in the mesenteric circulation, where they begin egg production (>32 days). the s. mansoni parasites are found predominantly in the small inferior mesenteric blood vessels surrounding the large intestine and caecal region of the host. each female lays approximately 300 eggs a day (one egg every 4.8 minutes), which are deposited on the endothelial lining of the venous capillary walls. most of the body mass of female schistosomes is devoted to the reproductive system. the female converts the equivalent of almost her own body dry weight into eggs each day. the eggs move into the lumen of the host's intestines and are released into the environment with the faeces. genome schistosoma mansoni has 8 pairs of chromosomes (2n = 16)—7 autosomal pairs and 1 sex pair. the female schistosome is heterogametic, or zw, and the male is homogametic, or zz. sex is determined in the zygote by a chromosomal mechanism. the genome is approximately 270 mb with a gc content of 34%, 4–8% highly repetitive sequence, 32–36% middle repetitive sequence and 60% single copy sequence. numerous highly or moderately repetitive elements are identified, with at least 30% repetitive dna. chromosomes range in size from 18 to 73 mb and can be distinguished by size, shape, and c banding. in 2000, the first bac library of schistosome was constructed. in june 2003, a ~5x whole genome shotgun sequencing project was initiated at the sanger institute. also in 2003, 163,000 ests (expressed sequence tags) were generated (by a consortium headed by the university of são paulo) from six selected developmental stages of this parasite, resulting in 31,000 assembled sequences and an estimated 92% of the 14,000-gene complement. in 2009 the genomes of both s. mansoni and s. japonicum were published, with each describing 11,809 and 13,469 genes, respectively. s. mansoni genome has increased protease families and deficiencies in lipid anabolism; which are attributed to its parasitic adaptation. proteases included the invadolysin (host penetration) and cathepsin (blood-feeding) gene families. in 2012, an improved version of the s. mansoni genome was published, which consisted of only 885 scaffolds and more than 81% of the bases organised into chromosomes. in 2019, ittiprasert, brindley and colleagues employed programmed crispr/cas9 knockout of the gene encoding the t2 ribonuclease of the egg of schistosoma mansoni, advancing functional genomics and reverse genetics in the study of schistosomes, and platyhelminths generally <https://doi.org/10.7554/elife.41337>. pathology a schistosoma mansoni egg with the characteristic lateral spine schistosome eggs, which may become lodged within the hosts tissues, are the major cause of pathology in schistosomiasis. some of the deposited eggs reach the outside environment by passing through the wall of the intestine; the rest are swept into the circulation and are filtered out in the periportal tracts of the liver, resulting in periportal fibrosis. onset of egg laying in humans is sometimes associated with an onset of fever (katayama fever). this "acute schistosomiasis" is not, however, as important as the chronic forms of the disease. for s. mansoni and s. japonicum, these are "intestinal" and "hepatic schistosomiasis", associated with formation of granulomas around trapped eggs lodged in the intestinal wall or in the liver, respectively. the hepatic form of the disease is the most important, granulomas here giving rise to fibrosis of the liver and hepatosplenomegaly in severe cases. 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. granuloma formation is initiated by antigens secreted by the miracidium through microscopic pores within the rigid egg shell, and the immune response to granuloma, rather than the direct action of egg antigens, causes the symptoms. the granulomas formed around the eggs impair blood flow in the liver and, as a consequence, induce portal hypertension. with time, collateral circulation is formed and the eggs disseminate into the lungs, where they cause more granulomas, pulmonary arteritis and, later, cor pulmonale. a contributory factor to portal hypertension is symmers' fibrosis, which develops around branches of the portal veins. this fibrosis occurs only many years after the infection and is presumed to be caused in part by soluble egg antigens and various immune cells that react to them. recent research has shown that granuloma size is consistent with levels of il-13, which plays a prominent role in granuloma formation and granuloma size. il-13 receptor α 2 (il-13rα2) binds il-13 with high affinity and blocks the effects of il-13. thus, this receptor is essential in preventing the progression of schistosomiasis from the acute to the chronic (and deadly) stage of disease. synthetic il-13rα2 given to mice has resulted in significant decreases in granuloma size, implicating il-13rα2 as an important target in schistosomiasis. s. mansoni infection often occurs alongside those of viral hepatitis, either hepatitis b virus (hbv) or hepatitis c virus (hcv). this is due to high prevalence of schistosomiasis in areas where chronic viral hepatitis is prevalent. one important factor was the development of large reservoir of infection due to extensive schistosomiasis control programs that used intravenously administered tartar emetic since the 1960s. co-infection is known to cause earlier liver deterioration and more severe illness. evasion of host immunity adult and larval worms migrate through the host's blood circulation avoiding the host's immune system. the worms have many tools that help in this evasion, including the tegument, antioxidant proteins, and defenses against host membrane attack complex (mac). the tegument coats the worm and acts as a physical barrier to host antibodies and complement. host immune defenses are capable of producing superoxide, but these are counterattacked by antioxidant proteins produced by the parasite. schistosomes have four superoxide dismutases, and levels of these proteins increase as the schistosome grows. antioxidant pathways were first recognised as a chokepoints for schistosomes, and later extended to other trematodes and cestodes. targeting of this pathway with different inhibitors of the central antioxidant enzyme thioredoxin glutathione reductase (tgr) results in reduced viability of worms. decay accelerating factor (daf) protein is present on the parasite tegument and protects host cells by blocking formation of mac. in addition, schistosomes have six homologues of human cd59 which are strong inhibitors of mac. diagnosis the presence of s. mansoni is detected by microscopic examination of parasite eggs in stool. a staining method called kato-katz technique is used for stool examination. it involves methylene blue-stained cellophane soaked in glycerine or glass slides. a costlier technique called formalin-ether concentration technique (fect) is often used in combination with the direct faecal smear for higher accuracy. serological and immunological tests are also available. antibodies and antigens can be detected in the blood using elisa to identify infection. adult worm antigens can be detected by indirect haemagglutination assays (ihas). polymerase chain reaction (pcr) is also used for detecting the parasite dna. circulating cathodic antigen (cca) in urine can be tested with lateral flow immune-chromatographic reagent strip and point-of-care (poc) tests. egg detection and immunologic tests are not that sensitive. polymerase chain reaction (pcr) based testing is accurate and rapid. they, however, are not frequency used in countries were the disease is common due to the cost of the equipment and the technical experience required to run them. using a microscope to detect eggs costs about us$0.40 per test well pcr is about $us7 per test as of 2019. loop-mediated isothermal amplification (lamp) are being studied as they are lower cost. lamp testing is not commercially available as of 2019. treatment the standard drug for s. mansoni infection is praziquantel at a dose of 40 mg/kg. oxamniquine is also used. epidemiology main article: schistosomiasis as of who report in 2016, 206.5 million people worldwide are having schistosomiasis due to different species of schistosoma. more than 105 million people were given medical treatment. s. mansoni is the major species causing an annual death of about 130,000. it is endemic in 55 countries and most prevalent in africa, the middle east, the caribbean, brazil, venezuela and suriname. about 80-85% of schistosomiasis is found in sub-saharan africa, where s. haematobium, s. intercalatum and s. mansoni are endemic. approximately 393 million africans are at risk of infection from s. mansoni, of which about 55 million are infected at any moment. annual death due to s. mansoni is about 130,000. the prevalence rate in different countries of africa are: 73.9% in northern ethiopia, 37.9% in western ethiopia, 56% in nigeria, 60.5% in kenya, 64.3% in tanzania, 19.8% in ghana, and 53.8% in côte d'ivoire. in egypt, 60% of the population in the northern and eastern parts of the nile delta and only 6% in the southern part are infected. s. mansoni is commonly found in places with poor sanitation. because of the parasite's fecal-oral transmission, bodies of water that contain human waste can be infectious. water that contains large populations of the intermediate host snail species is more likely to cause infection. young children living in these areas are at greatest risk because of their tendency to swim and bathe in cercaria-infected waters longer than adults . anyone travelling to the areas described above, and who is exposed to contaminated water, is at risk of schistosomiasis. history the intermediate hosts biomphalaria snails are estimated to originate in south america 95–110 million years ago. but the parasites schistosoma originated in asia. in africa, the progenitor species evolved into modern s. mansoni and s. haematobium around 2–5 million years ago. a german physician theodor maximillian bilharz was the first to discover the parasite in 1851, while working at kasr el-aini hospital, a medical school in cairo. bilharz recovered them from autopsies of dead soldiers, and noticed two distinct parasites. he described one of them as distomum haematobium (now s. haematobium) in 1852, but failed to identify the other. in one of his letters to his mentor karl theordor von siebold, he mentioned some of the eggs were different in having terminal spines while some had lateral spines. terminal-spined eggs are unique to s. haematobium, while lateral spines are found only in s. mansoni. bilharz also noted that the adult flukes were different in anatomy and number eggs they produced. he introduced the terms bilharzia and bilharziasis for the name of the infection in 1856. a german zoologist david friedrich weinland corrected the genus name to schistosoma in 1858; and introduced the disease name as schistosomiasis. the species distinction was first recognised by patrick manson at the london school of hygiene & tropical medicine. manson identified lateral-spined eggs in the faeces of a colonial officer earlier posted to the west indies, and concluded that there were two species of schistosoma. an italian-british physician louis westenra sambon gave the new names schistosomum haematobium and schistosomum mansoni in 1907, the latter to honour manson. sambon only gave partial description using a male worm. in 1908, a brazilian physician manuel augusto pirajá da silva gave a complete description of male and female worms, including the lateral-spined eggs. pirajá da silva obtained specimens from three necropsies and eggs from 20 stool examinations in bahia. he gave the name s. americanum. the species identity was confirmed in 1907 by british parasitologist robert thomson leiper, identifying the specific snail host, and distinguishing the egg structure, thereby establishing the life cycle.