Chapter 57: Trematodes

Of the many relationships that have developed between humans and helminths over the millennia of our mutual existence, perhaps the most destructive to our health and productivity is that forged by the trematodes, or “flukes.” Typically, the adults live for decades within human tissues and vasculature, where they resist immunologic attack and produce progressive damage to vital organs. Morphologically, trematodes are bilaterally symmetric, vary in length from a few millimeters to several centimeters, and possess two deep suckers from which they derive their name (“body with holes”). One surrounds the oral cavity, and the other is located on the ventral surface of the worm. These organs are used for both attachment and locomotion; movement is accomplished in a characteristic inchworm fashion.

The digestive tract begins at the oral sucker and continues as a muscular pharynx and esophagus before bifurcating to form bilateral ceca that end blindly near the posterior extremity of the worm. Undigested food is vomited through the oral cavity. The excretory system consists of a number of hollow, ciliated “flame” cells that excrete waste products into interconnecting ducts terminating in a posterior pore.

Trematodes are divided into two major categories, based on their reproductive systems: The hermaphrodites and the schistosomes (Table 57–1). The adult hermaphrodites contain both male and female gonads and produce operculated eggs (defined as having a lid). In contrast, the schistosomes have separate sexes, and the fertilized female deposits nonoperculated eggs. However, the two groups have similar life cycles. In both cases, eggs are excreted from the human host and—if they reach fresh water—hatch to release ciliated larvae called miracidia. These larvae find and penetrate a snail host specific for the trematode species. In this intermediate snail host, they are transformed by a process of asexual reproduction into thousands of tail-bearing larvae called cercariae, which are released from the snail over a period of weeks. The cercariae swim in fresh water, searching vigorously for their next host. In the case of schistosomal cercariae, this host is the human: When they contact the skin surface, they attach, discard their tails, and invade, thereby completing their life cycle. The cercariae of the hermaphroditic flukes, in contrast, encyst in or on an aquatic plant or animal, where they undergo a second transformation to become infective metacercariae. Their cycle is completed when this second intermediate host is ingested by a human.

Of the many trematodes that infect humans, only the five of greatest medical importance are discussed here: The blood flukes, all of which are members of the genus Schistosoma (S mansoni, S haematobium, and S japonicum); and the lung (Paragonimus spp.) and liver (Clonorchis sinensis) flukes, which are hermaphroditic. Basic details of these and other hermaphroditic tissue and intestinal flukes are listed in Table 57–2.

PARAGONIMUS SPECIES: PARASITOLOGY AND LIFE CYCLE

Several Paragonimus species may infect humans. Paragonimus westermani, which is widely distributed in East Asia, is the species most frequently involved. The short, plump (10 by 5 mm), reddish-brown adults are characteristically found encapsulated in the pulmonary parenchyma of their definitive host. The adults are often, but not always, found in pairs in these capsules, where they usually cross-fertilize each other. Here they deposit operculated, golden-brown eggs, which are distinguished by their size (50 by 90 μm) and prominent periopercular shoulder (Figure 57–1). Eggs may be released into a bronchiole before the capsule of human fibrous tissue is complete, or when a capsule erodes into a bronchiole. The eggs are then coughed up and spat out or swallowed and passed in the stool. In either case, if they reach fresh water, they embryonate for several weeks before the ciliated miracidia emerge through the open opercula. After invasion of an appropriate snail host, 3 to 5 months pass before cercariae are released. These larval forms invade the gills, musculature, and viscera of certain crayfish or freshwater crabs; over 6 to 8 weeks, the cercariae transform into metacercariae. When the raw or undercooked flesh of the second intermediate host is ingested by humans, the metacercariae encyst in the duodenum and burrow through the gut wall into the peritoneal cavity. Most then continue their migration through the diaphragm and reach maturity in the lungs 5 to 6 weeks later (Figure 57–2). However, some are retained in the intestinal wall and mesentery or wander to other foci such as the liver, pancreas, kidney, skeletal muscle, or subcutaneous tissue. Young worms migrating through the neck and jugular foramen may encyst in the brain, a common ectopic site. Paragonimiasis is a zoonosis: In addition to humans, other carnivores may serve as definitive hosts, including the rat, cat, dog, and pig. Immature ectopic adults in the striated muscles of the pig may infect humans after ingestion of undercooked pork.

PARAGONIMIASIS (LUNG FLUKE INFECTION)

EPIDEMIOLOGY

Although most of the 5 million human infections are concentrated in the Far East (eg, Korea, Japan, China, Taiwan, the Philippines, and Indonesia), paragonimiasis has been described in India, Africa (Paragonimus africanus), and Latin America (Paragonimus mexicanus). Paragonimus kellicotti, a parasite of mink, is widely distributed in eastern Canada and the United States but rarely produces human infection. Approximately 1% of recent Vietnamese immigrants to the United States were once found to be infected with P westermani. Infection of the snail host, which is typically found in small mountain streams located away from human habitation, is probably maintained by animal hosts other than humans. Human disease occurs when food shortages or local customs expose individuals to infected crabs. When these crustaceans are prepared for cooking, juice containing metacercariae may be left behind on the working surface and contaminate other foods subsequently prepared in the same area. Fresh crab juice, which has been used to treat infertility in Cameroon and measles in Korea, may also transmit the disease. In Southeast Asia, crabs are eaten after they have been lightly salted, pickled, or immersed briefly in wine (“drunken crab”), practices seldom lethal to the metacercariae. This has occurred in the United States as well. Children living in endemic areas may be infected while handling or ingesting crabs during the course of play.

PARAGONIMIASIS (LUNG FLUKE INFECTION): CLINICAL ASPECTS

MANIFESTATIONS

During their migration from the gut to the lungs, larvae may cause tender, raised subcutaneous nodules, which migrate slowly along the abdominal wall. Adult worms in the lung elicit an eosinophilic inflammatory reaction and, eventually, the formation of a 1 to 2 cm fibrous capsule that surrounds and encloses one or more parasites. An infected patient may harbor more than 20 such lesions. With the onset of oviposition, the capsule swells and erodes into a bronchiole, resulting in expectoration of the brownish eggs, blood, and an inflammatory exudate. Secondary bacterial infection of the evacuated cysts is common, producing a clinical picture of chronic bronchitis or bronchiectasis. When cysts rupture into the pleural cavity, chest pain and effusion can result.

Early in infection, chest X-rays demonstrate small segmental infiltrates; these are gradually replaced by round nodules that may cavitate. Eventually, cystic rings, fibrosis, and calcification occur, producing a picture closely resembling that of pulmonary tuberculosis. This confusion is compounded by the frequent coexistence of the two diseases.

Adult flukes in the intestine and mesentery produce pain, bloody diarrhea, and occasionally palpable abdominal or cutaneous masses; the latter is more characteristic of a related Chinese fluke, P skrjabini. In approximately 1% of the cases of paragonimiasis in Southeast Asia, more commonly in children, parasites lodge in the brain and produce a variety of neurologic manifestations, including epilepsy, paralysis, homonymous hemianopsia, optic atrophy, and papilledema.

DIAGNOSIS

Eggs are usually absent from the sputum during the first 3 months of overt infection; however, repeated examinations eventually demonstrate them in more than 75% of infected patients. When a pleural effusion is present, it should be checked for eggs. Stool examination is frequently helpful, particularly in children who swallow their expectorated sputum. Approximately 50% of patients with brain lesions demonstrate calcification on X-ray films of the skull. The cerebrospinal fluid in such cases shows elevated protein levels and eosinophilic leukocytosis. A diagnosis in these cases, however, often depends on the detection of circulating antibodies via immunoblot technique. Their presence usually correlates well with acute disease and eventually disappears with successful therapy.

TREATMENT AND PREVENTION

Lung fluke infection responds well to praziquantel therapy. Brain lesions may require anti-seizure medications, and a short course of corticosteroids before praziquantel is initiated. Control requires adequate cooking of shellfish before ingestion.

CLONORCHIS SINENSIS: PARASITOLOGY AND LIFE CYCLE

Flukes of the genera Fasciola, Opisthorchis, and Clonorchis all may infect the human biliary tract and at times produce manifestations of ductal obstruction (Table 57–2). Clonorchis sinensis, the “Chinese liver fluke,” is discussed here. The small, slender (5 by 15 mm) adult survives up to 50 years in the biliary tract of its host by feasting on its rich mucosal secretions. A cone-shaped anterior pole, a large oral sucker, and a pair of deeply lobular testes arranged one behind the other in the posterior third of the worm distinguish it from other hepatic parasites (Figure 57–1A). Approximately 2000 tiny (15 by 30 μm) fertilized ovoid eggs are discharged daily and find their way down the bile duct and into the fecal stream. The urn-shaped eggshells have a discernible shoulder at their opercular rim and a tiny knob on the broader posterior pole (Figure 57–1A). On reaching fresh water, they are ingested by their intermediate snail host, where they transform into cercariae (Figure 57–3A). These cercariae are released into the water, where they swim until they penetrate the tissues of freshwater fish, in which they encyst to form metacercariae. If the latter host is ingested by a fish-eating mammal, the larvae are released in the duodenum, ascend the common bile duct, migrate to the second-order bile ducts, and mature to adulthood over 30 days (Figure 57–4).

In addition to humans, rats, cats, dogs, and pigs may serve as definitive hosts.

CLONORCHIASIS (LIVER FLUKE INFECTION)

EPIDEMIOLOGY

Clonorchiasis is endemic in Southeast Asia, particularly in Korea, Japan, Taiwan, the Red River Valley of Vietnam, the Southern Chinese province of Guandong, and Hong Kong. In previous years, parasite transmission was perpetuated by the practice of fertilizing commercial fish ponds with human feces. Improvements in the disposal of human waste have diminished acquisition of the disease in many areas. However, the extremely long life span of these worms is reflected in a much slower decrease in the overall infection prevalence. In some villages in southern China, virtually the entire adult population is infected. A survey of stool specimens from immigrants from Hong Kong to Canada showed an infection rate of more than 15% overall and 23% in adults between 30 and 50 years of age. Clonorchiasis is acquired by eating raw, frozen, dried, salted, smoked, or pickled fish. Commercial shipment of such products outside of the endemic area may result in the acquisition of worms far from their original source.

CLONORCHIASIS (LIVER FLUKE INFECTION): CLINICAL ASPECTS

MANIFESTATIONS

Migration of the larvae from the duodenum to the bile duct may produce fever, chills, mild jaundice, eosinophilia, and liver enlargement. The adult worm induces epithelial hyperplasia, adenoma formation, and periductal inflammation. In light infection, clinical disease seldom results. However, numerous reinfections may produce worm loads of 500 to 1000, resulting in the formation of bile stones and sometimes bile duct carcinoma in patients with severe, long-standing infections. Calculus formation may be accompanied by asymptomatic biliary carriage of Salmonella enterica serovar Typhi. Dead worms may obstruct the common bile duct and induce secondary bacterial cholangitis, which may in turn be accompanied by bacteremia and endotoxic shock. Occasionally, adult worms are found in the pancreatic ducts, where they can produce ductal obstruction and acute pancreatitis.

DIAGNOSIS

Definitive diagnosis of clonorchiasis requires the recovery and identification of the distinctive egg from the stool or duodenal aspirates. In mild infections, repeated examinations may be required. Because most patients are asymptomatic, any individual with clinical manifestations of disease in whom Clonorchis eggs are found should be evaluated for the presence of other causes of illness. In acute symptomatic clonorchiasis, there is usually leukocytosis, eosinophilia, elevation of alkaline phosphatase levels, and abnormal computed tomography and ultrasonographic liver scans. Cholangiograms may reveal dilatation of the intrahepatic ducts, small filling defects compatible with the presence of adult worms, and occasionally cholangiocarcinoma.

TREATMENT AND PREVENTION

Praziquantel and albendazole have proved to be effective. Patients with acute obstructive cholangitis due to a worm or stone in the large collecting ducts should be managed as for any other cause of obstruction, including consideration of antibiotics for secondary infection and correction of the obstruction [eg, via endoscopic retrograde pancreatography cholangiopancreatography (ERCP)]. Prevention requires thorough cooking of freshwater fish and appropriate sanitary disposal of human feces.

SCHISTOSOMA SPECIES: PARASITOLOGY AND LIFE CYCLE

The schistosomes are a group of closely related flukes that inhabit the vascular system of a number of animals. Of the five species known to infect humans, S mansoni, S haematobium, and S japonicum are of primary importance. They infect 200 to 300 million persons in Africa, the Middle East, Southeast Asia, the Caribbean, and South America, and kill 1 million annually. The remaining two species are found in limited areas of West Africa (S intercalatum) and Southeast Asia (S mekongi), and are not discussed here in detail.

The adult worms can be distinguished from the hermaphroditic trematodes by the anterior location of their ventral sucker, by their cylindric bodies, and by their reproductive systems (ie, separate sexes). Adult specimens of different species are differentiated from one another only with difficulty. The 1 to 2 cm male possesses a deep ventral groove, or “schist.” Within this gynecophoral canal it carries the longer, more slender female in lifelong copulatory embrace. The schistosome life cycle (Figure 57–5) begins after mating in the hepato-portal circulation when the conjoined couple uses their suckers to ascend the mesenteric vessels against the flow of blood. Guided by unknown stimuli, S japonicum enters the superior mesenteric vein, eventually reaching the venous radicals of the small intestine and ascending colon; S mansoni and S haematobium are directed to the inferior mesenteric system. The destination of the former is the descending colon and rectum; the latter, however, passes through the hemorrhoidal plexus to the systemic venous system, ultimately coming to rest in the venous plexus of the bladder and other pelvic organs.

On reaching the submucosal venules, the worms begin to lay eggs. Each pair deposits 300 (S mansoni, S haematobium) to 3000 (S japonicum) eggs daily for the remainder of its 4- to 35-year life span. Enzymes secreted by the enclosed miracidium diffuse through the shell and digest the surrounding tissue. Ova lying immediately adjacent to the mucosal surface rupture into the lumen of the bowel (S mansoni, S japonicum) or bladder (S haematobium) and are passed to the outside in the excreta. Here, with appropriate techniques, they may be readily observed and differentiated. The eggs of S mansoni are oval, possess a sharp lateral spine, and measure 60 by 140 μm. Those of S haematobium differ primarily in the terminal location of their spine. The eggs of S japonicum, in contrast, are more nearly circular, measuring 70 by 90 μm. A minute lateral spine can be visualized only with care (Figure 57–1D–F).

The miracidia hatch quickly when the eggs are deposited in fresh water. On finding a snail host appropriate for their species, they invade and are transformed over 1 to 2 months into thousands of forked-tailed cercariae (Figure 57–3B). When released from the snail, these infectious larvae swim about vigorously for a few days. Cercariae coming in contact with human skin during this time attach, discard their tails, and penetrate. During a 1- to 3-day sojourn in the skin, the cercaria with three outer membrane layers develop into schistosomula with seven outer layers, a change that is thought to be critical to the survival of the parasite within the human body. These schistosomula enter small venules and find their way through the right side of the heart to the lung. After a delay of several days, the parasites enter the systemic circulation. Those surviving passage through the pulmonary and intestinal capillary beds return to the portal vein, where they mature to sexually active adults over 1 to 3 months, and find a mate of the opposite sex, thus completing the life cycle. Schistosomiasis is primarily a human condition, but may be zoonotic in exceptional circumstances, as demonstrated by the presence of S japonicum infection in cattle and water buffalo in southern China.

SCHISTOSOMIASIS (BLOOD FLUKE INFECTION)

EPIDEMIOLOGY

The widespread distribution and extensive morbidity of schistosomiasis make it the single most important helminthic infection in the world today. Currently, approximately 200 million people—almost 1 in 30 of all humans—are infected worldwide. Of these, roughly 200 000 die annually. The continued transmission of the parasite depends on the disposal of infected human urine and excrement into fresh water, the presence of appropriate snail hosts, and the exposure of humans to water infested with cercariae. The construction of modern sanitation and water purification facilities would break this cycle but exceeds the economic resources of many endemic nations. Paradoxically, several massive land irrigation projects launched for the express purpose of speeding economic development have resulted in the dispersion of infection to previously uninvolved areas. Schistosoma mansoni, the most widespread of the blood flukes, is the only one present in the Western Hemisphere. Perhaps originally introduced during slavery, S mansoni is now found in Venezuela, Brazil, Surinam, Puerto Rico, the Dominican Republic, St. Lucia, and several other Caribbean islands.

Because a suitable snail host is lacking, transmission of S mansoni does not occur within the continental United States; however, nearly half a million individuals residing in the United States have acquired schistosomiasis elsewhere. Puerto Rican, Yemenite, and Southeast Asian populations are predominantly involved. In the Eastern Hemisphere, the prevalence of S mansoni infection is highest in the Nile Delta and tropical Africa. Isolated foci are also found in East and South Africa, Yemen, Saudi Arabia, and Israel.

Schistosoma haematobium is largely confined to Africa and the Middle East, where its distribution overlaps that of S mansoni. Schistosoma japonicum affects the agricultural populations of several Southeast Asian countries, including China, the Philippines, and Sulawesi (it was eradicated from Japan in the 1990s). The closely related S mekongi is found in the Mekong and Mun River valleys of Vietnam, Thailand, Cambodia, and Laos.

Within the endemic areas of schistosomiasis, there are wide variations in both age-specific infection rates and worm loads. In general, both peak in the second decade of life and then decrease with advancing age. This finding has been explained in part by changes in the intensity of water exposure and in part by the gradual development of IgE-mediated immunity. Most infected patients carry fewer than 10 pairs of worms in the vascular system and, accordingly, lack clinical manifestations of disease. Individuals who develop much heavier worm loads as a result of repeated infections may experience serious morbidity or mortality.

PATHOGENESIS

There are three major clinicopathologic stages in schistosomiasis. The first stage is initiated by the penetration and migration of the schistosomula. The second or intermediate stage begins with oviposition and is associated with a complex of clinical manifestations. The third or chronic stage is characterized by granuloma formation and scarring around retained eggs.

IMMUNITY

The major clinicopathologic manifestations of schistosomiasis result from the host’s cell-mediated immune response to the presence of retained eggs. Not all eggs are excreted into the environment, and those left behind in tissue serve as antigenic stimuli for our immune system, which walls them off in eosinophilic granulomas (“Splendore-Hoeppli reactions”). With time, the intensity of this reaction is muted; granulomas formed in the later stages of infection are smaller and less damaging than those formed early. The mechanisms responsible for this modulation are not fully understood. Present evidence suggests that both suppressor T-lymphocyte activity and antibody blockade are involved. The correlation in humans between human leukocyte antigen (HLA) types A1 and B5 and the development of hepatosplenomegaly suggests that the extent of the immunoregulation is influenced, at least in part, by the genetic background of the host.

As evidenced by their prolonged survival, the adult worms are remarkably well tolerated by their hosts. In part, this tolerance may be attributable to the formation of IgG4 blocking antibodies early in the course of infection. Tolerance may also reflect the ability of the developing parasites to disguise themselves by adsorbing host molecules, including immunoglobulins, blood group glycolipids, and histocompatibility complex antigens. Nevertheless, as mentioned earlier, the prevalence and intensity of human infection begin to abate during adolescence, despite continuing exposure to infective cercariae. It has been suggested that schistosomula penetrating the skin after the primary infection are coated with specific antibodies, bound to eosinophils, and destroyed before they can reach the portal system. Although protection is not complete, a 60% to 80% kill rate is highly effective in controlling the intensity of parasitism. This condition, in which adult worms from a primary infection can survive in a host resistant to reinfection, is termed concomitant immunity. Eventually, production of blocking antibodies wanes whereas production of protective IgE antibodies active against adult worms increases, leading to a decrease in the host’s total worm population.

SCHISTOSOMIASIS (BLOOD FLUKE INFECTION): CLINICAL ASPECTS

EARLY STAGE

Within 24 hours of penetrating the skin, a large proportion of the schistosomula die. In S mansoni and S haematobium infections, immediate and delayed hypersensitivity to parasitic antigens results in an intensely pruritic papular skin rash, which increases in severity with repeated exposures to cercariae. As the viable schistosomula begin their migration to the liver, the rash disappears and the patient experiences fever, headache, and abdominal pain for 1 to 2 weeks.

Of note, a related condition happens in North America when certain schistosoma species adapted to aquatic birds mistakenly invade the skin of swimmers; unable to penetrate deeper into the human vascular systems, these cercariae remain trapped in the skin. The parasites die there without causing serious harm, but not before causing a localized pruritic, inflammatory reaction called cercarial dermatitis, or “swimmer’s itch.”

INTERMEDIATE STAGE

After 1 to 2 months of primary exposure, once the sexually mature adult worms begin to lay eggs (oviposition), patients with severe S mansoni or S japonicum infections may experience an acute febrile illness that bears a striking resemblance to serum sickness. This onset of oviposition leads to a state of relative egg antigen excess, with formation of soluble immune complexes that deposit in host tissues. Indeed, high levels of such complexes have been demonstrated in the peripheral blood and correlate well with the severity of illness. In addition to fever and chills, patients experience cough, urticaria, arthralgia, lymphadenopathy, splenomegaly, abdominal pain, and diarrhea. Sigmoidoscopic examination reveals an inflamed colonic mucosa and petechial hemorrhages; occasionally, patients with S japonicum infection develop clinical manifestations of encephalitis. Typically, leukocytosis, marked peripheral eosinophilia, and elevated levels of IgM, IgG, and IgE immunoglobulins are present. This symptom complex is commonly termed Katayama syndrome. It is more common and severe in visitors to endemic areas, in whom it may persist for 3 months or more. Occasionally it results in death.

CHRONIC STAGE

Approximately one-half of all deposited eggs reach the lumen of the bowel or bladder and are shed from the body. Retained eggs induce inflammation and scarring, initiating the final and most morbid phase of schistosomiasis. Soluble antigens excreted by the eggs stimulate the formation of T-lymphocyte–mediated eosinophilic granulomas. Early in the infection, the inflammatory response is vigorous, producing lesions more than 100-fold larger than the inciting egg itself. With time, the host’s inflammatory response moderates, leading to a significant decrease in granuloma size. Fibroblasts stimulated by factors released by both retained eggs and the granulomas lay down scar tissue, rendering the earlier, granuloma-induced vascular obstruction permanent. As would be expected, the severity of tissue damage is directly related to the total number of eggs retained.

In S haematobium infection, the bladder mucosa becomes thickened, papillated, and ulcerated. Hematuria and dysuria result; repeated hemorrhages produce anemia. In severe infections, the muscular layers of the bladder are involved, with loss of bladder capacity and contractibility. Vesicoureteral reflux, ureteral obstruction, and hydronephrosis may follow. Progressive obstruction may lead to renal failure and uremia. Calcification of the bladder wall is occasionally seen, and approximately 10% of patients harbor urinary tract calculi. Secondary bacterial infections are common. Chronic Salmonella bacteriuria with recurrent bouts of bacteremia has been reported in Egypt, where squamous cell bladder carcinoma is frequently seen as a late complication of disease. Other urogenital organs may also be involved, including the spermatic cord, testes, fallopian tubes, ovaries, and vagina.

In S mansoni and S japonicum infections, the bowel mucosa is congested, thickened, and ulcerated. Patients experience abdominal pain, diarrhea, and blood in the stool. Eggs deposited in the larger intestinal veins may be carried by the portal blood flow back to the liver, where they lodge in the presinusoidal capillaries. The resulting inflammatory reaction leads to the development of periportal fibrosis and hepatic enlargement. The frequency and severity with which the liver is involved appear to be genetically determined and associated with the patient’s HLA type. In contrast to cirrhosis, in most cases of schistosomiasis liver function is well preserved. Infected persons who subsequently acquire hepatitis B or C viruses develop chronic active hepatitis more frequently than those without schistosomiasis. Presinusoidal obstruction of blood flow can result in portal hypertension and serious manifestations of portal obstruction. Eggs that are carried around the liver in the portosystemic collateral vessels may lodge in the small pulmonary arterioles, where they produce interstitial scarring, pulmonary hypertension, and right ventricular failure. Immune complexes shunted to the systemic circulation may induce glomerulonephritis. Occasionally, eggs may be deposited in the central nervous system, where they may cause epilepsy or paraplegia.

Some differences between the clinical presentation of schistosomiasis mansoni and that of schistosomiasis japonicum have been noted. Manifestations of the latter disease typically occur earlier in the course of the infection and tend to be more severe. When involvement of the central nervous system develops, it is more likely to occur in the brain than in the spinal cord. On the other hand, immune complex nephropathy and recurrent Salmonella bacteremia are more commonly seen in hepatosplenic S mansoni infections. The latter phenomenon is apparently related to the ability of Salmonella to parasitize the gut and integument of the adult fluke, providing a persistent bacterial focus within the portal system of the infected patient. This focus cannot be eradicated without treatment of the schistosomal infection.

DIAGNOSIS

Definitive diagnosis of schistosomiasis requires the recovery of the characteristic eggs in urine, stool, or biopsy specimens. In S haematobium infections, eggs are most numerous in urine samples obtained at midday, especially the last drops voided. When examination of the sediment yields negative results, eggs may sometimes be recovered by filtering the urine through a fine membrane. Cystoscopy with biopsy of the bladder mucosa may be required for the diagnosis of mild infection. Eggs of S mansoni and S japonicum are passed in the stool. Concentration techniques such as formalin–ether or gravity sedimentation are necessary when the ova are scanty. Results of rectal biopsy may be positive when those of repeated stool examinations are negative.

Because dead eggs may persist in tissue for a long time after the death of the adult worms, active infection is confirmed only when the eggs are shown to be viable. This may be performed by observing the eggs microscopically for movement of flame cell cilia or by hatching them in water and watching for motile miracidia to emerge. Quantitation of egg output may be useful in estimating the severity of infection and in following response to treatment.

Conventional serologic tests detect circulating antibodies with sensitivities exceeding 90%, but cannot distinguish active from prior infection. Enzyme immunoassay (EIA)-based reagent strip (dipstick) tests, capable of detecting circulating, genus-specific, adult worm antigens in blood and urine, are rapid, simple, and sensitive. They are particularly helpful in the diagnosis of Katayama syndrome in those returning from endemic areas. Moreover, because antigen levels drop rapidly after successful therapy, these tests may prove helpful in distinguishing active from inactive disease.

TREATMENT

No specific therapy is available for the treatment of schistosomal dermatitis or Katayama syndrome. Antihistamines and corticosteroids may be helpful in ameliorating their more severe manifestations. The maturing organisms seem resistant to antiparasitic medications, thus no immediate postexposure prophylaxis after water exposure is possible. In the late stage of schistosomiasis, therapy is directed at interrupting egg deposition by killing or sterilizing the adult worms.

Several anthelmintic agents may be used. Praziquantel, which is active against all three species of schistosomes, is the agent of choice. Use of this drug is relatively contraindicated in early pregnancy. Unfortunately, reports suggest decreased efficacy of this single-dose oral agent in areas where it has been used in mass therapy programs; in this setting, repeat dosing is an option, although S mansoni infections acquired in such areas may be treated with oxamniquine (not available in the United States). Artemisinin derivatives have worked well in experimental settings, and may be useful in select cases; fostering Plasmodium resistance in patients coinfected with malaria is a real concern.

PREVENTION

Controlling this deadly disease has proved both difficult and expensive. Programs aimed at interrupting transmission by the provision of pure water supplies and the sanitary disposal of human feces are often beyond the economic reach of nations most seriously affected. Similarly, measures to deny snails access to newly irrigated lands are expensive. Chemical molluscicides have been effective in limited trials, but less successful when used over large areas for prolonged periods. Mass therapy of the infected human population has until recently been severely limited by the toxicity of older agents, or by unanticipated consequences, such as the unsanitary injection of tartrate emetic in Egypt, an antiparasitic drug that provided little benefit in terms of schistosomiasis but perversely transmitted Hepatitis C to thousands of patients. Praziquantel has proved to be more suitable for this purpose, albeit at the risk of selecting drug resistance. Furthermore, without other control measures, discontinuation of mass therapy can result in a rapid rebound of active disease.

In 2009, a report of an extensive controlled study in an area of Southeastern China that was hyperendemic for S japonicum yielded remarkable results that are most instructive. These included removal of cattle from snail-infested grasslands, providing mechanized equipment to farmers, improving sanitation of drinking water, building lavatories and latrines, providing boats with fecal matter containers, and implementing intensive health education programs. The infection rates fell dramatically in the intervention villages as compared to nonintervention areas. Thus, a multipronged approach such as this offers the best hope for lasting control.

Currently, there is intense interest in developing a vaccine suitable for human use. A vaccine made from irradiated S bovis cercariae, which was developed for cattle, appears to confer a significant degree of protection against infection. Although a similar live vaccine would not be practical for human populations, the success of the animal vaccine has provided clues to potential immunoprotective mechanisms in human schistosomiasis. Monoclonal antibodies have been used to identify a number of schistosomula and adult antigens thought to be capable of inducing protective immunity; more than a dozen antigens are now in various stages of investigation as vaccine candidates.