Annals of the Royal College of Surgeons of England (I979) vol 6i
Urinary schistosomiasis in Saudi Arabia D M Wallace CBE MS FRCS Professor of Urology, University of Riyadh, Saudi Arabia
Summary The distribution, aetiology, pathology, and clinical aspects of urinary schistosomiasis are outlined and it is emphasised that mortality from the disease is not due to the parasitic ova passed in the urine and faeces but to the complications caused by fibrotic immunological reactions to the retained ova. The treatment both of these complications and of the infestation itself is discussed. The special circumstances governing the transmission of the disease in Saudi Arabia are described and it is suggested that in view of these the energetic
application of hygienic, educational, and therapeutic measures should make the complete eradication of schistosomiasis possible in that country.
Introduction Schistosomiasis (bilharziasis) is a disease which, in one or more of its major forms, has infested over 200 million people in the world today. It is spreading in many parts of the world, yet all the means of prevention are known but are being inadequately applied. It is essentially a disease of the younger working man. In the endemic form, where infested man snail - man forms the cycle, it is present in Central and South America, most of Africa, the Middle East, and the Far East. In Saudi Arabia the disease is slightly different from that seen elsewhere inasmuch as the water of Arabia is largely drawn from underground reservoirs which are uncontaminated. Infestation of the snails thus occurs locally, at or near the well head, by the infested local population. In other countries, dependent on the big rivers for agricultural irrigation, the source of infestation may be many miles upstream, even in another country. It is because of the local nature of the disease cycle that in Saudi Arabia the disease could and should be completely eliminated. Education in hygiene, sanitary engineering, and intensive effective Hunterian Lecture delivered on
i4th
April I978
therapy could clear the disease completely from the whole Arabian peninsula. Until then both medical and surgical treatments are merely stopgap forms of therapy to control the complications of the disease.
Aetiology Bilharziasis is the clinical evidence of infestation by one or more of the three pathogenic schistosome worms Schistosoma (Bilharzia) japonicum, S. haematobium, and S. mansoni. It spread from Africa during the 17th and i8th centuries by the migration of labour-the slave trade-to America, where a suitable snail host was found to be present for S. mansoni. The present migration of labour from East to West may result in further spread, especially if a host snail for S. japonicum is present in the West. The disease may present in any one of three main forms: i) The endemic disease, in which infected man and snails coexist, when education of the patient is as important as the primary treatment. Reinfestation in an endemic area is common. 2) The clinical disease, in which the patient presents with haematuria or other symptoms but has a history of having been in an endemic area weeks or months previously. Here the diagnosis is usually made by the identification of ova in the urine or faeces. There may be no snails where the disease is recognised, so reinfestation is not a problem. 3) The occult disease, in which there is no evidence of ova in the urine or faeces but the patient has splenomegaly, portal hypertension, an enlarged liver, or obstructive or neoplastic uropathy. It is not generally recognised that both the clinical and the occult forms of the disease are now appearing in many centres where endemic bilharziasis does not exist, both in Europe and North America.
266
D M Wallace
TFhe life cycle of the schistosome is well known, but the critical times of survival may be less appreciated. When infested man passes the ova of either S. haematobium or S. mansoni the miracidia which develop from the ova have a life of only a few hours: unless they come into contact with a suitable snail host they die. There are several varieties of snail, Bulinus truncatuts or B. wrighti for S. haematobium and Biomphalaria for S. mansoni, but other species of snail can harbour schistosomes during the asexual cycle. Snails usually live in sluggish water, but when the water courses dry up they can burrow deep in the mud, only to emerge when water becomes plentiful again. Once the snail sheds the cercariae these again have only a short life, usually a day or two, before they must gain access to the human host. Storage of water or altering the chemical composition may kill cercariae before infestation of man can occur. Clinical aspects and diagnosis Shortly after the cercariae penetrate the skin of the host a brief fever may occur or an intensive itch due to the host reaction to cercariae which have died during the invasive stage. The history of a swimmer's itch is suggestive of infestation. In urinary schistosomiasis the characteristic terminal haematuria is not usually seen until some weeks after infestation. The life of a worm couple can be as long as 40 years, although they are not active sexually for all this period. During sexual activity a worm couple may shed 300-3ooo eggs per day, although possibly only half of these are passed to the exterior. However, patients are not killed by the ova passed in the urine or faeces; they die from the complications of fibrosis-immunological reactions to the retained ova. Double infestation by S. haematobium and S. mansoni is not infrequent; plaques of S. mansoni can often be found on the peritoneum or even in the appendix at the time of a urological exploration. The onset of haematuria, especially terminal, is typical of bilharziasis in any patient who has been in an endemic area. On cystoscopy the appearance is similar to that seen in a Hunner's ulcer. The mucosa cracks and begins to weep blood as the pressure is reduced. Not every specimen of urine will contain ova. It may be necessary to examine multiple
specimens, especially the mid-morning one and also the terminal urine. Small quantities of urine are frequently found to be negative for ova. Faeces also present difficulties, so that neither of these pathological tests is really suited for an overworked routine laboratory. Intradermal testing may be positive owing to a reaction with non-pathogenic schistosomes-avian or bovine-or a positive reaction may persist after adequate treatment. Rectal biopsy or cystoscopy may be required to confirm the diagnosis. The inability of a routine laboratory test to demonstrate schistosomal eggs is not proof that the disease does not exist. Patients with S. haematobium infestation may develop fibrosis of the ureter or dilatation of the ureter with formation of multiple secondary rounded stones. They can present with renal failure due to bilateral obstruction or with evidence of neoplasia. The investigation of these patients is not the exclusive domain of the tropical diseases expert but should be a team effort involving the physician, urologist, radiologist, and, as described later, the biochemist. TIhe radiological changes in patients infested with S. haematobium can be surprising (Fig. i). Calcification of the bladder wall and calcification of the ureters even up to the renal
__.+. 1~~
F-
FIG. I
c
baer
uts.
Ca.lcified bladder and ureters.
Urinary schistosomiasis in Saudi Arabia
267
but filling defects due to bilharzial polyposis or to neoplastic masses can be diagnostic. Biopsy may be necessary to differentiate between bilharzial polyposis and frank carcinoma. Renal function too can be evaluated by the evidence of obstructive uropathy and this is especially valuable in patients with multiple, small, rounded stones at the lower end of the ureter (Fig. 3). Retrograde pyelography using a Braasch or a Chevassu catheter may be required to delineate the lower ureter. In our series of 450 patients seen over an i8-month period one-quarter had obstructive changes. Cystoscopy is a method of diagnosis advocated by urologists, who are able to perform biopsy if necessary, but condemned by parasitologists, who fear the introduction of secondary infection. The use of the modern fibreoptic cystoscope, sterilised by low-pressure autoclaving, and of disposable irrigation units rarely results in infection when done under proper circumstances. Cystoscopy should not be attempted except under conditions of surgical asepsis and where facilities for biopsy and radiological studies are available. Cystoscopy may be essential in the occult cases to disFIG. 2 Multiple strictures of ureter, especially tinguish between the benign condition and the at pelviureteric junction.
pelvis may be found in patients with minimal symptoms. Obstruction can occur not merely at the ureterovesical junction but at any part of the ureter, including the pelviureteric junction (Fig. 2). In the postmicturition picture thickened folds of the bladder wall similar to those of a hypertrophic gastritis can be diagnostic. Calcification of the bladder and ureter was seen in half of our patients with S. haematobium infestation, but calcification has never been seen in our urological service in a man over the age of 50 years. This suggests that calcification is a cause of early mortality. Calcification becomes less marked in patients with the onset of neoplasia, but the incidence of neoplasia is low in Arabia, so it is unlikely to be the explanation of the absence of calcified bladders in the elderly. Intravenous pyelography is essential in the investigation of any man suspected of being infested with bilharzia. Not merely can the FIG. 3 Strictures at lower ends of both ureters diagnosis be confirmed by the rugae of the causing hyd-roureters and multiple rounded bladder wall in the postmicturition picture, secondary stones.
268
D M Wallace
early onset of neoplasia. In the early lesions the appearances are so typical that even the most inexperienced cystoscopist will recognise the sandy patches. A correct diagnosis is essential whatever the subsequent treatment. No true estimate of the incidence of this disease is possible since on routine screening by urine testing the occult disease will be missed. Multidisciplinary screening of a known population, including the women and children, is essential. Alio' tried to estimate the lethal impact of this disease by comparing two groups of schoolboys, one group from an endemic area, the other from a bilharzia-free area. In the first group 820/0 had living fathers and 6.4% living grandfathers, while in the second group go% had living fathers and 54% living grandfathers. This, combined with our own observation that calcified bladders are not seen after the age of 50, suggests that there is a mortality which affects mainly the middle-aged male and, coupled with our observation that a quarter of the patients with S. haematobium infestation have radiological obstructive changes in the ureters, is justification for a urological approach to the bilharzial patient.
FIG. 4 Bilharzial ova under the urothelium Surgical treatment of the obstructed of the upper ureter. ureter The treatment of the obstructed ureter is controversial. Reimplantation of the ureters may be successful in some cases, but in a urological service one sees many cases of presumed reimplantation, done in a variety of clinics, and not all are successful. Our own experience suggests that the cause of failure is inadequate excision. In all the ureters excised we have found ova deposited in the suburothelial layers at the upper end of the ex-
cised specimen (Fig. 4). Repeated dilatation, meatotomy, or other local attempts to enlarge the lower ureter would appear to be an invitation to infection. Where the bladder has been reasonably capacious we have tried using a Boari Ockerbladt flap, with results which have ranged from perfect recovery to complete fistulous failure requiring a loop conduit. In 2 cases in which only one ureter appeared to be involved we have attempted a ureteroureterostomy. One of these was a complete failure, resulting in bi-
lateral hydronephrosis due to bilharzial fibrosis at the site of the anastomosis. An ileal loop as a conduit replacement for one or both ureters was employed in 65 ureteric excisions. In some cases both ureters were implanted simultaneously at separate sites; in others, where only one kidney was functioning, a single end-to-end anastomosis was employed. Where both ureters were implanted the separate implants were found to be more satisfactory and safer than when a conjoined type of anastomosis was used. Wherever possible the anastomosis was made well above clinically evident disease, except in one patient in whom sandy patches were seen in the renal pelvis (Fig. 5). All ureteric replacements must be preceded by a cystoscopy since in one patient, at the time of performing the ileovesical anastomosis, an area of carcinoma was encountered. Reflux has been stated to be a reason for not constructing ileal loops. In our series free
Urinary schistosomiasis in Saudi Arabia
269
the ileal conduit was extended to include the caecum and the bladder was replaced by a caecourethroplasty. In one of these specimens a previously unsuspected widespread multifocal adenocarcinoma was found. This operation, ileocaecourethroplasty, is a difficult and hazardous intervention; 2 of our patients died in the postoperative period. It should only be attempted in specialised centres. There are many points of controversy concerning the treatment and pathology of this disease. The use of the oral drug Bilarcil in a dosage of Io mg/kg body weight, administered at a clinic to ensure that the dose is taken and repeated at 2-weekly intervals for 3 treatments, has resulted in a ioo% ova-free rate at 3 months. Other drugs which required regular dosage were frequently thrown away by the patient if nausea was caused as a side effect. Serial injections were often ineffective since patients either failed to come back because the symptoms improved or because they disliked the injections; single injections have had toxic side effects. Using Bilarcil, we have not seen any toxic reactions and practically all patients have completed the course. In a population which is nomadic or peripatetic the FIG. 5 Bilharzial ova calcified in renal pelvis. intermittent oral therapy has many practical advantages because the patient can take the away with him if necessary. tablets drainage of the obstructed upper tract was considered to be of more importance than reflux, especially if in the postoperative period Controversial aspects infection could be controlled. However, in There are many points of controversy, but the order to minimise reflux patients were in- two outstanding problems are those of sex structed to wear a strong leather belt and to and neoplasia. tighten it before micturition. Cystograms taken during micturition demonstrated that SEX this constriction could prevent reflux except It has been said that in Egypt women are immune because they are not exposed to the under very high intravesical pressures. water of the irrigation canals. In Saudi Arabia Restenosis at the vesicoileal junction has the little girls play with their brothers in what patients restenosis pools there may be, the women do the drawing not been seen, but in occurred at the renal pelvis anastomosis. of water, the washing, and the cooking, and Patients under dialysis did badly, most yet there were only 47o females among over dying within the year. Those patients in whom 700 patients in a 4-year period. Is the environrenal function did improve were able to con- mental factor the only explanation? It may tinue with their normal work. well be that there is an occult pool of female All the excised ureters had gross ova de- patients unwilling to visit a clinic or it may be position in the suburothelial layers and ova that in an oestrogenic environment in the were found in every specimen at the upper post-puberty woman the male worm lacks the margin of the excision. In none were any pre- libido to copulate. Robinson2, Purnell3, and malignant changes or tumours found. In 6 Taylor4 have shown in experimental animals patients, because of changes in the bladder, that progesterone and stilboestrol can affect 2
270
D M Wallace
the worm's behaviour. In 2 patients, young unmarried males, we have been able to reduce the ova load in the urine by a week of stilboestrol therapy. A full quantitative clinical trial would be justified to see whether the worms are susceptible to the sex hormones. Academic though this may appear, it is possible that increasing the sex drive by the use of testosterone might render the worm couples more vulnerable to conventional drugs. NEOPLASIA
fection have been carried out frequently. Which of these factors play a part in the neoplastic process is debatable, but the scientific evidence points very definitely to the presence of a carcinogen, possibly formed in the bladder as the consequence of bacterial action.
Conclusion The problem of urinary bilharziasis is far from solved, but all the factors necessary to eliminate this disease are known and understood. Up to the present, disease control has centred around destruction of the asexual host, the snail. Strategic planning would suggest that energetic and effective treatment and education of the infested man through the modern media of communication would protect the snails from infestation and so be a more practical and rapid method of breaking the disease cycle. Because of the local infestation of water, which at the well head is free from all risks, Saudi Arabia, like Red China"2, could easily be one of the first countries to eliminate this disease.
Neoplasia of the bladder following bilharziasis is believed in Egypt to be a causal relationship; in East Africa the relationship is believed to be indirect. In Saudi Arabia we have been struck by the relative infrequency of neoplasia in hospital practice and in particular by the complete absence of premalignant or malignant changes in the urothelium of ureters which are heavily infested by bilharzial ova. If the retained ova are carcinogenic why is the ureteric urothelium immune? The possibility that infection added to the bilharzial reaction is an essential part of the mechanism is plausible since infection in an obstructed bilharzial ureter will result in pyelonephritis References and renal death, while infection in a bilharzial I Alio, I (I967) Epidemiology of Schistosomiasis in Saudi Arabia. Riyadh, University of Riyadh Press. bladder is not a lethal condition. E J (I96o) Journal of Helminthology, Yet a further reaction has been suggested 2 Robinson, 8 i. 34, by Hicks5. Where there are large amounts of 3 Pumell, R E (I966) Annals of Tropical Medicine and Parasitology, 6o, 94. ingested nitrates in the diet-possibly as the result of the intensive use of fertilisers-de- 4 Taylor, M G, Denham, D A, and Nelson, G S (I971) Journal of Helminthology, 45, 223. gradation products from the nitrates, especially 5 Hicks, R M (I977) Proceedings of the Royal nitrosamines, could be produced by bacterioSociety of Medicine, 70, 4I3. logical action in the urine. Nitrosamines are 6 Hueper, W C (I969) Occupational and Environmental Cancers of the Urinary System, pp 277highly carcinogenic6. They are not found in New Haven, Yale University Press. the urine of patients in England with spon- 7 301. J Melzak, Paraplegia, 4, 85. taneous bladder cancer but can be isolated 8 Davies, J (I966) M (1I977) Proceedings of the Royal from the urine of patients with bilharzial canSociety of Medicine, 70, 4II. cer and from the infected urine of some para- 9 Urman, H K, Bulay, 0, Clayson, D B, and Shubik, P (I975) Cancer Letters, 1, 69. plegic patients7'8. io Bulay, 0, Urman, H, Clayson, D B, and Shubik, Both Egypt and Iraq, where bladder canP (I977) Journal of the National Cancer Institute, cer is common, are countries which have been 59, I 625. cultivated intensively for centuries and where i IBulay, 0, Clayson, D B, and Shubik, P (0978) Cancer Letters, 4, 305. drugs9-", especially heavy metals, have been Mao 'Farewell to the God of Plague', used as a routine treatment and also where I2 quotedTse-tung, by Sandbach, F R (I977) Social Science intravesical investigations with the risks of inand Medicine, II, 27.
Urinary schistosomiasis in Saudi Arabia D M Wallace CBE MS FRCS Professor of Urology, University of Riyadh, Saudi Arabia
Summary The distribution, aetiology, pathology, and clinical aspects of urinary schistosomiasis are outlined and it is emphasised that mortality from the disease is not due to the parasitic ova passed in the urine and faeces but to the complications caused by fibrotic immunological reactions to the retained ova. The treatment both of these complications and of the infestation itself is discussed. The special circumstances governing the transmission of the disease in Saudi Arabia are described and it is suggested that in view of these the energetic
application of hygienic, educational, and therapeutic measures should make the complete eradication of schistosomiasis possible in that country.
Introduction Schistosomiasis (bilharziasis) is a disease which, in one or more of its major forms, has infested over 200 million people in the world today. It is spreading in many parts of the world, yet all the means of prevention are known but are being inadequately applied. It is essentially a disease of the younger working man. In the endemic form, where infested man snail - man forms the cycle, it is present in Central and South America, most of Africa, the Middle East, and the Far East. In Saudi Arabia the disease is slightly different from that seen elsewhere inasmuch as the water of Arabia is largely drawn from underground reservoirs which are uncontaminated. Infestation of the snails thus occurs locally, at or near the well head, by the infested local population. In other countries, dependent on the big rivers for agricultural irrigation, the source of infestation may be many miles upstream, even in another country. It is because of the local nature of the disease cycle that in Saudi Arabia the disease could and should be completely eliminated. Education in hygiene, sanitary engineering, and intensive effective Hunterian Lecture delivered on
i4th
April I978
therapy could clear the disease completely from the whole Arabian peninsula. Until then both medical and surgical treatments are merely stopgap forms of therapy to control the complications of the disease.
Aetiology Bilharziasis is the clinical evidence of infestation by one or more of the three pathogenic schistosome worms Schistosoma (Bilharzia) japonicum, S. haematobium, and S. mansoni. It spread from Africa during the 17th and i8th centuries by the migration of labour-the slave trade-to America, where a suitable snail host was found to be present for S. mansoni. The present migration of labour from East to West may result in further spread, especially if a host snail for S. japonicum is present in the West. The disease may present in any one of three main forms: i) The endemic disease, in which infected man and snails coexist, when education of the patient is as important as the primary treatment. Reinfestation in an endemic area is common. 2) The clinical disease, in which the patient presents with haematuria or other symptoms but has a history of having been in an endemic area weeks or months previously. Here the diagnosis is usually made by the identification of ova in the urine or faeces. There may be no snails where the disease is recognised, so reinfestation is not a problem. 3) The occult disease, in which there is no evidence of ova in the urine or faeces but the patient has splenomegaly, portal hypertension, an enlarged liver, or obstructive or neoplastic uropathy. It is not generally recognised that both the clinical and the occult forms of the disease are now appearing in many centres where endemic bilharziasis does not exist, both in Europe and North America.
266
D M Wallace
TFhe life cycle of the schistosome is well known, but the critical times of survival may be less appreciated. When infested man passes the ova of either S. haematobium or S. mansoni the miracidia which develop from the ova have a life of only a few hours: unless they come into contact with a suitable snail host they die. There are several varieties of snail, Bulinus truncatuts or B. wrighti for S. haematobium and Biomphalaria for S. mansoni, but other species of snail can harbour schistosomes during the asexual cycle. Snails usually live in sluggish water, but when the water courses dry up they can burrow deep in the mud, only to emerge when water becomes plentiful again. Once the snail sheds the cercariae these again have only a short life, usually a day or two, before they must gain access to the human host. Storage of water or altering the chemical composition may kill cercariae before infestation of man can occur. Clinical aspects and diagnosis Shortly after the cercariae penetrate the skin of the host a brief fever may occur or an intensive itch due to the host reaction to cercariae which have died during the invasive stage. The history of a swimmer's itch is suggestive of infestation. In urinary schistosomiasis the characteristic terminal haematuria is not usually seen until some weeks after infestation. The life of a worm couple can be as long as 40 years, although they are not active sexually for all this period. During sexual activity a worm couple may shed 300-3ooo eggs per day, although possibly only half of these are passed to the exterior. However, patients are not killed by the ova passed in the urine or faeces; they die from the complications of fibrosis-immunological reactions to the retained ova. Double infestation by S. haematobium and S. mansoni is not infrequent; plaques of S. mansoni can often be found on the peritoneum or even in the appendix at the time of a urological exploration. The onset of haematuria, especially terminal, is typical of bilharziasis in any patient who has been in an endemic area. On cystoscopy the appearance is similar to that seen in a Hunner's ulcer. The mucosa cracks and begins to weep blood as the pressure is reduced. Not every specimen of urine will contain ova. It may be necessary to examine multiple
specimens, especially the mid-morning one and also the terminal urine. Small quantities of urine are frequently found to be negative for ova. Faeces also present difficulties, so that neither of these pathological tests is really suited for an overworked routine laboratory. Intradermal testing may be positive owing to a reaction with non-pathogenic schistosomes-avian or bovine-or a positive reaction may persist after adequate treatment. Rectal biopsy or cystoscopy may be required to confirm the diagnosis. The inability of a routine laboratory test to demonstrate schistosomal eggs is not proof that the disease does not exist. Patients with S. haematobium infestation may develop fibrosis of the ureter or dilatation of the ureter with formation of multiple secondary rounded stones. They can present with renal failure due to bilateral obstruction or with evidence of neoplasia. The investigation of these patients is not the exclusive domain of the tropical diseases expert but should be a team effort involving the physician, urologist, radiologist, and, as described later, the biochemist. TIhe radiological changes in patients infested with S. haematobium can be surprising (Fig. i). Calcification of the bladder wall and calcification of the ureters even up to the renal
__.+. 1~~
F-
FIG. I
c
baer
uts.
Ca.lcified bladder and ureters.
Urinary schistosomiasis in Saudi Arabia
267
but filling defects due to bilharzial polyposis or to neoplastic masses can be diagnostic. Biopsy may be necessary to differentiate between bilharzial polyposis and frank carcinoma. Renal function too can be evaluated by the evidence of obstructive uropathy and this is especially valuable in patients with multiple, small, rounded stones at the lower end of the ureter (Fig. 3). Retrograde pyelography using a Braasch or a Chevassu catheter may be required to delineate the lower ureter. In our series of 450 patients seen over an i8-month period one-quarter had obstructive changes. Cystoscopy is a method of diagnosis advocated by urologists, who are able to perform biopsy if necessary, but condemned by parasitologists, who fear the introduction of secondary infection. The use of the modern fibreoptic cystoscope, sterilised by low-pressure autoclaving, and of disposable irrigation units rarely results in infection when done under proper circumstances. Cystoscopy should not be attempted except under conditions of surgical asepsis and where facilities for biopsy and radiological studies are available. Cystoscopy may be essential in the occult cases to disFIG. 2 Multiple strictures of ureter, especially tinguish between the benign condition and the at pelviureteric junction.
pelvis may be found in patients with minimal symptoms. Obstruction can occur not merely at the ureterovesical junction but at any part of the ureter, including the pelviureteric junction (Fig. 2). In the postmicturition picture thickened folds of the bladder wall similar to those of a hypertrophic gastritis can be diagnostic. Calcification of the bladder and ureter was seen in half of our patients with S. haematobium infestation, but calcification has never been seen in our urological service in a man over the age of 50 years. This suggests that calcification is a cause of early mortality. Calcification becomes less marked in patients with the onset of neoplasia, but the incidence of neoplasia is low in Arabia, so it is unlikely to be the explanation of the absence of calcified bladders in the elderly. Intravenous pyelography is essential in the investigation of any man suspected of being infested with bilharzia. Not merely can the FIG. 3 Strictures at lower ends of both ureters diagnosis be confirmed by the rugae of the causing hyd-roureters and multiple rounded bladder wall in the postmicturition picture, secondary stones.
268
D M Wallace
early onset of neoplasia. In the early lesions the appearances are so typical that even the most inexperienced cystoscopist will recognise the sandy patches. A correct diagnosis is essential whatever the subsequent treatment. No true estimate of the incidence of this disease is possible since on routine screening by urine testing the occult disease will be missed. Multidisciplinary screening of a known population, including the women and children, is essential. Alio' tried to estimate the lethal impact of this disease by comparing two groups of schoolboys, one group from an endemic area, the other from a bilharzia-free area. In the first group 820/0 had living fathers and 6.4% living grandfathers, while in the second group go% had living fathers and 54% living grandfathers. This, combined with our own observation that calcified bladders are not seen after the age of 50, suggests that there is a mortality which affects mainly the middle-aged male and, coupled with our observation that a quarter of the patients with S. haematobium infestation have radiological obstructive changes in the ureters, is justification for a urological approach to the bilharzial patient.
FIG. 4 Bilharzial ova under the urothelium Surgical treatment of the obstructed of the upper ureter. ureter The treatment of the obstructed ureter is controversial. Reimplantation of the ureters may be successful in some cases, but in a urological service one sees many cases of presumed reimplantation, done in a variety of clinics, and not all are successful. Our own experience suggests that the cause of failure is inadequate excision. In all the ureters excised we have found ova deposited in the suburothelial layers at the upper end of the ex-
cised specimen (Fig. 4). Repeated dilatation, meatotomy, or other local attempts to enlarge the lower ureter would appear to be an invitation to infection. Where the bladder has been reasonably capacious we have tried using a Boari Ockerbladt flap, with results which have ranged from perfect recovery to complete fistulous failure requiring a loop conduit. In 2 cases in which only one ureter appeared to be involved we have attempted a ureteroureterostomy. One of these was a complete failure, resulting in bi-
lateral hydronephrosis due to bilharzial fibrosis at the site of the anastomosis. An ileal loop as a conduit replacement for one or both ureters was employed in 65 ureteric excisions. In some cases both ureters were implanted simultaneously at separate sites; in others, where only one kidney was functioning, a single end-to-end anastomosis was employed. Where both ureters were implanted the separate implants were found to be more satisfactory and safer than when a conjoined type of anastomosis was used. Wherever possible the anastomosis was made well above clinically evident disease, except in one patient in whom sandy patches were seen in the renal pelvis (Fig. 5). All ureteric replacements must be preceded by a cystoscopy since in one patient, at the time of performing the ileovesical anastomosis, an area of carcinoma was encountered. Reflux has been stated to be a reason for not constructing ileal loops. In our series free
Urinary schistosomiasis in Saudi Arabia
269
the ileal conduit was extended to include the caecum and the bladder was replaced by a caecourethroplasty. In one of these specimens a previously unsuspected widespread multifocal adenocarcinoma was found. This operation, ileocaecourethroplasty, is a difficult and hazardous intervention; 2 of our patients died in the postoperative period. It should only be attempted in specialised centres. There are many points of controversy concerning the treatment and pathology of this disease. The use of the oral drug Bilarcil in a dosage of Io mg/kg body weight, administered at a clinic to ensure that the dose is taken and repeated at 2-weekly intervals for 3 treatments, has resulted in a ioo% ova-free rate at 3 months. Other drugs which required regular dosage were frequently thrown away by the patient if nausea was caused as a side effect. Serial injections were often ineffective since patients either failed to come back because the symptoms improved or because they disliked the injections; single injections have had toxic side effects. Using Bilarcil, we have not seen any toxic reactions and practically all patients have completed the course. In a population which is nomadic or peripatetic the FIG. 5 Bilharzial ova calcified in renal pelvis. intermittent oral therapy has many practical advantages because the patient can take the away with him if necessary. tablets drainage of the obstructed upper tract was considered to be of more importance than reflux, especially if in the postoperative period Controversial aspects infection could be controlled. However, in There are many points of controversy, but the order to minimise reflux patients were in- two outstanding problems are those of sex structed to wear a strong leather belt and to and neoplasia. tighten it before micturition. Cystograms taken during micturition demonstrated that SEX this constriction could prevent reflux except It has been said that in Egypt women are immune because they are not exposed to the under very high intravesical pressures. water of the irrigation canals. In Saudi Arabia Restenosis at the vesicoileal junction has the little girls play with their brothers in what patients restenosis pools there may be, the women do the drawing not been seen, but in occurred at the renal pelvis anastomosis. of water, the washing, and the cooking, and Patients under dialysis did badly, most yet there were only 47o females among over dying within the year. Those patients in whom 700 patients in a 4-year period. Is the environrenal function did improve were able to con- mental factor the only explanation? It may tinue with their normal work. well be that there is an occult pool of female All the excised ureters had gross ova de- patients unwilling to visit a clinic or it may be position in the suburothelial layers and ova that in an oestrogenic environment in the were found in every specimen at the upper post-puberty woman the male worm lacks the margin of the excision. In none were any pre- libido to copulate. Robinson2, Purnell3, and malignant changes or tumours found. In 6 Taylor4 have shown in experimental animals patients, because of changes in the bladder, that progesterone and stilboestrol can affect 2
270
D M Wallace
the worm's behaviour. In 2 patients, young unmarried males, we have been able to reduce the ova load in the urine by a week of stilboestrol therapy. A full quantitative clinical trial would be justified to see whether the worms are susceptible to the sex hormones. Academic though this may appear, it is possible that increasing the sex drive by the use of testosterone might render the worm couples more vulnerable to conventional drugs. NEOPLASIA
fection have been carried out frequently. Which of these factors play a part in the neoplastic process is debatable, but the scientific evidence points very definitely to the presence of a carcinogen, possibly formed in the bladder as the consequence of bacterial action.
Conclusion The problem of urinary bilharziasis is far from solved, but all the factors necessary to eliminate this disease are known and understood. Up to the present, disease control has centred around destruction of the asexual host, the snail. Strategic planning would suggest that energetic and effective treatment and education of the infested man through the modern media of communication would protect the snails from infestation and so be a more practical and rapid method of breaking the disease cycle. Because of the local infestation of water, which at the well head is free from all risks, Saudi Arabia, like Red China"2, could easily be one of the first countries to eliminate this disease.
Neoplasia of the bladder following bilharziasis is believed in Egypt to be a causal relationship; in East Africa the relationship is believed to be indirect. In Saudi Arabia we have been struck by the relative infrequency of neoplasia in hospital practice and in particular by the complete absence of premalignant or malignant changes in the urothelium of ureters which are heavily infested by bilharzial ova. If the retained ova are carcinogenic why is the ureteric urothelium immune? The possibility that infection added to the bilharzial reaction is an essential part of the mechanism is plausible since infection in an obstructed bilharzial ureter will result in pyelonephritis References and renal death, while infection in a bilharzial I Alio, I (I967) Epidemiology of Schistosomiasis in Saudi Arabia. Riyadh, University of Riyadh Press. bladder is not a lethal condition. E J (I96o) Journal of Helminthology, Yet a further reaction has been suggested 2 Robinson, 8 i. 34, by Hicks5. Where there are large amounts of 3 Pumell, R E (I966) Annals of Tropical Medicine and Parasitology, 6o, 94. ingested nitrates in the diet-possibly as the result of the intensive use of fertilisers-de- 4 Taylor, M G, Denham, D A, and Nelson, G S (I971) Journal of Helminthology, 45, 223. gradation products from the nitrates, especially 5 Hicks, R M (I977) Proceedings of the Royal nitrosamines, could be produced by bacterioSociety of Medicine, 70, 4I3. logical action in the urine. Nitrosamines are 6 Hueper, W C (I969) Occupational and Environmental Cancers of the Urinary System, pp 277highly carcinogenic6. They are not found in New Haven, Yale University Press. the urine of patients in England with spon- 7 301. J Melzak, Paraplegia, 4, 85. taneous bladder cancer but can be isolated 8 Davies, J (I966) M (1I977) Proceedings of the Royal from the urine of patients with bilharzial canSociety of Medicine, 70, 4II. cer and from the infected urine of some para- 9 Urman, H K, Bulay, 0, Clayson, D B, and Shubik, P (I975) Cancer Letters, 1, 69. plegic patients7'8. io Bulay, 0, Urman, H, Clayson, D B, and Shubik, Both Egypt and Iraq, where bladder canP (I977) Journal of the National Cancer Institute, cer is common, are countries which have been 59, I 625. cultivated intensively for centuries and where i IBulay, 0, Clayson, D B, and Shubik, P (0978) Cancer Letters, 4, 305. drugs9-", especially heavy metals, have been Mao 'Farewell to the God of Plague', used as a routine treatment and also where I2 quotedTse-tung, by Sandbach, F R (I977) Social Science intravesical investigations with the risks of inand Medicine, II, 27.
