Amoebiasis

 Amoebiasis is an infection of human gastrointestinal tracts by a protozoan, Entamoeba histolytica which starts invading the intestine and then to the other organs including liver, lungs, brain, and spleen etc. According to WHO, it is one of the fourth leading causes of mortality accounting for 70 thousand deaths among protozoal infections after malaria, Chagas disease, and leishmaniasis. It also causes significant morbidity to the patients after malaria and trichomoniasis. The degree of pathogenesis and diseases outcome by Entamoeba histolytica depends mainly on three major factors such as parasite, host and environmental.

 

Cysts and trophozoites are passed in feces 1 . Cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool. Infection with Entamoeba histolytica (and E. dispar) occurs via ingestion of mature cysts 2 from fecally contaminated food, water, or hands. Exposure to infectious cysts and trophozoites in fecal matter during sexual contact may also occur. Excystation 3 occurs in the small intestine and trophozoites 4 are released, which migrate to the large intestine. Trophozoites may remain confined to the intestinal lumen (A: noninvasive infection) with individuals continuing to pass cysts in their stool (asymptomatic carriers). Trophozoites can invade the intestinal mucosa (B: intestinal disease), or blood vessels, reaching extraintestinal sites such as the liver, brain, and lungs (C: extraintestinal disease). Trophozoites multiply by binary fission and produce cysts 5, and both stages are passed in the feces 1. Cysts can survive days to weeks in the external environment and remain infectious in the environment due to the protection conferred by their walls. Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment (https://www.cdc.gov/dpdx/amebiasis/index.html)

Pathogenesis:

Pathogen factors: E. histolytica has many virulence factors including lectin, amoebic pore forming proteins, many different kinds of proteases, antiphagocytic mechanism of trophozoites etc.  After adherence to epithelial mucous layer through Gal/GalNAc lectin, it produces glycosidases and proteases which degrade the epithelial lining of human small intestine.  E. histolytica then produces many different kinds of cysteine proteases to overcome pathogenesis and host immune response. EhCP4 degrades sIgA, EhCP5 cuts to form amoeba pore, EhCPLf disrupts the tight junctions and so on. Likewise, CXXC rich proteins have erythrophagocytosis activities. These cysteine proteases play 70-80% role in pathogenesis. The trophozoites then interact with intestinal epithelial linings and other host tissues inducing apoptosis. The more is the expression of such virulence factors; the more is the severity of disease.  Hence the burden also depends on the expression level of different virulent genes on the host body by different strains. Some strains also gain resistant to antiprotozoal drugs which can be more pathogenic. The emerging new strains of the protozoa is more virulent and the infection caused by such strains are difficult to manage.

Host factors: The first defence lining of host is anti-lectin IgA circulating in their gut which can easily avoid the symptomatic infections by E. histolytica. These sIgA neutralizes the protozoa preventing excystation. The adherence of Gal/GalNAc lectin induces the production of IL-2 and gamma interferon in T-cell and inducible nitric oxide synthase through TNF alpha production. These immune responses provide the protection against the colitis and abscess in amoebic infections. The host who are pre-exposed may have already preformed immune responses and avoid the symptomatic infections. Besides, one of the studies also reported the higher prevalence of amoebic liver abscess among males than in females due to lack of sufficient gamma interferon in their serum. Likewise, the immunocompetent population have less chance of symptomatic infections whereas in immunocompromised individuals like HIV/AIDS, malnourished children, organ transplant patients and those having chronic infections with heart, pulmonary and liver may have severe amoebic infections with higher rate of mortality and morbidity.

Environment in gut: The role of microbiome in gut of human is another important factor in E. histolytica pathogenesis and diseases outcomes. E. histolytica normally grazes on intestinal bacteria for nutrients especially gram-negative enteric bacteria including Escherichia coli and Shigella dysenteriae. One of the studies from Northern India reported that the decreased microbial load in Bacteroides, Clostridium coccidias sub-group, Clostridium leptum sub-group Lactobacillus, Campylobacter and Eubacterium among amoebic patients while Bifidobacterium load is increased. The ingestion of few of these bacteria enhance the over expression of lectin, a major virulent factor in E. histolytica which increases cytopathic effect. Children with Prevotella copri as microbiome in the gut have more common E. histolytica related diarrhea while those with Clostridia related bacteria are more resistant to E. histolytica infection.

Others: The severity and number of cases also depends on geographical distribution, socioeconomic status and personal hygiene. Although it is a world widely distributed, a higher number of diseases occur in the developing and underdeveloped countries due to contaminated drinking water supplies. The lack of unawareness, ignorance, overpopulated, poor sanitation and poor hygiene in food preparation in such low-income countries are major predisposing factors for burden and outcomes of diseases among those communities.  An increased occurrence of E. histolytica infections are observed among those who practice homosexual activities and oro-anal sex. Moreover, they present severe symptoms than those of immunocompetent individuals.  Individuals with habitual eating out-side foods may also have a higher rate of amoebic diarrhoea rather than direct exposure to human and animal excreta. Few vectors including flies play a significant role in the transmission of amoebic cysts to such open food products.

 

Clinical manifestations of amoebic liver abscess

Over 90% of amoebiasis is asymptomatic, while only 4-10% of infected patients present different kinds of clinical signs and symptoms. As the colonization of Entamoeba histolytica starts from the intestine, the majority of cases are related to intestinal amoebiasis showing diarrhea, dysentery, colitis as general syndromes. However, E. histolytica can also disseminate to other organs through the portal blood circulation causing extraintestinal infections. Among the invasive amoebiasis, 10-15% of adults develop amoebic liver abscess, which is one of the most common extraintestinal infections by E. histolytica. The disease is a persistently progressive and may lead to fatality. However, the rate of fatality decreases with advances in treatment and diagnostic procedures. The amoebic liver abscess starts with spreading of hematophagous trophozoites from colonic mucosa via the portal circulation. The individuals with amoebic liver abscess hence also present amoebic colitis but amoebic dysentery like symptoms as in intestinal amoebiasis is absent. Even no trophozoites and cysts form of E. histolytica is observed under stool microscopy. The infected persons have a fever with chills and profuse sweating in the afternoon and night. The patients also have abdominal pain in the upper quadrant, especially in right hypochondrium. The pain may increase when an individual deeply breathes, cough, and step right foot on walking. The individual with epigastric pain feels intense pain in the liver region during digital pressure and fist percussion.

The patients having single and multiple abscesses in the liver suffer hepatic tenderness and painful hepatomegaly. However, around 8% of individual with liver abscess have mild jaundice, unless complication of multiple abscesses occurs.  Other general symptoms are anorexia, nausea, vomiting, fatigue, and weight loss. The symptoms may last for less than 10 days however, in chronicity, anorexia and weight loss are very common.

Besides, a few pulmonary like symptoms such as cough, dullness, and rales in the right lung base may be present. During amoebic liver abscess, leukocytosis without eosinophilia, mild anemia, raised concentration of alkaline phosphatase and high rate of RBC sedimentation are common clinical findings used in the diagnosis of it.