Schistosomiasis is a parasitic tropical disease, also called bilharzia, that is caused by flukes (parasitic flatworms) called schistosomes, and acquired from infested lakes, rivers, or other waters.
The larvae penetrate the skin and develop in the body into adult flukes, which settle in the veins of the bladder and intestines. Their eggs cause inflammatory reactions; there may be bleeding and ulceration in the bladder and intestinal walls, and the liver may be affected.
The first symptom is usually tingling and an itchy rash where the flukes have entered the skin. An influenza-like illness may develop many weeks later, when the adults produce eggs.
Subsequent symptoms include blood in the urine or faeces, abdominal or lower back pain, and enlargement of the liver or spleen.
Complications of long-term infestation include liver cirrhosis, bladder tumours, and kidney failure.
Treatment is with the drug praziquantel. No vaccine is available, so people visiting infested areas should avoid bathing or wading in fresh water.
Schistosomiasis in detail - technical
Schistosomiasis is caused by trematode worms Schistosoma spp., whose life cycle requires a definitive vertebrate host and an intermediate freshwater snail host. Transmission to humans occurs through exposure to fresh water containing infectious larvae, which can penetrate intact skin before developing into blood-dwelling adult worms. The disease is patchily distributed in parts of South America, Africa, the Middle East, China, and South East Asia, with about 200 million people infected and 20 million suffering severe consequences of infection.
Most infected people living in endemic areas have few (if any) overt symptoms, but clinical manifestations (when present) depend on the stage of infection.
Stage of invasion—larval invasion causes a transient immediate hypersensitivity reaction with intense itching (‘swimmer’s itch’) and rash (cercarial dermatitis).
Stage of maturation (acute schistosomiasis or Katayama fever)—most marked in primary infections in nonimmune adults; an acute pyrexial illness associated with many non-specific symptoms and signs, and which can (rarely) be fatal. Eosinophilia is almost always present.
Established infection—(1) Urinary schistosomiasis (Schistosoma haematobium)—active disease most commonly presents with painless, terminal haematuria; chronic disease is associated with calcification, ulceration, and the development of papillomas in the bladder, and with ureteric fibrosis. (2) Intestinal schistosomiasis (S. mansoni and S. japonicum)—clinical features are generally encountered in those with high-intensity infections, including diarrhoea, hepatomegaly and splenomegaly; liver disease may progress to presinusoidal periportal fibrosis with portal hypertension. (3) Other manifestations—these include (a) nervous system—myelopathy and radiculopathy; (b) lungs—pulmonary hypertension and/or cor pulmonale; (c) renal—glomerulonephritis.
A history of exposure to potentially contaminated water in geographically defined areas is important, especially in travellers and immigrants. Definitive diagnosis depends on direct microscopic detection of eggs in urine or stool samples, biopsies or (rarely) secretions such as seminal fluid. Serodiagnosis is not useful within endemic areas, but demonstration of schistosome-specific antibodies is helpful in travellers with a history of exposure and suspected schistosomiasis in whom eggs have not been detected.
Treatment and prognosis
Praziquantel is the drug of choice, with corticosteroids added in cases of Katayama fever to suppress the hypersensitivity reaction. Acute schistosomiasis responds well to early drug therapy, leaving little residual damage: chronic disease responds less well, although some improvement can occur. However, rapid re-exposure and reinfection are common, particularly in young children, unless control measures are implemented at the community level.
In areas of high transmission, population-based chemotherapy or treatment of schoolchildren (who have the heaviest worm burdens and contribute most to ongoing transmission) can reduce the prevalence and severity of morbidity. In areas of less intense transmission, treatment can be restricted to diagnosed cases. Health education should be aimed at improving practices of water use and preventing indiscriminate urination and defecation.
Schistosomiasis, also known as bilharzia, is caused by infection with parasitic trematode worms (flukes) of the genus Schistosoma. Disease is usually associated with chronic infections contracted by exposure to fresh water containing infective cercarial larvae that penetrate intact skin and develop into blood-dwelling worms. Most human infections are caused by one of three species, S. mansoni, S. haematobium, or S. japonicum. Two species, S. intercalatum and S. mekongi, are less significant. Schistosomiasis is patchily distributed in parts of South America, Africa, the Middle East, China, and South-East Asia. An estimated 779 million people are at risk of schistosomiasis worldwide, of whom 207 million are infected (Steinmann et al., 2006). Although simple diagnosis and effective drug treatment is available for individual uncomplicated cases, the world disease burden caused by these parasites has increased from an estimated 114 million human infections in 1947. Diagnosis and treatment are often not available to exposed rural populations, and drug-based control programmes are hampered by the continued susceptibility to reinfection of those who have been treated, particularly children. Human schistosomiasis is most often an insidious and chronic disease with a range of pathological manifestations involving the intestine and liver, or the urogenital tract. Mortality estimates are difficult, but 20 000 to 200 000 deaths may be directly associated with schistosomiasis each year.
Parasitic life cycle
The schistosome life cycle requires two host species: a definitive vertebrate host, in which adult male and female worms develop and sexual reproduction occurs, and an intermediate freshwater snail host, in which the parasite multiplies asexually. Transmission between these hosts is achieved by two different free-swimming larval stages. For species that infect humans, miracidia hatch from eggs excreted in the faeces or urine of the vertebrate host, and then seek out and infect snails. Cercariae are released from the snail and are able actively to penetrate intact human skin. Different schistosome species have their own, often very restricted, range of snail hosts. Schistosomiasis is thus closely associated with particular freshwater habitats, and its geographical distribution is restricted by the availability of particular snail species. S. mansoni and S. haematobium are confined to aquatic snails (genera Biomphalaria and Bulinus respectively) that inhabit ponds, lakes, irrigation canals, slow-flowing streams, and rivers. S. japonicum is transmitted by amphibious snails of the genus Oncomelania that, in addition to a variety of freshwater habitats, are also present in damp soil and vegetation, such as paddy fields.
Schistosomes that infect humans can also infect other mammals. This is important in the transmission of S. japonicum, a zoonotic infection in which cattle, water buffalo, pigs, dogs, and rodents can act as reservoir hosts of the human parasite. S. mansoni infects a narrower range of mammals, and only a few rodent species and baboons have any potential to act as occasional reservoirs. In nature S. haematobium is essentially specific to humans. The sites of maturation of the adult worms vary between schistosome species, affecting both the transmission of the infection and its clinical sequelae.
Once shed from freshwater snails, cercariae live for about 24 h, but their effective period of infectivity is probably shorter under field conditions. Cercarial behaviour and the timing of their release enhance their chance of contacting their vertebrate host of choice. Light and increasing temperature trigger the release of S. mansoni and S. haematobium cercariae during the day, and they use their tails actively to maintain their position near the water surface. S. japonicum cercariae are shed late in the day and are closely associated with the meniscus, perhaps reflecting their wider host range, as species specific for rodents are shed at night. Contact with skin triggers adherence mechanisms, and proteolytic enzymes and muscular movements allow penetration of the skin in minutes. Penetration initiates transformation into a schistosomular larva, with loss of the tail and of the protective outer glycocalyx layer, and the addition of an extra lipid bilayer to the surface membrane of the parasite’s syncytial outer tegument. This tegument now forms the main parasite–host interface and so has physiological and immunological functions vital to long-term survival in the hostile environment of the bloodstream. These include uptake of nutrients, response to injury, and surface adsorption of host antigens to provide an immunological disguise.
Newly transformed schistosomula remain in the epidermis for several days before migrating, via the bloodstream, lungs, and systemic circulation, to the hepatic portal system. Here the schistosomula mature and differentiate into adult worms, pair, and migrate against the portal blood flow to the small venules draining the genitourinary tract (S. haematobium) or the large and, to a lesser extent, small intestine (S. mansoni, S. japonicum, S. intercalatum, S. mekongi). Male and female worms are 1 to 2 cm long and morphologically distinct. Paired worms remain permanently coupled, with the shorter, flatter, more muscular male gripping the female in its gynaecophoric canal. Worms ingest blood cells into their blind-ending bifurcated gut, producing a haematin-like pigment that is regurgitated into the blood. Adult worms have average lifespans in humans of 3 years (S. haematobium) to 7 years (S. mansoni), although active infections are reported in individuals who have left endemic areas more than 20 years previously. Female worms start to produce eggs between 5 and 12 weeks after infection, at rates of 300 (S. mansoni) to 3000 (S. japonicum) per day. A few days after an egg is laid, a single miracidium develops within the rigid eggshell, the shape and size of which is characteristic for each species. S. mansoni and S. haematobium eggs are ellipsoid, 65 × 150 µm, the former having a lateral spine and the latter a terminal spine. S. japonicum eggs are more spherical, 70 × 90 µm, with a small lateral knob that is not always apparent microscopically. Embryonated eggs pass from the venules into the gut or bladder lumen. This is facilitated by host immune responses to secreted egg antigens, as egg excretion is inhibited in immunosuppressed experimental hosts and HIV infected individuals. The passage of the eggs causes tissue damage, as does the granulomatous reactions to eggs that fail to escape from the bloodstream and get swept into the liver by the portal blood flow.
Eggs deposited in fresh water rapidly hatch in response to osmotic changes, releasing the miracidium. This ciliated and actively swimming larva lives for about 6 h, and can chemically detect the proximity of snails, modifying its swimming behaviour as it approaches a potential host. The parasite actively penetrates the snail’s tissues and transforms into a primary sporocyst. Asexual replication gives rise to daughter sporocysts that migrate to the snail’s hepatopancreas where cercariae are asexually generated within each sporocyst. Thus, snails infected with a single miracidium release cercariae that are all of the same sex. Cercariae are first released from snails 3 to 6 weeks after infection, depending on parasite species and ambient temperature. Infected snails can shed hundreds of cercariae daily over several months. Schistosomiasis is associated with poor living conditions and inadequate sanitation and water supply. Its distribution has changed over the last 50 years. In some areas sustained control strategies have been successful. However, environmental changes, development of water resources, population increases, and migration, have led to its spread into previously nonendemic areas or areas with a low rate of infection. S. japonicum and S. haematobium have decreased, whereas S. mansoni has increased to become the most prevalent and widespread species. S. japonicum has been controlled effectively in many areas and is now endemic only in China, where it is much reduced, Indonesia, the Philippines, and Thailand. S. mekongi is found in Cambodia and Laos, and S. intercalatum is found in 10 countries within the rainforest belt of central Africa. S. mansoni is present in most countries of sub-Saharan Africa, and in Madagascar, the Nile delta and valley, as well as Saudi Arabia, Yemen, Oman, Libya, northern and eastern Brazil, Suriname, Venezuela, and some Caribbean islands. S. haematobium is widespread in sub-Saharan Africa and Madagascar, and is more prevalent than S. mansoni in North Africa and the Middle East.
Stage of invasion: cercarial dermatitis or ‘swimmer’s itch’
When cercariae penetrate the skin they can cause a skin reaction, called cercarial dermatitis or ‘swimmer’s itch’. This is frequently seen after exposure to avian schistosomes, and is associated with the death of cercariae in the skin. It is seen both in areas endemic for human schistosomiasis and in non-endemic areas. In people exposed for the first time, the invasion causes a transient immediate hypersensitivity reaction with intense itching. Within 12 to 24 h it is followed by a delayed reaction characterized by a small, red, pruritic, macular rash progressing to papules after 24 h. The rash may persist for up to 15 days and residual pigmentation may persist for months. Following repeated exposure, the signs and symptoms increase dramatically and start earlier. A similar reaction can be seen after re-exposure to human cercariae, predominantly S. mansoni and S. japonicum. Treatment, if needed, is symptomatic.
Stage of maturation: acute schistosomiasis or Katayama fever
The early stages of a primary infection can be associated with a severe systemic reaction that resembles serum sickness. This acute illness, called acute toxaemic schistosomiasis or Katayama fever, can occur following initial infection with any schistosome infecting humans, although it is more common in S. japonicum and S. mansoni infections. Acute schistosomiasis is most marked in primary infections in nonimmune adults, but acute S. japonicum infection can occur in re-exposed individuals. Symptoms appear 2 to 6 weeks after exposure. The clinical picture resembles an acute pyrexial illness with fever as a prime characteristic. The patient feels ill, and may have rigors, sweating, headache, malaise, muscular aches, profound weakness, weight loss, and a nonproductive irritating cough. Anorexia, nausea, abdominal pain, and diarrhoea can occur. Physical examination may reveal a generalized lymphadenopathy, an enlarged tender liver, and, sometimes, a slightly enlarged spleen and an urticarial rash. Eosinophilia is almost always present. Patients may become confused or stuporose or present with visual impairment or papilloedema. Severe cerebral or spinal cord manifestations may occur, and this is an indication for urgent investigative measures. Even light infections may cause severe illness and the syndrome can, in rare cases, be fatal.
Differential diagnoses include infections such as typhoid (leucopenia, no eosinophilia), brucellosis, malaria, infectious mononucleosis, miliary tuberculosis, leptospirosis, and other conditions with fever of unknown origin. Fever and eosinophilia occur in trichinosis, tropical eosinophilia, invasive ankylostomiasis, strongyloidiasis, visceral larva migrans, and infections with Opisthorchis and Clonorchis species.
Urinary schistosomiasis (Schistosoma haematobium)
The signs and symptoms of S. haematobium infection relate to the worms’ predilection for the veins of the genitourinary tract, and result from deposition of eggs in the bladder, ureters, and to some extent the genital organs. In the phase of established infection two stages can be recognized:
- ◆ an active stage mainly in children, adolescents, and younger adults with egg deposition in the urinary tract, egg excretion in the urine with proteinuria and macroscopic or microscopic haematuria
- ◆ a chronic stage in older patients with sparse or absent urinary egg excretion but the presence of urinary tract pathology
In the active stage many patients will have minimal symptoms. The most frequently encountered complaint is a painless, characteristically terminal, haematuria, the prevalence and severity of which is related to the intensity of infection. In communities where S. haematobium is highly endemic, macroscopic haematuria among boys is considered a natural sign of puberty. Dysuria, frequency, and suprapubic discomfort or pain is associated with schistosomal cystitis and may continue throughout the course of active infection. Initially the eggs may give rise to an intense inflammatory response in the mucosa. This may cause ureteric obstruction leading to hydroureter and hydronephrosis. Cytoscopy reveals friable masses or polyps extending into the bladder, petechiae, and granulomas. These early inflammatory lesions, including the obstructive uropathy, are usually reversible after treatment with antischistosomal drugs. The bladder lesions and obstructive uropathy can be visualized by ultrasonography.
As the infection progresses, the inflammatory component decreases, possibly due to modulation by the host immune response, and fibrosis increases. Various changes occur in the bladder, including calcification, ulceration, and the development of papillomas. Cytoscopy reveals ‘sandy patches’ composed of large numbers of calcified eggs surrounded by fibrous tissue and an atrophic mucosal surface. The bladder lesions may lead to nocturia, precipitancy, retention of urine, dribbling, and incontinence. Calculus formation is common, as is secondary bacterial infection, usually due to Escherichia coli, pseudomonas, klebsiella, enterobacter, or salmonella. the ureters are less commonly involved, but ureteric fibrosis can cause irreversible obstructive uropathy which can progress to uraemia. Bilateral ureteric involvement is common, although lesions may predominate on one side. Despite damage to the ureters, symptoms may be absent or minimal.
Egg deposition may also cause granulomas and lesions to develop in the genital organs, most commonly in the cervix and vagina in women and the seminal vessels in men. Dyspareunia, contact bleeding, and lower back pain may result in women, and perineal pain and painful ejaculation in men. Symptoms such as haematospermia and perineal discomfort have been described in travellers returning from Malawi. In some of these patients, eggs have been demonstrated in seminal fluid but not in urine. The impact of genital lesions caused by S. haematobium infection on the spread of HIV needs to be elucidated. Although small numbers of S. haematobium eggs are frequently detected in faeces and rectal biopsies, intestinal symptoms are uncommon.
In some areas in Africa, an association between S. haematobium infection and squamous cell carcinoma of the urinary bladder has been described. The aetiological significance of the parasite in the causation of this cancer is not proven, but is suggested by the finding that the prevalence of carcinoma of the bladder is correlated with intensity of S. haematobium infection. In the established stage, S. haematobium should be distinguished from renal tuberculosis with haematuria, haemoglobinuria, and cancer of the urogenital tract.
In most early S. mansoni and S. japonicum infections, symptoms are mild or absent. Clinical features are generally encountered in those with high-intensity infections. They include diarrhoea, sometimes with blood or mucus in the surface of the stool, abdominal discomfort, and hypogastric pain or colicky cramps. Severe dysentery is rare, but can occur. The liver, especially the left lobe, may be enlarged and tender; the spleen may also be enlarged, but is usually soft. At this stage, the condition is entirely reversible by antischistosomal treatment, but the relative lack of symptoms may cause it to pass unnoticed until irreversible complications set in. Later stages present as intestinal or hepatosplenic disease. Intestinal schistosomiasis is associated with granuloma formation , inflammation, and fibrosis, primarily in the large intestine. Focal dense deposits of S. mansoni or S. japonicum eggs in the large intestine can induce the formation of inflammatory polyps. The major clinical manifestation is intermittent diarrhoea with or without passage of blood or mucus, occasionally associated with protein-losing enteropathy and anaemia. Intestinal schistosomiasis in S. japonicum infection may also involve the stomach, with gastric bleeding and pyloric obstruction.
Differential diagnosis includes irritable bowel syndrome, amoebiasis, giardiasis, intestinal helminth infection, ulcerative colitis, Crohn’s disease, and tuberculosis.
Hepatosplenic schistosomiasis is a chronic manifestation of S. mansoni and S. japonicum infection. The term covers two distinct clinical entities: early inflammatory and late hepatosplenic disease with periportal fibrosis. Early inflammatory hepatosplenic schistosomiasis is the main cause of hepatosplenic schistosomiasis in children and adolescents. The liver is enlarged, especially the left lobe, and is smooth and firm. The spleen is enlarged, often extending below the umbilicus and firm or hard. Generally no hepatic fibrosis can be demonstrated by ultrasonography. Early inflammatory hepatosplenic schistosomiasis may be found in up to 80% of infected children and the severity is related to intensity of infection. This type of hepatosplenomegaly may also be associated with concomitant chronic exposure to malaria.
Presinusoidal periportal fibrosis (clay pipe stem or Symmers’ fibrosis) develops later in life, generally in young and middle-aged adults with long-standing intense exposure to infection. Patients with periportal fibrosis may excrete very few or no eggs in faeces. During the early stages the liver is enlarged, especially the left lobe; it is smooth, firm, and sometimes tender. Later, in many cases, it becomes small firm and nodular. The spleen is enlarged, often massively, due to passive congestion and reticuloendothelial hyperplasia. The patient may be asymptomatic or may complain of a left hypochondrial mass with discomfort and anorexia. Anaemia may be present. There may be reduced growth, infantilism, and amenorrhoea, especially in S. japonicum infection. Severe hepatosplenic schistosomiasis may lead to portal hypertension, but hepatic function usually remains normal. Ascites, attributable both to the portal hypertension and to hypoalbuminaemia, may be seen, especially in S. japonicum infection. Patients with severe hepatosplenic disease and portal hypertension may develop oesophageal varices detectable by endoscopy or ultrasound. These patients may experience repeated bouts of haematemesis, melaena, or both. This is the most severe, potentially fatal, complication of hepatosplenic schistosomiasis, and death may result from massive loss of blood.
Differential diagnoses of hepatosplenic schistosomiasis include kala-azar (visceral leishmaniasis), tropical splenomegaly syndrome associated with malaria, leukaemia, lymphoma, alcoholic, or viral cirrhosis, and some of the haemoglobinopathies. Some regression of periportal fibrosis may occur after specific antischistosomal therapy, as judged by ultrasonography examination of the liver, but in most individuals with periportal fibrosis and clinical manifestations of hepatosplenic disease, regression does not occur.
In comparison with S. japonicum and S. mansoni infections, clinical symptoms of disease in S. intercalatum infection are commonly mild or absent, and it is not regarded as a serious public health problem. Active infection is seen in children and adolescents and pathology is detected only in those with egg excretion exceeding 400 eggs/g faeces. The usual clinical presentation is one of diarrhoea, often with blood in the stool and lower abdominal pain or discomfort. S. mekongi infections are usually asymptomatic but may produce a clinical picture similar to that of S. japonicum, although the infections are usually milder. Hepatosplenomegaly can occur.
Nervous system manifestations
Nervous system involvement in S. mansoni and S. haematobium infections most frequently affect the spinal cord following acute infection. This manifestation is not related to the intensity of infection. A myelopathy and radiculopathy results from the inflammatory reaction, caused by the deposition of eggs around the spinal cord, and presents as an ascending flaccid paralysis with sensory level and sphincter involvement. The lesion is usually in the region of the cauda equina. Although paraparesis is seen most commonly during acute schistosomiasis, it may also be a late-stage complication of S. mansoni infection in endemic areas with high rates of transmission. Myelography, CT, and MRI are of diagnostic value. In acute cases lesions are seen on MRI scans as a diffuse swelling of the lumbar cord with central softening or cyst formation.
The brain is the major site of central nervous system involvement in S. japonicum infections. About 2% of acutely infected patients experience symptoms that mimic acute encephalitis or a focal neurological process. CT shows multiple enhancing lesions. In chronic infections, patients may present with focal brain lesions that can resemble tumours and present as focal epilepsy. These lesions contain masses of eggs and granulomas. Uncontrolled studies suggest that treatment with a combination of antischistosomal drugs and glucocorticoids is effective.
Eggs may be deposited in the lungs. Granulomatous reactions and fibrosis develop in the pulmonary vasculature leading to pulmonary hypertension and/or cor pulmonale. This is normally seen secondary to hepatosplenic schistosomiasis in patients with portal fibrosis and portal hypertension, but pulmonary hypertension may also result from accumulation of S. haematobium eggs in the lungs. A syndrome of cough with multiple small radiographic lesions and eosinophilia has been described. Symptoms include fatigue, palpitations, dyspnoea, cough, and sometimes haemoptysis. Patients may progress to decompensation with congestive cardiac failure. In endemic areas schistosomiasis must always be considered as a possible cause of cor pulmonale.
Glomerulonephritis is common in chronic S. mansoni infection in Brazil, especially in patients with hepatosplenic disease. Immunoglobulins, complement components, and schistosome antigens are deposited in the mesangial area. The condition is manifested clinically as proteinuria and/or nephrotic syndrome, sometimes with hypertension.
Patients infected with any of the three major schistosome species and subsequently infected with salmonella may develop a prolonged intermittent febrile illness. Prolonged excretion of salmonella in the urine and intermittent bacteraemia has been demonstrated in S. haematobium infection. Treatment for the salmonella infection alone is often not effective without treatment of the underlying schistosome infection.
Diagnosis and investigations
Information about geographical area and history of exposure by wading, bathing, washing, or showering in potentially contaminated fresh water is important for diagnosis of schistosomiasis, especially in travellers and immigrants. This can indicate the likelihood of infection and point to the schistosome species involved. A definitive diagnosis is made by the direct demonstration of schistosome eggs by microscopy of urine or stool samples, biopsies or, on rare occasions, secretions such as seminal fluid. In epidemiological studies it is usually important to obtain quantitative estimates of egg output to provide information about intensity of infection within a population.
Direct parasitological methods
In S. haematobium infection, eggs can be detected in urine after filtration, sedimentation, or centrifugation followed by microscopy. Ideally, urine should be passed around midday and the terminal part of the stream examined. The most commonly used method in epidemiological studies in endemic areas is filtration of 10 to 20 ml of urine using a syringe and a polycarbonate (e.g. Nucleopore), polyamide (e.g. Nytrel), or paper filter. Infection intensity is expressed as eggs/10 ml of urine. This may not be sufficiently sensitive for detection of low-intensity infections in travellers. In such cases, diagnosis is often based on filtration of 24-h urine samples.
For S. mansoni, S. japonicum, S. mekongi, and S. intercalatum eggs in the faeces, sedimentation of the eggs followed by microscopy is a useful and simple technique. However, the Kato thick smear technique is the most widely used method in epidemiological studies. This is based on microscopic examination of a smear of a small but fixed amount of faecal sample (usually 20–50 mg). Coarse particles and fibrous material are first removed from the sample by passing it through a sieve. A fixed sample volume is obtained by the use of a template. This is placed on a microscope slide and squashed with either a piece of cellophane soaked in glycerol or a glass coverslip. After leaving the slide for 6 to 24 h to allow the preparation to clear, the eggs are counted and the level of infection expressed as eggs/g faeces. Unfortunately, watery or diarrhoeal stools cannot be processed this way, and low-intensity infections may not be detected, since only small faecal samples are examined and eggs may be clumped unevenly in the stool. Increased sensitivity is obtained by increasing the number of samples examined. For diagnosis of light infections in previously unexposed travellers, microscopic examination of a rectal tissue snip crushed between glass slides is often the most sensitive direct diagnostic method. This method can also be used for biopsies. The crushed tissue sample is far better than a sectioned biopsy for the detection and identification of eggs.
Other direct methods
Recently, sensitive enzyme immune assays (ELISA) have been developed to detect circulating schistosome antigens in serum or urine. These antigens, circulating anodic antigen and circulating cathodic antigen, are derived from the gut of the adult schistosomes. The assays have almost 100% specificity and high sensitivity, and are excellent epidemiological tools as they provide a direct estimate of worm burden and can be used to monitor the efficacy of chemotherapy. They are less well suited for diagnosis of light infections in travellers.
Indirect diagnostic techniques
In S. haematobium infections, chemical reagent strips for detection of microhaematuria are widely used in endemic areas as a diagnostic measure. The method can be used in areas of both high and low transmission and there is a consistent significant correlation between microhaematuria and intensity of infection. In intestinal schistosomiasis, blood may be found in the stools, but it is not as useful an indicator of infection. In urinary schistosomiasis, eosinophiluria, with high numbers of eosinophil granulocytes in the urine, is a characteristic finding. Recently, detection of the eosinophil granule protein ECP (eosinophil cationic protein) in urine has been used for the qualitative assessment of eosinophil infiltration of the bladder mucosa, and hence local inflammation. Measurement of ECP in urine has proved useful in following post-treatment resolution of urinary tract morbidity in endemic areas. Eosinophilia is often found in acutely infected travellers. In cases where eggs are difficult to find, eosinophilia plus a history of exposure may suggest the need for further examination for schistosomiasis including serodiagnosis.
In cases of suspected schistosomiasis in which eggs have not been detected, serology can be used to demonstrate specific antibodies. An indirect immunofluorescence test using sections of adult worms for detection of specific immunoglobulins (IgM and IgG) is widely used. For travellers, a positive antibody result combined with a history of exposure should lead to treatment. Serodiagnosis is not useful in endemic areas because of the high levels of specific antibodies found in naturally exposed populations.
Ultrasonography is noninvasive, portable, has no biological hazards for the patient, and can be used to either complement or replace many invasive diagnostic techniques. It is the technique of choice for grading schistosomal periportal fibrosis, portal hypertension, hydronephrosis, and urinary bladder lesions. Ultrasonography is especially useful for monitoring decreases in morbidity after chemotherapy programmes.
Schistosome eggs can be trapped in the tissues, often the walls of the intestines or, depending on species, the urinary bladder or ureters. They may be seen in cone biopsies of the uterine cervix. The eggs of S. mansoni and S. japonicum are swept into the liver via the portal system, where they embolize into the portal radicles and give rise to vascular and granulomatous changes. Granulomatous pyelophlebitis and peripyelophlebitis is responsible for development of portal hypertension, while granulomata with subsequent fibrosis may be responsible for the periportal fibrosis. The characteristic lesion in the liver is a presinusoidal periportal fibrosis (Symmers’ fibrosis. There is typically no bridging between the fibrous tracts, no nodule formation, and no hepatic cell damage. Increased portal pressure can result in the development of portosystemic collaterals and eggs may pass directly from the portal vein to the pulmonary circulation. Here the combination of vascular and granulomatous changes is responsible for pulmonary hypertension.
Today the drug of choice is praziquantel, available as 600 mg tablets. It is administered orally, normally in a single dose, 40 mg/kg body weight and is effective against all schistosome species infecting humans. It is also effective for most other trematode infections and against adult cestodes. The drug is safe and well tolerated. After a single dose of 40 mg/kg up to 85% of those treated cease to excrete eggs, and egg counts are reduced by 95% or more in those not cured. In endemic areas, this level of efficacy is generally acceptable since very light residual infections do not lead to severe morbidity. In patients who are not cured by the initial treatment, the same dose can be repeated at weekly intervals for 2 weeks. A repeat dose 6–12 weeks later can be administered to cure prepatent infections, especially if eosinophilia or symptoms persist despite treatment.
Praziquantel has not been shown to be teratogenic in animals and it is now judged to be safe to use for the treatment of pregnant and lactating women and young children. Any side effects are generally mild, resolving spontaneously over a few hours and rarely requiring medication. Gastrointestinal side effects include abdominal pain or discomfort and sometimes vomiting. They occur more frequently in individuals with high infection intensities. Urticarial skin reactions and periorbital oedema may occur in about 2% of treated individuals. General side effects including headache, dizziness, fever, and fatigue can also occur, but less frequently.
As a general principle, all patients with acute schistosomiasis should be treated with praziquantel. Corticosteroids can be added in case of Katayama fever to suppress the hypersensitivity reaction. Since immature schistosomes are not susceptible to praziquantel, treatment should be repeated 4–6 weeks later. Use of praziquantel for cerebral S. japonicum infections is effective, resulting in rapid dissipation of cerebral oedema and resolution of cerebral masses. However, corticosteroids and anticonvulsants are sometimes needed in addition to praziquantel in cases with neuroschistosomiasis. Praziquantel should be administered with great caution in the case of concurrent neurocysticercosis. Chemotherapy is only part of the management of schistosomiasis-associated portal hypertension, since the main complications are due to obstructive pathology. Management of portal hypertension and prevention of bleeding from oesophageal varices is beyond the scope of this chapter. Praziquantel has largely replaced other drugs for treatment of schistosomiasis. Oxamniquine (marketed as Mansil in South America) is only effective against S. mansoni and is mainly used in Brazil. Artemisinin derivatives are effective against immature stages of S. mansoni, S. japonicum, and probably also S. haematobium. Their use for management of acute schistosomiasis or as prophylaxis is currently under investigation, but they cannot be used in malaria endemic areas due to the risk of inducing artimisinin resistance in malaria parasites.
Most infected people have few, if any, overt symptoms. Acute schistosomiasis can be fatal or can lead to severe residual damage to the nervous system if not treated, but responds well to antischistosomal therapy if started early. Early infections respond extremely well to treatment and the pathological lesions regress leaving little residual damage. However, in endemic areas individuals, particularly young children, are rapidly re-exposed and reinfected unless control measures are taken at the community level. Chronic infections with severe periportal fibrosis respond less well to specific antischistosomal treatment, although some regression of hepatosplenic disease with periportal fibrosis has been seen after treatment. The lifetime prognosis is worst in patients with severe hepatosplenic schistosomiasis and oesophageal varices. Previous episodes of haematemesis indicate a 70% risk of rebleeding.
Transmission and epidemiology
Each successful cercarial penetration of human skin has the potential to give rise to a single male or female adult worm, but it is probable that many cercariae die naturally in the epidermis. People tend to accumulate worms with continued exposure to infection. However, human populations in endemic areas do not just continue to accumulate worms with age. Intensities of infection increase in children during their younger years (as estimated by numbers of excreted eggs), peaking around the age of 12 years, before falling to lower levels in adulthood. This is probably due to the death of older worms, which are not replaced at a similar rate in older people. This age–infection intensity profile is more pronounced if study populations are given chemotherapy to remove existing infections and then monitored for levels of reinfection over several subsequent years. In these circumstances, it is clear that young children are much more susceptible to reinfection than older children or adults, and that a striking change in susceptibility to reinfection occurs after 12 years of age. The slower acquisition of worms in adulthood could be due to reduced exposure to infection or to age-dependent changes in innate resistance or acquired immunity. In many endemic areas children have more contact with water than adults, but careful observation of water-associated behaviour has shown that age profiles of water contact are variable between communities, whereas profiles of reinfection intensities are remarkably consistent. This suggests that host-related factors other than exposure influence susceptibility to reinfection. This has been most convincingly shown in fishing communities in areas with high S. mansoni transmission on Lake Albert, Uganda. Here occupational water contact results in adults having greater exposure to infection than their children, yet, within 12 months of treatment, it is the children under 12 years of age that suffer much higher reinfection intensities. Current research is focused on assessing the relative roles of innate resistance and acquired immunity in this age-dependent resistance and whether the onset of puberty or the length of time spent living in endemic areas might be important. For example, it is not known if this age-dependent resistance to infection holds true for travellers exposed to infection for the first time. Immune responses to schistosomes also differ between children and adults. Specific IgE and other characteristically Th2-type responses against the parasite are associated with resistance to reinfection. Whatever mechanisms underlie the contrasting susceptibilities of children and adults, continued exposure can be expected to result in reinfection, especially amongst younger children.
Prevention and control
Despite the high risk of reinfection, chemotherapy is usually highly beneficial at both the individual and population levels, as those suffering high intensities of infection are at greatest risk of the more severe forms of schistosomiasis. Furthermore, even low-intensity infections may lead to anaemia and have a negative impact on the well-being of the infected individual. This is specially important among vulnerable groups such as children and pregnant women. Various chemotherapy-based control strategies can be employed depending on intensity of transmission and the available resources. In the Nile delta region of Egypt, injections of tartar emetic were used for mass treatment from the 1960s to the 1980s. Tragically, the needles were not adequately sterilized and, as a result, hepatitis C virus was widely spread in this population to reach its highest recorded prevalence. In areas of high transmission, population-based chemotherapy can avoid the time and expense required for diagnosis and reduce the prevalence and severity of morbidity. Alternatively, schoolchildren can be targeted for treatment, as they invariably have the heaviest worm burdens and contribute most to ongoing transmission. In areas of less intense transmission, treatment can be restricted to diagnosed cases. The provision of safe water supplies and sanitation, where it can be achieved, will make an important additional contribution. Mortality can be prevented and morbidity best controlled by a combination of health education, chemotherapy, provision of safe water supplies and sanitation, and, where appropriate, snail control. Health education should be aimed at improving practices of water use and preventing indiscriminate urination and defecation. The role of molluscicides in control programmes depends on the local epidemiological and ecological circumstances and the resources available. Within the context of a larger concerted intervention, focal mollusciciding of major transmission sites can be useful. Eradication of host snail species is not usually feasible, although modification of the environment to eliminate snails has been successful in parts of China. In general, it has only been through sustained effort with integrated control strategies that disease control has been achieved.
In May 2001 the World Health Assembly passed Resolution 54.19, which called for efforts to reduce morbidity caused by schistosomiasis and soil-transmitted helminths in school-aged children. As a response to this call, the Schistosomiasis Control Initiative (SCI), supported by the Bill and Melinda Gates Foundation, with the objective of encouraging the development of sustainable schistosomiasis control programmes throughout sub-Saharan Africa, was launched in Uganda in March 2003. Five additional countries have now been enrolled: Zambia, Tanzania, Mali, Burkina Faso, and Niger. The goal is to reduce the level of morbidity in schistosomiasis endemic areas throughout sub-Saharan Africa with praziquantel treatment.
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