Amoebiasis
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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 Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
may develop due to prolonged gastric bleeding. Cysts of ''Entamoeba'' can survive for up to a month in soil or for up to 45 minutes under fingernails. Invasion of the intestinal lining results in bloody diarrhea. If the parasite reaches the bloodstream it can spread through the body, most frequently ending up in the liver where it can cause amoebic liver abscesses.
Liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
abscesses can occur without previous diarrhea. Diagnosis is made by stool examination using
microscopy Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical mic ...
, but it can be difficult to distinguish ''E. histolytica'' from other harmless '' entamoeba'' species. An increased white blood cell count may be present in severe cases. The most accurate test is finding specific antibodies in the blood, but it may remain positive following treatment. Bacterial colitis can result in similar symptoms. Prevention of amoebiasis is by improved
sanitation Sanitation refers to public health conditions related to clean drinking water and treatment and disposal of human excreta and sewage. Preventing human contact with feces is part of sanitation, as is hand washing with soap. Sanitation systems ...
, including separating food and water from faeces. There is no vaccine. There are two treatment options depending on the location of the infection. Amoebiasis in tissues is treated with either
metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
, tinidazole,
nitazoxanide Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is ...
, dehydroemetine or chloroquine. Luminal infection is treated with diloxanide furoate or iodoquinoline. Effective treatment against all stages of the disease may require a combination of medications. Infections without symptoms may be treated with just one
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
, and infections with symptoms are treated with two antibiotics. Amoebiasis is present all over the world, though most cases occur in the
developing world A developing country is a sovereign state with a less-developed industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. There is also no clear agreeme ...
. It is estimated that approximately 50 million people worldwide are infected with ''Entamoeba histolytica'' each year, with approximately 100,000 deaths among them. The first case of amoebiasis was documented in 1875. In 1891, the disease was described in detail, resulting in the terms ''amoebic
dysentery 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 dehyd ...
'' and ''amoebic liver abscess''. Further evidence from the Philippines in 1913 found that upon swallowing cysts of ''E. histolytica'' volunteers developed the disease.


Signs and symptoms

Most infected people, about 90%, are
asymptomatic Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...
, but this disease has the potential to become serious. It is estimated that about 40,000 to 100,000 people worldwide die annually due to amoebiasis. Infections can sometimes last for years if there is no treatment. Symptoms, if present, can take anywhere from days to years to develop, but usually it is about two to four weeks. Symptoms can range from mild diarrhea to
dysentery 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 dehyd ...
with blood, coupled with intense abdominal pains. Extra-intestinal complications might also arise as a result of invasive infection which includes colitis, liver, lung, or brain abscesses. The blood comes from bleeding lesions created by the amoebae invading the lining of the colon. In about 10% of invasive cases the amoebae enter the bloodstream and may travel to other organs in the body. Most commonly this means the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, as this is where blood from the intestine reaches first, but they can end up almost anywhere in the body. Onset time is highly variable and the average asymptomatic infection persists for over a year. It is theorized that the absence of symptoms or their intensity may vary with such factors as strain of amoeba, immune response of the host, and perhaps associated
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
and
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es. In asymptomatic infections, the amoeba lives by eating and digesting bacteria and food particles in the gut, a part of the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
. It does not usually come in contact with the intestine itself due to the protective layer of mucus that lines the gut. Disease occurs when amoeba comes in contact with the cells lining the intestine. It then secretes the same substances it uses to digest bacteria, which include
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that destroy
cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
s and
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s. This process can lead to penetration and digestion of human tissues, resulting first in flask-shaped ulcerations in the intestine. ''Entamoeba histolytica'' ingests the destroyed cells by
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
and is often seen with red blood cells (a process known as erythrophagocytosis) inside when viewed in stool samples. Especially in
Latin America Latin America is the cultural region of the Americas where Romance languages are predominantly spoken, primarily Spanish language, Spanish and Portuguese language, Portuguese. Latin America is defined according to cultural identity, not geogr ...
, a
granuloma A granuloma is an aggregation of macrophages (along with other cells) that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such sub ...
tous mass (known as an amoeboma) may form in the wall of the ascending colon or
rectum The rectum (: rectums or recta) is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. Before expulsion through the anus or cloaca, the rectum stores the feces temporarily. The adult ...
due to long-lasting immunological cellular response, and is sometimes confused with
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. The ingestion of one viable cyst may cause an infection. Steroid therapy can occasionally provoke severe amoebic colitis in people with any ''E. histolytica'' infection. This bears high mortality: on average more than 50% with severe colitis die.


Cause

Amoebiasis is an infection caused by the amoeba ''Entamoeba histolytica''.


Transmission

Amoebiasis is usually transmitted by the fecal-oral route, but it can also be transmitted indirectly through contact with dirty hands or objects as well as by anal-oral contact. Infection is spread through ingestion of the cyst form of the
parasite Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted str ...
, a semi-dormant and hardy structure found in
feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...
. Any non-encysted amoebae, or '' trophozoites'', die quickly after leaving the body but may also be present in stool: these are rarely the source of new infections. Since amoebiasis is transmitted through contaminated food and water, it is often endemic in regions of the world with limited modern
sanitation Sanitation refers to public health conditions related to clean drinking water and treatment and disposal of human excreta and sewage. Preventing human contact with feces is part of sanitation, as is hand washing with soap. Sanitation systems ...
systems, including México, Central America, western
South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a considerably smaller portion in the Northern Hemisphere. It can also be described as the southern Subregion#Americas, subregion o ...
,
South Asia South Asia is the southern Subregion#Asia, subregion of Asia that is defined in both geographical and Ethnicity, ethnic-Culture, cultural terms. South Asia, with a population of 2.04 billion, contains a quarter (25%) of the world's populatio ...
, and western and southern
Africa Africa is the world's second-largest and second-most populous continent after Asia. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 20% of Earth's land area and 6% of its total surfac ...
. Amoebic dysentery is one form of traveler's diarrhea. It is more prevalent in long-term travelers with stays of longer than six months as opposed to travelers who spend less than one month in an endemic area. Diarrhea is more likely to be caused by a parasite, such as ''E. histolytica'', if it has subacute or chronic characteristics.


Pathogenesis

Amoebiasis results from tissue destruction induced by the ''E. histolytica'' parasite. ''E. histolytica'' causes tissue damage by three main events: direct host cell killing, inflammation, and parasite invasion. The pathogenesis of amoebiasis involves interplay of various molecules secreted by E. histolytica such as LPPG, lectins, cysteine proteases, and amoebapores. Lectins help in the attachment of the parasite to the mucosal layer of the host during invasion. The amoebapores destroy the ingested bacteria present in the colonic environment. Cysteine proteases lyse the host tissues. Other molecules such as PATMK, myosins, G proteins, C2PK, CaBP3, and EhAK1 play an important role in the process of phagocytosis.


Diagnosis

With colonoscopy it is possible to detect small ulcers of between 3–5mm, but diagnosis may be difficult as the mucous membrane between these areas can look either healthy or inflamed. Trophozoites may be identified at the ulcer edge or within the tissue, using immunohistochemical staining with specific anti-E. histolytica antibodies. Asymptomatic human infections are usually diagnosed by finding cysts shed in the stool. Various flotation or sedimentation procedures have been developed to recover the cysts from fecal matter and stains help to visualize the isolated cysts for microscopic examination. Since cysts are not shed constantly, a minimum of three stools are examined. In symptomatic infections, the motile form (the trophozoite) is often seen in fresh feces. Serological tests exist, and most infected individuals (with symptoms or not) test positive for the presence of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
. The levels of antibody are much higher in individuals with
liver abscess A liver abscess is a mass filled with pus inside the liver. Common causes are abdominal conditions such as appendicitis or diverticulitis due to haematogenous spread through the portal vein. It can also develop as a complication of a liver injury. ...
es. Serology only becomes positive about two weeks after infection. More recent developments include a kit that detects the presence of amoeba proteins in the feces, and another that detects amoeba DNA in feces. These tests are not in widespread use due to their expense. Microscopy is still by far the most widespread method of diagnosis around the world. However it is not as sensitive or accurate in diagnosis as the other tests available. It is important to distinguish the ''E. histolytica'' cyst from the cysts of nonpathogenic intestinal protozoa such as '' Entamoeba coli'' by its appearance. ''E. histolytica'' cysts have a maximum of four nuclei, while the commensal ''Entamoeba coli'' cyst has up to 8 nuclei. Additionally, in ''E. histolytica,'' the endosome is centrally located in the nucleus, while it is usually off-center in ''Entamoeba coli.'' Finally, chromatoidal bodies in ''E. histolytica'' cysts are rounded, while they are jagged in ''Entamoeba coli''. However, other species, '' Entamoeba dispar'' and ''E. moshkovskii'', are also commensals and cannot be distinguished from ''E. histolytica'' under the microscope. As ''E. dispar'' is much more common than ''E. histolytica'' in most parts of the world this means that there is a lot of incorrect diagnosis of ''E. histolytica'' infection taking place. The WHO recommends that infections diagnosed by microscopy alone should not be treated if they are asymptomatic and there is no other reason to suspect that the infection is actually ''E. histolytica''. Detection of cysts or trophozoites stools under microscope may require examination of several samples over several days to determine if they are present, because cysts are shed intermittently and may not show up in every sample. Typically, the organism can no longer be found in the feces once the disease goes extra-intestinal. Serological tests are useful in detecting infection by ''E. histolytica'' if the organism goes extra-intestinal and in excluding the organism from the diagnosis of other disorders. An Ova & Parasite (O&P) test or an ''E. histolytica'' fecal antigen assay is the proper assay for intestinal infections. Since antibodies may persist for years after clinical cure, a positive serological result may not necessarily indicate an active infection. A negative serological result, however, can be equally important in excluding suspected tissue invasion by ''E. histolytica''. Stool antigen detection tests have helped to overcome some of the limitations of stool microscopy. Antigen detection tests are easy to use, but they have variable sensitivity and specificity, especially in low-endemic areas.
Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR) is considered the gold standard for diagnosis but remains underutilized. Image:Ehistdisp cyst wtmt.jpg, Immature ''E. histolytica/E. dispar'' cyst in a concentrated wet mount stained with iodine. This early cyst has only one nucleus and a glycogen mass is visible (brown stain). Image:Amoebic dysentery in colon biopsy (1).jpg, Amoebae in a colon biopsy from a case of amoebic dysentery. File:Immunohistochemical staining of trophozoites (brown) using specific anti–Entamoeba histolytica macrophage migration inhibitory factor antibodies in a patient with amebic colitis.jpg, Immunohistochemical staining of trophozoites (brown) using specific anti–Entamoeba histolytica macrophage migration inhibitory factor antibodies in a patient with amoebic colitis.


Prevention

To help prevent the spread of amoebiasis around the home : * Wash hands thoroughly with soap and hot running water for at least 10 seconds after using the
toilet A toilet is a piece of sanitary hardware that collects human waste (urine and feces) and sometimes toilet paper, usually for disposal. Flush toilets use water, while dry or non-flush toilets do not. They can be designed for a sitting p ...
or changing a baby's diaper, and before handling food. * Clean bathrooms and
toilet A toilet is a piece of sanitary hardware that collects human waste (urine and feces) and sometimes toilet paper, usually for disposal. Flush toilets use water, while dry or non-flush toilets do not. They can be designed for a sitting p ...
s often; pay particular attention to toilet seats and taps. * Avoid sharing
towel A towel () is a piece of absorption (chemistry), absorbent cloth or paper used for drying or wiping a surface. Towels draw moisture through direct contact. Bathing towels and hand towels are usually made of cotton, linen, bamboo and Microfiber, ...
s or face washers. To help prevent infection: * Avoid raw vegetables when in
endemic Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...
areas, as they may have been fertilized using human feces. * Boil water or treat with iodine tablets. * Avoid eating street foods especially in public places where others are sharing sauces in one container Good sanitary practice, as well as responsible sewage disposal or treatment, are necessary for the prevention of ''E. histolytica'' infection on an endemic level. ''E.histolytica'' cysts are usually resistant to chlorination, therefore sedimentation and filtration of water supplies are necessary to reduce the incidence of infection. ''E. histolytica'' cysts may be recovered from contaminated food by methods similar to those used for recovering '' Giardia lamblia'' cysts from feces. Filtration is probably the most practical method for recovery from drinking water and liquid foods. ''E. histolytica'' cysts must be distinguished from cysts of other parasitic (but nonpathogenic) protozoa and from cysts of free-living protozoa as discussed above. Recovery procedures are not very accurate; cysts are easily lost or damaged beyond recognition, which leads to many falsely negative results in recovery tests.


Treatment

''E. histolytica'' infections occur in both the intestine and (in people with symptoms) in tissue of the intestine and/or liver. Those with symptoms require treatment with two medications, an amoebicidal tissue-active agent and a luminal cysticidal agent. Individuals that are asymptomatic only need a luminal cysticidal agent.


Prognosis

In the majority of cases, amoebas remain in the gastrointestinal tract of the hosts. Severe ulceration of the gastrointestinal mucosal surfaces occurs in less than 16% of cases. In fewer cases, the parasite invades the soft tissues, most commonly the liver. Only rarely are masses formed (amoebomas) that lead to intestinal obstruction (mistaken for caecum and appendicular mass). Other local complications include bloody diarrhea, pericolic and pericaecal abscess. Complications of hepatic amoebiasis includes subdiaphragmatic abscess, perforation of diaphragm to pericardium and pleural cavity, perforation to abdominal cavital ''(amoebic peritonitis)'' and perforation of skin ''( amoebiasis cutis)''. Pulmonary amoebiasis can occur from liver lesions by spread through the blood or by perforation of pleural cavity and lung. It can cause lung abscess, pulmono pleural fistula, empyema lung and broncho pleural fistula. It can also reach the brain through blood vessels and cause amoebic brain abscess and amoebic meningoencephalitis. Cutaneous amoebiasis can also occur in skin around sites of colostomy wound, perianal region, region overlying visceral lesion and at the site of drainage of liver abscess. Urogenital tract amoebiasis derived from intestinal lesion can cause amoebic vulvovaginitis ''(May's disease)'', rectovesicle fistula and rectovaginal fistula. ''Entamoeba histolytica'' infection is associated with malnutrition and stunting of growth in children.


Epidemiology

An estimated 500 million people worldwide are infected with ''Entamoeba'', the majority of whom are infected with ''E. dispar'' and an estimated 10% are infected with ''E. histolytica''. Mortality from invasive ''E. histolytica'' infection is estimated at 100,000 per year. Amoebiasis caused about 55,000 deaths worldwide in 2010, down from 68,000 in 1990. Although usually considered a tropical parasite, the first case reported (in 1875) was actually in St Petersburg in Russia, near the Arctic Circle. Infection is more common in warmer areas, but this is because of both poorer hygiene and the parasitic cysts surviving longer in warm moist conditions.


History

Amoebiasis was first described by Fedor A. Lösch in 1875, in northern Russia. The most dramatic incident in the US was the Chicago World's Fair outbreak in 1933, caused by contaminated drinking water. There were more than a thousand cases, with 98 deaths. It has been known since 1897 that at least one non-disease-causing species of ''Entamoeba'' existed (''Entamoeba coli''), but it was first formally recognized by the WHO in 1997 that ''E. histolytica'' was two species, despite this having first been proposed in 1925. In addition to the now-recognized ''E. dispar'', evidence shows there are at least two other species of ''Entamoeba'' that look the same in humans: '' E. moshkovskii'' and ''Entamoeba bangladeshi''. The reason these species haven't been differentiated until recently is because of the reliance on appearance. Joel Connolly of the Chicago Bureau of Sanitary Engineering brought the outbreak to an end when he found that defective plumbing permitted sewage to contaminate drinking water. In 1998 there was an outbreak of amoebiasis in the Republic of Georgia. Between 26 May and 3 September 1998, 177 cases were reported, including 71 cases of intestinal amoebiasis and 106 probable cases of liver abscess. The Nicobarese people have attested to the medicinal properties found in '' Glochidion calocarpum'', a plant common to India, saying that its bark and seed are most effective in curing abdominal disorders associated with amoebiasis.


Society and culture

An outbreak of amoebic dysentery occurs in Diana Gabaldon's novel '' A Breath of Snow and Ashes''.


References


External links


''Amoebiasis''
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Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
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