Schistosoma
Encyclopedia
A genus
of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworm
s 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 socioeconomically devastating parasitic disease
, next only to malaria
, with hundreds of millions infected worldwide.
Adult worms
parasitize mesenteric blood vessels
. They are unique among trematodes or any other flatworms in that they are dioecious
with distinct sexual dimorphism
between male
and female
. Eggs are passed through urine
or feces
to fresh water
, where larva
must pass though an intermediate snail host
, before a different larval stage of the parasite emerges that can infect a new mammalian host by directly penetrating the skin.
were first seen by Theodor Maximilian Bilharz, a German
pathologist working in Egypt
in 1851 who found the eggs of Schistosoma haematobium
during the course of a post mortem. He wrote two letters to his former teacher von Siebold in May and August 1851 describing his findings. Von Siebold wrote a paper (published in 1852) summarizing Bilharz's findings. Bilharz wrote a paper in 1856 describing the worms
more fully and he named them Distoma haematobium. Their unusual morphology
meant that they could not be comfortably included in Distoma. So in 1856 Meckel von Helmsback created the genus
Bilharzia for them. In 1858 Weinland proposed the name Schistosoma (Greek: 'split body') after the male worms
' morphology. Despite Bilharzia having precedence the genus
name Schistosoma was officially adopted by the International Commission on Zoological Nomenclature
. The term Bilharzia to describe infection with these parasites
is still in use in medical circles.
Bilharz also described Schistosoma mansoni
but this species was redescribed by Louis Westenra Sambon in 1907 at the London School of Tropical Medicine who named it after his teacher Patrick Manson
.
In 1898, all the then known species
were placed in a subfamily by Stiles and Hassel. This was then elevated to family
status by Looss
in 1899. Poche in 1907 corrected a grammatical
error in the family
name. The life cycle
was determined by da Silva in 1908.
In 2009, the genome
s of Schistosoma mansoni
and Schistosoma japonicum
were decoded opening the way for new targeted treatments. In particular, the study discovered that the genome
of S. mansoni
contained 11,809 genes
including many which produce enzymes for breaking down proteins which enable the parasite to bore through tissue. Also, S. mansoni
does not have an enzyme
to make certain fats
so that it must rely on its host to produce these.
s remain unclear. For many years it was believed that this genus
had an African origin but DNA sequencing
suggests that the species
(S. edwardiense and S. hippopotami) that infect the hippo (Hippopotamus amphibius) could be basal. Since hippos were present in both Africa
and Asia
during the Cenozoic
era the genus
might have originated as parasites
of hippos.
The original hosts for the South East Asian species were probably rodent
s.
The sister group to Schistosoma is a genus
of elephant
-infecting schistosomes - Bivitellobilharzia.
The cattle
, sheep, goat
and cashmere goat
parasite Orientobilharzia turkestanicum appears to be related to the African schistosomes.
Within the haematobium group S. bovis and S. curassoni appear to be closely related as do S. leiperi and S. mattheei.
S. mansoni appears to have evolved in East Africa
0.43-0.30 million years ago.
S. incognitum and S. nasale are more closely related to the African species rather than the japonicum group.
S. sinensium appears to have radiated during the Pliocene
.
S. mekongi appears to have invaded South East Asia
in the mid-Pleistocene
.
Estimated speciation dates for the japonicum group: ~3.8 million years ago for S. japonicum/South East Asian schistosoma and ~2.5 million years ago for S. malayensis/S. mekongi.
Schistosoma as currently defined is paraphyletic so revisions are likely. Currently twenty one species
are recognised within this genus
.
The genus
has been divided into four groups - indicum, japonicum, haematobium and mansoni. The affinities of the remaining three species
are still being clarified.
Twelve species
are found in Africa
. Eleven of these are divided into two groups - those with a lateral spine on the egg (mansoni group) and those with a terminal spine (haematobium group).
The four mansoni group species
are: S. edwardiense, S. hippotami, S. mansoni
and S. rodhaini.
The eight haematobium group species
are: S. bovis, S. curassoni, S. intercalatum
, S. guineensis, S. haematobium
, S. leiperi, S. margrebowiei and S. matthei.
S. spindale is widely distributed in Asia
but is also found in Africa
.
The other species
occur in Asia
and India
The indicum group has three species
: S. indicum
, S. nasale
and S. spindale
. This group appears to have evolved during the Pleistocene
. All use pulmonate snails as hosts.
S. indicum is found in India
and Thailand
.
The japonicum group has three species
: S. japonicum
, S. malayensis
and S. mekongi
.
S. sinensium is a sister clade
to the S. japonicum group and is found in China
.
S. ovuncatum
forms a clade
with S. sinensium and is found in northern Thailand
. The definitive host is the rat (Rattus rattus) and the intermediate host is the snail
Tricula bollingi
. This species
is known to use snails of the family
Pomatiopsidae
as hosts.
S. incognitum appears to be basal in this genus
. It may be more closely related to the African/India
n species
than to the South East Asian group. This species uses pulmonate snails as hosts.
based on 18S ribosomal RNA
, 28S ribosomal RNA
, and partial cytochrome-c oxidase I
(COI) genes shows phylogenic relations of species in the genus Schistosoma:
schistosomiasis
. An anti-schistosome drug is a schistosomicide
.
and Africa
.
, Schistosoma nasale
, Schistosoma leiperi are all parasites of ruminant
s.
Schistosoma edwardiense and Schistosoma hippopotami are parasites of the hippo.
tegument
, a blind-ending digestive system consisting of mouth
, oesophagus and bifurcated caeca
; the area between the tegument and alimentary canal filled with a loose network of mesoderm cells
, and an excretory or osmoregulatory system based on flame cell
s. Adult worms tend to be 10–20 mm (0.4-0.8 in) long and use globin
s from their hosts' hemoglobin
for their own circulatory system.
- i.e., the sexes are separate. The two sexes display a strong degree of sexual dimorphism
, and the male is considerably larger than the female. The male surrounds the female and encloses her within his gynacophoric canal for the entire adult lives of the worms, where they reproduce sexually.
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworm
Flatworm
The flatworms, known in scientific literature as Platyhelminthes or Plathelminthes are a phylum of relatively simple bilaterian, unsegmented, soft-bodied invertebrate animals...
s which are responsible for a highly significant parasitic infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of humans by causing 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...
, and are considered by the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
as the second most socioeconomically devastating parasitic disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, next only to malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
, with hundreds of millions infected worldwide.
Adult worms
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
parasitize mesenteric blood vessels
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
. They are unique among trematodes or any other flatworms in that they are 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...
with distinct sexual dimorphism
Sexual dimorphism
Sexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
between male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
and female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
. Eggs are passed through urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
or feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
to fresh water
Fresh Water
Fresh Water is the debut album by Australian rock and blues singer Alison McCallum, released in 1972. Rare for an Australian artist at the time, it came in a gatefold sleeve...
, where 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...
must pass though an intermediate snail host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
, before a different larval stage of the parasite emerges that can infect a new mammalian host by directly penetrating the skin.
History
The eggs of these parasitesParasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
were first seen by Theodor Maximilian Bilharz, a German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
pathologist working in Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
in 1851 who found the eggs of Schistosoma haematobium
Schistosoma haematobium
Schistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....
during the course of a post mortem. He wrote two letters to his former teacher von Siebold in May and August 1851 describing his findings. Von Siebold wrote a paper (published in 1852) summarizing Bilharz's findings. Bilharz wrote a paper in 1856 describing the worms
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
more fully and he named them Distoma haematobium. Their unusual morphology
Morphology (biology)
In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....
meant that they could not be comfortably included in Distoma. So in 1856 Meckel von Helmsback created the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
Bilharzia for them. In 1858 Weinland proposed the name Schistosoma (Greek: 'split body') after the male worms
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
' morphology. Despite Bilharzia having precedence the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
name Schistosoma was officially adopted by the International Commission on Zoological Nomenclature
International Commission on Zoological Nomenclature
The International Commission on Zoological Nomenclature is an organization dedicated to "achieving stability and sense in the scientific naming of animals". Founded in 1895, it currently comprises 28 members from 20 countries, mainly practicing zoological taxonomists...
. The term Bilharzia to describe infection with these parasites
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
is still in use in medical circles.
Bilharz also described Schistosoma mansoni
Schistosoma mansoni
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....
but this species was redescribed by Louis Westenra Sambon in 1907 at the London School of Tropical Medicine who named it after his teacher 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....
.
In 1898, all the then known species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
were placed in a subfamily by Stiles and Hassel. This was then elevated to family
Family
In human context, a family is a group of people affiliated by consanguinity, affinity, or co-residence. In most societies it is the principal institution for the socialization of children...
status by Looss
Arthur Looss
Arthur Looss was a German zoologist and parasitologist. Looss was born in 1861 in Chemnitz, and was educated both there and in Łódź, Poland ...
in 1899. Poche in 1907 corrected a grammatical
Grammar
In linguistics, grammar is the set of structural rules that govern the composition of clauses, phrases, and words in any given natural language. The term refers also to the study of such rules, and this field includes morphology, syntax, and phonology, often complemented by phonetics, semantics,...
error in the family
Family
In human context, a family is a group of people affiliated by consanguinity, affinity, or co-residence. In most societies it is the principal institution for the socialization of children...
name. The life cycle
Biological life cycle
A life cycle is a period involving all different generations of a species succeeding each other through means of reproduction, whether through asexual reproduction or sexual reproduction...
was determined by da Silva in 1908.
In 2009, the 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....
s of Schistosoma mansoni
Schistosoma mansoni
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....
and Schistosoma japonicum
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...
were decoded opening the way for new targeted treatments. In particular, the study discovered that the 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....
of S. mansoni
Schistosoma mansoni
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....
contained 11,809 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...
including many which produce enzymes for breaking down proteins which enable the parasite to bore through tissue. Also, S. mansoni
Schistosoma mansoni
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....
does not have an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
to make certain fats
Fats
Fats may refer to:*Fat, a generic term for a class of lipids in biochemistry*Fats Domino, rock and roll pianist*Fats Waller, jazz pianist*Fats Navarro, jazz trumpeter*Singing Fats, master of ceremonies*Obesity...
so that it must rely on its host to produce these.
Evolution
The origins of this genuGenu
Latin for "knee", genu is a term commonly encountered in studies of anatomy. It is used to refer to several anatomical structures, including :* conditions affecting the knees, such as genu valgum and genu varum...
s remain unclear. For many years it was believed that this genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
had an African origin but DNA sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
suggests that the species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
(S. edwardiense and S. hippopotami) that infect the hippo (Hippopotamus amphibius) could be basal. Since hippos were present in both Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
and Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
during the Cenozoic
Cenozoic
The Cenozoic era is the current and most recent of the three Phanerozoic geological eras and covers the period from 65.5 mya to the present. The era began in the wake of the Cretaceous–Tertiary extinction event at the end of the Cretaceous that saw the demise of the last non-avian dinosaurs and...
era the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
might have originated as parasites
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
of hippos.
The original hosts for the South East Asian species were probably rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....
s.
The sister group to Schistosoma is a genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of elephant
Elephant
Elephants are large land mammals in two extant genera of the family Elephantidae: Elephas and Loxodonta, with the third genus Mammuthus extinct...
-infecting schistosomes - Bivitellobilharzia.
The cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
, sheep, goat
Goat
The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
and cashmere goat
Goat
The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
parasite Orientobilharzia turkestanicum appears to be related to the African schistosomes.
Within the haematobium group S. bovis and S. curassoni appear to be closely related as do S. leiperi and S. mattheei.
S. mansoni appears to have evolved in East Africa
East Africa
East Africa or Eastern Africa is the easterly region of the African continent, variably defined by geography or geopolitics. In the UN scheme of geographic regions, 19 territories constitute Eastern Africa:...
0.43-0.30 million years ago.
S. incognitum and S. nasale are more closely related to the African species rather than the japonicum group.
S. sinensium appears to have radiated during the Pliocene
Pliocene
The Pliocene Epoch is the period in the geologic timescale that extends from 5.332 million to 2.588 million years before present. It is the second and youngest epoch of the Neogene Period in the Cenozoic Era. The Pliocene follows the Miocene Epoch and is followed by the Pleistocene Epoch...
.
S. mekongi appears to have invaded South East Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
in the mid-Pleistocene
Pleistocene
The Pleistocene is the epoch from 2,588,000 to 11,700 years BP that spans the world's recent period of repeated glaciations. The name pleistocene is derived from the Greek and ....
.
Estimated speciation dates for the japonicum group: ~3.8 million years ago for S. japonicum/South East Asian schistosoma and ~2.5 million years ago for S. malayensis/S. mekongi.
Taxonomy
The genusGenus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
Schistosoma as currently defined is paraphyletic so revisions are likely. Currently twenty one species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
are recognised within this genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
.
The genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
has been divided into four groups - indicum, japonicum, haematobium and mansoni. The affinities of the remaining three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
are still being clarified.
Twelve species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
are found in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
. Eleven of these are divided into two groups - those with a lateral spine on the egg (mansoni group) and those with a terminal spine (haematobium group).
The four mansoni group species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
are: S. edwardiense, S. hippotami, S. mansoni
Schistosoma mansoni
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....
and S. rodhaini.
The eight haematobium group species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
are: S. bovis, S. curassoni, S. intercalatum
Schistosoma intercalatum
Schistosoma intercalatum is an important parasite. It is one of the major agents of schistosomiasis.A freshwater snail Bulinus forskalii is an intermediate host for Schistosoma intercalatum....
, S. guineensis, S. haematobium
Schistosoma haematobium
Schistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....
, S. leiperi, S. margrebowiei and S. matthei.
S. spindale is widely distributed in Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
but is also found in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
.
The other species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
occur in Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
The indicum group has three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
: S. indicum
Schistosoma indicum
Schistosoma spindale is a species of digenetic trematode in the family Schistosomatidae.The parasite is widespread in India and other Asian countries....
, S. nasale
Schistosoma nasale
Schistosoma nasale is a species of digenetic trematode in the family Schistosomatidae.Schistosoma nasale was identified in 1933 by Dr. M. A. N...
and S. spindale
Schistosoma spindale
Schistosoma spindale is a species of digenetic trematode in the family Schistosomatidae. It causes intestinal schistosomiasis of cattle.The distribution of Schistosoma spindale include Sri Lanka, India, Bangladesh, Thailand, Malaysia and Laos....
. This group appears to have evolved during the Pleistocene
Pleistocene
The Pleistocene is the epoch from 2,588,000 to 11,700 years BP that spans the world's recent period of repeated glaciations. The name pleistocene is derived from the Greek and ....
. All use pulmonate snails as hosts.
S. indicum is found in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
.
The japonicum group has three species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
: S. japonicum
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...
, S. malayensis
Schistosoma malayensis
Schistosoma malayensis is a schistome parasite. It was first described in 1988 in Peninsular Malaysia and appears to be a zooenotic infection. The species is named after the country of Malaysia. The natural vertebrate host is van Müller's rat .Among humans exposed to this parasite the lifetime...
and S. mekongi
Schistosoma mekongi
Schistosoma mekongi is a trematode, also known as a flatworm or fluke. It is one of the five major schistosomes that account for all human infections, the other four being S. haematobium, S. mansoni, S. japonicum, and S. intercalatum...
.
S. sinensium is a sister clade
Clade
A clade is a group consisting of a species and all its descendants. In the terms of biological systematics, a clade is a single "branch" on the "tree of life". The idea that such a "natural group" of organisms should be grouped together and given a taxonomic name is central to biological...
to the S. japonicum group and is found in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
.
S. ovuncatum
Schistosoma ovuncatum
Schistosoma ovuncatum is a schistozome parasite, first described in 2002. Its recognition as a new species only occurred when zoologists were re examining specimens originally described in 1984...
forms a clade
Clade
A clade is a group consisting of a species and all its descendants. In the terms of biological systematics, a clade is a single "branch" on the "tree of life". The idea that such a "natural group" of organisms should be grouped together and given a taxonomic name is central to biological...
with S. sinensium and is found in northern Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
. The definitive host is the rat (Rattus rattus) and the intermediate host is the 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...
Tricula bollingi
Tricula bollingi
Tricula bollingi is a species of freshwater snail, a gastropod in the Pomatiopsidae family....
. This species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
is known to use snails of the family
Family
In human context, a family is a group of people affiliated by consanguinity, affinity, or co-residence. In most societies it is the principal institution for the socialization of children...
Pomatiopsidae
Pomatiopsidae
Pomatiopsidae is a family of small mainly freshwater snails with gills and an operculum, aquatic gastropod mollusks in the superfamily Rissooidea ....
as hosts.
S. incognitum appears to be basal in this genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
. It may be more closely related to the African/India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
n species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
than to the South East Asian group. This species uses pulmonate snails as hosts.
Cladogram
A cladogramCladogram
A cladogram is a diagram used in cladistics which shows ancestral relations between organisms, to represent the evolutionary tree of life. Although traditionally such cladograms were generated largely on the basis of morphological characters, DNA and RNA sequencing data and computational...
based on 18S ribosomal RNA
18S ribosomal RNA
18S ribosomal RNA is a part of the ribosomal RNA. The S in 18S represents Svedberg units. 18S rRNA is a component of the small eukaryotic ribosomal subunit...
, 28S ribosomal RNA
28S ribosomal RNA
28S ribosomal RNA is the eukaryotic nuclear homologue of the prokaryotic 23S ribosomal RNA; this is the structural RNA for the large component of eukaryotic cytoplasmic ribosomes, and thus one of the basic components of all eukaryotic cells....
, and partial cytochrome-c oxidase I
Main subunit of cytochrome c oxidase
Cytochrome C and Quinol oxidase polypeptide I is main subunit of cytochrome c oxidase complex.Cytochrome c oxidase is a key enzyme in aerobic metabolism. Proton pumping heme-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes...
(COI) genes shows phylogenic relations of species in the genus Schistosoma:
Schistosomiasis
Schistosoma causes the parasitic diseaseDisease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
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...
. An anti-schistosome drug is a schistosomicide
Schistosomicide
A schistosomicide is a drug used to combat schistosomiasis.Examples listed in MeSH include:* amoscanate* arteether* artemether* chloroxylenol* hycanthone* lucanthone* meclonazepam* niridazole* oltipraz* oxamniquineAnother example is praziquantel....
.
Species infecting humans
Parasitism of humans by Schistosoma appears to have evolved at least three occasions in both AsiaAsia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
.
- S. guineensis, a recently described species, is found in West AfricaWest AfricaWest Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries and an area of approximately 5 million square km:-Flags of West Africa:...
. Known snailSnailSnail 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...
intermediate hosts include Bulinus forskaliiBulinus forskaliiBulinus forskalii is a species of a tropical freshwater snail with a sinistral shell, an aquatic gastropod mollusk in the family Planorbidae, the ramshorn snails and their allies.- Distribution :...
.
- S. haematobiumSchistosoma haematobiumSchistosoma haematobium is an important digenetic trematode, and is found in the Middle East, India, Portugal and Africa. It is a major agent of schistosomiasis; more specifically, it is associated with urinary schistosomiasis....
, commonly referred to as the bladder fluke, originally found in Africa, the Near EastNear EastThe Near East is a geographical term that covers different countries for geographers, archeologists, and historians, on the one hand, and for political scientists, economists, and journalists, on the other...
, and the Mediterranean basin, was introduced into India during World War II. Freshwater snails of the BulinusBulinusBulinus is a genus of small tropical freshwater snails, aquatic gastropod mollusks in the family Planorbidae, the ramshorn snails and their allies....
genus are an important intermediate host for this parasite. Among final hosts humans are most important. Other final hosts are rarely baboons and monkeys.
- S. intercalatumSchistosoma intercalatumSchistosoma intercalatum is an important parasite. It is one of the major agents of schistosomiasis.A freshwater snail Bulinus forskalii is an intermediate host for Schistosoma intercalatum....
. The usual final hosts are humans. Other animals can be infected experimentally.
- S. japonicumSchistosoma japonicumSchistosoma 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...
whose common name is simply blood fluke is found widely spread in Eastern Asia and the southwestern Pacific region. In TaiwanTaiwanTaiwan , also known, especially in the past, as Formosa , is the largest island of the same-named island group of East Asia in the western Pacific Ocean and located off the southeastern coast of mainland China. The island forms over 99% of the current territory of the Republic of China following...
this species only affects animals, not humans. Freshwater snails of the OncomelaniaOncomelaniaOncomelania is a genus of very small tropical freshwater snails, aquatic gastropod mollusks in the family Pomatiopsidae.These Oncomelania snails are distantly related to the marine periwinkle, and more closely related to the small marine snails of the family Rissoidae.-Species:There are two species...
genus are an important intermediate host for S. japonicum. Final hosts are humans and other mammals including cats, dogs, goats, horses, pigs, rats and water buffalo.
- S. malayensisSchistosoma malayensisSchistosoma malayensis is a schistome parasite. It was first described in 1988 in Peninsular Malaysia and appears to be a zooenotic infection. The species is named after the country of Malaysia. The natural vertebrate host is van Müller's rat .Among humans exposed to this parasite the lifetime...
This species appears to be a rare infection in humans and is considered to be a zoonosisZoonosisA zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...
. The natural vertebrate host is von Muller's rat (Rattus muelleri). The snail host(s) are not yet known.
- S. mansoniSchistosoma mansoniSchistosoma 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....
, found in AfricaAfricaAfrica is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, BrazilBrazilBrazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
, VenezuelaVenezuelaVenezuela , officially called the Bolivarian Republic of Venezuela , is a tropical country on the northern coast of South America. It borders Colombia to the west, Guyana to the east, and Brazil to the south...
, SurinameSurinameSuriname , officially the Republic of Suriname , is a country in northern South America. It borders French Guiana to the east, Guyana to the west, Brazil to the south, and on the north by the Atlantic Ocean. Suriname was a former colony of the British and of the Dutch, and was previously known as...
, the lesser AntillesAntillesThe Antilles islands form the greater part of the West Indies in the Caribbean Sea. The Antilles are divided into two major groups: the "Greater Antilles" to the north and west, including the larger islands of Cuba, Jamaica, Hispaniola , and Puerto Rico; and the smaller "Lesser Antilles" on the...
, Puerto RicoPuerto RicoPuerto Rico , officially the Commonwealth of Puerto Rico , is an unincorporated territory of the United States, located in the northeastern Caribbean, east of the Dominican Republic and west of both the United States Virgin Islands and the British Virgin Islands.Puerto Rico comprises an...
, and the Dominican RepublicDominican RepublicThe Dominican Republic is a nation on the island of La Hispaniola, part of the Greater Antilles archipelago in the Caribbean region. The western third of the island is occupied by the nation of Haiti, making Hispaniola one of two Caribbean islands that are shared by two countries...
. It is also known as Manson's blood fluke or swamp fever. Freshwater snails of the BiomphalariaBiomphalariaBiomphalaria is a genus of air-breathing freshwater snails, aquatic pulmonate gastropod mollusks in the family Planorbidae, the ram's horn snails and their allies.Biomphalaria is the type genus of the tribe Biomphalariini....
genus are an important intermediate host for this trematode. Among final hosts humans are most important. Other final hosts are baboons, rodents and raccoons.
- S. mekongiSchistosoma mekongiSchistosoma mekongi is a trematode, also known as a flatworm or fluke. It is one of the five major schistosomes that account for all human infections, the other four being S. haematobium, S. mansoni, S. japonicum, and S. intercalatum...
is related to S. japonicum and affects both the superior and inferior mesenteric veins. S. mekongi differs in that it has smaller eggs, a different intermediate host (Neotricula apertaNeotricula apertaNeotricula aperta is a species of freshwater snail, an aquatic gastropod mollusk in the family Pomatiopsidae.This species serves as an intermediate host for Schistosoma mekongi.-Distribution:This species occurs:...
) and longer prepatent period in the mammalian host. Final hosts are humans and dogs. The snail Tricula aperta can also be experimentally infected with this species.
| Scientific Name | First Intermediate Host | Endemic Area |
|---|---|---|
| Schistosoma guineensis | Bulinus forskalii Bulinus forskalii Bulinus forskalii is a species of a tropical freshwater snail with a sinistral shell, an aquatic gastropod mollusk in the family Planorbidae, the ramshorn snails and their allies.- Distribution :... |
West Africa West Africa West Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries and an area of approximately 5 million square km:-Flags of West Africa:... |
| Schistosoma intercalatum | Bulinus Bulinus Bulinus is a genus of small tropical freshwater snails, aquatic gastropod mollusks in the family Planorbidae, the ramshorn snails and their allies.... spp |
Africa Africa Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area... |
| Schistosoma haematobium | Bulinus Bulinus Bulinus is a genus of small tropical freshwater snails, aquatic gastropod mollusks in the family Planorbidae, the ramshorn snails and their allies.... spp. |
Africa Africa Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area... , Middle East Middle East The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East... |
| Schistosoma japonicun | Oncomelania Oncomelania Oncomelania is a genus of very small tropical freshwater snails, aquatic gastropod mollusks in the family Pomatiopsidae.These Oncomelania snails are distantly related to the marine periwinkle, and more closely related to the small marine snails of the family Rissoidae.-Species:There are two species... spp. |
China China Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture... , East Asia East Asia East Asia or Eastern Asia is a subregion of Asia that can be defined in either geographical or cultural terms... , Philippines Philippines The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam... |
| Schistosoma malayensis | Not known | South East Asia |
| Schistosoma mansoni | Biomphalaria Biomphalaria Biomphalaria is a genus of air-breathing freshwater snails, aquatic pulmonate gastropod mollusks in the family Planorbidae, the ram's horn snails and their allies.Biomphalaria is the type genus of the tribe Biomphalariini.... spp. |
Africa Africa Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area... , South America South America South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east... , Caribbean Caribbean The Caribbean is a crescent-shaped group of islands more than 2,000 miles long separating the Gulf of Mexico and the Caribbean Sea, to the west and south, from the Atlantic Ocean, to the east and north... , Middle East Middle East The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East... |
| Schistosoma mekongi | Neotricula aperta Neotricula aperta Neotricula aperta is a species of freshwater snail, an aquatic gastropod mollusk in the family Pomatiopsidae.This species serves as an intermediate host for Schistosoma mekongi.-Distribution:This species occurs:... |
South East Asia |
Species infecting animals other than humans
Schistosoma indicumSchistosoma indicum
Schistosoma spindale is a species of digenetic trematode in the family Schistosomatidae.The parasite is widespread in India and other Asian countries....
, Schistosoma nasale
Schistosoma nasale
Schistosoma nasale is a species of digenetic trematode in the family Schistosomatidae.Schistosoma nasale was identified in 1933 by Dr. M. A. N...
, Schistosoma leiperi are all parasites of ruminant
Ruminant
A ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...
s.
Schistosoma edwardiense and Schistosoma hippopotami are parasites of the hippo.
Morphology
Adult schistosomes share all the fundamental features of the digenea. They have a basic bilateral symmetry, oral and ventral suckers, a body covering of a syncytialSyncytium
In biology, a syncytium is a large cell-like structure; filled with cytoplasm and containing many nuclei. Most cells in eukaryotic organisms have a single nucleus; syncytia are specialized forms used by various organisms.The term may also refer to cells that are connected by specialized membrane...
tegument
Integumentary system
The integumentary system is the organ system that protects the body from damage, comprising the skin and its appendages...
, a blind-ending digestive system consisting of mouth
Mouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
, oesophagus and bifurcated caeca
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 area between the tegument and alimentary canal filled with a loose network of mesoderm cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, and an excretory or osmoregulatory system based on flame cell
Flame cell
right|frameA flame cell is a specialized excretory cell found in the simplest freshwater invertebrates, including flatworms , rotifers and nemerteans; these are the simplest animals to have a dedicated excretory system. Flame cells function like a kidney, removing waste materials...
s. Adult worms tend to be 10–20 mm (0.4-0.8 in) long and use globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
s from their hosts' hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
for their own circulatory system.
Reproduction
Unlike other trematodes, the schistosomes are dioeciousDioecious
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...
- i.e., the sexes are separate. The two sexes display a strong degree of sexual dimorphism
Sexual dimorphism
Sexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
, and the male is considerably larger than the female. The male surrounds the female and encloses her within his gynacophoric canal for the entire adult lives of the worms, where they reproduce sexually.
External links
- British Department for International Development Control of Schistosomiasis
- The World Health Organisation page on Schistosomiasis
- University of Cambridge Schistosome Laboratory
- Schistostoma parasites overview, biology, life cycle image at MetaPathogen
- Ross A. G., Sleigh A. C., Li Y., Davis G. M., Williams G. M., Jiang Z., Feng Z. & McManus D. P.(2001). "Schistosomiasis in the People's Republic of China: Prospects and Challenges for the 21st Century". Clinical Microbiology ReviewsClinical Microbiology ReviewsClinical Microbiology Reviews is an academic journal published by the American Society for Microbiology. The title is commonly abbreviated CMR and the ISSN is 0893-8512 for the print version, and 1098-6618 for the electronic version....
14(2): 270-295. , , doi:10.1128/CMR.14.2.270-295.2001.