Schistosomiasis is one of the most widespread of the parasitic diseases that afflict man: well over 200 million people are infected and a further 600 million are at risk. The number of countries endemic for schistosomiasis is increasing, and it continues to be a major public health problem in most of Africa, in parts of Asia, the Caribbean, and South America. The majority of infections are caused by Schistosoma haematobium, S. mansoni, and S. japonicum but S. intercalatum and S. mekongi are also becoming epidemiologically important. Up to 500 000 deaths annually are attributable to schistosomiasis.

Worms of the genus Schistosoma comprise several blood parasites of humans and other animals; they belong to the family Schistosomatidae, the class Trematoda, and phylum Platyhelminthes (flatworms). The intermediate hosts are various species of freshwater snails which shed the infective larval form (cercariae) into the surrounding water. Man is exposed on coming into contact with infected water: cercariae penetrate the skin and those that survive ultimately mature into adult worms which live in pairs in veins. There the female worms shed a large number of ova (eggs), some of which are excreted in the host's urine or stool where they go on to complete the life cycle. The remaining ova lodge in the host's tissues, where they stimulate a granulomatous response.

As international travel becomes more widespread the surgeon may encounter schistosomiasis anywhere in the world. Its manifestations are protean and in its acute and chronic stages it may mimic a number of other diseases ( Table 2 641 and Table 3 642. It is probably the most common cause of portal hypertension in the world and may present for the first time with massive variceal haemorrhage. The urologist deals with its fibrotic and malignant sequelae, but schistosomiasis also leads to end-stage renal failure, to be investigated and treated by the transplant surgeon. The neurosurgeon may see a patient with spinal cord schistosomiasis who improves with chemotherapy alone. The general surgeon will be consulted for an acute abdomen, an abdominal mass, or because of bloody diarrhoea, while the cardiothoracic surgeon may be confronted by a massive pulmonary artery in a patient with cor pulmonale. A gynaecologist may not realize the aetiology of a ruptured ectopic pregnancy until he sees a report from the pathologist. A patient with schistosomiasis may present with a prolonged fever due to chronic salmonellosis. When schistosomiasis is suspected the surgeon may be requested to perform a biopsy of the rectum or of another affected organ, to help with splenoportography, or undertake a laparoscopy. When sclerotherapy does not control variceal haemorrhage, the surgeon may need to perform a shunt or another surgical procedure, and he may even contemplate a liver transplant. Patients with hepatosplenic schistosomiasis are often chronic carriers of hepatitis B, perhaps due to a state of relative immunosuppression. They therefore present a hazard to the surgeon. Schistosomiasis has also been linked to a number of malignancies, the most important of which is squamous cell carcinoma of the urinary bladder.

Unlike other trematodes, which are hermaphrodite, schistosomes are dioecious, existing as separate male and female forms in the definitive host. Sex is determined at the time of fertilization of the ova, and all subsequent progeny of asexual reproduction remain the same sex. They are digenetic, with an asexual reproductive phase in the snail and a sexual reproductive phase in the definitive host.

On entering the definitive host the cercaria sheds its forked tail, becoming a schistosomulum, and its metabolism changes from an efficient tricarboxylic acid cycle form to a mainly anaerobic form. Within a few days schistosomula that survive the skin phase reach the lungs, mainly via the bloodstream. From the lungs the developing worms reach the portal system of the liver, probably via arterial blood and mesenteric veins; alternative, but unlikely, routes to the liver from the lungs are through the diaphragm or by retrograde movement through the right heart to the hepatic veins and thence to the portal system. Here they mature and then, with the female clasped in the gynaecophoral canal of the male, they migrate in pairs against portal blood flow to settle in mesenteric veins, or in vesical veins in the case of S. haematobium. There they live attached to the vein wall by their ventral suckers, continuing to lay their eggs for an average of about 5 years, but in rare instances for over 30 years. S. japonicum produces up to 3000 eggs/day while S. mansoni produces about 300/day. For this enormous energy expenditure, up to one-fifth of the worm's weight of glucose is used up every hour. To save the female's energy for egg production, even movement within the veins is largely undertaken by the male, who probably also helps to feed the female: the male worm's role as a supplier of muscle power may be biologically more important than its role as a fertilizer of eggs. Nutrition is derived from the blood through the tegument and intestines. A female S. mansoni in the laboratory mouse ingests about 330 000 erythrocytes/h, while a male ingests 39 000. The haemoglobin is broken down by haemoglobinases; the pigment is excreted and then taken up by macrophages.

Many of the observations are based on experimental schistosome infections. Despite the success of schistosomes as parasites, the host produces an immune response and only a small proportion of schistosomula survive to become adult worms.

Concomitant immunity, a term borrowed from tumour immunology, describes the condition seen when an actively infested host partially or completely resists a subsequent challenge infection by the same type of organism. Epidemiological evidence suggests that concomitant immunity occurs in schistosome-infected humans, although it may be slow to develop. Both cellular and humoral mechanisms are involved in eliminating schistosomula in the skin. In some rodent models, the lungs are thought to be an important site for the immune elimination of schistosomula. In the vaccinated guinea-pig model, immunity to juvenile schistosomes appears to reside predominantly in the liver. Some of the immune mechanisms have only recently been elucidated; these include the ability of IgE antibodies and various cytokines to arm macrophages, eosinophils, and platelets for effective antibody-dependent cell-mediated cytotoxicity reactions against schistosomula. The cytokine interleukin-5 (IL-5) appears to be particularly important in preparing eosinophils for this function. Eosinophils seem to be more important in the skin, while macrophages are more important in lung and liver phase resistance. Inhibition of parasite migration may be a crucial feature of both skin and lung phase immunity in different rodent species. A variety of antibodies is produced at various stages, directed against both structural components and excreted and secreted products of eggs, schistosomula, and the adult worm. Deposition of an egg in the tissues is followed by a granulomatous response: this is an example of the delayed type hypersensitivity reaction. The evasion mechanisms that allow some of the schistosomes to achieve a successful state of parasitism include rapid turnover of membrane components, enzymatic cleavage of attached antibodies and complement (e.g. by serine proteases), tegumental structural development, the coating (or masquerade) of the parasite surface with host antigenic components, (e.g. ABO blood group antigens, MHC antigens, low density lipoproteins), antigenic mimicry, direct immunosuppressive effects, and the induction of humoral and cellular immunoregulatory mechanisms, including anti-idiotypic networks. Another fascinating mechanism is the insertion of the host's decay acceleration factor on to the parasite's surface. Decay acceleration factor normally controls the activation of the host's alternative complement pathway; its presence on the worm's surface ensures that host complement will not be activated there. Furthermore, as the worm matures, its defences against oxidant damage appear to increase progressively.

A genetically engineered schistosome glutathione-S-transferase molecule (P28 GST) has been developed as a vaccine. It is effective in cattle and in 1992 was due to be tested for safety in man.

The prevalence and intensity of infection in man generally decreases with age; this is especially true for S. haematobium and S. mansoni. Although there has been some controversy as to whether this is due to true immunological resistance, or to reduced water contact with age, recent evidence favours the development of true resistance. Butterworth and colleagues in Kenya, and Hagan and colleagues in The Gambia, have confirmed that a significant degree of protective immunity against S. haematobium infection gradually develops in children. The age-related decline in intensity and prevalence of infection was most developed after 15 years of age. Measurement of the serological response during reinfection (after praziquantel treatment) demonstrated for the first time that IgE antibodies in man can be beneficial. The slow build up of IgE levels over the years, and the early production of IgG4 antibodies, which may block IgE pathways, are thought to be responsible for delaying the development of protective immunity to S. haematobium.

The number of countries endemic for schistosomiasis is increasing: the disease now affects at least 79 countries with a population of about 3 billion. S. haematobium and S. mansoni infections occur in Africa, where 40 per cent of the population are infected, and in West Asia. Schistosomal eggs have been found in the tissues of 3000-year-old Egyptian mummies. Only S. mansoni infections occur in the New World, where it is thought to have been carried from Africa by the slave trade. S. japonicum occurs mainly in the Orient, especially in China and the Philippines. S. intercalatum is now endemic in Equatorial Guinea and is also found in several other West and Central African countries. S. mekongi infection occurs in the Mekong delta.

Schistosomiasis is the most prevalent of the water-borne diseases affecting man, and it is a major occupational risk for agricultural workers in rural areas of the tropics and subtropics, where its socioeconomic and public health importance is second only to malaria among parasitic infections. The epidemiology of schistosomiasis varies within and between endemic countries and may be altered by major development projects, such as dams and irrigation schemes, especially if these attract human settlement without the provision of sanitation facilities. Military personnel may be particularly at risk. The crisis in the Arabian (Persian) Gulf resulted in the deployment of large numbers of American and other military personnel to the Middle East in 1991. Non-battle casualties have outnumbered casualties resulting from battles in all wars fought by the United States so far: schistosomiasis is one of the most commonly reported infectious and parasitic diseases afflicting military forces deployed in the Middle East.

The peak prevalence and intensity of infection by S. haematobium occurs in children aged between 10 and 14 years: prevalence rates may reach 100 per cent in some areas. In older age groups both prevalence and intensity of infection are low. Most of those heavily infected with S. mansoni are in the 10 to 14 age group, but in most endemic areas the prevalence is generally greatest in the 10 to 19 age group, and it tends to remain at higher levels in the older age group compared to S. haematobium infection. S. japonicum infection shows great variation, with no typical age prevalence and intensity distribution, but bimodal age prevalence curves with peaks in the 10 to 14 and 35 to 44 age groups have been reported.

Most of the morbidity in schistosomiasis is related to egg deposition in tissues, and postmortem studies have confirmed the relationship between morbidity and intensity of infection. Since adult schistosomes do not themselves replicate within the human body, the number of eggs shed depends upon the number of worms in residence and their longevity. Community studies have revealed a high degree of aggregation or ‘over-dispersion’: a small proportion of individuals harbour most of the worms and these individuals are predisposed to heavy reinfection following chemotherapy. Severe disease is found only in such individuals. In addition to intensity of infection, its duration, and age, severity of disease is affected by concomitant infections, nutritional status, and parasitic strain differences. In endemic areas maternal infection probably modifies the subsequent immune response of the child to schistosome infection. Genetic differences may also play a role: severity of hepatosplenic disease is associated with certain HLA haplotypes in Egypt, and in vitro human T-cell responsiveness to S. japonicum soluble egg antigen may be determined by a gene in the HLA-DQ locus. Genetic studies in Brazil suggest presence of a codominant major gene controlling human susceptibility to infection: there is a 0.2 to 0.25 frequency of the deleterious allele. A racial predisposition is suggested by the observation that in Brazil white people develop hepatosplenomegaly, while black Brazilians with an equal infective load do not.

Two factors make S. japonicum more difficult to control: it has at least 31 definitive hosts, including many domestic animals, and these act as reservoirs of infection. Secondly, its intermediate snail host is amphibious and is itself much more difficult to eradicate. The peak prevalence of S. mekongi in the floating villages of Kampuchea occurs in children below age 10. It causes a disease similar to S. japonicum and there is a higher rate of portal hypertension: 50 per cent of schoolchildren have hepatomegaly, and one third of these also have splenomegaly. The clinical manifestations of S. intercalatum and S. mansoni infection are similar.

Schistosomiasis, caused by a parasite resembling S. japonicum, has been found in the aboriginals (Orang Asli) of peninsular Malaysia. Little is known about the clinical manifestation of this infection in man, and this parasite is presumed to cause a zoonotic infection. It is not of public health significance so far.

The insidious nature of schistosomiasis makes it difficult to measure population morbidity objectively. In many instances the measured morbidity, especially in the first two decades of life, correlates with intensity of infection. Recent studies have shown a 20 to 30 per cent reduction in oxygen intake in S. mansoni-infected Sudanese farmers during agricultural tasks. In Burundi there was a significant association between intensity of infection and diarrhoea, fatigue, hepatomegaly, and splenomegaly. Such symptoms improve following treatment. In S. haematobium-infected Kenyan schoolchildren, physical fitness and appetites improved after chemotherapy. Reduced haemoglobin levels correlate with intensity of infection, and in communities with low iron intake anaemia may be common.

The heights of Egyptian children with schistosomal hepatic fibrosis can be more than two standard deviations below the mean for their age and sex, circulating levels of insulin-like growth factor free T4, and cortisol may be significantly reduced. Delayed puberty, hypogonadism, and amenorrhoea have been reported in several endemic areas.

A gene coding for pro-opiomelanocortin, the precursor of both &bgr;-endorphin and ACTH, has recently been identified in S. mansoni. Both &bgr;-endorphin and ACTH are produced by the schistosomes, and since such peptides are implicated in gonad endocrine regulation or gonadotrophin release, this might be related to the hypogonadism reported in infected humans and animals.

Although the majority of the infected population carries few worms and has little severe morbidity, over 200 million people harbour schistosomes, and the small proportion who develop severe morbidity cause a major health problem in endemic countries. The World Health Organization estimates that between 300 000 and 500 000 deaths per year can be attributed to schistosomiasis. Acute toxaemic schistosomiasis, more common in S. japonicum infection, may be lethal. Schistosomiasis (both japonica and mansoni) is the leading cause of portal hypertension around the world, and in endemic areas this may be the leading cause of death from upper gastrointestinal haemorrhage. S. haematobium infection causes severe urological disease and contributes to the high incidence of end-stage renal failure in countries such as Egypt, where many uraemic patients die due to lack of dialysis and transplant facilities. Cor pulmonale and neuroschistosomiasis, caused by all three major species, are potentially lethal. There is also evidence that schistosomiasis may potentiate other liver diseases, such as hepatitis, cirrhosis, and hepatocellular carcinoma.

Clinically, acute schistosomiasis affects mainly children and young adults. The chronic disease follows an insidious course. The early stages of infection with all the three major schistosomes are similar; differences become apparent once the infection is well established and different host systems are involved. Infection by S. japonicum causes a spectrum of disease similar to that observed for S. mansoni infections, but a more severe clinical picture is ascribed to S. japonicum. This is perhaps due to the higher egg output and the tendency for the eggs to be laid in large aggregates, which stimulate a more severe reaction.

This occurs in previously sensitized individuals and is due to a reaction to cercariae which have just penetrated the skin, many of which die at this stage. Although this is well described following exposure to the three main human species, it is more severe following penetration by non-human schistosomes. Itching of the exposed parts, usually the legs, occurs upon leaving the water, and lasts for a few hours to a few days. Petechial haemorrhages may occur at the site of penetration. A pruritic papular rash develops 5 to 15 h later. The papules may become filled with serum and dry to leave a scab: scratching leaves a discoloured spot which may persist for 2 to 3 months. Histologically the penetration sites show marked round cell infiltration of the dermis and epidermis. In Egypt, a positive history of itching after exposure to infected canal water was elicited in 68 per cent of people, and scratch marks are commonly seen on the legs of children.

The acute phase, lasting 1 or 2 months, is usually asymptomatic, especially in previously infected individuals. However in previously unexposed individuals clinical manifestations of varying intensity may occur 3 to 8 weeks after infection; this phase has been named Katayama fever. It is most frequent and severe in S. japonicum infection, has been well described in S. mansoni infection, but is rare in S. haematobium infection. The disease, which resembles serum sickness, and is probably caused by immune complexes, may last several weeks, and usually coincides with the onset of egg laying. Its severity correlates with intensity of infection and therefore with numbers of eggs, although the fever and other symptoms may subside after a few weeks despite high levels of egg excretion. The symptoms include fever, chills, headache, sweating, weakness, anorexia, cough, abdominal pain, and diarrhoea. An urticarial rash may develop and there is tender enlargement of the liver, with accompanying splenomegaly and lymphadenomegaly. The sedimentation rate is raised and there is leucocytosis with an eosinophilia of 30 to 40 per cent. The Paul-Bunnel reaction may become positive. The differential diagnosis at this stage includes typhoid fever, brucellosis, infectious mononucleosis, and other acute parasitoses, including hookworm, strongyloidiasis, and amoebiasis. A more severe toxaemic form may also develop, causing disseminated granulomas in many organs; an ulcerative enterocolitis may develop and may perforate leading to purulent peritonitis. This toxaemic form may be confused with typhoid fever, malaria, tuberculosis, pneumonia, kala-azar, prolonged salmonella septicaemia, severe strongyloidiasis, acute amoebiasis, bacillary dysentery, and surgical infections of the abdomen.

Many of the eggs that are shed pass through the wall of the venules, pass through the tissues and are excreted when they enter the lumen of the gut or urinary bladder; the remainder are trapped in local tissue sites and cause the chronic pathology.

The eggs elicit a granulomatous response which is essentially a delayed type hypersensitivity reaction. In time the granuloma is spontaneously suppressed (modulated) with marked reduction in both its size and in the amount of inflammation around new eggs entering the tissues. This modulation is mediated by T-suppressor cells and specific and non-specific lymphokines. In S. japonicum infection modulation is primarily mediated by a series of anti-idiotype antibodies which appear at different times in the course of infection. The cells comprising the granuloma secrete cytokines which stimulate fibroblasts; at least one of these has recently been purified. It is a heparin-binding growth factor which differs from other fibroblast growth factors and has been designated ‘fibroblast stimulating factor-1’. Collagen synthesis is accompanied by collagen degradation, and the total amount of fibrosis is related to the imbalance between these two processes. The granulomatous response gives rise to early chronic features such as haematuria and intestinal symptoms, while the resultant fibrosis is the cause of late chronic pathology. Infection with S. mansoni and S. japonicum is associated with hepatosplenic disease with portal hypertension, while S. haematobium causes urinary pathology. All three can give rise to pulmonary hypertension. Cerebral schistosomiasis may be an early or late consequence of S. japonicum infection. In addition ‘ectopic’ deposition of eggs or location of worms can give rise to pathology in practically any tissue in the body (see Table 2 641). Wide dissemination in a ‘panvisceral’ form can give rise to several clinical syndromes concurrently.

Interruption of these complex processes by chemotherapy at an early stage may reverse them and may also result in more modulation, with the effect that even reinfection may not lead to further pathology. Even advanced disease has been shown to improve to a greater or lesser extent after chemotherapy.

Eggs carried to the liver in portal blood are trapped in the vicinity of the portal veins and cause a periportal fibrosis. After a period of 5 to 10 years the liver becomes hard with protruberances on its surface; sections of the liver show the pathognomonic lesions of coarse periportal, ‘clay pipe-stem’ fibrosis, known as Symmer's fibrosis. A tangled mass of new vessels form around the tributaries of the portal vein. Hepatic blood flow is partly maintained by the compensatory hypertrophy of the hepatic artery (which may explain the raised wedge hepatic vein pressure in some patients with severe disease). Immunoglobin may be deposited in the spaces of Disse, and collagen may be desposited in the subendothelial basement membrane, with capillarization of hepatic sinuoids and the formation of a barrier between the hepatocytes and the circulating blood. The haemodynamic disturbances give rise to a presinusoidal type of portal hypertension resulting in the appearance of varices, which may bleed, collateral circulation, which may carry eggs to the lungs, and splenomegaly, giving rise to hypersplenism. Spleen enlargement is initially due to hyperplasia of the cellular components but later is a result of the raised portal pressure. Associated immunological disturbances lead to other complications, including immune complex deposition in the kidneys. Hepatic function is usually well preserved.

Autopsy and hospital record studies in Egypt have shown that about 50 per cent of patients with heavy S. mansoni infection have hepatosplenic disease. Longitudinal community studies revealed that 20 to 34 per cent of S. mansoni-infected individuals develop hepatosplenic disease. The physical signs in the abdomen include an enlarged firm liver, with left lobe prominence. The spleen may be grossly enlarged and superficial collaterals may develop. In the late stages the liver may shrink, and ascites and oedema may develop. The main complication is variceal haemorrhage, with fulminant or repetitive haematemesis and melaena: rupture often occurs at the gastro-oesophageal junction. Up to about one-third of patients with hepatosplenic disease will suffer a haematemesis.

Barium and endoscopic studies confirm the presence of varices and the site of haemorrhage and rule out bleeding from other causes. Splenoportography confirms the raised portal pressure, usually to more than 200 mmH&sub2;O of water, but the wedge hepatic vein pressure is usually normal. Echography confirms Symmer's fibrosis (Fig. 2) 2682 and gives information regarding the portal veins and the collaterals. A portal vein diameter of more than 1.7 cm and a splenic vein diameter of more than 1.2 cm indicates the presence of oesophageal varices in almost all cases. The direction (usually hepatopetal) and velocity of flow can be measured by Doppler ultrasonography. Laparoscopy has also been found useful for assessing pathology and obtaining biopsies. Granulocytopenia, thrombocytopenia, and anaemia result from hypersplenism, but the marrow may show failure of granulocyte maturation due possibly to an inhibitory serum factor.

Since hepatocyte function is generally well preserved, liver function tests are usually normal. However, patients with hepatosplenic schistosomiasis appear to have a higher incidence of viral hepatitis and the disease also occurs in areas where cirrhosis is common. S. japonicum infection may itself give rise to a cirrhotic pathology. Some patients ultimately develop hepatic decompensation, and liver function tests may be grossly altered. A form of disseminated intravascular coagulopathy has recently been described in patients with advanced disease.

Hepatosplenic schistosomiasis has to be differentiated from malaria, which is common in many of the endemic areas, and which may give rise to the tropical splenomegaly syndrome. It also needs to be differentiated from portal vein thrombosis, kala-azar, lymphoma, and cirrhosis. Liver biopsy is useful in differentiating these conditions but a needle biopsy alone will often not provide an adequate specimen for diagnosis of schistosomal fibrosis.

The onset of haemorrhage is unpredictable and there is probably no role for prophylactic surgery. The outcome of uncomplicated haemorrhagic episodes is much better than that in patients with alcoholic cirrhosis, largely because of the well-preserved hepatocyte function. The general management of an acute haemorrhage includes blood transfusions, administration of vasopressin, and balloon tamponade. Emergency injection sclerotherapy may be needed, although very large bleeding gastric varices may be technically difficult to inject. Propranolol has been claimed to be particularly suitable in schistosomiasis both while awaiting surgery and in the longer term. Given over 3 months, doses sufficient to lower the resting pulse by 25 per cent led to a significant and sustained reduction in portal pressure, with a reduction in spleen size, in about half the patients studied. However, this observation needs confirmation.

Failure of long-term sclerotherapy in variceal bleeding is difficult to define, but repeated major bleeds are an indication for a surgical shunt procedure. The classical portocaval shunt is unacceptable in this condition: there is a high incidence of portosystemic encephalopathy. The Hassab procedure is associated with a low incidence of encephalopathy, but the recurrent bleeding rate is high and it is no longer routinely used in Egypt, although it is still used by some in Sudan and China. The distal splenorenal shunt is currently the best shunt procedure for schistosomal variceal haemorrhage and it is now widely used in Egypt. Shunt patency rates are high and adequate portal blood flow into the liver is maintained in the majority of patients.

The recent addition of splenopancreatic disconnection as an adjunct to the distal splenorenal shunt appears to be well suited to this condition. Although this addition makes the operation significantly longer and there is a higher incidence of pancreatitis, it further reduces the incidence of encephalopathy and chronic hyperbilirubinaemia. Orthotopic liver transplanation should be considered in patients who are badly decompensated, or who have very poor functional hepatic reserve.

Splenectomy, with or without gastro-oesophageal devascularization, eliminates abdominal discomfort, corrects hypersplenism, improves the general state of the patient, and may reduce portal pressure by about 40 per cent. It has also been claimed to improve or cure infantilism. Splenectomized patients living in a malarial area should receive lifelong antimalarial prophylaxis. The long term value of segmental splenectomy has not yet been adequately assessed.

Chronic S. mansoni and S. japonicum infection can involve the intestines; the rectosigmoid is also frequently infected by S. intercalatum. S. mansoni eggs and granulomas have been found throughout the gastrointestinal tract, including the stomach, small and large intestines, pancreas, gallbladder, the peritoneum, and the liver. The resultant granulomas, fibrosis, and vascular changes, however, do not always produce symptoms, although symptoms may develop even after a very long time. Hepatosplenic and hepatointestinal disease are usually more severe in Egypt than in the Caribbean and South America. Gross intestinal lesions are present at autopsy in 16 per cent of patients with schistosomiasis in Egypt; these are most common in the colon. S. mansoni is the main cause, although S. haematobium eggs are commonly found in rectal biopsies, in the appendix, and in polyps.

Bowel symptoms, including nausea, abdominal pain, anorexia, weight loss, and lassitude and myalgia, occur in about 40 per cent of those with S. mansoni infection in Egypt, especially in the 10 to 14 age group. Bloody diarrhoea with mucus is much more common in Egypt than in Brazil because of the higher incidence of colonic polyposis. Blood and protein loss is worse in patients with malnutrition. Pellagra has been found in 24 per cent and finger clubbing in 35 per cent of patients with polyposis.

On examination, the colon may be tender and thickened, and a pericolic mass is present in 16 per cent of patients with polyposis. The polyps may be sessile or pedunculated and may slough, ulcerate, and become secondarily infected. They are most common in the sigmoid colon but may be present anywhere in the large bowel and may vary from just a few to a very large number. The mucosa is granular and hyperaemic and bleeds easily. Barium enema, especially double contrast, demonstrates the polyps well. Colonic polyps are significantly reduced in size after parasitological cure, and this is accompanied by increases in haemoglobin, serum albumin, and iron.

A pseudoneoplastic form involving the colon, ileum, mesentery, or retroperitoneum may achieve a considerable size and may present as an abdominal mass (bilharzioma), with abdominal pain or with obstruction. The bowel may be thickened, giving rise to a rigid tube known as ‘schistosomal colonic cord’; this can develop into a stenotic segment.

Deposition of eggs in the small intestine is less common, but it may lead to partial villous atrophy, heavy round cell infiltration of the lamina propria, and thickening of the muscularis mucosa. Ballooned empty villi resembling the pathognomonic lesion of intestinal lymphangiectasia may be seen.

Schistosomiasis per se rarely causes appendicitis, except when fibrosis occludes the lumen of the appendix or if there is heavy infection of the appendix. In endemic areas, schistome ova are often found in appendices removed for clinical appendicitis, or at autopsy. Appendicitis is an important complication of hepatointestinal S. japonicum infection. In S. haematobium infection the density of eggs is often higher in the appendix than in adjacent regions, and appendicitis may become symptomatic during heavy infections. In Nigeria, 1 per cent of surgically removed appendices examined in 1984 contained schistosome ova. Half of these were removed for clinical appendicitis, and of these 70 per cent showed suppurative changes.

Migration of schistosomula through the lung may be associated with bronchospasm, fever, and cough. During treatment, dying or dead adult worms may sometimes reach the lung, where they can cause a ‘verminous’ pneumonia. Spontaneous pneumothorax has also been reported, but is rare. The major pulmonary complication of chronic schistosomiasis is pulmonary hypertension, leading to cor pulmonale. This develops after the onset of significant portal hypertension, when the collateral circulation allows shunting of S. mansoni and S. japonicum eggs to the pulmonary circulation. S. haematobium eggs, which enter the systemic venous system directly from the vesical veins, are often found in high concentration in the lungs, but cor pulmonale is rare in S. haematobium infection.

Egg deposition results in pulmonary necrotizing arteriolitis which destroys the intima and occludes blood vessels, while newly formed vessels may progress into an angiomatoid lesion. There is also medial hypertrophy of neighbouring vessels. Significant venoarterial shunting may develop. The increased arteriolar resistance, loss of adaptability, and presence of fibrosis give rise to pulmonary hypertension, which, when severe, may itself lead to further vascular damage. The pulmonary arteries become extremely dilated or even aneurysmal. The end result is cor pulmonale. While a large proportion of patients with S. masoni infection may have some lung disease, only about 15 per cent of those with Symmer's fibrosis develop clinically important chronic lung changes. The peak incidence is between 12 and 35 years, and males are more frequently affected than females. S. japonicum infection may also present with chronic bronchitis, bronchiectasis, and emphysema. With the exception of evidence of schistosomal portal hypertension, the clinical features are similar to other cases of pulmonary hypertension and cor pulmonale. The differential diagnosis includes primary pulmonary hypertension, parenchymal diseases, and multiple pulmonary emboli. A pulmonary biopsy is helpful if the diagnosis is in doubt. Chinese physicians have successfully used fibreoptic bronchoscopy to diagnose pulmonary schistosomiasis: the findings included redness, swelling, ulceration of the mucosa, and the presence of miliary nodules.

Some patients with hepatosplenomegaly do not develop cor pulmonale, but instead develop cyanosis and clubbing with no or minimal pulmonary hypertension. The cyanosis often develops after splenectomy. Possible explanations for this syndrome include pulmonary arteriovenous shunts, portopulmonary anastomoses, or a reduction in the affinity of haemoglobin for oxygen.

Antischistosomal chemotherapy and supportive care can produce symptomatic improvement in patients with low grade pulmonary hypertension, but not in patients with cyanosis. Chemotherapy should be given to all actively infected patients, however, if only to reduce further egg deposition.

Ureteric strictures and urolithiasis contribute to renal damage through hydronephrosis and pyelonephritis. In one study , 14 per cent of 150 Egyptian children with S. haematobium infection had hydronephrosis. The kidney, however, may be affected in all three main schistosomal infections.

Immune complexes are deposited consistently in the renal glomeruli in S. haematobium infections. The extent to which they contribute to clinical disease is unknown, but in Egypt the nephrotic syndrome is prevalent in areas with high endemicity of S. haematobium infection. In a recent Egyptian investigation, 48 (20 per cent) of 240 patients with active S. mansoni infection but no symptoms suggestive of glomerular disease had proteinuria; of these, 15 agreed to biopsy and eight were positive: the most common lesion was focal mesangial proliferation, with IgM and C3 deposits. It seems, therefore, that both S. haematobium and S. mansoni infection contribute to the high prevalence of renal disease in Egypt, where the incidence of end-stage renal failure is 160 to 180 new patients/million population/year. In Brazil, where only S. mansoni infection occurs, practically all types of glomerulopathy have been seen in hepatosplenic schistosomiasis, but the most frequent type is a generalized membranoproliferative glomerulonephritis, presenting with the nephrotic syndrome. Deposits of IgG, IgM, IgE, and IgA have been found. Focal glomerular sclerosis is also common. Schistosomal antigens have on occasion been found in both basement membranes and in the mesangium.

End-stage renal disease due to schistosomiasis can be managed by renal transplanation, which is now rapidly increasing in many countries where schistosomiasis is endemic. Both the donor and the recipient should be carefully assessed. Individuals with anatomical changes should not, on the whole, be used as living donors, but the same changes per se in the recipient are not a contraindication. Schistosomiasis has been passed from a donor to a recipient in a transplanted kidney when the adult worms survived the procedure.

All three main schistosomes can cause CNS disease: S. japonicum more commonly affects the cerebrum, while the other two more commonly affect the spinal cord. Eggs are thought to reach the CNS through pathologically altered pulmonary vessels, arteriovenous anastomoses, or by way of the vertebral venous system. Rarely, adult S. mansoni worms have been observed in cerebral vessels, possibly arriving from the mesenteric veins by entering Batson's intercommunicating plexus during periods of increased intra-abdominal pressure. Adult S. haematobium worms have been observed in both cerebral and spinal meningeal veins. The greater number of eggs laid by S. japonicum may account for the higher incidence of CNS disease, as well as for the more rapid development of acute cerebral and systemic symptoms. In the acute form the picture may resemble an encephalitis, and this must be differentiated from cerebral malaria, tuberculosis, and abscesses. A granulomatous mass or blockage of cerebrospinal fluid may cause intracranial hypertension. If the diagnosis is confirmed or suspected, chemotherapy should be instituted immediately.

Because CNS disease may be asymptomatic, its frequency in chronic schistosomiasis may have been underestimated. The frequency of the cerebral form of schistosomiasis japonica is about 0.1 per cent, although some autopsy studies in the Philippines have revealed brain lesions in 6.5 per cent of infected individuals. Abnormal electroencephalograms have been found in about half of patients with chronic S. japonicum infection and subjective symptoms of fatigue, mild headaches, or dizziness. S. japonicum infection is considered to be an important cause of focal epilepsy in the Far East: in the Philippines the most frequent manifestations are Jacksonian and psychomotor seizures, the onset of which occurs after 21 years of age. Among individuals with seizure activity as the first symptom, 20 per cent later develop hemi- or monoparesis with or without motor aphasia. Blindness has been reported, and pituitary involvement may lead to hypopituitarism. Chemotherapy results in improvement and disappearance of seizures in most patients.

Spinal cord schistosomiasis may present with a granulomatous mass mimicking a tumour, or as a radiculitis, but the most common manifestation of infections due to S. mansoni and S. haematobium is a transverse myelitis.

In endemic areas a high index of suspicion is necessary: there are no clinical features specific for schistosomiasis of the CNS, and treatment may need to be instituted even if eggs are not found. Laboratory investigations are of limited value except in travellers to endemic areas. In those with myelopathy, eosinophilia of the cerebrospinal fluid is inconstant. The cerebrospinal fluid circumoval precipitin test may help distinguish cerebral from non-cerebral S. japonicum infection since serum precipitins do not cross the blood - brain barrier. Depending on the pathology, myelograms may reveal an irregular, partial, or complete block. Both CT scan and MRI are useful in reaching a diagnosis.

Chemotherapy should be given to all patients with suspected or confirmed spinal schistosomiasis. Acute spinal cord compression from an intramedullary mass may resolve rapidly and completely after chemotherapy; if given in time this may avoid the need for surgical intervention.

This may occur in patients with schistosomiasis, especially the hepatosplenic form. The salmonellae adhere to the surface of the worm, especially the male, and can also be found in their gut. More than 20 species of Salmonella of both human and animal origin have been found to cause this syndrome. The fever, of slow onset, may last up to 2 years. It is high, irregular, continuous or intermittent, and is often accompanied by headache, sweating, chills, weight loss, diarrhoea, abdominal pain, and hepatosplenomegaly with mild lymphadenopathy. Epistaxis, petechiae, purpuric lesions, haematuria, and proteinuria may develop. The diagnosis is based on the history of schistosomiasis and prolonged fever, and is confirmed by blood culture. Salmonella may also be found in stool, urine, bile, or bone marrow. The Widal reaction is usually positive for Salmonella typhi or Salmonella paratyphi. The differential diagnosis from kala-azar can be very difficult.

Both the salmonellosis and schistosomiasis must be treated with appropriate chemotherapy, otherwise there is risk of relapse.

Trematodes have frequently been associated with an increased risk of developing malignancies in man. While the role of schistosomiasis in the aetiology of some malignancies is still controversial, there is strong evidence linking S. haematobium with squamous cell carcinoma of the bladder. Advanced S. mansoni infection has been associated with follicular lymphoma of the spleen.

The mean age of S. japonicum-infected individuals with carcinoma of the colon or rectum is 10 years less than that of uninfected individuals, and the rate of carcinoma of the colon in one autopsy study was 25 times greater in infected than in uninfected persons. The carcinoma is usually a well differentiated adenocarcinoma with pseudopolyps and calcified eggs in the tissues. In China, patients with the epithelial hyperplastic type of colonic polyps are considered to be at risk for the development of colon carcinoma. S. japonicum infection has also been linked with hepatocellular carcinoma.

The clinical manifestations of schistosomiasis are protean, but in endemic areas the manifestations, and especially the specific syndromes of chronic schistosomiasis, are easily recognized. In addition to the clinical presentation, a history of residence or visit to an endemic area and of water contact is important. Definitive diagnosis is made by finding live ova in excreta or in biopsy specimens.

The standard of laboratory diagnosis is the visualization of the ova. Stool examination using a direct smear may miss eggs in lightly infected individuals, and is not quantitative. The formal-ether sedimentation method is semiquantitative, relatively easy, and is useful on preserved specimens. The Bell method, in which the stool is passed through a piece of Whatman filter paper and the trapped eggs stained blue with ninhydrin, was the first quantitative method to be extensively used in field studies, but the Kato slide method, especially the Kato-Katz modification, is now routinely used. In this technique, in which glycerol is used to clear the specimen of faeces, only the egg shell and not the miracidium can be visualized. Methods of examining urine for S. haematobium eggs are discussed elsewhere. When the diagnosis is clinically suspected and eggs are not visualized in the stool or urine, 1 to 2 mm snips of rectal mucosa may be obtained with biopsy forceps, pressed between two slides, and examined under the microscope. This method is also applicable to other biopsy specimens. Alternatively the slides may be fixed and stained with haematoxylin and eosin: this allows identification of granulomas and eggs. An eosinophilic centre in the egg is suggestive of the presence of a live miracidium at the time of biopsy.

These are generally available at present only as research tools. With few exceptions their sensitivity, specificity, and reproducibility are less than those of the parasitological methods. In the past, antigen preparations for detecting serum antibodies have been poorly standardized and the tests have generally been unable to distinguish between past and present infection. On the whole they have had little practical application in individual cases in endemic areas but are of some value in population studies. Soluble egg antigen preparations are a more sensitive indicator of infection than antigens of adult worms, especially in S. japonicum infection. Serodiagnosis of S. haematobium is even less well developed. Antibodies against excretory or secretory antigens of the worm's intestinal tract have recently been found to be a marker of early infection in previously unexposed visitors to endemic areas. Circulating schistosomal antigens are beginning to be used in immunodiagnosis and a recent monoclonal antibody used in a sandwich enzyme-linked immunosorbent assay was able to differentiate between past and current infections. Exposure to animal schistosomes may cause false-positive results in serological tests. The advantages of serodiagnosis are that they may be automated, and it is impossible in large population surveys for donors to switch specimens, as can happen with urine or stool samples.

Those used in urinary schistosomiasis are described elsewhere. Ultrasonography is a valuable non-invasive tool in the epidemiological assessment and individual diagnosis of both urinary and hepatosplenic schistosomiasis. The appearance of Symmer's fibrosis on ultrasound is pathognomonic of this condition. This shows multiple rounded, sheet or band like echogenic areas with a characteristic and fairly central sonolucent area. Plain radiology is useful in identifying schistosomal calcification in tissues, but this is better seen on CT scans. ‘Turtleback’ calcification of the liver is also pathognomonic for S. japonicum infection. Both CT and MRI are helpful in the diagnosis of CNS schistosomiasis.

Chemotherapy is currently the most effective and practical strategy to control human schistosomiasis, both in individuals and in populations. Antimony compounds, hycanthone, and niridazole have now been replaced by metriphonate, oxamniquine, and praziquantel (Table 5) 644. These chemically unrelated drugs have different mechanisms of action but share important characteristics: they are all safe, stable, effective orally, well absorbed, and rapidly distributed. They have few if any demonstrable effects on the immunological status of the host.

Praziquantel, the most versatile antischistosomiasis drug now available, comes close to fulfilling the criteria for an ideal drug; it is easily administered, effective against all species of human schistosomes, generally well tolerated, and is relatively inexpensive. Metriphonate is effective only against S. haematobium but it is well tolerated, safe, and is the least expensive of the three. If cost is a concern, it is the drug of choice in treating S. haematobium infection of the urinary tract, but because treatment requires administration of three doses at 2-weekly intervals, it is less effective in treating large numbers of individuals. Oxamniquine is a relatively safe drug of choice against S. mansoni. It has been more effective against South American schistosome strains.

Treatment should generally be given to individuals only after the diagnosis has been confirmed, unless central nervous system schistosomiasis is suspected. Complete cure is achievable in non-endemic areas, but is unnecessary in endemic areas, where a reduction of egg output by 90 per cent is enough to eliminate serious morbidity.

‘Swimmer's itch’ is generally mild and may be treated with antihistamines: none of the antischistosomal drugs is effective against cercariae or schistosomula. Treatment of Katayama fever is difficult, but the addition of steroids to antischistosomal drugs may be life saving. Many apparently irreversible lesions of chronic schistosomiasis, especially in the young, may resolve partly or completely with chemotherapy. Hepatosplenic disease responds well, with a marked reduction in the size of the liver and spleen in about half of the patients treated. Decompensated liver disease has a poor prognosis but may be treated safely, although improvement is probably related to better care and diet than to therapy alone. Colonic polyps shrink with improvement in symptoms and in the anaemia and hyperproteinaemia. Neuroschistosomiasis is frequently cured or markedly improved.

Drug treatment should also be given before surgery, particularly before shunting procedures for portal hypertension, to avoid prolonged embolization of the lungs by eggs passing through the surgically created shunt.

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