Pathology depends on the stage of the infection. Chronic symptoms are related to the total worm load (= number of worms in the body). Usually, light infections are asymptomatic. The likelihood of symptoms increases with an increase in the degree of infection. Sometimes parasites are found at ectopic sites (e.g. spinal cord), in which case there can be severe consequences, even in mild infections. Most people in endemic areas acquire some immunity over the course of the years. Many adults exhibit few signs of infection. This immunity is directed towards new infections, against schistosomula. Adult worms evade the immune system in various ways so that they can survive in their host. The immunological reaction directed towards the eggs is responsible for most pathology.

A local cutaneous itch can occur where cercariae penetrate. Slight erythema and pruritic papules develop. This is well known with S. mansoni, S. haematobium and with S. japonicum. The itch is more frequent and violent in infections with animal schistosomes, probably because the cercariae die after penetration in humans (e.g. avian schistosomiasis, which also occurs in areas with a moderate climate).

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Animal schistosomes that can enter humans accidentally:

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• Katayama fever tends to occur in patients who are not previously exposed, although in the case of S. japonicum this syndrome can also occur on re-infection.
• History of recent exposure, freshwater contact in endemic area
• Respiratory disorder and abdominal discomfort with fever and eosinophilia (DD trichinellosis, fascioliasis, filariasis, Strongyloides hyperinfection, etc.)
• Note that the eggs usually only appear later in the faeces. Failure to detect eggs thus does not rule out Katayama fever.
• Serology is initially still negative in early samples, but will become positive a couple of weeks later.
• Treatment consists of praziquantel and steroids. Repeat the course of praziquantel after a few months. Praziquantel is only active against adult worms.

Sometimes eggs or adult worms can cause lesions of the spinal cord, known as transverse myelitis (principally S. haematobium and S. mansoni), or of the brain (principally S. japonicum). These take the form respectively of spastic paraparesis and CVA (hemiplegia, epilepsy, etc...). Treatment consists of praziquantel together with steroids. Sometimes eggs can reach the skin, where they can cause papular dermatitis. This rare condition can only be diagnosed by biopsy. Even more rare is localisation in the vocal chords, with nodules and hoarseness.

The live larvae (miracidia) in the eggs excrete products that digest the surrounding tissues. In this way, eggs can reach the rectal lumen or the bladder after their migration through the intestinal mucosa (S. mansoni and S. japonicum) or the bladder mucosa (S. haematobium). In general, 50% or less of the eggs are eliminated with the faeces or urine. The remaining eggs either die locally or are transported with the venous blood until they reach the liver or another organ where the blood vessels become too small for their further passage. At this point, the eggs and the digestive juices which they secrete can cause local inflammation. The lesions of chronic schistosomiasis can be explained almost exclusively by the local inflammatory reaction to these eggs (formation of granulomata containing numerous eosinophils). Inflammation granulomata can reach up to 100 x the size of the original egg. Fibrous thickening and loss of elasticity of the tissues occurs. If massive infestation is present, pseudopolyps occur in the intestine or bladder. The symptoms in chronic schistosomiasis differ according to the location.

Diarrhoea, sometimes with some blood and mucus, can be caused by S. mansoni and S. japonicum. Pseudopolyps can occur in the colon. There is no increased incidence of intestinal cancer. In severe, chronic infections, fibrosis of the intestine can occur. S. mekongi is also found in the intestine, but usually does not cause severe pathology.

When S. mansoni eggs are carried in the portal venous bloodstream as far as the liver, they cause a physical obstruction of the bloodstream. Local inflammation around the eggs exacerbates this. The result is increased pressure in the portal circulation (portal hypertension). Clinically, it takes the form of:

• Enlargement of the spleen (splenomegaly)
• Collateral circulation with oesophageal varices and increased venous markings on the abdominal skin, principally around the navel, the so-called "caput medusa". Eggs can also reach other organs subsequently via this collateral circulation (lung).
• Ascites is a late sign.

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Because the eggs obstruct the branches of the portal venous system and fibrosis occurs around these foreign bodies, periportal fibrosis develops. This is also known as Symmers pipestem fibrosis. The white fibrotic bands in the liver are in fact long and hollow like pipestems (in the centre is a branch of the portal vein). Liver function remains surprisingly well preserved for a long time (normal blood coagulation, no severe hypoproteinaemia, no gynaecomastia). This stands in contrast with chronic aggressive hepatitis B and alcoholic cirrhosis. S. japonicum lesions are usually more severe because the worms produce ten times more eggs per day (3000 as opposed to 300) than S. mansoni. People with severe, chronic infections often die from bleeding from oesophageal varices.

The precise aetiopathogenic mechanism of ascites is still not fully established. Ascites is promoted by portal hypertension with increased hydrostatic pressure, hypo-albuminaemia with a reduction in colloidal osmotic pressure, peripheral vasodilatation and secondary hyperaldosteronism with disturbance of water and salt balance (stimulation of renin-angiotensin-aldosterone chain resulting in sodium and fluid retention). The normal pressure in the portal circulation is 5-10 mm Hg. An increase in pressure above 20 mm Hg has serious consequences. In treatment, salt restriction, fluid restriction and diuretics of the spironolactone type, whether or not supplemented with thiazide diuretics, beta-blockade and possibly nitro-derivatives are indicated. Ascites aspiration (4-6 litres), preferably with IV albumin administration (very expensive), can relieve the patient. This intervention carries a risk of precipitating prerenal kidney failure due to relative volume depletion. In better equipped centres a peritoneovenous or portocaval shunt (LeVeen or Denver shunt) or a transjugular intrahepatic portosystemic shunt (TIPS) can be inserted. The most recent technique involves the insertion of an expandable metal stent between the hepatic vein and the portal vein. The stent is introduced via the internal jugular vein. Shunt occlusion, shunt infection and the induction of hepatic encephalopathy are known complications. Docarpamine is a new oral dopamine prodrug that has been used experimentally in refractory ascites. Its administration results in renal vasodilatation and increased glomerular filtration. Spontaneous bacterial peritonitis is a serious complication of chronic ascites. Various organisms may be responsible and often include Escherichia coli or pneumococci. Portal-systemic encephalopathy may be induced by gastro-intestinal bleeding, hypovolaemia (avoid excessively large peritoneal tapping), infections or hypokalaemia (avoid excessive use of loop diuretics). If confronted with hepatic encephalopathy, any bleeding should be stopped and protein-rich food should be withheld (source of nitrogen). Ranitidine or a proton pump inhibitor will be given. Purgation and administration of lactulose and oral neomycin or metronidazole are indicated. Lactulose acidifies the colonic contents, which promotes the production of NH₄⁺ (non absorbable) over NH₃ (absorbable). Vitamin K analogues can be given. Narcotics and sedatives are best avoided.

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Oesophageal varices occur in 30% of patients with hepatic cirrhosis within two years of their first appearance. The severity of this complication is reflected in its 30% mortality. The risk of repeat bleeding within one year is 70%. Prophylaxis with non-selective beta-blockers (propanol or nadolol) reduces the risk to 15-18%. Combination of propanol (Inderal®) with isosorbide mononitrate causes the risk to fall still further to 8-10%. Propanolol is titrated until a pulse rate of 55/minute is obtained or until there is a reduction of 25% in the original pulse rate. Bleeding oesophageal varices often require endoscopic sclerosis or ligature. Balloon tamponade can be used as an emergency measure, but rebleeding after decompression is the rule. Splenectomy with oesophagogastric devascularisation is a major surgical procedure. Octeotride or vapreotide, somatostatin analogues (octeotride 25-50 µg/hour with or without bolus), or terlipressin, a synthetic vasopressin analogue (2 mg every four hours for the first four hours, and then 1 mg every four hours) may be given and should be administered for 24-48 hours. Bleeding stops in 80% of cases, but usually this medication is not available.

S. haematobium eggs lie grouped together in the bladder wall and surrounding organs (rectum, prostate, vagina, cervix, ovaries). This leads to the formation of very small (sandpaper-like) to a few mm large fleshy polyps and ulcerations. S. haematobium infection is a cause of genital lesions which are often mistaken for "warts". The lesions in the urinary tract cause blood to be passed in the urine. In endemic areas this occurs typically in children of school age. The severity of the haematuria and proteinuria is related to the degree of infection. Ureteral strictures occur mostly in the distal third (mainly in the intravesical part). Ureteral obstruction can occur with resultant hydro-ureter and hydronephrosis. Because of the impairment of the normal anatomical relations, vesico-ureteral reflux can also occur. Initially, these lesions are still reversible. S. mansoni can give rise to a deposit of immune complexes in the kidney, leading to glomerulonephritis. This happens in about 0.5% of cases, usually in those with severe infections. In S. haematobium schistosomiasis, the bladder wall can thicken. This resembles the thickening that can occur in tuberculous cystitis, chronic interstitial cystitis, radiation cystitis, chronic chemical cystitis or as a result of muscular hypertrophy with obstruction due to prostatic hypertrophy or neoplasia or with a neurogenic bladder. The bladder wall can also calcify, which is clearly visible on X-ray film.

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In the event of obstruction of the urinary tract, consideration should be given to (1) pelvi-ureteral junctional stenosis, (2) calculus, tumour, blood or lymph clots, necrotic papillae in sickle cell or analgesic nephropathy, (3) stricture due to tumour, tuberculosis, bilharziasis or retroperitoneal fibrosis, (4) extrinsic invasion of the ureter by a cervical, rectal or sigmoid neoplasia, (5) bladder tumour, (6) prostatic enlargement, (7) urethral valves and urethral stenosis (sequela of gonorrhoea).

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After severe, chronic infection, the following serious problems can occur:

• Reduced bladder capacity.
• Increased incidence of bladder carcinoma.
• Lesions of the female genitalia with cervical erosions, papillomatous lesions, sterility, increased risk of ectopic pregnancy.
• Lesions of the male genitalia e.g. localisation in the ductus spermaticus.
• Irreversible obstruction of the urinary tract with hydro-ureter and hydronephrosis.
• Renal stones can form. Recurrent bacterial urinary infections are frequent, including Salmonella.
• Nephrotic syndrome can occur, as well as hypertension.
• Finally, chronic renal insufficiency may ensue.
• Remember that chronic glomerulonephritis can be caused by S. mansoni which is localised in the intestines (and eggs in the liver).

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S. haematobium eggs can reach the systemic circulation and only rarely reach the portal circulation. This parasite is not a cause of hepatosplenomegaly. These eggs then reach the lungs. The same can happen with severe portal hypertension when S. mansoni or S. japonicum eggs reach the lung via the collateral circulation. Inflammation occurs in the lungs, resulting in fibrosis and pulmonary hypertension. Right heart failure then occurs with development of cor pulmonale, with congested jugular veins, peripheral oedema and congested swollen liver. It used to be common in Brazil and Egypt. In the last few years it has become much less common.

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Pulmonary hypertension needs to be severe before marked changes appear on chest X-ray. An enlarged heart with right ventricular hypertrophy is apparent. The pulmonary hili are enlarged. Distally, the pulmonary arteries become thinner somewhat abruptly. Beneath the aortic arch a prominent pulmonary artery can be seen, which is sometimes confused with hilar lymphadenopathy.

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The symptomatic medical treatment of pulmonary hypertension includes administration of prostanoids (prostacyclin PGI₂-derivatives) such as epoprostenol (IV), treprostinil (SC), iloprost (inhalation) beraprost (PO) and/or endothelin receptor antagonists (e.g. bosentan). Most of this kind of medication is too expensive for most hospitals in third world countries. Determination of the 6-minute walking test (assessment of exercise capacity) is important in making a prognosis of this serious complication.

Patients with schistosomiasis (S. mansoni, S. haematobium and S. japonicum) are at increased risk of being Salmonella carriers. These bacteria are found in the intestinal tract of the worm. Urinary schistosomiasis often results in recurrent bacterial urinary tract infections.