CLINICAL PRESENTATION, PATHOGENESIS, TREATMENT AND PREVENTION OF AMEBIASIS

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Amebiasis (amebic dysentery) is a parasitic disease that is characterized by abscesses in the liver and ulcers in the intestines. The disease occurs worldwide, and it is usually associated with poor sanitary conditions. Amebiasis, which is mainly transmitted through the feacal-oral route, thrives in places where personal hygiene and adequate public sanitation is poor or lacking. The disease is widespread in temperate regions, occurring in both tropical and subtropical countries of the world including Africa.

Amebiasis is majorly caused by Entamoeba histolytica, an anaerobic amoebic protozoan found in the genus Entamoeba. Entamoeba species are found in the Phylum Amoebozoa, Class Lobosea, Order Amoebida, and Genus Entamoeba. Other species of Entamoeba that parasitizes the intestinal tract of humans include: Entamoeba coli (E. coli), E. dispar, E. gingivalis, E. hartmanni, and E. polecki. E. histolytica is the most invasive protozoan in the genus Entamoeba, and it is responsible for the most severe forms of amebiasis including amoebic liver abscesses and amoebic dysentery. Other species of Entamoeba are nonpathogenic (noninvasive) and usually cause asymptomatic colonization of the human gut especially the intestines.

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Type and morphology of Entamoeba histolytica

E. histolytica is a non-flagellated but pseudopod-like protozoan. Morphologically, E. histolytica exist in only two forms viz: trophozoites (noninfectious vegetative form that multiplies rapidly in the gut) and cysts (infectious forms with hard cell wall that helps it to survive gastric acid in stomach and chlorine in water). The trophozoites of E. histolytica have a variable shape and size that ranges between 10-50 µm. they are motile and possess finger-like pseudopodia that enables them to move. Trophozoites are the only form of E. histolytica found in tissues, and they also have a centrally placed nucleus and may ingest red blood cells (a process known as erythrophagocytosis). Erythrophagocytosis is the ingestion of erythrocytes by the trophozoites of E. histolytica. It is the only morphological feature that can be used to differentiate E. histolytica from E. dispar, a nonpathogenic parasite. The cyst of E. histolytica is nonmotile, round in shape and measures about 10-20 µm in size. Mature cysts of E. histolytica are quadrinucleate (i.e. it contains four nuclei only), and they have very thick walls made of hyaline. Immature cysts are uninucleate (i.e. they contain only one nuclei), and they also possess chromatoid bodies and glycogen vacuoles which all disappear when the immature cyst transforms into a mature cyst through nuclear division. Cysts are present in the lumen of the large intestine (colon) of their human host, and they are excreted in the feaces of infected individuals together with trophozoites or alone. However, trophozoites (which are invasive in nature) are normally excreted and found in diarrheal (watery) stool while cysts (which are infectious but noninvasive) are found and excreted in formed stool of persons infected with E. histolytica.

Vector, reservoir and habitat of Entamoeba histolytica

E. histolytica do not have an insect vector. Human beings are the only primary reservoir and host of E. histolytica. E. histolytica is a parasite that thrives in the gut of its human host, and has no other intermediate host other than this. The parasite can be transmitted from one human host to another via the ingestion of E. histolytica cysts excreted in the feaces of an infected individual.  

Clinical signs and symptoms Entamoeba histolytica infection

Clinically, the signs and symptoms of amebiasis are inconsistent, and infected patients may remain clinically well over an extended period of time even though they harbour E. histolytica. However, some of the signs and symptoms of E. histolytica infection may include: diarrhea containing mucus and blood, vomiting, nausea, dehydration, fever, abdominal cramp and flatulence. Other significant syndrome of the disease which may develop after long periods of covertness in infected persons or after some weeks of infection include liver abscess, colitis and ulceration of the intestinal mucosa. E. histolytica is notorious in invading the mucosa of its human host from where it moves to the liver to produce an abscess. In most cases, E. histolytica can live in the human gut for a long period of time as normal commensal organism even without causing any significant clinical episode that is characteristic of amebiasis.  

Pathogenesis of Entamoeba histolytica infection

Human infection with E. histolytica begins with the ingestion of mature cysts of the parasite (known as metacysts) either through feacally-contaminated hand, food or water (Figure 1). After ingestion, the cysts undergo excystation in the small intestines to produce trophozoites which find their way to the colon (large intestine) where they can invade host tissues and live as commensal organisms in the lumen of the intestine while feeding on erythrocytes, bacteria and yeast. The feeding of erythrocytes by trophozoites of E. histolytica is known as erythrophagocytosis. Trophozoites of E. histolytica is notorious for mucosal and luminal invasion, and disease usually results following the invasion of the intestinal epithelium by trophozoites. The trophozoites of E. histolytica may also migrate to the appendix and even block the lumen due to their growth, thus resulting in further chronic secondary infections.

Figure 1. Life cycle of Entamoeba. 1. Cysts and trophozoites of E. histolytica are passed in human feces. 2. Human infection is initiated following the ingestion of mature cysts of E. histolytica in feacally contaminated food, water, or hands. 3. The mature cystsundergo excystation in the small intestine to release trophozoites. 4. Thetrophozoites migrate to the large intestine, multiply by binary fission and produce cysts. Both cysts and trophozoites are again passed in the feaces of human hosts. While the cysts (with walls that confer protection) of E. histolytica passed in stool can survive for days to weeks in the external environment, the trophozoites are rapidly destroyed once outside the body, and if ingested by humans, it would not survive exposure to the gastric environment. Invasion of trophozoites can result in three distinct manifestations: A. Noninvasive infection (when the trophozoites remain confined to the intestinal lumen). B. Intestinal disease (when the trophozoites invade the intestinal mucosa). C. Extraintestinal disease (when the trophozoites invade extraintestinal sites such as the liver, brain, and lungs). CDC

Migration of the parasite to other sites of the body excluding the intestines can culminate to extraintestinal amebiasis of which liver abscess is a typical example. Metastasis may also occur to other vital organs of the body including the brain, spleen, and lungs after first migrating to the liver where it causes liver abscess (amoebic hepatitis). Jaundice and anaemia may result in patients with multiple liver abscesses. However, extraintestinal E. histolytica infection is rare in most cases of the disease. Host factors including its immunologic prowess may help modulate the invasiveness of the invading E. histolytica strain, thus reducing tissue damage of the disease. Other host factors that may also help to restrain the pathogenicity of the parasite include gut motility and the absence of a suitable Enterobacteriaceae that encourages the growth of E. histolytica in the gut. Both trophozoites and cysts of E. histolytica are passed in the stool of infected patients, but only the resistant cyst form of the parasite can survive outside the human host, and serve as route via which the protozoan is transmitted from persons to persons through the feacal-oral route.

Laboratory diagnosis of Entamoeba histolytica infection

The laboratory diagnosis of E. histolytica infection is primarily based on the demonstration and microscopical detection of trophozoites (Figure 2) and cysts (Figure 3) in feaces of infected persons through concentration technique, staining or wet mount. Trophozoites can also be detected in host tissues due to its ability to invade them. If detected in feaces, trophozoites of E. histolytica must be differentiated from nonpathogenic Entamoeba species such as E. dispar which do not ingest and harbour erythrocytes like E. histolytica since their cysts are morphologically indistinguishable. While fresh and watery stool is required for detecting trophozoites, a formed stool is most appropriate for cysts detection. Serological tests to detect antigens of E. histolytica are also available for clinical use. Other available methods for the laboratory diagnosis of E. histolytica include PCR which detect the parasites DNA, colonoscopy for diagnosis of amoebic colitis and imaging techniques such as MRI and CT scan which is preferable for diagnosing amoebic abscesses. 

Figure 2. E. histolytica trophozoite in a direct wet mount stained with iodine (A) and trichromestainedE. histolytica trophozoite with ingested red blood cells (B). CDC
Figure 3. Concentrated wet mount of stool containing cysts of E. histolytica stained with iodine (A)  and unstained concentrated wet mount of stool containing cysts of E. histolytica (B).The chromatoid body of the parasite with blunt, rounded ends is shown (arrowhead). CDC

Treatment of Entamoeba histolytica infection

Untreated amebiasis can result to complications leading to death due to the invasion of vital organs including the brain, lung and liver by the trophozoites of the parasite. The treatment of E. histolytica should be directed at replacing lost body fluids and eradication of the parasite from the host. Metronidazole, iodoquinol (Yodoxin), paramomycin, and diloxanide furoate are often the drugs of choice for the effective treatment and management of amebiasis. While paramomycin, iodoquinol and diloxanide furoate (which are generally referred to luminal amebicides) are very effective for asymptomatic amebiasis; metronidazole (Flagyl) in concomitant with any of the above luminal agent is most appropriate for symptomatic E. histolytica infection. Cyst-passing individuals (i.e. those that are asymptomatic) should also be properly treated with the correct amebicide whether or not they show any clinical episode of the disease because they embody the most essential reservoir of the protozoan in any population. Luminal amebicides are antiprotozoal agents that target invasive intestinal and extraintestinal forms of E. histolytica while systemic amebicides are antiprotozoal drugs that are used primarily for the purpose of managing and treating asymptomatic E. histolytica infections. Surgery can also be contemplated in very severe invasive forms of the disease. Though a possible reinfection is common with E. histolytica infection especially in endemic regions, amebiasis can be cured spontaneously even without a treatment – suggesting that the host immune system is plays a vital role in resolving the disease episode.

Control and prevention of Entamoeba histolytica infection

Amebiasis is a disease that often results from poor hygiene and lack of proper sanitary facilities. Adequate sewage treatment and the practice of good personal hygiene are required to keep the infection rate at a very low incidence. Cysts of E. histolytica are hard and can survive for weeks outside its human host. Iodination and hyperchlorination are required to kill viable cyst forms of E. histolytica in water. Other preventive measures for E. histolytica infection include: proper washing of hands after defeacating and before eating, boiling and filtering of drinking water, covering of foods and water, not defeacating in the open and proper washing of fruits and vegetables before eating.

Amebiasis is also common among male homosexuals including heterosexuals who practice anal sex. Proper advocacy about E. histolytica infection to schools, health institutions, local communities and amongst food handlers is also significant in preventing and controlling the spread of the disease. No chemoprophylactic drug currently exist for E. histolytica infection, thus local, state, and federal authorities must take drastic measures to improve on the environmental, food and sanitary conditions of their areas such as provision of good drinking water and public latrines. Food and water contamination with human feaces from leaking sewage or septic tanks should be avoided, and wells or boreholes should not be dug close to septic tanks or sewages. Also, travelers/tourists visiting endemic regions should take precautions in terms of what they eat and drink. 

FURTHER READING

Chiodini P.L., Moody A.H., Manser D.W (2001). Atlas of medical helminthology and protozoology. 4th ed. Edinburgh: Churchill Livingstone.

Ghosh S (2013). Paniker’s Textbook of Medical Parasitology. Seventh edition. Jaypee Brothers Medical Publishers,

Gillespie S.H and Pearson R.D (2001). Principles and Practice of Clinical Parasitology. John Wiley and Sons Ltd. West Sussex, England.

Gutierrez Y (2000). Diagnostic pathology of parasitic infections with clinical correlations. 2nd ed. New York: Oxford University Press.

John D and Petri W.A Jr (2013). Markell and Voge’s Medical Parasitology. Ninth edition.

Mandell G.L., Bennett J.E and Dolin R (2000). Principles and practice of infectious diseases, 5th edition. New York: Churchill Livingstone. 

Roberts L, Janovy J (Jr) and Nadler S (2012). Foundations of Parasitology. Ninth edition. McGraw-Hill Publishers, USA.

Schneider M.J (2011). Introduction to Public Health. Third edition. Jones and Bartlett Publishers, Sudbury, Massachusetts, USA.

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