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Trichomonas vaginalis origins, molecular pathobiology and clinical considerations
Abstract
To integrate a selection of the most recent data on Trichomonas vaginalis origins, molecular cell biology and T. vaginalis interactions with the urogenital tract microbiota with trichomoniasis symptoms and clinical management.
Transcriptomics and proteomics datasets are accumulating, facilitating the identification and prioritization of key target genes to study T. vaginalis pathobiology. Proteins involved in host sensing and cytoskeletal plasticity during T. vaginalis amoeboid transformation were identified. T. vaginalis was shown to secrete exosomes and a macrophage migration inhibitory factor-like protein that both influence host-parasite interactions. T. vaginalis co-infections with Mycoplasma species and viruses were shown to modulate the inflammatory responses, whereas T. vaginalis interactions with various Lactobacillus species inhibit parasite interactions with human cells. T. vaginalis infections were also shown to be associated with bacterial vaginosis. A broader range of health sequelae is also becoming apparent. Diagnostics for both women and men based on the molecular approaches are being refined, in particular for men.
New developments in the molecular and cellular basis of T. vaginalis pathobiology combined with data on the urogenital tract microbiota and immunology have enriched our knowledge on human-microbe interactions that will contribute to increasing our capacity to prevent and treat T. vaginalis and other sexually transmitted infections.
Supplementary resource (1)
... M. girerdii" with premature birth has yet to be adequately assessed. Notably, T. vaginalis infections are associated with several pregnancy and postpartum complications, including low birth weight, premature rupture of membranes, and preterm delivery (33). Notably, comorbidities are increasingly recognized to have important implications for diagnostics and treatment regimens during pregnancy (34). ...
... These results support the hypothesis suggested by the RNA-Seq data that the presence of M. hominis and "Ca. M. girerdii" influences positively both the capacities for T. vaginalis hemolysis and adhesion to host epithelial cells, two important features of T. vaginalis pathobiology (33,54,60). ...
... The ability of T. vaginalis to act in concert with endosymbiotic bacteria and viruses in the vaginal environment is an intriguing aspect of protozoan pathobiology (13,21,33,61) and represents a fascinating and unique case of comorbidity from distinct microbes involved in different combinations of endosymbiosis, which can involve various combinations of up to two Mycoplasma species and up to four TVVs. Notably, multimorbidities are increasingly recognized to represent significant contributors to both mortality and morbidity rates during pregnancy (34), and the acquisition of T. vaginalis during gestation represents an additional risk for adverse pregnancy outcomes (61,62). ...
Trichomonas vaginalis can host the endosymbiont Mycoplasma hominis, an opportunistic pathogenic bacterium capable of modulating T. vaginalis pathobiology. Recently, a new noncultivable mycoplasma, "Candidatus Mycoplasma girerdii," has been shown to be closely associated with women affected by trichomoniasis, suggesting a biological association. Although several features of "Ca. M. girerdii" have been investigated through genomic analysis, the nature of the potential T. vaginalis-"Ca. M. girerdii" consortium and its impact on the biology and pathogenesis of both microorganisms have not yet been explored. Here, we investigate the association between "Ca. M. girer-dii" and T. vaginalis isolated from patients affected by trichomoniasis, demonstrating their intracellular localization. By using an in vitro model system based on single-and double-Mycoplasma infection of Mycoplasma-free isogenic T. vaginalis, we investigated the ability of the protist to establish a relationship with the bacteria and impact T. vagi-nalis growth. Our data indicate likely competition between M. hominis and "Ca. M. girer-dii" while infecting trichomonad cells. Comparative dual-transcriptomics data showed major shifts in parasite gene expression in response to the presence of Mycoplasma, including genes associated with energy metabolism and pathogenesis. Consistent with the transcriptomics data, both parasite-mediated hemolysis and binding to host epithe-lial cells were significantly upregulated in the presence of either Mycoplasma species. Taken together, these results support a model in which this microbial association could modulate the virulence of T. vaginalis. IMPORTANCE T. vaginalis and M. hominis form a unique case of endosymbiosis that modulates the parasite's pathobiology. Recently, a new nonculturable mycoplasma species ("Candidatus Mycoplasma girerdii") has been described as closely associated with the protozoon. Here, we report the characterization of this endosymbiotic relationship. Clinical isolates of the parasite demonstrate that mycoplasmas are common among trichomoniasis patients. The relationships are studied by devising an in vitro system of single and/or double infections in isogenic protozoan recipients. Comparative growth experiments and transcriptomics data demonstrate that the composition of different microbial consortia influences the growth of the parasite and significantly modulates its transcriptomic profile, including metabolic enzymes and virulence genes such as adhe-sins and pore-forming proteins. The data on modulation from RNA sequencing (RNA-Seq) correlated closely with those of the cytopathic effect and adhesion to human target cells. We propose the hypothesis that the presence and the quantitative ratios of endosymbionts may contribute to modulating protozoan virulence. Our data highlight
... Beyond the gut, an interesting set of data for Trichomonas vaginalis and Trichomonas tenax, infecting respectively the urogenital tract (Hirt and Sherrard, 2015) and oral cavities (Marty et al., 2017) also highlight the importance of specific and sensitive diagnostics and the knowledge of their distributions beyond humans (Maritz et al., 2014). Through carefully testing the specificity of a molecular diagnostic tool used for T. vaginalis it was discovered that some infections of the urogenital tract (three male urine samples) could be due to T. tenax rather than T. vaginalis (Brosh-Nissimov et al., 2019). ...
... Arguably one of the most fascinating and complex examples includes Trichomonas vaginalis that infect the urogenital tracts (UGT) of humans (Hirt and Sherrard, 2015). A complex set of interactions between T. vaginalis, RNA viruses infecting T. vaginalis (TVV), the bacteria Mycoplasma hominis forming symbiosis with T. vaginalis and other bacteria associated with bacterial vaginosis, are all thought to contribute in concert to symptomatic infections, adverse pregnancy outcomes and increase transmission and acquisition of human infecting viruses, including HIV, HPV and HSV-2 (Hirt and Sherrard, 2015;Kissinger, 2015). ...
... Arguably one of the most fascinating and complex examples includes Trichomonas vaginalis that infect the urogenital tracts (UGT) of humans (Hirt and Sherrard, 2015). A complex set of interactions between T. vaginalis, RNA viruses infecting T. vaginalis (TVV), the bacteria Mycoplasma hominis forming symbiosis with T. vaginalis and other bacteria associated with bacterial vaginosis, are all thought to contribute in concert to symptomatic infections, adverse pregnancy outcomes and increase transmission and acquisition of human infecting viruses, including HIV, HPV and HSV-2 (Hirt and Sherrard, 2015;Kissinger, 2015). This is thought to be mediated through several mechanisms including, boosting the inflammatory tone of the UGT, increasing the population of target immunocytes for HIV and induction of microlesions disrupting the mucosal barrier (Kissinger, 2015). ...
Microbial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.
... Otherwise, the culture of the sample in a liquid or semi-solid medium, mainly in Diamond's broth, has been considered for many years the reference technique for Trichomonas vaginalis detection (Lawing et al. 2000). However, its sensitivity is also low (60-80%), and an incubation time of 2-7 days is required for parasite identification (Sherrard et al. 2014;Hirt and Sherrard 2015). ...
... Current techniques in the diagnosis of trichomoniasis through urine have low sensitivity, so a vaginal secretion sample is preferred (Lawing et al. 2000;Sherrard et al. 2014). Among the most current diagnostic methods are those based on nucleic acid hybridization and rapid tests, which can be used as point-of-care testing (POCT) (Herath et al. 2021;Schwebke and Burgess 2004;Galán et al. 2018;Hirt and Sherrard 2015), although they are not authorized on male samples. Furthermore, the only current diagnostic methods in men are culture and nucleic acid amplification tests (Sood et al. 2007;Nye et al. 2009;Hardick et al. 2003). ...
Trichomoniasis, a disease caused by Trichomonas vaginalis, is the most common non-viral sexually transmitted infection worldwide. The importance of its diagnosis lies in its ease of transmission and the absence of symptoms in most cases, as occurs in men, which have a significant role as asymptomatic carriers. The most widely used diagnostic methods are the fresh examination of vaginal or urethral secretions and molecular techniques. However, as they have some disadvantages and, sometimes, low sensitivity, new trichomoniasis diagnostic methods are necessary. Volatile organic compounds in clinical samples are effective in the diagnosis of different diseases. This work aimed to study, for the first time, those present in vaginal discharge and urine of patients with Trichomonas vaginalis infection to look for volatile biomarkers. The results showed that volatile compounds such as 2-methyl-1-propanol and cyclohexanone could serve as biomarkers in vaginal discharge samples, as well as 2-octen-1-ol and 3-nonanone in urine. Moreover, 3-hydroxy-2,4,4-trimethylpentyl 2-methylpropanoate found in vaginal discharge, highly correlated to positive patients, is also highly related to urines of patients with trichomoniasis. The biomarkers described in this study might be a promising diagnostic tool.
Key Points
• The incidence of Trichomonas vaginalis infection is increasing
• Trichomonas vaginalis VOC study in vaginal discharge and urine was performed
• The identification of volatile biomarkers could allow a new diagnostic method
... 50 The clinical manifestations of trichomoniasis include dysuria, pruritus, and frothy yellowish or greenish vaginal discharge. 51 The disease is associated with preterm birth and other perinatal morbidities such as PPROM and small for gestational age infants. 52 Lipophosphoglycan (LPG) is the major adhesion molecule of T. vaginalis and it is recognized by TLR-4. ...
... Indonesian Journal of Tropical and Infectious Disease, Vol. 9 No. 1 January-April 2021:[45][46][47][48][49][50][51][52][53][54][55][56] ...
Genital tract infection (GTI) remains a significant health concern. It is estimated that in 2016, there were 370 million people who suffer from chlamydia, gonorrhea, and trichomoniasis; and 708 million others suffer from genital herpes and condyloma acuminatum. It has been reported that in pregnant women, GTI is associated with preterm delivery. The mechanisms of GTI-associated preterm delivery need to be further understood to prevent neonatal mortality and morbidity that could be the risk factor for neonates’ growth and development disorders. This article aims to describe various types of GTI and the associated pathogenesis causing preterm birth. A literature search was conducted to retrieve recent articles published in English from online databases including Pubmed, ScienceDirect, and Google Scholar. This literature study found that GTI evokes inflammatory responses that trigger several mechanisms leading to preterm delivery. The inflammatory responses in GTI include the production of proinflammatory cytokines and robust activation of neutrophils. The key mechanisms that stimulate preterm delivery in GTI include the events of early uterine contraction, preterm premature rupture of membranes, and induction of cervical ripening; which are under normal circumstances in a full-term pregnancy, those mechanisms are regulated by progesterone and prostaglandin levels along with suppression of the inflammatory responses. In conclusion, this paper has described the underlying mechanisms of preterm delivery in pregnant women with ISG. However, such mechanisms remain unclear in candida and gonococcal infection; thus, prompting the need for further studies.
... Trichomonas vaginalis is a unicellular and anaerobic pathogenic protozoon facultative that reproduces by binary fusion [1]. This parasite causes the most common human non-viral sexually transmitted infection worldwide, known as trichomoniasis [2][3][4], which causes about 250 million infections each year [1]. T. vaginalis is a parasite that colonizes the urogenital tract of both women and men [1,4], although it has also been detected and isolated from the respiratory tracts of infants [5] and adults [6]. ...
... This parasite causes the most common human non-viral sexually transmitted infection worldwide, known as trichomoniasis [2][3][4], which causes about 250 million infections each year [1]. T. vaginalis is a parasite that colonizes the urogenital tract of both women and men [1,4], although it has also been detected and isolated from the respiratory tracts of infants [5] and adults [6]. In women, this pathogen adheres to and damages vaginal epithelial cells and causes urethritis, vaginitis, and cervicitis [1], causing symptoms ranging from a relatively asymptomatic state to severe inflammation [7]. ...
This report describes a functional and structural analysis of fused glucose-6-phosphate dehydrogenase dehydrogenase-phosphogluconolactonase protein from the protozoan Trichomonas vaginalis (T. vaginalis). The glucose-6-phosphate dehydrogenase (g6pd) gene from T. vaginalis was isolated by PCR and the sequence of the product showed that is fused with 6pgl gene. The fused Tvg6pd::6pgl gene was cloned and overexpressed in a heterologous system. The recombinant protein was purified by affinity chromatography, and the oligomeric state of the TvG6PD::6PGL protein was found as tetramer, with an optimal pH of 8.0. The kinetic parameters for the G6PD domain were determined using glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP+) as substrates. Biochemical assays as the effects of temperature, susceptibility to trypsin digestion, and analysis of hydrochloride of guanidine on protein stability in the presence or absence of NADP+ were performed. These results revealed that the protein becomes more stable in the presence of the NADP+. In addition, we determined the dissociation constant for the binding (Kd) of NADP+ in the protein and suggests the possible structural site in the fused TvG6PD::6PGL protein. Finally, computational modeling studies were performed to obtain an approximation of the structure of TvG6PD::6PGL. The generated model showed differences with the GlG6PD::6PGL protein (even more so with human G6PD) despite both being fused.
... Most prominent among these protozoa are Giardia lamblia, a major cause of protracted diarrheal disease and growth retardation in children in the developing world [2], and Entamoeba histolytica, which can cause dysentery and liver abscesses [3]. In addition, Mz is employed against Trichomonas vaginalis, a sexually transmitted infection that causes vaginitis, adverse pregnancy outcomes, increased susceptibility to HIV, and cervical and prostate cancers [4,5], and several important anaerobic bacterial pathogens, particularly Helicobacter pylori and Clostridium difficile [1]. ...
... To further test the potential therapeutic utility of the identified drug targets, we selected two representative targets and their inhibitors, the ADI inhibitor canavanine and the peroxiredoxin inhibitor conoidin A, and evaluated them for in vitro cytotoxicity and in vivo efficacy. Testing in human HeLa cells revealed pCC50 values of 4.08 ± 0.19 and 5.87 ± 0.07 for canavanine and conoidin A, respectively (mean ± SE; n = [4][5]. Together with the findings on giardicidal potency (Fig 6), these data show that canavanine had modest selectivity for the parasite (selectivity index = 2.5), while conoidin A had no selectivity (selectivity index, 0.04). ...
Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multi-dimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5'-nitroimidazole-sensitive and -resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5'-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.
... Trichomoniasis is the most common sexually transmitted nonviral infection worldwide. 1 The World Health Organization estimated that there were 276.4 million cases in 2008 with 90% of these cases occurring in resource-limited areas. 1 In the United States, an estimated 3.7 million cases were reported by the Centers for Disease Control and Prevention. 2 Once infected, a person is more likely to become infected with chlamydia, gonorrhea, herpes simplex viruses type-1 and type-2, HIV, syphilis, and other sexually transmitted diseases. 2−4 Infections also increase the risk of developing bacterial vaginosis, candidiasis, pelvic inflammatory disease, and cervical and prostate cancer; pregnant women infected with trichomoniasis have an increased risk for low birth weight and preterm delivery. ...
... 1 The World Health Organization estimated that there were 276.4 million cases in 2008 with 90% of these cases occurring in resource-limited areas. 1 In the United States, an estimated 3.7 million cases were reported by the Centers for Disease Control and Prevention. 2 Once infected, a person is more likely to become infected with chlamydia, gonorrhea, herpes simplex viruses type-1 and type-2, HIV, syphilis, and other sexually transmitted diseases. 2−4 Infections also increase the risk of developing bacterial vaginosis, candidiasis, pelvic inflammatory disease, and cervical and prostate cancer; pregnant women infected with trichomoniasis have an increased risk for low birth weight and preterm delivery. ...
Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis. The increasing prevalence of strains resistant to the current 5-nitroimidazole treatments creates the need for novel therapies. T. vaginalis cannot synthesize purine and pyrimidine rings and requires salvage pathway enzymes to obtain them from host nucleosides. The uridine nucleoside ribohydrolase was screened using an ¹⁹F NMR-based activity assay against a 2000-compound fragment diversity library. Several series of inhibitors were identified including scaffolds based on acetamides, cyclic ureas or ureas, pyridines, and pyrrolidines. A number of potent singleton compounds were identified, as well. Eighteen compounds with IC50 values of 20 μM or lower were identified, including some with ligand efficiency values of 0.5 or greater. Detergent and jump-dilution counter screens validated all scaffold classes as target-specific, reversible inhibitors. Identified scaffolds differ substantially from 5-nitroimidazoles. Medicinal chemistry using the structure–activity relationship emerging from the fragment hits is being pursued to discover nanomolar inhibitors.
... By far the best studied trichomonad is Trichomonas vaginalis, which thrives in the human urogenital tract [1,2] and infects close to 300 million people annually [3,4]. Symptomatic infection is significantly more frequent in females than in males, but only a minority lead to a fully-developed trichomoniasis [5,6]. Given that most T. vaginalis infections remain unnoticed, this poses a problem since asymptomatic infections can still elevate the risk of developing cancer, facilitate the acquisition and transmission of HIV and other viruses, and are associated with a number of adverse pregnancy outcomes [5][6][7][8]. ...
... Symptomatic infection is significantly more frequent in females than in males, but only a minority lead to a fully-developed trichomoniasis [5,6]. Given that most T. vaginalis infections remain unnoticed, this poses a problem since asymptomatic infections can still elevate the risk of developing cancer, facilitate the acquisition and transmission of HIV and other viruses, and are associated with a number of adverse pregnancy outcomes [5][6][7][8]. Treatments with a 5-nitroimidazole-based derivate are quite effective [9,10], although about 10% of Trichomonas strains diagnosed display some tolerance or even resistance towards metronidazole-based drugs [10]. ...
Background:
Trichomonas vaginalis is a human-infecting trichomonad and as such the best studied and the only for which the full genome sequence is available considering its parasitic lifestyle, T. vaginalis encodes an unusually high number of proteins. Many gene families are massively expanded and some genes are speculated to have been acquired from prokaryotic sources. Among the latter are two gene families that harbour domains which share similarity with proteins of Bacteroidales/Spirochaetales and Chlamydiales: the BspA and the Pmp proteins, respectively.
Results:
We sequenced the transcriptomes of five trichomonad species and screened for the presence of BspA and Pmp domain-containing proteins and characterized individual candidate proteins from both families in T. vaginalis. Here, we demonstrate that (i) BspA and Pmp domain-containing proteins are universal to trichomonads, but specifically expanded in T. vaginalis; (ii) in line with a concurrent expansion of the endocytic machinery, there is a high number of BspA and Pmp proteins which carry C-terminal endocytic motifs; and (iii) both families traffic through the ER and have the ability to increase adhesion performance in a non-virulent T. vaginalis strain and Tetratrichomonas gallinarum by a so far unknown mechanism.
Conclusions:
Our results initiate the functional characterization of these two broadly distributed protein families and help to better understand the origin and evolution of BspA and Pmp domains in trichomonads.
... By far the best studied trichomonad is Trichomonas vaginalis, which thrives in the human urogenital tract [1,2] and infects close to 300 million people annually [3,4]. Symptomatic infection is significantly more frequent in females than in males, but only a minority lead to a fully-developed trichomoniasis [5,6]. Given that most T. vaginalis infections remain unnoticed, this poses a problem since asymptomatic infections can still elevate the risk of developing cancer, facilitate the acquisition and transmission of HIV and other viruses, and are associated with a number of adverse pregnancy outcomes [5][6][7][8]. ...
... Symptomatic infection is significantly more frequent in females than in males, but only a minority lead to a fully-developed trichomoniasis [5,6]. Given that most T. vaginalis infections remain unnoticed, this poses a problem since asymptomatic infections can still elevate the risk of developing cancer, facilitate the acquisition and transmission of HIV and other viruses, and are associated with a number of adverse pregnancy outcomes [5][6][7][8]. Treatments with a 5-nitroimidazole-based derivate are quite effective [9,10], although about 10% of Trichomonas strains diagnosed display some tolerance or even resistance towards metronidazole-based drugs [10]. ...
Trichomonas vaginalis is one of the most widespread, sexually transmitted pathogens. The infection involves a morphological switch from a free-swimming pyriform trophozoite to an amoeboid cell upon adhesion to host epithelial cells. While details on how the switch is induced and to what proteins of the host surface the parasite adheres remain poorly characterized, several surface proteins of the parasite itself have been identified as potential candidates. Among those are two expanded protein families that harbor domains that share similarity to functionally investigated surface proteins of prokaryotic oral pathogens; these are the BspA proteins of Bacteroidales and Spirochaetales, and the Pmp proteins of Chlamydiales. We sequenced the transcriptomes of five Trichomonads and screened for the presence of BspA and Pmp domain-containing proteins and tested the ability of individual T. vaginalis candidates to mediate adhesion. Here we demonstrate that (i) BspA and Pmp domain-containing proteins are specifically expanded in T. vaginalis in comparison to other Trichomonads, and that (ii) individual proteins of both families have the ability to increase adhesion performance in a non-virulent T. vaginalis strain and Tetratrichomonas gallinarum, a parasite usually known to infect birds but not humans. Our results initiate the functional characterization of these two broadly distributed protein families, whose origin we trace back to the origin of Trichomonads themselves.
... Members of the genus Trichomonas are microaerophilic microbial eukaryotes and obligate symbionts of birds and mammals within the family Trichomonadidae, class Trichomonadea, phylum Parabasalia (Cepicka et al., 2010). Trichomonas vaginalis is the most prevalent cellular sexually transmitted pathogen in humans (Rowley et al., 2019), and is of particular importance due to its association with increased risk of HIV transmission, prenatal and postpartum complications and cervical cancer (Hirt and Sherrard, 2015;Menezes et al., 2016). Trichomonas gallinae is an avian parasite of the upper digestive tract (including the mouth and crop; Amin et al., 2014), most strongly associated with columbiforms (Peters et al., 2020) but also found in passerines and raptors (Amin et al., 2014). ...
Introduction
The protozoan parasite Trichomonas vaginalis is the most common cellular sexually transmitted disease in humans, and the closely related species Trichomonas gallinae is an avian parasite of ecological and economic importance. Phylogenetic evidence suggests T. vaginalis arose during bird to human transmission of a T. gallinae -like ancestor. Trichomonas vaginalis shares a strong clinical association with the independent sexually transmitted pathogen Metamycoplasma (formerly Mycoplasma ) hominis , and the uncultured bacterium “ Candidatus Malacoplasma (formerly Mycoplasma ) girerdii,” with the latter association being an order of magnitude stronger. Both bacterial species have been shown to profoundly influence T. vaginalis growth, energy production and virulence-associated mechanisms.
Methods
Evidence for a novel Malacoplasma sp. was discovered by in vivo Illumina metatranscriptomics sequencing of the T. gallinae -infected pigeon mouth. We leveraged published 16S rDNA profiling data from digestive tract of 12 healthy and 24 T. gallinae -infected pigeons to investigate association between the novel Malacoplasma sp. and T. gallinae . We utilised Illumina metagenomics sequencing targeted to pigeon oral and crop samples infected with the novel Malacoplasma sp. to generate its full-length genome sequence. Sequence similarity network analysis was used to compare annotated proteins from the novel Malacoplasma sp. with a range of other related species.
Results
Here we present evidence for a novel Malacoplasma species, related to “ Ca. M. girerdii,” that is strongly associated with T. gallinae in the upper digestive tract of domestic pigeons. Analysis of the genome sequence revealed gene features apparently specific to a Trichomonas -symbiotic Malacoplasma lineage.
Discussion
These data support a model of long-term association between Trichomonas and Malacoplasma spp. that has been conserved across diversification of the Trichomonas lineage and the host species barrier from birds to human.
... TV infection can cause vaginitis, urethritis and prostatitis, and other diseases (Schwebke and Burgess 2004). In addition, it is an important source of reproductive diseases, a promoter of HIV transmission and acquisition (Masha et al. 2019, Raffone et al. 2021, associated with infertility, premature labour, and possibly a higher incidence of cervical cancer (Hirt and Sherrard 2015). Studies have found that TV infection might determine an increased risk of HPV persistence by inducing inflammatory response in the cervico-vaginal epithelium, impairing vaginal epithelial cells, degrading cervical mucus, and cleaving immunoglobulin A (Raffone et al. 2021). ...
Trichomonas vaginalis (TV) may have an impact on other reproductive tract infections. Studies on the connection between the infection of TV and human papillomavirus (HPV) have been inconsistent. We performed a systematic review of the relevant articles through keywords that satisfy the criteria and filtered the articles according to the inclusion and exclusion criteria. A total of 16 eligible studies were screened for the meta-analysis, involving a total of 150,605 women. RevMan 5.4 software was used for meta-analysis of the selected literatures. The results showed that the papers included in this study had good homogeneity and no significant publication bias was found in the current analysis. The pooled estimates using a fixed-effects model showed that TV was more prevalent in HPV-infected women than in non-infected women [odds ratio (OR): 1.51, 95% confidence interval (CI): 1.29–1.75]; In turn, HPV was more widespread in TV-infected women than in uninfected women (OR: 3.62, 95% CI: 2.71–4.85). Moreover, the interaction between TV and HPV infection was insensitive to the deletion of some studies and correlation coefficients, consequently, the results were robust and reliable. These results suggested that TV is positively associated with HPV infection, and HPV is also a risk factor for TV infection.
... Trichomoniasis is the most common non-viral sexually transmitted infection (STI) worldwide caused by T. vaginalis with an estimated global incidence of 156 million cases (Rowley et al. 2019). The infection can be chronic leading to health complications such as pelvic inflammatory disease, pregnancy outcomes, infertility, cervical and prostate cancers, and acts as a cofactor in HIV transmission (Hirt and Sherrard 2015;Menezes et al. 2016;Masha et al. 2019). Drugs currently recommended by the Food and Drug Administration (FDA, USA) are metronidazole and tinidazole; however, with side effects such as nausea, vomiting, headache, insomnia, dizziness, and drowsiness (Bouchemal et al. 2017;Workowski et al. 2021). ...
Trichomoniasis is the most common non-viral sexually transmitted infection (STI) in the world caused by Trichomonas vaginalis. Failures in the treatment with the 5-nitroimidazole class including parasite resistance to metronidazole elicit new alternatives. Marine natural products are sources of several relevant molecules, presenting a variety of metabolites with numerous biological activities. In this work, we evaluated the anti-T. vaginalis activity of fungi associated with marine invertebrates by mass spectrometry-based metabolomics approaches. After screening of six marine fungi, extract from Penicillium citrinum FMPV 15 has shown to be 100% active against T. vaginalis, and the gel permeation column on Sephadex LH-20® yielded twelve organic fractions which five showed to be active. Metabolomics and statistical analyses were performed with all the samples (extract and fractions), and several compounds were suggested to be related to the activity. These components include citrinin, dicitrinin C, citreoisocoumarin, dihydrocitrinone, decarboxycitrinin, penicitrinone C, and others. The minimum inhibitory concentration (MIC) value of anti-T. vaginalis activity of citrinin was 200 µM. The marine fungi metabolites show potential as new alternatives to overcome drug resistance in T. vaginalis infections.
... Studies in the past found that the hydrogenosome of TV turns arginine into citrulline and ammonia through arginine deiminase (ADI). This step is a part of the energy production process of putrescine biosynthesis through the ADH pathway [24,25]. In addition, TV hydrogenosomes produce more NO and enhance hydrogenosomal membrane potential in an iron-restricted environment to maintain cell survival [26]. ...
Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith–Waterman and Needleman–Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.
... It is caused by Trichomonas vaginalis, a flagellated protist lacking a cyst stage. In women, the infection is often asymptomatic and the usual symptoms include vaginal discharge, spotting, and bleeding [2], while in men it usually presents as a transient asymptomatic infection, but can be associated with urethritis and prostatitis [3]. The presence of T. vaginalis in the urogenital tract has been also associated with the persistence of most carcinogenic HPV types, cervical and prostate cancer, and a higher risk of HIV and HPV infection [4,5]. ...
Trichomoniasis, the most common non-viral sexually transmitted infection worldwide, is caused by the protozoon Trichomonas vaginalis. The 5-nitroimidazole drugs, of which metronidazole is the most prescribed, are the only effective drugs to treat trichomoniasis. Resistance against met-ronidazole is increasingly reported among T. vaginalis isolates. T. vaginalis can establish an endo-symbiosis with two Mycoplasma species, Mycoplasma hominis and Candidatus Mycoplasma girerdii, whose presence has been demonstrated to influence several aspects of the protozoan pathobiology. The role of M. hominis in T. vaginalis resistance to metronidazole is controversial, while the influence of Ca.M. girerdii has never been investigated. In this work, we investigate the possible correlation between the presence of Ca.M. girerdii and/or M. hominis and the in vitro drug susceptibility in a large group of T. vaginalis isolated in Italy and in Vietnam. We also evaluated, via RNA-seq analysis, the expression of protozoan genes involved in metronidazole resistance in a set of syngenic T. vaginalis strains, differing only for the presence/absence of the two Mycoplasmas. Our results show that the presence of M. hominis significantly increases the sensitivity to metronidazole in T. vaginalis and affects gene expression. On the contrary, the symbiosis with Candidatus Mycoplasma girerdii seems to have no effect on metronidazole resistance in T. vaginalis.
... Three independent experiments were performed in triplicate. Standard curves were generated with the mean Ct values of all experiments and regression analysis was performed using Excel v. 16.59 (Microsoft). ...
Tetratrichomonas gallinarum and Trichomonas gallinae are pathogenic avian parasites that infect a wide range of bird species. The pathologic potential of T. gallinarum is controversial, whereas T. gallinae causes disease in many avian species. Infections are often asymptomatic in doves and pigeons; thus, columbids are presumed to represent the natural hosts for trichomonads. The detection of T. gallinarum and T. gallinae is based on direct microscopic observation or a conventional PCR assay. Microscopy is not very sensitive, and identification of the trichomonads at the genus or species level is not possible. Conventional PCR assays have been developed primarily for phylogenetic studies, which detect a wide range of Trichomonas spp. but do not allow their differentiation. We developed a duplex real-time PCR (rtPCR) assay for the simultaneous detection and differentiation of T. gallinarum and T. gallinae. We found that the rtPCR assay detected 10 ² plasmid DNA copies of T. gallinarum and as few as 10 ¹ plasmid DNA copies of T. gallinae.
... In addition, trichomoniasis is associated with adverse outcomes during pregnancy and may contribute to pelvic inflammatory disease (Silver et al., 2014;Yagur et al., 2021). In men, T. vaginalis infection is in over 75% of cases asymptomatic with parasites hidden in the prostate that represent a reservoir for transmission (Hirt and Sherrard, 2015). The symptomatic infections include urethritis and prostatitis, and the trichomonads have been found in prostate tissue from benign prostatic hyperplasia (Mitteregger et al., 2012;Van Gerwen et al., 2021). ...
Trichomonas vaginalis is a parasitic protist that infects the human urogenital tract. During the infection, trichomonads adhere to the host mucosa, acquire nutrients from the vaginal/prostate environment, and release small extracellular vesicles (sEVs) that contribute to the trichomonad adherence and modulate the host-parasite communication. Approximately 40–70% of T. vaginalis strains harbor a double-stranded RNA virus called Trichomonasvirus (TVV). Naked TVV particles have the potential to stimulate a proinflammatory response in human cells, however, the mode of TVV release from trichomonads to the environment is not clear. In this report, we showed for the first time that TVV particles are released from T. vaginalis cells within sEVs. The sEVs loaded with TVV stimulated a higher proinflammatory response of human HaCaT cells in comparison to sEVs from TVV negative parasites. Moreover, a comparison of T. vaginalis isogenic TVV plus and TVV minus clones revealed a significant impact of TVV infection on the sEV proteome and RNA cargo. Small EVs from TVV positive trichomonads contained 12 enriched and 8 unique proteins including membrane-associated BspA adhesine, and about a 2.5-fold increase in the content of small regulatory tsRNA. As T. vaginalis isolates are frequently infected with TVV, the release of TVV via sEVs to the environment represents an important factor with the potential to enhance inflammation-related pathogenesis during trichomoniasis.
... Recent evidence has proved that TV infection is changed by the microbiome of women [42,43] and TV treatment is altered through using the microbiome [44]. The cluster analysis was performed to further visualize the association between TV and the composition of vaginal microbiota. ...
Background:
To investigate the associations between Vaginal Pathogenic Community with Bacterial vaginosis, Candida vaginitis, and Trichomonas vaginalis in Chinese women.
Method:
In this experiment, ten BV, nine VVC, eight TV patients, and four non-infected healthy women were recruited. The vaginal samples were collected from the vaginal orifice, the middle of the vagina, and vaginal fornix from every participant and conducted with next-generation sequencing (NGS). The NGS was based upon the analysis of bacterial 16S rRNA genes by using the Illumina Miseq system.
Results:
No significant difference in microbiome community structures was observed for the three sampling sites from the same subject. Compared with the healthy population, patients with BV and TV showed more diverse symptoms and had a lower amount of Lactobacillus but a higher number of BV-related bacteria like Atopobium, Dialister, Sneathia, Mobiluncus, and Prevotella. On the contrary, the species composition of the VVC group is relatively simple, which has a significantly high abundance of Lactobacillus. Eight genera, including Arcanobacterium, Clostridium, Moryella, Mobiluncus, Shuttleworthia, Dialister, Bulleidia, and Megasphaera, were closely correlated with BV. Among vaginal pathogenic bacteria, Anaerococcus, Lysobacter, Mycoplasma, Peptoniphilus, Sneathia, and Prevotella were more common, with higher copy numbers in the TV group.
Conclusions:
The data outlined the overall structure of vaginal communities, indicating that BV and TV were touching related to a sharp increase in the rich taxonomy and diversity of vaginal microbiota. VVC group presented a lower variety, with a significantly high abundance of Lactobacillus.
... 13 Once binding occurs, the typical pyriform shape of the parasite differentiates to an amoeboid shape, increasing contact with the epithelial cell surface; exosomes containing T. vaginalis proteins and RNA play a vital role in the host−parasite interactions. 1,6 T. vaginalis also releases polyamine metabolites, such as putrescine, resulting in cell damage and, in in vitro experiments, cell apoptosis. 14 The host inflammatory response is countered through phagocytosis, supplying the parasite with nutrients not only from epithelial cells but also from lactobacilli, leukocytes, and, most importantly, iron-rich erythrocytes released after inducing vaginal bleeding, promoting survival. ...
... It infects Human only, causes trichomoniasis, which is a worldwide disease. This parasites infects females mainly and males to a lesser extent (Hirt & Sherrard, 2015). The parasite is transmitted directly from one host to another during intercourse or indirectly through a medical examination when using a contaminated vaginal scope, as some research indicated that it can be transmitted through contaminated toilets or uses patient tools (Nouraddin & Alsakee, 2015). ...
Background: Trichomoniasis is a sexually transmitted disease. It is a public health risk factor. This disease associated with many sexual diseases and is likely to be a cause of infertility, abortion, and the birth of low-weight babies. The purpose of the study is to establish a database of parasite infection in the city, especially with no previous research on the rate of infection among men. Materials and method: Two hundred forty serum samples were collected from 120 couples between 18-43 years old, for the period from 2 Jan. 2020 to 25 jun. 2020, all of which were examined by ELISA test to detect immunoglobulin IgM and IgG. All results were analyzed by SPSS 20. Result:The study recorded a high rate of infection (27.9%). Infection rates in women were higher than men, when it recorded a total infection rate (31.7%), while the infection rate among men was (24.2%). This infection differentiation among residence, education, use a condom, and presence of symptom. Our study recorded association between Trichomoniasis and infertility, abortion, and the birth of loos weight children. Conclusion: The study showed a relatively high incidence rate among couples, perhaps due to the use of the serological method in detection. It is the first study in the city among couples in general and men in particular.
... It can cause trichomoniasis in both men and women (1,2). Trichomoniasis infection is more common in women and is associated with several clinical problems and symptoms, including awful smell vaginal discharge, painful urination, genital excitability, disorders after sexual intercourse, premature rupture of membranes, preterm birth, low birth weight, and increased risk of infection with HIV (1,(3)(4)(5). The worldwide studies and statistics indicate that in developed countries, a significant percentage (more than 50%) of patients referring to STD clinics suffer from trichomoniasis, and the rate of infection is increasing (6,7). ...
Background: Trichomoniasis is the most common non-viral sexually transmitted disease caused by a flagellated protozoan living in the genitourinary tract, which infects both men and women. Metronidazole is the treatment of choice for trichomoniasis. Researchers are seeking an alternative to metronidazole because of its inevitable side effects and toxicity. Objectives: This study aimed to evaluate the effect of the methanolic extract of Sambucus nigra against Trichomonas vaginalis in vitro. Methods: Plants were collected from different areas of Mazandaran Province, northern Iran. Fruits were separated, shade-dried, milled, and their methanolic extract was prepared in concentrations of 100, 200, 400, and 800 µg/mL. Parasites were obtained from patients referring to different health centers of Mazandaran province, cultured in Dorset medium, and incubated at 37°C. The effects were evaluated and compared to a control group. The data were analyzed by SPSS 18 using the ANOVA test. Results: The exposure time and concentration of the extracts had a direct effect on anti-parasitic activity so that increasing extract concentration and incubation time heightened the anti-trichomoniasis effects. The concentrations of 400 and 800 µg/ml of the plant had 100% efficacy after 72 and 48 hours, respectively. Conclusions: It can be concluded from our results that the methanolic extract of S. nigra has a remarkable ability to destroy T. vaginalis and it can be considered an effective drug against T. vaginalis with further studies in human and animal models.
... Trichomonas vaginalis (Tv) is a human-specific extracellular, flagellated protozoan parasite responsible for the third most common sexually transmitted infection (STI) in the United States (US) and worldwide, called trichomoniasis [1][2][3]. Worldwide, trichomoniasis case numbers approach 400 million, making it the most common non-viral sexually transmitted infection [4]. Despite the high prevalence of Tv infection, trichomoniasis is classified as a neglected infectious disease in the US owing to its high prevalence and the relative lack of research regarding the infection [3]. ...
Trichomoniasis is the third most common sexually transmitted infection in humans and is caused by the protozoan parasite, Trichomonas vaginalis ( Tv ). Pathogenic outcomes are more common in women and generally include mild vaginitis or cervicitis. However, more serious effects associated with trichomoniasis include adverse reproductive outcomes. Like other infectious agents, pathogenesis from Tv infection is predicted to be the result of both parasite and host factors. At the site of infection, neutrophils are the most abundant immune cells present and probably play key roles in both parasite clearance and inflammatory pathology. Here, we discuss the evidence that neutrophils home to the site of Tv infection, kill the parasite, and that in some circumstances, parasites possibly evade neutrophil-directed killing. In vitro , the parasite is killed by neutrophils using a novel antimicrobial mechanism called trogocytosis, which probably involves both innate and adaptive immunity. While mechanisms of evasion are mostly conjecture at present, the persistence of Tv infections in patients argues strongly for their existence. Additionally, many strains of Tv harbour microbial symbionts Mycoplasma hominis or Trichomonasvirus , which are both predicted to impact neutrophil responses against the parasite. Novel research tools, especially animal models, will help to reveal the true outcomes of many factors involved in neutrophil- Tv interactions during trichomoniasis.
... Symptoms such as exudation, itching and smell can cause distress and embarrassment. Vaginitis can cause several gynaecologic complications, such as pelvic inflammatory disease (PID), postoperative infections, cervicitis, vulvitis, positive urine cultures in neonates and neonates respiratory tract infection, preterm labour and chorioamnionitis [2][3][4][5][6][7]. ...
Vaginal infections are one of the major reasons women visit a gynecologist. Increased resistance to conventional antibiotics is one of the main factors mitigating the development of new antimicrobial agents, especially those of natural origin. In traditional Persian medicine, Trachyspermum ammi has been claimed to clear vagina from excessive discharge. Therefore, in this study, the antimicrobial activity of Ajwain essential oil was evaluated against some vaginal pathogens. The essential oil of ajwain was picked up and the minimum inhibitory and bactericidal concentrations (MIC and MBC) were revealed. The most frequently detected microorganisms involved in genital infections including Candida spp., Gardnerella vaginalis, Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae and Lactobacillus acidophilus were considered. Evaluation of the essential oil of Trichomonas vaginalis was done by calculation of percent of growth inhibition. The essential oil showed a remarkable activity against the studied bacteria and fungi with MIC at a range of 0.0315 - 0.5 mg/ml and MBC at a range of 0.125 - 4 mg /ml. The highest inhibition and bactericidal activity was observed in S. agalactiae and G. vaginalis. 100% inhibition of T. vaginalis growth was shown at a concentration of 2000 μg/ml after 48 h by essential oil. The antimicrobial activity of the essential oil was more than that of thymol. Supposedly essential oil of Trachyspermum ammi fruit could inhibit vaginal pathogens growth .Further preclinical and clinical studies are required to confirm the efficacy of this natural agent in vaginitis.
... Trichomoniasis is the most common non-viral sexually transmitted disease (STD), with more than 275 million individuals infected annually worldwide. It is caused by the infection with the flagellated protist parasite Trichomonas vaginalis [1,2]. Symptoms include vaginitis, preterm delivery, urethritis, prostatitis and infertility. ...
Trichomonas vaginalis is the protozoan parasite responsible for the most prevalent, non-viral, sexually transmitted disease, which affects millions of people around the world. The main treatment against this disease is metronidazole and some other nitroimidazole derivatives. However, between five and 20% of clinical cases of trichomoniasis are caused by parasites resistant to these drugs. Here we present three compounds that were selected using an innovative strategy, to propose them as possible drugs to combat trichomoniasis, using the glycolytic enzyme triose phosphate isomerase (TvTIM) as the drug target. In the genome of Trichomonas vaginalis there are two genes that encode for two isoforms of TvTIM, known as TvTIM1 and TvTIM2, varying by four out of 254 aminoacid residues. In this study, we used high-throughput virtual screening to search molecules that bind specifically to TvTIM isoforms, in which 34 compounds were selected from a library of nearly 450,000 compounds. The effects of the 34 compounds on the conformation and enzymatic activity of both TvTIM isoforms and their human homolog (HsTIM) were evaluated. We found three compounds that bind specifically, modify the conformation and inhibit TvTIM2 only; although the sequence of both isoforms of TvTIM is almost identical. The selectivity of these compounds towards TvTIM2 is explained by the lower conformational stability of this isoform and that these interactions can inhibit the activity of this enzyme and have an effect against this parasite. These compounds represent promising alternatives for the development of new therapeutic strategies against trichomoniasis.
... Recent studies have confirmed that vaginal microbiome changes during TV [151,152]. L. acidophilus leads to increase in adherence of T. vaginalis to vaginal epithelial cells, during the early stages of infection [149]. As the number of L. acidophilus increases, the T. vaginalis become incapable of growing, while, vice versa occurs with decrease in number of L. acidophilus at the end of menses and during menopause, consequently leading to increase in TV symptoms [153]. ...
Recurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and different Trichomonas vaginalis strains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale for Lactobacilli dominance and changes that occur in healthy VMB throughout a women's life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. "VMB dominated with Lactobacilli is healthier than a diverse VMB". These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women's response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.
... Kinetoplastids include the agents of Chagas, leishmaniasis, Kala-azar, and the African sleeping sickness (Gibson, 2016). Similarly, beaver fever (Adam, 2001), trichomoniasis (Hirt & Sherrard, 2015) or the infamous brain eating amoeba, Naegleria fowleri (John, 1982) are all excavates. ...
Awareness of the roles that host‐associated microbes play in host biology has escalated in recent years. However, microbiome studies have focused essentially on bacteria, and overall, we know little about the role of host‐associated eukaryotes outside the field of parasitology. Despite that, eukaryotes and microeukaryotes in particular are known to be common inhabitants of animals. In many cases, and/or for long periods of time, these associations are not associated with clinical signs of disease.
Unlike the study of bacterial microbiomes, the study of the microeukaryotes associated with animals has largely been restricted to visual identification or molecular targeting of particular groups. So far, since the publication of the influential Human Microbiome Project Consortium paper in 2012, few studies have been published dealing with the microeukaryotes using a high‐throughput barcoding ‘microbiome‐like’ approach in animals.
Nonetheless, microeukaryotes have an impact on the host physiology and lifestyle and also on the diversity and composition of the wider symbiotic community of bacteria and viruses. Beyond being parasites, microeukaryotes have many different roles in animals. For example, they directly interact with the host immune system in mammals; they have a key role on cellulose degradation, lignocellulose in xylophage termites and cockroaches; and they have an essential role in providing photosynthates to reef‐building corals.
Certain microeukaryotic lineages have diversified within hosts more than others. These cases of co‐evolution led to different forms of symbiosis: from mutualism (like Symbiodinium in corals or parabasalians in termites), to commensalism ( Blastocystis in humans) or to strict parasitism (apicomplexans or microsporidians in a broad range of hosts). We will review the ecological context and the evolutionary mechanisms that ended up in these different symbiotic scenarios, across the taxonomic range of both symbionts and their metazoan hosts.
Host‐associated microeukaryotes have impacts at many levels, from individual animal health to ecosystems and to agroeconomy. Therefore, it is crucial to have a better understanding of their diversity and roles. Novel methodologies are being developed to access the eukaryotic fraction of the microbiome using high‐throughput methods. From ‐omics, to imaging and barcoding approaches biased against metazoans, these novel methodologies and strategies are helping us to increase and improve our knowledge of microeukaryotes in animal‐associated environments.
A free Plain Language Summary can be found within the Supporting Information of this article.
... More people are infected by T. vaginalis than any other eukaryotic pathogen, and trichomoniasis is more prevalent than all bacterial STIs combined (2). T. vaginalis causes vaginitis, cervicitis, urethritis, and pelvic inflammatory disease and may lead to adverse pregnancy outcomes (3,4). Trichomoniasis also increases the risk of HIV transmission and has been correlated with increased incidence and severity of cervical and prostate cancers (5)(6)(7)(8)(9). ...
Significance
Extracellular vesicles (EVs) produced by one cell and internalized by a different cell are widely used for cellular communication and protein and RNA exchange between cells. Cancer metabolism and immune and neuronal responses are modulated by mammalian EVs. The uptake of parasite EVs by host cells also modifies host:pathogen interactions. Our research identifies surface components of both the host cell and EVs produced by the parasite Trichomonas vaginalis and defines cellular mechanisms critical for EV internalization and cross-talk between different cell types. Our findings reveal mechanisms that a pathogen can use to communicate with its host. This study is also instructive in guiding medical therapeutics aimed at exploiting EVs for drug and vaccine delivery.
... Keywords: Quercus; Medicinal plant; Gallic acid; Vaginitis; Trichomoniasis; Vaginal candidiasis monas vaginalis (TV) and is the most common non-viral sexually transmitted infection (STI) with the baseline prevalence of 14.6%, and cumulative 6-month of 7.5% in the USA [11,12]. [12,15,[17][18][19][20]. Azole-drug (metronidazole and tinidazole), nystatin and clindamycin are the standard treatments for vaginal Quercus gall and gallic acid on vaginal pathogens M. Mehri Ardestani et al. infections [2,18,21]. ...
Vaginal infections are one of the most common reasons a woman visits a gynecologist. The increased resistance to conventional antibiotics is one of the main reasons for searching and developing new antimicrobial agents, especially those of natural origin. In traditional Persian medicine, the gall of Quercus infectoria has been claimed to eliminate vagina and cervix from excessive discharge. So, the aim of the present study was to evaluate the antimicrobial activity of ethanolic extract of Quercus infectoria gall as well as its active constituent, gallic acid, against some vaginal pathogens. In this study, the ethanolic extract of Quercus infectoria gall was obtained by maceration and standardized based on amount of gallic acid. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of this extract as well as its active compound, gallic acid, were determined against Candida spp., Gardnerella vaginalis, Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, Trichomonas vaginalis and Lactobacillus acidophilus. The results demonstrated remarkable activity of ethanolic extract of Quercus infectoria gall against investigated pathogens with MIC and MBC in the range between 0.125 mg/ml and 16 mg/ml. The most inhibitory and bactericidal activity was observed on Streptococcus agalactiae and Staphylococcus aureus. The effects of gall dried ethanolic extract on Trichomonas vaginalis showed 100 % inhibition of the parasitic growth with concentration of 800 µg/ml after 24 h incubation. The antimicrobial and anti-trichomonas activity of extract was more than gallic acid. It seems that ethanolic extract of Quercus infectoria gall could inhibit the growth of vaginal pathogens. Further preclinical and clinical studies are required to confirm the efficacy of this natural extract in vaginitis.
... The clinical presentation of trichomoniasis in women may vary from asymptomatic to severe vaginitis, while the infection is mainly asymptomatic in men. Trichomoniasis is associated with a number of pregnancy and postpartum complications, such as preterm birth, premature membrane rupture and low birth-weight (Petrin et al., 1998;Fichorova, 2009;Edwards et al., 2014;Hirt and Sherrard, 2015). Furthermore, T. vaginalis infection has been associated with an increased risk of invasive cervical cancer (Yap et al., 1995), prostate cancer and of human immunodeficiency virus (HIV) acquisition and shedding (McClelland et al., 2007). ...
Trichomonas vaginalis is an anaerobic protist, responsible for the most prevalent non-viral sexually transmitted infection in humans. One of the most intriguing aspects of T. vaginalis pathobiology is the complex relationship with intracellular microbial symbionts: a group of dsRNA viruses belonging to family of Totiviridae ( T. vaginalis virus), and eubacteria belonging to the Mycoplasma genus, in particular Mycoplasma hominis . Both microorganisms seem to strongly influence the lifestyle of T. vaginalis , suggesting a role of the symbiosis in the high variability of clinical presentation and sequelae during trichomoniasis. In the last few years many aspects of this unique symbiotic relationship have been investigated: M. hominis resides and replicates in the protozoan cell, and T. vaginalis is able to pass the bacterial infection to both mycoplasma-free protozoan isolates and human epithelial cells; M. hominis synergistically upregulates the proinflammatory response of human monocytes to T. vaginalis . Furthermore, the influence of M. hominis over T. vaginalis metabolism and physiology has been characterized. The identification of a novel species belonging to the class of Mollicutes (Candidatus Mycoplasma girerdii ) exclusively associated to T. vaginalis opens new perspectives in the research of the complex series of events taking place in the multifaceted world of the vaginal microbiota, both under normal and pathological conditions.
Neutrophils are the most abundant polymorphonuclear granular leukocytes in human blood and are an essential part of the innate immune system. Neutrophils are efficient cells that eliminate pathogenic bacteria and fungi, but their role in dealing with protozoan parasitic infections remains controversial. At sites of protozoan parasite infections, a large number of infiltrating neutrophils is observed, suggesting that neutrophils are important cells for controlling the infection. Yet, in most cases, there is also a strong inflammatory response that can provoke tissue damage. Diseases like malaria, trichomoniasis, leishmaniasis, Chagas disease, and amoebiasis affect millions of people globally. In this review, we summarize these protozoan diseases and describe the novel view on how neutrophils are involved in protection from these parasites. Also, we present recent evidence that neutrophils play a double role in these infections participating both in control of the parasite and in the pathogenesis of the disease.
This chapter defines the characteristics of protozoan parasites including important species of the flagellates, amoebae, trypanosomes, Leishmania species and Coccidia (including species of the genera Isospora, Cyclospora, Cryptosporidium, Sarcocystis, Toxoplasma, Plasmodium, Babesia, Balantidium, Pneumocystis, Blastocystis, Enterocytozoon, Septata, Encephalitozoon and Nosema). Each species description contains the single topics: name, geographic distribution, biology/morphology, symptoms of disease, diagnosis, pathway of infection, prophylaxis, incubation period, prepatent period, patency, chemotherapy and further reading.
Background:
Sexually Transmitted Infections (STIs) can be caused by viruses, bacteria, and parasites. The World Health Organization estimated more than 300 million new global cases of curable STIs among individuals of reproductive age. Infection by Trichomonas vaginalis is one of the most prevalent curable STI. Despite the current treatments available, the diagnosis of T. vaginalis can be difficult, and the resistance to the treatment increased concern for the healthcare system.
Objectives:
The aim of this study was to determine the prevalence and factors associated with Trichomonas vaginalis infection among women of reproductive age attending community-based services for cervical screening.
Patients and methods:
A total of 1477 reproductive-aged women attending 18 Primary Health Care Units in Botucatu, Brazil, from September to October 2012, were enrolled. A structured questionnaire was used for individual face-to-face interviews for obtaining data on sociodemographic, gynecologic, and obstetrics history, sexual and hygiene practices, among others. Cervicovaginal samples were obtained for detection of T. vaginalis by culture using Diamond's medium and microscopic vaginal microbiota classification according to Nugent. A multivariable logistic regression analysis was carried out to estimate Odds Ratios (OR) and 95% Confidence Intervals (95% CI) for the association between participants' sociodemographic, behavioral factors, and clinical factors with T. vaginalis infection.
Results:
Median age of study participants was 33 years (ranging from 18 to 50). The overall prevalence of T. vaginalis infection was 1.3% (n = 20). Several factors were independently associated with T. vaginalis infection, such as self-reporting as black or Pardo for ethnicity (OR = 2.70; 95% CI 1.03‒7.08), smoking (OR=3.18; 95% CI 1.23‒8.24) and having bacterial vaginosis (OR = 4.01; 95%CI = 1.55-10.38) upon enrollment. A protective effect of higher educational level (having high school degree) was observed (OR = 0.16; 95% CI 0.05‒0.53).
Conclusions:
Our data suggest that screening programs to correctly detect T. vaginalis infection can be helpful to guide prevention strategies to the community. Our study supports an association between abnormal vaginal microbiota and T. vaginalis infection.
Background: Abnormal vaginal discharge in a pregnant woman increases risk of complications such as abortion, premature rupture of fetal membranes, low birth weight and transmission of HIV to the fetus. Objective: To determine the microbial isolates and antimicrobial sensitivity pattern of abnormal vaginal discharge in pregnant women in Nuhu Bamali maternity hospital Kano. Methods: This was a cross-sectional descriptive study where semi structured interviewer administered questionnaires were employed to a sample of 200 respondents using a simple random sampling technique. High vaginal swab samples were collected from pregnant women with abnormal vaginal discharge at the antenatal clinic. Result: Prevalence of abnormal vaginal discharge among pregnant women in this study was 5.25%. Young maternal age, low parity, lack of western education and unemployment were found to be associated with risk of abnormal vaginal discharge (p˂0.001). The prevalence of positive culture was 83.5% in women with abnormal vaginal discharge; C. albicans (33%), E. coli (23%), S. aureus (17.5%), Klebseilla sp. (7.5%), and Streptococcus sp. (2.5%). Eighty-three percent of microorganism were sensitive to Augmentin, 79% to erythromycin, 62% to Ofloxacin and 41% to gentamicin. Most of the organisms were resistant to amoxicillin and ampicillin. Conclusion: The prevalence of abnormal vaginal discharge in pregnancy is 5.25% with C. albicans and E. coli being the commonest causes. Most of the organisms are sensitive to Augmentin and Erythromycin. Both antibiotics are safe in pregnancy.
Vulvovaginitis occurs in mostly reproductive aged women. Recurrent vaginitis affects overall quality of life, with a large financial burden on the patient, family, and health system. This review discusses a clinician's approach to vulvovaginitis with specific attention to the 2021 updated Center for Disease Control and Prevention guidelines. The authors discuss the role of the microbiome in vaginitis and evidence-based approaches for diagnosis and treatment of vaginitis. This review also provides updates on new considerations, diagnosis, management, and treatment of vaginitis. Desquamative inflammatory vaginitis and genitourinary syndrome of menopause are discussed as differential diagnosis of vaginitis symptoms.
Trichomoniasis is the most common nonviral sexually transmitted infection, affecting an estimated 275 million people worldwide. The causative agent is the parasitic protozoan Trichomonas vaginalis. Although the disease itself is typically mild, individuals with trichomonal infections have a higher susceptibility to more serious conditions. The emergence of parasite strains resistant to current therapies necessitates the need for novel treatment strategies. Since T. vaginalis is an obligate parasite that requires nucleoside salvage pathways, essential nucleoside ribohydrolase enzymes are promising new drug targets. Fragment screening and X-ray crystallography have enabled structure-guided design of inhibitors for two of these enyzmes. Linkage of enzymatic and antiprotozoal activity would be a transformative step toward designing novel, mechanism-based therapeutic agents. While a correlation with inhibition of purified enzyme would be mechanistically suggestive, a correlation with inhibition of in-cell enzyme activity would definitively establish this linkage. To demonstrate this linkage, we have translated our NMR-based activity assays that measure the activity of purified enzymes for use in T. vaginalis cells. The 19F NMR-based activity assay for the pyrimidine-specific enzyme translated directly to in-cell assays. However, the 1H NMR-based activity assay for the purine-specific enzyme required a switch from adenosine to guanosine substrate and the use of 13C-editing to resolve the substrate 1H signals from cell and growth media background signals. The in-cell NMR assays are robust and have been demonstrated to provide inhibition data on test compounds. The results described here represent the first direct measurement of enzyme activity in protozoan parasite cells.
The eukaryotic phylum Parabasalia is composed primarily of anaerobic, endobiotic organisms such as the veterinary parasite Tritrichomonas foetus and the human parasite Trichomonas vaginalis, the latter causing the most prevalent, non-viral, sexually transmitted disease world-wide. Although a parasitic lifestyle is generally associated with a reduction in cell biology, T. vaginalis provides a striking counter-example. The 2007 T. vaginalis genome paper reported a massive and selective expansion of encoded proteins involved in vesicle trafficking, particularly those implicated in the late secretory and endocytic systems. Chief amongst these were the hetero-tetrameric adaptor proteins or 'adaptins', with T. vaginalis encoding ∼3.5 times more such proteins than do humans. The provenance of such a complement, and how it relates to the transition from a free-living or endobiotic state to parasitism, remains unclear. In this study, we performed a comprehensive bioinformatic and molecular evolutionary investigation of the heterotetrameric cargo adaptor-derived coats, comparing the molecular complement and evolution of these proteins between T. vaginalis, T. foetus and the available diversity of endobiotic parabasalids. Notably, with the recent discovery of Anaeramoeba spp. as the free-living sister lineage to all parabasalids, we were able to delve back to time points earlier in the lineage's history than ever before. We found that, although T. vaginalis still encodes the most HTAC subunits amongst parabasalids, the duplications giving rise to the complement took place more deeply and at various stages across the lineage. While some duplications appear to have convergently shaped the parasitic lineages, the largest jump is in the transition from free-living to endobiotic lifestyle with both gains and losses shaping the encoded complement. This work details the evolution of a cellular system across an important lineage of parasites and provides insight into the evolutionary dynamics of an example of expansion of protein machinery, counter to the more common trends observed in many parasitic systems.
Trichomonas vaginalis is the causative parasitic protozoan of the disease trichomoniasis, the most prevalent, nonviral sexually transmitted disease in the world. T. vaginalis is a parasite that scavenges nucleosides from the host organism via catalysis by nucleoside hydrolase (NH) enzymes to yield purine and pyrimidine bases. One of the four NH enzymes identified within the genome of T. vaginalis displays unique specificity toward purine nucleosides, adenosine and guanosine, but not inosine, and atypically shares greater sequence similarity to the pyrimidine hydrolases. Bioinformatic analysis of this enzyme, adenosine/guanosine-preferring nucleoside ribohydrolase (AGNH), was incapable of identifying the residues responsible for this uncommon specificity, highlighting the need for structural information. Here, we report the X-ray crystal structures of holo, unliganded AGNH and three additional structures of the enzyme bound to fragment and small-molecule inhibitors. Taken together, these structures facilitated the identification of residue Asp231, which engages in substrate interactions in the absence of those residues that typically support the canonical purine-specific tryptophan-stacking specificity motif. An altered substrate-binding pose is mirrored by repositioning within the protein scaffold of the His80 general acid/base catalyst. The newly defined structure-determined sequence markers allowed the assignment of additional NH orthologs, which are proposed to exhibit the same specificity for adenosine and guanosine alone and further delineate specificity classes for these enzymes.
The development of new drugs is continuous in the world; currently, saving resources
(both economic ones and time) and preventing secondary effects have become
a necessity for drug developers. Trichomoniasis is the most common nonviral
sexually transmitted infection affecting more than 270 million people around the
world. In our research group, we focussed on developing a selective and more
effective drug against Trichomonas vaginalis, and we previously reported on a
compound, called A4, which had a trichomonacidal effect. Later, we determined
another compound, called D4, which also had a trichomonacidal effect together with
favorable toxicity results. Both A4 and D4 are directed at the enzyme triosephosphate
isomerase. Thus, we made combinations between the two compounds, in
which we determined a synergistic effect against T. vaginalis, determining the IC50
and the toxicity of the best relationship to obtain the trichomonacidal effect. With
these results, we can propose a combination of compounds that represents a promising
alternative for the development of a new therapeutic strategy against
trichomoniasis.
Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3'-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures.
With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.
Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.
The high prevalence and serious long-term sequelae of Trichomonas vaginalis (TV) infection worldwide is of a particular concern; however, data regarding the differences in the composition of the vaginal microbiome in cases of single TV infection or mixed infections (i.e., presence of TV and bacterial vaginosis) are scarce. We employed metagenomic sequencing analyses to study gene expression in the vaginal microbiota of women with single TV infection and mixed infection. Women infected with only TV had significantly higher abundance of Mycoplasma, Prevotella, and Streptococcus compared to women without vaginal infection (control). Women infected with mixed infections had a significantly higher abundance of Mycoplasma, Prevotella, Streptococcus, Anaerococcus, Dialister, Peptostreptococcus, Peptoniphilus and a significantly lower abundance of Lactobacillus than TV alone. Mixed infections had a significantly higher abundance of Prevotella, Anaerococcus and Dialister. Our findings suggest that the bacterial community composition varies among healthy women, women with TV alone, and those with mixed infection, and we hypothesize that these bacterial vaginosis (BV)-associated bacterium may play a role in the pathogenesis and recurrence of TV. Probiotic pessaries may necessarily be the answer because shifting the vaginal microbiome and host responses is probably a complex undertaking.
Trichomoniasis, caused by the protozoan
Trichomonas vaginalis
Trichomonas is a genus of amitochondriate flagellated protozoans, that possess four anterior flagella and an undulating membrane. Trichomonas vaginalis is the causative agent of the most common non-viral sexually transmitted disease, trichomoniasis. Establishment and maintenance of infection are mediated through several mechanisms including morphogenesis and cytoadherence, cytotoxicity, phagocytosis, endocytosis and immune evasion strategies. Moreover, the parasite settles symbiotic relationships with different microorganisms. Untreated or persistent infection can be associated with adverse health outcomes in both women and men. Trichomonas tenax, a protozoon inhabiting the oral cavity, has been linked to the occurrence and/or the severity of periodontitis.
„Sexually transmitted infections“ (STI) sind überwiegend oder ausschließlich sexuell übertragene Krankheiten. Die Genitoanalregion bietet diversen Erregern besondere Lebensräume. Wichtige Pathogenitätsfaktoren sind Feuchtigkeit, Wärme und Okklusion. Beim Geschlechtsverkehr können selbst empfindliche, gewebeständige Keime wie T. pallidum übertragen werden. Harnröhre und Analkanal beider Geschlechter sowie Vagina, Uterus und Eileiter der Frau ermöglichen eine direkte Erregerausbreitung. Gonokokken und Chlamydien können über aufsteigende Infektionen zu regionalen und systemischen Komplikationen (z. B. disseminierten Gonokokkeninfektionen) führen. Extragenitale STI können sich durch direkte Infektion empfindlicher Schleimhäute in der Mundhöhle, aber auch an den Augen manifestieren. Da v. a. die pharyngealen Infektionen häufig asymptomatisch sind, bleiben sie oft lange unentdeckt und sind dadurch epidemiologisch relevante Infektionsquellen. Auch die sexuell übertragbaren Allgemeininfektionen Syphilis, HIV-Erkrankung und Hepatitis A–C gehen meist von der Genitoanalregion aus. Neben der somatischen Seite besitzen sie wichtige psychosoziale Komponenten („Tabuzone“, Partnerkonflikte, soziale Verurteilung).
Incidental detection of Trichomonas vaginalis from asymptomatic patients is common in Pap smear. However, some clinicians are not emphasizing the finding of this protozoa infection based on Pap smear due to the reported low negative predictive value and high false-positive result. If these patients were left untreated, chronic infection eventually may lead to more severe complications and they may also act as a reservoir for transmission to their sexual partners. In this retrospective study, conventional Pap smears were reexamined for the presence of Trichomonas vaginalis microscopically in order to evaluate the effectiveness of Papanicolaou stained smears in term of sensitivity, specificity, positive and negative predictive values and interobservers reproducibility. Eighty two Papanicolaou stained conventional Pap smears from asymptomatic patients were reexamined and interpreted for the presence or absence of Trichomonas vaginalis by two screeners. The results were compared with the wet mount reports. The sensitivity of the Papanicolaou stained smears for the two screeners to detect Trichomonas vaginalis is range from 88% to 93%. Both screeners had achieved 83% of specificity. The kappa value showed that there was substantial agreement between the two screeners in term of interobservers reproducibility. Papanicolaou stained smears has clinical significance as a screening tool for the detection of asymptomatic genital trichomoniasis in this study population.
Trichomonas is a significant protist genus, and includes T. vaginalis, the most prevalent sexually transmitted non-viral infection of humans, and T. gallinae of rock doves (Columba livia), one of the earliest known avian pathogens. New Trichomonas genotypes, including T. vaginalis-like isolates, have been discovered in American columbid hosts, suggesting geographically widespread cryptic diversity of Trichomonas in pigeons and doves. We sampled 319 birds from 22 columbid species in Australia, Papua New Guinea, New Zealand and southern Africa and uncovered 15 novel lineages of Trichomonas, more than doubling the known diversity of this parasite genus and providing evidence for frequent host-switching that eventually gave rise to T. vaginalis in humans. We show that Trichomonas has a columbid origin and likely underwent Miocene expansion out of Australasia. Our chronological topology for Trichomonas is calibrated on the evolution of a host phenotypic trait associated with ecological entrapment of the most basal extant lineage of Trichomonas in Ptilinopus fruit-doves.
Vaginal infections are one of the most common reasons a woman visits a gynecologist. The increased resistance to conventional antibiotics is one of the main reasons for searching and developing new antimicrobial agents, especially those of natural origin. In traditional Persian medicine, the gall of Quercus infectoria has been claimed to eliminate vagina and cervix from excessive discharge. So, the aim of the present study was to evaluate the antimicrobial activity of ethanolic extract of Quercus infectoria gall as well as its active constituent, gallic acid, against some vaginal pathogens. In this study, the ethanolic extract of Quercus infectoria gall was obtained by maceration and standardized based on amount of gallic acid. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of this extract as well as its active compound, gallic acid, were determined against Candida spp., Gardnerella vaginalis, Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, Trichomonas vaginalis and Lactobacillus acidophilus. The results demonstrated remarkable activity of ethanolic extract of Quercus infectoria gall against investigated pathogens with MIC and MBC in the range between 0.125 mg/ml and 16 mg/ml. The most inhibitory and bactericidal activity was observed on Streptococcus agalactiae and Staphylococcus aureus. The effects of gall dried ethanolic extract on Trichomonas vaginalis showed 100 % inhibition of the parasitic growth with concentration of 800 µg/ml after 24 h incubation. The antimicrobial and anti-trichomonas activity of extract was more than gallic acidIt seems that ethanolic extract of Quercus infectoria gall could inhibit the growth of vaginal pathogens. Further preclinical and clinical studies are required to confirm the efficacy of this natural extract in vaginitis.
Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis, and is the most prevalent, non-viral sexually transmitted disease. The parasite has shown increasing resistance to the current 5-nitroimidazole therapies indicating the need for new therapies with different mechanisms. T. vaginalis is an obligate parasite that scavenges nucleosides from host cells and then uses salvage pathway enzymes to obtain the nucleobases. The adenosine/guanosine preferring nucleoside ribohydrolase was screened against a 2,000-compound diversity fragment library using a ¹H NMR-based activity assay. Three classes of inhibitors with more than five representatives were identified: bis-aryl phenols, amino bicyclic pyrimidines, and aryl acetamides. Among the active fragments were 10 compounds with ligand efficiency values greater than 0.5, including five with IC50 values < 10 μM. Jump-dilution and detergent counter screens validated reversible, target-specific activity. The data reveals an emerging SAR that is guiding our medicinal chemistry efforts aimed at discovering compounds with nM potency.
Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as "Mnola." In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from four discrete mid-vaginal samples, one of which was obtained from a pregnant woman with trichomoniasis who delivered prematurely. These bacteria harbor several putative virulence factors and display unique metabolic strategies. Genes encoding proteins with high similarity to potential virulence factors include two collagenases, a hemolysin, an O-sialoglycoprotein endopeptidase and a feoB-type ferrous iron transport system. We propose the name "Candidatus Mycoplasma girerdii" for this potential new pathogen.
Trichomonads are common parasites of many vertebrate and invertebrate species, with four species classically recognized as human parasites: Dientamoeba fragilis, Pentatrichomonas hominis, Trichomonas vaginalis, and Trichomonas tenax. The latter two species are considered human-specific; by contrast, D. fragilis and P. hominis have been isolated from domestic and farm mammals, demonstrating a wide host range and potential zoonotic origin. Several new studies have highlighted the zoonotic dimension of trichomonads. First, species typically known to infect birds and domestic mammals have been identified in human clinical samples. Second, several phylogenetic analyses have identified animal-derived trichomonads as close sister taxa of the two human-specific species. It is our opinion, therefore, that these observations prompt further investigation into the importance of zoonotic trichomonads for human health.
Significance
Prostate cancer is the most common nonskin cancer in America and the fifth most common cancer worldwide. Inflammation is implicated in the initiation and progression of prostate cancer; however, sources of inflammation remain unidentified. Trichomonas vaginalis is a prevalent parasite that infects prostate epithelium and is associated with an increase in aggressive prostate cancer. Here, we demonstrate that a secreted T. vaginalis protein homologous to human macrophage migration inhibitory factor elicits antibodies in infected individuals, increases prostate cell proliferation and invasiveness, and induces cellular pathways linked to inflammation. This study demonstrates that a specific parasite-derived protein can mimic its human homolog to increase inflammation and cell proliferation, which, in turn, may result in the promotion and progression of prostate cancer.
Trichomonas vaginalis is the most prevalent non-viral sexually transmitted parasite. Although the protist is presumed to reproduce asexually, 60% of its haploid genome contains transposable elements (TEs), known contributors to genome variability. The availability of a draft genome sequence and our collection of >200 global isolates of T. vaginalis facilitate the study and analysis of TE population dynamics and their contribution to genomic variability in this protist.
We present here a pilot study of a subset of class II Tc1/mariner TEs that belong to the T. vaginalis Tvmar1 family. We report the genetic structure of 19 Tvmar1 loci, their ability to encode a full-length transposase protein, and their insertion frequencies in 94 global isolates from seven regions of the world. While most of the Tvmar1 elements studied exhibited low insertion frequencies, two of the 19 loci (locus 1 and locus 9) show high insertion frequencies of 1.00 and 0.96, respectively. The genetic structuring of the global populations identified by principal component analysis (PCA) of the Tvmar1 loci is in general agreement with published data based on genotyping, showing that Tvmar1 polymorphisms are a robust indicator of T. vaginalis genetic history. Analysis of expression of 22 genes flanking 13 Tvmar1 loci indicated significantly altered expression of six of the genes next to five Tvmar1 insertions, suggesting that the insertions have functional implications for T. vaginalis gene expression.
Our study is the first in T. vaginalis to describe Tvmar1 population dynamics and its contribution to genetic variability of the parasite. We show that a majority of our studied Tvmar1 insertion loci exist at very low frequencies in the global population, and insertions are variable between geographical isolates. In addition, we observe that low frequency insertion is related to reduced or abolished expression of flanking genes. While low insertion frequencies might be expected, we identified two Tvmar1 insertion loci that are fixed across global populations. This observation indicates that Tvmar1 insertion may have differing impacts and fitness costs in the host genome and may play varying roles in the adaptive evolution of T. vaginalis.
Trichomonas vaginalis is known as the most common cause of sexually transmitted infection. However, its prevalence may have been underestimated. Trichomonads are detected in prostatic tissue in benign prostatic hyperplasia, prostatitis, and prostate cancer. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate epithelium.
The cytokine production by human prostate epithelial cell (RWPE-1) activated with T. vaginalis was determined by ELISA and real-time PCR. Intracellular ROS was evaluated by flow cytometry or spectrofluorometry. The protein levels of MAP kinase, NF-κB were analyzed by Western blot. The migration of neutrophil and monocyte were performed in 24-well microplates with filter insert.
Incubation of cells of a human prostate epithelial cell line with a live T. vaginalis T016 isolate increased expression of the inflammatory mediators IL-1β, CCL2, and CXCL8. In addition, ROS, MAPK, and NF-κB activities increased, while inhibitors of ROS, ERK, and NF-κB reduced IL-1β production. Medium conditioned by incubation of RWPE-1 cells with T. vaginalis contained IL-1β and stimulated the migration of human neutrophils and monocytes (THP-1 cell line).
We conclude that T. vaginalis may increase IL-1β expression in human prostate epithelium through activation of ROS, ERK, and NF-κB, and this in turn may induce the migration of neutrophils and monocytes and lead to an inflammatory response. This research is the first attempt to confirm inflammatory reaction caused by T. vaginalis in prostate epithelial cell. Prostate © 2013 Wiley Periodicals, Inc.
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.
We report an unusual case of extragenital infection with Trichomonas vaginalis of the conjunctiva of a 32-year-old man. Only one other similar case has been reported in the English language literature.
The present report reinforces the widening pathologic spectrum of trichomonads in humans, especially in the context of emerging
extragenital infections.
Objectives:
Trichomoniasis is a common sexually transmitted disease, and adhesion of the pathogen Trichomonas vaginalis to the host vaginal cells is the first step in establishing infection. For this to happen, the pathogen has to overcome a natural protective barrier composed mostly of lactobacilli. The objective of this study was to understand the role of lactobacilli in the adhesion of T vaginalis to host cells.
Methods:
Adhesion assays were carried out by incubating vaginal epithelial cells (VECs) with T vaginalis and lactobacilli together and compared with non-lactobacilli recipient controls. By varying incubation parameters and testing several microbial isolates, the number of pathogens that adhered to the VECs was determined by flow cytometry.
Results:
Overall, but with few exceptions, lactobacilli caused inhibition of T vaginalis adhesion to a variable degree. Lactobacillus gasseri ATCC 9857 and CBI3 (ambiguous Lactobacillus plantarum or Lactobacillus pentosus) caused the highest level of parasite adhesion inhibition and enhancement, respectively. These isolates of Lactobacillus can profoundly alter the adhesive properties of low-adherent and high-adherent strains of T vaginalis in a dose-dependent manner. Additionally, the effects of lactobacilli on T vaginalis adhesion are strictly contact-dependent, and surface lipoglycans of T vaginalis are most likely not involved in this modulation of adhesion mediated by the bacteria.
Conclusions:
Lactobacilli can modulate adhesion of T vaginalis by significantly modifying the natural adhesive properties of various T vaginalis strains. This study highlights the importance of considering the role of the vaginal microbiota in the pathogenesis of trichomoniasis.
The elusive nature of Trichomonas vaginalis, the most common, non-viral, sexually transmitted pathogen has hampered our knowledge of its significance for human health for over 150 years. The combination of epidemiology, molecular cell biology, immunology and more recently genomics and other allied omics data, are all contributing at shedding new light onto what is increasingly recognised as a significant human pathogen leading to important health sequelae due to multifaceted interactions with its human host, the human microbiota, bacterial pathogens and viruses. The integrations of these various data are contributing in important ways to refining our understanding of the parasite pathobiology and virulent factors. Indeed, it is increasingly recognised that to rationalise the development of effective prophylactic and therapeutic treatments for human pathogens it is important to integrate the broadest possible spectrum of human-microbial-parasite-virus interactions in relation to qualitative and quantitative variations in the human innate and adaptive defence responses. This short review aims at providing an integrative overview of T vaginalis virulent factors by taking into account the importance of the human-microbiota-parasite-virus interplay in human health. It also highlights selected cellular characteristics of the parasite often overlooked in the biological and medical literature.
Objectives:
Trichomonas vaginalis is the causative agent of trichomoniasis, one of the most common sexually transmitted diseases worldwide. In recent years we have described the symbiotic relationship between T vaginalis and Mycoplasma hominis. How this biological association might affect the pathogenicity of one or both the microorganisms is still unknown. Since local inflammation is thought to play a central role in T vaginalis infection, we investigated the in vitro response of human macrophages to naturally mycoplasma-free T vaginalis, as compared to a mycoplasma-infected trichomonad isolate.
Methods:
THP-1 cells were stimulated with two isogenic T vaginalis isolates, one naturally mycoplasma-free and one stably associated with M hominis, and secreted cytokines measured by ELISA. Nuclear factor κB (NFκB) involvement in THP-1 response to T vaginalis and M hominis was evaluated by means of a reporter system based on detection of alkaline phosphatase activity.
Results:
We found that the presence of M hominis upregulates the expression of a panel of proinflammatory cytokines in a synergistic fashion. We also found that the upregulation of the proinflammatory response by THP-1 cells involves the transcription factor NFκB.
Conclusions:
These findings suggest that the presence of M hominis in T vaginalis isolates might play a key role in inflammation during trichomoniasis, thus affecting the severity of the disease. The synergistic upregulation of the macrophage proinflammatory response might also affect some important clinical conditions associated with T vaginalis infection, such as the increased risk of acquiring cervical cancer or HIV, which are thought to be affected by the inflammatory milieu during trichomoniasis.
Trichomonas vaginalis is a parasite of the urogenital tract in men and women, with a worldwide presence and significant implications for global public health. T. vaginalis research entered the age of genomics with the publication of the first genome sequence in 2007, but subsequent utilization of other 'omics' technologies and methods has been slow. Here, we review some of the tools and approaches available to interrogate T. vaginalis biology, with an emphasis on recent advances and current limitations, and draw attention to areas where further efforts are needed to examine effectively the complex and intriguing biology of the parasite.
Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted to the human genitourinary tract, infects globally ∼250 million each year rendering them more susceptible to devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer. While first-line antibiotic treatment (metronidazole) commonly kills the protozoan pathogen, it fails to improve reproductive outcome. We show that endosymbiotic Trichomonasvirus, highly prevalent in T. vaginalis clinical isolates, is sensed by the human epithelial cells via Toll-like receptor 3, triggering Interferon Regulating Factor -3, interferon type I and proinflammatory cascades previously implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatment amplified these proinflammatory responses. Thus, a new paradigm targeting the protozoan viruses along with the protozoan host may prevent trichomoniasis-attributable inflammatory sequelae.
Nitroimidazoles (metronidazole and tinidazole) are the only recommended drugs for treating Trichomonas vaginalis infection, and previous samples that assessed resistance of such isolates have been limited in geographic scope. We assessed the prevalence of in vitro aerobic metronidazole and tinidazole resistance among T. vaginalis isolates from multiple geographic sites in the United States. Swab specimens were obtained from women who underwent routine pelvic examinations at sexually transmitted disease clinics in 6 US cities. Cultured T. vaginalis isolates were tested for nitroimidazole resistance (aerobic minimum lethal concentration [MLC] >50 µg/mL). Of 538 T. vaginalis isolates, 23 (4.3%) exhibited low-level in vitro metronidazole resistance (minimum lethal concentrations 50-100 µg/mL). No isolates exhibited moderate- to high-level metronidazole resistance or tinidazole resistance. Results highlight the possibility that reliance on a single class of antimicrobial drugs for treating T. vaginalis infections may heighten vulnerability to emergence of resistance. Thus, novel treatment options are needed.
The draft genome of the common sexually transmitted pathogen Trichomonas vaginalis encodes one of the largest known proteome with 60,000 candidate proteins. This provides parasitologists and molecular cell biologists alike with exciting, yet challenging, opportunities to unravel the molecular features of the parasite's cellular systems and potentially the molecular basis of its pathobiology. Here, recent investigations addressing selected aspects of the parasite's molecular cell biology are discussed, including surface and secreted virulent factors, membrane trafficking, cell signalling, the degradome, and the potential role of RNA interference in the regulation of gene expression.
Trichomoniasis is a common sexually transmitted disease associated with preterm birth, low birth weight, and increased susceptibility
to infection with other pathogenic sexually transmitted microorganisms. Nucleic acid amplification tests for Trichomonas vaginalis have improved sensitivity for detecting infected individuals compared to existing culture-based methods. This prospective,
multicenter U.S. clinical trial evaluated the performance of the automated Aptima T. vaginalis assay for detecting T. vaginalis in 1,025 asymptomatic and symptomatic women. Vaginal swab, endocervical swab, ThinPrep PreservCyt, and urine specimens were
collected. Subject infection status was determined by wet-mount microscopy and culture. Aptima T. vaginalis assay performance was determined for each specimen type by comparison to subject infection status. Of 933 subjects analyzed,
59.9% were symptomatic. Aptima T. vaginalis clinical sensitivity and specificity were, respectively, 100% and 99.0% for vaginal swabs, 100% and 99.4% for endocervical
swabs, 100% and 99.6% in ThinPrep samples, and 95.2% and 98.9% in urine specimens. Aptima T. vaginalis performance levels were similar in asymptomatic and symptomatic subjects. This study validates the clinical performance of
the Aptima T. vaginalis assay for screening asymptomatic and symptomatic women for T. vaginalis infection.
Since the early 1950s when sexually transmitted infections (STIs) were first proposed as a possible risk factor for prostate cancer, numerous epidemiologic studies have been conducted. Initially, these studies were primarily small case-control studies with retrospective, self-reported assessments of a narrow range of STIs, typically either any STIs, or gonorrhea and syphilis. However, as new STIs have been discovered/recognized, new and better tests to detect histories of STIs have been developed, and new resources for prostate cancer research have been created, epidemiologic studies have expanded to include a wide range of STIs, and have moved towards more rigorous, prospective study designs and serological assessment of STI histories. The results of these studies are reviewed and discussed, as well as possible new avenues of research, such as Trichomonas vaginalis infection and infections not typically considered to be sexually transmitted.
The identification of surface proteins on the plasma membrane of pathogens is of fundamental importance in understanding host-pathogen interactions. Surface proteins of the extracellular parasite Trichomonas are implicated in the initial adherence to mucosal tissue and are likely to play a critical role in the long term survival of this pathogen in the urogenital tract. In this study, we used cell surface biotinylation and multidimensional protein identification technology to identify the surface proteome of six strains of Trichomonas vaginalis with differing adherence capacities to vaginal epithelial cells. A combined total of 411 proteins were identified, and of these, 11 were found to be more abundant in adherent strains relative to less adherent parasites. The mRNA levels of five differentially expressed proteins selected for quantitative RT-PCR analysis mirrored their observed protein levels, confirming their up-regulation in highly adherent strains. As proof of principle and to investigate a possible role in pathogenesis for differentially expressed proteins, gain of function experiments were performed using two novel proteins that were among the most highly expressed surface proteins in adherent strains. Overexpression of either of these proteins, TVAG_244130 or TVAG_166850, in a relatively non-adherent strain increased attachment of transfected parasites to vaginal epithelial cells approximately 2.2-fold. These data support a role in adhesion for these abundant surface proteins. Our analyses demonstrate that comprehensive profiling of the cell surface proteome of different parasite strains is an effective approach to identify potential new adhesion factors as well as other surface molecules that may participate in establishing and maintaining infection by this extracellular pathogen.
Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins.
Data mining of the T. vaginalis genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from Clostridium difficile pathogenic strains and C. difficile phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male T. vaginalis infected patients were also demonstrated.
The biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology at the host-pathogen interface.
Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery.
We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation.
Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9).
Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.
The in vitro activities of tinidazole and metronidazole against Trichomonas vaginalis isolates clinically resistant to metronidazole were compared. Minimal lethal concentrations (MLCs) of tinidazole were significantly
lower than MLCs of metronidazole. Increased metronidazole resistance correlated with increased tinidazole resistance. These
data support a role for tinidazole in the treatment of trichomoniasis.
The genome of Trichomonas vaginalis, the first from a parabasalid to be sequenced, was published in 2007, the culmination of a project marked by several surprises and not a little distress. The ~160 Mb genome was found to be significantly larger than first described, presenting new challenges to the standard genome sequencing pipeline, as well as to continued funding. Here we present an overview of the project, including both a historical synopsis of how the project was conceived and carried out, as well as a summary of the fascinating biology revealed by analysis of the genome. To illustrate the utility of the complete genome sequence, specific areas of the parasite's biology - including membrane trafficking and mode of reproduction - are expanded and brought up-to-date.
Social and medical aspects remain associated in the social context of human Chagas disease (HCD). Poverty, huts, economic instability, a lack of favorable production relations, and the usual absence of political and social priorities by the Latin American governments are some of the general historical factors influencing the expansion and control of the disease. In spite of evidence of its existence among very ancient indigenous settlements in South America, for example, by the detection of Trypanosoma cruzi DNA in Chilean and Peruvian mummies aged up to eight centuries before Christ, dispersion of Chagas disease occurred mainly after the time of Columbus. Its epidemiological apex occurred during the twentieth century as a result of extremely deep social and economic changes throughout the whole region. The appearance of the disease as endemic depended basically on the economic and social scenery of Latin American colonization involving complex and different anthropic factors, such as migration, inequity in the productive/extractive process, and very unstable and precarious ways of living. However, by the nineteenth century, other factors were involved, such as the complete absence of official planning for human settlement, mainly in terms of public health, public education, and environmental policy. The classical pattern of HCD has expanded throughout the poorest Latin American rural areas over many decades, particularly from the start of the twentieth century until 1990, when insecticide campaigns were launched in several endemic countries, and the classical rural urban migration process began to reverse in all regions.
Objective: To determine the prevalence and clinical manifestations of trichomoniasis among sexually active men. Design: Survey of two groups of men attending a sexually transmitted disease clinic. Subjects had a comprehensive sexual history and clinical examination plus cultures for Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. Participants: The study included 147 sexual partners of women with trichomoniasis and 300 subjects selected randomly from heterosexual men coming to the same clinic for evaluation of new problems. Main Outcome Measures: Isolation of T. vaginalis was compared with urogenital signs and symptoms
Objectives:
Some vaginal bacterial communities are thought to prevent infection by sexually transmitted organisms. Prior work demonstrated that the vaginal microbiota of reproductive-age women cluster into 5 types of bacterial communities; 4 dominated by Lactobacillus species (L. iners, L. crispatus, L. gasseri, L. jensenii) and 1 (termed community state type (CST) IV) lacking significant numbers of lactobacilli and characterized by higher proportions of Atopobium, Prevotella, Parvimonas, Sneathia, Gardnerella, Mobiluncus, and other taxa. We sought to evaluate the relationship between vaginal bacterial composition and Trichomonas vaginalis.
Methods:
Self-collected vaginal swabs were obtained cross-sectionally from 394 women equally representing 4 ethnic/racial groups. T. vaginalis screening was performed using PCR targeting the 18S rRNA and β-tubulin genes. Vaginal bacterial composition was characterized by pyrosequencing of barcoded 16S rRNA genes. A panel of 11 microsatellite markers was used to genotype T. vaginalis. The association between vaginal microbiota and T. vaginalis was evaluated by exact logistic regression.
Results:
T. vaginalis was detected in 2.8% of participants (11/394). Of the 11 T. vaginalis-positive cases, 8 (72%) were categorized as CST-IV, 2 (18%) as communities dominated by L. iners, and 1 (9%) as L. crispatus-dominated (P = 0.05). CST-IV microbiota were associated with an 8-fold increased odds of detecting T. vaginalis compared with women in the L. crispatus-dominated state (OR: 8.26, 95% CI: 1.07-372.65). Seven of the 11 T. vaginalis isolates were assigned to 2 genotypes.
Conclusion:
T. vaginalis was associated with vaginal microbiota consisting of low proportions of lactobacilli and high proportions of Mycoplasma, Parvimonas, Sneathia, and other anaerobes.
The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV).
Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7-10; intermediate = 4-6; normal = 0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition.
In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits, and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21-2.19; BV: aHR, 2.40; 95% CI, 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10-2.14; BV: aHR, 2.23; 95% CI, 1.75-2.84).
Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.
To establish an infection in the vagina, T. vaginalis must adapt to various environmental cues for survival and further replication. Nutrients competition by lactobacilli, the major normal vaginal flora, is one of the mechanisms to limit the growth of other microorganisms. Additionally, lactobacilli produce H2O2 that can reduce the genital infections caused by other pathogens. Thus, the ability to overcome the metabolic stresses, such as glucose restriction (GR), as well as the oxidative stresses, is critical for T. vaginalis to establish an infection.
To gain insights into the molecular mechanisms of adaptation to GR, We utilized next-generation RNA sequencing (RNA-seq) to quantify the gene expression changes upon GR. Autophagy, a cytoprotective response to starvation, was monitored by using autophagy-specific staining, autophagy inhibition assay, and co-localization of autophagosomes with lysosomes.
We demonstrated that GR promotes the survival of T. vaginalis. Besides, GR-cultivated cells exhibit higher H2O2 resistance. Our RNA-seq data revealed that genes involved in general energy metabolism were downregulated, whereas genes encoding glutamate metabolism-related aminotransferases were strikingly upregulated under GR. Furthermore, autophagy was first identified and characterized in T. vaginalis under GR.
These data suggest that GR induces a metabolic reprogramming, enhancing antioxidant ability and autophagy for cellular homeostasis to maintain survival.
Our work not only led to significant advances in understanding the transcriptional changes in response to GR but also provided possible strategies elicited by GR for T. vaginalis to adapt to the vaginal microenvironment.
We briefly examine the clinical significance and pathogenesis of Trichomonas vaginalis and provide a comprehensive summary of non-molecular and molecular diagnostics for the organism. Transcription-mediated amplification (TMA) identifies more cases of trichomoniasis than other detection modalities. In our high-prevalence sexually transmitted infection community, TMA has allowed us to investigate female and male trichomoniasis epidemiology. Distribution of the organism is community-wide and similar between Caucasian-majority geographical areas and African-American-majority locales. First-void urine provides an excellent means for laboratory diagnosis of T. vaginalis in both genders. While trichomoniasis affects older age demographics, urine screening in younger females demonstrates elevated T. vaginalis prevalence. These data promote widespread adoption of TMA for diagnosis of T. vaginalis and further epidemiological assessments. Since trichomoniasis is the most-prevalent non-viral etiology of sexually transmitted infection worldwide, utilization of TMA would enhance accurate treatment with oral nitroimidazole agents that have cure rates of 90-100%.
Trichomonas vaginalis is a sexually transmitted pathogen with an annual worldwide incidence of over 180 million infections, the highest of all curable and non-viral STI. In actuality this measure is a gross underestimation due to prevalence of asymptomatic cases, underdiagnosis and under-recognition by conventional diagnostic tools, and T. vaginalis as a non-reportable infection. Infection has significant implications on maternal and fetal health outcomes as well as higher probability of HIV transmission and susceptibility. Metronidazole resistance hinders the usefulness of implementing screening and treatment programs. Based on data from current vaccination studies in animal models, a human vaccine is achievable to intervene on the expanding incidence of infection.
The human pathogen Trichomonas vaginalis has the largest protozoan genome known, potentially encoding approximately 60,000 proteins. To what degree these genes are expressed is not well known and only a few key transcription factors and promoter domains have been identified. To shed light on the expression capacity of the parasite and transcriptional regulation during phase transitions, we deep sequenced the transcriptomes of the protozoan during two environmental stimuli of the early infection process: exposure to oxygen and contact with vaginal epithelial cells. Eleven 3' fragment libraries from different time points after exposure to oxygen only and in combination with human tissue were sequenced, generating more than 150 million reads which mapped onto 33,157 protein coding genes in total and a core set of more than 20,000 genes represented within all libraries. The data uncover gene family expression regulation in this parasite and give evidence for a concentrated response to the individual stimuli. Oxygen stress primarily reveals the parasite's strategies to deal with oxygen radicals. The exposure of oxygen-adapted parasites to human epithelial cells primarily induces cytoskeletal rearrangement and proliferation, reflecting the rapid morphological transition from spindle shaped flagellates to tissue-feeding and actively dividing amoeboids.
Recent advances in tests for the sexually transmitted protozoan parasite Trichomonas vaginalis have increased opportunities for diagnosis and treatment of this important sexually transmitted infection. This review summarises currently available tests, highlighting their performance characteristics, advantages and limitations. The recent development of molecular tests for the detection of T vaginalis, including rapid antigen detection and nucleic acid amplification tests, has significantly improved the quality of diagnostics for trichomoniasis, particularly in women. In light of the expanded menu of testing options now available, improved recognition and better control of trichomoniasis are in sight, which should enable the eventual reduction of adverse reproductive consequences associated with T vaginalis infection.
The aim is to describe and quantify the association between genitourinary tract infections and preterm birth.
Recent studies confirm the importance of identifying and treating both asymptomatic and symptomatic bacteriuria in pregnancy, which is reflected in current antenatal screening guidelines. These guidelines do not recommend routine screening for other asymptomatic lower genital infections (bacterial vaginosis, trichomonas and gonorrhoea) reflecting inconsistent study results, which may reflect differences in study design, size, diagnostics and the timing of screening in pregnancy. Screening for group B Streptococcus (GBS) late in pregnancy is recognized to reduce neonatal disease, but there is a striking lack of robust studies, specifically randomized controlled trials (RCTs), considering the effect of GBS screening earlier in pregnancy on adverse pregnancy outcomes.
The potential for screening and treatment of genitourinary tract infections in pregnancy to reduce preterm birth rates has been demonstrated in some RCTs. Current guidelines do not reflect these data because of inconsistencies across the body of evidence. There is a need for robust RCTs to confirm or refute earlier data, to inform the optimal timing for screening in pregnancy and to better quantify the contribution of individual infections to the burden of preterm birth.
The human pathogen Trichomonas vaginalis has the largest protozoan genome known, potentially encoding around 60,000 proteins. To what degree these genes are expressed is not well known and only a few key transcription factors and promoter domains have been identified. To shed light on the expression capacity of the parasite and transcriptional regulation during phase transitions, we deep sequenced the transcriptomes of the protozoan during two environmental stimuli of the early infection process: exposure to oxygen and contact with vaginal epithelial cells. We sequenced eleven 3’-fragment libraries from different time points after exposure to just oxygen and in combination with human tissue, generating more than 150 million reads, which mapped onto 33,157 protein coding genes in total and a core set of more than 20,000 genes represented within all libraries. The data uncover gene family expression regulation in this parasite and give evidence for a concentrated response to the individual stimuli. Oxygen stress primarily reveals the parasite’s strategies to deal with oxygen radicals. The exposure of oxygen-adapted parasites to human epithelial cells primarily induces cytoskeletal rearrangement and proliferation, reflecting the rapid morphological transition from spindle shaped flagellates to tissue-feeding and actively dividing amoeboids.
Trichomonas vaginalis is the most common curable sexually transmitted infection worldwide. T vaginalis infections in women can range from asymptomatic to acute inflammatory vaginitis. In men, this infection is typically asymptomatic but is increasingly being recognised as a cause of non-gonococcal urethritis. Diagnosis of T vaginalis has traditionally been made by direct microscopic examination of a wet mount of vaginal fluid or through the use of culture. The recent commercial availability of nucleic acid amplification tests for the detection of T vaginalis has seen these replace culture as the gold standard for diagnosis. Nitroimidazoles (ie, metronidazole and tinidazole) are the mainstay of therapy. In the case of treatment failure due to drug resistance or in the case of a severe nitroimidazole allergy, alternative intravaginal therapies exist, although their effectiveness has not been evaluated systematically. Novel systemic agents other than nitroimidazoles for the treatment of T vaginalis are needed, and efforts to promote and support antimicrobial drug development in this setting are necessary.
In premature newborn twins with respiratory disease, Trichomonas vaginalis infection was diagnosed by chance findings in respiratory samples and was confirmed by PCR of urine and vaginal samples from the boy and girl, respectively. Modern molecular detection techniques can help in the diagnosis.
Trichomonas vaginalis is the most widespread non-viral pathogen of the human urogenital tract, infecting ∼3% of the world's population annually. At the onset of infection the protist changes morphology within minutes: the flagellated free-swimming cell converts into the amoeboid-adherent stage. The molecular machinery of this process is not well studied, but is thought to involve actin reorganization. We have characterized amoeboid transition, focusing in particular on TvFIM1, the only expressed protein of the fimbrin family in Trichomonas. Addition of TvFIM1 to actin polymerization assays increases the speed of actin filament assembly and results in bundling of F-actin in a parallel and anti-parallel manner. Upon contact with vaginal epithelial cells, the otherwise diffuse localization of actin and TvFIM1 changes dramatically. In the amoeboid TvFIM1 associates with fibrous actin bundles and concentrates at protrusive structures opposing the trailing ends of the gliding amoeboid form and rapidly redistributes together with actin to form distinct clusters. Live cell imaging demonstrates that Trichomonas amoeboid stages do not just adhere to host tissue, rather they actively migrate across human epithelial cells. They do so in a concerted manner, with an average speed of 20 μm/min and often using their flagella and apical tip as the leading edge.
Background:: Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome.
Goal:: To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women.
Study Design:: At University‐affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid‐gestation, tested for T. vaginalis by culture, and followed up until delivery.
Results:: The prevalence of T. vaginalis infection at enrollment was 12.6%. Race‐specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with T. vaginalis at mid‐gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites.
Conclusions:: After considering other recognized risk factors including co‐infections, pregnant women infected with T. vaginalis at mid‐gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks.
This review focused on potential regulatory mechanisms of Trichomonas vaginalis virulence properties, cytoadherence, cytotoxicity, phagocytosis, hemolysis, induction of apoptosis, and immune evasion in response to environmental factors of the human urogenital tract, iron, zinc, and polyamines. Understanding the multifactorial nature of trichomonal pathogenesis and its regulation may help to unravel the survival strategies of trichomonads and to implement prevention policies, opportune diagnosis, and alternative treatments for control of trichomoniasis.
The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection. Here, we report the cellular analyses of T. vaginalis tetraspanin 6 (TvTSP6). This family of membrane proteins has been implicated in cell adhesion, migration and proliferation in vertebrates. We observed that TvTSP6 expression is upregulated upon contact with vaginal ectocervical cells (VECs) and that parasite strains that are highly adherent to VECs express higher levels of TvTSP6 mRNA relative to poorly adherent strains. TvTSP6 is localized predominantly on the flagella of parasites cultured in the absence of host cells; however, adherence of the parasite to VECs initially results in a redistribution of the protein to intracellular vesicles and the plasma membrane of the main body of the cell. We found that a 16-amino-acid C-terminal intracellular tail of TvTSP6 is necessary and sufficient for flagellar localization and protein redistribution when the parasite is in contact with VECs. Additionally, deletion of the C-terminal tail reduced parasite migration through Matrigel, a mimic of the extracellular matrix. Together, our data support roles for TvTSP6 in parasite migration in the host and sensory reception during infection.
Trichomonas vaginalis is a sexually transmitted obligate extracellular parasite that colonizes the human urogenital tract. Despite being of critical importance to the parasite's survival relatively little is known about the mechanisms employed by T. vaginalis to establish an infection and thrive within its host. Several studies have focused on the interaction of the parasite with host cells and extracellular matrix, identifying multiple suspected T. vaginalis adhesins. However, with the exception of its surface lipophosphoglycan, the evidence supporting a role in adhesion is indirect or controversial for many candidate molecules. The availability of the T. vaginalis genome sequence paved the way for genomic analyses to search for proteins possibly involved in host-parasite interactions. Several proteomic analyses have also provided insight into surface, soluble and secreted proteins that may be involved in Trichomonas pathogenesis. Although the accumulation of molecular data allows for a more rational approach towards identifying drug targets and vaccine candidates for this medically important parasite, a continued effort is required to advance our understanding of its biology. In the present chapter, we review the current status of research aimed at understanding T. vaginalis pathogenesis. Applied experimental approaches, an overview of significant conclusions drawn from this research and future challenges are discussed.
Vaginitis due to Trichomonas vaginalis is one of the most common of sexually transmitted diseases. Trichomoniasis affects women during pregnancy as well but it is not clearly established whether it causes preterm birth and other pregnancy complications.
The objective of this review was to assess the effects of various treatments for trichomoniasis during pregnancy.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2011).
Randomized trials comparing anti-trichomonas agents during pregnancy. Trials including symptomatic or asymptomatic women with trichomoniasis were eligible.
Two review authors assessed eligibility and trial quality.
We included two trials with 842 pregnant women. In both trials around 90% of women were cleared of trichomonas in the vagina after treatment. In the US trial, women with asymptomatic trichomoniasis between 16 and 23 weeks were treated with metronidazole on two occasions at least two weeks apart. The trial was stopped before reaching its target recruitment because metronidazole was not effective in reducing preterm birth and there was a likelihood of harm (risk ratio 1.78; 95% confidence interval 1.19 to 2.66). The South African trial recruited women later in pregnancy and did not have the design and power to address adverse clinical outcomes. We excluded two recent studies, identified for the current update, because they did not address the primary question.
Metronidazole, given as a single dose, is likely to provide parasitological cure for trichomoniasis, but it is not known whether this treatment will have any effect on pregnancy outcomes. The cure rate could probably be higher if more partners used the treatment.
To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women.
Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms.
Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P < 0.05)] and at 3 months [11.0% (8 of 73) versus 24.1% (19 of 79) (relative risk: 0.46, 95% confidence interval = 0.21, 0.98; P = 0.03)] compared with the single-dose arm.
The 7-day MTZ dose was more effective than the single dose for the treatment of TV among HIV+ women.
We report a case of Trichomonas vaginalis (TV) presenting as vulval ulceration in a 41-year-old woman. There was complete resolution of her symptoms only after oral tinidazole. The delayed diagnosis and importance of using the correct tests for the diagnosis of TV are discussed.
Trichomonas vaginalis (T. vaginalis) is the most common nonviral sexually transmitted infection in the world. Despite the coexisting global epidemics of T. vaginalis and HIV, little attention has focused on the emerging evidence that T. vaginalis increases susceptibility to, and potentially transmission of, HIV.
We evaluated T. vaginalis infection in the context of a multisite, randomized controlled trial amongst women in South Africa and Zimbabwe, to determine first, if risk of HIV acquisition was increased among women recently infected with T. vaginalis, and second, if risk of T. vaginalis acquisition was increased among women infected with HIV.
After controlling for potential confounders, participants infected with T. vaginalis were more likely to test positive for HIV at their following visit, compared to participants uninfected with T. vaginalis (adjusted hazard ratio = 2.05; 95% CI, 1.05-4.02). Similarly, HIV-positive participants were twice as likely to have acquired T. vaginalis infection at the following visit, compared to HIV-negative participants (adjusted hazard ratio = 2.12; 95% CI, 1.35-3.32).
We found an increased risk of both HIV acquisition associated with T. vaginalis infection and risk of T. vaginalis acquisition associated with HIV infection. This bidirectional relationship represents a potentially important factor in sustaining the HIV epidemic in populations where T. vaginalis is endemic.
Although there have been reports of the results of treating trichomoniasis with metronidazole 2 g in a single dose, no randomised double-blind comparison of this treatment with a multiple-dose regimen has been reported. In such a comparison, 96 women were treated with metronidazole 2 g in a single dose and 96 women with metronidazole 400 mg twice daily for five days. Forty-eight of 52 women followed for 14 days after the single dose were cured, as were 61 of 66 women followed for 14 days after the start of the five-day regimen. These results compare favourably with previous reports. Side effects were trivial, and we recommend the single 2-g dose, for it is effective, economical, and can be given under supervision in the clinic.
This randomized, double-blind evaluation of metronidazole therapy for trichomonal vaginitis compared the efficacy and side effects of a single 2-g dose and the standard seven-day regimen (250 mg three times daily). Eighty (86%) of the 93 women examined seven to 21 days after therapy with the 2-g regimen, and 76 (91.6%) of 83 examined after the seven-day regimen, were cured. These cure rates were not significantly different. In addition, symptom duration and the occurrence of side effects and yeast infection were not significantly different for the two treatment groups. Because the efficacy and side effects of the two regimens are comparable and the 2-g dose is easier to administer and less expensive, we recommend the 2-g dose as standard treatment for trichomoniasis.
(JAMA 244:1219-1220, 1980)
To determine the prevalence and clinical manifestations of trichomoniasis among sexually active men.
Survey of two groups of men attending a sexually transmitted disease clinic. Subjects had a comprehensive sexual history and clinical examination plus cultures for Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis.
The study included 147 sexual partners of women with trichomoniasis and 300 subjects selected randomly from heterosexual men coming to the same clinic for evaluation of new problems.
Isolation of T. vaginalis was compared with urogenital signs and symptoms.
The prevalence of T. vaginalis was 33 of 147 (22% [95% CI, 16% to 29%]) among sexual contacts of women with trichomoniasis and 17 of 300 (6% [CI, 3% to 9%]) among heterosexual men attending the same clinic. Men with trichomoniasis alone were more likely to complain of urethral discharge (P < 0.01), to have discharge on examination (P < 0.03), and to have inflammatory cells in their urethral secretions (P < 0.01) than were men who did not have T. vaginalis, N. gonorrhoeae, or C. trachomatis. Trichomonas vaginalis remained associated with nongonococcal nonchlamydial urethritis (adjusted odds ratio 3.8; CI, 1.1 to 11.2) after adjustment for race, age, number of sex partners in the previous 6 months, exposure to a partner with trichomoniasis, and history of trichomoniasis, urethritis, or gonorrhea.
Trichomoniasis was common among men at risk for sexually transmitted diseases and was associated with symptoms and signs of urethritis.
Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome.
To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women.
At University-affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid-gestation, tested for T. vaginalis by culture, and followed up until delivery.
The prevalence of T. vaginalis infection at enrollment was 12.6%. Race-specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with T. vaginalis at mid-gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites.
After considering other recognized risk factors including co-infections, pregnant women infected with T. vaginalis at mid-gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks.
Around 120 million women worldwide suffer from Trichomonas vaginalis vaginitis every year. The infection is sexually transmitted and is believed to facilitate HIV transmission. The objective of the review is to assess the effects of various treatment strategies for trichomoniasis in women.
We searched the Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Trials were also identified from reference lists of reviews, through pharmaceutical companies, and by informal discovery. Only published data were used in this review. Date of the most recent search: May, 1999.
Randomized or quasi-randomized trials in women with trichomoniasis of different treatment strategies, different antitrichomonal drugs or doses were eligible.
Trial quality was assessed and data extracted by two reviewers independently using standard criteria.
Fifty-two trials were included. Nitroimidazoles seem to be effective in achieving parasitological cure in the short term follow-ups. Partner treatment can be effective in decreasing longer term re-infection rates.
Parasitological cure can be achieved by single oral dose of nitroimidazoles. Further research should focus on developing effective partner treatment strategies to prevent re-infections and reduce trichomoniasis prevalence.