Amoebiasis as a Major Risk to Human Health: A Review  

Ali Raza1 , Zafar Iqbal2 , Ghulam Muhammad1 , Mansoor Ahmad Khan3 , Kashif Hanif4
1. Department of Clinical Medicine and Surgery, University of Agriculture, Faisalabad, Pakistan;
2. Department of Parasitology, University of Agriculture, Faisalabad, Pakistan;
3. Livestock and Dairy Development Department, Government of Punjab, Pakistan;
4. Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan
Author    Correspondence author
International Journal of Molecular Medical Science, 2013, Vol. 3, No. 3   doi: 10.5376/ijmms.2013.03.0003
Received: 10 Mar., 2013    Accepted: 15 Mar., 2013    Published: 17 Jun., 2013
© 2013 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:

Raza et al., 2013, Amoebiasis as a Major Risk to Human Health: A Review, International Journal of Molecular Medical Science, Vol.3, No.3 13-24 (doi: 10.5376/ijmms.2013.03.0003)

Abstract

Entamoeba histolytica has diverse distribution and is a substantial risk in almost all the countries where barrier between human feces, food and water source are ordinary. There are at least 8 different amoebas that live in the human intestinal lumen however those are generally accepted as commensals except for E. histolytica. The parasite imposes a major threat to public health in most parts of world and has re-emerged in some previously dormant areas as it is categorized as second leading cause of death from parasitic disease worldwide. In most of E. histolytica infection, symptoms remain absent or very mild whereas most frequent clinical manifestation are colitis and liver abscess due to amoebic infection. Laboratory diagnosis of amoebiasis is usually made on the basis of microscopical and serological methods Nitromidazole derivatives like metronidazole, tinidazole and ornidazole are considered as foundation stone of the treatment for amoebiasis. Lack of effective vaccination is one of the major hurdles for the control of amoebiasis that may prevent transmission of the parasite and or at least progression of the infected individuals into active invasive disease. The aim of this article is to comprehensively review the epidemiology, disease pathology and treatment of this parasitic zoonotic disease.

Keywords
Amoebiasis; Entamoeba histolytica; Food and water borne; Parasitic disease

1 Introduction
Entamoeba histolytica has cosmopolitan distribution and is a substantial risk in almost all the countries where barrier between human feces, food and water source are mediocre (Stanley, 2003). The recent reclassification of E. histolytica into different species now including the pathogenic Entamoeba histolytica and the non-pathogenic Entamoeba dispar and  Entamoeba moshkovskii  has further added to the complication of the epidemiology of amoebiasis since these three species cannot be differentiated by microscopy that is the most frequently used diagnostic method predominantly in tropical  countries where resources are limited, but can only be differentiated by the use of molecular methods such as the polymerase chain reaction based methodologies (Ali et al., 2003; Fotedar et al., 2007; Khairnar et al., 2007).

There are at least 8 different amoebas (E. histolytica, E. dispar, E. moshkovskii, E. coli, E. hartmanni, E. polecki, Iodamoeba butschlii, and Endolimax nana) that live in the human intestinal lumen (Garcia and Bruckner, 1997; Clark, 1998; Haque et al., 1998; Leber, and Novak, 1999) however these are usually accepted as commensals except for E. histolytica (Garcia and Bruckner, 1999; Leber and Novak, 1999; Petri and Singh, 1999).

Amoebiasis is accountable for an approximate 40~50 million cases each year, mainly in tropical and subtropical countries (Walsh, 1986; WHO, 1997). A range of 80%~90% of infected individuals are asymptomatic; however the primary target organ colonized by the parasite is the intestinal mucosa of the sigmoid and colon. The highly invasive strains of E. histolytica species can display their invasive potential by producing tissue damage (Ali et al., 2008; Gathiram and Jackson, 1987; WHO, 1985). Therefor, 10% of the world’s total population was infected by amoeba and only 1% of infected personages developed the aggressive form of disease. The annual mortality rate appraised at that time for invasive forms of amebiasis was around 100,000 deaths. The majority of deaths were a concern of severe complications associated with intestinal or extra-intestinal offensive disease (Clark and Diamond, 1993). Intestinal amoebiasis is widespread in the tropics, but the prevalence of invasion and incidence of the disease show geogr- aphical variation, probably because of transmission and invasiveness vary with ecological and social conditions.   

2 Life cycles
The life cycle of E. histolytica is simple and consists of an infective stage i.e. cyst (10 to 15 μm in diameter) and a multiplying trophozoite stage (10 to 60 μm in diameter). Like other protozoa, E. histolytica appears unable to de novo synthesize purine (Nozaki and Nakada-Tsukui, 2006). Biochemical analysis showed that glutathione is not present. For this reason, E. histolytica differs from their counter parts i.e. higher eukaryotes and it uses pyrophosphate instead of ATP (McLaughlin and Aley, 1985). Mature cysts in the large intestine leave the host in large numbers and remain viable and infective in a moist, cool environment for at least 12 days. In water, cysts can live for up to 30 days. Nonetheless, they are rapidly killed by desiccation, and temperatures below 5℃ and above 40℃. Mature cysts are also resistant to chlorine levels normally used to disinfect water (Stenmark, 2009). When swallowed, cysts pass through the stomach unharmed. In the small intestine, where conditions are alkaline and as a result of nuclear division, eight motile trophozoites are produced. These motile trophozoites settled in the large intestine lumen, where they divide by binary fission and feed on host cells, bacteria and food particles. This is the first chance of the parasite making contact with the mucosa (Chatterjee et al., 2009). 

3 Epidemiology of Amoebiasis
E. histolytica has diverse distribution (Table 1) and is a significant health risk in almost all over the world where contamination of food and water is high. The parasite is categorized as second leading cause of death from parasitic disease worldwide and imposes a major threat to public health throughout the world (Stanley, 2003). The prevalence of amoebiasis depends on socioeconomic conditions of the population and varies between countries and areas with accordingly as sometimes up to 50% of the population is affected in the areas with poor sanitary conditions (Caballero-Salcedo et al., 1994). According to a Jackson (2000), this parasitic disease directly affects over 50 million people leading to loss of manpower and economic damage. Poor sanitary and unhygienic conditions are responsible for amoebiasis and people living in developing countries with such type of surroundings have greater risk to develop amoebiasis than do those in developed countries (Fuchs et al., 1988).

 
Table 1 Prevalence and methods of diagnosis of Amoebiasis


4 Disease pathology
In most of E. histolytica infection symptoms remainabsent or very mild. The patients with non-invasive disease excrete cysts for a short period of time and get clear from infection within 12 months. Whereas, most frequent clinical manifestation are amoebic colitis and amoebic liver abscess (Stanley, 2003). The actual host parasite interaction which determines the disease course is still a mystery. However, the best understood three virulence factors include a surface protein of parasite (lectin), cytoproteins (cysteine proteases) and ameobapore (Stauffer and Ravdin, 2003). The surface protein of trophozoit (lectin) advert N-acetylgalactosamine (GalNAc) and sugars galactose on host cell surface (Ravdin and Guerrant, 1981; Petri et al., 1987). The interface of lectin and host mucins lining is the disease course defining moment (Chadee and Petri, 1987). Disease remains non-invasive if lectin attaches to host mucin glycoproteins.

Colitis results when the trophozoites penetrate the mucand in layer lectin attaches to intestinal epithelium. The penetration depends on genetic makeup of parasite to produce proteolytic enzymes and resistance to complement mediated lyses (Eckmann et al., 1995). Thro-phozoites invasion initated by destroying epithelial cell lining and inflammatory cells (Seydel et al., 1998). Once invasion started then encystment will not occur and life cycle will not compete successfully. After contact a pore forming protein complex is inserted by parasite almost similar to human complement system (Leippe et al., 1991). After few seconds of contact with host cell, calcium level increases twenty folds and cell death occurs within 15 minutes (Ravdin et al., 1988). Cysteine proteases degrade extracellular proteins that help amoeba to avoid any inflammatory response of host (Que and Reed, 1997). The virulence of E. histolytica is directly proportional to its ability to apoptosis and then phagocytize the dead cell, this process considerably limit the host inflammatory response (Huston et al., 2003).

5 Diagnosis of Amoebiasis
Several methods are being used by the researchers to diagnose amoebiasis (Table 2). Laboratory diagnosis of amoebiasis is usually made microscopically and on the basis of serological methods including enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination assay and latex agglutination assay (Tanyuksel and Petri, 2003). Accurate diagnosis is not only important for the parents with dysentery but also for the 90% patients of E. histolytica that are asymp- tomatic as they may shed the infective stages of the organism particularly in developing countries with poor hygienic measures (Jackson, 2000).

 
Table 2 Different assays and test used for the diagnosis of amoebiasis


6 Treatment
Nitromidazole derivatives like metronidazole, tinidazole and ornidazole are considered as foundation stone of the treatment for amoebiasis (Stanley, 2003). Amoebiasis is treatment by metronidazole followed by luminal agents (Paromomycin, Iodoquinol) to eradicate colonization especially in amoebic colitis (Powell et al., 1969; Pehrson and Bengtsson, 1984). Asymptomatic patients carrying E. histolytica should be treated with the luminal agents to eradicate infection; this is suggested because of the known risk of development of disease in the carrier and the chances that this individual can shed the cysts of E. histolytica and pose a threat to public health (Gathiram and Jackson, 1987; Haque et al., 2001). E. dispar does not require treatment but should make the physician vigilant that the individual has been exposed to contaminated food or water (Stanley, 2003). Surgically drainage of liver abscess is generally unnecessary and should be avoided (Powell et al., 1969) as liver abscess in amoebiasis can be treated with single dose of metronidazole without drainage (Lasserre et al., 1983; Akgun et al., 1999). A number of reports are available about the efficacy of different drugs to treat amoebiasis (Table 3).

 
Table 3 Different drugs used for the treatment of amoebiasis


7 Immunology
Development and application of suitable vaccines are the major constraint for the efficient control of infectious diseases. Lack of effective vaccination is one of the major hurdles for the control of amoebiasis that may prevent transmission of the parasite and or at least progression of the infected individuals into active invasive disease (Lotter and Tannich, 2006). A sum of amoeba proteins has been identified as potential vaccine candidates because of their efficacy to inhibit and prevent liver abscess formation in experimental trials in rodents (Table 4) (Petri and Ravdin, 1991).

 
Table 4 Different vaccine strategies attempted to counter amoebiasis


8 Control
Amoebiasis can be controlled by adopting proper sanitation and hygienic measures worldwide but this is unlikely to happen in the probable future (Abd-Alla and Ravdin, 2002). Effective recombinant antigen based vaccine have been developed that prevents liver abscess due to amoebic infections and generate mucosal antiamoebic antibody immune response in animals but the problem is that no single product has yet been tested in human (Stanley, 2000). One of the limitations with development of amoebiasis vaccine is that natural infection of E. histolytica does not elicit long term immunity as reflected by the reinfection of the recovered individuals (Haque et al., 2001; Blessman et al., 2002). The fact along with the experience of vaccine development for other parasitic diseases proposes that development of vaccine against amoeba will be a formidable task but the need is far greater than we imagined so good sanitation and hygienic life style must be emphasized for the better control of amoebiasis.

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