Schistosomiasis

Synonyms - Also called Bilharzia, snail fever, Katayama fever, Swimmer's itch and Blood fluke.
Katayama fever is the acute disease. Swimmer's itch is an urticarial response for a few days after the fluke has penetrated the skin.

• The parasite is in the phylum Platyhelminthes (flatworms), class Trematodea (flukes), order Strigeatoidea, family Schistosomatoidae.
• There are 5 human species that cause schistosomiasis:
  • S. japonicum
  • S.mansoni
  • S.haematobium (these 3 being the most important)
  • S.intercalatum
  • S.mekongi
• This disease is second only to malaria in human impact among tropical diseases and is the third most prevalent parasitic disease in the world.
• Other schistosomes with avian or non-human mammalian primary hosts may cause dermatitis, or insignificant infection.

• Schistosomiasis infects over 200 million people with severe morbidity and mortality. That is about 1 person in 30 in the world.¹
• 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.²
• Prevalence is greatest in 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, Eastern Mediterranean and the Middle East.
• S.intercalatum occurs in 10 countries in the rainforest belt of Africa.
• S.mansoni is found in over 52 countries in Africa, Caribbean, Eastern Mediterranean and is the only species in Latin America.
• S.japonicum and S.mekongi cause intestinal schistosomiasis and are prevalent in Africa and the Pacific region.

• Like Fascioliasis, and Paragonimiasis (the liver and lung flukes respectively), the intermediate host is a snail, in this case the freshwater snail, each species having 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 freshwater up to 48 hours when they must attach to skin of a human or another susceptible mammal host, or die.
• Cercariae attach to humans by suckers and migrate through intact skin. Over the next 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, in their integuments.
• 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 portal blood flow, to veins surrounding the intestines (S.mansoni, S.japonicum) or 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 be swept back to the portal or to pulmonary circulation.

• Avoid paddling, wading or swimming in freshwater in endemic areas.
• Avoid unchlorinated tap water or swimming pools.

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

Acute Syndrome

The commonest acute syndrome is Katayama 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. The acute reaction is due to the sudden release of highly antigenic eggs. 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.

Symptoms

• 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.

Signs

• 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 CNS.

Symptoms

• Bloody diarrhoea.
• Abdominal pain, right upper quadrant pain, cramps.
• Haematemesis 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.

Signs

• Hepatosplenomegaly.
• Abdominal tenderness.
• Positive stool occult blood or bloody diarrhoea.
• Ascites with portal hypertension.
• Seizures and/or altered mental state (with cerebral infection.³)

• Diagnosis uses urine filtration and faecal smear techniques.
• Concentration methods are important and these remain the gold standard⁴ for diagnosis but they 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.²
• 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 3pm 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.

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 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.

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 choice¹ in most cases. It comes in 600mg tablets and the dose is usually 40mg/kg given as a single dose.
• Use of the only alternative, oxamniquine, used in intestinal infections in Africa and S America, where praziquantel is less effective, is declining, mainly on cost grounds.
• Metrifonate which was effective in urinary cases, 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.
• In the acute Katanyan fever, corticosteroids are very important to subdue the hypersensitivity reaction.

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.² It has been shown to be a very safe drug with low toxicity⁵ and the WHO believe that it is even safe in pregnanacy, lactation and in children off less than 24 months old.²

Surgical

• Tissue biopsy of suspected tissues eg. Colonic biopsy, or cystoscopy may be used for diagnosis.
• Endoscopy and sclerotherapy can treat oesophageal varices.¹

Urinary Tract

• In the urinary system there may be secondary bacterial infection and stones.
• 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 if the disease is treated this will reverse, suggesting that the renal parenchyma is compressed but not destroyed and renal function is not markedly impaired.

Alimentary Canal

• 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.
• Portal hypertension can produce oesophageal varices that may bleed and ascites.
• Porto-caval shunting predisposes to pulmonary infestation and problems of pulmonary hypertension.

• Acute schistosomiasis has a mortality rate 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.²
• 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.⁶
• 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.

• 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.⁷
• Drainage of marsh areas where snails breed, or use of molluscicides is of limited value as total elimination is not feasible.
• Introduction of bio-control agents, such as predatory snails.⁸
• Travellers should take care if going to an endemic area:
  • Heating bathing water or drinking water to 50YC for 5 minutes kills cercariae.
  • Alternatives such as iodine or chlorine treatment may be used.
  • Filtering water with paper coffee filters removes cercariae.
  • Since they rarely survive longer than 48hrs, allowing bathing water to stand for 3 days is effective.

The World Health Organisation states that the basis of control must be population based chemotherapy.

• The science of palaeoparasitology is generally regarded as beginning with the discovery of S. haematobium eggs in 20th dynasty (1250-1000BC) Egyptian mummies by the British scientist and Professor of Bacteriology at Cairo Medical School, Marc Ruffer in 1910.
• Some experts believe papyri from 1950BC record information about urinary or bladder infections, and may refer to urinary schistosomiasis, although this is contentious.
• Some x-rays of Egyptian mummies have shown an arc arising from the pelvis. This is a calcified bladder from schistosomiasis infection.
• The first clinical description of epidemic haematuria is credited to the French army surgeon A J Renoult in Napoleon's army in Egypt in 1798.
• The German physician and parasitologist, Theodor Maximilian Bilharz, first discovered and described Distomum haematobium in 1851 at the age of 27, making the association with the disease endemic haematuria a year later (co-credit going to his mentor in Germany, Siebold, in the former case, and with his superior Griesinger, director of Egyptian Department of Hygiene, in the latter case), and describing the peculiar pathological changes in bladder, ureters, intestines, and seminal glands. He died of typhoid fever aged 37, his name immortalized in the disease Bilharziasis by decision of the International Commission on Zoological Nomenclature in 1954, when the Bilharzia worm was ascribed to the genus Schistosoma, in the Bilharz Research Institute in Cairo, and on an Egyptian stamp commemorating the 100th anniversary of his death.
• The Scot, Sir Patrick Manson, who was one of the founders of the London School of Tropical Medicine, first suggested the existence of 2 species of human Schistosoma in 1902, though it was left to Robert Leiper, helminthologist to the London School of Tropical Medicine, to formerly identify the intestinal schistosome S.mansoni in 1915, the same year he elucidated the life cycle of S.haematobium in the snail.
• The 3rd most important schistosome is S. japonica, that causes Katayama disease. It is an ancient disease described by Dairo Fujii in 1847. A report coming to light in 1909. Various Japanese workers identified the worm, and elucidating the life cycle in the snail by 1913, 2 years before Leiper's description of S.haematobium.
• S. intercalatum (Fisher 1934) & S.mekongi (1978) are discoveries of the 20th century.