Urinary bilharziasis affects some 200 million people in endemic regions of Africa and south-west Asia. In Europe, a small focus of infection existed in Algarve, southern Portugal, but this is now either dead or dying out. The causative parasite Schistosoma haematobium, is one of three main schistosome species whose primary host is man. The other varieties, S. mansoni, which coexists with S. haematobium and is also prevalent in South America and some Caribbean islands, and S. japonicum, found in the Far East, are responsible for the intestinal forms of the disease. Any area of fresh water that can support the secondary host, an amphibean snail of the Bulinus species, is a potential source of infection once the schistosome ova have been deposited in the water by contamination with urine or faeces from an infected individual.

The morbidity of bilharziasis relates little to the acute infection, which is now easily and safely treated with effective oral anti-schistosomal agents, but more to the lingering sequelae of host reaction to the eggs of the parasite, manifested by progressive urinary tract dysfunction and the potential development of bladder carcinoma. The impact of the disease on mortality in an area of high endemicity may be judged from an autopsy study performed in Cairo over a 4-month period in 1974. Urinary bilharziasis was recorded in 61 per cent of individuals examined and was the direct or contributory cause of death in almost 10 per cent. There have been several approaches towards controlling infestation, but these have failed either because of difficulties with public education or due to the over-riding need to preserve local ecological milieux. Bilharziasis is therefore likely to remain a major health problem for the forseeable future.

The pathological effects of S. haematobium infection in man are chiefly the result of an intense and evolving tissue reaction to the eggs. Unlike intestinal bilharziasis, the liver is not significantly affected and the main target organs are the bladder, distal ureters, the prostate, seminal vesicles, and spermatic cord. For reasons that are not entirely clear, bilharziasis rarely affects females, but when it does lesions may also develop in the uterus, vagina, and vulva.

The adult worms reside mainly in the retrovesical plexus of veins, where the eggs are deposited, deep in the wall of the bladder. Each egg develops a miracidium within a week of being shed and excites an intense local histiolytic tissue reaction that carries it through the lamina propria and urothelium to be shed into the bladder lumen, together with extravasated blood. The characteristically fusiform and terminally spined eggs are readily identified on urine microscopy.

When infected urine reaches a body of fresh water, the eggs hatch and the released miracidia swim actively around in search of a suitable snail host. The larval form of S. haemotobium develops exclusively within a specific Bulinus species, where it matures in about 30 days. The released cercaria, which are actively mobile in water, are able to penetrate intact human skin to continue the sexual phase of the life-cycle. The larvae, or schistosomulae, gain access to the venous or lymphatic systems and are thence carried through the heart and lungs into the portal vein. Here, the adult worms mature within a few weeks, the female being carried in the gynaecophoric canal of the male during the final stage of their odyssey down to the pelvic veins.

Clinical manifestations are rare before release of the parasite eggs into the urine, usually some 3 months after exposure. Initially, there is painless passage of blood at the end of micturition; later symptoms are those of an intense haemorrhagic cystitis with dysuria, pain, and frequency. In some highly endemic areas, blood in the urine is not considered abnormal and is even regarded as a sign of puberty in boys. Patients may occasionally complain of lassitude, body aches, and late afternoon fever. When bladder ulceration occurs pain is usually intense, being referred to the perineum and the tip of the penis. In this active phase of infestation, there is heavy excretion of eggs in the urine, accompanied by pyuria, and sometimes bacteriuria. Anaemia and eosinophilia may also be evident.

Ninety per cent of the deposited eggs are distributed in the bladder wall where, initially, a granulomatous lesion develops in the lamina propria or, rarely, deep in the interstitial tissue between muscle bundles. The ova secrete a histiolytic antigen that is tissue-fixed and evokes a cell-mediated immune response in surrounding host tissue. The granulomatous reaction is characterized by an eosinophilic, cellular infiltrate and the overlying urothelium grows inflamed and proliferative. The extent of the primary lesion and its subsequent evolution through the healing and chronic phases depend on several factors, including the intensity of the tissue egg load, frequency of reinfestation, the nutritional state of the host, the timing of antischistosomal treatment, and any superimposed bacterial infection. The pattern of the developing urothelial lesions is extraordinarily varied and may take the form of atrophic, proliferative, or metaplastic change.

Atrophic changes, manifested by erosions of the surface epithelium, may progress to chronic, indolent ulceration if the underlying mass of ova has compromised the blood supply. Papillomata are usually evident during the active phases of bilharzial infection and may persist as benign fibrous or fibrocalcific polyps. The subepithelial collections of ova may present ‘pseudotubercles’ or ‘sulphur granules’—raised, seed-like, golden yellow specks—at cystoscopy (Fig. 3) 2685. These tubercles are initially surrounded by hyperaemia, but in the chronic stages of the disease the urothelium becomes atrophic and thin, so that the masses of underlying ova show through as a characteristic ‘sandy patch’. These, together with the generalized waxy-yellow appearance of the bladder epithelium, are unmistakeable cystoscopic evidence of past bilharzial infection.

Metaplastic change is most common in areas of high endemicity and is probably related to the severity and frequency of infestation and to superadded bacterial infection. Squamous metaplastic lesions develop surface keratinization in up to 30 per cent of cases, and may then present as leukoplakia. Columnar metaplasia is typified by predominant glandularis or cystica change, and occasionally there are epithelial enclosures. It is not unusual to find all of these metaplastic changes coexisting in the same bilharzial bladder lesion. Although cystitis cystica is undoubtedly a benign lesion, both glandular metaplasia and leukoplakia are premalignant in nature. S. haematobium infection is closely associated with bladder cancer, and recent evidence suggests that this relationship may be indirect: the irritant stimulus of the erupting schistosome ova may potentiate the effect of a pre-existing latent carcinogenic agent, possibly an environmental or bacterially produced nitrosamine. This sequence produces an irreversible change that is later accelerated to tumour growth by a further factor or by a threshold population of tumour-initiated urothelial cells. Bacterial infection thus plays an important role in the biogenesis of potentially malignant change in the bladder associated with bilharziasis. This inference is supported by reports that the rate of urinary tract infection is at least 10 times higher in regions of endemic bilharziasis than elsewhere. Two-thirds of bilharzial bladder cancers show squamous cell differentiation, and squamous metaplasia occurs in around 65 per cent of cases overall.

Severe and prolonged bilharzial cystitis may be complicated by bladder contracture or by bladder outlet obstruction due to involvement of the posterior urethra. The characteristic dystrophic calcification that is often a sign of past bilharzial infection (Fig. 5) 2688 causes surprisingly little bladder dysfunction, and these patients usually have normal bladder capacity and compliance.

The incidence of upper tract change appears to vary widely from one endemic region to another, being chiefly influenced by the intensity of infestation and tissue egg burdens. In comparable autopsy studies of schistosomal uropathy, hydronephrosis was present in one-sixth of individuals studied in Nigeria but in more than one-third of those studied in Egypt.

The early exudative and polypoid lesions present as obstruction and ureteral filling defects on urography (Fig. 6) 2689. These appear to be more common in children, and usually resolve with adequate antischistosomal treatment. At a later stage, the mucosa becomes roughened and may contain tiny tubercles, like sago grains, or cystica change. In the vicinity of egg deposition sites, the ureteral wall muscle becomes damaged by the toxic effect of the surrounding granulomatous reaction, resulting in segmental dilatation and peristaltic dysfunction (Fig. 7) 2690. These focal changes are not usually obstructive and the related kidney is little changed.

Repeated or intense infestation is associated with necrosis of the ureteral wall, with disappearance of muscle fibres around sites of ova deposition and consequent dilatation, toxic atonicity, and tortuosity of the affected segment. The loss of muscle contractibility, both circular and longitudinal, leads to flaccid elongation with folding and kinking that becomes fixed by periureteric adhesions. The extending retroperitoneal fibrosis results in the whole ureter becoming encased, thickened, and pulled medially. Until it was realized that dilatation occurred at the site of, rather than above, the diseased ureteric segment, it was widely believed that the principal lesion in the bilharzial ureter was that of stricture, a stenosis with fibrosis. Although up to two-thirds of ureters affected in this way show reflux, the true incidence of stricture is probably not more than 5 per cent. The reflux is usually low pressure and, in the absence of infection, renal damage has not been demonstrated to occur over observation periods of up to 20 years.

Ureteric calcification is seen in at least one-third of ureters affected by bilharziasis, and is most common in the distal segment. A characteristic punctate type of calcification may follow cystica change (ureteritis calcinosa). Although stone frequently coexists with bilharzial uropathy, there is no evidence that the incidence is significantly greater in endemic areas. The widely dilated and obstructed ureter is predisposed to the development of stasis stones and often these are of giant size.

In view of the protean nature of these changes, it is surprising that long-term effects on renal function are rare. In regions of high endemicity, however, up to 13.5 per cent of bilharzial patients over the age of 20 will present with one non-functioning kidney and a few will progress to end-stage renal failure.

The seminal vesicles are affected in around 80 per cent of patients with bilharzial uropathy: infection probably occurs by reflux from the posterior urethra via the ejaculatory ducts. Haematospermia is a characteristic clinical feature, and rectal examination discloses bilaterally enlarged, firm and nodular or cystic seminal vesicles. In about one-third of cases, seminal ejaculate contains bilharzial ova. Plain radiographs will sometimes show ‘honeycomb’ calcification of the vesicles. Even in severe cases, however, the ampullary canals and ejaculatory ducts remain patent, and bilharziasis is unlikely to play a direct role in the development of obstructive infertility in males. Bilharzial prostatitis is relatively uncommon, and the epididymis and testis are rarely involved.

Schistosomiasis rarely involves the female genital tract. When it does, papillomatous lesions may present in the vulva and vagina, usually before the age of puberty. In adults, cervical ulceration is more common, and lesions may rarely occur in the uterus, ovaries, or fallopian tubes.

The symptom complex of painful micturition, haematuria, and frequency in a man from an endemic area is virtually diagnostic; diagnosis is quickly confirmed when viable ova are seen on urine microscopy. Endoscopy is not useful in the acute disease and the risk of bacterial infection may increase the morbidity.

The recent introduction of the antischistosomal drug praziquantel has revolutionized the medical treatment of bilharziasis. An isoquinolone-pyrazine derivative, praziquantel has few side-effects and is almost 100 per cent effective against all three princial pal schistosomes. A single oral dose of 40 mg/kg is recommended for S. haematobium infection and this can be safely repeated for the treatment of subsequent reinfestation.

In addition to its schistosomicidal action, praziquantel may also reduce the intensity of the pathological lesion. Ultrasonographic studies have demonstrated that fibrosis accompanying the hepatomegaly associated with intestinal bilharziasis is markedly diminished by this treatment, and there is also abundant urographic evidence of resolution of granulomatous polyps and upper tract obstruction in S. haematobium infection. There is, therefore, some basis for repeating medical treatment when patients present with florid, indolent lesions and seemingly burnt-out disease, with no evidence of fresh infestation.

In endemic regions, patients exposed to repeated infestations usually experience persistent and varying degrees of micturition dysfunction, occasionally with dysuria and perineal discomfort, for the rest of their lives. When symptoms are severe, urodynamic investigation can differentiate among patients with significant bladder outlet obstruction, high voiding pressures, and poor flow rates, and those showing detrusor dysfunction with low voiding pressures and instability. In the former group, endoscopic incision or surgical Y - V revision of the bladder neck may be indicated. Surgery is not generally helpful in the latter.

Chronic upper tract disease usually manifests as ‘tiredness’, with vague loin pains or aching in the iliac fossae. Occasionally, patients present with silent renal failure and imaging investigations will reveal grossly dilated ureters and irreversibly damaged, hydronephrotic kidneys. It is not uncommon for patients to be unaware of, or to deny, previous bilharzial infection: the first sign of past disease is often the chance finding of the characteristic ‘onion-leaf’ bladder calcification on plain radiographs (Fig. 5) 2688.

As noted earlier, upper tract changes, especially in children, may resolve appreciably with medical treatment. In the majority of the remainder, the infection has a minimal effect on renal function, and is non-obstructive, so that treatment is not required. Stenotic lesions are uncommon and usually affect the distal, juxtavesical ureter. These require resection and reimplantation with a cuffed or ‘nipple’ type of neo-ureterocystostomy. It is unwise to attempt a tunnel reimplantation in thickened bladder walls of patients with bilharzia: reflux is more acceptable than the risk of restenosis. Surgical tailoring of the wide and thickened ureters seen in these patients is also complicated and carries the risk of restenosis or fistula. Lengthy strictures may require treatment with a Boari flap reconstruction and, despite the thickened bladder wall, these are generally successful.

Extensive surgical lysis and straightening of thickened and tortuous megaureters should only be undertaken if X-ray fluoroscopy demonstrates the presence of reasonably effective ureteric peristalsis. Replacement of a wide and atonic megaureter by a pedicled ileal loop should be considered if a trial period of percutaneous nephrostomy drainage shows that kidney function is salvageable. Total ileal replacement of the ureters in bilharziasis has proved functionally rewarding over the long term.

The incidence of bladder cancer in schistosomiasis occurs between 35 and 45 years of age, approximately a decade earlier than in non-infected individuals. Patients frequently present with the same symptoms of a haemorrhagic cystitis experienced during the course of acute bilharzial infections, and this may explain why the disease is usually at an advanced stage when first diagnosed. About one-quarter of patients have inoperable disease at primary evaluation.

The tumours are massive and of the fungating type, occupying the vault, posterior walls, or lateral walls of the bladder (Fig. 10) 2693. Despite their size, however, the frequency of spread to the regional lymph nodes is relatively low, ranging from 15 to 17 per cent in radical cystectomy specimens. The majority of these tumours are of low-grade malignancy and the overall 5-year survival following radical cystectomy approaches 33 per cent. Radiotherapy is of little benefit, because of the associated post-bilharzial fibrosis and the fact that most of these tumours are of the squamous cell variety.

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