Harrison's Practice: Schistosomiasis

Harrison's Practice

Schistosomiasis

Definition

Schistosomiasis, also known as bilharziasis, is a blood fluke (trematode) infection caused by any of 5 Schistosoma species.
- Intestinal schistosomiasis
  - S. mansoni (South America, Africa, Middle East)
  - S. japonicum (China, Philippines, Indonesia)
  - S. mekongi (Southeast Asia)
  - S. intercalatum (West and Central Africa)
- Urinary schistosomiasis
  - S. haematobium (Africa, Middle East)
Except for the allergic response in the acute syndrome, symptoms are due primarily to chronic host inflammatory responses to schistosome eggs.
Other schistosome species (e.g., avian species)
- May invade human skin, then die in subcutaneous tissue; cause only self-limiting cutaneous manifestations

Epidemiology

Disease burden
- 5 Schistosoma species infect an estimated 200–300 million people in South America, the Caribbean, Africa, the Middle East, and Southeast Asia (30–50% of the at-risk population).
Geography
- S. mansoni: Africa, South America, Middle East, a few Caribbean countries
- S. japonicum: China, Philippines, Indonesia
- S. intercalatum: West and Central Africa
- S. mekongi: Southeast Asia
- S. haematobium: Africa, Middle East
Age-related prevalence
- Prevalence appreciable by 3–4 years of age
- Builds to a maximum that varies by endemic region (up to 100%) in the 15- to 20-year age group
- Stabilizes or decreases slightly in older age groups (>40 years)
In the U.S.
- Avian schistosomes cause a form of cercarial dermatitis around freshwater lakes in the northern U.S., particularly in the spring.

Risk Factors

Environment
- Residence in or travel to an endemic region
- Exposure to freshwater bodies containing infected snails
Human host
- Age
  - Intensity of infection (measured by fecal or urinary egg counts, which correlate with adult worm burdens in most circumstances) increases up to 15–20 years of age and then decreases markedly in older age groups.
  - The decrease with age may reflect acquisition of resistance or may be due to changes in water contact patterns (with older people exposed less).
- Genetic susceptibility
- Schistosomal hepatomegaly is associated with certain class I and class II human leukocyte antigen (HLA) markers.
- Concurrent chronic viral hepatitis (B or C) predisposes to cirrhosis and to a worse outcome than schistosomiasis alone

Etiology

Human infection/transmission cycle
- Infection is initiated by penetration of intact skin by infective cercariae (the form of the parasite released from snails—the intermediate host—in freshwater bodies).
- In subcutaneous tissue, the cercariae transform into schistosomulae.
- Within 2–4 days, schistosomulae begin to migrate via venous or lymphatic vessels, reaching the lungs and finally the liver parenchyma.
- Sexually mature worms descend into the venous system at specific anatomical locations: intestinal veins (S. mansoni, S. japonicum, S. mekongi, S. intercalatum) and vesical veins (S. haematobium).
- Adult gravid females deposit ova intravascularly.
  - Worms, which do not multiply within the definitive mammalian/human host, have a relatively long lifespan, ranging from a few months to a few years.
- Ova move through the venous wall and host tissues to reach the lumen of the intestinal or urinary tract.
  - Voided with stools or urine
- ~50% of ova are retained in host tissues locally (intestines or urinary tract) or are carried by venous blood flow to the liver and other organs.
Pathogenesis
- In chronic schistosomiasis, most disease manifestations are due to eggs retained in host tissues.
  - Granulomatous lesions reach a size many times that of the eggs, inducing organomegaly and obstruction.
  - Later, fibrosis results in more permanent disease sequelae.
- Liver disease
  - The hepatosplenic phase begins during the first year of infection, particularly in children.
  - Hepatomegaly develops in 15–20% of infected persons (more often in children) and correlates roughly with intensity of infection.
    - Due to parasite-induced granulomatous lesions at presinusoidal sites
  - In subsequent phases of infection, presinusoidal blockage of blood flow leads to portal hypertension and splenomegaly; portal hypertension may lead to esophageal varices.
  - Fibrotic liver changes in late-stage disease
    - Characteristically periportal (Symmers’ clay pipe–stem fibrosis), but may be diffuse
- Urinary schistosomiasis
  - Granuloma formation at the lower end of the ureters obstructs urinary flow, with subsequent development of hydroureter and hydronephrosis.
  - Similar lesions in the urinary bladder cause the protrusion of papillomatous structures into its cavity; these may ulcerate and/or bleed.
  - The chronic stage of infection is associated with scarring and deposition of calcium in the bladder wall.

Associated Conditions

Viral infections of the liver (especially hepatitis B and C) or nutritional deficiencies may accelerate or exacerbate the deterioration of hepatic function in chronic schistosomiasis, with associated cirrhosis and risk of hepatocellular carcinoma.
In endemic areas, an association between squamous-cell carcinoma of the bladder and S. haematobium infection has been observed.
Bacterial infections (classically salmonellosis) are associated with schistosomiasis.

Symptoms & Signs

Cercarial invasion (swimmers’ itch)

Itchy maculopapular rash developing after 2–3 days in region of parasitic invasion
Most frequently caused by S. mansoni or S. japonicum, but most severe if due to avian schistosomes, which invade human skin but then die in subcutaneous tissue

Acute schistosomiasis (Katayama fever)

A serum sickness–like illness, with fever, generalized lymphadenopathy, hepatosplenomegaly, and peripheral-blood eosinophilia
Occurs 4–8 weeks after skin invasion—during worm maturation and at the beginning of oviposition
Parasite-specific antibodies may be detected before schistosome eggs are identified in excreta.

Chronic schistosomiasis (intestinal species)

The intestinal phase may begin a few months after infection and may last for years.
- Colicky abdominal pain
- Bloody diarrhea
- Fatigue, inability to perform daily routine functions
- Growth retardation
- Severity related to worm burden
The hepatosplenic phase begins during the first year of infection, particularly in children.
- Hepatomegaly in 15–20% of patients, more often in children
- Right upper-quadrant "dragging" pain
- Portal hypertension and splenomegaly
  - Hematemesis may be the first clinical manifestation of this phase (esophageal varices).
  - Left upper-quadrant pain develops as splenomegaly progresses.
Fibrotic liver changes in late-stage disease
- Ascites, hypoalbuminemia, defects in coagulation

Chronic schistosomiasis (urinary species)

Clinical manifestations occur early, involve a relatively high percentage of persons, and correlate with intensity of infection.
Urinary bladder granulomas, ulceration
- Up to 80% of infected children have dysuria, frequency, and hematuria, which may be terminal.
- Obstruction of the lower end of the ureters results in hydroureter and hydronephrosis, which are seen in 25–50% of infected children.
Bladder granulomas undergo fibrosis as infection progresses.
- Scarring and deposition of calcium in the bladder wall

Pulmonary schistosomiasis

Embolized eggs lodge in small arterioles, producing acute necrotizing arteriolitis, granuloma formation, and finally fibrous tissue deposition.
- Leads to endarteritis obliterans, pulmonary hypertension, cor pulmonale
- Uncommon presentation during chronic schistosomiasis
  - Most common symptoms: cough, fever, dyspnea
  - Less common: ascites, hemoptysis
  - Frank evidence of right-sided heart failure may be seen in late cases.

Central nervous system (CNS) schistosomiasis

Less common than pulmonary schistosomiasis
Characteristically occurs as cerebral disease due to S. japonicum infection
- Migratory worms deposit eggs in the brain and induce a granulomatous response.
- Occurs in 2–4% of persons in some endemic areas (e.g., the Philippines)
  - Jacksonian epilepsy due to S. japonicum infection is the second most common cause of epilepsy in these areas.
Transverse myelitis associated with S. mansoni and S. haematobium infections; due to eggs migrating to the venous plexus around the spinal cord
- Usually acute or rapidly progressing lower-leg weakness, accompanied by sphincter dysfunction
- S. mansoni: usually seen in the chronic stage after development of portal hypertension and portosystemic shunts; few reports in early S. mansoni infection
- S. haematobium: may occur at any stage of infection

Differential Diagnosis

Schistosomal fever in travelers
- Viral infections (e.g., dengue fever)
- Bacterial infections (e.g., enteric fever, leptospirosis)
- Rickettsial infections
- Protozoal infections (e.g., malaria)
Schistosomal hepatomegaly
- Viral hepatitis of all etiologies
- Miliary tuberculosis
- Visceral leishmaniasis
- Ethanol abuse
- Causes of hepatic and portal vein obstruction
Hematuria in S. haematobium infection
- Bacterial cystitis
- Tuberculosis
- Urinary stones
- Cancer

Diagnostic Approach

Diagnosis is based on epidemiologic risk (exposure to freshwater body in an endemic area), clinical presentation, and laboratory testing.
Acute schistosomiasis (Katayama fever)
- Prompt diagnosis is essential.
- Laboratory testing
  - Detection of high-level peripheral-blood eosinophilia
  - Positive serologic assay for schistosomal antibodies
  - In some cases, detection of ova in stool or urine
Chronic schistosomiasis
- Peripheral-blood eosinophilia in some cases
- Detection of the relevant stage of the parasite in excreta, sputum, or (rarely) tissue samples
- Positive serologic tests

Laboratory Tests

Nonspecific laboratory tests
- Blood eosinophilia is often documented.
- Anemia/thrombocytopenia may occur with chronic disease.
- Urine examination (S. haematobium infection)
  - Hematuria, albuminuria, urinary sediment cellular metaplasia
Specific laboratory tests
- Serologic assay for schistosomal antibodies
  - 2 tests available at the Centers for Disease Control and Prevention
    - Falcon assay screening test/enzyme-linked immunosorbent assay
    - Confirmatory enzyme-linked immunoelectrotransfer blot
    - Both tests are highly sensitive and ~96% specific.
- Other assays
  - Detection of circulating schistosomal antigens
    - May be applied to blood and other body fluids, including cerebrospinal fluid
- Ova identification
  - Stool examination: Kato thick smear or any other concentration method generally identifies schistosomal eggs in all but the most lightly infected persons.
  - Urine examination: microscopy of sediment or filtration of a known volume through Nuclepore filters

Imaging

Chest radiography
- Cor pulmonale: prominent right side of the heart and dilation of the pulmonary artery in pulmonary schistosomiasis
Abdominal/genitourinary imaging
- Ultrasonography
  - May show ascites, periportal fibrosis around portal vein tributaries, splenomegaly with late S. japonicum and S. mansoni infection
  - May show hydronephrosis/ureteral strictures from S. haematobium infection
- CT may show a characteristic pattern of liver abnormality.

Diagnostic Procedures

Rectal biopsy
- Microscopy for ova identification may be positive even when stool samples are negative.
Cystoscopy
- Fibrotic bladder granulomas in S. haematobium infection
- Visible presence of typical sandy patches
- May find ova in bladder tissue biopsy, but usually not necessary for diagnosis

Treatment Approach

Treatment depends on the stage of infection and the clinical presentation.
The effect of antischistosomal treatment on disease manifestations varies by stage.
- Early hepatomegaly and bladder lesions are known to resolve after chemotherapy.
- Late manifestations, such as fibrosis, do not change.
All patients with positive serology or demonstrated ova should receive antiparasitic treatment.
Additional management modalities are necessary for other manifestations, such as hepatocellular failure or recurrent hematemesis.
- Interventions are guided by general medical and surgical principles.

Specific Treatments

Cercarial dermatitis caused by avian schistosomes

Topical dermatologic applications to relieve itching
No other specific treatment indicated

Acute schistosomiasis (Katayama fever)

Treatment is adjusted appropriately for each case, with goals of optimally managing acute critical phase symptoms with supportive measures prior to initiation of specific antischistosomal treatment.
Antischistosomal chemotherapy is indicated as for chronic infection (see below) but does not address immediate pathologic changes.
Severe acute schistosomiasis
- Management in an acute-care setting is necessary.
- Institute supportive measures and consider glucocorticoid treatment.
- Specific chemotherapy is indicated once the acute critical phase is over.

Chronic schistosomiasis

Antischistosomal treatment to eradicate the parasite
- Praziquantel
  - S. mansoni, S. intercalatum, S. haematobium: 20 mg/kg, 2 doses in 1 day given 4–6 hours apart
  - S. japonicum, S. mekongi: 20 mg/kg, 3 doses in 1 day given 4–6 hours apart
  - Few side effects
- Other antischistosomal chemotherapeutic agents are currently considered only as alternatives to use when praziquantel is unavailable.

Monitoring

Monitor effectiveness of chemotherapy.
- Microscopy to assess ova burden
  - Stool: Kato thick smear
  - Urine: Nuclepore filtration microscopy
  - In nonendemic areas (where there is no risk of intercurrent reinfection), re-examination at 3 and 6 months is recommended.
- Antigen testing
  - After successful treatment, antigen tests become negative in 5–10 days.
- Eosinophil levels may increase after therapy and may not return to normal for 12 weeks.

Complications

Chronic schistosomiasis
- Intestinal species: esophageal varices, liver dysfunction
- Significant disease may develop in other organs (i.e., the lungs and CNS).
- Other sites (i.e., the skin and the genital organs) are affected far less frequently.
- Pulmonary schistosomiasis
  - Endarteritis obliterans
  - Pulmonary hypertension
  - Cor pulmonale
- CNS schistosomiasis
  - Seizures
  - Paralysis
- S. haematobium infection
  - Hydroureter
  - Hydronephrosis
  - Bacterial urinary tract infection
  - Bladder cancer
- Systemic bacterial infection
- Kidney failure
- Death

Prognosis

Cercarial invasion
- Self-limiting clinical entity
Acute schistosomiasis
- Course generally benign
- Deaths occasionally reported in association with heavy schistosome exposure
Chronic intestinal schistosomiasis
- Rarely progresses to a functional level (e.g., malabsorption) or to anatomical lesions of the gut
- Exception: colonic polyposis seen in some endemic areas, such as Egypt
Praziquantel treatment results in parasitologic cure in ~85% of cases.
- Reduces egg counts by >90% even among patients whose infections are not cured
- Re-treatment of residual infection is curative in 80% of cases.
Overall prognosis depends on the degree of pathologic abnormalities before treatment.
- Late-stage fibrosis, esophageal varices, and cor pulmonale are not reversible.

Prevention

Travelers
- Avoidance of contact with all freshwater bodies in endemic regions of the world
  - Regardless of the speed of water flow or unsubstantiated claims of safety
- If exposure occurs, a follow-up visit with a health care provider is strongly recommended.
Inhabitants of endemic areas
- Current recommendations emphasize the use of multiple approaches.
  - Application of molluscicides
  - Provision of sanitary water
  - Provision of means for sewage disposal
  - Chemotherapy
  - Health education

ICD-9-CM

120._ Schistosomiasis [bilharziasis], (specific type specified by fourth digit)
120.9 Schistosomiasis, unspecified