Blastocystis hominis
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Blastocystis is an intestinal microscopic parasite present in humans and a wide range of animals. The species that infects humans is known as Blastocystis hominis. An infection with B. hominis is known as blastocystosis. Studies have suggested that B. hominis is zoonotic in nature, i.e., it is able to transmit disease from animals, such as rats, pigs, and chickens, to human. Animals have been suggested to be a reservoir for human infection. The study of this ubiquitous organism, which was previously named Blastocystis enterocola, was initiated by Alexeieff in 1911 and Brumpt in 1912, in which the name Blastocystis hominis was coined for the organism isolated from human fecal material. The suggestion made by Zierdt in 1991 that it may be a cause of intestinal disease, renewed interest in this parasite.
Despite its worldwide distribution, infections are apparently more common in developing countries compared to industrialized countries. Travelers to tropical and under-developed countries with poor hygiene and sanitation facilities seem to be at a higher risk of infection.
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[edit] BIOLOGY
[edit] Scientific Classification
The appropriate classification of B. hominis remains controversial. Back in 1912, Brumpt described the organism as a harmless yeast due to its yeast-like glistening appearance in fresh wet mounts and the absence of pseudopodia and locomotion. This was then refuted by Zierdt who reclassified it under subphylum Sporozoa based on some distinctive protistan features that the Blastocystis cell has, such as the presence of nuclei, smooth and rough endoplasmic reticulum, Golgi complex, and mitochondrion-like organelles. Its sensitivity to antiprotozoal drugs and its inability to grow on fungal media further indicated that it was a protozoan. However, some revisions were made to the classification system recently based on modern molecular approaches to classification and studies have shown that Blastocystis is neither yeast nor a protozoan. It is placed in a new Class, known as Blastocystea, under the Subphylum Opalinata, Infrakingdom Heterokonta, Subkingdom Chromobiota, Kingdom Chromista (Cavalier-Smith, 1998).
[edit] Morphology
The great diversity of forms in which Blastocystis exists in poses identification and diagnostic problems. Four commonly described forms are the vacuolar (otherwise known as central body), granular, amoeboid, and cyst forms. The appearance of the organism is largely dependent upon environmental conditions.
- Vacuolar form
- The vacuolar form is the typical cell form of Blastocystis and is often used for the identification of the organism. These vacuolar forms vary greatly in size, with diameters ranging between 2 µm and 200µm. The vacuolar form is otherwise known as central body form because it has a large central vacuole surrounded by a thin band of peripheral cytoplasm which contains other organelles. Flocculent material has been described as being scattered unevenly throughout the vacuole. The function of the vacuole is still unclear, however, it has been suggested that, like for many eukaryotic cells, it is for storage purposes. Other functions, such as cell division during reproduction and the deposition of apoptotic bodies, have been proposed, although more tests need to be done to validate these roles.
- Granular form
- The granular form is somewhat morphologically identical to the vacuolar forms except that distinct granules were observed in the central vacuole and / or cytoplasm. Within the central vacuole, these granules appear in different forms too. Three types were suggested – metabolic, lipid, and reproductive granules. Metabolic granules play a role in chemical processes that are necessary for the maintenance of life in the organism. It was also put forward that reproductive granules were involved in the development of progeny cells. These hypothesis were made based on microscopy, which may be deemed misleading because of its existence of various cell types, hence more need to be done before making a definite conclusion.
- Amoeboid form
- The other form that exists is the amoeboid form. An amoeba is a single-celled organism that is able to acquire different shapes and has temporary projections, known as pseudopodia or false feet. It captures its prey by surrounding it with its quick developing pseudopodia, forming a dome that disables the prey from escaping. The Blastocystis cells can also occur in an amoeba-like form, which is rather rare in occurrence, more often found in old or drug-treated cultures and fecal samples. They are irregular in shape and have pseudopodia. Also, like an amoeba, foreign bodies were seen being engulfed and digested by the Blastocystis cell. However, there are again conflicting reports – Tan et al. (1996) and Zierdt (1973) reported to have observed a different morphology for the amoeboid forms. Unlike the descriptions made by Dunn et al. in 1989, a central vacuole was seen and granules were present in it. Despite the contradictory information that is presented to us, there is still a general similarity, in which pseudopodia are present in the amoeboid form and also in which a phagocytic role is proposed.
- Cyst form
- The Blastocystis cyst form is a more recent discovery and has helped in the advancement of understanding the way it transmits disease. As compared to the other forms, it is generally smaller in size and has a thick multilayered cyst wall. It lacks a central vacuole but few nuclei, multiple vacuoles and food storage deposits were observed. The cyst form is the most resistant form of this parasite and is able to survive in harsh conditions because of its thick multilayered cyst wall. Experiments have been carried out to show its ability to withstand acidic gastric juices. Besides, the cysts did not lyse when placed in distilled water and could survive well at room temperature for up to 19 days, indicating its strong resistance (Zaman et al., 1995; Moe et al., 1996). In another experiment, the cyst form was even able to survive in culture medium containing antiprotozoal drugs! This further supports the idea that the cyst form is the most resistant of the four forms.
[edit] Life Cycle
Due to the lack of an animal model, controversy has always been revolving around the life cycle of B. hominis. Many life cycles that have been proposed were based mainly on microscopy but were not fully substantiated by corroborating evidence. Based on the most recent findings, it was proposed that infection occurs in human when the fecal cyst form is being ingested. After ingestion, the cyst develops into other forms which may in turn re-develop into cyst forms. Through human feces, the cyst forms enter the external environment and are being transmitted to human and animals via the fecal-oral route, repeating the entire cycle.
[edit] CULTURE AND DIAGNOSIS
[edit] Culturing in the Laboratory
B. hominis can be grown in liquid culture medium. New methods have been developed to grow them as colonies on solid culture medium using a synthetic medium added with supplements (Tan et al., 1996a; Tan et al., 1996b). Nonetheless, these methods are only carried out in specialized laboratories.
[edit] Laboratory Diagnosis
- Microscopic examinations
- One of the traditional methods used in the diagnosis of B. hominis is by light microscopy and an indicator of infection is based on the observation of vacuolar, granular forms and more recently, cyst forms. Density gradient-based approaches have been developed to obtain concentrated samples and various staining methods have been used to aid in its identification.
- Immunological approaches
- Another traditional method used is to carry out serological tests that make use of the level of antibodies to detect the presence of B. hominis. In response to this parasite, infected humans will elicit an increase in the level of antibodies and this can be detected by methods like ELISA. Another useful approach, which is currently not available, is to develop an appropriate specific antibody that will detect B. hominis, easing the diagnosis of it. It is also vital that its ability to produce various antigens should be taken into consideration while developing such antibodies for these diagnostic tests.
- Molecular approaches
- Molecular approaches have been developed more recently with the advancement of technology and are useful in the laboratory identification of B. hominis. They include using polymerase chain reaction (PCR), electrophoretic karyotyping, DNA sequencing, and restriction fragment length polymorphism (RFLP) analysis. However, these are expensive methods and might not be a feasible method in hospitals and clinics.
[edit] CLINICAL ASPECTS
[edit] Signs and Symptoms
Not all Blastocystis infections display symptoms; and even when symptoms are present, they are not specific to Blastocystis infections. Common symptoms attributed to B. hominis infection are diarrhea, abdominal cramps, and nausea; and in more acute cases, profuse watery diarrhea and fever. Other possible associated symptoms include fatigue, anorexia, flatulence, and other gastrointestinal effects. Some other symptoms reported are presence of white blood cells in feces, rectal bleeding, increase in the number of eosinophiles (a type of white blood cells), enlarged liver and / or spleen, rashes, itching, and joint pains and swelling. These clinical symptoms are however inconclusive because these are based on epidemiological and case studies and furthermore, these symptoms may not necessarily be caused by Blastocystis infections.
[edit] Disease-causing Mechanism
The lack of an animal model was a major hindrance in the understanding of how B. hominis causes disease. Recent studies have shown that B. hominis is able to produce a protease that breaks up antibodies produced and secreted into the gastrointestinal tract lumen. These antibodies, known as immunoglobulin A (IgA), make up the immune defense system of human by preventing the growth of harmful microorganisms in the body and by neutralizing toxins secreted by these microorganisms. By breaking up the antibodies, it allows the persistence of B. hominis in the human gut. Another more recent study has also shown and proposed that, in response to the proteases secreted by Blastocystis, the intestinal host cells would signal a series of events to be carried out, eventually leading to the self-destruction of the host cells – a phenomenon known as “apoptosis” (Puthia et al., 2006).
Besides, the study has also demonstrated that Blastocystis has the ability to alter the arrangement of F-actin in intestinal epithelial cells. Actin filaments are important in stabilizing tight junctions; they in turn stabilize the barrier, which is a layer of cells, between the intestinal epithelial cells and the intestinal content. The parasite causes the actin filaments to rearrange, and so compromising barrier function. This has been suggested to contribute to the diarrheal symptoms sometimes observed in Blastocystis patients. (Puthia et al., 2006)
However, these studies are inconclusive as the experiments were only carried out using cell cultures, hence may not totally reflect what really happens in the human body. Further research should be done to reach an affirmative conclusion.
[edit] Frequency and Prevalence of Disease
Epidemiological studies have shown that it has a worldwide distribution even though there may be higher prevalence rate in tropical, subtropical, and developing countries. It has also been speculated that infections are related to weather conditions, in which incidence rate tends to be higher during hot weather and pre-monsoonal months. There is also evidence that B. hominis is an opportunistic pathogen, i.e. patients who are already suffering from other disease conditions or infections are more susceptible to Blastocystis infections. In particular to patients suffering from HIV infections, comparative studies have shown that they are more prone to Blastocystis infection than healthy individuals. This can be explained by the fact that HIV-positive patients have a weaker immune system, hence a lower level of production of IgA, giving rise to a conducive environment for B. hominis to live in.
[edit] Transmission
B. hominis is transmitted by the fecal contamination of drinking water and foods. Cyst forms of B. hominis are resistant to damage from external environment and are therefore transmissible forms through contaminated water. Blastocystosis can also be transmitted from animals to humans. Some studies have also shown that B. hominis appears to be commonly found in homosexual men and it has been suggested that the parasite could have been transmitted through ano-oral sexual contact.
[edit] TREATMENT
The need for treatment is still highly debatable because the disease-causing mechanism is not yet fully understood. Some physicians believe that treatment of B. hominis infection is warranted if unexplained symptoms are present and no other cause of disease has been identified after a thorough examination. Nevertheless, it should also be considered that Blastocystis infection can generally be resolved spontaneously due to its self-limiting nature. In the case when treatment is needed, antibiotic treatment with metronidazole is usually recommended. Metronidazole and other nitroimidazoles appear to be the more common treatment used even though resistance has been reported for some individuals. Other drugs that have been tested to be effective are emetine, furazolidone, trimethoprim- sulfamethoxazole (TMP-SMX), and iodoquinol. However some of these drugs are not widely used due to their toxicity.
[edit] CONCLUSION
Over the century since the study of B. hominis was initiated, numerous studies have been done to improve our understanding of this ubiquitous organism in terms of its biological and clinical aspects. Nonetheless, some aspects are still inconclusive and sometimes contradictory. Thus more research needs to be done. An example is to identify a suitable animal model to get a clearer picture of its disease-causing ability.
[edit] References
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