Materiały źródłowe

• #1 Schistosomiasis (Bilharzia): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/228392-overview

  Schistosomiasis is due to immunologic reactions to Schistosoma eggs trapped in tissues. Antigens released from the egg stimulate a granulomatous reaction involving T cells, macrophages, and eosinophils that results in clinical disease. Symptoms and signs depend on the number and location of eggs trapped in the tissues. Initially, the inflammatory reaction is readily reversible. In the latter stages of the disease, the pathology is associated with collagen deposition and fibrosis, resulting in organ damage that may be only partially reversible. […] The pathology of chronic schistosomiasis, which is far more common than the acute form of the infection, results from egg-induced immune response, granuloma formation, and associated fibrotic changes. Although cercarial and adult worms are minimally immunogenic, schistosomal eggs are highly immunogenic and induce vigorous circulating and local immune responses.

• #1 Schistosomiasis (Bilharzia): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/228392-overview

  Egg retention and granuloma formation in the bowel wall (usually S mansoni or S japonicum) may cause bloody diarrhea, cramping, and, eventually, inflammatory colonic polyposis. […] Eggs can penetrate the bowel adjacent to mesenteric vessels where adult worms are residing. Unshed eggs, which are swept back to the portal circulation, lodge there and induce granulomatous reactions in the portal tracts. […] Heavy infestations are more likely to produce hepatic disease. Eventually, severe periportal fibrosis in a characteristic pipestem pattern (Symmers pipestem fibrosis) may occur. […] Egg retention and granuloma formation in the urinary tract (S haematobium) can lead to hematuria, dysuria, bladder polyps and ulcers, and even obstructive uropathies. […] Ectopic egg deposition can lead to additional clinical syndromes, including involvement of skin, lungs, brain, muscles, adrenal glands, genitalia, and eyes. CNS involvement can result in transverse myelitis and/or cerebral disease. Local tissue invasion of eggs brings about the release of toxins and enzymes and provokes a TH-2 mediated immune response.

• #2

  https://www.who.int/news-room/fact-sheets/detail/schistosomiasis

  Schistosomiasis is an acute and chronic disease caused by parasitic worms. […] People become infected when larval forms of the parasite released by freshwater snails penetrate the skin during contact with infested water. […] In the body, the larvae develop into adult schistosomes. Adult worms live in the blood vessels where the females release eggs. Some of the eggs are passed out of the body in the faeces or urine to continue the parasites lifecycle. Others become trapped in body tissues, causing immune reactions and progressive damage to organs. […] Symptoms of schistosomiasis are caused mainly by the bodys reaction to the worms eggs. […] Chronic schistosomiasis may affect peoples ability to work and in some cases can result in death. […] The economic and health effects of schistosomiasis are considerable and the disease disables more than it kills. […] Praziquantel is the recommended treatment against all forms of schistosomiasis. It is effective, safe and low-cost. Even though re-infection may occur after treatment, the risk of developing severe disease is diminished and even reversed when treatment is initiated and repeated in childhood.

• #3 CDC – DPDx – Schistosomiasis Infection

  https://www.cdc.gov/dpdx/schistosomiasis/index.html

  Symptoms of schistosomiasis are not caused by the worms themselves but by the body’s reaction to the eggs. […] Pathology associated with S. mansoni and S. japonicum schistosomiasis includes various hepatic complications from inflammation and granulomatous reactions, and occasional embolic egg granulomas in brain or spinal cord. […] Pathology of S. haematobium schistosomiasis includes hematuria, scarring, calcification, squamous cell carcinoma, and occasional embolic egg granulomas in brain or spinal cord.

• #4 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11097794/

  Schistosomiasis can manifest as either an acute or chronic condition. […] The acute form includes cercarial dermatitis and Katayama fever or syndrome. […] Symptoms typically improve within 2 to 10 weeks, but in severe cases, patients may experience persistent symptoms such as breathlessness, weight loss, and hepatomegaly. […] In endemic areas, most infections progress directly to the chronic phase of the disease due to repeated exposure, and acute schistosomiasis is rare. […] Symptoms arise from the inflammatory responses generated against the eggs. […] The severity of the disease is directly related to the number of eggs infiltrating the tissues. […] Chronic schistosomiasis causes bladder cancer by inducing inflammation of the bladder wall. […] Eggs that are not excreted trigger a strong inflammatory response, leading to the formation of granulomas.

• #4 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11097794/

  Initially, a Th-1-like response is predominant. […] This response is subsequently reduced and gives way to a Th2-like response as the schistosome matures. […] Around 12 to 16 weeks after infection, granulomas start to form, leading to a gradual decrease in the Th2-like response. […] Indirect diagnostic methods, such as immunochromatography, ELISA, Western blot, and indirect haemagglutination, can be used to differentiate between active and past infections.

• #4 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11097794/

  The observed association between Schistosoma infection and infertility in both men and women may be explained by chronic inflammation, scar tissue formation, and severe granulomatous reactions. […] In women, schistosomiasis can cause progressive fibrosis in the ovaries and fallopian tubes, leading to tubal occlusion and affecting the reproductive system. […] In contrast, male infertility is usually caused by infections of the prostate, testes, and seminal vesicles, which are promoted by schistosomiasis. […] S. haematobium infection may increase the risk of HIV infection, especially in women. […] The fragile epithelium, which is prone to frequent bleeding, can facilitate HIV transmission. […] The immune response in individuals infected with Schistosoma spp. varies depending on the stage of infection.

• #5 Schistosomiasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554434/

  Schistosoma haematobium eggs are excreted from the human host via urine into freshwater. Each egg contains a mature ciliated form, known as a miracidium. Upon contacting freshwater, the egg hatches and releases the miracidium, which can penetrate the soft tissue of its intermediate host, the Bulinus snail. […] Adult worms of the species S. haematobium live within the urogenital venules, where they primarily digest erythrocytes. The involvement of the urogenital organs varies markedly and correlates with vascularity; with the bladder, lower ureters, urethra, seminal vesicles, uterus, vagina, and cervix most commonly affected. Unlike other schistosomes that live within the mesenteric venules and release their eggs into the hosts intestines, S. haematobium releases its eggs into the urinary tract. Therefore their eggs are excreted via the hosts urine.

• #5 Schistosomiasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554434/

  Up to half of the thousands of eggs that are released throughout the adult trematodes average lifespan of 3 to 7 years (ranging from 20 to 290 eggs per day in S. haematobium) are not excreted, but instead, become lodged in the urogenital system. This is the primary mechanism of chronic sequelae from infection as the eggs induce a granulomatous host response and subsequent tissue inflammation.

• #6 Schistosomiasis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/trematodes-flukes/schistosomiasis

  Adult Schistosoma worms live and copulate within venules of the mesentery (typically S. mekongi, S. intercalatum, S. japonicum and S. mansoni) or bladder (typically S. haematobium). […] Some eggs penetrate the intestinal or bladder mucosa and are passed in stool or urine; other eggs remain within the host organ or are transported through the portal system to the liver and occasionally to other sites (eg, lungs, central nervous system, spinal cord). Excreted eggs hatch in freshwater, releasing miracidia (first larval stage), which enter snails. After multiplication, thousands of free-swimming, forked-tailed cercariae are released. […] Cercariae penetrate human skin within a few minutes after exposure. When they penetrate the skin, they lose their forked tail and transform into schistosomula, which travel through the bloodstream to the liver, where they mature into adults. The adults then migrate to their ultimate home in the intestinal veins or the venous plexus of the genitourinary tract.

• #6 Schistosomiasis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/trematodes-flukes/schistosomiasis

  Eggs appear in stool or urine 1 to 3 months after cercarial penetration. […] Chronic schistosomiasis results primarily from granulomatous host responses to eggs retained in tissues. […] Granulomatous reactions to eggs of S. mansoni, S. japonicum, S. mekongi, and S. intercalatum in the liver usually do not compromise liver function, but they may cause fibrosis and cirrhosis, which can lead to portal hypertension, resulting in splenomegaly, and esophageal varices. […] Eggs in the lungs may produce granulomas and focal obliterative arteritis, which may ultimately result in pulmonary hypertension and cor pulmonale. […] Bladder involvement with S. haematobium produces ulcerations in the bladder wall that may cause dysuria, hematuria, and urinary frequency. Over time, chronic cystitis develops. […] Chronic schistosomiasis results primarily from granulomatous host responses to eggs retained in tissues. […] Ova in the liver trigger a granulomatous reaction that can lead to fibrosis and portal hypertension, resulting in splenomegaly, esophageal varices, and hematemesis.

• #7 How a Schistosoma Parasite Prevented a War

  https://asm.org/articles/2021/october/how-a-schistosoma-parasite-prevented-a-war

  Upon sensing specific chemicals from the human skin, like fatty acids and L-arginine, cercariae migrate toward and penetrate the skin by degrading host proteins, including elastin, keratin and collagen, that serve as barriers to invasion. […] During penetration, cercariae shed their forked tails to form schistosomulae, which subsequently migrate via blood circulation to different parts of the body. […] Once there, the parasites feed on blood while they inhabit their hosts blood vessels. […] As the parasites feed, they also mature into separate-sex adults. […] It is estimated that an adult male S. mansoni can ingest ~39,000 erythrocytes per hour, while the female can ingest ~10-fold higher, as it requires additional energy for egg production. […] The male-female pair continue their adventures from the liver to their final destination where they lay their eggs.

• #8 Schistosomiasis – Wikipedia

  https://en.wikipedia.org/wiki/Schistosomiasis

  The eggs make their way through the tissues to the intestinal or bladder lumen with proteolytic enzymes, however, a large number of eggs are unable to finish their journey and remained stuck within the tissues where they can elicit an immune response. […] The granulomatous response is a cellular immune response mediated by CD4+ T cells, neutrophils, eosinophils, lymphocytes, macrophages, and monocytes, and this chronic inflammatory response elicited by the eggs can cause fibrosis, tissue destruction, and granuloma nodules that disrupt the functions of the organs involved. […] The specific clinical symptoms and severity of the disease this causes depends on the type of schistosome infection, duration of infection, number of eggs, and the organ at which the eggs are deposited.

• #9 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis in: European Journal of Microbiology and Immunology Volume 14 Issue 2 (2024)

  https://akjournals.com/view/journals/1886/14/2/article-p86.xml

  In endemic areas, most infections progress directly to the chronic phase of the disease due to repeated exposure, and acute schistosomiasis is rare. This form of schistosomiasis is characterised by the presence of adult worms producing large numbers of eggs. In contrast to adult worms, schistosome eggs lack surface antigens and are therefore susceptible to the host’s immune system. Symptoms arise from the inflammatory responses generated against the eggs. Soluble glycoproteins secreted by schistosome eggs react with CD4+ and T-helper-2 (Th-2) lymphocytes. The eggs are shed into the bladder lumen and form granulomas at sites of maximum infestation, leading to fibrotic lesions in the host tissue. Treatment with drugs that kill the adult forms can partially reverse infection in patients with active schistosomiasis. As the disease progresses to a chronic state, there is a progressive decrease in the proliferative responses of the lymphocytes induced by the soluble egg antigens. Due to its chronic nature, bilharzia is a significant public health problem. The severity of the disease is directly related to the number of eggs infiltrating the tissues. Intestinal and urogenital schistosomiasis are distinguished by the species involved.

• #9 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis in: European Journal of Microbiology and Immunology Volume 14 Issue 2 (2024)

  https://akjournals.com/view/journals/1886/14/2/article-p86.xml

  Schistosomiasis can manifest as either an acute or chronic condition. The acute form includes cercarial dermatitis and Katayama fever or syndrome. The latter is named after the Katayama District of Hiroshima prefecture in Japan, where the first human case of S. japonicum was reported in 1904. Cercarial dermatitis, which is a maculopapular skin rash, appears at the site of cercarial entry and typically occurs within 27 days of infection. The condition is usually caused by a hypersensitive immune response to the parasite and typically resolves within 15 days. Katayama syndrome is characterised by fever, abdominal pain, diarrhoea, diffuse myalgia, haematuria (in individuals infected with S. haematobium), asthma, non-productive cough, pulmonary infiltrates, and marked eosinophilia. This disease is commonly observed in individuals who have been infected while travelling to endemic areas or living in areas with high transmission rates. These symptoms are usually caused by systemic hypersensitivity to antigens released by schistosomes or eggs. The acute form of the disease may develop in non-immune individuals several weeks or months after exposure. Acute schistosomiasis is a condition that is not well understood and is often not diagnosed. Symptoms typically improve within 2-10 weeks, but in severe cases, patients may experience persistent symptoms such as breathlessness, weight loss, and hepatomegaly.

• #9 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis in: European Journal of Microbiology and Immunology Volume 14 Issue 2 (2024)

  https://akjournals.com/view/journals/1886/14/2/article-p86.xml

  Intestinal infection caused by S. mansoni, S. japonicum, S. intercalatum and S. mekongi begins with bloody diarrhoea and sideropenic anaemia due to mucosal ulceration. This condition can progress to a more severe state, which is characterized by portal hypertension, polyposis, microabscess formation, organomegaly, and hepatic fibrosis. In some cases, this may eventually lead to cirrhosis. Urogenital schistosomiasis is characterised by the presence of numerous calcified eggs in the bladder wall and genital organs, resulting in polyposis, hyperplasia and severe ulceration that can lead to haemorrhage. In advanced stages of the disease, the bladder may calcify, leading to urethral obstruction, hydronephrosis and ultimately renal failure. Women with genital schistosomiasis experience pain and bleeding during sexual intercourse, while men have elevated levels of pro-inflammatory cytokines and leukocytes in the seminal fluid. Possible factors contributing to the schistosomal carcinogenic process include inflammatory gene damage, -glucuronidase and nitrosamines. Although S. haematobium lesions may increase the exposure of the bladder epithelium to mutagenic substrates such as tobacco, it is important to note that this is still under investigation. In addition, female genital schistosomiasis has been found to increase the risk of human immunodeficiency virus (HIV) transmission.

• #9 Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis in: European Journal of Microbiology and Immunology Volume 14 Issue 2 (2024)

  https://akjournals.com/view/journals/1886/14/2/article-p86.xml

  IARC has classified S. haematobium as a class 1 carcinogen due to its association with squamous cell carcinoma (SCC), a form of bladder cancer. Chronic schistosomiasis causes bladder cancer by inducing inflammation of the bladder wall. Eggs that are not excreted trigger a strong inflammatory response, leading to the formation of granulomas. Bladder fibrosis may result in bacterial infection, which can convert nitrite and dietary nitrates into nitrosamines. Nitrosamines are carcinogenic and affect metaplastic squamous epithelium, leading to the development of SCC. Numerous epidemiological studies have demonstrated that the prevalence of cancer decreases in areas where schistosomiasis control interventions are implemented and infection prevalence decreases. As bladder cancer remains a common problem in regions where schistosomiasis is endemic, it is advisable to monitor individuals testing positive for schistosomiasis for prognostic indicators of bladder cancer. The observed association between Schistosoma infection and infertility in both men and women may be explained by chronic inflammation, scar tissue formation, and severe granulomatous reactions. In women, schistosomiasis can cause progressive fibrosis in the ovaries and fallopian tubes, leading to tubal occlusion and affecting the reproductive system. In contrast, male infertility is usually caused by infections of the prostate, testes, and seminal vesicles, which are promoted by schistosomiasis. S. haematobium infection may increase the risk of HIV infection, especially in women. Female genital schistosomiasis can cause significant damage to the cervix and vaginal epithelium, resulting in inflammation, ulceration, and trauma due to the calcification of uncleared eggs. The fragile epithelium, which is prone to frequent bleeding, can facilitate HIV transmission. Observational studies have shown that schistosomiasis may modify the immune response and potentially facilitate HIV infection. In individuals infected with schistosomes, there is a decrease in the Th-1 immune response and an increase in CD4+ receptors and chemokines, which are co-receptors used by the virus to infect cells. Therefore, praziquantel therapy is considered critical in regions with a high prevalence of HIV. Studies suggest that praziquantel may be effective in reducing HIV viral load.

• #10 Schistosoma antigens: A future clinical magic bullet for autoimmune diseases? | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2024/01/parasite240121/parasite240121.html

  It is acknowledged that schistosomiasis is not caused by the worms themselves but by the body’s reaction to the eggs. Trapped eggs continuously release soluble egg antigen (SEA). The body’s initial immune response against SEA involves local secretion of Th1 cytokines such as TNF- and IL-2, leading to monocyte, neutrophil, and lymphocyte infiltration. The influx of these cells results in phagocytosis and granuloma formation. Omega-1, a glycosylated T2 ribonuclease (RNase) from one of the many components of SEA, activates dendritic cells (DCs), which promotes a shift towards a Th2 immune response. This shift from a Th1- to Th2-skewed response significantly contributes to liver fibrosis in schistosomiasis, characterized by a decrease in IFN- (Th1 cytokine) and an increase in IL-4, IL-5, and IL-13 (Th2 cytokines) profiles. IFN- suppresses hepatic stellate cell (HSC) activation, while IL-4 and IL-13 induce its activation. Together, the imbalance of these cytokines gives rise to the progression of liver fibrosis.

• #11 SciELO Brazil – Experimental models of Schistosoma mansoni infection Experimental models of Schistosoma mansoni infection

  https://www.scielo.br/j/mioc/a/yFMPnbsbJm5d3Kp5y8gwGrD/?lang=en

  After the 8th wk of infection there is downmodulation of the immune reaction and granulomas around recently deposited eggs become progressively smaller. […] The balance being determined by the variable ability of the host to kill worms, to inhibit worm fecundity and to destroy eggs and repair tissue damage. […] The intense blood and tissue eosinophilia and high IgE antibody levels associated with schistosome infections suggest a Th2-type reaction. […] Treatment of injected or infected mice with IFN-g results in decreased granuloma size and hepatic fibrosis while chronically infected (immunologically downregulated) mice treated with IL-4 make larger granulomas than do untreated animals. […] The earliest hepatic granulomas form in a Th1 environment with downregulation of Th1 and upregulation of Th2 responses 6 wk after infection.

• #11 SciELO Brazil – Experimental models of Schistosoma mansoni infection Experimental models of Schistosoma mansoni infection

  https://www.scielo.br/j/mioc/a/yFMPnbsbJm5d3Kp5y8gwGrD/?lang=en

  Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. […] Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver. […] We concentrate here on the anatomic and parasitologic features of various models and on the use of models to address mechanisms of pathogenesis. […] Most pathology in schistosome infected animals is attributed to the host’s reaction to the eggs which is maximal by the 8th wk of infection. […] Granulomas are composed principally of macrophages, eosinophils and lymphocytes with the proportion of cells varying in different organs.

• #11 SciELO Brazil – Experimental models of Schistosoma mansoni infection Experimental models of Schistosoma mansoni infection

  https://www.scielo.br/j/mioc/a/yFMPnbsbJm5d3Kp5y8gwGrD/?lang=en

  The regulation of fibrosis is often independent of the regulation of granuloma size, i.e. larger granulomas are not always associated with greater hepatic fibrosis. […] Hepatic fibrosis in schistosome infected mice is clearly linked to IL-13 and the Th2 response, although fibrosis also clearly sometimes occurs around granulomas formed in the Th1 milieu.

• #12 Urogenital Schistosomiasis—History, Pathogenesis, and Bladder Cancer

  https://www.mdpi.com/2077-0383/10/2/205

  Importantly, bladder cancer is a frequent and dire complication of chronic UGS. The incidence of SCC associated to UGS is estimated in 3–4 cases per 100,000. Untreated patients often develop schistosome-related bladder cancer. The tumors are found in a relatively younger age group, commonly present as well differentiated SCC locally advanced and have poor overall survival. The severity and frequency of UGS sequelae are related to the intensity and duration of the infection. Genetic alterations, chromosomal aberrations, and cytological changes have been described in carcinomas associated with UGS. N-nitroso compounds have been implicated as tentative etiologic agents in the process of bladder carcinogenesis. Elevated levels of DNA alkylation damage in carcinomas associated with UGS and a high frequency of G to A transitions in the H-ras gene and in the CpG sequences of the p53 tumor suppressor gene have also been reported. These outcomes indicate that UGS-associated SCC arises through a progressive accumulation of genetic changes in epithelial cells. Positive correlation between UGS and increased the levels of oxidative stress accompanied by continuous DNA damage and repair in urothelial carcinomas has been observed by several groups.

• #12 Urogenital Schistosomiasis—History, Pathogenesis, and Bladder Cancer

  https://www.mdpi.com/2077-0383/10/2/205

  An oestrogen-DNA adduct mediated pathway in UGS-associated bladder cancer has been postulated. S. haematobium eggs and adult worm lysates stimulate cellular proliferation, interfere with apoptosis, increase oxidative stress, and induce a genotoxicity on HCV-29 cells, derived from urothelial cells. In addition, we have identified and characterized oestrogen-like metabolites in the lysates and secretions of S. haematobium worms and eggs, and in sera and urine of UGS cases. […] The expression of p53 in urothelial carcinomas is intense and involves both cell clones of malignant cells as well as adjacent, apparently normal urothelial cells of the mucosa. What is the role of p53 in UGS-associated bladder cancer? The studies covering this issue showed that the tumor suppressor protein p53 was overexpressed in bladder urothelial mucosa in individuals with UGS or SCC-associated to UGS.

• #13 Schistosomiasis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Schistosomiasis_pathophysiology

  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, 6, tumor necrosis factor-, and circulating immune complexes participates in the pathogenesis of the acute phase of the disease. […] Both the early and late manifestations of schistosomiasis are immunologically mediated. […] The pathogenesis of acute human schistosomiasis is 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-, and by circulating immune complexes participates in the pathogenesis of the acute phase of the disease.

• #14 Schistosomiasis (bilharzia)

  https://www.nhs.uk/conditions/schistosomiasis/

  You often don’t have any symptoms when you first become infected with schistosomiasis, but the parasite can remain in the body for many years and cause damage to organs such as the bladder, kidneys and liver. […] Without treatment, the worms can keep laying eggs for several years. […] Some people with schistosomiasis, regardless of whether they had any initial symptoms or not, eventually develop more serious problems in parts of the body the eggs have travelled to. This is known as chronic schistosomiasis. […] Without treatment, affected organs can become permanently damaged.

• #15 Urinary schistosomiasis and the associated bladder cancer: update | Journal of the Egyptian National Cancer Institute | Full Text

  https://jenci.springeropen.com/articles/10.1186/s43046-020-00055-z

  Schistosoma haematobium (SH) infecting the urinary bladder was considered by the IARC as group 1 definitive biological carcinogenic agent. Several carcinogenic pathways have been postulated but the exact mechanism(s) are not defined yet. […] The continuous deposition and retention of eggs in the bladder wall with subsequent traversal of the eggs through the urothelium results in tissue damage. The H-IPSE released from the eggs counteracts the urothelial damage by increasing cell proliferation leading to the development of bladder cancer. […] The most common genetic change is the loss of heterozygosity (LOH) on chromosomes 9p and 9q, regardless of tumor grade or stage. There was no difference demarcating SA-BC from Schistosoma-non-associated BC (SNA-BC) in this loss of heterozygosity. […] Tumor suppressor gene TP53 dysfunction leads to tumor cell apoptosis and increased accumulation of p53 protein that correlates with tumor histological grade.

• #16 Intestinal Schistosomiasis Caused by Schistosoma japonicum: A Literature Review

  https://www.infectiologyjournal.com/articles/intestinal-schistosomiasis-caused-by-emschistosoma-japonicumem-a-literature-review.html

  The physiopathology of chronic schistosomiasis results from the eggs lodging, inducing immune response, granuloma formation, fibrotic changes, damaging the organs and tissues of the human host. Adult worms absorb host proteins so if not attacked by the immune system, they can live coated with host antigens for years. The shed eggs penetrate the bowel adjacent to mesenteric vessels, whereas unshed eggs go back to portal circulation, lodge and induce granulomatous reaction. In the liver the chronic progression causes periportal fibrosis, called Symmers piperstem fibrosis, if left untreated it will lead to portal hypertension with all the cirrhosis complications.

• #17 Schistosomiasis. Bilharzia

  https://dermnetnz.org/topics/schistosomiasis

  Schistosomiasis is passed on by infected people urinating or defaecating into freshwater. Schistosoma eggs hatch in the water and develop inside particular snail species. These snails release thousands of larvae back into the water. Larvae can penetrate unbroken human skin when humans enter the water to bathe or swim. Within a few weeks, worms grow inside blood vessels and produce eggs. Some of these eggs migrate to the bladder or bowel and are released in the urine or faeces. Other eggs become trapped in body tissues, producing an immune reaction. […] Chronic features are due to an intense immune response against the schistosomal eggs, with granuloma (ball-like collection of immune cells) formation and scarring. […] Granuloma formation in the liver can cause portal hypertension (raised blood pressure within the liver). This can lead to an enlarged spleen, ascites (fluid in the abdominal cavity), and oesophageal varices (bleeding in the oesophagus). Collateral blood vessels can form, which redirect blood flow from the liver to the lungs and allow egg migration. Granuloma formation in the lungs causes pulmonary hypertension (raised blood pressure within the lungs) and cor pulmonale (heart failure). […] Eggs can also be deposited and produce complications in almost any organ, such as lungs, brain, spinal cord, muscles, genitals, and eyes.

• #18 SciELO Brazil – Neuroschistosomiasis due to Schistosoma mansoni: a review of pathogenesis, clinical syndromes and diagnostic approaches Neuroschistosomiasis due to Schistosoma mansoni: a review of pathogenesis, clinical syndromes and diagnostic approache

  https://www.scielo.br/j/rimtsp/a/J3phvZdWh7WqVXsCXvm9Dzz/?lang=en

  Neuroschistosomiasis (NS) is the second most common form of presentation of infection by the trematode, Schistosoma mansoni. Granulomatous inflammatory reaction occurs as a result of schistosome eggs being transmitted to spinal cord or brain via the vascular system, or by inadvertent adult worm migration to these organs. […] The granulomatous reaction of the host to the presence of the ova is the major factor in the pathogenesis of schistosomiasis. Granulomas are strictly mediated by CD4+ T helper (Th) cells specific for egg antigens; the best studied and most abundant egg component is the Sm-p40 antigen. In addition to it, Sm-PEPCK and Sm-TPx-1 have been described and Sm-p40 and Sm-PEPCK have demonstrated immunogenicity in humans. […] The most common site of clinically significant NS is the spinal cord. The prominent lateral spine of S. mansoni’s egg probably hampers the egg from reaching the brain. The pathological findings include a granulomatous intramedullary mass in the caudal spinal cord, radicular involvement with granulomatous changes surrounding the conus medullaris and nerve roots of the cauda equina, necrotic exudative granulomas and haemorrhage, and asymptomatic deposition of ova in the spinal cord. […] In summary, it is believed that the deposition of S. mansoni ova in the brain is more common in the hepatosplenic form of schistosomiasis mansoni, although the clinical manifestations are quite rare in this situation and the deposition of S. mansoni ova may occur in any form of the disease.

• #19 Advances in the study of the interaction between schistosome infections and the host’s intestinal microorganisms | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06245-1

  Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis. […] The relationship between schistosome infections and host intestinal microbiota is a vigorously investigated area of research, and it has the potential to provide new insights into the course of infection of the disease. […] While worm eggs and host immune response are the two most important factors driving granuloma formation, recent studies have identified gut microbiota as a third factor. […] Recent evidence suggests that the host gut microbiota plays a crucial role in the interaction between schistosomes and host immunity. […] Schistosome infections lead to granuloma and fibrotic lesions in the intestine, which is also the site of survival for the intestinal microbiota.

• #19 Advances in the study of the interaction between schistosome infections and the host’s intestinal microorganisms | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06245-1

  Schistosomes manipulate the innate and adaptive immune system of the host for their own benefit. […] The adult schistosome worms appear to alter their interaction with the blood microbiome, contributing to the interaction between the host and schistosomes after parasitism. […] Schistosome infection induces ecological dysbiosis of the gut microbiota in animals and humans, as well as acute or chronic liver injury, such as advanced schistosomiasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma, the most important clinical complication of which is periportal liver fibrosis, and there is growing evidence of significant changes in the gut microbiota profile in liver disease induced by schistosome infections. […] This further illustrates the association between schistosomiasis gut microbiota and liver injury.

• #19 Advances in the study of the interaction between schistosome infections and the host’s intestinal microorganisms | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06245-1

  The gut flora play an important role in schistosomiasis-mediated disease through the pathway of the gut-liver axis, based on the model of the gut-liver axis in other liver diseases and the interaction between the liver, intestine, and microbiota after schistosome infections. […] Schistosomiasis-induced liver injury is thought to be marked by reduced levels of acetate, butyrate, and propionate. […] A reduction in butyrate is associated with a weakening of intestinal tight junctions and, therefore, permeability. […] Given the limitations of PZQ, many groups have been working to evaluate new therapeutic alternatives for schistosomiasis. […] Probiotic therapy stands out from traditional approaches. […] Modulation of the gut microbiota through the use of probiotics is an emerging and promising treatment for gut-liver axis dysfunction and schistosomiasis infection.

• #19 Advances in the study of the interaction between schistosome infections and the host’s intestinal microorganisms | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06245-1

  Probiotics are defined by the Food and Agriculture Organization of the United Nations (FAO)/WHO as live microorganisms that are beneficial to host health when administered in adequate amounts. […] The findings from these experiments suggest that certain strains of Lactobacillus and Bacillus genera have the potential to serve as probiotics for the treatment of schistosomiasis. […] The mode of action of these probiotics can be strain-specific or a combination of different mechanisms. […] Probiotics exhibit antioxidant properties through scavenging of reactive oxygen species (ROS) and activation of superoxide dismutase (SOD) and catalase (CAT) to reduce oxidative stress. […] Therefore, more in-depth studies are needed, including extended clinical studies, and using more defined protocols with specific probiotics and experimental models. […] Integrating the knowledge gained in these two research areas will make it possible to fully utilize the potential of microbial-based interventions for schistosomiasis and translate them into new and reliable strategies for the management and control of schistosomiasis.

• #20 Therapeutic challenges of schistosomiasis: mechanisms of action and current limitations | springermedizin.de

  https://www.springermedizin.de/therapeutic-challenges-of-schistosomiasis-mechanisms-of-action-a/50597276

  Schistosomiasis, a parasitic disease caused by Schistosoma species, affects millions of people worldwide. […] This review explores the therapeutic challenges of schistosomiasis, focusing on the mechanisms of action of current treatments and their limitations. Praziquantel, the standard therapy, induces lesions and muscle contractions in the parasites, thereby facilitating their clearance by the host immune system. However, the biological complexity of schistosomes and their ability to modulate the immune response present hurdles to sustained treatment efficacy. […] Challenges include the emergence of resistance, adverse side effects, and inconsistent cure rates. Additionally, the remarkable longevity of schistosomes spanning years to decades complicates the evaluation of treatment outcomes. […] This paper underscores the importance of understanding schistosome biology and advocates for comprehensive strategies to improve the management and control of this debilitating parasitic infection.

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