Monday, January 9, 2017

The Hitchhiker’s Guide to the Amoeba

By OS

                  Most people enjoy traveling and want to experience different parts of the world. Some people, like Todd, even have it on their bucket lists to visit every country. Traveling comes with many risks though, and one major concern for travelers is disease. Unfortunately Todd discovered this for himself when he visited India. Shortly after Todd arrived in India, he went out to an unsanitary restaurant because it was the only one nearby and he did not feel like going shopping on his first night there. While there, he noticed that the water didn’t look completely clean. He figured that water in India just looked like that, so he drank it anyway. In doing so, he exposed himself to the amoeba Entamoeba histolytica, which is the pathogen responsible for amebiasis. Amebiasis causes disease when its cysts are ingested and is responsible for an estimated 100,000 deaths each year (1). This disease is common in areas with poor sanitation, including Central America, South America, Africa, and parts of Asia, so Todd should have been more careful (2). By staying away from unsanitary restaurants and not drinking potentially unsafe water, Todd could have avoided being infected by this parasite.
                  Todd didn’t realize it for a while, but his body was under attack. The water he drank carried E. histolytica cysts down his throat, through his stomach, and into his small intestine (figure 1). Once the cysts reached his small intestine, the parasite escaped its cyst and replicated asexually three times, forming eight trophozoites (3). Trophozoites are the motile form of the parasite that feeds on the host using porins and proteolytic enzymes. The trophozoites traveled to his large intestine and adhered to its mucosal lining. Here they degraded the layer of protective mucous and attacked the epithelial cells of the large intestine. This was followed by the release of porins, which caused some of Todd’s cells to lyse. The proteolytic enzymes were then released to partially degrade the ruptured cells. Finally, the amoeba engulfed the dead cells and used them as a food source. The parasite was literally eating him alive! The death of Todd’s cells and inflammation of his colon caused him to experience some of the symptoms associated with amebiasis, including pain and diarrhea.  The symptoms began to appear five days after infection. At this point, Todd knew something was wrong, but he figured it was just food poisoning and that it would be done shortly. He thought his immune system would fight off the infection, but he was wrong.

Figure 1. Life cycle of E. histolytica.   
                  Todd’s complement, which is part of his innate immune system, could not clear the infection. E. histolytica is resistant to the lysis that the complement system normally uses to kill infections (3). Additionally, some of his IgA antibodies were unable to help fight the disease. Antibodies normally bind pathogens and either block further infection or help immune cells destroy the pathogens. However, E. histolytica is able to quickly degrade IgA, allowing for its self-preservation. The parasite also prevented Todd’s T cells from functioning properly. T cells are immune cells that normally help eliminate specific pathogens. However, Todd’s T cells were unable to clear the infection because the parasites were secreting proteins to decrease the T cell activity (4). Todd’s other immune responses were insufficient to kill all of the parasites, so his body could not clear the amebiasis on its own.
The trophozoites kept replicating asexually and continued attacking his cells. Some trophozoites formed into cysts, which were excreted in his feces and waited until they found another person to infect (3). After another week, his amebiasis became more severe and the trophozoites reached his bloodstream. From here, they could have traveled to any tissue in his body, including his lungs or brain. Wherever the parasites travel, they kill cells, so travel to other areas of Todd’s body may have caused serious damage. Todd was lucky that the E. histolytica cells did not infect his brain or lungs. Infection of these areas is rare, but can be very serious. However, they did travel to his liver. When the E. histolytica infection reached Todd’s liver, it killed some of his liver cells and formed abscesses, which are clusters of dead cells, immune cells, and parasitic cells (5). As his liver was infected, Todd started experiencing fever, coughing, and other flu-like symptoms, as well as intense pain. When he noticed his symptoms weren’t getting better, he finally went to see the doctor.
The doctor asked about his ailment and determined the cause may have been due to an ingested parasite. He ordered a blood test in order to precisely determine the cause. The blood was sent to be analyzed and an enzyme-linked immunosorbent assay (ELISA) was performed. This ELISA was done in order to see if Todd had antibodies against several parasites, including E. histolytica (6). This can show if someone is infected because the human body normally creates antibodies to fight against infectious pathogens. The presence of antibodies specific to a pathogen shows that the body is actively fighting against the pathogen. The test showed that Todd’s blood did contain antibodies to E. histolytica, so the doctor concluded that amebiasis was the cause of his symptoms. Because of this, the doctor was able to prescribe him metronidazole, which is an amebicidal drug that is very effective at killing E. histolytica (7). This helped Todd to finally clear the infection.
Fortunately for Todd, his infection had not spread too far and it went away after treatment. However, being more careful could have prevented him from being infected at all. It is always important to be careful about what you eat and drink, but paying attention can mean the difference between life and death for immunocompromised or other vulnerable people. People with AIDS, SCID, or other immune deficiencies need to pay special attention because amebiasis can be very severe for people with weak immune systems. Todd plans to continue traveling the world, but now he knows to be more careful and take precautions to stay healthy. Amebiasis, as well as many other diseases, can be prevented by taking the necessary precautions when living in or traveling to areas without proper sanitation. In addition to avoiding consumption of potentially unsafe food and water, amebiasis can be prevented by washing your hands often, keeping raw foods away from cooked foods, and ensuring meat is thoroughly cooked. By spreading this information, hopefully the prevalence of amebiasis can be reduced.


Bibliography

1.              Ali IKM, Clark CG, Petri Jr WA. 2008. Molecular epidemiology of amebiasis. Infect Genet Evol. 8:698-707
2.              Wertheim HFL, Horby P, Woodall JP. 2012. Atlas of Human Infectious Diseases. Wiley-Blackwell, Chichester
3.              Ravdin JI. 1995. Amebiasis. Clin Infect Dis. 20:1453-1464
4.              Salata RA, Martinez-Palomo A, Canales L, Murray HW, Trevino N, Ravdin JI. 1990. Suppression of T-Lymphocyte Responses to Entamoeba histolytica Antigen by Immune Sera. Infect Immun. 58:3941-3946
5.              Espinosa-Cantellano M, Martinez-Palomo A. 2000. Pathogenesis of Intestinal Amebiasis: From Molecules to Disease. Clin Microbiol Rev. 13:318-331
6.              Tanyuksel M, Petri Jr WA. 2003. Laboratory Diagnosis of Amebiasis. Clin Microbiol Rev. 16:713-729

7.              Lasserre R. 1979. Treatment of Amebiasis. Phil J Microbiol Infect Dis. 8:1-6.

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