Tropical diseases Schistosomiasis (Bilharzia)
This infection with one or more of four different species of parasitic blood flukes (trematodes) is one of the most common and widespread diseases suffered by humanity. The life cycle of the fluke requires warm water and a specific snail, so the disease is only acquired in the tropics. If brought back by travellers into colder climates, further spread of the infection is unlikely. Schistosomiasis is endemic in many tropical countries: at least 200 million persons are infected, together with other primates and many mammals. How much cross-infection occurs between human and other species is debatable.
The life cycle is of clinical significance, and complex. Infection may occur without the patient being aware that it has happened. It starts with an infected snail, which, together with the schistosome sporocyst can tolerate several dry weeks. The snail is normally in water which must never fall below 15° C, and should be placid, stagnant or slow moving. Any fresh water in the tropics, natural or artificial, may be part of the life-cycle.
Under the stimulus of sunlight, the snails release larval cercaria, which penetrate the bather's skin, unrecognized except perhaps for irritation and erythema which may last for a few days - the "swimmer's itch". Often this is thought to be "sunburn". Then the larvae take a 10-21 day migration by way of the lymphatics and thoracic duct, the heart and the lungs until the portal system is reached and maturation starts. Copulation occurs only in the liver, where a pair of flukes may live 15-20 years or more. The adults do not multiply in man but do not waste their time: depending on the species, one pair may produce from 300 to 3000 eggs per day. These are swept away to their predestined site, e.g. for S. haematobium, the walls of the urinary bladder and ureters. This selective distribution explains the clinico-pathological disease patterns for each type of schistosomiasis.
The flukes are strictly intravenous parasites and cause no clinical diseases while alive (if one can ignore all those ova). Dead worms embolize and cause a granulomatous re action. No organ escapes. Granulomas are also caused by the ova. Most ova die and calcify, which is why organs appear to be calcified, for example a calcified bladder. Some ova cause an acute allergic reaction: the whole series of events is very dependent on many host factors, from re-infection rates, diet, and even differences in the schistosomes. As a result, what happens in one country or region and group of people may not happen elsewhere.
If the ova are not caught, to become granulomas, they leave the host after ulcerating through the wall of the intestine or urinary tract, (depending on the species). This is another complex re action. In fresh water the ova hatch and release miracidia which infect the host snail, thus starting the cycle again.
There are many varieties of schistosomes, but only four which are particularly important in man.
S. haematobium occurs throughout Africa and in Arabia, South West Asia, and around the Mediterranean. The urinary tract and the portal system are mainly affected, but the lungs and colon do not escape, and the central nervous system may occasionally be involved.
S. mansoni is also prevalent throughout Africa, particularly in the north, in Arabia, and in the north of South America. It mainly affects the colon, the portal system and the lungs, very rarely the central nervous system.
S. japonicum is found mostly in Asia; in China and Japan, the Philippines, and other Pacific islands. It primarily affects the colon and small intestine, the portal system and the lungs, rarely the central nervous system.
The fourth variety, S. intercalatum, is much less common and occurs only in equatorial Africa, particularly Zaire, and affects the digestive tract and the portal system.There is one other, S. mekongi, clinically similar to S. japonicum, but found only in the Mekong river basin.
There is considerable variation in the distribution of the four main varieties with overlap causing combined infections. Re-infection is common.
The clinical diagnosis is confirmed microscopically by recognising the characteristic ova, and by serological and skin tests. None indicate the severity or extent of the disease, and many remain positive after successful treatment. Rectal biopsy may be necessary, because other laboratory examinations (e.g. of urine) may be unreliable. The clinical symptoms are very variable, and may be acute or chronic, mild or severe. As the disease becomes chronic, there will be the clinical results of portal cirrhosis, such as oesophageal varices and chronic rectal bleeding (see
below), together with bowel or urinary tract complications.
The Katayama syndrome
All varieties of schistosomiasis start with a similar reaction, known as "Katayama disease". Patients who have been previously exposed to schistosomes do not develop this syndrome, but those who have never had schistosomiasis, and who have been exposed to infected water within the previous 3-9 weeks, may present with a "flu-like" illness. They almost always complain of a fever and persistent cough. Questioning may elucidate the recent history of skin irritation after swimming in fresh water (in the tropics). Patients often complain of headache, and rarely may have meningeal and neurological symptoms. However, the majority will be diagnosed clinically as having flu or bronchitis, except that almost every patient will have a raised eosinophil peripheral count (20-60%). The chest radiograph will show faintly increased vascular markings throughout both lungs, with mild hilar and mediastinal lymphadenopathy (Fig. 4). All the findings are very non-specific. If a correct diagnosis is made and treatment given at this stage, a few patients may then have an acute allergic re action to the de ad larvae. Later, there may be calcification of the resulting granulomas, but in the vast majority the illness improves after a few weeks even without treatment. The chest x-ray clears and the original cause of the infection may have been overlooked. What happens next will depend on the type of schistosome.
 | Figure 5.S.haematobium
a) The bladder is full, the ureters show strictures and dilatation.
b) After micturition the bladder is empty but strictures in the lower ureters cause ureteric dilatation and delayed emptying. (Nigeria) |
S. haematobium
Schistosomiasis haematobium mainly involves the urinary tract. Haematuria may be the first clinical indication, apart from tiredness and generalized ill health. All the early imaging findings are in the urinary tract. Plain radiography at this stag e is not helpful, and ultrasound is very dependent on the skill of the observer. A contrast urogram may show persistent filling of the lower segment of the ureters (Fig. 5). Careful ultrasound scanning may show thickening and nodularity of the ureteric walls. Next, the lower ureteric segment becomes dilated, due to constriction within the bladder wall. These early changes, although minimal, are important because they can still be reversed by treatment.
In the next stage the lower ureters are shown by contrast urography or ultrasound to be nodular, beaded or irregularly dilated. As these changes progress, the dilatation may affect the whole ureter or be segmental, usually most marked at 2-5 cm above the bladder. Multiple strictures and dilatations then develop, always bilateral but seldom symmetrical (Fig. 6 a). At this stage, fine ureteric calcification may be seen radiographically and on ultrasound (Fig. 6 b). Later, these calcified areas coalesce
 a | Figure 6.S. haematobium
a) Markedly dilated ureters with lower third strictures. There is calcification in the walls of the bladder. (Nigeria)
b) This heavily calcified bladder has contracted completely (arrowheads). There is also calcification in the ureters (arrows). (No contrast has been used.) (Nigeria) |
 b |
and the ureters appear "
calcified", even along their full length.
The bladder changes progress in a similar way. First, on contrast cystography, there is "haziness" in the bladder outline, due to submucosal oedema, then multiple small flat papillomas can be seen. Ultrasound will demonstrate the early thickening of the bladder wall, then the papillomas and the calcifications. Changes in the upper urinary tract only develop as the ureteric obstruction increases. If there are renal abnormalities found during what is thought to be the early stage of schistosomiasis, renal tuberculosis must be excluded. Tuberculosis seldom causes calcification in the ureter. After treatment for a tumour there may be a small localized area of calcification in the bladder, a very different appearance.
 a | Figure 7. S. haematobium
a) A contrast cystogram showing reflux up both ureters, which are stenosed and dilated irregularly. (Nigeria)
b) A contrast urogram in the late stages of schistosomiasis. There is bilateral hydronephrosis and hydroureter, with irregular strictures in the lower thirds of the ureters. (Egypt)
c) A large bladder calculus and a slightly smaller calculus in the lower end of the left ureter. There is the same calcification in the bladder wall. (Egypt)
d) A contrast urogram showing a large malignant tumour in the bladder, displacing the contrast to the left. The bladder walls are calcified, the ureters are dilated and stenosed, and there is delayed emptying. (Nigeria) |
 b |
 c | |
 d | |
If schistostomiasis is untreated, the ureteric
obstruction and
nodular changes will increase, there may be marked cystitis and patchy ureteric and bladder
calcification visible radiographically. On
ultrasound, the bladder walls will be thickened and may be so heavily
calcified that they appear solid. However, because the
calcification is in the ova which lie in the submucosa, in the early stages this does not alter the ability of the bladder to distend or empty(Fig. 5 a, b; Fig. 6 b).
CT will show similar
calcified ova in the perirectal and periureteric tissues, but this has no clinical significance, and there is no indication for this examination. Treatment may result in improvement and the
calcification may be less visible as the ova are excreted. Eventually, the ureters become unalterably fibrosed, stenosed and/or dilated, there is reflux from the bladder, and the end-result is kidney infection with severe hydronephrosis (Fig. 7 a, b). However, as already note d, if there is evidence of kidney involvement early in the patient's illness, tuberculosis is much more likely than schistosomiasis, which is not primarilya
renal disease.
Because of the repeated urinary infection, bladder calculi and occasionally ureteric calculi may be found (Fig. 7 c, d). There is close epidemiological association between chronic S. haematobium infection and carcinoma of the bladder, so any localized thickening of the bladder wall, or a mass within the bladder, should cause suspicion of malignancy. This should lead to cystoscopy and biopsy to establish the diagnosis, unless ultrasound has shown definite tumour invasion of the bladder wall.
Ultrasound, because there is no ionising radiation, has an important role in the diagnosis and management of schistosomiasis. For S. haematobium infections, ultrasound can be used in epidemiological surveys (recording the results with the WHO protocol) and to assess the effects of treatment. Particularly, the state of the ureters and bladder, and later, the degree of hydronephrosis can be observed. The eventual fibrotic (hyperechoic) changes in the kidney will indicate that the renal damage is irreversible.
However, it must be stressed that in the early stages of schistosomiasis, both experience and high quality ultrasound images are essential if the assessment is to be reliable. A negative ultrasound scan does not exclude early schistosomiasis (nor does a normal contrast urogram) and at no stage can ultrasound alone assess renal function.
CT and MR can demonstrate almost all the pathological changes, but for practical purposes ultrasound is as efficient, less expensive, available in the field and without any hazard.
S. haematobium rarely can affect the colon and central nervous system, but is almost always associated with urinary tract infection.
 a | Figure 8.S. mansoni
a) Multiple mucosal polyps in the descending and sigmoid colon (barium enema). (Egypt)
b) Severe sigmoid polyposis coalescing into a mass (barium enema) (Egypt) |
 b |
S. Mansoni
The earliest findings are in the colon, starting with oedema and mucosal ulceration, followed by loss of haustration. These changes can be demonstrated with a barium enema or ultrasound, and if untreated will progress to multiple mucosal polyps, usually in the rectum, sigmoid or descending colon (Fig. 8). The polyps are very fragile, on a short stalk, bleed easily, and may cause intussusception or obstruction. Where there is combined infection with S. haematobium and S. mansoni, polyps are even more common. Severe schistosomiasis can cause extensive colonic ulceration leading eventually to pericolic inflammation, with strictures. A solitary bilharzioma, resembling an amoeboma, may occur in either the large or small bowel. In teenage patients particularly, there can be severe enteritis. S. Mansoni infection does not seem to be associated with an increased risk of cancer, except perhaps in the rectum. As the infection continues, calcification may be seen, particularly around the rectum, but often in multiple areas throughout the length of the colon. It is asymptomatic and usually of no significance. As occurs in the bladder, the calcification is in ova rather than in fibrotic scars. Neither in the bowel or the bladder does the extent of calcification indicate the severity or activity of infection. The end-result of the S. mansoni infection can be a smooth colon, very similar to the end-result of ulcerative colitis and causing similar clinical disabilities.
S. mansoni can occasionally affect the small bowel, and even the bladder. In the duodenum there can be quite marked oedema, and the symptoms may resemble peptic ulceration.
S. Japonicum
S. japonicum can be an acute or chronic infection which mainly affects the small bowel, but also the descending and sigmoid colon, and the rectum. These are the parts of the gut with venous drainage into the inferior mesenteric vein. The ova cause wide-spread submucosal granulomas. On ultrasound, and particularly contrast radiography, there is oedema of the bowel with a cobble-stone appearance of the mucosa (Fig. 9). Eventually, the bowel mucosa will become coarse and irregular, particularly in the upper small bowel. There may be areas of dilatation and decreased motility with excess mucus. A retroperitoneal inflammatory granuloma has been reported (and can also occur in S. haematobium). S. japonicum has also been known to cause intestinal polyps.
 a | Figure 9.S. japonicum
a) Oedema of the duodenal loop (barium meal) (China)
b) Early colitis, especially in the descending colon (barium enema). (China) |
 b |
The lungs in schistosomiasis
The pulmonary radiographic findings vary with the type of schistosome, although in the stag e of acute infection all can cause the Katayama syndrome if the patient has never previously had schistosomiasis (see above). The end-result of this first stag e is always a normal chest radiograph.
In S. haematobium infection the majority of chest radiographs will be normal, in spite of the fact that histological sections will show multiple ova in about 50% of all cases. A few elderly patients may develop generalised, symmetrical interstitial fibrosis, which histologically is due to numerous peribronchial ova and associated diffuse fibrosis. Emphysema and clinical cor pulmonale are uncommon, but may develop later in a few patients.
 | Figure 10.S. mansoni
Aneurysmal dilatation of the main pulmonary arteries and pulmonary conus: there is decreased peripheral lung vasculature. (Egypt) |
In
S. mansoni infection the lung changes are more important. The ova may embolize and penetrate the
pulmonary arterioles, causing a localised inflammatory reaction. Some cause distinct bilharziomas, but in the majority of patients the arterioles narrow and many are obliterated. This causes
pulmonary artery hypertension. Radiographically the main
pulmonary arteries become prominent, but seldom symmetrically. The peripheral
vascular markings decrease, particularly at the lung bases. Because there may be ova damaging the
pulmonary artery walls, the main
pulmonary arteries may become aneurysmal, especially the main
pulmonary trunk (Fig. 10). Apart from this excessive and asymmetrical dilatation, there is nothing to distinguish the
radiographic changes due to schistosomiasis from other causes of
pulmonary fibrosis and
hypertension. It is unlikely that the
calcified granulomas would be mistaken for miliary tuberculosis, varicella pneumonia or histoplasmosis.
The liver in schistosomiasis
Although the changes in the urinary tract and bowel which result from schistosomiasis are both clinically and radiologically important, it is the damage which the organisms do to the liver which is more likely to be fatal in the majority of cases.
All schistosomes cause severe liver damage. The ova obstruct and penetrate the small portal veins, and the surrounding inflammatory reaction causes periportal fibrosis, resulting in presinusoidal blockage and portal hypertension. This occurs long before there is damage to liver function.
 a | Figure 11.S. mansoni
a) Ultrasound. Typical appearance of hepatic periportal fibrosis (arrowheads). (Nigeria)
b) Atrophy of the right lobe of the liver and periportal fibrosis (Brazil; Courtesy of Professor G. Cerri) |
 b |
Clinically, the liver and spleen enlarge in the early stages. The portal pressure rises, but ascites does not immediately develop and haematemesis is unlikely. It is not untillater, as the
fibrosis increases, that varices develop: a collateral circulation is opened, and there is ascites with all the clinical sequelae. (Fig. 13 a)
Schistosomal cirrhosis is readily recognized on ultrasound and CT: both show the periportal fibrosis. The earliest stages seen on ultrasound are diffuse, scattered echogenic areas, usually either rounded, in sheets or in bands (Fig. 11 a). Characteristically, there are faint, central sonolucent areas. The portal tract is thickened by fibrosis, and it is common to find atrophy of the right lobe of the liver, with associated hypertrophy of the left lobe (Fig. 11 b and Fig. 12 d). There is a standard WHO protocol to grade the degree of periportal fibrosis, which should be used to assess progress and for epidemiological surveys.
 a | Figure 12.CT scanning of S. japonicuma
a) Subcapsular and interlobular calcification in the liver. (China)
b) Interstitial calcification in the liver (arrows). (China)
c) Calcification in the wall of the portal vein and splenic vein. (China)
d) Atrophy of the right lobe of the liver with enlargement of the left and caudate lobes. (China) |
 b |
 c | |
 d | |
As the
cirrhosis progresses, the portal, splenic and mesenteric veins are always dilated, the splenic veins particularly.
Doppler ultrasound does not show any reduced flow velocity in the portal system. The hepatic
artery is reduced in diameter, the hepatic veins are unchanged. Both
ultrasound and
CT images during the early stages might be mistaken for metastases, but the schistosomal changes are more uniformly distributed. As the
fibrosis increases, the spleen enlarges. It usually retains a homogeneous pattern, unless there are siderotic nodules causing a more
nodular ultrasound appearance.
CT can demonstrate
calcification in the liver
capsule, and less commonly in the portal, splenic and mesenteric veins (Fig. 12). There are seldom any biliary polyps, but there can be thickening of the wall of the gallbladder and there may be
fibrosis eventually. There is dose correlation between the
ultrasound findings and the degree of portal
hypertension. Oesophageal and gastric varices result in
 a | Figure 13. The results of schistosomal cirrhosis, leading to portal hypertension and collateral circulation.
a) A barium swallow shows extensive oesophageal varices. (Egypt)
b) Early selective angiography showing an enlarged spleen with dilated splenic and portal veins. (Egypt)
c) Later stage of angiography, confirming the markedly dilated splenic and portal system, with collaterals and varices (arrow) at the gastric cardia. (Egypt) |
 b |
 c | |
haemorrhage as the many collaterals develop.
Angiography may be necessary if surgery is contemplated (Fig, 13), but
ultrasound, including
Doppler flow studies, is helpful in monitoring treatment and to exclude other causes of portal
hypertension, Schistosomiasis is a widespread, slow, chronic disease which is preventable and easily curable in the early stages. lf allowed to progress, or if re-infection occurs continuously, there will be irreversible changes in the urinary tract, the bowel, the lungs and, most importantly, the liver. Death seldom occurs in the early stages, but in many parts of the world every one is so familiar with the symptoms that their significance is ignored. In all types of schistosomiasis there is considerable morbidity and mortality in the later stages.
Philip E.S. Palmer, with Stanley P. Bohrer, Carlos Bruguera, Xing-Rong Chen, Mahmoud R. EImeligi, Hassen A. Gharbi, S.B. Lagundoye, M. W. Wachira