Trichomonas vaginalis
Trichomonas vaginalis is an anaerobic, flagellated protozoan parasite and the causative agent of a sexually transmitted disease called trichomoniasis. It is the most common pathogenic protozoan that infects humans in industrialized countries. Infection rates in men and women are similar but women are usually 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. It is 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 either metronidazole or tinidazole. More recent studies on Trichomonas vaginalis have shed light on the parasite's evolution, genomic complexity, and pathogenesis processes. New population studies and genomic sequences illustrate the genetic variability of the parasite and the parasite's possible resistance to treatment. Understanding of host-pathogen interaction and prevention strategies remains a driving force behind public health.
Clinical
History
[Image:Trichomonas vaginalis infection - phase contrast.mpg|thumb|right|Trichomonas vaginalis from a vaginal swab. This is a heavy infection; there were probably thousands of trichomonads in the vagina.]Alfred Francois Donné was the first to describe a procedure to diagnose trichomoniasis through "the microscopic observation of motile protozoa in vaginal or cervical secretions" in 1836. He published this in the article entitled, "Animalcules observés dans les matières purulentes et le produit des sécrétions des organes génitaux de l'homme et de la femme" in the journal, Comptes rendus de l'Académie des sciences. With it, he created the binomial name of the parasite as Trichomonas vaginalis. 80 years after the initial discovery of the parasitic protozoan, Hohne declared Trichomoniasis as a clinical entity in 1916.
Signs and symptoms
Image:Pap test trichomonas.JPG|thumb|right|Pap smear, showing infection by Trichomonas vaginalis. Papanicolaou stain, 400×Most women and men infected with T. vaginalis do not have symptoms. Half of these women can develop symptoms within 6 months and can have vaginal erythema, dyspareunia, dysuria, and vaginal discharge, which is often diffuse, malodorous, and yellow-green, along with itching in the genital region. "Strawberry cervix," occurs in about 5% of women. In men, it can cause urethritis, epididymitis and prostatitis.
Complications
Some of the complications of Trichomonas vaginalis in women include: preterm delivery, low birth weight, and increased mortality as well as predisposing to human immunodeficiency virus infection, AIDS, and cervical cancer. Trichomonas vaginalis can be seen in diverse locations within the body, such as," in the urinary tract, fallopian tubes, and pelvis and can cause pneumonia, bronchitis, and oral lesions."Diagnosis
Classically, with a cervical smear, infected women may have a transparent "halo" around their superficial cell nucleus but more typically the organism itself is seen with a, "slight cyanophilic tinge, faint eccentric nuclei, and fine acidophilic granules." It is unreliably detected by studying a genital discharge or with a cervical smear because of their low sensitivity. Trichomonas vaginalis is also routinely diagnosed via a wet mount, in which motility is 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.Prevention and Treatment
Infection is treated and cured with metronidazole or tinidazole. The CDC recommends a one time dose of 2 grams of either metronidazole or tinidazole as the first-line treatment; the alternative treatment recommended is 500 milligrams of metronidazole, twice daily, for seven days if there is failure of the single-dose regimen. Medication should be prescribed to any sexual partner as well because they may be asymptomatic carriers. Trichomoniasis due to T. vaginalis ranks as the most prevalent non-viral sexually transmitted disease, and there were about 156 million new cases in 2020 reported worldwide. It is a curable infection that occurs through unprotected intercourse. Measures for prevention include the use of a condom consistently and screening in sexually active participants. Symptoms include urethral or vaginal irritation, unusual discharge, itching in the genitals, frequent urination, and dysuria. Antigen detection and the use of nucleic acid amplification tests are able to be used in diagnosis. A single dose of oral metronidazole or tinidazole and other regimens for resistant strains are the recommended treatments. Despite the relatively low rate of resistance, it remains a rising public concern. There is no vaccine for trichomoniasis and the prevention and early treatment of the disease are hence vital.Pathogenesis
T. vaginalis causes a very common sexually transmitted disease by adhering to vaginal epithelial cells and breaking them down. It secretes extracellular vesicles that disrupt immune function and increase adhesion. Some strains have intracellular viruses or bacteria within them that worsen infections. The parasite is associated with disruptions to vaginal microflora. Neutrophils are the primary immune cell associated with infection, which can kill the parasite through trogocytosis.Morphology
Trichomonas vaginalis exists in only one morphological stage, a trophozoite, and cannot encyst This protozoan does not typically adhere to one shape, as in different conditions, the parasite has the ability to change. When in culture separate from the host, it usually displays a more "pear" or oval shaped morphology, but when present in a living host, specifically on the epithelial cells of the vaginal wall, the shape is more "amoeboid". It is slightly larger than a white blood cell, measuring 9 × 7 μm. In both forms, Trichomonas vaginalis has five flagella – four protruding from the front or anterior of the parasite and the fifth on the back or posterior end. The functionality of the fifth flagellum is not known. In addition, a barb-like axostyle projects opposite the four-flagella bundle. All of these flagella are connected to an "undulating" membrane. The axostyle may be used for attachment to surfaces and may also cause the tissue damage seen in trichomoniasis. The nucleus is usually elongated, and is located near the anterior end of the protozoan within the cytoplasm which contains many hydrogenosomesWhile Trichomonas vaginalis does not have a cyst form, the organism can survive for up to 24 hours in urine, semen, or even water samples. A nonmotile, round, pseudocystic form with internalized flagella has been observed under unfavorable conditions. This form is generally regarded as a degenerate stage as opposed to a resistant form, although viability of pseudocystic cells has been occasionally reported. The ability to revert to trophozoite form, to reproduce and sustain infection has been described, along with a microscopic cell staining technique to visually discern this elusive form.
Metabolism
Trichomonas vaginalis is an anaerobe. There is an absence of cytochrome C and mitochondria, thus making oxygen uptake and synthesis of adenosine triphosphate via oxidative phosphorylation difficult. Although it contains no mitochondria, an analogous structure called a hydrogenosome, which is the site of fermentative oxidation of pyruvate, carries out many of the same metabolic processes. Carbohydrates, specifically those with alpha1,4- glycosidic linkages, are metabolized and eventually fermented to produce products such as acetate, lactate, malate, glycerol and CO2 under aerobic conditions. Hydrogen is produced under anaerobic conditions. Outside the hydrogenosome, carbohydrate metabolism also occurs freely in the cytoplasm. The Embden–Meyerhof–Parnas pathway is used to convert glucose into phosphoenolpyruvate which ultimately becomes pyruvate.Virulence factors
Although Trichomonas vaginalis exists as a trophozoite in its infective form, its amoeboid form is also an important characteristic that adds to how well it is able to infect its host. The amoeboid form, which is pancake shaped, allows for greater surface area contact with epithelial cells of the vagina, cervix, urethra, and prostate. The pseudocyst form is also a way in which the microbe can infect more efficiently, but this only induced when exposed to cold and other stressors. These various forms are accompanied with differing protein phosphorylation profiles which are triggered by environmental pressures.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 being pH, time, and temperature dependent. A variety of virulence factors mediate this process some of which are the microtubules, microfilaments, bacterial adhesins, 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 vaginal epithelial cells. The best characterized surface molecule associated with one of the four adhesins is called Trichomonas vaginalis lipoglycans. This molecule is the most abundant on the surface of Trichomonas vaginalis, aids in sticking to vaginal epithelial cells, and can also influence how the human immune system responds, affecting inflammatory responses and macrophages in the body. 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 Trichomonas vaginalis genome is approximately 160 megabases in size – ten times larger than predicted from earlier gel-based chromosome sizing. As much as two-thirds of the Trichomonas vaginalis sequence consists of repetitive and transposable elements, indicative of a recent drastic, evolutionarily expansion of the genome. The total number of predicted protein-coding genes is ~60,000, with the genome being around 65% repetitive. Approximately 26,000 of the protein-coding genes have been classed as 'evidence-supported', 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 accumulate.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 Trichomonas vaginalis sequence project data, several expressed sequence tag libraries, and tools for data mining and display. TrichDB is part of the functional genomics database project funded by the National Institutes of Health and National Institute of Allergy and Infectious Diseases.