Schistosomiasis - Causes and Pathogenesis

Causes of Schistosomiasis

Schistosomiasis is caused by schistosomes, which belong to the phylum Plathelminthes, class Trematoda, family Schistosomatidae. Five species of schistosomes: Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalation and Schistosoma mekongi - are the causative agents of helminthiasis in humans. Schistosomes differ from all other representatives of the class Trematoda in that they are separate sexes and have sexual dimorphism. The body of sexually mature schistosomes is elongated, cylindrical, covered with a cuticle. There are suckers located close to each other - oral and abdominal. The body of the female is longer and thinner than that of the male. Along the body of the male there is a special copulatory groove (gynecoform canal), in which the male holds the female. The male and female are almost constantly together. The outer surface of the male is covered with spines or tubercles, the female has spines only on the anterior end of the body, the rest of the surface is smooth. Schistosomes live in the smallest venous vessels of the final host - humans and some animals, feed on blood through the digestive tube and partially adsorb the liquid part through the cuticle. In the uterus of S. haematobium there are no more than 20-30 eggs at a time. The female S. japonicum has the greatest reproductive capacity, laying from 500 to 3500 eggs per day. The larva in the schistosome egg, laid in the small veins of the host, matures in the tissues for 5-12 days. Migration of eggs from blood vessels occurs due to the presence of a spine, proteolytic activity of the larval secretion, and also under the influence of contractile movements of the muscular layer of the vessel walls, intestines and urinary bladder. Eggs enter the environment with urine (S. haematobium) or feces (S. mansoni, etc.). Further development occurs in water, where the egg shell is destroyed; miracidia emerge from them. The development cycle of schistosomes is associated with a change of host. Their intermediate host is freshwater mollusks, in whose body miracidia undergo a complex process of formation of cercariae (generations of invasive larvae capable of penetrating the body of the final host) over 4-6 weeks. After penetrating the human body, the larvae lose their tail appendage. The lifespan of miracidium is up to 24 hours, cercariae - up to 2-3 days. sexually mature schistosomes are 5-8 years old.

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Pathogenesis of schistosomiasis

Schistosomes do not reproduce in the body of the final host, so their number can increase only due to reinvasion. The pathogenic effect of parasites begins from the moment of penetration of cercariae through the skin. Secretions of the glands of migrating larvae, decay products of some of them are strong antigens that cause reactions of GNT and DTH. Clinically, this is manifested by a transient papular itchy rash and is known as cercarial hepatitis (swimmer's scabies). Larvae that have lost their tail appendage (schistosomula), penetrating into peripheral lymphatic and venous vessels, migrate and enter the right sections of the heart, the lungs, then reach the vessels of the liver, where they develop and mature into adults. Mature females and males mate and migrate to vessels of permanent localization - to the mesenteric vein system (intestinal varieties of schistosomes) or the urinary bladder and small pelvis - S. haematobium. Four to six weeks after infection, during the period of completion of schistosomula migration and the beginning of egg laying by mature females, allergic reactions sharply increase, which underlie the acute ("toxemic") phase of the disease, also called Katayama disease. In terms of the nature of clinical manifestations, this phase resembles serum sickness. It is more often observed during S. japonicum invasion, much less often - after infection with S. mansoni and other types of the pathogen.

Of the total number of schistosome eggs laid by females in small venous vessels feeding the intestinal or bladder walls, no more than 50% enter the environment: the rest are retained in the tissues of the affected organs or are carried by the bloodstream to other organs. The basis of pathological changes in the chronic period of the disease is a set of inflammatory changes around the schistosome eggs (the formation of a specific cellular infiltrate - granuloma, followed by fibrosis and calcification). T-lymphocytes, macrophages, eosinophils participate in the formation of granuloma around the eggs. Initially, the process is reversible, but with the deposition of collagen and the development of fibrosis, morphological changes in the tissues become irreversible. Granulomatous reaction and fibrosis cause disturbances in the blood supply in the organ wall, which causes secondary dystrophic changes in the mucous membrane, ulceration. Hyperplasia and metaplasia of the mucosal epithelium may also result from constant and prolonged irritation of tissues by parasite eggs, waste products of the larvae in them, and their decay. In the urinary bladder, the submucosal layer is the main site of lesions associated with the deposition of S. haematobium eggs in 85% of cases: the muscular layer is affected less frequently. In the ureters, on the contrary, the deeply located layers are affected more often. Since the causative agent of intestinal schistosomiasis S. mansoni is localized in the veins of the hemorrhoidal plexus and in the inferior mesenteric vein, and the eggs deposited there also accumulate, the main pathological changes develop mainly in the distal parts of the colon. S. japonicum, unlike other species, lays not single eggs, but groups, and they are subject to calcification more quickly. In all forms of schistosomiasis, eggs are also carried to other organs, primarily the liver and lungs. The most severe liver damage, leading to cirrhosis, develops with Japanese and intestinal schistosomiasis (with S. mansoni invasion - Simmers' tubular-indurative fibrosis). When eggs enter the lungs, they lead to obstructive-destructive arteritis, arteriovenous anastomoses - as a result, hypertension of the pulmonary circulation develops, which causes the formation of a "pulmonary" heart. It is possible for schistosome eggs to be carried (more often with S. japonicum invasion) to the spinal cord and brain.

Symptoms of schistosomiasis largely depend on the intensity of the invasion, i.e. ultimately on the number of eggs laid by female parasites and their accumulation in the affected tissues. At the same time, the size of granulomas around the eggs, the severity of fibrosis in the tissues of organs depend on the characteristics of the host's immune response, in particular on the level of production of antibodies, immune complexes, the activity of T-lymphocyte suppressors, macrophages. Genetic factors are of certain importance, which, for example, affect the development of tubular-indurative fibrosis in the liver. Mature schistosomes are resistant to the effects of immune factors. An important role in this is played by the phenomenon of antigen mimicry, which is characteristic of these parasites. Schistosomiasis can be a factor in carcinogenesis, as evidenced by the fact that tumors of the genitourinary system and colon are relatively common in the foci of this helminthiasis. Tumor growth in schistosomiasis is explained by the development of fibrosis in organs, epithelial metaplasia, immunosuppression, as well as the synergism of the action of schistosomes, exogenous and endogenous carcinogens.