Entamoeba histolytica

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Entamoeba histolytica
Entamoeba histolytica trophozoite.png
Entamoeba histolytica trophozoite
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Phylum: Amoebozoa
Family: Entamoebidae
Genus: Entamoeba
Species:
E. histolytica
Binomial name
Entamoeba histolytica
Schaudinn, 1903
Life-cycle of Entamoeba histolytica Entamoeba histolytica life cycle-en.svg
Life-cycle of Entamoeba histolytica

Entamoeba histolytica is an anaerobic parasitic amoebozoan, part of the genus Entamoeba . [1] Predominantly infecting humans and other primates causing amoebiasis, E. histolytica is estimated to infect about 35-50 million people worldwide. [1] E. histolytica infection is estimated to kill more than 55,000 people each year. [2] Previously, it was thought that 10% of the world population was infected, but these figures predate the recognition that at least 90% of these ball infections were due to a second species, E. dispar . [3] Mammals such as dogs and cats can become infected transiently, but are not thought to contribute significantly to transmission.

Contents

The word histolysis literally means disintegration and dissolution of organic tissues.

Transmission

The active (trophozoite) stage exists only in the host and in fresh loose feces; cysts survive outside the host in water, in soils, and on foods, especially under moist conditions on the latter. The infection can occur when a person puts anything into their mouth that has touched the feces of a person who is infected with E. histolytica, swallows something, such as water or food, that is contaminated with E. histolytica, or swallows E. histolytica cysts (eggs) picked up from contaminated surfaces or fingers. [4] The cysts are readily killed by heat and by freezing temperatures; they survive for only a few months outside of the host. [5] When cysts are swallowed, they cause infections by excysting (releasing the trophozoite stage) in the digestive tract. The pathogenic nature of E. histolytica was first reported by Fedor A. Lösch in 1875, [1] but it was not given its Latin name until Fritz Schaudinn described it in 1903. E. histolytica, as its name suggests (histolytic = tissue destroying), is pathogenic; infection can be asymptomatic, or it can lead to amoebic dysentery or amoebic liver abscess. [6] [7] Symptoms can include fulminating dysentery, bloody diarrhea, weight loss, fatigue, abdominal pain, and amoeboma. The amoeba can 'bore' into the intestinal wall, causing lesions and intestinal symptoms, and it may reach the blood stream or peritoneal cavity. [8] From there, it can reach vital organs of the human body, usually the liver, but sometimes the lungs, brain, and spleen. [9] A common outcome of this invasion of tissues is a liver abscess, which can be fatal if untreated. [8] Ingested red blood cells are sometimes seen in the amoeba cell cytoplasm. [10]

Risk factors

Poor sanitary conditions are known to increase the risk of contracting amebiasis E. histolytica. [11] In the United States, there is a much higher rate of amebiasis-related mortality in California and Texas (this might be caused by the proximity of those states to E. histolytica-endemic areas, such as Mexico), parts of Latin America, and Asia. [12] E. histolytica is also recognized as an emerging sexually transmissible pathogen, especially in male homosexual relations, causing outbreaks in non-endemic regions. [13] As such, high-risk sex behaviour is also a potential source of infection. [14] Although it is unclear whether there is a causal link, studies indicate a higher chance of being infected with E. histolytica if one is also infected with human immunodeficiency virus (HIV). [15] [16]

Genome

The E. histolytica genome was sequenced, assembled, and automatically annotated in 2005. [17] The genome was reassembled and reannotated in 2010. [18] The 20 million basepair genome assembly contains 8,160 predicted genes; known and novel transposable elements have been mapped and characterized, functional assignments have been revised and updated, and additional information has been incorporated, including metabolic pathways, Gene Ontology assignments, curation of transporters, and generation of gene families. [19] The major group of transposable elements in E. histolytica are non-LTR retrotransposons. These have been divided in three families called EhLINEs and EhSINEs (EhLINE1,2,3 and EhSINE1,2,3). [20] EhLINE1 encode an endonuclease (EN) protein (in addition to reverse transcriptase and nucleotide-binding ORF1), which have similarity with bacterial restriction endonuclease. This similarity with bacterial protein indicates that transposable elements have been acquired from prokaryotes by horizontal gene transfer in this protozoan parasite. [21]

The genome of E. histolytica has been found to have snoRNAs with opisthokont-like features. [22] The E. histolytica U3 snoRNA (Eh_U3 snoRNA) has showed sequence and structural features similar to Homo sapiens U3 snoRNA. [23]

Pathogen interaction

E. histolytica may modulate the virulence of certain human viruses and is itself a host for its own viruses.[ citation needed ]

For example, acquired immunodeficiency syndrome (AIDS) accentuates the damage and pathogenicity of E. histolytica. [16] On the other hand, cells infected with HIV are often consumed by E. histolytica. Infective HIV remains viable within the amoeba, although there has been no proof of human reinfection from amoeba carrying this virus. [24]

A burst of research on viruses of E. histolytica stems from a series of papers published by Diamond et al. from 1972 to 1979. In 1972, they hypothesized two separate polyhedral and filamentous viral strains within E. histolytica that caused cell lysis. Perhaps the most novel observation was that two kinds of viral strains existed, and that within one type of amoeba (strain HB-301) the polyhedral strain had no detrimental effect but led to cell lysis in another (strain HK-9). Although Mattern et al. attempted to explore the possibility that these protozoal viruses could function like bacteriophages, they found no significant changes in Entamoeba histolytica virulence when infected by viruses. [25]

Immunopathogenesis

E. histolytica causes tissue destruction which leads to clinical disease. E. histolytica induces tissue damage by three main events: direct host cell death, inflammation, and parasite invasion. Once the trophozoites are excysted in the terminal ileum region, they colonize the large bowel, remaining on the surface of the mucus layer and feeding on bacteria and food particles. Occasionally, and in response to unknown stimuli, trophozoites move through the mucus layer where they come in contact with the epithelial cell layer and start the pathological process. E. histolytica has a lectin that binds to galactose and N-acetylgalactosamine sugars on the surface of the epithelial cells, The lectin normally is used to bind bacteria for ingestion. The parasite has several enzymes such as pore forming proteins, lipases, and cysteine proteases, which are normally used to digest bacteria in food vacuoles but which can cause lysis of the epithelial cells by inducing cellular necrosis and apoptosis when the trophozoite comes in contact with them and binds via the lectin. Enzymes released allow penetration into intestinal wall and blood vessels, sometimes on to liver and other organs. The trophozoites will then ingest these dead cells. This damage to the epithelial cell layer attracts human immune cells and these in turn can be lysed by the trophozoite, which releases the immune cell's own lytic enzymes into the surrounding tissue, creating a type of chain reaction and leading to tissue destruction. This destruction manifests itself in the form of an 'ulcer' in the tissue, typically described as flask-shaped because of its appearance in transverse section. This tissue destruction can also involve blood vessels leading to bloody diarrhea, amebic dysentery. Occasionally, trophozoites enter the bloodstream where they are transported typically to the liver via the portal system. In the liver a similar pathological sequence ensues, leading to amebic liver abscesses. The trophozoites can also end up in other organs, sometimes via the bloodstream, sometimes via liver abscess rupture or fistulas. Similarly, when the trophozoites travel to the brain, they can cause amoebic brain abscess. [26]

Diagnosis

Diagnosis is confirmed by microscopic examination for trophozoites or cysts in fresh or suitably preserved faecal specimens, smears of aspirates or scrapings obtained by proctoscopy, and aspirates of abscesses or other tissue specimen. A blood test is also available, but it is recommended only when a healthcare provider believes the infection may have spread beyond the intestine to some other organ of the body, such as the liver. However, this blood test may not be helpful in diagnosing current illness, because the test can be positive if the patient has had amebiasis in the past, even if they are not infected at the time of the test. [27] Stool antigen detection and PCR are available for diagnosis, and are more sensitive and specific than microscopy. [2]

Treatment

There are a number of effective medications. Several antibiotics are available to treat Entamoeba histolytica. The infected individual will be treated with only one antibiotic if the E. histolytica infection has not made the person sick, and will most likely be prescribed two antibiotics if the person has been feeling sick. [28] Otherwise, below are other options for treatments.

Intestinal infection

Usually nitroimidazole derivatives (such as metronidazole) are used, because they are highly effective against the trophozoite form of the amoeba. Since they have little effect on amoeba cysts, usually this treatment is followed by an agent (such as paromomycin or diloxanide furoate) that acts on the organism in the lumen. [2]

Liver abscess

In addition to targeting organisms in solid tissue, primarily with drugs like metronidazole and chloroquine, treatment of liver abscess must include agents that act in the lumen of the intestine (as in the preceding paragraph) to avoid re-invasion. Surgical drainage is usually not necessary, except when rupture is imminent. [29]

People without symptoms

For people without symptoms (otherwise known as asymptomatic carriers), non-endemic areas should be treated by paromomycin; other treatments include diloxanide furoate, and iodoquinol.[ citation needed ] There have been problems with the use of iodoquinol and iodochlorhydroxyquin, so their use is not recommended. Diloxanide furoate can also be used by mildly symptomatic persons who are just passing cysts.[ citation needed ]

Genus and speciesEntamoeba histolytica
Etiologic agent of: Amoebiasis; amoebic dysentery; extraintestinal amoebiasis, usually amoebic liver abscess; "anchovy sauce"); amoeba cutis; amoebic lung abscess ("liver-colored sputum")
Infective stageTetranucleated cyst (having 2–4 nuclei)
Definitive hostHuman
Portal of entryMouth
Mode of transmissionIngestion of mature cyst through contaminated food or water
HabitatColon and cecum
Pathogenic stage Trophozoite
Locomotive apparatusPseudopodia ("false foot”")
MotilityActive, progressive and directional
Nucleus'Ring and dot' appearance: peripheral chromatin and central karyosome
Mode of reproductionBinary fission
PathogenesisLytic necrosis (it looks like “flask-shaped” holes in Gastrointestinal tract sections (GIT)
Type of encystmentProtective and Reproductive
Lab diagnosisMost common is direct fecal smear (DFS) and staining (but does not allow identification to species level); enzyme immunoassay (EIA); indirect hemagglutination (IHA); Antigen detection – monoclonal antibody; PCR for species identification. Sometimes only the use of a fixative (formalin) is effective in detecting cysts. Culture: From faecal samples – Robinson's medium, Jones' medium
Treatment Metronidazole for the invasive trophozoites PLUS a lumenal amoebicide for those still in the intestine. Paromomycin (Humatin) is the luminal drug of choice, since Diloxanide furoate (Furamide) is not commercially available in the United States or Canada (being available only from the Centers for Disease Control and Prevention). A direct comparison of efficacy showed that Paromomycin had a higher cure rate. [30] Paromomycin (Humatin) should be used with caution in patients with colitis, as it is both nephrotoxic and ototoxic. Absorption through the damaged wall of the intestinal tract can result in permanent hearing loss and kidney damage. Recommended dosage: metronidazole 750 mg three times a day orally, for 5 to 10 days followed by paromomycin 30 mg/kg/day orally in 3 equal doses for 5 to 10 days or Diloxanide furoate 500 mg 3 times a day orally for 10 days, to eradicate lumenal amoebae and prevent relapse. [31] [32]
Trophozoite stage
Pathognomonic/diagnostic featureIngested RBC; distinctive nucleus
Cyst Stage
Chromatoidal body'Cigar' shaped bodies (made up of crystalline ribosomes)
Number of nuclei1 in early stages, 4 when mature
Pathognomonic/diagnostic feature'Ring and dot' nucleus and chromatoid bodies

Meiosis

In sexually reproducing eukaryotes, homologous recombination (HR) ordinarily occurs during meiosis. The meiosis-specific recombinase, Dmc1, is required for efficient meiotic HR, and Dmc1 is expressed in E. histolytica. [33] The purified Dmc1 from E. histolytica forms presynaptic filaments and catalyzes ATP-dependent homologous DNA pairing and DNA strand exchange over at least several thousand base pairs. [33] The DNA pairing and strand exchange reactions are enhanced by the eukaryotic meiosis-specific recombination accessory factor (heterodimer) Hop2-Mnd1. [33] These processes are central to meiotic recombination, suggesting that E. histolytica undergoes meiosis. [33]

Several other genes involved in both mitotic and meiotic HR are also present in E. histolytica. [34] HR is enhanced under stressful growth conditions (serum starvation) concomitant with the up-regulation of HR-related genes. [35] Also, UV irradiation induces DNA damage in E. histolytica trophozoites and activates the recombinational DNA repair pathway. [34] In particular, expression of the Rad51 protein (a recombinase) is increased about 15-fold by UV treatment. [34]

See also

Related Research Articles

<i>Entamoeba</i> Genus of internal parasites

Entamoeba is a genus of Amoebozoa found as internal parasites or commensals of animals. In 1875, Fedor Lösch described the first proven case of amoebic dysentery in St. Petersburg, Russia. He referred to the amoeba he observed microscopically as Amoeba coli; however, it is not clear whether he was using this as a descriptive term or intended it as a formal taxonomic name. The genus Entamoeba was defined by Casagrandi and Barbagallo for the species Entamoeba coli, which is known to be a commensal organism. Lösch's organism was renamed Entamoeba histolytica by Fritz Schaudinn in 1903; he later died, in 1906, from a self-inflicted infection when studying this amoeba. For a time during the first half of the 20th century the entire genus Entamoeba was transferred to Endamoeba, a genus of amoebas infecting invertebrates about which little is known. This move was reversed by the International Commission on Zoological Nomenclature in the late 1950s, and Entamoeba has stayed 'stable' ever since.

<span class="mw-page-title-main">Dysentery</span> Inflammation of the intestine causing diarrhea with blood

Dysentery, historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications may include dehydration.

<i>Entamoeba coli</i> Species of parasitic amoeba

Entamoeba coli is a non-pathogenic species of Entamoeba that frequently exists as a commensal parasite in the human gastrointestinal tract. E. coli is important in medicine because it can be confused during microscopic examination of stained stool specimens with the pathogenic Entamoeba histolytica. This amoeba does not move much by the use of its pseudopod, and creates a "sur place (non-progressive) movement" inside the large intestine. Usually, the amoeba is immobile, and keeps its round shape. This amoeba, in its trophozoite stage, is only visible in fresh, unfixed stool specimens. Sometimes the Entamoeba coli have parasites as well. One is the fungus Sphaerita spp. This fungus lives in the cytoplasm of the E. coli. While this differentiation is typically done by visual examination of the parasitic cysts via light microscopy, new methods using molecular biology techniques have been developed. The scientific name of the amoeba, E. coli, is often mistaken for the bacterium, Escherichia coli. Unlike the bacterium, the amoeba is mostly harmless, and does not cause as many intestinal problems as some strains of the E. coli bacterium. To make the naming of these organisms less confusing, "alternate contractions" are used to name the species for the purpose making the naming easier; for example, using Esch. coli and Ent. coli for the bacterium and amoeba, instead of using E. coli for both.

<span class="mw-page-title-main">Amoebozoa</span> Phylum of protozoans

Amoebozoa is a major taxonomic group containing about 2,400 described species of amoeboid protists, often possessing blunt, fingerlike, lobose pseudopods and tubular mitochondrial cristae. In traditional classification schemes, Amoebozoa is usually ranked as a phylum within either the kingdom Protista or the kingdom Protozoa. In the classification favored by the International Society of Protistologists, it is retained as an unranked "supergroup" within Eukaryota. Molecular genetic analysis supports Amoebozoa as a monophyletic clade. Modern studies of eukaryotic phylogenetic trees identify it as the sister group to Opisthokonta, another major clade which contains both fungi and animals as well as several other clades comprising some 300 species of unicellular eukaryotes. Amoebozoa and Opisthokonta are sometimes grouped together in a high-level taxon, named Amorphea. Amoebozoa includes many of the best-known amoeboid organisms, such as Chaos, Entamoeba, Pelomyxa and the genus Amoeba itself. Species of Amoebozoa may be either shelled (testate) or naked, and cells may possess flagella. Free-living species are common in both salt and freshwater as well as soil, moss and leaf litter. Some live as parasites or symbionts of other organisms, and some are known to cause disease in humans and other organisms.

A trophozoite is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing Plasmodium falciparum and those of the Giardia group. The complementary form of the trophozoite state is the thick-walled cyst form. They are often different from the cyst stage, which is a protective, dormant form of the protozoa. Trophozoites are often found in the host's body fluids and tissues and in many cases, they are the form of the protozoan that causes disease in the host. In the protozoan, Entamoeba histolytica it invades the intestinal mucosa of its host, causing dysentery, which aid in the trophozoites traveling to the liver and leading to the production of hepatic abscesses.

Dientamoebiasis is a medical condition caused by infection with Dientamoeba fragilis, a single-cell parasite that infects the lower gastrointestinal tract of humans. It is an important cause of traveler's diarrhea, chronic abdominal pain, chronic fatigue, and failure to thrive in children.

<i>Balamuthia mandrillaris</i> Species of pathogenic Amoebozoa

Balamuthia mandrillaris is a free-living amoeba that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). B. mandrillaris is a soil-dwelling amoeba and was first discovered in 1986 in the brain of a mandrill that died in the San Diego Wild Animal Park.

<i>Entamoeba gingivalis</i> Species of amoeba

Entamoeba gingivalis is an opportunistic Amoebozoa and is the first amoeba in humans to be described.

<span class="mw-page-title-main">Protozoan infection</span> Parasitic disease caused by a protozoan

Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. These organisms are now classified in the supergroups Excavata, Amoebozoa, Harosa, and Archaeplastida. They are usually contracted by either an insect vector or by contact with an infected substance or surface.

An amebicide is an agent that is destructive to amoeba, especially parasitic amoeba that cause amoebiasis.

<span class="mw-page-title-main">Amoebiasis</span> Human disease caused by amoeba protists

Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba Entamoeba histolytica. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulcerations, abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. Anemia may develop due to prolonged gastric bleeding.

<span class="mw-page-title-main">Amoebic liver abscess</span> Medical condition

A amoebic liver abscess is a type of liver abscess caused by amebiasis. It is the involvement of liver tissue by trophozoites of the organism Entamoeba histolytica and of its abscess due to necrosis.

<span class="mw-page-title-main">Amoebic brain abscess</span> Medical condition

Amoebic brain abscess is an affliction caused by the anaerobic parasitic protist Entamoeba histolytica. It is extremely rare; the first case being reported in 1849. Brain abscesses resulting from Entamoeba histolytica are difficult to diagnose and very few case reports suggest complete recovery even after the administration of appropriate treatment regimen.

Cutaneous amoebiasis, refers to a form of amoebiasis that presents primarily in the skin. It can be caused by Acanthamoeba or Entamoeba histolytica. When associated with Acanthamoeba, it is also known as "cutaneous acanthamoebiasis". Balamuthia mandrillaris can also cause cutaneous amoebiasis, but can prove fatal if the amoeba enters the bloodstream It is characterized by ulcers. Diagnosis of amebiasis cutis calls for high degree of clinical suspicion. This needs to be backed with demonstration of trophozoites from lesions. Unless an early diagnosis can be made such patients can develop significant morbidity.

<span class="mw-page-title-main">Dehydroemetine</span> Chemical compound

Dehydroemetine is a synthetically produced antiprotozoal agent similar to emetine in its anti-amoebic properties and structure, but it produces fewer side effects. In the United States, it is manufactured by Roche.

Entamoeba polecki is an intestinal parasite of the genus Entamoeba. E. polecki is found primarily in pigs and monkeys and is largely considered non-pathogenic in humans, although there have been some reports regarding symptomatic infections of humans. Prevalence is concentrated in New Guinea, with distribution also recorded in areas of southeast Asia, France, and the United States.

<i>Dientamoeba fragilis</i> Parasite of humans, pigs and gorillas

Dientamoeba fragilis is a species of single-celled excavates found in the gastrointestinal tract of some humans, pigs and gorillas. It causes gastrointestinal upset in some people, but not in others. It is an important cause of traveller's diarrhoea, chronic diarrhoea, fatigue and, in children, failure to thrive. Despite this, its role as a "commensal, pathobiont, or pathogen" is still debated. D. fragilis is one of the smaller parasites that are able to live in the human intestine. Dientamoeba fragilis cells are able to survive and move in fresh feces but are sensitive to aerobic environments. They dissociate when in contact or placed in saline, tap water or distilled water.

Entamoeba moshkovskii is part of the genus Entamoeba. It is found in areas with polluted water sources, and is prevalent in places such as Malaysia, India, and Bangladesh, but more recently has made its way to Turkey, Australia, and North America. This amoeba is said to rarely infect humans, but recently this has changed. It is in question as to whether it is pathogenic or not. Despite some sources stating this is a free living amoeba, various studies worldwide have shown it contains the ability to infect humans, with some cases of pathogenic potential being reported. Some of the symptoms that often occur are diarrhea, weight loss, bloody stool, and abdominal pain. The first known human infection also known as the "Laredo strain" of Entamoebic mushkovskii was in Laredo, Texas in 1991, although it was first described by a man named Tshalaia in 1941 in Moscow, Russia. It is known to affect people of all ages and genders.

Entamoeba invadens is an amoebozoa parasite of reptiles, within the genus Entamoeba. It is closely related to the human parasite Entamoeba histolytica, causing similar invasive disease in reptiles, in addition to a similar morphology and lifecycle.

<i>Naegleria fowleri</i> Species of free-living excavate form of protist

Naegleria fowleri, also known as the brain-eating amoeba, is a species of the genus Naegleria. It belongs to the phylum Percolozoa and is classified as an amoeboflagellate excavate, an organism capable of behaving as both an amoeba and a flagellate. This free-living microorganism primarily feeds on bacteria but can become pathogenic in humans, causing an extremely rare, sudden, severe, and almost always fatal brain infection known as naegleriasis or primary amoebic meningoencephalitis (PAM).

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