The term schistosomiasis (bilharzia) encompasses the acute and chronic inflammatory disorders caused by human infection with Schistosoma spp.

parasiteS. Disease is related to both the systemic and the focal effects of schistosome infection and its consequent host immune responses triggered by parasite eggs deposited in the tissueS. For the affected individuals, this frequently manifests as disabling chronic morbidity.

Etiology

Schistosoma organisms are the trematodes, or flukes , that parasitize the bloodstream.

Five schistosome species infect humans: Schistosoma haematobium, S. mansoni, S. japonicum, S. intercalatum, and S. mekongi .

Humans are infected through contact with water contaminated with cercariae , the free-living infective stage of the parasite.

These motile, forked-tail organisms emerge from infected snails and are capable of penetrating intact human skin.

As they reach maturity, adult worms migrate to specific anatomic sites characteristic of each schistosome species: S. haematobium adults are found in the perivesical and periureteral venous plexus, S. mansoni in the inferior mesenteric veins, and S. japonicum in the superior mesenteric veinS. S. intercalatum and S. mekongi are usually found in the mesenteric vesselS. Adult schistosome worms (1-2 cm long) are clearly adapted for an intravascular existence.

The female accompanies the male in a groove formed by the lateral edges of its body.

On fertilization, female worms begin oviposition in the small venous tributarieS. The eggs of the 3 main schistosome species have characteristic morphologic features: S. haematobium has a terminal spine, S. mansoni has a lateral spine, and S. japonicum has a smaller size with a short, curved spine (Fig. 326.1 ).

Parasite eggs provoke a significant granulomatous inflammatory response that allows them to ulcerate through host tissues to reach the lumen of the urinary tract or the intestineS. They are carried to the outside environment in urine or feces (depending on the species), where they will hatch if deposited in freshwater.

Motile miracidia emerge, infect specific freshwater snail intermediate hosts, and divide asexually.

After 4-12 wk, the infective cercariae are released by the snails into the contaminated water.

Epidemiology

Schistosomiasis infects more than 300 million people worldwide and puts more than 700 million people at risk, primarily children and young adultS. There are 3.3 million disability-adjusted life-years (DALYs) attributed to schistosomiasis, making it the 2nd most disabling parasitic disease after malaria.

Prevalence is increasing in many areas as population density increases and new irrigation projects provide broader habitats for vector snails .

Humans are the main definitive hosts for the 5 clinically important species of schistosomes, although S. japonicum is also a zoonosis, infecting animals such as dogs, rats, pigs, and cattle.

S. haematobium is prevalent in Africa and the Middle East; S. mansoni is prevalent in Africa, the Middle East, the Caribbean, and South America; and S. japonicum is prevalent in China, the Philippines, and Indonesia, with some sporadic foci in parts of Southeast Asia.

The other 2 species are less prevalent.

S. intercalatum is found in West and Central Africa, and S. mekongi is found only along the upper Mekong River in the Far East.

Transmission depends on water contamination by human excreta, the presence of specific intermediate snail hosts, and the patterns of water contact and social habits of the population (Fig. 326.2 ).

The distribution of infection in endemic areas shows that prevalence increases with age, to a peak at 10-20 yr old.

Exposure to infected water starts early in life for children living in endemic areaS. Passive water contact by infants (accompanying mothers in their daily household activities) evolves to more active water contact as preschool and school-age children pursue recreational activities such as swimming and wading.

Measuring intensity of infection (by quantitative egg count in urine or feces) demonstrates that the heaviest worm loads are found in school-age and adolescent children.

Even though schistosomiasis is most prevalent and most severe in older children and young adults, who are at maximal risk for suffering from its acute and chronic sequelae, preschool children can also exhibit significant disease manifestationS. Pathogenesis

Both early and late manifestations of schistosomiasis are immunologically mediated.

Acute schistosomiasis, known as snail fever or Katayama syndrome , is a febrile illness that represents an immune complex disease associated with early infection and oviposition.

The major pathology of infection occurs later, with chronic schistosomiasis, in which retention of eggs in the host tissues is associated with chronic granulomatous injury.

Eggs may be trapped at sites of deposition (urinary bladder, ureters, intestine) or may be carried by the bloodstream to other organs, most frequently the liver and less often the lungs and central nervous system (CNS).

The host response to these eggs involves local as well as systemic manifestationS. The cell-mediated immune response leads to granulomas composed of lymphocytes, macrophages, and eosinophils that surround the trapped eggs and add significantly to the degree of tissue destruction.

Granuloma formation in the bladder wall and at the ureterovesical junction results in the major disease manifestations of schistosomiasis haematobia: hematuria, dysuria, and obstructive uropathy.

Intestinal as well as hepatic granulomas underlie the pathologic sequelae of the other schistosome infections: ulcerations and fibrosis of intestinal wall, hepatosplenomegaly, and portal hypertension caused by presinusoidal obstruction of blood flow.

In terms of systemic disease, antischistosome inflammation increases circulating levels of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6, associated with elevated levels of C-reactive protein.

These responses are associated with hepcidin-mediated inhibition of iron uptake and use, leading to anemia of chronic inflammation.

Schistosomiasis-related undernutrition may be the result of similar pathways of chronic inflammation.

Acquired partial protective immunity against schistosomiasis has been demonstrated in some animal species and may occur in humanS.

Clinical Manifestations

Two main chronic clinical syndromes arise from Schistosoma spp.

infection: urogenital schistosomiasis caused by S. haematobium and intestinal schistosomiasis caused by S. mansoni or S. japonicum.

Most chronically infected individuals experience mild symptoms and may not seek medical attention; the more severe symptoms of schistosomiasis occur mainly in those who are heavily infected or who have been infected over longer periodS. In addition to organ-specific morbidities, infected patients frequently demonstrate anemia, chronic pain, diarrhea, exercise intolerance, and chronic undernutrition manifesting as growth stunting.

Cercarial penetration of human skin may result in a papular pruritic rash known as schistosomal dermatitis or swimmer's itch .

It is more pronounced in previously exposed individuals and is characterized by edema and intense cellular infiltrates in the dermis and epidermiS. Acute schistosomiasis (Katayama syndrome) may occur, particularly in heavily infected individuals, 4-8 wk after exposure; this is a serum sickness–like syndrome manifested by the acute onset of fever, cough, chills, sweating, abdominal pain, lymphadenopathy, hepatosplenomegaly, and eosinophilia.

Acute schistosomiasis typically presents in first-time visitors to endemic areas who experience primary infection at an older age.

Symptomatic children with chronic urogenital schistosomiasis usually complain of frequency, dysuria, and hematuria.

Urine examination shows erythrocytes, parasite eggs, and occasional eosinophiluria.

In endemic areas, moderate to severe pathologic lesions have been demonstrated in the urinary tract of >20% of infected children.

The extent of disease correlates with the intensity of infection, but significant morbidity can occur even in lightly infected children.

The advanced stages of urogenital schistosomiasis are associated with chronic renal failure, secondary infections, and squamous carcinoma of the bladder.

An important complication of S. haematobium infection is female genital schistosomiasis .

Eggs migrate from the vesical plexus to lodge in the female genital tract where they induce a granulomatous inflammatory response that can manifest as contact bleeding, pain, and eventual infertility.

Symptoms start as early as 10 yr of age, with an apparent 3-4–fold greater risk of HIV transmission.

Pathognomonic lesions can be visualized in the cervix by photocolposcopy.

Male genital schistosomiasis can also present with hematospermia, pain, and lumpy semen.

Children with chronic schistosomiasis mansoni, japonica, intercalatum, or mekongi may have intestinal symptoms; colicky abdominal pain and bloody diarrhea are the most common.

However, the intestinal phase may remain subclinical, and the late syndrome of hepatosplenomegaly, portal hypertension, ascites, and hematemesis may then be the first clinical presentation.

Liver disease is caused by granuloma formation and subsequent periportal fibrosis ; no appreciable liver cell injury occurs, and hepatic function may be preserved for a long time.

Schistosome eggs may escape into the lungs, causing pulmonary hypertension and cor pulmonale.

S. japonicum worms may migrate to the brain vasculature and produce localized lesions that cause seizureS. Transverse myelitis , spinal compression, and other CNS involvement (meningoencephalitis) are rare but well-known complications in children or young adults with either acute or chronic S. haematobium or S. mansoni infection.

Although end-organ scarring is pathognomonic, affected children may also have persistent long-term systemic effects of infection, including poor growth, anemia, decreased aerobic capacity, and cognitive impairment.

Diagnosis

Schistosome eggs are found in the excreta of infected individuals; quantitative methods should be used to provide an indication of the burden of infection.

For diagnosis of S. haematobium infection, a volume of 10 mL of urine should be collected around midday, the time of maximal egg excretion, and filtered for microscopic examination.

Stool examination by the Kato-Katz thick smear procedure and detection of parasite antigen in patient serum or urine are the methods of choice for diagnosis and quantification of other schistosome infections (S. mansoni and S. japonicum ).

The unique schistosome antigens circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) may also be detected in the urine or plasma.

Treatment

Treatment of children with schistosomiasis should be based on an appreciation of the intensity of infection and the extent of disease.

The recommended treatment for schistosomiasis is praziquantel (40 mg/kg/day orally [PO] divided twice daily [bid] for 1 day for schistosomiasis haematobia, mansoni, and intercalatum; 60 mg/kg/day PO divided 3 times daily [tid] for 1 day for schistosomiasis japonica and mekongi).

Children <5 yr old with S. mansoni may need up to 60 mg/kg/day PO tid for 1 day to achieve clearance.

A 2nd treatment 4-6 wk after the 1st course may help in eliminating residual infection.

Prevention

Transmission in endemic areas may be decreased by reducing the parasite load in the human population.

The availability of oral, single-dose, effective chemotherapeutic agents may help achieve this goal.

When added to national drug-based control programs, other measures such as improved sanitation, antiparasitic treatment given at well-child visits, focal application of molluscicidals, and animal vaccination may prove useful in breaking the cycle of transmission.

Ultimately, control of schistosomiasis is closely linked to economic and social development.