Thursday, December 15, 2011

Amoebiasis



This week at Infection Landscapes, we will conclude the extended series on gut infections. This final installment will cover amoebiasis. This is another parasitic infection of the gut, but this infection has the potential to cause invasive disease and is associated with greater mortality than the other parasitic gut infection we covered last time, giardiasis. Indeed, amoebiasis is responsible for the world's third highest mortality attributable to a parasite.

The Pathogen. Amoebiasis is caused by Entamoeba histolytica, which is another anaerobic protozoan parasite, though E. histolytica is not flagellated:

Entamoeba histolytica trophozoites. Two of the trophozoites have ingested red blood cells, which are apparent as dark spots in the endoplasm.

Similar to G. lamblia, the life cycle of E. histolytica is comprised to two distinct stages: the cyst and the trophozoite. As we saw with G. lamblia, infection is initiated when the cysts are ingested and excyst in the gut tract releasing the trophozoite, which is the feeding stage of the parasite. Each successfully excysted cyst will produced 8 trophozoites. These trophozoites migrate to the colon, replicate by binary fission and target the mucous membrane associated with the epithelium of the large intestine. In response to the immunologic pressure of the host, some trophozoites undergo encystation in the colon and pass out of the gut in feces in order to survive and infect new hosts. While the majority of infections are asymptomatic, the pathogenicity of a given organism is strongly influenced by a specific lectin (galactose and N-acetyl-D-galactosamine-specific lectin), which determines the adherence and lytic activity of the parasite. Quorum sensing of the expression of this lectin by other members of the E. histolytica colony, as well as the parasites' interaction with the host's natural microbiome, are also likely involved in the virulence transition. The life cycle of E. histolytica is depicted in the following graphic by the Centers for Disease Control and Prevention:



Another nice depiction of the life cycle by Mariana Ruiz Villarreal that clearly distinguishes between invasive and non-invasive disease is shown here:


Here is simplistic and somewhat over-dramatized animated video depicting the parasite's activity:


The Disease. As mentioned above, the majority of E. histolytica infections are subclincal. In fact, as many as 90% may cause no apparent disease in the infected individual. When infections are symptomatic, disease can range from watery diarrhea to frank dysentery, the latter resulting from an invasive infection of the colon tissue, to severe disseminated disease potentially involving the liver, kidney, spleen, lung or brain. Invasive infection occurs as a result of the trophozoites breaching the mucous membrane of the colon. When this happens, the parasite consume the host cells by phagocytosis in the same way it consumes contents of the gut lumen (bacteria and food particles) in non-invasive infections when it lives commensally with the host. A breach of the protective mucous membrane in the lower intestine results in ulcers and dysentery. Some of these ulcers can be quite severe and lead to the characteristic flask-shaped penetrating holes in the tissue:


If the parasites breach the lower intestinal wall, then they can spread via the circulation and cause disseminated disease in multiple organ systems, which if untreated is often life threatening. The most common disseminated focus of complicated infection is the liver, where abscess formation follows the parasite's invasion of the hepatic tissue:


The Epidemiology and the Landscape. Globally, there are approximately 50 million cases of clinically apparent amoebiasis each year, with up to 100,000 deaths. The burden of these cases follows the same geographic distribution as that seen for almost all of the gut infections we have covered in this series: areas with limited sanitation and water infrastructure are the areas where amoebiasis is endemic. And areas with limited infrastructure tend to be the resource poor areas of the developing world. Amoebiasis does indeed occur in developed areas of the world as well, but in these settings it is typically limited to sporadic cases.

Transmission of E. histolytica is by the fecal-oral route with water and food being the primary vehicles of transmission and direct person to person contact playing a secondary, but still important, role. Sexual transmission of E. histolytica is another potential route of transmission when oral and anal sex are combined between an infected and a susceptible individual. 


Control and PreventionControl and prevention of amoebiasis begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. In most settings in the world where amoebiasis is a significant source of morbidity and mortality, improved infrastructure that can maintain adequate water resources is a first priority in its prevention.



Secondarily, personal hygiene at the individual level, especially in the context of food preparation, can also be very important in preventing the spread of E. histolyticaconsistent hand washing, boiling water, and thoroughly cooking food are all important in stopping the chain of transmission



14 comments:

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  3. Improving water sanitation in places like sub-Saharan Africa, Latin America, and south Asia will go a long way toward reducing transmission of the infection. I wonder how many of the estimated 50 million cases are asymptomatic and chronic, and how many are new incidents accumulate in an average year. 100,000 annual deaths is a considerable burden.

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    1. Nathan,
      Above, it says that many cases are subclinical, up to 90% as the high end of the estimate. It also says that there are 50 million *clinically apparent* cases per year. If that's all true, then there may be up to 500 million infections in a given year. I would guess that it is a recurring infection, though, so it may include repeat cases in the same person (e.g. I get infected 10 times in a year, and only once do I suffer any symptoms).

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    2. Alexandr PinkhasovJuly 11, 2014 at 2:58 PM

      Nathan, I agree with you that improving water sanitation will likely reduce the transmission of infection. However, it should be noted that poor water sanitation and limited access to fresh water is usually a result of poor infrastructure. Geographic regions that have poor infrastructure typically also have limited access to healthcare services. Going along with what Tamara said, one of the reasons there could be recurring diseases is because of the limited access to these two essential resources.

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  4. Liver abscess with amoebiasis is a major issue. Deaths in amoebiasis are usually from liver abscess. Surprisingly, it is quite often seen in NYC from frequent holidaying in Mexico and Caribbean countries. I suppose subclinical infection would also exist but due to sanitary hygiene does not spread within US.
    Colonization of colon with other species of Entamoeba can co-occur and their cysts could be difficult to differentiate. However, other Entamoeba species are usually commensals or non-pathogenic. Fecal antigen assay and serologic tests can help validate or negate the diagnosis.
    Amoebicide used for luminal infections – paromomycin is quite toxic. Metronidazole, on the other hand, used for systemic infections is usually well tolerated aside from GI side effects.

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  5. When I read that 90% of cases are subclinical, I definitely did not expect the disease burden to be so high in terms of morbidity. If 50 million cases are recorded globally, then I could only imagine how many actual cases there are. The sporadic cases in developed countries are usually due to poor personal hygiene? Are enemas really as source as well, as mentioned in the case study we read?

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    1. Racquel BreretonJuly 5, 2014 at 11:22 PM

      In response to the case study I believe you're referring to, "Outbreak Investigations Around the World, by Mark Dworkin" he presents a chapter on a pseudo-outbreak of Amebiasis in Los Angeles County. After receiving several reports of smears positive for Entamoeba histolytica by a hospital laboratory, further evaluation by a reference laboratory returned with corrected reports negative for the parasite. It's important to note that the hospital laboratory was a teaching hospital affiliated with a school of medicine and a school of public health. If laboratories of this caliber and training are making these errors, I'm curious as to how many of the reported cases in developed countries are true positives. In the case study, of the seventy plus positive reported smears, only two were confirmed by the reference laboratory as truly positive.

      Dworkin notes that to the untrained eye, Entamoeba histolytica can be mistaken for fecal leukocytes. To what extent are the sporadic cases in developed countries attributed to incorrect identification by laboratories.

      On that same note, I wouldn't be skeptical of the reported prevalence in developing countries as the incidence is a reflection of poor sanitation and insufficient infrastructure. However, I'm still curious of the actual true cases in developed countries.

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    2. Also noted in that article from “Outbreak Investigations Around the World,” was the incidence of amoebiasis in men who have sex with men (MSM). As Dr. Walsh points out, “Sexual transmission of E. histolytica is another potential route of transmission when oral and anal sex are combined between an infected and a susceptible individual.” I looked into this and it seems that indeed MSM may be at greater risk for amoebiasis. A study (1) from 1991 detected E. histolytica in 37% from the sample of 128 Australian gay men. This was surprising because Australia is a developed country, where ameobiasis is uncommon. Another study (2) from 2010 found the seroprevalence rate of E. histolytica infection in high risk HIV positive MSM in Australia to be 5.13%, compared to the rate of 0.44% for uninfected controls. Both studies emphasize the need for public health officials to alert the gay community to the dangers of a potentially life threatening infection. The studies also highlight the need to carefully watch the incidence of amoebiasis in developed countries as sexual practices among heterosexual couples expand to include anal sex. A 2011 study (3) by the CDC reports that 44% of men and 36% of women questioned had heterosexual anal sex. As anal sex becomes more common, epidemiologists must be wary of an uptick in the number of amoebiasis cases.

      (1) http://www.ncbi.nlm.nih.gov/pubmed/1958719
      (2) http://www.ajtmh.org/content/83/4/914.short
      (3) http://www.cdc.gov/nchs/data/nhsr/nhsr036.pdf, see Figure 1

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    3. In response to Racquel,

      I agree with what you said, however, I do think we need to be more skeptical about the reported prevalence. As previously mentioned, the disease symptomology is not necearilly specific to E. histolytica as other organisms can lead to inflammatory diarrhea or meningitis. The problem with the lab in the Dworkin chapter was that the new technician was making thinner slices with better resolution. Thus, the lab (who had personnel trained in identifying this pathogen) continued to falsely identify the organism, which mimics macrophages. Moreover, labs in developing countries that are not up to standards may experience the reverse problem, i.e., their resolution may be so bad that symptomology and inflammatory diarrhea are used for E. histolytic diagnosis without lab confirmation. I wonder if the disease prevalence and the number of subclinical cases are overestimated.

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    4. In response to Mohammed,
      I agree that public health officials should bring attention to this alarming infection and make the general public aware of its dangers and to re-emphasize safe sex practices. E. histolytica can be asymptomatic and all sexually active adults who have anal sex are at risk for infection or may already be infected and don't know, then pass it on to their partner(s). Also, because there are no symptoms of infection in some cases, the numbers mentioned above could be far greater if the 'asymptomatically infected persons' were included.

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  6. I appreciate the inclusion of the informative and easy-to-understand CDC diagram of the life cycle of E. histolytica. Including the graphic by Mariana Ruiz Villarreal, which clearly distinguishes between invasive and non-invasive disease, was also a good idea as the reader can sometimes gain a better understanding of an issue, especially if the issue is cyclical in nature, from viewing a picture rather than from reading text. You know what they say, a picture is worth a thousand words!

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  7. The more I read about these diseases, the more I realize that having a proper water infrastructure and sewage system really goes a long way to prevent many different types of diseases. Amoebiasis might be asymptomatic in 90% of the cases, but in cases where symptoms occur, especially when it's invasive. E. hystolitca can basically wreak havoc on any organ or organ system ranging from the brain to the liver. The graphic about abscess forming in the liver seems like an especially scary outcome of the disease.
    It is interesting to note that even though the main vehicle of transmission is through contaminated water and food sources, person to person contact as well as sexual intercourse plays somewhat of a role as well. This allows Amoebiasis to occur sporadically even in developed nations where the water infrastructure and the sewage system is adequate.

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  8. Arifin you point out many valid points as another commenter pointed out above the 90% of cases are asymptomatic and there are aprox. 50 symptomatic cases a year. Thus, there may be up to 500 million cases a year. Bearing this in mind the liver damage will only appear in a percent of the infected population with symptomatic E. hystolitca.
    I was unaware that infection can occur through sexual transmission. The infectious route seems to be fecal-oral and therefore I would assume the pathogen needs to enter the digestive tract in order to tack hold. Although, I'm sure there are some sexual acts that allow for such transmission to occur, anal sex probably would not and is thus probably not a valid for of transmission.

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