Schistosomiasis

What is schistosomiasis?

Synonyms: Bilharzia, Katayama fever, swimmer's itch.

Schistosomiasis is a trematode (fluke) infection caused by species of the genus Schistosoma.¹ The species that cause schistosomiasis (the first three are the most important) include:

• S. japonicum.

• S. mansoni.

• S. haematobium.

• S. intercalatum.

• S. mekongi.

• S. guineensis.
  

Other schistosomes with avian or non-human mammalian primary hosts may cause dermatitis, or insignificant infection. Schistosome transmission requires:²

• Contamination of water by faeces or urine containing eggs.

• A specific freshwater snail as the intermediate host; and

• Human contact with water inhabited by the intermediate host snail.

Various animals (eg, dogs, cats, rodents, pigs, horses and goats) act as reservoirs for S. japonicum, and dogs for S. mekongi.³

Schistosomiasis epidemiology^{1 3 4}

Schistosomiasis affects almost 240 million people worldwide, and more than 700 million people live in endemic areas. The infection is prevalent in tropical and sub-tropical areas, in poor communities without potable water and adequate sanitation. Urogenital schistosomiasis is caused by Schistosoma haematobium and intestinal schistosomiasis by S. guineensis, S. intercalatum, S. mansoni, S. japonicum, or S. mekongi.

• S. mansoni is found primarily across sub-Saharan Africa and some South American countries (Brazil, Venezuela, Suriname) and the Caribbean.

• S. haematobium is found in Africa and pockets of the Middle East.

• S. japonicum is found in China, the Philippines, and Sulawesi. Despite its name, it has long been eliminated from Japan.

The other, less common human-infecting species include:

• S. mekongi - occurs focally in parts of Cambodia and Laos.

• S. intercalatum - has only been found in the Democratic Republic of the Congo.

• S. guineensis - is found in West Africa.

Schistosomiasis is more rampant in poor rural communities, especially places where fishing and agricultural activities are dominant.⁵

Life cycle^{3 6 7}

• The intermediate host is a snail - in this case, the freshwater snail. Each species has one or more unique snail species.

• In water, eggs mature into miracidia which penetrate the snail host where they undergo asexual changes. Later, free-swimming cercariae are released that can survive in fresh water for up to 48 hours, by which time they must attach to the skin of a human or another susceptible mammal host, or die.

• Cercariae attach to humans by suckers and migrate through intact skin. Over the subsequent few days they reach the pulmonary vessels. During this migration, the cercariae metamorphose and become highly resistant to host immune responses.

• The organisms, now called schistosomula, incorporate host proteins including histocompatibility and blood group antigens.

• The worms migrate through the pulmonary capillaries to the systemic circulation and the portal veins where they mature (schistosomes are atypical amongst trematodes in having both male and female sexual adult forms).

• Within the portal vessels they mate. Together they migrate along the endothelium, against the portal blood flow, to veins surrounding the intestines (S. mansoni, S. japonicum, S. intercalatum, S. mekongi) or the bladder (S. haematobium), where they produce eggs.

• The eggs number hundreds per day in African species and thousands per day in Asian species.

• The eggs are highly antigenic and induce an intense granulomatous response which is the primary cause of morbidity. They migrate through the bowel or bladder wall to be shed in faeces or urine and complete the cycle.

• Eggs that are not shed may remain in the tissues or may be swept back to the portal circulation or into the pulmonary circulation.

Schistosomiasis symptoms^{3 8}

• Infection can be acute or chronic. Physical findings vary with the stage of illness, worm burden, worm location and the organs involved.

• Schistosomiasis is associated with anaemia, chronic pain, diarrhoea, exercise intolerance and malnutrition.²

Acute schistosomiasis (Katayama fever)

• The acute reaction is due to the sudden release of highly antigenic eggs. The most common acute syndrome is Katayama fever.

• Most acute infections are asymptomatic.

• It usually occurs in children or young adults with no past exposure to the disease and is most likely with S. japonicum.

• Acute schistosomiasis (Katayama fever) is a systemic hypersensitivity reaction that may occur weeks after the initial infection, especially by S. mansoni and S. japonicum.

• Clinical features include systemic symptoms/signs including fever, cough, abdominal pain, diarrhoea, hepatosplenomegaly, and eosinophilia.

• A local cutaneous hypersensitivity reaction following skin penetration by cercariae may occur and appears as small, itchy maculopapular lesions.

• As travellers present several weeks after contact with infested water, it is necessary to obtain a careful travel history, including drinking water sources and activities such as swimming.

Chronic disease

• Chronic schistosomiasis can present months to years after exposure, making diagnosis difficult.

• It is endemic in poor, rural areas.

• Many patients have not had an acute syndrome.

• Symptoms may be few or mild. They may be nonspecific or reflect the site of egg production in the mesentery or bladder wall, the extent of damage to liver or spleen, the degree of lung involvement, and possibly other sites including the central nervous system (CNS).

Symptoms

• Bloody diarrhoea, abdominal pain, right upper quadrant pain, cramps, haematemesis, which can occur from oesophageal varices with portal hypertension.

• Haematuria, dysuria:
  

  • The first feature may be frequency of micturition.

  • Initially, haematuria is only terminal but, as it becomes more severe, the blood produces red urine throughout the stream.

  • There is proteinuria.

• Pulmonary hypertension may produce:
  

  • Fatigue.

  • Dyspnoea on exertion.

  • Cough.

  • Atypical chest pain.

• Hepatosplenomegaly.

Signs

• Abdominal tenderness.

• Ascites with portal hypertension.

• Seizures and/or altered mental state (with cerebral infection).

Investigations⁹

Schistosomiasis is diagnosed through the detection of parasite eggs in stool or urine specimens. Antibodies and/or antigens detected in blood or urine samples are also indications of infection.

• Microscopic examination of stool or urine is the gold standard for diagnosis but requires the adult worms to be producing eggs.²

• Serology can diagnose less advanced infections:²
  

  • Antigen detection is used in endemic areas and antibody tests elsewhere. It usually takes 4-8 weeks for seroconversion to occur, although it can be up to 22 weeks and serology remains positive for two years after eradication.¹⁰

  • The antibody test cannot be used to differentiate active and past illness (therefore, it is not useful in endemic areas) and does not allow quantification of the egg burden.

• FBC shows eosinophilia and anaemia.

• Renal function may be impaired if the urinary tract is obstructed.

Microscopy

• S. haematobium produces gross and microscopic haematuria.

• Stool specimens may be positive for occult blood or grossly bloody and may show parasites.

• Eggs in the urine or stool support a definite diagnosis and may be present as soon as 6-8 weeks after infection. The best time to collect urine is between noon and 3 pm or after physical exercise.

• Hatching assays can be performed on fresh specimens to distinguish active from treated infection because dead eggs may be shed for up to one year after treatment.

• Tissue biopsy of suspected tissues (eg, colonic biopsy or cystoscopy) may be used for diagnosis.

Imaging, ECG and endoscopy

• Ultrasound is a sensitive way to assess hepatosplenic disease and urinary obstruction.

• ECG can show pulmonary hypertension and cor pulmonale.

• CXR may indicate pulmonary hypertension and cor pulmonale.

• MRI scan or CT scan may be useful in the evaluation of CNS disease.

• Plain abdominal X-ray may show the line of a calcified bladder wall. This has been seen in the X-rays of ancient Egyptian mummies.

• Endoscopy may demonstrate oesophageal varices.

• Cystoscopy may show bladder lesions.

Schistosomiasis treatment and management

Emergency treatment may be required for acute complications - eg, acute intestinal bleeding.

Drugs

• Praziquantel is the drug of choice in most cases.³ Praziquantel is effective for urinary schistosomiasis and has few adverse events.¹¹

• The World Health Organization (WHO) advises that praziquantel is safe in pregnancy and lactation and in children under the age of 24 months.¹⁰

• Praziquantel paralyses adult worms with great rapidity but it has no effect on eggs or immature worms. Follow-up at 4-6 weeks is recommended with repeat of treatment in 6-12 weeks.¹⁰

• Oxamniquine is the only alternative; it is used in intestinal infections in Africa and South America, where praziquantel is less effective. The use of oxamniquine is declining but is effective.¹²

• Metrifonate, which was effective for urinary infections, has been withdrawn from the market.

• In acute Katayama fever, corticosteroids are very important to subdue the hypersensitivity reaction.

• Corticosteroids and anticonvulsants may be needed as adjuvants to praziquantel in neuroschistosomiasis.²

Surgical

• Endoscopy and sclerotherapy can treat oesophageal varices.

• A ventriculoperitoneal shunt and corticosteroids are required to treat hydrocephalus and raised intracranial pressure in cerebral schistosomiasis.²

Complications³

Complications associated with S. mansoni and S. japonicum schistosomiasis include various hepatic complications from inflammation and granulomatous reactions, and occasional embolic egg granulomas in brain or spinal cord.

Complications of S. haematobium schistosomiasis include haematuria, scarring, calcification, squamous cell carcinoma, and occasional embolic egg granulomas in the brain or spinal cord.

Occasionally, schistosomiasis may lead to central nervous system lesions. Cerebral granulomatous disease may be caused by ectopic S. japonicum eggs in the brain, and granulomatous lesions around ectopic eggs in the spinal cord may occur in S. mansoni and S. haematobium infections. Continuing infection may cause granulomatous reactions and fibrosis in the affected organs (eg, liver and spleen) with associated signs/symptoms.

Urinary tract

• Secondary bacterial infection and renal stones may occur.

• There is an increased risk of squamous cell carcinoma of bladder that has been noticed especially in Egypt. It is possible that the infestation and the carcinogens in tobacco smoke have a synergistic effect.

• Hydronephrosis may occur but will reverse if the disease is treated, suggesting that the renal parenchyma is compressed but not destroyed and renal function is not markedly impaired.

• Schistosomal nephropathy leading to chronic kidney disease may occur.

• Female urogenital schistosomiasis may be a risk factor for HIV infection.²

Alimentary canal

Gastrointestinal complications include gastrointestinal bleeding, gastrointestinal obstruction, malabsorption and malnutrition.

• Lesions tend to bleed and there is loss of blood and protein, causing iron-deficiency anaemia and hypoproteinaemia. These lesions are mostly in the colon and rectum.

• Fibrosis of the liver occurs, producing portal hypertension. S. mansoni infection invariably results in liver fibrosis.¹³

• Portal hypertension can produce oesophageal varices that may bleed, and ascites.

• Portocaval shunting predisposes to pulmonary infestation and problems of pulmonary hypertension.

• Co-infection with hepatitis, HIV and malaria can increase the risk of hepatocellular carcinoma and increase the risk of mortality.⁴

Other complications

• Chronic septicaemic salmonellosis (prolonged fever with enlargement of the liver and spleen) may occur in schistosoma-infected individuals who are co-infected with salmonella.¹⁴

• Pulmonary hypertension.

• Cor pulmonale.

• Neuroschistosomiasis (includes increased intracranial pressure, myelopathy and radiculopathy).²

Prognosis^{5 10}

• Although schistosomiasis is rarely fatal, it causes long-term morbidity such as anaemia and other complications.

• The overall mortality rate of schistosomiasis is around 14,000 deaths a year worldwide.

• End-stage hepatosplenic disease with variceal bleeding, pulmonary hypertension with cor pulmonale, and CNS disease are associated with high mortality rates.

• Early disease usually improves with treatment. Patients with greater worm infestations are less likely to improve and are more likely to require repeated treatment.

• Anthelmintic treatment may not reverse fibrosis.

• Hepatosplenic schistosomiasis has a relatively good prognosis because liver function is usually preserved until the end of the disease.

• Treatment is indicated for patients with end-stage complications of portal hypertension and severe pulmonary hypertension but these patients are much less likely to benefit from treatment; cor pulmonale usually does not improve significantly with treatment.

• Re-infection is very common in people who either live in or return to endemic areas. It is then necessary to have repeated treatment(s) to prevent disease progression.

Prevention^{15 16}

Current control strategies rely primarily on treatment with praziquantel, as no vaccine is available. However, treatment alone does not prevent re-infection.

The WHO has recommended preventative drug treatment for at-risk populations in endemic areas.¹ Other aspects of prevention include providing a safe water supply and snail control.

• The control of schistosomiasis is with drugs (single-dose praziquantel), education, improved water supplies and sanitation.

• There is no vaccine, although development of one may be feasible.¹⁷

• Drainage of marsh areas where snails breed.

• Use of molluscicides. This is of limited value, as total elimination is not feasible.

• Introduction of bio-control agents, such as predatory snails.

• Travellers should take care if going to an endemic area:
  

  • Avoid paddling, wading or swimming in fresh water in endemic areas.

  • Avoid untreated tap water or unchlorinated swimming pools. Heating bathing water or drinking water to 50°C for five minutes kills cercariae. Alternatives such as iodine or chlorine treatment may be used.

  • Filtering water with paper coffee filters removes cercariae.