|T. vaginalis phase contrast microscopy|
Trichomonas vaginalis is an anaerobic, flagellated protozoan parasite and the causative agent of trichomoniasis. It is the most common pathogenic protozoan infection of humans in industrialized countries. Infection rates between men and women are similar with women being symptomatic, while infections in men are usually asymptomatic. Transmission usually occurs via direct, skin-to-skin contact with an infected individual, most often through vaginal intercourse. The WHO has estimated that 160 million cases of infection are acquired annually worldwide. The estimates for North America alone are between 5 and 8 million new infections each year, with an estimated rate of asymptomatic cases as high as 50%. Usually treatment consists of metronidazole and tinidazole.
Mechanism of infection
Trichomonas vaginalis, a parasitic protozoan, is the etiologic agent of trichomoniasis, and is a sexually transmitted infection. More than 160 million people worldwide are annually infected by this protozoan.
Trichomoniasis, a sexually transmitted infection of the urogenital tract, is a common cause of vaginitis in women, while men with this infection can display symptoms of urethritis. 'Frothy', greenish vaginal discharge with a 'musty' malodorous smell is characteristic.
Only 2% of women with the infection will have a "strawberry" cervix (colpitis macularis, an erythematous cervix with pinpoint areas of exudation) or vagina on examination. This is due to capillary dilation as a result of the inflammatory response.
Some of the complications of T. vaginalis in women include: preterm delivery, low birth weight, and increased mortality as well as predisposing to HIV infection, AIDS, and cervical cancer. T. vaginalis has also been reported in the urinary tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions. Condoms are effective at reducing, but not wholly preventing, transmission.
Recent research also suggests a link between T. vaginalis infection in males and subsequent aggressive prostate cancer.
Classically, with a cervical smear, infected women have a transparent "halo" around their superficial cell nucleus. It is unreliably detected by studying a genital discharge or with a cervical smear because of their low sensitivity. T. vaginalis was traditionally diagnosed via a wet mount, in which "corkscrew" motility was observed. Currently, the most common method of diagnosis is via overnight culture, with a sensitivity range of 75-95%. Newer methods, such as rapid antigen testing and transcription-mediated amplification, have even greater sensitivity, but are not in widespread use. The presence of T. vaginalis can also be diagnosed by PCR, using primers specific for GENBANK/L23861.
Infection is treated and cured with metronidazole or tinidazole. Metronidazole would normally be prescribed for a 7 day period and Tinidazole as a two day course, which appears to have a higher success rate than the single dose option. Medication should be prescribed to any sexual partner(s) as well because they may be asymptomatic carriers.
Unlike other parasitic protozoa (Giardia lamblia, Entamoeba histolytica etc.), Trichomonas vaginalis exists in only one morphological stage, a trophozoite, and cannot encyst. The T. vaginalis trophozoite is oval as well as flagellated, or "pear" shaped as seen on a wet-mount. It is slightly larger than a white blood cell, measuring 9 × 7 μm. Five flagella arise near the cytostome; four of these immediately extend outside the cell together, while the fifth flagellum wraps backwards along the surface of the organism. The functionality of the fifth flagellum is not known. In addition, a conspicuous barb-like axostyle projects opposite the four-flagella bundle. The axostyle may be used for attachment to surfaces and may also cause the tissue damage seen in trichomoniasis infections.
While T. vaginalis does not have a cyst form, organisms can survive for up to 24 hours in urine, semen, or even water samples.
T. vaginalis lacks mitochondria and therefore necessary enzymes and cytochromes to conduct oxidative phosphorylation. T. vaginalis obtains nutrients by transport through the cell membrane and by phagocytosis. The organism is able to maintain energy requirements by the use of a small amount of enzymes to provide energy via glycolysis of glucose to glycerol and succinate in the cytoplasm, followed by further conversion of pyruvate and malate to hydrogen and acetate in an organelle called the hydrogenosome.
One of the hallmark features of Trichomonas vaginalis is the adherence factors that allow cervicovaginal epithelium colonization in women. The adherence that this organism illustrates is specific to vaginal epithelial cells (VECs) being pH, time and temperature dependent. A variety of virulence factors mediate this process some of which are the microtubules, microfilaments, adhesins (4), and cysteine proteinases. The adhesins are four trichomonad enzymes called AP65, AP51, AP33, and AP23 that mediate the interaction of the parasite to the receptor molecules on VECs. Cysteine proteinases may be another virulence factor because not only do these 30 kDa proteins bind to host cell surfaces but also may degrade extracellular matrix proteins like hemoglobin, fibronectin or collagen IV.
Genome sequencing and statistics
The T. vaginalis genome was found to be approximately 160 megabases in size – ten times larger than predicted from earlier gel-based chromosome sizing  (The human genome is ~3.5 gigabases by comparison.) As much as two-thirds of the T. vaginalis sequence consists of repetitive and transposable elements, reflecting a massive, evolutionarily recent expansion of the genome. The total number of predicted protein-coding genes is ~98,000, which includes ~38,000 'repeat' genes (virus-like, transposon-like, retrotransposon-like, and unclassified repeats, all with high copy number and low polymorphism). Approximately 26,000 of the protein-coding genes have been classed as 'evidence-supported' (similar either to known proteins, or to ESTs), while the remainder have no known function. These extraordinary genome statistics are likely to change downward as the genome sequence, currently very fragmented due to the difficulty of ordering repetitive DNA, is assembled into chromosomes, and as more transcription data (ESTs, microarrays) accumulate. But it appears that the gene number of the single-celled parasite T. vaginalis is, at minimum, on par with that of its host H. sapiens.
In late 2007 TrichDB.org was launched as a free, public genomic data repository and retrieval service devoted to genome-scale trichomonad data. The site currently contains all of the T. vaginalis sequence project data, several EST libraries, and tools for data mining and display. TrichDB is part of the NIH/NIAID-funded EupathDB functional genomics database project.
Increased susceptibility to HIV
The damage caused by Trichomonas vaginalis to the vaginal epithelium increases a woman's susceptibility to an HIV infection. In addition to inflammation, the parasite also causes lysis of epithelial cells and RBCs in the area leading to more inflammation and disruption of the protective barrier usually provided by the epithelium. Having Trichomonas vaginalis also may increase the chances of the infected woman transmitting HIV to her sexual partner(s).
The biology of T. vaginalis has implications for understanding the origin of sexual reproduction in eukaryotes. T. vaginalis is not known to undergo meiosis, a key stage of the eukaryotic sexual cycle. However, when Malik et al. examined T. vaginalis for the presence of 29 genes known to function in meiosis, they found 27 such genes, including 8 of 9 genes that are specific to meiosis in model organisms. These findings suggest that the capability for meiosis, and hence sexual reproduction, was present in recent ancestors of T. vaginalis. Twenty-one of the 27 meiosis genes were also found in another parasite Giardia lamblia (also called Giardia intestinalis), indicating that these meiotic genes were present in a common ancestor of T. vaginalis and G. intestinalis. Since these two species are descendants of lineages that are highly divergent among eukaryotes, Malik et al. noted that these meiotic genes were likely present in a common ancestor of all eukaryotes. These considerations, as well as data from other species, further suggest that meiosis, and hence sexual reproduction, was present in the common ancestor of all eukaryotes.
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