SCHISTOSOMIASIS / MedUrgent

SCHISTOSOMIASIS

Though hematuria, ascites and scrotal edema were well documented in the ancient Egyptian papyri and temples, it was Theodore Bilharz in 1851 who identified S. Haematobium as the cause of haematuria in Egyptian patients. Sir Patrick Manson, in the early twentieth century differentiated the three major disease - causing species of schistosomes.

The disease is caused by blood-fluke (trematode) of the genus Schistosome that lives inside blood vessels of man who is the definitive host for the three commonly known types of schistosomes: 

• Schistosoma mansoni which prevails in the Middle East and Africa.

• Schistosoma haematobuim is mainly found in the Middle East and Africa.

• Schistosoma japonicum occurs primarily in Japan and China. Other species that affect animals include s. Kongi, s. Intercalatum, s. Mattheer, s. Bovis, S. Rodhaini, s. Margrebowiei, s. Spindale and s. Incognitum.

LIFE CYCLE 

The eggs are passed by an individual harbering the infection, and under suitable conditions they hatch within minutes forming miracidia. These enter their intermediate host, the snail, where they develop further into cercariae. One miracidium is capable of giving rise to 3.000 cercariae which are usually of the same sex.

The cercariae are released from the snail in 4-6 weeks where they are capable of surviving for 48 to 72 hours. During this period, man will be infected by cercariae which use their tails and the penetration gland to enter through the skin when they then lose their tail and form schistosomules. These travel via the lymphatic to the veins to reach the lungs, heart and finally settle in the liver where they mature.

S. mansoni adult worms travel to the mesenteric veins, and those of S. haematobium migrate against the portal flow to the vesical and bladder veins. At these points, the respective adults copulate and release their eggs that penetrate respective organ walls and pass into the intestine and bladder respectively.

TRANSMISSION

The adult worm is thick and short, the female is slender and long and it lies folded within the schist in the male body. Adult worms mate in the liver blood vessels and then migrates to mesenteric plexus to deposit eggs according to their ultimate preferred site e.g. S. haematobium is concentrated near the bladder, s. mansoni in the inferior mesenteric vessels of the large intestine and s. japonicum in the superior mesenteric vessels of the large and small intestines. Life span of the adult worm is 3 - 30 years.

From this coupling the fertilized ovum is passed in the urine or stools, relieves a single miracidium when it comes in contact with mesh water.

Meracidia penetrates the appropriate snail (the intermediate host) where it changes into sporocyst and then metamorphoses into forked-tail cercariae that emerge from the snail into fresh water. Cercaria lives up to 3 days in water, penetrates human skin, loses its tail, and migrates through blood vessels as a schistosomules that transforms into adult worm within 1 - 4 weeks.

Factors necessary for the transmission of these parasites include:

A) Suitable snails i.e. S. haematobium requires the snail Bulinius truncalius, and S. mansoni requires one from the Biomphalaria genus.

B) Contamination of the snail-containing waters is through eggs passed by infected individuals. Suitable environment for the snails to grow is slow running streams. Presence of vegetations, optimal temperature and abundant sun-light are all necessary for their development. These conditions prevail in ponds and canals of new irrigation schemes that provide favorable breeding environment for these snails. Man-water contact is important for transmission of the disease.

C) The spread of the disease among children, who are likely to swim in pond and canals containing viable cercaria. For adult farmers, the disease is an occupational hazard.

D) In the Sudan Gezira scheme, the incidence of S. haematobium has been greatly reduced, and S. mansoni has become the most prevalent parasite due to the fact that this parasite is more dominant and replaces S. haematobium.

E) S. haematobium usually infest new irrigation schemes like Nuba Mountains and Northern provinces in the Sudan or spread with immigrants to new settlements as in Gezira area.

PATHOLOGY

This occurs in four stages.

STAGE 1: (THE STAGE OF INVASION)

When cercaria enters through the skin, it remains deep near the portal of entry for 4-5 days where it leads to itchy nodules known as cercarial swimmers dermatitis. This is particularly common when one is infected by an animal schistosome. There may be a mild inflammatory reaction in the skin, lungs and liver.

STAGE 2: (THE STAGE OF MIGRATION)

This begins around 4-8 weeks after the infection. It is due to the migration of the schistomoules within the body and is characterized by an acute febrile reaction with severe eosinophilia. Katayama-like syndrome, which is commonly seen in S. japonicum, may be considered a reaction of a similar nature. The patient may present with fever, abdominal pain, cough, dyspnea and hepatosplenomegaly.

STAGE 3: (ESTABLISHED INFECTION)

Signs begin around 10-12 weeks after the infection. There is heavy egg production by the adult parasites in S. mansoni, the eggs are excreted mainly in the stools but in rare cases may be seen in the urine. In S. haematobium the opposite is also true. In S.mansoni heavy egg deposition may occur in the intestine, appendix, gall bladder, liver and lungs. In S. haematobium the egg deposition is within the bladder walls. They form granulomatous reaction that could lead to ulceration and polyp formation of the bladder wall. Cancer of the bladder has also been reported and there may be ureterial fibrosis leading to hydronephrosis.

STAGE 4: (COMPLICATIONS AND FIBROSIS)

Eggs of s. mansoni are carried to the liver in huge amounts. They block the portal veins and as a result, cause a reaction of dense fibrosis known as Symmer's fibrosis. They cause periportal fibrosis that gives the clay pipe stem appearance. At this stage, hepatomegaly, portal hypertension and splenomegaly commonly occur. In the intestine the egg deposition leads to fibrosis, polyp formation, ulceration and bleeding.

When portal hypertension develops, eggs may pass into the systemic circulation via the porto_systemic anastomoses. This is the period when may be deposited in various organs where they can cause additional complications.

In the lungs they could cause cor pulmonali and pulmonary hypertension. Fibrosis of the lungs can also occur. This is rather common with S.mansoni occurring in Egypt and S. America, however, this feature is not common in the Sudan.

In the CNS, granulomata may develop and lead to epilepsy. Eggs may lodge in the spinal cord, leading to cord compression and may result in paraplegia. Due to immune complexes formed and granulomas, transverse myelitis may also occur.

If the immune complexes are deposited in the glomeruli of the kidneys, this may lead to amyloidosis and give rise to nephrotic syndrome.

The pathological effects are related to the infecting dose of eggs and the intensity of the infection and are related to the clinical and biochemical changes. The anemia in schistosomiasis is due to malnutrition, blood loss and auto-immune processes. These are also responsible for thrombocytopenia and leucopenia but eosinophilia is related to the degree of infection.

Certain gram-negative organism such as Salmonella and E.coli live within the tissues of the schistosomes and may cause systemic infections. Salmonella infections, in particular, are known to live for long periods leading to 'schisto-salmonellosis' which is associated with protracted intermittent fever.

 IMMUNOLOGY

Partial immunity and IgG and IgM antibodies are developed against eggs, cercaria, and adult worm's antigens and IgG are mainly responsible for enlargement of the spleen. This is in contrast to tropical splenomegaly, where the causative antibody is considered to be due to IgM.

Granuloma is considered to provide a protective mechanism which in turn competes with the cercaria antigens as shown by "Symmer's fibrosis". 

CLINICAL MANIFESTATIONS

1. Early manifestations 

• Swimmer's Itch or Kaburi Itch. Topical steroids and aspirin may help alleviate the condition.

• Katayama fever may present after 4-6 weeks of infection

2. Late manifestations

• Granulomata in different organs

• Intestinal schistosomiasis

This is commonly seen with s.mansoni and s. japonicum. The large intestine is more involved than the small intestine. Abdominal pain and bloody diarrhea are the early manifestations. Formation of granulomata, polyps and ulcers lead to anemia, protein-losing enteropathy, obstruction, intussusceptions, rectal prolapse, ano-rectal fistula, perianal abscess and colonic carcinoma.

• Hypertrophic Arthropathy and clubbing may occur in chronic cases.

• Urinary schistosomiasis

This is mostly caused by s. haematobium. Dysuria, urinary frequency and terminal haematuria are the earliest symptoms. Chronic untreated infection leads to obstructive uropathy which affects the lower third of ureter and the bladder leading to hydroureter, hydronephrosis, pyelonephritis and renal failure.

• Chronic bacteruria: Commonly caused by salmonella species and coliform bacteria.

• Bladder cancer follows chronic infection with s. haematobium by 10 - 20 years.

• Bladder calcification which may resolve completely after antibilharzial treatment.

• Nephrotic Syndrome which complicates both s. haematobium and s. mansoni infection due to secondary amyloidosis.

• Cardiopulmonary schistosomiasis

Primary lung disease leading to heart disease is caused by all 3 types of schistosoma parasites. Pneumonitis occurs early during cercarial migration to the lungs and a similar condition may occur during treatment of schistosomiasis. There is marked eosinophilia and the x-ray shows basal mottling. Cor pulmonale results secondary to lung disease.

• C.N.S

This results due to deposition of eggs and formation of granuloma in the C.N.S. It may present with symptoms and signs of space occupying lesion in the brain or as transverse myelitis when it deposit in the spinal cord.

• Salmonella - Schistosomiasis Syndrome which presents with history of prolonged indolent fever with no prostration or delirium. A petechial rash on the extremities is common.

SCHISTOSOMA HAEMATOBIUM

 The incubation period is unknown, but symptoms appear approximately 2 months after the infection. The early signs are those of fatigue, a slight fever, terminal haematuria and a dull pain usually felt in the hypogastrium and sometimes it may be abdominal. Other signs that can appear include urinary tract obstruction, dysuria, urgency and frequency. Some cases may present with dysenteric symptoms with blood and mucus in the stools. Complications mentioned above may develop during the course of the disease.

SCHISTOSOMA MANSONI

Cercarial dermatitis is seen in the first 24 hours. Three to four days later, fever, cough and eosinophilia usually occurs. This is followed by toxemic and hypersensitivity stage; a Katayama- like reaction 2-3 weeks after infection. Dysenteric symptoms appear 2-6 weeks after the infection. The onset is usually associated with abdominal pain which is either colicky or gripping in nature. Fatigue is an important early symptom and there might be a low grade fever; and clinical examination reveals abdominal tenderness.

Chronic intestinal disease consists of a wide-spread involvement of the intestines by a granuloma reaction, fibrosis and ulceration. This presents with chronic dysentery with bloody mucoid stools, abdominal pain and fatigue. Polyps may be formed in the rectum, large bowel and occasionally in the small intestine. Acute granuomalatous mass (bilharzioma) may lead to eventual intestinal obstruction. Anemia is a characteristic feature due to blood loss from varicies and bloody diarrhea. An auto-immune hemolytic process due to hypersplenism is an additional cause. Periportal fibrosis occurs in the liver (true cirrhosis is not usually seen) and ascites may develop as a result. Cardio-pulmonary complications mentioned above may also occur. 

DAIGNOSIS

S. haematobium:

1. History of hematuria in endemic regions may suggest the diagnosis.

2 Terminal spine ova are usually found in the urine, stools and rectum. A rectal snip may confirm the diagnosis. Urine examination should be done in several occasions using concentration or filtration methods.

3. Radiological and ultrasonic examinations determine renal and ureteric abnormalities.

S. mansoni:

1. History and clinical features of the disease in endemic regions suggests the diagnosis.

2. The lateral spined eggs can be isolated from the stools or urine by concentration methods. Egg count is useful for subsequent evaluation of treatment. The Hatching Test: determines viability of ova confirms cure. Rectal snip reveals ova and sigmoidoscopy reveals presence of polyps in the large bowel.

3. Serology: Circumoval Precipitin Test (COPT), Cercaria Hullen Reaction, Miracidium Immobilization Test, Cercaria Fluorescent Antibody Test, Haemagglutination and Elisa Tests.

4. Chest X-ray shows signs of pulmonary hypertension. Mottling of the lungs may be seen. 

5.Barium studies or endoscopy are used to demonstrate esophageal and gastric varices. 

6.Liver biopsy demonstrates periportal fibrosis.

TREATMENT

ANTI-BILHARZIA DRUGS: Various antibilharzia remedies are used for different species of schistosomiasis and the cure rate varies accordingly. Cure might not be declared until clinical symptoms disappear and viable ova are not recovered from excreta or snips 3 months after treatment provided that reinfection is excluded.

Action of antibiharzial drugs and contraindications

1. Trivalent Antimony CompoundsSitbacaptate (Astiban) acts by inhibition of phosphorylase active enzymatic systems and it interfere with glycogen production in the worm. Tartar Emetics (sodium or potassium antimony tartrates), this drug is more effective than Astiban, but it is potentially more toxic. Contra-indications include heart disease, severe anemia and liver or kidney disease

2. Niridazole (Ambilhar) It acts by damaging the vitelline duct and cells of the female worms and thus kills the parasite. Contra-indications are history of psychiatric disease, apsy, portal hypertension, severe anemia, liver and kidney disease and patients on INH or some other anti-T.B. drugs

3. Lucanthone (Miracil D)

4. Hycanthone (Etrenol) This is a hydroxmethyl derivative of lucanthone. It acts by killing the worm. Contra-indications are history of recent jaundice, presence of liver disease, gross hepatomegaly, portal hypertension, renal failure and severe anemia.

5. Metrifonate (Bilarcil)

This is an organophosphorous cholinesterase inhibitor that was originally produced as an insecticide.

6. Oxaminquine (Vansil)

This is a tetrahydroquinolone derivative that is effective against S. mansoni infections only. The drug is contra-indicated in pregnancy.

7. Praziquantel Currently, it is the drug of chioce for the treatment of all forms of schistosomiasis. It is well tolerated and the side-effects are mild including GIT disturbances and vertigo. Treatment of complications:

• Obstructive uropathy and intestinal polyposis are treated by antibilharzial drugs (surgery only in complicated cases).

• Splenectomy is often indicated for severe anemia due to hypersplenism.

• Paracentesis for the relief of severe ascites may be done.

• Porto-venous shunt may be necessary for treatment of portal hypertension and varicial bleeding.

Control measures:

• Prohibit passing urine and stools in water canals.

• Provide safe water supply to reduce contact with snails

• Use insecticides to kill the snails or other methods to eradicate the snails, e.g. telabia fish

• Health education regarding the disease and its control measures.