eMedicine Specialties > Infectious Diseases > Parasitic Infections

Trematode Infection: Differential Diagnoses & Workup

Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Coauthor(s): Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine; Shekhar Koirala, MD, Vice Chancellor, Department of Medicine, BP Koirala Institute of Health, Dharan, Nepal
Contributor Information and Disclosures

Updated: Nov 13, 2009

Differential Diagnoses

Other Problems to Be Considered

Intestinal helminthic infections
Neurocysticercosis
Epilepsy
Acute nephritis

Workup

Laboratory Studies

• Microscopy
  • Diagnosis is made after microscopic demonstration of eggs in the stool (intestinal schistosomiasis; intestinal, liver, and lung fluke infections), sputum (pulmonary paragonimiasis), or urine (genitourinary schistosomiasis).
  • For improving the sensitivity of sputum examination for pulmonary paragonimiasis, serial samples (up to 6) should be examined.
  • Less frequently, nonoperculate terminal-spined eggs of S haematobium can be demonstrated in the rectal biopsy and aspiration findings obtained with proctoscopy or cystoscopy.
  • The flask-shaped eggs of C sinensis can also be demonstrated in the duodenal contents. Examination of fluid obtained from duodenal intubation is diagnostically more sensitive than examination of 2 stool specimens.
  • Formalin ether and/or ethyl acetate concentration is the most sensitive method for processing stool specimens for egg examination.
  • The Kato-Katz technique is a simple and sensitive quantitation technique used successfully in the field.³ It is a commonly used semiquantitative method for counting eggs in persons with intestinal schistosomiasis and allows the degree of infection and treatment response to be assessed.
  • Schistosomal species can be differentiated based on the morphology of the eggs.
  • Urine, the specimen of choice for diagnosing urinary schistosomiasis, is collected between noon and 2 pm, the period when an increased number of eggs are excreted. The eggs in the urine are concentrated by centrifugation or membrane filtration.
  • The eggs of Fasciola and Fasciolopsis species are morphologically similar and indistinguishable. Similarly, the eggs of Clonorchis, Heterophyes, Metagonimus, and Opisthorchis species are also morphologically similar and indistinguishable.
  • In Fasciola and Paragonimus species infections, the eggs cannot be demonstrated during the migratory phase of infection or in ectopic infections because no eggs are passed in the stool.
• Coproantigen detection: Detection of antigen in the stool (coproantigen) is a nonmicroscopic method of diagnosis. An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody to an 89-kd antigen of O viverrini has been used to detect coproantigen in the stool of individuals with Opisthorchis infection. This test has been found to be highly sensitive and specific.
• Soluble egg antigen (SEA) detection: A dip-stick ELISA can be used to assess urine samples for SEA; this method provides an effective diagnosis of schistosomiasis and correlates well with quantitation egg count⁴ . A sandwich ELISA, which yields better sensitivity and specificity, has also been evaluated for use.
• Circulating 28.5kDa tegumental antigen detection: Immunodiagnosis of fasciolosis via detection of circulating 28.5kDa tegumental antigen is also being evaluated.⁵
• Serology
  • Several serologic tests, which can be used to detect either specific antibodies or antigens in the serum, are used in diagnosing trematode infections.
  • Various antibody-based serologic tests are used in the diagnosis of most trematode infections. These tests are used for diagnosis and for seroepidemiologic studies. Commonly used tests include indirect hemagglutination, indirect immunofluorescence, and ELISA. ELISA is most sensitive and practical.
  • These serologic tests are especially useful in the following situations:
    • Prepatent period and in chronic and ectopic cases of schistosomiasis, in which the eggs are difficult to demonstrate in the stool
    • Acute fascioliasis, because the eggs are not passed in the stool for as many as 4 months of infection
    • Cerebral and abdominal paragonimiasis, because the eggs are not passed in the sputum or stool
  • A major disadvantage of antibody-based serologic tests is the inability to differentiate between recent and past infections because antibodies remain in the serum even after parasitologic cure of the disease. Low sensitivity and cross-reactions between trematodes are other noted disadvantages.
  • Detection of specific antigen in serum and urine is particularly useful during acute and end-stage disease, when excretion of eggs is minimal. Knowing whether infection is recent or old is also useful because, in active or recent infection, the circulating antigen is present in the serum or urine but is absent in patients with older or treated infection.
  • Falcon assay screening test (FAST) ELISA is sensitive (95%) and specific (99%) for the diagnosis of urinary schistosomiasis. This test uses S hematobium adult worm microsomal antigen (HAMA) to reveal serum antibodies.
  • In schistosomiasis, antigen titers in serum and urine correlate well with the degree of infection, as demonstrated by the egg counts. ELISA is used for detection of proteoglycan gut-associated antigens such as circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in the urine and serum. The sensitivities of the urine CCA and serum CAA ELISA are substantially higher than those of a single egg count. The sensitivity of these assays increases with egg output. Both CAA and CCA can also be detected in sera and urine of egg-negative individuals.
  • For its convenience, ELISA has replaced the complement fixation test in the diagnosis of paragonimiasis. For serologic diagnosis, the criterion standard is a western blot assay, which yields a sensitivity and specificity of nearly 99%. Newer techniques such as the dot immunogold filtration assay (DIGFA) are of supplementary value.
  • Immunoblot is a specific and sensitive test to detect schistosomiasis.
  • The circulating antigen has been detected in the sera of patients with C sinensis infection with the ELISA double-sandwich method.
  • A dip-stick ELISA can be used to assess urine samples for SEA; this method provides an effective diagnosis of schistosomiasis and correlates well with quantitation egg count.
  • Protein banding patterns after isoelectric focusing has been used to differentiate F hepatica from F gigantica.
  • This is useful for monitoring therapeutic studies. No cross-reaction with heterophyid flukes has been reported.
• Skin tests
  • Intradermal skin testing has been used for epidemiologic studies but cannot be used to differentiate past from current infection.
  • Skin testing using extracts of adult C sinensis or P westermani antigens has been used in Korea and China as an epidemiologic tool.
• Molecular methods
  • Molecular methods are still in the experimental stage. A polymerase chain reaction (PCR) using the primer named OV-6F/OV-6R has been developed for the detection of O viverrini in experimentally infected hamsters. The method has been found to be 100% sensitive in hamsters.⁶
  • Multiplex PCR is now available for identification and differentiation of S haematobium, S japonicum, and S mansoni using clinical specimens.
  • A real-time PCR protocol and a loop-mediated isothermal amplification protocol are available for the diagnosis of S japonicum infections.⁷ Real-time PCR (targeting the internal-transcribed-spacer-2 sequence of the parasite) to detect C sinensis -specific DNA in fecal samples was found to correlate with the egg counts in the stool, thus also being useful for quantification.
• Other parameters
  • A complete blood cell count may reveal eosinophilia in patients with fasciolopsiasis, schistosomiasis, heterophyiasis, metagonimiasis, early stages of paragonimiasis, and acute Clonorchis species infection (disappears in chronic Clonorchis species infection).
  • Anemia may be found in patients with schistosomiasis, fascioliasis, and paragonimiasis.
  • Gross and microscopic hematuria may be found in individuals with schistosomiasis.
  • Neutropenia may be found in patients with fasciolopsiasis.
  • Elevation of cerebrospinal fluid (CSF) pressure and pleocytosis and eosinophilia in the CSF may occur in individuals with cerebral paragonimiasis.

Imaging Studies

• Radiography
  • Chest radiographs in patients with schistosomiasis may reveal cor pulmonale and pulmonary hypertension, if present.
  • Radiographs of the liver exhibit tractlike small abscesses and subcapsular lesions in patients with fascioliasis.
  • Patchy foci of fibrotic change with a characteristic "ring shadow" (ie, circular or oval thin-walled cyst with a crescent-shaped opacity along one side) is the characteristic finding on chest radiographs in patients with paragonimiasis.
• Ultrasonography
  • Ultrasonography is useful in evaluating the gall bladder and biliary tract in individuals with fascioliasis. Adult worms may be visible on sonograms or may appear as curvilinear lucent areas in the contrast medium on cholangiograms.
  • This is a sensitive procedure used to demonstrate urinary obstruction and hepatosplenic disease in persons with schistosomiasis.⁸
  • Portable ultrasonography can be used for determining the extent of pathological changes, particularly in the liver and bladder, and can be used to screen populations at the community level. In addition, it can be used to assess the effects of chemotherapy.
• CT scan
  • CT scan is useful in the study of CNS manifestations of trematode infections.
  • In persons with cerebral paragonimiasis, long-standing cerebral infection forms and cystlike structures may calcify and may be seen as clusters similar in appearance to soap bubbles.
  • CT scan helps detect parenchymal lesions in individuals with fascioliasis
• MRI: MRI may be useful in the study of CNS manifestations of trematode infections. MRI can also reveal granuloma of the liver parenchyma in cases of fascioliasis.
• Cholangiography: In individuals with fascioliasis, this study reveals the multiple cystic dilatations of the ducts. Large cystic dilatation, small cystic ectasias, and mulberrylike dilatation are considered diagnostic of fascioliasis.

Procedures

• Colonic biopsy: This biopsy is a sensitive and specific procedure to aid in identifying parasite eggs in biopsy specimens for the diagnosis of intestinal schistosomiasis and intestinal trematode infections.
• Cystoscopy: This procedure is useful to help identify schistosome eggs in mucosal biopsy specimens from the urinary bladder and to exclude other causes of hematuria.

Histologic Findings

Egg granuloma is the typical pathologic lesion in urinary schistosomiasis. These are found in the ureter and urinary bladder. The granuloma consists mainly of eosinophils, macrophages, and lymphocytes surrounding the egg at the center. In chronic infection, fibroblast proliferation and fibrosis are characteristic.

Finger-sized fibrosis in the portal areas is characteristic of S mansoni infection.

Periportal fibrosis, Symmers fibrosis, and perisinusoidal blockage are the typical findings in S japonicum infection.

Adult Paragonimus flukes elicit an acute inflammatory reaction with formation of eosinophilic granulomas and small multiple fibrous cysts in the liver. The eggs also elicit an acute inflammatory reaction consisting of eosinophils, formation of a fibrous capsule, rupture of cysts in bronchioles, eosinophilic empyema, and, finally, calcification. The cystic encapsulation of the eggs in the lung and, less frequently in the brain and in other abdominal organs, is the key pathologic feature in paragonimiasis.

During the acute stage of fascioliasis, the liver is enlarged and exhibits hemorrhagic necrotic tracts in the subcapsular areas infiltrated by eosinophils and other inflammatory cells. In chronic infection, the bile duct exhibits epithelial hyperplasia with minimal pericholangitis and proliferation of tissues.

The infection of the biliary tract by C sinensis, O viverrini, and O felineus demonstrates adenomatous hyperplasia, periductal inflammation, periductal fibrosis, and diffuse or localized dilatation of ducts and may be associated with cholangiocarcinoma in C sinensis.

Ulceration of gut epithelium and localized inflammation are the features of infection caused by F buski and other intestinal flukes.

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