Schistosomiasis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The pathogenesis of acute human schistosomiasis is mainly related to egg deposition and liberation of antigens of adult worms and eggs. A strong inflammatory response characterized by high levels of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumor necrosis factor-α, and by circulating immune complexes participates in the pathogenesis of the acute phase of the disease. Schistosomes have a typical trematode vertebrate-invertebrate lifecycle, with humans being the definitive host. The life cycles of all five human schistosomes are broadly similar. Infection can occur by penetration of the human skin by cercaria or following the handling of contaminated soil. Cercaria gets transformed into migrating schistosomulum stage in the skin. The incubation period for acute schistosomiasis is usually 14-84 days. Both the early and late manifestations of schistosomiasis are immunologically mediated. The major pathology of infection occurs with chronic schistosomiasis in which retention of eggs in the host tissues is associated with chronic granulomatous injury.

Pathophysiology

Life Cycle

Schistosomes have a typical trematode vertebrate-invertebrate lifecycle, with humans being the definitive host. The life cycles of all five human schistosomes are broadly similar.

Snail cycle

• Parasite eggs are released into the environment from infected individuals, hatching on contact with fresh water to release the free-swimming miracidium.
• Miracidia infect fresh-water snails by penetrating the snail's foot.
• After infection, the miracidium transforms into a primary (mother) sporocyst.
• Germ cells within the primary sporocyst will then begin dividing to produce secondary (daughter) sporocysts, which migrate to the snail's hepatopancreas.
• Once at the hepatopancreas, germ cells within the secondary sporocyst begin to divide producing thousands of new parasites, known as cercariae, which are the larvae capable of infecting mammals.
• Cercariae emerge daily from the snail host in a circadian rhythm, dependent on ambient temperature and light.
• Young cercariae are highly motile, alternating between vigorous upward movement and sinking to maintain their position in the water.
• Cercarial activity is particularly stimulated by water turbulence, by shadows and by chemicals found on human skin.

Schistosomiasis life cycle. Source: CDC

Human cycle

• Penetration of the human skin occurs after the cercaria have attached to and explored the skin.
• The parasite secretes enzymes that break down the skin's protein to enable penetration of the cercarial head through the skin.
• As the cercaria penetrates the skin it transforms into a migrating schistosomulum stage.
• The newly transformed schistosomulum may remain in the skin for 2 days before locating a post-capillary venule. The schistosomulum travels from the skin to the lungs where it undergoes further developmental changes necessary for subsequent migration to the liver.
• Eight to ten days after penetration of the skin, the parasite migrates to the liver sinusoids.
• S. japonicum migrates more quickly than S. mansoni, and usually reaches the liver within 8 days of penetration.
• Juvenile S. mansoni and S. japonicum worms develop an oral sucker after arriving at the liver. During this period that the parasite begins to feed on red blood cells.
• The nearly-mature worms pair, with the longer female worm residing in the gynaecophoric channel of the male.
• Adult worms are about 10 mm long. Worm pairs of S. mansoni and S. japonicum relocate to the mesenteric or rectal veins.
• S. haematobium schistosomula ultimately migrate from the liver to the perivesical venous plexus of the bladder, ureters, and kidneys through the hemorrhoidal plexus.
• Parasites reach maturity in six to eight weeks, at which time they begin to produce eggs.
• Adult S. mansoni pairs residing in the mesenteric vessels may produce up to 300 eggs per day during their reproductive lives.
• S. japonicum may produce up to 3000 eggs per day. Many of the eggs pass through the walls of the blood vessels, and through the intestinal wall, to be passed out of the body in faeces.
• S. haematobium eggs pass through the ureteral or bladder wall and into the urine. Only mature eggs are capable of crossing into the digestive tract, possibly through the release of proteolytic enzymes, but also as a function of host immune response, which fosters local tissue ulceration.
• Up to half the eggs released by the worm pairs become trapped in the mesenteric veins, or will be washed back into the liver, where they will become lodged.
• Worm pairs can live in the body for an average of four and a half years but may persist up to 20 years.
• Trapped eggs mature normally, secreting antigens that elicit a vigorous immune response.
• The eggs themselves do not damage the body rather it is the cellular infiltration resultant from the immune response that causes the pathology classically associated with schistosomiasis.

Pathogenesis

Transmission

Infection can occur by penetration of the human skin by cercaria or following the handling of contaminated soil or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables).

Dissemination

Cercaria gets transformed into migrating schistosomulum stage in the skin. Then migrating schistosomulum are transported via the blood stream to respective organ system.

Incubation period

The incubation period for acute schistosomiasis is usually 14-84 days. However, many people are asymptomatic and have subclinical disease during both acute and chronic stages of schistosomiasis.

Infective stages

• Cercaria are the infective stage of schistosomiasis to humans

Diagnostic stages

• Miracidium are diagnostic for schistosomiasis.

Pathogenesis

• The pathogenesis of acute human schistosomiasis is mainly related to egg deposition and liberation of antigens of adult worms and eggs.
• A strong inflammatory response characterized by high levels of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumor necrosis factor-α, and by circulating immune complexes participates in the pathogenesis of the acute phase of the disease.

Immune response

• Both the early and late manifestations of schistosomiasis are immunologically mediated.
• The major pathology of infection occurs 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 be carried by the bloodstream to other organs, most commonly the liver and less often the lungs and central nervous system.
• 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) due to pre-sinusoidal 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.

Associated conditions

• Recurrent Salmonella infections can occur in patients with schistosomiasis. Salmonella bacteria live in symbiosis within the parasite's integument, allowing them to evade eradication by many antibiotics.
• Chloramphenicol-sensitive Salmonella entericaserotype Typhi has been shown to be refractory to chloramphenicol therapy in patients coinfected with Schistosoma.
• Patients coinfected with hepatitis C virus and Schistosoma have increased progression of liver fibrosis compared to patients with hepatitis C alone.
• Urogenital schistosomiasis is a co-factor in the spread and progression of human immunodeficiency virus (HIV) infection and other sexually transmitted infections, especially in women, and also is associated with female infertility.

Microscopic Findings

• Adult worms are about 10 mm long

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