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

Trematodes

Trematodes are parasitic flatworms commonly referred to as flukes. All species have complex life cycles with 1 or more intermediate hosts; in all species that parasitize humans, the first intermediate host is a freshwater or terrestrial snail. Most adult trematodes are hermaphroditic, the major exception being Schistosoma spp, in which individual adult males and females live as a coupled pair, with mature females residing in a gynecophorol canal along the male's body. Structurally, most trematodes are flat and elongated, often tapering on 1 or both ends and appearing leaf-shaped. Adults are characterized by having 2 muscular suckers: an oral sucker that surrounds the mouth and a ventral sucker (acetabulum) located further down the body. Both suckers function for attachment to host tissue. Although self-fertilization is possible among the hermaphroditic species, mating between 2 individual flukes is the optimal method of reproduction for genetic variation. Eggs shed by flukes may be unembryonated or embryonated, and possess an operculum (non-Schistosoma spp) or lack an operculum but possess a terminal or lateral spine (Schistosoma spp).[69]

Diagnosis of trematode infections varies by the species and location in the host, but most trematode infections can be diagnosed by finding eggs in clinical specimens (stool, urine, respiratory specimens). Trematode eggs are often shed intermittently and in low numbers, so concentration procedures and examination of multiple collections are recommended to enhance detection. Serologic examination is also available for some species.

Most trematode infections are endemic to tropical and subtropical areas of South America and the Caribbean, Mediterranean, Middle East, Africa, and Southeast Asia. Few trematode infections are naturally acquired in North America.

Fasciola hepatica (Fascioliasis). General Considerations: Fasciola hepatica is a large trematode that resides in the large biliary ducts of its definitive hosts (Figure 2C). Fasciola hepatica has a nearly worldwide distribution: cattle, sheep, and goats are its normal definitive hosts. A second species, F. gigantica, causes human infection in Africa and Asia.

Gravid flukes discharge unembryonated eggs into the biliary ducts that are eventually passed via the feces of the definitive host into fresh water. Eggs embryonate in the water and release the first-stage larva, known as a miracidium. The miracidium infects an appropriate snail host and undergoes several asexual cycles, resulting in the formation of motile cercariae. The cercariae leave the snail host and encyst as metacercariae on aquatic vegetation, such as watercress and water parsley. The definitive host becomes infected after eating undercooked or raw vegetable matter containing infectious metacercariae. In the definitive host, metacercariae excyst in the duodenum, and the young flukes penetrate the intestinal wall and invade the peritoneal cavity. Then, they penetrate the capsule of the liver and migrate throughout the liver parenchyma, leaving inflammation and fibrosis in their wake. They eventually penetrate bile ducts, where they mature to adults. Ectopic colonization of other organs, such as the intestine, brain, skin, pharyngeal mucosa, and lungs, can also occur on rare occasions. The time between ingestion of metacercariae and maturation to an adult is approximately 3–4 weeks.[70]

Like the natural definitive host, humans also become infected after ingesting metacercariae on contaminated plants or water in which such plants are growing. Humans can also ingest eggs after eating the infected liver of herbivores and pass the eggs in stool. Such shedding of eggs is spurious and needs to be distinguished from true infection (see the Laboratory Diagnosis section later herein).

Clinical manifestations and pathologic findings: Patients generally experience symptoms such as fever and abdominal pain during the initial migration of larval flukes throughout the peritoneum and liver, as well as nausea, vomiting, lack or loss of appetite for food, and diarrhea. Eosinophilia and urticaria are also common, with dermatographism being a distinctive feature during early infection.[6] In heavy infections, significant fibrosis and even cirrhosis can occur due to the damage caused by larval migration. Additional location-specific symptoms may occur in cases of ectopic migration. Once the flukes reach the bile ducts, they cause mechanical irritation and obstruction of the biliary tree due to their large size, resulting in epigastric pain, biliary colic, fat intolerance, jaundice, right upper quadrant tenderness, hepatomegaly, ascites, and choledocalithiasis.[5,6,8] Mild to high levels of eosinophilia are common throughout all stages of infection, as well as anemia, an elevated sedimentation rate, hyperbilirubinemia, and elevated IgE levels. Unlike the other flukes, Fasciola does not respond to praziquantel and instead must be treated with triclabendazole. This drug is not commercially available in the United States and can only be obtained after consultation with the CDC through an investigational use protocol.[2,15]

Laboratory Diagnosis: Diagnosis of fascioliasis is made primarily by finding eggs during O&P examination of stool (Figure 3I). Often, eggs are shed intermittently and in small numbers, so concentration procedures and multiple collections are required. Eggs in fresh clinical specimens are unembryonated and measure 130–150 μm long by 63–90 μm wide and have a small, inconspicuous operculum. The eggs are morphologically indistinguishable from the trematodes Fasciolopsis buski and Gastrodiscoides hominis, which are endemic to India and Southeast Asia.[1] Adults and eggs may be detected in liver biopsy specimens. Eggs observed in biopsy specimens should be distinguished from those of Schistosoma spp, which are roughly the same size but possess a fully developed miracidium.[8] As mentioned previously herein, eggs may be found in the stool of patients who consumed the infected livers of cattle or other herbivores. In these cases, the passage is spurious, and additional collections should be performed to rule out true infection. Serologic examination is available for fascioliasis at the CDC in the United States.[71]

Paragonimus kellicotti (Paragonimiasis). General Considerations: Paragonimus is a genus of trematodes that infects the lungs of its definitive hosts. There are roughly 8 to 9 species that cause clinical disease in humans, but only P. kellicotti (Figure 2D) is endemic to North America, where it is found in streams and rivers in the Mississippi River Basin, including the central United States west to the Rocky Mountains. Primary definitive hosts for P. kellicotti include domestic cats, bobcats, skunks, foxes, coyotes, and minks.

Sexual reproduction between 2 individuals is the norm for Paragonimus species. Paired adults of P. kellicotti reside in cysts in the pleural space of the definitive host. After mating, the cysts rupture, releasing eggs into the lungs that are coughed up and expelled in respiratory secretions or swallowed and passed in feces. Eggs embryonate fully in fresh water, followed by the release of a miracidium. The miracidium infects an appropriate snail host and undergoes several cycles of asexual reproduction, resulting in the formation of cercariae. Cercariae leave the snail host and infect the next intermediate host: crayfish. Within the crayfish host, cercariae encyst as infective metacercariae. The definitive host becomes infected after eating crayfish harboring infective metacercariae. The metacercariae excyst in the small intestine, and the young fluke penetrates the intestinal tissue and migrates to the peritoneal cavity. After about 2 to 3 weeks, the flukes migrate through the diaphragm to the pleural space, where they mature. Experiment evidence suggests that some Paragonimus will not develop to the adult fluke stage until they come in contact with an appropriate mate.[72–74] Like the natural definitive host, humans become infected after eating undercooked or raw crayfish infected with metacercariae. Ectopic cerebral paragonimiasis is a rare but well-described phenomenon.[6]

Clinical manifestations and pathologic features: Patients are often asymptomatic during the initial migration stage of infection, although some develop diarrhea and abdominal pain.

Once in the lung, the presence of the flukes within a cystic cavity elicits an inflammatory response associated with cough and expectoration of rusty-colored, foul-smelling sputum (described as having a fishy odor).[6] Chest pain and night sweats may also occur, which clinically mimic symptoms of tuberculosis (TB). In cases of heavy infection, complications such as pneumothorax, hydropneumothorax, and pleural effusion may occur.[6] Eosinophilia ranging from 10% to >90% is seen in most patients and is a useful differentiating feature from TB. Over time, patients will often continue to experience fever and cough, as well as fatigue, myaligia, clubbing of fingers, and rales.[6] In cases of cerebral paragonimiasis, the flukes and their eggs evoke a brisk inflammatory response with abscess and granuloma formation.[5,6,8] Symptoms include headache, vomiting, seizures, and focal neurologic deficits. Treatment is usually with praziquantel.[15]

Laboratory Diagnosis: Diagnosis of paragonimiasis is usually made by finding eggs in respiratory specimens or O&P examination of stool. Eggs in fresh clinical specimens (Figure 3J) are unembryonated and measure 80–120 μm long × 45–70 μm wide, with a moderately thick shell and an obvious operculum and prominent opercular shoulders. The abopercular end is often thickened, but there is not a defined abopercular knob.[1] Adults and eggs can also be found in lung biopsies. Paragonimus eggs are birefringent (having 2 different refractive indices) under polarized light in histopathology specimens.

Serologic testing is available for paragonimiasis. Also, Western blot assay has been optimized to detect infection caused by P. kellicotti.[75]

Nanophyetus salmincola (Nanophyetiasis).General Considerations: Nanophyetus salmincola is an intestinal fluke that parasitizes fish-eating mammals and birds in the Pacific Northwest. Natural definitive hosts include foxes, raccoons, otters, coyotes, skunks, herons, and mergansers. The primary intermediate hosts are fish in the family Salmonidae, and the definitive hosts becomes infected after eating infected fish harboring metacercariae. Dogs can experience a fatal rickettsial disease called salmon poisoning that is carried by the flukes.[76]

Human infection also comes from the ingestion of metacercariae in infected salmon and related fish, although there is at least 1 case of a fish handler becoming infected after necropsying coho salmon without wearing protective gloves; the infection probably resulted from the incidental ingestion of metacercariae after contact with contaminating environmental sources.[76] Despite being common in naturally infected hosts, there are less than 50 documented human cases.[77,78]

Clinical manifestations and pathologic features: There are too few documented cases of human nanophyetiasis to get a complete sense of its clinical picture, but patients have presented with abdominal discomfort, diarrhea or increased number of bowel movements, fatigue, nausea, vomiting, weight-loss, and eosinophilia.[77] The pathologic response to human nanophyetiasis is undescribed in the literature, to our knowledge. Nanophyetus salmincola can host 2 species of Neorickettsia that cause salmon poisoning disease, a fatal rickettsial disease in dogs;[79] humans do not appear to be affected by the bacterium. Praziquantel is the drug of choice for nanophyetiasis.[80]

Laboratory diagnosis: Human nanophyetiasis is diagnosed by finding eggs during O&P examination of stool. Eggs are unembryonated and measure 64–97 μm long × 34–55 μm wide. The operculum is relatively inconspicuous, and the abopercular end is blunt and thickened.[1]

Metorchis conjunctus (Metorchiasis).General considerations: Metorchis conjunctus is a liver fluke that parasitizes fish-eating mammals, such as bears, foxes, wolves, raccoons, minks, and fishers in Canada and the northeastern United States. Domestic dogs and cats can also serve as definitive hosts. The primary intermediate host and known source of human infections is the white sucker, Catostomus commersonii.[81,82] Human infections are rare but have been documented sporadically in Canada.[75,81,83]

Clinical manifestations and pathologic features: Althought there are only a few case reports, patients with metorchiasis have presented with abdominal pain, fever, headache, lack or loss of appetite for food, nausea, backache, elevated liver enzymes, and increased eosinophilia.[78,81] The pathologic response has not been described in the human host. Patients have responded well to praziquantel.[81]

Laboratory Diagnosis: Diagnosis of metorchiasis has been made based on the finding of eggs during O&P examination of stool. Eggs measure 30 μm long × 17 μm wide and, like other opisthorchids, are shed embryonated with a mature miracidium and have a prominent operculum.[82]

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