Schistosomiasis Diagnostics

Schistosomiasis is diagnosed by detecting eggs in urine (Schistosoma haematobium) or stool (S. mansoni, S. japonicum, S. mekongi, S. intercalatum), by antigen and antibody tests, and by molecular tests.

Microscopy is the reference method: urine filtration (10 mL passed between 10:00 and 14:00 hours) for terminal spined eggs of S. haematobium, and the Kato-Katz thick smear (41.7 mg of stool) for lateral spined eggs of S. mansoni and round eggs with a small lateral spine of S. japonicum.

Sensitivity of a single Kato-Katz smear falls to 40 to 60% in light infections, and repeated smears over 3 days or the point-of-care circulating cathodic antigen (POC-CCA) urine test improve detection. Serology (enzyme immunoassay for soluble egg antigen and adult worm antigen) has sensitivity of 90 to 99% in travellers, but does not separate current from past infection.

Real time PCR on stool, urine and serum has sensitivity over 90% and specificity over 95%.

Schistosomiasis affects over 240 million people, with 700 million at risk, and over 90% of cases are in sub-Saharan Africa. It causes about 200 000 deaths a year. Infection follows contact with fresh water containing cercariae from snails.

Acute schistosomiasis (Katayama syndrome) appears 2 to 8 weeks after exposure with fever, cough, urticaria, eosinophilia, hepatosplenomegaly and often negative egg tests.

Chronic disease causes haematuria, bladder fibrosis, hydronephrosis, bladder cancer (S. haematobium), hepatosplenic fibrosis and portal hypertension (S. mansoni and S. japonicum), pulmonary hypertension, and spinal cord and cerebral disease (ectopic eggs).

Indications. Terminal haematuria, dysuria or frequency in a person from or travelling to an endemic area. Chronic diarrhoea with blood, abdominal pain and hepatosplenomegaly. Unexplained eosinophilia in a returned traveller. Fever, cough and rash 2 to 8 weeks after freshwater exposure (Katayama syndrome). Unexplained portal hypertension, pulmonary hypertension or myelopathy.

Female genital lesions (post-coital bleeding, infertility). Screening of travellers and migrants from endemic areas, and community surveys. Test of cure at 3 to 6 months after treatment.

Specimen. Urine: terminal portion of a midday sample (10 to 14 hours), 10 mL filtered through a polycarbonate filter, stained and read at once, or sedimented. Stool: fresh sample for Kato-Katz (within 1 hour, as hookworm eggs clear quickly) or formol ether concentration, repeated on 3 days. Rectal biopsy (crush preparation) when stool is negative and suspicion is high.

Bladder or genital biopsy. Serum for antibody and antigen. Urine for POC-CCA. Blood for full blood count with differential.

Reference values. No eggs in urine or stool. Serology negative. Eosinophils 0.04 to 0.4 times 10 to the power 9/L (up to 0.5). Egg counts are graded as eggs in 10 mL urine (light 1 to 49, heavy 50 or more) and eggs in each gram of stool (S. mansoni light 1 to 99, moderate 100 to 399, heavy 400 or more).

Interpretation.

• Eggs in urine or stool: current infection, species identified by egg morphology (S. haematobium terminal spine in urine, S. mansoni lateral spine in stool, S. japonicum small lateral spine, S. intercalatum terminal spine in stool). Viable miracidia can be shown by hatching tests or flame cell activity.
• Positive serology in a traveller: exposure and probably infection, but antibodies persist for years after cure, so it cannot show treatment response. It is positive from 4 to 12 weeks after infection, and may be negative in Katayama syndrome.
• Positive POC-CCA urine (S. mansoni): active infection, with a trace result debated, and S. haematobium is detected poorly. False positives occur with urinary tract infection, pregnancy and other conditions.
• Negative serology after 12 weeks from exposure: excludes infection with high confidence.
• Eosinophilia with negative eggs and serology early in infection: repeat tests in 3 to 6 weeks.
• Haematuria, proteinuria and eggs in urine, with ultrasound showing bladder wall thickening, calcification, hydronephrosis: urogenital disease.
• Ultrasound of the liver showing periportal fibrosis, splenomegaly and portal hypertension: hepatosplenic schistosomiasis, graded by image patterns.
• Cystoscopy and biopsy: sandy patches, polyps, squamous cell carcinoma.
• Egg negative serology positive in a returned traveller with eosinophilia: treat on clinical grounds.

Critical values and findings needing immediate action.

• Katayama syndrome with neurological symptoms, or confirmed neuroschistosomiasis (myelopathy, cauda equina syndrome, seizures): urgent praziquantel with corticosteroids, and imaging.
• Haematemesis from oesophageal varices in hepatosplenic disease: resuscitation, endoscopy and variceal band ligation.
• Obstructive uropathy with raised creatinine: urgent urological assessment.
• Haematuria with a bladder mass in a patient from an endemic area: cystoscopy and biopsy for squamous cell carcinoma.
• Pulmonary hypertension: echocardiography and right heart catheterisation.
• Coinfection with HIV, hepatitis B and C: additional management and monitoring.

Interferences and pitfalls.

• A single stool or urine sample misses light infections. Egg excretion fluctuates day to day, so three samples over several days are needed in returning travellers.
• Urine for S. haematobium must be collected at midday, because egg excretion peaks then and is increased by exercise. Haematuria alone is not specific.
• Eggs can be calcified or dead after treatment. Viability is judged by the presence of flame cells or hatching.
• Praziquantel kills adult worms but not immature stages, so repeat treatment 4 to 6 weeks later is needed in recent exposure (Katayama), and treatment failure can be due to immature worms.
• Antigen and PCR tests are not available everywhere.
• Serology cross-reacts with other helminths (Fasciola, Strongyloides, filarial worms), and the sensitivity of some assays is lower for S. haematobium.
• Eosinophilia may be absent in chronic infection and in people with HIV or on corticosteroids, and is common with other helminths.
• In the sub-Saharan region, bladder cancer from chronic S. haematobium is a leading cancer in some areas.
• Test of cure by egg counts at 3 to 6 months, and reinfection is common in people who continue to use infested water.

Special groups.

• Children and adolescents: highest prevalence and intensity, with growth faltering, anaemia and reduced cognition, and school based mass praziquantel treatment is used.
• Pregnancy: praziquantel is considered safe in the second and third trimester and given when benefit exceeds risk.
• Travellers: acute illness and disease after short exposures (Lake Malawi, Nile, rivers in Africa).
• Women: female genital schistosomiasis increases susceptibility to HIV infection, and is often unrecognised.
• Immunocompromised patients: reduced antibody responses, so antigen or PCR is preferred.
• Regions: S. mansoni in Africa, the Arabian peninsula and the Americas (Brazil), S. haematobium in Africa and the Middle East, S. japonicum in China, the Philippines and Indonesia, S. mekongi in Laos and Cambodia, S. intercalatum in Central Africa.

Follow up tests. Full blood count with eosinophils, haemoglobin, creatinine and urinalysis, liver function and platelets, abdominal and renal ultrasound, cystoscopy, upper gastrointestinal endoscopy for varices, chest radiograph and echocardiography, MRI spine and brain in neurological disease, stool microscopy for other helminths, strongyloides serology before corticosteroids,

hepatitis B and C and HIV tests, repeat egg count at 3 to 6 months, PCR and antigen tests, and cervical and vaginal examination in women.