Trematode parasites 101

Trematodes, parasitic organisms commonly known as flatworms or flukes, infect many species worldwide. They get their name from the Greek trematos, meaning pierced with holes, referring to the “sucker” organ of attachment. Trematodes can be categorized into 3 groups based on the primary system they affect: gastrointestinal (GI), pulmonary, and hepatic.

Figure 1. The trematode life cycle. Graphic by Brayden Routh, DVM, BluePearl Specialty and Emergency Pet Hospital, Sandy Springs, Georgia.

Trematodes of dogs and cats have indirect life cycles requiring 1 or 2 intermediate hosts to reach the adult stage of development. Life cycles are dependent on water access (Figure 1). Prepatent periods vary among species, ranging from 3 to 5 weeks or longer. The cycle begins when the parasites shed their eggs in the feces of the infected dog or cat (definitive host). The eggs are formed by sexual reproduction in the definitive host and can be identified by their operculum. They hatch in water in a ciliated form called the miracidium. This penetrates the first intermediate host, which is typically a snail. There, it develops into a sporocyst, which then forms a cercaria through asexual reproduction and is ready to infect the second intermediate host. Within the second intermediate host, it develops into an encysted metacercaria. The final host organisms (dogs and cats) ingest the second intermediate host and become infected with the adult trematode.

Identification can be achieved by concentrating the ova with fecal sediment. This method is preferred to standard fecal flotation. The diagnosis of trematode infections may benefit from high-density sucrose flotation because trematode eggs are less buoyant than those of other parasites. Once isolated and identified through evaluation of an operculum, morphology, and size allow for further characterization.

No products are labeled for the treatment of trematodes in dogs or cats. Some effective off-label therapies that have been studied include praziquantel, fenbendazole, and albendazole.

Gastrointestinal flukes

Alaria alata, Alaria canis, and Alaria marcianae

In these small (2-4 mm) fluke species, the adults develop in the small intestine and are not usually associated with disease.¹ In addition to dogs and cats, they infect various other wild carnivores. Eggs of these species are oval, light brown, and large (98-134 × 62-68 mm).¹ These flukes are acquired by dogs and cats through the ingestion of a wide variety of paratenic and intermediate hosts. The life cycle includes freshwater snails (eg, Helisoma spp) as the first intermediate host. Cercariae develop into metacercariae after penetrating the skin of tadpoles.² Frogs, snakes, and mice become infected by ingesting the tadpoles. Dogs and cats then become infected after ingesting the intermediate host.

Migration of the immature cercariae through the diaphragm and lungs can cause a cough, pulmonary hemorrhage, and other respiratory signs in some patients. Praziquantel dosed at 20 to 25 mg/kg once subcutaneously (SC) or orally (PO) can eliminate the organism.²

Nanophyetus salmincola

The adult N salmincola fluke is small (0.5-0.3 mm) and oval. It is found in the intestinal tract of dogs, cats, and many wild mammals in the Pacific Northwest (ie, southern British Columbia, California, Oregon, and Washington).^2-5

The eggs, which are light brown, small, and heavy (72-97 × 35-55 mm), are passed in the feces of infected hosts shortly after infection starts.^1,2 The first intermediate hosts are snails (Oxytrema silicula).^2-5 The cercariae from the snails encyst as metacercariae in the muscle and organs of salmonoid fish after penetrating their skin. There, the organism can retain infectivity through ocean migration for up to 3 years before returning to freshwater.³ Dogs and cats become infected when they eat the raw, infected fish.

Infection with the fluke in and of itself causes only mild enteritis, but N salmincola serves as a vector for Neorickettsia helminthoeca, a rickettsial organism that causes salmon poisoning disease in dogs.^3-5 Elokomin fluke fever is another disease caused by a very similar Neorickettsia species that can be transmitted by N salmincola, producing similar but less severe signs.^2-5 Clinical disease commonly includes fever, vomiting, diarrhea, dehydration, lymphadenopathy, and thrombocytopenia. Less common findings include hematochezia, hematemesis, and central nervous system signs.^3-6 Illness usually develops within 5 to 7 days of ingesting the uncooked fish, but incubation can be as long as a month.^2-5 Mortality rates are high in the absence of supportive intravenous (IV) fluid treatment and antibiotics.

When zinc sulfate fecal flotation and fecal sedimentation are performed together in patients with associated clinical signs, sensitivity for identifying the eggs is above 90%.⁵ Polymerase chain reaction (PCR) testing for N helminthoeca can be performed on lymph node aspirates, feces, or tissues, but a well-validated commercial test is not currently available. N helminthoeca organisms may be identified cytologically on aspirates or biopsies of various tissues (lymph node, spleen) as 0.3-µm cocci or coccobacilli within macrophages (morula) in about 70% of patients.⁵

Deworming for the trematode can include praziquantel (20-30 mg/kg PO once) and fenbendazole (50 mg/kg/day for 10-14 days).^2,3 Aggressive IV fluid therapy, anti-nausea medications, GI protectants, and other supportive measures are needed in most patients. Treatment of the rickettsial organism usually results in a rapid improvement in clinical signs within 1 to 2 days and includes administration of a tetracycline (eg, doxycycline 5 mg/kg PO twice daily) for 1 to 2 weeks.^3,5 If vomiting and nausea are severe, parenteral administration may be necessary.

Pulmonary flukes

Paragonimus kellicotti, Paragonimus westermani

Infection with adult pulmonary trematodes causes lung cysts in both dogs and cats. The adult flukes are reddish-brown and oval and measure about 14 by 7 mm.⁶ Eggs are golden brown and measure 75 to 118 by 42 to 67 mm.¹ The eggs are passed through the lung cyst wall, where they are coughed up, swallowed, and passed in the feces. The life cycle includes several snail species as the first intermediate host and crayfish or crabs as the second. Patients become infected via ingestion of raw crayfish or a paratenic host infected with the metacercariae.⁶ The trematode penetrates the intestinal wall, and within the peritoneal cavity, the flukes can pass through the diaphragm where they enter the lungs and establish an infection.

Lateral (A) and ventrodorsal (B) radiographs illustrating a pneumothorax and pulmonary bulla, both of which can be seen in Paragonimus infections.

Many infected animals may not have any clinical signs. Some present with coughing, dyspnea, bronchiectasis, and hemoptysis. Infections can lead to cyst and bulla formation within the lungs and, rarely, pneumothorax (Figure 2).^6,7 Pulmonary cysts may be evident on radiographs, and eggs may be identified by transtracheal wash or bronchoscopy (Figure 3). Fecal sedimentation is preferred to fecal flotation.⁶

Cytology of a bronchioalveolar wash in a dog with lungworm (Paragonimus) infection demonstrating eggs in the wash (A), as well as the operculum in the fecal sediment (B) in the same dog. (Images courtesy of Jennifer Neel, DVM, DACVP (Clinical), assistant dean of student development and professor of pathology, North Carolina State University College of Veterinary Medicine)

Treatment with 50 mg/kg of fenbendazole once daily for 10 to 14 days has experimentally cleared the infection in dogs.⁸ Praziquantel given at 25 mg/kg PO 3 times daily for 3 days can also eliminate lung flukes and improve radiographic changes in dogs and cats.⁷

Hepatic flukes

Platynosomum concinnum, Platynosomum fastosum

Found in Florida and other areas in the southeastern United States,P concinnum and P fastosum are small (about 2 × 6 mm) flukes of cats that migrate through the biliary and pancreatic ducts. Other similar species include Eurytrema procyonis and Fasciola hepatica.²

Eggs measure 34 to 50 by 20 to 35 mm.¹ The life cycle is complex and includes snails (Subulina octona and Eulota similaris) as the first intermediate host and terrestrial isopods (eg, sowbugs, ) as the secondary intermediate host, with lizards as paratenic hosts. Infections occur due to the ingestion of lizards and other reptiles.⁹ Unlike other flukes, Platynosomum has a terrestrial life cycle that does not require water. After infection, young flukes emerge in the intestines and migrate into the common bile duct, gallbladder, or hepatic ducts, where they mature within 8 to 12 weeks. Embryonated eggs then pass from bile into the alimentary canal, where they may be detected in feces as early as 12 weeks after infection.⁹

General fecal evaluations (sediment, direct, sucrose, zinc sulfate) have a low sensitivity (25%-50%) due to low numbers of eggs that are shed in the feces (2-10/g).⁹ A tentative diagnosis can be made through clinical signs, ultrasound findings, and geographic location.

Infections with this trematode are referred to as “lizard poisoning." Clinical signs depend on the severity (parasite burden) and chronicity of infection. However, most infected cats remain asymptomatic.⁹ Elevated liver enzymes and eosinophilia may be present. Symptomatic cats develop progressive lethargy, fever, hepatomegaly, and abdominal distention. Jaundice from elevated total bilirubin levels can occur, and the patients may become emaciated secondary to anorexia, vomiting, and mucoid diarrhea. Ultrasound may demonstrate dilated, thickened, and distended gallbladders and biliary ducts with enlarged and irregular livers.⁹ Severe cholangiohepatitis and obstructive biliary disease can occur as the biliary system becomes fibrotic and hyperplastic over time, ultimately leading to cirrhosis and liver failure in severely affected patients.⁹ Some patients may also develop malignant transformation with cholangiocarcinomas.¹⁰

Haptic flukes can be difficult to eliminate, but praziquantel (20 mg/kg/day PO for 3-5 days repeated 12 weeks later) has been shown to be successful.⁹

Heterobilharzia americana

This liver fluke causes canine schistosomiasis. The reservoir hosts are raccoons with nutria and other wild animals in the south Atlantic and Gulf Coast states.

Eggs are 74 to 113 by 60 to 80 mm.¹ Miracidia hatch from the eggs within minutes of contact with water and can infect the snail intermediate hosts where cercariae are produced through asexual reproduction.¹¹ The cercariae can escape into water and infect the definitive host through direct skin penetration, unlike other trematodes that require ingestion of an intermediate snail host.¹¹ The cercariae migrate through the host as schistosomula and reach the lungs within 5 to 9 days, arriving in the liver by 7 to 45 days.¹² They become adults and migrate to the mesenteric veins where they reproduce. Most trematodes are hermaphroditic, but H americana has 2 sexes. The mature worms live in the mesenteric veins where they mate, and females produce eggs. The eggs migrate to the bowel lumen with the help of proteolytic enzymes and exit the infected dog through the feces (Figure 4).^11,12 The prepatent period is 84 days on average.¹²

Figure 4. Heterobilharzia americana eggs in the intestinal tract of a 6-year-old female spayed Labrador retriever with chronic diarrhea and hyperglobulinemia. (Image from endoscopic biopsies performed by Idexx Laboratories)

Although some infections are subclinical and the patient may have normal complete blood cell count and biochemistry profiles, infected patients can develop liver, GI, and kidney disease. As the eggs pass through the tissues, they can cause diarrhea, vomiting, weight loss, lethargy, polyuria, polydipsia, hypercalcemia, hyperglobulinemia, and hyporexia.¹³ The eggs cause a severe granulomatous reaction that occurs within the intestine and the liver. Healing of the host tissues leads to scar formation and organ injury that can result in liver failure and GI malabsorption. Kidney failure can develop from the hypercalcemia that is seen in almost 50% of patients and from glomerulonephritis associated with immune-complex deposition.^14,15 Patients with hypercalcemia can have decreased parathyroid hormone concentrations and increased parathyroid hormone-related protein concentrations, which could lead to a false diagnosis of hypercalcemia of malignancy.¹³

Diagnosis of H americana infection is made by finding the eggs of the trematode in the feces, intestine, or liver. Ultrasound imaging can help diagnose suspected disease because more than 80% of these patients have pinpoint hyperechoic foci in the small intestinal submucosa, muscularis, or liver (Figure 5).¹⁶ The eggs do not float in a routine fecal. The preferred method for identification is sedimentation using 0.85% saline, which help separate the eggs from ingesta and prevent them from hatching.² Direct saline smears may also reveal the eggs. Because the eggs are passed intermittently, they may not always be found in the feces in every sample. Therefore, several samples may need to be tested. In addition, a commercial PCR test available at Texas A&M University can detect 1 to 2 eggs per gram of feces and was positive in 1 study with 44 of 55 confirmed cases.^16,17

Figure 5. Ultrasound image of the same patient as in Figure 4 demonstrating hyperechoic and thickened intestinal wall in the submucosa layers.

Treatment with fenbendazole at 50 mg/kg PO for 10 days and/or praziquantel at 25 mg/kg 4 times daily SC or PO for 2 days effectively clears these infections; the medications have been used both individually and in combination. Prognosis is good with treatment. In 1 study, hypercalcemia resolved in all patients treated with praziquantel. In some patients, kidney injury and ascites were also resolved.¹³

Nicolas Berryessa, DVM, DACVIM, is a small animal internist at BluePearl Specialty and Emergency Pet Hospital in Sandy Springs, Georgia, where he has practiced for more than 10 years. He earned his veterinary degree from Cornell University College of Veterinary Medicine and did his residency training at the University of California, Davis. Berryessa’s clinical interests are endocrinology, gastrointestinal and infectious diseases, and interventional procedures.

References

1. Zajac AM, Conboy GA. Veterinary Clinical Parasitology, 8th ed. Wiley-Blackwell; 2012.
2. Peregrine AS. Flukes in small animals. Merck Veterinary Manual. Updated October 2014. Accessed April 7, 2021. www.merckvetmanual.com/digestive-system/gastrointestinal-parasites-of-small-animals/flukes-in-small-animals?query=Alaria
3. Gorham JR, Foreyt WJ, Sykes JE. Salmon poisoning disease. in Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO; 2012;220-224.
4. Greiman SE, Kent ML, Betts J, Cochell D, Sigler T, Tkach VV. Nanophyetus salmincola, vector of the salmon poisoning disease agent Neorickettsia helminthoeca, harbors a second pathogenic Neorickettsia species. Vet Parasitol. 2016;229:107-109. doi:10.1016/j.vetpar.2616.10.003
5. Sykes JE, Marks SL, Mapes S, et al. Salmon poisoning disease in dogs: 29 cases. J Vet Intern Med. 2010;24(3):504-513. doi:10.1111/j.1939-1676.2010.0493.x
6. Kuehn NF. Lung flukes in dogs.Merck Veterinary Manual. Updated June 2018. Accessed April 7, 2021. www.merckvetmanual.com/dog-owners/lung-and-airway-disorders-of-dogs/lung-flukes-in-dogs?query=paragonimus%20westermani
7. Bowman DD, Frongillo MK, Johnson RC, Beck KA, Hornbuckle WE, Blue JT. Evaluation of praziquantel for experimentally induced paragonimiasis in dogs and cats. Am J Vet Res. 1991;52(1):68-71.
8. Dubey JP, Miller TB, Sharma SP. Fenbendazole for treatment of Paragonimus kellicotti infection in dogs. J Am Vet Med Assoc. 1979;174(8):835-837.
9. Basu AK, Charles RA. A review of the cat liver fluke Platynosomum fastosum Kossack, 1910 (Trematoda: Dicrocoeliidae). Vet Parasitol. 2014;200(1-2):1-7. doi:10.1016/j.vetpar.2013.12.016
10. Andrade RLFS, Dantas AFM, Pimental LA, et al.Platynosomum fastosum-induced cholangiocarcinomas in cats. Vet Parasitol. 2012;190(1-2):277-280. doi:10.1016/j.vetpar.2012.04.015
11. Goff WL, Ronald NC. Certain aspects of the biology and life cycle of Heterobilharzia americana in east central Texas. Am J Vet Res. 1981;42;1775-1777.
12. Thrasher JP. Canine schistosomiasis. J Am Vet Med Assoc. 1964;144:1119-1126.
13. Fabrick C, Bugbee A, Fosgate G. Clinical features and outcome of Heterobilharzia americana infection in dogs. J Vet Intern Med. 2010;24(1):140-144. doi:10.1111/j.1939-1676.2009.0429.x
14. Ruth J. Heterobilharzia americana infection and glomerulonephritis in a dog. J Am Anim Hosp Assoc. 2010;46(3):203-208. doi:10.5326/0460203
15. Rodriguez JY, Lewis BC, Snowden KF. Distribution and characterization of Heterobilharzia americanain dogs in Texas. Vet Parasitol. 2014;203(1-2):35-42. doi:10.1016/j.vetpar.2014.03.026
16. Moshnikova VS, Gilmour LJ, Cook AK, Fabiani M. Sonographic findings of pinpoint hyperechoic foci in the small intestine, liver, and mesenteric lymph nodes are indicative of canine Heterobilharzia americana infection. Vet Radiol Ultrasound. 2020;61(5):583-591. doi:10.111/vru.12874
17. Bischop MA, Suchodolski JS, Steiner JM. Development of a PCR test for the detection of Heterobilharzia americana DNA in dog feces. Abstract presented at: 26th Annual American College of Veterinary Internal Medicine Forum; June 4-7, 2008; San Antonio, TX.