Schistosomiasis Workup

Blood tests are occasionally useful in supporting the diagnosis or assessing the severity of schistosomal infection. Serologies and polymerase chain reaction (PCR) assay–based testing can confirm a diagnosis.^{[37, 38]} Considerations in laboratory testing include the following:

• Complete blood count (CBC) - May reveal peripheral eosinophilia, particularly in acute infection and/or anemia
• Increased alkaline phosphatase level and gamma-glutamyltransferase (GGT) level - Are observed with hepatic granulomatosis
• Transaminase levels - Generally are not affected, and elevations are usually caused by coexisting hepatitis
• Renal function - May be decreased if obstructive nephropathy is severe
• Blood cultures - Are indicated for patients with persistent or recurrent fever and for persons who may have developed recurrent Salmonella infection with severe enteric schistosomiasis

Acute illness is often associated with eosinophilia in the blood and tissues. With chronic illness, peripheral eosinophilia may be minimal or absent, while tissue eosinophilia persists.

Urinary and fecal microbiology

Urinary microbiology is key when diagnosing vesicular infection from S haematobium. Gross and microscopic hematuria is common. Concentration methods may be necessary, and a rough determination of egg load can be obtained. However, this should not be used as a firm measure of disease severity, as egg counts can vary markedly between specimens in a single patient.

Fecal microbiology, usually on thick smears, is essential when diagnosing schistosomiasis with primary bowel infection. Stool specimens may be positive for heme or grossly bloody. Concentration methods will be needed to identify light infestations. Rough quantitation can also be performed in these specimens with the same limitation as above.

In an experienced lab, morphologic details and staining can identify single and mixed schistosomal species in an infected individual.

PCR assay

Using patient urine samples, polymerase chain reaction (PCR) assay was 94.4% sensitive and 99.9% specific for the diagnosis of schistosomiasis.^[37] PCR can detect and quantify schistosome deoxyribonucleic acid (DNA) in stool or urine.^[39]

Identify and speciate the eggs in the stool or urine. Quantification of the egg excretion is calculated by collecting 24-hour urine or stool, homogenizing the sample, and counting the eggs in a measured sample. Urine or stool egg count in a 24-hour collection quantitates the severity of the infection. (However, urinary excretion of eggs is not uniform. The urine is most likely to be positive for S hematobium from 10 am until 2 pm.^[40] )

Fewer than 100 eggs per gram of stool or 10mL of urine indicates a light infection; 100-400 eggs per gram of stool or 10mL of urine indicates a moderate infection, and more than 400 eggs per gram of stool or 10mL of urine indicates a heavy infection.

Determination of the intensity of infection is an important tool in endemic areas, as many of the complications of schistosomiasis are related to the parasite burden. Intensity determination is made via quantitative sampling of 20-50g of stool (Kato-Katz technique) or a standardized volume of urine through a Nuclepore membrane.^[41]

This test is important for assessing the effectiveness of treatment. Because persons with inactive infection may continue to shed dead eggs into stool and urine for months, tests for egg viability, such as egg hatching or microscopic examination of eggs for the movement of flame cells, should be performed.

Viability testing requires mixing the stools or urine with room-temperature distilled water and observing for hatching miracidia. An active infection produces viable eggs, while treated or past infection results in nonviable eggs and an absence of miracidia.

The following tests are performed in the diagnosis of urinary schistosomiasis:

• Urinary analysis and culture for hematuria, proteinuria, leukocyturia, and associated urinary infections
• Urinary syringe filtration techniques - Provide a quantitative estimate of eggs in the urine
• Blood chemistries, including renal function tests - Should include blood cultures for Salmonella bacteremia and a CBC for anemia and eosinophilia (a Salmonella urinary tract infection should always lead to suspicion of schistosomiasis)

Points to consider in testing for intestinal and liver schistosomiasis include the following:

• Direct stool examination is not a sensitive test for intestinal and liver schistosomiasis (both of which occur in chronic disease)
• Concentration techniques, such as a Kato-Katz thick smear, are needed; this demonstrates the number of eggs excreted per day
• Blood in the stool should be ruled out
• Tests should include a CBC for anemia and eosinophilia
• Thrombocytopenia is secondary to splenic sequestration
• Additional testing for HIV and HPV should be considered in female genital schistosomiasis
• Diagnostic tests for hepatitis B and C should be considered in liver schistosomiasis

Liver function test results usually are within the reference range until the end stage of disease. Mild elevation of alkaline phosphatase and gamma-glutamyl transferase levels may occur. If liver function test results are abnormal, look for other co-infections or diseases.

Antibody testing is epidemiologically useful but cannot be used to differentiate active and past illness. It also does not allow quantification of egg burden.

Serologic findings can be used to reach a diagnosis in a patient from a nonendemic area, because a negative antibody test result would be expected.

Detection of antibodies to S mansoni, S haematobium, and S japonicum adult worm microsomal antigens (ie, mansoni adult worm microsomal antigen [MAMA], haematobium adult worm microsomal antigen [HAMA], japonicum adult worm microsomal antigen [JAMA]) has been reported to be highly specific for all 3 species when the Falcon assay screening test (FAST), enzyme-linked immunoassay (ELISA), and immunoblot assays have been used.^[42]

The sensitivity and specificity of ELISA tests currently in use are generally reported to be greater than 90% and 95%, respectively. Western blot tests are often used to confirm ELISA results.^[43]

Antibody tests are generally negative during the acute presentation of Katayama syndrome, although serology often becomes positive before eggs become detectable. Seroconversion generally occurs 4-8 weeks after infection.

Because these tests measure parasite antigen as opposed to host antibody response, they reflect active infection. The tests are still investigational. With effective treatment, a reduction in antigenemia is expected.

The 2 proteoglycan, gut-associated antigens that appear most promising are circulating anodic antigen (CAA) and circulating cathodic antigen (CCA). These antigens can be found in urine or serum.^[44]

Studies are underway to evaluate the sensitivity and specificity of these investigational antigen tests. A reagent strip using monoclonal antibodies to detect somatic schistosome antigens in urine has a sensitivity of more than 85% and is suitable for use in the field.^[45]

Antigen titers also correlate well with the determination of infection intensity by egg counts and with clinical severity of disease.^[46]

Antigen titers can be used to assess treatment efficacy posttherapy, since loss of circulating antigens indicates cure. Antigen tests may become negative as early as 5 to 10 days posttreatment.^[44]

Ultrasonography (US) is a sensitive means of assessing hepatosplenic disease with periportal fibrosis or urinary obstruction. It can demonstrate periportal fibrosis, splenomegaly, portal collaterals, periportal adenopathy, ureteral obstruction, and obstructive nephropathy.

Echocardiography and/or invasive hemodynamic studies can demonstrate pulmonary hypertension and cor pulmonale, if present.

Chest radiographs may show patchy infiltrates in acute schistosomiasis and can indicate pulmonary hypertension and cor pulmonale in end-stage chronic infection, if present.

Computed tomography (CT) or magnetic resonance imaging (MRI) scanning may be useful in the evaluation of CNS disease or in the detection of periportal fibrosis.

Acute schistosomiasis

With acute schistosomiasis, a chest radiograph sometimes demonstrates a generalized increase in vascular and interstitial marking and mild lymphadenopathy.

Urinary schistosomiasis

Imaging tests for urinary schistosomiasis can include the following:

• Plain abdominal radiography - May demonstrate bladder and ureteral calcifications; the characteristic appearance is often referred to as "fetal head" calcification
• Ultrasonography - Hydronephrosis, hydroureters, and bladder wall irregularities may be visible
• Urography - May demonstrate abnormalities in the ureter and bladder wall
• Intravenous pyelography (IVP) - Ureteric strictures may be detected

Liver and intestinal schistosomiasis

Imaging tests for liver and intestinal schistosomiasis can include the following:

• Barium swallow or endoscopy - Esophageal varices are visualized^[47]
• Ultrasonography of the liver and spleen - Used to reach an early and accurate diagnosis of periportal fibrosis and a diagnosis of hepatosplenomegaly and ascites
• CT scanning of the liver - Calcified capsules and septa are visible
• Contrast studies of the intestine - Mucosal irregularities are revealed

Lung schistosomiasis

Imaging tests for lung schistosomiasis include the following:

• CT scanning - May demonstrate early interstitial fibrosis.
• Echocardiography - Findings reflect pulmonary hypertension due to egg emboli to pulmonary vasculature

CNS schistosomiasis

A CT or MRI scan of the brain and spinal cord may show lesions in CNS schistosomiasis. Nodular and ring-enhancing lesions with surrounding edema are seem on CT and MRI brain scans. Eggs reach the lower spinal cord through the Batson plexus with S haematobium and S mansoni infection. These produce granulomatous lesions of the cauda equine and conus medularis.

Biopsy is helpful when stool sample findings are negative or in light infection. Mucosal biopsy is effective for visualizing eggs. Obtain multiple biopsy samples and crush them between slides to increase egg-detecting sensitivity. In one study, 61% of patients had eggs detected on rectal biopsy, whereas only 39% of patients had ova detected in stool.^[48]

Liver biopsy has also been used for egg detection and may be appropriate in patients with unclear diagnoses or suspected co-infections.

Procedures used in the diagnosis of schistosomiasis include the following:

• Sigmoidoscopy/proctoscopy - Can be used to obtain mucosal biopsies (including rectal) for diagnosis and to identify complications such as pedunculated and sessile polyps
• Cystoscopy - Cystoscopy may be useful in schistosomiasis with primary bladder involvement for definitive diagnosis or to evaluate secondary ulcers and polyps, to biopsy for malignancy, to rule out other sources of hematuria and dysuria, and to identify eggs in mucosal biopsy specimens
• Surgical biopsy - Findings may be used to diagnose ectopic schistosomiasis
• Bronchoscopic washings or transbronchial biopsies - Eggs can be detected in individuals with pulmonary involvement^{[49, 50]}
• Lumbar puncture - Eosinophils may be present in the cerebrospinal fluid (CSF) of individuals with neurologic involvement. One review showed that 41% of individuals with spinal cord involvement had eosinophils present in their CSF; 85% of these patients also had antischistosomal antibodies detected in spinal fluid.^[51]
• Upper endoscopy - Can assess for esophageal varices; treat upper intestinal bleeding with endoscopic sclerotherapy