Synonyms: Bilharzia, snail fever, Katayama's fever, swimmer's itch and blood fluke

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

• S. japonicum
• S. mansoni
• S. haematobium
• S. intercalatum
• S. mekongi

Other schistosomes with avian or non-human mammalian primary hosts may cause dermatitis, or insignificant infection. Human contact with water is necessary for infection by schistosomes. Various animals (e.g. dogs, cats, rodents, pigs, horses and goats) act as reservoirs for S. japonicum, and dogs for S. mekongi.²

Epidemiology¹

• Schistosomiasis is second only to malaria in human impact among tropical diseases and is the third most prevalent parasitic disease in the world. More than 207 million people are infected worldwide, with an estimated 700 million people at risk in 74 endemic countries.
• Despite the complications that may occur, mortality appears to be low, in that with 200 millions cases, there are an estimated 14,000 deaths per year.[R33348
• Prevalence is greatest during teenage years with higher rates among boys than girls.
• It is endemic in 74 developing countries with more than 80% of infected people living in sub-Saharan Africa.
• In Egypt and rural central China it is the major health risk.
• S. haematobium causes urinary schistosomiasis, and is the most prevalent and widespread species in Africa and the Middle East.
• S. intercalatum occurs in 10 countries in the rainforest areas of central Africa.
• S. mansoni is found in over 52 countries in Africa, the Caribbean and the Middle East, and in Brazil, Venezuela and Suriname (it is the only species in Latin America).
• S. japonicum is found in China, Indonesia and the Philippines.
• S. mekongi are prevalent in several districts of Cambodia and the Lao People's Democratic Republic.

Life cycle

• The intermediate host is a snail, in this case the fresh water 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 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.

Presentation

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

Acute syndrome

• The acute reaction is due to the sudden release of highly antigenic eggs.
• The most common acute syndrome is Katayama's fever. It usually occurs in children or young adults with no past exposure to the disease, as they are often travellers, and is most likely with S. japonicum.
• 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.

• Most acute infections are asymptomatic.
• The first sign may be swimmer's itch in which there is an urticarial response for a few days after the parasite has penetrated the skin.
• Malaise.
• Arthralgia or myalgia.
• Cough.
• Diarrhoea.
• Right upper quadrant pain.

• Fever.
• Hepatosplenomegaly.
• Right upper quadrant pain or tenderness.
• Urticaria may be seen occasionally.
• Lymphadenopathy.
• Initial invasion of skin and infection with non-human species may cause itching and rash.

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).

• Bloody diarrhoea.
• Abdominal pain, right upper quadrant pain, cramps.
• Haematemesis, which can occur from oesphageal 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.

• Abdominal tenderness.
• Ascites with portal hypertension.
• Seizures and/or altered mental state (with cerebral infection).

Investigations

• Stool or urine analysis to identify the eggs remains the main method of diagnosis but can miss light infection.
• Serology can be helpful:
  • Antigen detection is used in endemic areas and antibody tests elsewhere. It usually takes 4 to 8 weeks for seroconversion to occur, although it can be up to 22 weeks and serology remains positive for 2 years after eradication.³
  • 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.⁴
• FBC shows eosinophilia and anaemia.⁴
• 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 (e.g. 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.

Management

Emergency treatment may be required for acute complications, e.g. acute intestinal bleeding.⁴

Drugs

In the early days the drugs were possibly more toxic than the disease but the 1970s saw the advent of safer drugs:

• Praziquantel is the drug of choice in most cases.² It comes in 600 mg tablets and the dose is usually 40 mg/kg given as a single dose.
• Praziquantel paralyses adult worms with great rapidity but it has no effect on eggs or immature worms. Follow-up at 4 to 6 weeks is recommended with repeat of treatment in 6 to 12 weeks.³
• Praziquantel has been shown to be a very safe drug with low toxicity⁵ and the World Health Organization (WHO) believes that it is even safe in pregnancy, lactation and in children under the age of 24 months.³
• 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, mainly on cost grounds.
• Metrifonate, which was effective for urinary infections, has been withdrawn from the market.
• Derivatives of artemisinin, the antimalarial, are under consideration for use in combination with one or more of the above, as praziquantel resistance appears. There is currently not enough evidence to evaluate artemisinin compounds.⁶
• In acute Katayama's fever, corticosteroids are very important to subdue the hypersensitivity reaction.

Surgical

• Endoscopy and sclerotherapy can treat oesophageal varices.⁷

Complications

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 renal failure may occur.⁴

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.⁸
• Portal hypertension can produce oesophageal varices that may bleed, and ascites.
• Portocaval shunting predisposes to pulmonary infestation and problems of pulmonary hypertension.

Other complications⁴

• Chronic septicaemic salmonellosis (prolonged fever with enlargement of the liver and spleen) may occur in schistosoma-infected individuals who are co-infected with salmonella.⁹
• Pulmonary hypertension.
• Cor pulmonale.
• Neuroschistosomiasis.

Prognosis

• Acute schistosomiasis has a mortality rate of up to 25% in some series. Heavy infestation increases risk. By and large, the mortality is not high with around 14,000 deaths a year worldwide.³
• Most people with chronic schistosomiasis have few or no symptoms but complications do occur.
• Drugs cure 60-98% of cases and reduce egg load in the rest. Dead eggs may be shed for months, but treatment arrests egg-laying, granuloma formation and future complications.
• Whilst gross fibrosis may not reverse, portal and pulmonary hypertension from granulomatous changes may improve significantly after treatment, particularly in the young.
• Pulmonary disease is less reversible.¹⁰
• Almost all patients improve with treatment.
• Most patients with early disease or without severe end-organ complications recover completely.
• Patients with heavier worm burdens are less likely to improve and are more likely to require re-treatment.
• Patients with end-stage complications of portal hypertension and severe pulmonary hypertension are less likely to benefit from treatment.

Prevention

The WHO has recommended preventative drug treatment for at-risk populations in endemic areas.⁴ 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.¹¹
• Drainage of marsh areas where snails breed.
• Use of molluscicides is of limited value as total elimination is not feasible.
• Introduction of bio-control agents, such as predatory snails.¹²
• 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 5 minutes kills cercariae. Alternatives such as iodine or chlorine treatment may be used.
  • Filtering water with paper coffee filters removes cercariae.

Document references

1. Schistosomiasis, World Health Organization (WHO)
2. DPD-CDC Schistosomiasis
3. Gryseels B, Polman K, Clerinx J, et al; Human schistosomiasis. Lancet. 2006 Sep 23;368(9541):1106-18. [abstract]
4. Kogulan P et al; Schistosomiasis, eMedicine, Feb 2010
5. Dayan AD; Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Trop. 2003 May;86(2-3):141-59. [abstract]
6. Danso-Appiah A, Garner P, Olliaro PL, et al; Treatment of urinary schistosomiasis: methodological issues and research needs Parasitology. 2009 Nov;136(13):1837-49. Epub 2009 Jun 3. [abstract]
7. Elliott DE; Schistosomiasis. Pathophysiology, diagnosis, and treatment. Gastroenterol Clin North Am. 1996 Sep;25(3):599-625. [abstract]
8. Andrade ZA; Schistosomiasis and liver fibrosis. Parasite Immunol. 2009 Nov;31(11):656-63. [abstract]
9. Muniz-Junqueira MI, Tosta CE, Prata A; (Schistosoma-associated chronic septicemic salmonellosis: evolution of knowledge Rev Soc Bras Med Trop. 2009 Jul-Aug;42(4):436-45. [abstract]
10. Morris W, Knauer CM; Cardiopulmonary manifestations of schistosomiasis. Semin Respir Infect. 1997 Jun;12(2):159-70. [abstract]
11. Wu ZD, Lu ZY, Yu XB; Development of a vaccine against Schistosoma japonicum in China: a review. Acta Trop. 2005 Nov-Dec;96(2-3):106-16. Epub 2005 Sep 28. [abstract]
12. Madsen H; Biological methods for the control of freshwater snails. Parasitol Today. 1990 Jul;6(7):237-41. [abstract]

Internet and further reading

• Center for Disease Control (USA); Information including endemic areas
• University of Cambridge; Schistosomiasis Research Group

Acknowledgements