargana can be found nearly anywhere in the body, including the pleural and peritoneal cavities, breast, orbit of the eye, brain, abdominal viscera, and spinal cord, and can continue to migrate. Most patients have a single sparganum, but infection with multiple spargana have been described.[6] Patients with sparganosis involving the subcutaneous tissues are commonly asymptomatic but may report a painful, occasionally migrating, nodule. Lesions of the breast have a similar presentation and may be noted as an incidental nodule on screening mammography.[6,56]

CNS involvement may present with a spectrum of symptoms, including seizures, headache, and focal neurologic deficits, depending on the site of the brain affected. Finally, a particular form of sparganosis caused by the related pseudophyllidean cestode referred to as Sparganum proliferum manifests as an expansile lesion comprised of multiple plerocercoids.[2] If not removed, continued proliferation can result in death to the host.[57] Although a living sparganum usually escapes detection by the host's immune system, a dying sparganum elicits a marked acute immune response, with surrounding abscess formation, and eventually, a granulomatous response. Excision is the recommended therapy for sparganosis because the spargana are resistant to praziquantel.[6]

Laboratory Diagnosis: Sparganosis is diagnosed by the finding of spargana during histological examination of biopsy specimens (Figure 4F) or intact spargana extracted from tissues or the eye. Spargana extracted from the eye need to be differentiated from nematodes that are collected in the same manner. Intact spargana are long, thin, ribbon-like, and lack true segmentation; they often have an invagination at the anterior end. Because Spirometra species do not develop to adults in the human host, neither eggs nor proglottids will be found in stool specimens. Thus, O&P examinations of stool are not useful for diagnosis.

Cyclophyllidean Cestodes

Cyclophyllidean cestodes are characterized by a scolex with 4 suckers and proglottids with a single lateral or 2 bilateral genital pores. Some species have an anterior rostellum (snout-like protuberance) armed with hooklets. The eggs of cyclophyllidean cestodes are shed embryonated with an infectious oncosphere containing 6 hooklets. Several species are adapted to use humans as definitive hosts: Taenia solium, T. saginata, T. asiatica, Dipylidium caninum, Hymenolepis nana, and H. diminuta.

Several other species cause zoonotic infections as larvae, most notably canine Taenia species and members of the genus Echinococcus. A report of suspect Raillietina was presented by a field biologist who lives in Utah.[58,59] Although a definitive diagnosis was not possible in that case due to the presence of proglottids only (no scolex was present), the patient's clinical history, epidemiological risk factors such as aspirating insect specimens (the intermediate host) and raising chickens, and residence in Utah suggested Raillietina rectractilis, a parasite of rabbits and ground squirrels in Western North America, or R. cesticillus, a widespread parasite of chickens.[60]

Dipylidium caninum (Dipylidiasis, Dog Tapeworm Disease).General considerations: Dipylidium caninum is a cosmopolitan parasite of dogs and cats, although humans can also serve as a definitive host. Adults reside in the small intestine of the definitive host, and gravid proglottids are shed individually or in short chains in the feces. Proglottids (or eggs liberated from them) are ingested by insects, such chewing lice or the larvae of fleas. Within the insect intermediate host, the oncosphere develops into a cysticercoid larva. The cysticercoid larvae remain viable within flea larvae even during the metamorphosis of the flea through pupation and development into an adult. The definitive host becomes infected after ingesting infected adult fleas or lice that contain infectious cysticercoids.[61] Humans infection occurs worldwide and is initiated after the incidental ingestion of infected insects in contaminated environmental sources or pet saliva. Children are particularly at risk due to their habits of putting a pet dog's or cat's tail in their mouth.

Clinical manifestations and pathologic features: Infected individuals are often asymptomatic. When present, symptoms may include weight loss, colic, episodic vomiting, nocturnal irritability, and in severe cases, failure to thrive. In rare instances, patients have had urticarial or eosinophilia. In many cases, infection only comes to the attention of the caregiver when individual motile proglottids are noted in the child's diaper.[1,6] No specific pathologic changes are noted at the site of intestinal attachment. Treatment is with praziquantel.[15]

Laboratory Diagnosis: The diagnosis of dipylidiasis is usually made by finding characteristic double-pored proglottids in stool specimens. Individual proglottids are small and shaped like elongated/ovals; they are often described as resembling pumpkin seeds or grains of rice (Figure 2B). Physical "teasing" or manipulation of proglottids may reveal characteristic egg packets containing approximately 8 to 15 eggs (Figure 3F); individual eggs are 25–40 μm in diameter and possess a thin shell and an oncosphere with 6 hooklets. Less commonly, proglottids will rupture, and the egg packets may be observed in O&P examinations of stool.[1]

Hymenolepis nana, H. diminuta (Hymenolepiasis, Dwarf Tapeworm Disease).General considerations: Hymenolepid tapeworms are primarily parasites of rodents. Two species implicated in human infection are Hymenolepis nana (the dwarf tapeworm) and H. diminuta (the rat tapeworm). Both species are nearly cosmopolitan in distribution, although H. diminuta is reported more sporadically than H. nana.[61]

Hymenolepis nana and H. diminuta colonize the small intestine of their rodent hosts. Because proglottids usually deteriorate while still in the host, primarily only the eggs are shed into the environment via the feces. Eggs contain a mature, infective oncosphere that when consumed by an arthropod intermediate host, such as fleas and granary beetles, invades the host insect's tissue and develops into a cysticercoid larva. The definitive host becomes infected after eating insects harboring cysticercoid larvae. Hymenolepis nana is unique in that it can bypass the insect intermediate host and that vertebrate hosts can become infected directly by the ingestion of eggs. Intestinal autoinfection also occurs with H. nana, whereby oncospheres are released from eggs while still in the intestinal tract of the definitive host. The oncospheres colonize the intestinal mucosa and develop into cysticercoid larvae. After 2 to 3 weeks, the cysticercoid larvae become adult tapeworms.[61] Humans become infected after the incidental ingestion of infected insects or directly from the ingestion of eggs from contaminated environmental sources. As with the rodent host, autoinfection can also occur in humans.

Clinical manifestations and pathologic features: Most infections are asymptomatic. However, massive infections produce symptoms such as abdominal pain, weight loss, nausea, vomiting, and diarrhea. Epileptiform convulsions and failure to thrive have also been reported in children.[6] Moderate peripheral eosinophilia may be present. No specific pathologic changes are noted at the site of intestinal attachment. As with infections with other adult intestinal tapeworms, praziquantel is the treatment of choice.[15]

Laboratory Diagnosis: Hymenolepiasis is diagnosed primarily by finding eggs during O&P examinations of stool. Because proglottids usually deteriorate while in the intestinal tract of the definitive host, proglottids and scoleces are rarely seen in stool specimens, although they may be detected during colonoscopy or in colonic washings. The eggs are round to oval-shaped and have an inner 6-hooked embryo (onchosphere) surrounded by a membrane and separated from the outer shell. H. nana eggs (Figure 3G) are 30–37 μm in diameter and have a thin, hyaline shell. The oncosphere contains 6 hooklets and 2 polar thickenings from which 4–8 filaments arise and extend towards the outer shell. H. diminuta eggs (Figure 3H) are 60–85 μm in diameter and have a thicker shell than H. nana eggs. The 6-hooked oncosphere, which is generally well-separated from the outer shell, lacks the polar filaments seen in H. nana eggs. The differences in size and presence/absence of polar filaments should readily distinguish the eggs of these 2 species.[1]

Mesocestoides species (Mesocestoidiasis). General considerations: Mesocestoides is an enigmatic genus of cestodes for which the natural life cycle still is not completely understood. Also, the taxonomy of the genus is not well understood, but human infection acquired in North America has historically been attributed to M. lineatus (synonymous with M. variabilis).

Mesocestoides is believed to have a 3-host life cycle. Adults of M. lineatus parasitize the small intestine of cats, whereas other species parasitize dogs and other carnivores or birds. Proglottids are shed in the feces of the definitive host. It is believed that arthropods or other invertebrates serve as the first intermediate host, but nothing has been described definitively in nature. However, oncospheres experimentally fed directly to vertebrate intermediate hosts have not resulted in infection, suggesting there is an additional host. The presumed second-stage larva (tetrathyridium) occurs in the peritoneal cavity or musculature of a variety of mammals, including rodents, birds, reptiles, and amphibians. Cats become infected after eating small vertebrate hosts containing tetrathyridia, and the parasite develops to an adult in the cat's small intestine. On rare occasions, the tetrathyridia will migrate through the intestinal wall and colonize extraintestinal sites as tetrathyridia, never becoming adults.[62]

Human infection usually occurs after the consumption of raw or undercooked reptiles, amphibians, poultry, or wild game containing infective tetrathyridia. Because human mesocestoidiasis is usually diagnosed by the finding of proglottids in feces, humans must serve as an adequate definitive host for this parasite.[63,64]

Clinical manifestations and pathologic features: Patients are generally asymptomatic. When present, symptoms may include abdominal pain, weight loss, and irritability.[6] No specific pathologic changes are noted at the site of intestinal attachment. Treatment is with praziquantel.[15]

Laboratory Diagnosis: Human mesocestoidiasis is diagnosed by finding proglottids in stool specimens. Mature, gravid proglottids are longer than they are wide and possess a parauterine organ that contains a mass of eggs. Individual eggs are approximately 19–24 μm long and possess a membranous wall surrounding the 6-hooked oncosphere.[1]

Taenia serialis (coenurosis). General considerations: Coenurosis is a zoonotic cestode infection caused by various canine Taenia species, including T. multiceps, T. serialis, and T. brauni. In North America, human coenurosis is usually attributed to T. serialis.

Adult T. serialis resides in the small intestine of the canine host. Proglottids and individual eggs are shed in the feces. Eggs are shed, containing a fully developed, infectious oncosphere. Intermediate hosts, such as rabbits, hares, and rodents, become infected after ingesting infectious eggs. In the intermediate host, the liberated oncosphere penetrates the intestinal wall and is carried via the bloodstream to other organs, including the CNS, muscles, and soft tissues, where it develops into a cysticercoid larva (coenurus). The definitive host becomes infected after eating intermediate hosts harboring cysticercoid larvae.[55,65]

Humans serve as an intermediate host for T. serialis and are also a dead-end host. Infection is usually acquired through ingestion of infective eggs in environmental sources contaminated with dog feces and results in further infection of the subcutaneous tissues (most common) and other sites. Taenia serialis cannot develop to an adult in the human host.[65]

Clinical presentation and pathologic features: Like infections with other larval tapeworms, the clinical presentation can vary greatly depending on location of the larva (coenurus) in the body. Subcutaneous involvement (which is usually caused by T. serialis) commonly presents as a painless or moderately tender nodule.[6] More severe manifestations may occur with involvement of the orbit or CNS, including visual impairment, seizures, nausea, and vomiting (with increased intracranial pressure), and focal neurologic deficits (ocular and CNS involvement is more likely to be caused by T. multiceps). While it is alive, the coenurus is usually separated from host tissue by a host-derived fibrous wall. On its death, however, exposed parasite antigens will trigger an acute inflammatory response that will subsequently give rise to chronic inflammation, fibrosis, and calcification.[5,6] Treatment is usually via surgical excision. Praziquantel may also be used, with the caution that the host immune response to the dying coenuri may cause significant pathology.

Laboratory Diagnosis: Coenurosis is diagnosed by the finding of coenuri in biopsy specimens (Figure 4G). Coenuri have a morphologic appearance that is similar to some other larval cestodes. The presence of multiple protoscoleces rules out cysticercosis caused by T. solium. Hydatid cysts cause by Echinococcus may also have multiple protoscoleces, but the cysts arise from a germinal membrane along a laminated layer. Unlike cysticercosis and echinococcosis, there are no serologic assays available for coenurosis. Because T. serialis cannot develop to adult form in the human host, O&P examinations of stool are not useful for diagnosis human infection.

Echinococcus granulosus (cystic hydatid disease). General Considerations: Cystic hydatid disease is caused by Echinococcus granulosus, a small tapeworm of dogs and wild canids that occurs nearly worldwide. Generally, life cycle patterns are described as domestic, in which the disease cycles between domestic dogs and livestock, or sylvatic, in which the disease cycles between wild canids and ungulates. Human infection in North America is most common in agricultural communities where sheep, goats, and other livestock that serve as intermediate hosts are raised, and cycles between domestic dogs and the sheep strain (G1) of E. granulosus.

Mature tapeworms shed eggs containing an infectious oncosphere into the feces of the definitive host. After eggs are ingested by a suitable intermediate host, the oncosphere is released in the small intestine, penetrates the intestinal wall, and is carried via the bloodstream to various organs, including the liver, lungs, and musculature. The oncosphere attaches to host tissue and develops into a hydatid cyst that enlarges over time, forming protoscoleces and daughter cysts that fill the interior of the parent cyst. The definitive host becomes infected after eating the flesh of intermediate hosts harboring hydatid cysts. In the intestinal tract of the definitive host, the protoscoleces evaginate, attach to the intestinal mucosa, and mature to adult tapeworms.[66] Humans become infected after ingesting eggs in environmental sources contaminated with dog feces. Human assume the role of the intermediate host and only harbor hydatid cysts, never adult tapeworms; the most common site of infection in humans is the liver, followed by the lungs. Less commonly, the brain, muscles, eyes, heart, bones, and spleen can be affected.

Clinical manifestations and pathologic features: The spectrum of clinical manifestations is highly dependent on the location of the hydatid cyst, its size, and whether rupture/leakage has occurred. Many cysts remain asymptomatic over many years as they slowly expand. Some anatomic locations such as the abdomen can accommodate a large (>20 cm diameter) cyst that may not be noticed for decades. However, cysts within confined spaces, such as the bones, eyes, and CNS, may quickly come to medical attention. Infection may be life-threatening when it compresses a vital organ.

Generally, in the liver, cysts do not come to attention until they reach 10 cm in diameter.[6] Patients may note a palpable abdominal mass, and jaundice may occur with compression of the biliary tree. Patients may report chest pain, cough, dyspnea, and hemoptysis. Rupture of the cyst into the bronchial tree classically results in expectoration of ruptured cysts and fluid.

Regardless of the location, cyst rupture can cause a potentially life-threatening systemic response, due to exposure of parasite antigens to the host immune system, and may invoke urticaria, vomiting, and anaphylactic shock.[6] Intact cysts are initially surrounded by a mild inflammatory response, but this quickly subsides and is replaced with host-derived fibrous wall encapsulating the cyst. External to the cyst and fibrous wall is a surrounding rim of compressed tissue. Cyst rupture evokes a brisk granulomatous inflammatory response that will eventually destroy the parasite.[6]

Treatment is based on the location of the cyst, its amenability to surgical removal or percutaneous aspiration, and its stage (eg, unilocular, multilocular, collapsed, or calcified). When suitable, the PAIR procedure (Percutaneous Aspiration of cyst contents, Injection of a scolicidal agent, and Reaspiration), is the preferred treatment. Concomitant therapy with albendazole, antihistamines, and steroids is commonly used with the PAIR approach.[15] In other cases, chemotherapy only, surgical procedures, or even a watch-and-wait approach may be used.[2]

Laboratory Diagnosis: The diagnosis of cystic hydatid disease is made based on the findings from radiographic techniques (such as ulstrasonography and computed tomography) in conjunction with positive serologic results.[66] Cystic hydatid disease also can be identified by morphologic techniques, such as the observation of cysts in biopsy specimens (Figure 4H) or the presence of protoscoleces or liberated calcareous corpuscles and hooklets (hydatid sand) in body fluid aspirates. Because E. granulosus cannot develop to adult form in the human host, O&P examination of stool is not useful for diagnosis echinococcosis.

Echinococcus multilocularis (alveolar hydatid disease).General Considerations: Alveolar hydatid disease is caused by Echinococcus multilocularis, which is distributed throughout the Northern Hemisphere. The life cycle is similar to that of E. granulosus (described earlier herein) and usually cycles between dogs, foxes, coyotes, wolves, and wild felids as definitive hosts and rodents as intermediate hosts, although domestic dogs can also host the larval stage. The site of infection in the intermediate host is almost exclusively the liver, where it forms an alveolar cyst. As with hydatid cystic disease, humans become infected with E. multilocularis from the incidental ingestion of eggs in environmental sources contaminated with canine or feline feces.[66]

The risk factors for alveolar hydatid disease are not well known, and human infection is relatively uncommon, given the prevalence of E. multilocularis in its natural definitive hosts. Occupational or behavioral factors are believed to play a role in human disease. Two groups in North America that are believed to be at increased risk are hunters or trappers that come in contact with infected definitive hosts[67] and Eskimos who live closely with their dogs in houses built directly on the tundra without a gravel or permanent foundation.[68] The most common site of infection in humans is the liver, where the larva manifests as a slow-growing destructive tumor-like cyst, occasionally with metastatic lesions in the brain, lungs, peritoneum, and other areas of the body.

Clinical manifestations and pathologic features: Alveolar hydatid disease is characterized by slow, progressive proliferation of cysts that encompass normal structures and cross tissue planes, much like a malignant neoplasm.[5,6,8] This disease is usually fatal if untreated. Given the infiltrative nature of the infection, extensive surgical debridement (with complete removal when possible) is the mainstay of treatment, accompanied by albendazole therapy for a minimum of 2 years.[15] Lifelong suppression with albendazole may be necessary when complete surgical excision is not achieved.

Laboratory Diagnosis: As with cystic hydatid disease, diagnosis of alveolar hydatid disease is made based on the findings from radiographic techniques in conjunction with positive serologic results.[66] Also, as with hydatid cyst disease, humans cannot serve as definitive hosts for E. multilocularis. Therefore, O&P examination of stool is not appropriate.

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