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.<ref name=Soper_2004>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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%.<ref name=Hook_1999>Template:Cite journal</ref> Usually treatment consists of either metronidazole or tinidazole.<ref>Template:Cite web</ref> More recent studies on Trichomonas vaginalis have shed light on the parasite's evolution, genomic complexity, and pathogenesis processes.<ref name="WHO Fact Sheet">World Health Organization (2023). "Trichomoniasis". WHO Fact Sheets. World Health Organization. Retrieved 5 May 2025.</ref> 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

Trichomonas vaginalis protozoa. Colorized SEM

The structure of Trichomonas vaginalis

History

File:Trichomonas vaginalis infection - phase contrast.mpg Alfred Francois Donné (1801–1878) 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.<ref name="Donné 1836">Template:Cite journal</ref> With it, he created the binomial name of the parasite as Trichomonas vaginalis.<ref>Template:Cite journal</ref> 80 years after the initial discovery of the parasitic protozoan, Hohne declared Trichomoniasis as a clinical entity in 1916.<ref>Template:Cite journal</ref>

Signs and symptoms

Pap smear, showing infection by Trichomonas vaginalis. Papanicolaou stain, 400×

Most women (85%) and men (77%) 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.<ref name="pmid35416973">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> 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."<ref>Template:Cite journal</ref>

Diagnosis

File:Trichomonas vaginalis.webm

Trichomonas vaginalis Gram stain (arrows)

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."<ref>Template:Cite journal</ref> 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,<ref name=Ohlermeyer_1998>Template:Cite journal</ref><ref name=Sood_2007>Template:Cite journal</ref> with a sensitivity range of 75–95%.<ref name=pmid17578778>Template:Cite journal</ref> Newer methods, such as rapid antigen testing and transcription-mediated amplification, have even greater sensitivity, but are not in widespread use.<ref name=pmid17578778/>

Prevention and Treatment

Infection is treated and cured with metronidazole<ref>Template:Cite web</ref> 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.<ref>Template:Cite journal Erratum in: MMWR Recomm Rep. 2011 Jan 14;60(1):18.</ref> Medication should be prescribed to any sexual partner(s) as well because they may be asymptomatic carriers.<ref name=Cudmore_2004>Template:Cite journal</ref> 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<ref name="WHO Fact Sheet"/> 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<ref>Mercer F, Johnson PJ (August 2018). "Trichomonas vaginalis: pathogenesis, symbiont interactions, and host cell immune responses". Trends in Parasitology. 34 (8): 683–693. doi:10.1016/j.pt.2018.05.006. PMC 11132421. PMID 30056833.</ref> 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 May–Grünwald–Giemsa staining. The spike-like axostyle can be seen on the left.

Trichomonas vaginalis exists in only one morphological stage, a trophozoite, and cannot encyst (or form cysts.) 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".<ref>Template:Cite journal</ref> 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.<ref name=":6" /> In addition, a barb-like axostyle projects opposite the four-flagella bundle. All of these flagella are connected to an "undulating" membrane.<ref name=":6">Template:Cite web</ref> The axostyle may be used for attachment to surfaces and may also cause the tissue damage seen in trichomoniasis.<ref name=Sherris>Template:Cite bookTemplate:Page needed</ref> The nucleus is usually elongated, and is located near the anterior end of the protozoan within the cytoplasm which contains many hydrogenosomes (closed-membrane organelle with the ability to produce both adenosine triphosphate and hydrogen while in anaerobic conditions.)<ref name="pmid30056833">Template:Cite journal</ref>

While 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.<ref name="Petrin1998">Template:Cite journal</ref> This form is generally regarded as a degenerate stage as opposed to a resistant form,<ref name=Petrin1998/> although viability of pseudocystic cells has been occasionally reported.<ref name=Mielczarek2015>Template:Cite journal</ref> The ability to revert to trophozoite form, to reproduce and sustain infection has been described,<ref name=Hussein2008>Template:Cite journal</ref> along with a microscopic cell staining technique to visually discern this elusive form.<ref>Template:Cite journal</ref>

Metabolism

File:Trichomonas vaginalis 02.webm Trichomonas vaginalis is an anaerobe.<ref name=":3" /> There is an absence of cytochrome C and mitochondria, thus making oxygen uptake and synthesis of adenosine triphosphate via oxidative phosphorylation difficult.<ref name=":3">Template:Cite journal</ref> 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.<ref name=":2">Template:Cite journal</ref> Outside the hydrogenosome, carbohydrate metabolism also occurs freely in the cytoplasm. The Embden–Meyerhof–Parnas pathway<ref name=":2" /> 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.<ref name=":0" /> 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.<ref name=":0" /> These various forms are accompanied with differing protein phosphorylation profiles which are triggered by environmental pressures.<ref name=":0">Template:Cite journal</ref>

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.<ref name=":1" /> A variety of virulence factors mediate this process some of which are the microtubules, microfilaments, bacterial 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 vaginal epithelial cells.<ref>Template:Cite journal</ref> The best characterized surface molecule associated with one of the four adhesins is called Trichomonas vaginalis lipoglycans.<ref name=":0" /> 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.<ref name=":0" /> 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.<ref name=":1">Template:Cite journal</ref>

Genome sequencing and statistics

The Trichomonas vaginalis genome is approximately 160 megabases in size<ref>Template:Cite journal</ref> – ten times larger than predicted from earlier gel-based chromosome sizing.<ref>Template:Cite journal</ref> (The human genome is ~3.5 gigabases by comparison.<ref>Template:Cite journal</ref>) 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 (virus-like, transposon-like, retrotransposon-like, and unclassified repeats, all with high copy number and low polymorphism).<ref name=":4">Template:Cite journal</ref> Approximately 26,000 of the protein-coding genes have been classed as 'evidence-supported' (similar either to known proteins, or to expressed sequence tags), while the remainder have no known function.<ref name=":4" /> 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 (expressed sequence tags, microarrays) accumulate.<ref name=":4" />

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 Trichomonas vaginalis sequence project data, several expressed sequence tag libraries, and tools for data mining and display.<ref name=":5" /> TrichDB is part of the EupathDB functional genomics database project funded by the National Institutes of Health and National Institute of Allergy and Infectious Diseases.<ref name=":5">Template:Cite journal</ref>

Genetic diversity

A 2023 study<ref>Squire DS, Lymbery AJ, Walters J, Brigg F, Paparini A, Thompson RCA (August 2020). "Population structure and genetic diversity of Trichomonas vaginalis clinical isolates in Australia and Ghana". Infection, Genetics and Evolution. 82: 104318. doi:10.1016/j.meegid.2020.104318. PMID 32278146.</ref> conducted using next-generation multilocus sequence typing found high genetic variation in T. vaginalis isolates of geographically disparate populations in Australia and Ghana. Among 178 clinical isolates, scientists found 36 alleles and 48 distinct sequence types, of which nearly half were not previously recorded. In spite of the variation, there was high linkage disequilibrium showing that the population was predominantly clonal and subjected to very little recombination. Because there was a third genetic group that was unassigned implies that there might have been historical recombination events that have structured the population in the way that it currently exists. These findings highlight the need for more studies to establish how genetic variability affects pathogenicity as well as the efficacy of treatment.

Increased susceptibility to human immunodeficiency virus

In addition to inflammation that Trichomonas vaginalis causes, the parasite also causes lysis of epithelial cells and red blood cells 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 human immunodeficiency virus to her sexual partner(s).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Evolution

The biology of Trichomonas vaginalis has implications for understanding the origin of sexual reproduction in eukaryotes. Trichomonas vaginalis is not known to undergo meiosis, a key stage of the eukaryotic sexual cycle. However, when Malik et al.<ref name=Malik>Template:Cite journal</ref> examined Trichomonas vaginalis for the presence of 29 genes known to function in meiosis, they found 27 homologous genes to the ones found in animals, fungi, plants and other protists, including eight of nine genes that are specific to meiosis in model organisms.<ref name="Malik" /> These findings suggest that Trichomonas vaginalis has the capability for meiotic recombination, and hence "parasexual" reproduction.<ref name="Malik" /> 21 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 Trichomonas vaginalis and G. intestinalis.<ref name="Malik" /> Since these two species are descendants of lineages that are highly divergent among eukaryotes, these meiotic genes were likely present in a common ancestor of all eukaryotes.<ref name="Malik" /> T. vaginalis's evolution also manifests in an unusually huge and complicated genome that comprises about 160 megabases and about 60,000 genes. The genome comprises repetitive and noncoding sequences<ref>Twu O, de Miguel N, Lustig G, Stevens GC, Vashisht A, Wohlschlegel JA, Johnson PJ (July 2014). "Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host–parasite interactions". PLOS Pathogens. 10 (7): e1004489. doi:10.1371/journal.ppat.1004489. PMC 4727577. PMID 25033096.</ref> which signify a gene duplication and possible gene loss history. T. vaginalis does not appear to undergo traditional meiosis despite the fact that there are genes related to meiosis. The reproductive process in this organism seems to result in genetic variability that has a bearing on adaptability as well as drug resistance.

Global prevalence and infection risk factors

A systematic review and meta-analysis based on 425 articles, published in 2025, outlined the following results.<ref name="Tian2025"/> The global prevalence rate of T. vaginalis is 8%, with country-specific rates ranging from 1% to 35%. The prevalence was correlated with behavior and was significantly higher in subgroups including smoking, drug use, and not using condoms, and in the group with other sexually transmitted infections, including HIV, HSV, and Chlamydia infection. Socioeconomic factors such as being unmarried, having a low income, and unstable employment were associated with an increased risk.<ref name="Tian2025">Template:Cite journalTemplate:Creative Commons text attribution notice</ref>

See also

• List of parasites (human)

Further reading

• Template:Cite journal

External links

• TIGR's Trichomonas vaginalis genome sequencing project.
• TrichDB: the Trichomonas vaginalis genome resource
• NIH site on trichomoniasis.
• Taxonomy
• eMedicine article on trichomoniasis.
• Patient UK
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