The ameboma is an inflammatory thickening of the intestinal wall around the ulcer which can be confused with a tumor. Amebiasis can also progress to a systemic, or extraintestinal infection.
Dissemination from the primary intestinal lesion is predominantly via the blood stream, but can also occur by direct extension of the lesion.
The liver is the most commonly affected organ and this is probably due to the direct transport of trophozoites from the large intestine to the liver via the hepatic portal vein Figure. Initially the lesions are small foci of necrosis which tend to coalesce into a single abscess as they expand. This hepatic abscess will continue to enlarge as the trophozoites progressively destroy and ingest host cells.
The center of the abscess, consisting of lysed hepatocytes, erythrocytes, bile and fat, may liquefy and this necrotic material sometimes incorrectly called pus will range in color from yellowish to reddish brown. Hematogenous spread of trophozoites to other sites, such as the lungs or brain, is rare, but does occur.
The second most common extraintestinal site after the liver is the lungs. Pulmonary infections generally result from a direct extension of the hepatic lesion across the diaphragm and into the pleura and lungs. Cutaneous lesions formed as a result of hepatic or intestinal fistula can also occur, although extremely rare. Other cutaneous lesions include perianal ulcers and involvement of the genitalia, including the penis of homosexuals.
These later manifestations are likely due to the skin or mucous membranes coming in contact with invasive trophozoites. As discussed above , E. Some of this difference in virulence is explained by the existence of the morphologically identical, but avirulent, E.
In contrast, anti-ameba humoral responses are observed in both asymptomatic and symptomatic E. This suggests that even in asymptomatic cases there is a limited amount of invasion. However, infection with E. The factors responsible for the pathogenesis of E.
One approach to understanding the pathogenesis is to compare possible virulence factors between these two closely related species. Possible Virulence Factors. Pathology results from host-parasite interactions, and therefore, host factors, parasite factors or a combination of both may contribute to the disease state.
For example, the development of invasive disease could be due to quantitative or qualitative aspects of the host immune response. Recruitment of neutrophils and intense inflammation are noted in the early phases of amebic invasion. However, inflammation surrounding established ulcers and abscesses if often minimal given the degree of tissue damage. The nature of protective immune responses is not clear. Innate or nonspecific immunity, as well as acquired immunity, are probably both important for the prevention of invasive disease.
The mucous layer covering the epitheilial cells can prevent contact between trophozoite and host cells. In addition, mucosal IgA responses do occur as a result of infection and fecal IgA against a trophozoite surface lectin see Eh-lectin are associated with a lower incidence of new E. High titers of serum antibodies also develop in patients with liver abscesses.
However, since the invasive disease is often progressive and unremitting, the role of these anti-ameba antibodies is in question. Cell-mediated responses appear to play a role in limiting the extent of invasive amebiasis and protecting the host from recurrence following successful treatment. Resistance to the host immune response is another possible virulence factor which could contribute to the development and exacerbation of invasive disease.
For example, one phenotypic difference between E. Lysis of neutrophils could also release toxic products which contribute to the destruction of host tissue. However, the role of these various phenomena in pathogenesis is not known. Invasion of intestinal mucosa by E.
Trophozoites adhere to the mucus layer step 1. This adherence per se probably does not contribute to pathogenesis and is simply a mechanism for the ameba to crawl along the substratum. Depletion of the mucus barrier allows for the trophozoite to come in contact with epithelial cells. Epithelial cells are killed in a contact dependent manner leading to a disruption of the intestinal mucosa step 2.
The trophozoites will continue to kill host cells in the submucosa and further disrupt the tissue as they advance step 3. Disruption of the intestinal wall step 4 or metastasis via the circulatory system step 5 is also possible. Adherence, cytotoxicity, and disruption of the tissues are important factors in the pathogenesis of E. Parasite proteins which could play a role in these processes include: the Eh-lectin , amebapore , and proteases.
Skip detailed discussions of Eh-lectin, amebapore, and proteases and go to clinical symptoms. Adherence of E. The contact-dependent killing of target cells is almost completely inhibited by galactose or GalNAc and target cells lacking terminal galactose residues on their surface glycoproteins are resistant to trophozoite adherence and cytotoxicity.
In addition, the Eh-lectin is involved in resistance to complement mediated lysis. The Eh-lectin is a heterodimer consisting of a kDa heavy chain and a kDa light chain joined by disulfide bonds. An intermediate subunit of kDa is noncovalently associated with the heterodimer. The heavy chain has a transmembrane domain and a carbohydrate binding domain. All of subunits are encoded by multigene families.
There are five members of the heavy chain family, members of the light chain family and 30 members of the intermediate chain family. Both E. Mucus is composed of glycoproteins called mucins. The predominant mucin found on the intestinal mucosa is Muc2 which is extensively glycosylated with O-linked GalNAc residues.
The sequence of the light and heavy chain genes from E. It is not known whether these sequence differences can account for the differences in virulence between E. Adherence is obviously important for both species, but it is possible that the adherence is qualitatively or quantitatively different between the two species.
A family of pore-forming polypeptides has been identified in E. The three family members are designated as amebapore A, B and C with amebapore A being predominant expressed. The mature polypeptide is 77 amino acids long and forms dimers at low pH Three of these dimers then assemble into a hollow ring-shaped structure.
This hexamer then can intercalate into membranes and introduce 2 nm pores i. The pore-forming activity is dependent on this assembly process beginning with the dimerization. In addition, the E. This difference in pore-forming activity has been attributed to a glutamate residue at position 2 in the E. This particular amino acid residue is important for the formation of the dimers and it is believed that the dimers of E. Amebapore is localized to vacuolar compartments eg, food vacuoles within the trophozoite and is most active at acidic pH suggesting that the major function of amebapore is to lyse ingested bacteria.
Nonetheless, amebapore is implicated as a virulence factor in that genetic manipulation of E. Similarly, modified E.
However, these amebas are able to cause inflammation and tissue damage in models for amebic colitis. Proteases are enzymes that degrade other proteins and could contribute to the pathogenesis cause by E. In this regard, E.
Cysteine proteases have been shown to disrupt the polymerization of MUC2, the major component of colonic mucus. This degraded mucus is less efficient at blocking adherence of trophozoites to epithelial cells. Destruction of the extracellular matrix ECM by proteases may also facilitate trophozoite invasion.
Inhibitors of cysteine proteases can decrease liver abscess size in experimental models. Twenty different cysteine protease genes have been identified in E. Orthologs of two of the E. One of these, designated CP5, is expressed at high levels on the trophozoite surface. Mutants expressing lower levels of CP5 had a reduced ability to generate liver abscesses in a hamster amebiasis model. However, these mutants also had a reduced growth rate and lower erythrophagocytic activity, thus it is not clear whether CP5 directly participates in the invasiveness of E.
Interestingly, over expression of CP2 in E. However, the over expression of CP2 did not lead to the ability of E. Therefore, it is not clear the precise roles proteases may play in pathogenesis. In summary, the pathogenesis associated with E.
Several potential virulence factors have been identified see Table. However, it is not clear the exact role these various virulence factors play in the development of invasive disease. One approach to understanding the pathogenesis is to compare these factors from E.
These two species are closely related and the potential virulence factors are found in both species. Adherence, cytolytic activity and proteolytic activity are inherent biological features of both species and these activities do not necessarily lead to pathology.
However, there are qualitative and quantitative differences between E. These genetic differences between E. However, pathogenesis is probably due to the combined effects of several host and parasite factors, and the virulence may represent the degree to which the host can control trophozoite invasion and replication.
The incubation period can range from a few days to months or years with weeks being the most common. Transitions from one type of intestinal syndrome to another can occur and intestinal infections can give rise to extraintestinal infections.
Clinical Syndromes Associated with Amebiasis. The majority of individuals diagnosed with E. This state can persist or progress to a symptomatic infection. Symptomatic nondysenteric infections exhibit variable symptoms ranging from mild and transient to intense and long lasting.
Typical symptoms include: diarrhea, cramps, flatulence, nausea, and anorexia. The diarrhea frequently alternates with periods of constipation or soft stools. Stools sometimes contain mucus, but there is no visible blood. Amebic dysentery usually starts slowly over several days with abdominal cramps, tenesmus, and occassional loose stools, but progresses to diarrhea with blood and mucus. Blood, mucus and pieces of necrotic tissue become more evident as the number of stools increases or more per day and stools will often contain little fecal material.
A few patients may develop fever, vomiting, abdominal tenderness, or dehydration especially children as the severity of the disease increases. Fulminant, or grangrenous, colitus is a rare but extremely severe form of intestinal amebiasis. Patients present with severe bloody diarrhea, fever, and diffuse abdominal tenderness. A chronic amebiasis, characterized by recurrent attacks of dysentery with intervening periods of mild or moderate gastrointestinal symptoms, can also occur. Amebomas present as painful abdominal masses which occur most frequently in the cecum and ascending colon.
Obstructive symptoms or hemorrhages may also be associated with an ameboma. Amebomas are infrequent and can be confused with carcinomas or tumors. Perianal ulcers are a form of cutaneous amebiasis that result from the direct spread of the intestinal infection. Amebic liver abscesses are the most common form of extraintestinal amebiasis. The onset of hepatic symptoms can be rapid or gradual.
Hepatic infections are characterized by hepatomegaly, liver tenderness, pain in the upper right quadrant, fever and anorexia. Fever sometimes occurs on a daily basis in the afternoon or evening. Liver function tests are usually normal or slightly abnormal and jaundice is unusual. Liver abscesses will occasionally rupture into the peritoneum resulting in peritonitis. Pulmonary amebiasis is generally results from the direct extension of the liver abscess through the diaphragm. Clinical symptoms most often include cough, chest pain, dyspnea difficult breathing , and fever.
The sputum may be purulent or blood-stained and contain trophozoites. A profuse expectoration ie, vomica of purulent material can also occur. Primary metastasis to the lungs is rare, but does occur. Similarly, infection of other organs eg. Clinical symptoms are related to the affected organ. Cutaneous amebiasis is the result of skin or mucus membranes being bathed in fluids containing trophozoites.
This contact can be the result of fistula intestinal, hepatic, perineal or an invasion of the genitalia. Cutaneous lesions have a wet, granular, necrotic surface with prominent borders and can be highly destructive. Clinical diagnosis is difficult and is usually considered with epidemiological risk factors eg. Definitive diagnosis of amebiasis requires the demonstration of E. Stool specimens should be preserved and stained and microscopically examined. Cysts will tend to predominate in formed stools and trophozoites in diarrheic stools see morphology.
Fresh stools can also be immediately examined for motile trophozoites which exhibit a progressive motility. Sigmoidoscopy may reveal the characteristic ulcers, especially in more severe disease.
Aspirates or biopsies should also be examined microscopically for trophozoites. Antigen detection kits are available for the positive identification of these species. One such rapid antigen detection test is the E. Serology is especially useful for the diagnosis of extraintestinal amebiasis. However, the antibodies can persist for years and distinguishing past and current infections may pose problems in endemic areas.
Non-invasive imaging techniques eg. It is also possible to aspirate hepatic abscesses. However, this is rarely done and only indicated in selected cases eg.
The aspirate is usually a thick reddish brown liquid that rarely contains trophozoites. Trophozoites are most likely to be found at the abscess wall and not in the necrotic debris at the abscess center. Several drugs are available for the treatment of amebiasis and the choice of drug s depends on the clinical stage of the infection Table. The prognosis following treatment is generally good in uncomplicated cases.
In cases where E. However, in many endemic areas, where the rates of reinfection are high and treatment is expensive, the standard practice is to only treat symptomatic cases.
Metronidazole or tinidazole if available is recommended for all symptomatic infections. This treatment should be followed by or combined with lumenal antiamebic drugs as described for asymptomatic patients.
In the cases of fulminant amemic colitis or perforation of the intestinal wall a broad spectrum antibiotic can also be used to treat intestinal bacteria in the peritoneum. Necrotic colitis requires urgent hospitalization to restore fluid and electrolyte balance. In addition, emetine or dehydroemetine are sometimes co-administered with the nitroimidazole. This is only done in the most severe cases due to the toxicity of these drugs. Surgery may also be needed to close perforations or a partial colostomy.
Abscess drainage of hepatic lesions ie, needle aspiration or surgical drainage is now rarely performed for therapeutic purposes and is only indicated in cases of large abscesses with a high probability of rupture. Prevention and control measures are similar to other diseases transmitted by the fecal-oral route see Risk Factors or discussion of Giardia control.
The major difference is that humans are the only host for E. Control is based on avoiding the contamination of food or water with fecal material. Health education in regards to improving personal hygiene, sanitary disposal of feces, and hand washing are particularly effective. Protecting water supplies will lower endemicity and epidemics. Like Giardia , Entamoeba cysts are resistant to standard chlorine treatment, but are killed by iodine or boiling. Sedimentation and filtration processes are quite effective at removing Entamoeba cysts.
Chemoprophylaxis is not recommended. Blastocystis hominis is a common organism found in human stools. Since its initial description approximately years ago, it has been variously classified as an ameba, a yeast, a sporozoan, and the cyst stage of a flagellate.
Analysis of the small subunit rRNA sequence indicates that Blastocystis is most closely related to the stramenopiles, a complex assemblage of unicellular and muticellular protists. Other stramenopiles include diatoms, brown algae, and water molds. Many of the characteristics of Blastocystis are unknown or controversial. The mode of transmission, mechanism of cell replication, and other features of the life cycle have not conclusively demonstrated. Similarly, the status of Blastocystis as a pathogen, commensal, or opportunistic organism is unknown.
Blastocystis is polymorphic in that a variety of morphological forms are found in feces and in vitro culture. This large vacuole pushes the nuclei and other organelles to the periphery of the cell. The vacuole is sometimes filled with a granular material.
Small resistant cyst-like forms have been identified from in vitro cultures and occasionally observed in feces. Furthermore, the cysts do not lyse when placed in water suggesting that they are resistant to environmental conditions. Presumably Blastocystis is transmitted via a fecal-oral route. However, this has not been conclusively demonstrated. There have been several reports suggesting Blastocystis causes disease, as well as many reports suggesting the opposite.
Diarrhea, cramps, nausea, vomiting and abdominal pain have been associated with large numbers of organisms in the stool. In addition, some studies have shown that treatment alleviates the symptoms and clears the organisms. However, the drugs used against Blastocystis eg. The inability to rule out other organisms as the source of symptoms and the observation that many infected persons exhibit no symptoms makes it difficult to draw any definitive conclusions about the pathogenesis of Blastocystis.
Furthermore, it could be that Blastocystis is primarily a commensal, but can exhibit virulence under specific host conditions like concomitant infections, poor nutrition, or immunosuppression.
Blastocystis is also found in a wide range of animals, including mammals, birds, reptiles, amphibians and even insects, and exhibits a wide range of molecular diversity. The genetic distance between Blastocystis isolates is greater than the genetic distance between E. This complicates the designation of species and historically human isolates have been designated as B. However, phylogenetic analysis reveals that there are no exclusively human clades and human isolates are found in all of the clades.
This raises the possibility that Blastocystis is not host specific and can be transmitted zoonotically. It was renamed Giardia lamblia by Stiles in in honor of Professor A.
Giard of Paris and Dr. Lambl of Prague. However, many consider the name Giardia duodenalis to be the correct taxonomic name for this protozoan. Giardia is protected by an outer shell called a cyst that allows it to survive outside the body for long periods of time and makes it somewhat tolerant to chlorine disinfection. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Parasites - Giardia. Section Navigation. Facebook Twitter LinkedIn Syndicate.
Pathogen and Environment. It can be isolated from the culture supernatant of Giardia lamblia , a parasitic flagellate in human and other mammals, and efficiently infects other virus-free G. A single-stranded copy of the viral RNA can be electroporated into uninfected G. Giardiavirus genomic cDNA of nt was constructed and its sequence revealed two large open reading frames that are separated by a -1 frameshift and share an overlap of nt.
A heptamer-pseudoknot structure much like those found at ribosomal slippage sites in retroviruses and yeast killer virus was identified within this overlap. Immunostudies using antisera against synthesized peptides from four regions in the two open reading frames indicated that the and kDa viral proteins share a common domain in the amino-terminal area. But the kDa protein makes a -1 switch of its reading frame beyond the presumed slippage heptamer and is therefore a -1 frameshift fusion protein similar to the gag-pol fusion protein found in retroviruses paraphrased from Wang reference, listed at bottom of page.
It has twin nuclei and an adhesive disk which is a rigid structure reinforced by supelicular microtubules. There are two median bodies of unknown function, but their shape is important for differentiating between species. There are 4 pairs of flagella, one anterior pair, two posterior pairs and a caudal pair. These organisms have no mitochondria, endoplasmic reticulum, golgi, or lysosomes.
Giardia has a two-stage life cycle consisting of trophozoite and cyst. These trophozoites attach to the surface of the intestinal epithelium using a ventral sucking disk and then reproduce by binary fission. Giardia' s main food source, glucose, is obtained by a process of diffusion or by pinocytosis. Like amoebae, they are aerotolerant anaerobes and require a reducing environment.
Food reserves are stored in the form of glycogen. Glucose catabolism via the glycolytic pathway results in production of the end products ethanol, acetate and carbon dioxide.
Giardia is found worldwide and infects humans as well as domestic and wild animals e. Giardia is found in soil, food, water, or surfaces that have been contaminated with the feces from infected humans or animals. One can become infected after accidentally swallowing the parasite, but one cannot become infected through contact with blood.
0コメント