Schistosoma mansoni
Encyclopedia
Schistosoma mansoni is a significant parasite of humans, a trematode
that is one of the major agents of the disease schistosomiasis
. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis.
Schistosomes are atypical trematodes in that the adult stages have two sexes (dioecious
) and are located in blood vessels of the definitive host. Most other trematodes are hermaphroditic and are found in the intestinal tract or in organs, such as the liver. The lifecycle of schistosomes includes two hosts: a definitive host (i.e. human) where the parasite undergoes sexual reproduction, and a single intermediate snail host where there are a number of asexual reproductive stages.
S. mansoni is named after Sir Patrick Manson
, who first identified it in Formosa (Taiwan).
The female has a cylindrical body, longer and thinner than the male (1.2 to 1.6 cm long by 0.016 cm wide). The female parasite is darker, and it looks gray. The darker color is due to the presence of a pigment (hemozoin
) in its digestive tube. This pigment is derived from the digestion of blood. The ovary
is elongated and slightly lobulated and is located on the anterior half of the body. A short oviduct conducts to the ootype which continues with the uterine tube. In this tube it is possible to find 1 to 2 eggs (rarely 3 to 4) but only 1 egg is observed in the ootype at any one time. The genital pore opens ventrally. The posterior two-thirds of the body contain the vittelogenic glands and their winding canal, which unites with the oviduct
a little before it reaches the ootype.
The digestive tube begins at the anterior extremity of the worm, at the bottom of the oral sucker. The digestive tube is composed of an esophagus
which divides in two branches (right and left) and that reunite in a single cecum
. The intestines end blindly, meaning that there is no anus
.
caused by all the Schistosoma
species infects over 200 million people.)
S. mansoni is the most widespread of the human-infecting schistosomes, and is present in 54 countries. These countries are predominantly in South America and the Caribbean, Africa including Madagascar
, and the Middle East.
hatches out of the egg. The hatching happens in response to temperature, light and dilution of faeces with water. The miracidium searches for a suitable freshwater snail
(Biomphalaria glabrata
, Biomphalaria straminea
, Biomphalaria tenagophila
or Biomphalaria sudanica
) to act as an intermediate host and penetrates it. Following this, the parasite develops via a so-called mother-sporocyst and daughter-sporocyst generation to the cercaria. The purpose of the growth in the snail is the numerical multiplication of the parasite. From a single miracidium result a few thousand cercaria, every one of which is capable of infecting man.
Libora et al. (2010) have detected in Venezuela, that a land snail Achatina fulica can also serve as a host of Schistosoma mansoni.
The cercaria emerge from the snail during daylight and they propel themselves in water with the aid of their bifurcated tail, actively seeking out their final host. When they recognise human skin
, they penetrate it within a very short time. This occurs in three stages, an initial attachment to the skin, followed by the cercaria creeping over the skin searching for a suitable penetration site, often a hair follicle
, and finally penetration of the skin into the epidermis using proteolytic secretions from the cercarial post-acetabular, then pre-acetabular glands.
On penetration, the head of the cercaria transforms into an endoparasitic larva
, the schistosomule. Each schistosomule spends a few days in the skin and then enters the circulation starting at the dermal lymphatics and venule
s. Here they feed on blood, regurgitating the haem as hemozoin
. The schistosomule migrates to the lungs (5–7 days post-penetration) and then moves via circulation through the left side of the heart
to the hepatoportal circulation (>15 days) where, if it meets a partner of the opposite sex, it develops into a sexually mature adult and the pair migrate to the mesenteric veins. Such pairings are monogamous.
Male schistosomes undergo normal maturation and morphological development in the presence or absence of a female, although behavioural, physiological and antigenic differences between males from single-sex, as opposed to bisex, infections have been reported. On the other hand, female schistosomes do not mature without a male. Females schistosomes from single-sex infections are underdeveloped and exhibit an immature reproductive system. Although the maturation of the female worm seems to be dependent on the presence of the mature male, the stimuli for female growth and for reproductive development seem to be independent from each other.
The adult female worm resides within the adult male worm's gynaecophoric canal, which is a modification of the ventral surface of the male forming a groove. The paired worms move against the flow of blood to their final niche 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.
by a chromossomal mechanism. The Schistosoma 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 have been identified, and their frequency in genomic sequence data also suggests at least 30% repetitive DNA
. Chromosomes range in size from 18 to 73 MB and can be distinguished by size, shape and C banding. There are estimated to be 15–20 thousand expressed genes
.
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
. Together with the shotgun data being generated by TIGR
, an ~8x coverage of the genome will be obtained, assembled and annotated. Also in 2003, 163,000 ESTs (expressed sequence tag
s) 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. Analysis of the S. mansoni genome highlighted expansions in protease families and deficiencies in lipid anabolism; both observations can be directly related S. mansoni's parasitic lifestyle. The former included the invadolysin (host penetration) and cathepsin (blood feeding) gene families, while the latter encompassed several enzymes required for the de novo synthesis of fatty acids and sterols (so the worm must rely on its host for these products). The results open the way for research on new targeted treatments.
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 there is strong evidence that the vigorous granulomatous response, rather than the direct action of parasite egg antigens, is responsible for the pathologic tissue manifestations in schistosomiasis. The granulomas formed around the eggs impair blood flow in the liver and consequently 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 occur only many years after the infection and apparently is caused in part by soluble egg antigens and various immune cells which 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.
Tegument
The tegument coats the worm and acts as a physical barrier to host antibodies and complement.
Antioxidant proteins
Host immune defenses are capable of producing superoxide, which has a tremendous detrimental effect on the worm. However, they are able to produce a number of antioxidant proteins that block the effect of superoxide. Schistosomes have four superoxide dismutases, and levels of these proteins increase as the schistosome develops and matures.
Defense against host MAC
Schistosomes have evolved ways to block host complement proteins. Immunocytochemistry techniques have found decay accelerating factor (DAF) protein on the tegument. DAF is found on host cells and protects host cells by blocking formation of MAC. It has also been found that the schistosome genome consists of human CD59 homologs. CD59 inhibits MAC.
, commonly referred to as "swimmer's itch
", due to irritation at the point of entrance. The rash that may develop can mimic scabies
and other types of rashes. Other symptoms can occur two to ten weeks later and can include fever
, aching, cough
, diarrhea
, or gland enlargement. These symptoms can also be related to avian schistosomiasis which does not cause any further symptoms in humans.
. This immune response can lead to obstruction of the colon and blood loss. The infected individual may have what appears to be a potbelly. Eggs can also become lodged in the liver, leading to high blood pressure through the liver, enlarged spleen, the buildup of fluid in the abdomen, and potentially life-threatening dilations or swollen areas in the esophagus or gastrointestinal tract that can tear and bleed profusely (esophageal varices). Rarely, the central nervous system is affected. Individuals with chronic active schistosomiasis may not complain of typical symptoms.
(a semi-quantitative stool examination technique). Other methods which can be used are enzyme linked immunosorbent assay (ELISA), circumoval precipitation test (COPT) and alkaline phosphatase immunoassay (APIA).
Currently there are two drugs available, praziquantel
and oxamniquine
, for the treatment of schistosomiasis.
They are considered equivalent in relation to efficacy and safety. Due to its lower cost per treatment, praziquantel is generally considered the first option for treatment. The recommended dose is: praziquantel, 60 mg/kg of body weight for children up to 15 years old, and 50 mg/kg of body weight for adults; oxamniquine, 15 mg/kg for adults, and 20 mg/kg for children up to 15 years old. The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All confirmed cases should be treated.
Trematoda
Trematoda is a class within the phylum Platyhelminthes that contains two groups of parasitic flatworms, commonly referred to as "flukes".-Taxonomy and biodiversity:...
that is one of the major agents of the disease schistosomiasis
Schistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis.
Schistosomes are atypical trematodes in that the adult stages have two sexes (dioecious
Dioecious
Dioecy is the property of a group of biological organisms that have males and females, but not members that have organs of both sexes at the same time. I.e., those whose individual members can usually produce only one type of gamete; each individual organism is thus distinctly female or male...
) and are located in blood vessels of the definitive host. Most other trematodes are hermaphroditic and are found in the intestinal tract or in organs, such as the liver. The lifecycle of schistosomes includes two hosts: a definitive host (i.e. human) where the parasite undergoes sexual reproduction, and a single intermediate snail host where there are a number of asexual reproductive stages.
S. mansoni is named after Sir Patrick Manson
Patrick Manson
Sir Patrick Manson was a Scottish physician who made important discoveries in parasitology and was the founder of the tropical medicine field....
, who first identified it in Formosa (Taiwan).
Morphology of adult schistosomes
Schistosomes, unlike other trematodes, are long and slim worms. The male S. mansoni is approximately 1 cm long (0.6–1.1 cm) and is 0.1 cm wide. It is white, and it has a funnel-shaped oral sucker at its anterior end followed by a second pediculated sucker. The external part of the worm is composed of a double bilayer, which is continually renewed as the outer layer, known as the membranocalyx, is shed continuously. The tegument bears a large number of small tubercules. The suckers have small thorns in their inner part as well as in the buttons around them. The male genital apparatus is composed of 6 to 9 testicular masses, situated dorsally. There is one deferent canal beginning at each testicle which is connected to a single deferent that dilates into a reservatory, the seminal vesicle, located at the beginning of the gynacophoric canal. The copula happens through the coaptation of the male and female genital orifices.The female has a cylindrical body, longer and thinner than the male (1.2 to 1.6 cm long by 0.016 cm wide). The female parasite is darker, and it looks gray. The darker color is due to the presence of a pigment (hemozoin
Hemozoin
Hemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as Malaria parasites , Rhodnius and Schistosoma digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin...
) in its digestive tube. This pigment is derived from the digestion of blood. The ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
is elongated and slightly lobulated and is located on the anterior half of the body. A short oviduct conducts to the ootype which continues with the uterine tube. In this tube it is possible to find 1 to 2 eggs (rarely 3 to 4) but only 1 egg is observed in the ootype at any one time. The genital pore opens ventrally. The posterior two-thirds of the body contain the vittelogenic glands and their winding canal, which unites with the oviduct
Oviduct
In non-mammalian vertebrates, the passageway from the ovaries to the outside of the body is known as the oviduct. The eggs travel along the oviduct. These eggs will either be fertilized by sperm to become a zygote, or will degenerate in the body...
a little before it reaches the ootype.
The digestive tube begins at the anterior extremity of the worm, at the bottom of the oral sucker. The digestive tube is composed of an esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
which divides in two branches (right and left) and that reunite in a single cecum
Cecum
The cecum or caecum is a pouch, connecting the ileum with the ascending colon of the large intestine. It is separated from the ileum by the ileocecal valve or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic...
. The intestines end blindly, meaning that there is no anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
.
Epidemiology
Schistosoma mansoni infects about 83.31 million people worldwide, causing the disease intestinal schistosomiasis (schistosomiasisSchistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
caused by all the Schistosoma
Schistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
species infects over 200 million people.)
S. mansoni is the most widespread of the human-infecting schistosomes, and is present in 54 countries. These countries are predominantly in South America and the Caribbean, Africa including Madagascar
Madagascar
The Republic of Madagascar is an island country located in the Indian Ocean off the southeastern coast of Africa...
, and the Middle East.
Life cycle
After the eggs of the human-dwelling parasite are emitted in the faeces and into the water, the ripe miracidiumMiracidium
Trematodes are small parasitic flatworms that use vertebrates as their definitive host, and molluscs as their intermediate host. In order to accomplish this, they have several varied lifecyle stages....
hatches out of the egg. The hatching happens in response to temperature, light and dilution of faeces with water. The miracidium searches for a suitable freshwater snail
Snail
Snail is a common name applied to most of the members of the molluscan class Gastropoda that have coiled shells in the adult stage. When the word is used in its most general sense, it includes sea snails, land snails and freshwater snails. The word snail without any qualifier is however more often...
(Biomphalaria glabrata
Biomphalaria glabrata
Biomphalaria glabrata is a species of air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Planorbidae, the ram's horn snails....
, Biomphalaria straminea
Biomphalaria straminea
Biomphalaria straminea is a species of air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Planorbidae, the ram's horn snails....
, Biomphalaria tenagophila
Biomphalaria tenagophila
Biomphalaria tenagophila is a species of air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Planorbidae, the ram's horn snails....
or Biomphalaria sudanica
Biomphalaria sudanica
Biomphalaria sudanica is a species of air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Planorbidae, the ram's horn snails.- Distribution :This species is African, and occurs mainly in East Africa:...
) to act as an intermediate host and penetrates it. Following this, the parasite develops via a so-called mother-sporocyst and daughter-sporocyst generation to the cercaria. The purpose of the growth in the snail is the numerical multiplication of the parasite. From a single miracidium result a few thousand cercaria, every one of which is capable of infecting man.
Libora et al. (2010) have detected in Venezuela, that a land snail Achatina fulica can also serve as a host of Schistosoma mansoni.
The cercaria emerge from the snail during daylight and they propel themselves in water with the aid of their bifurcated tail, actively seeking out their final host. When they recognise human skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, they penetrate it within a very short time. This occurs in three stages, an initial attachment to the skin, followed by the cercaria creeping over the skin searching for a suitable penetration site, often a hair follicle
Hair follicle
A hair follicle is a skin organ that produces hair. Hair production occurs in phases, including a growth phase , and cessation phase , and a rest phase . Stem cells are principally responsible for the production of hair....
, and finally penetration of the skin into the epidermis using proteolytic secretions from the cercarial post-acetabular, then pre-acetabular glands.
On penetration, the head of the cercaria transforms into an endoparasitic larva
Larva
A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...
, the schistosomule. Each schistosomule spends a few days in the skin and then enters the circulation starting at the dermal lymphatics and venule
Venule
A venule is a very small blood vessel in the microcirculation that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins. Venules range from 8 to 100μm in diameter and are formed when capillaries unite .Venules are blood vessels that drain blood...
s. Here they feed on blood, regurgitating the haem as hemozoin
Hemozoin
Hemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as Malaria parasites , Rhodnius and Schistosoma digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin...
. The schistosomule migrates to the lungs (5–7 days post-penetration) and then moves via circulation through the left side of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
to the hepatoportal circulation (>15 days) where, if it meets a partner of the opposite sex, it develops into a sexually mature adult and the pair migrate to the mesenteric veins. Such pairings are monogamous.
Male schistosomes undergo normal maturation and morphological development in the presence or absence of a female, although behavioural, physiological and antigenic differences between males from single-sex, as opposed to bisex, infections have been reported. On the other hand, female schistosomes do not mature without a male. Females schistosomes from single-sex infections are underdeveloped and exhibit an immature reproductive system. Although the maturation of the female worm seems to be dependent on the presence of the mature male, the stimuli for female growth and for reproductive development seem to be independent from each other.
The adult female worm resides within the adult male worm's gynaecophoric canal, which is a modification of the ventral surface of the male forming a groove. The paired worms move against the flow of blood to their final niche 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
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
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
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
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 zygoteZygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...
by a chromossomal mechanism. The Schistosoma genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
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 have been identified, and their frequency in genomic sequence data also suggests at least 30% repetitive DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. Chromosomes range in size from 18 to 73 MB and can be distinguished by size, shape and C banding. There are estimated to be 15–20 thousand expressed genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
.
In 2000, the first BAC library of Schistosome was constructed. In June 2003, a ~5x whole genome shotgun sequencing
Shotgun sequencing
In genetics, shotgun sequencing, also known as shotgun cloning, is a method used for sequencing long DNA strands. It is named by analogy with the rapidly-expanding, quasi-random firing pattern of a shotgun....
project was initiated at the Sanger Institute
Sanger Institute
The Wellcome Trust Sanger Institute is a non-profit, British genomics and genetics research institute, primarily funded by the Wellcome Trust....
. Together with the shotgun data being generated by TIGR
TIGR
TIGR, abbreviation for Trst , Istra , Gorica and Reka , with the full name Revolutionary Organization of the Julian March T.I.G.R. was a militant anti-Fascist and insurgent organization active in the 1920s and the 1930s in the eastern Italian border region known as the Julian March.The...
, an ~8x coverage of the genome will be obtained, assembled and annotated. Also in 2003, 163,000 ESTs (expressed sequence tag
Expressed sequence tag
An expressed sequence tag or EST is a short sub-sequence of a cDNA sequence. They may be used to identify gene transcripts, and are instrumental in gene discovery and gene sequence determination. The identification of ESTs has proceeded rapidly, with approximately 65.9 million ESTs now available in...
s) were generated (by a consortium
Consortium
A consortium is an association of two or more individuals, companies, organizations or governments with the objective of participating in a common activity or pooling their resources for achieving a common goal....
headed by the University of São Paulo
University of São Paulo
Universidade de São Paulo is a public university in the Brazilian state of São Paulo. It is the largest Brazilian university and one of the country's most prestigious...
) 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. Analysis of the S. mansoni genome highlighted expansions in protease families and deficiencies in lipid anabolism; both observations can be directly related S. mansoni's parasitic lifestyle. The former included the invadolysin (host penetration) and cathepsin (blood feeding) gene families, while the latter encompassed several enzymes required for the de novo synthesis of fatty acids and sterols (so the worm must rely on its host for these products). The results open the way for research on new targeted treatments.
Pathology
Schistosoma japonicum
Schistosoma japonicum is an important parasite and one of the major infectious agents of schistosomiasis.This parasite has a very wide host range, infecting at least 31 species of wild mammals, including 9 carnivores, 16 rodents, one primate , two insectivores and three artiodactyls and therefore...
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
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
of the liver and hepatosplenomegaly
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
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
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
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 there is strong evidence that the vigorous granulomatous response, rather than the direct action of parasite egg antigens, is responsible for the pathologic tissue manifestations in schistosomiasis. The granulomas formed around the eggs impair blood flow in the liver and consequently induce portal hypertension
Portal hypertension
In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...
. With time, collateral circulation
Collateral circulation
Collateral circulation is when an area of tissue or an organ has a number of different pathways for blood to reach it. This is often as a result of anastamoses - branches formed between adjacent blood vessels....
is formed and the eggs disseminate into the lungs, where they cause more granulomas, pulmonary arteritis and, later, cor pulmonale
Cor pulmonale
Cor pulmonale or pulmonary heart disease is enlargement of the right ventricle of the heart as a response to increased resistance or high blood pressure in the lungs ....
. A contributory factor to portal hypertension is Symmers' fibrosis, which develops around branches of the portal veins. This fibrosis occur only many years after the infection and apparently is caused in part by soluble egg antigens and various immune cells which 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.
Evasion of host immunity
Adult and larval worms must migrate through the host's blood circulation and avoid 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).Tegument
The tegument coats the worm and acts as a physical barrier to host antibodies and complement.
Antioxidant proteins
Host immune defenses are capable of producing superoxide, which has a tremendous detrimental effect on the worm. However, they are able to produce a number of antioxidant proteins that block the effect of superoxide. Schistosomes have four superoxide dismutases, and levels of these proteins increase as the schistosome develops and matures.
Defense against host MAC
Schistosomes have evolved ways to block host complement proteins. Immunocytochemistry techniques have found decay accelerating factor (DAF) protein on the tegument. DAF is found on host cells and protects host cells by blocking formation of MAC. It has also been found that the schistosome genome consists of human CD59 homologs. CD59 inhibits MAC.
Symptoms
Many individuals do not experience symptoms. If symptoms do appear, it usually takes four to six weeks from the time of infection. The first symptom of the disease may be a general ill feeling. Within twelve hours of infection, an individual may complain of a tingling sensation or light rashRash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, commonly referred to as "swimmer's itch
Swimmer's itch
Swimmer’s itch, also known as lake itch, duck itch, cercarial dermatitis, and Schistosome cercarial dermatitis, is a short-term, immune reaction occurring in the skin of humans that have been infected by water-borne schistosomatidae...
", due to irritation at the point of entrance. The rash that may develop can mimic scabies
Scabies
Scabies , known colloquially as the seven-year itch, is a contagious skin infection that occurs among humans and other animals. It is caused by a tiny and usually not directly visible parasite, the mite Sarcoptes scabiei, which burrows under the host's skin, causing intense allergic itching...
and other types of rashes. Other symptoms can occur two to ten weeks later and can include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, aching, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, or gland enlargement. These symptoms can also be related to avian schistosomiasis which does not cause any further symptoms in humans.
Katayama fever
Another primary condition, called Katayama fever, may also develop from infection with these worms, and it can be very difficult to recognize. Symptoms include fever, lethargy, the eruption of pale temporary bumps associated with severe itching (urticarial) rash, liver and spleen enlargement, and bronchospasm.Intestinal schistosomiasis
In intestinal schistosomiasis, eggs become lodged in the intestinal wall and cause an immune system reaction called a granulomatous reactionGranuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
. This immune response can lead to obstruction of the colon and blood loss. The infected individual may have what appears to be a potbelly. Eggs can also become lodged in the liver, leading to high blood pressure through the liver, enlarged spleen, the buildup of fluid in the abdomen, and potentially life-threatening dilations or swollen areas in the esophagus or gastrointestinal tract that can tear and bleed profusely (esophageal varices). Rarely, the central nervous system is affected. Individuals with chronic active schistosomiasis may not complain of typical symptoms.
Diagnosis and treatment
Diagnosis of infection is confirmed by the identification of eggs in stools. Eggs of S. mansoni are approximately 140 by 60 µm in size, and have a lateral spine. The diagnosis is improved by the use of the Kato-Katz techniqueKato technique
The Kato technique is a laboratory method for preparing human stool samples prior to searching for parasite eggs.- Indications :...
(a semi-quantitative stool examination technique). Other methods which can be used are enzyme linked immunosorbent assay (ELISA), circumoval precipitation test (COPT) and alkaline phosphatase immunoassay (APIA).
Currently there are two drugs available, praziquantel
Praziquantel
Praziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....
and oxamniquine
Oxamniquine
Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine is a potent single-dose agent for treatment of S...
, for the treatment of schistosomiasis.
They are considered equivalent in relation to efficacy and safety. Due to its lower cost per treatment, praziquantel is generally considered the first option for treatment. The recommended dose is: praziquantel, 60 mg/kg of body weight for children up to 15 years old, and 50 mg/kg of body weight for adults; oxamniquine, 15 mg/kg for adults, and 20 mg/kg for children up to 15 years old. The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All confirmed cases should be treated.
External links
- Collins J. J. III, King R. S., Cogswell A., Williams D. L. & Newmark P. A. (2011). "An Atlas for Schistosoma mansoni Organs and Life-Cycle Stages Using Cell Type-Specific Markers and Confocal Microscopy". PLoS Neglected Tropical DiseasesPLoS Neglected Tropical DiseasesPLoS Neglected Tropical Diseases is an open access, online scientific journal devoted to the study of neglected tropical diseases. Submissions go through pre-publication peer review for scientific rigor and relevance to a specific set of overlooked diseases, including helminth, bacterial, viral,...
5(3): e1009. doi:10.1371/journal.pntd.0001009.