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PubMed2006

Patient-delivered partner treatment for Trichomonas vaginalis infection: a randomized controlled trial.

OBJECTIVES: Infections with Trichomonas vaginalis (TV) are common and recurrence rates are high. Better methods of treating partners of women with trichomoniasis are needed. GOAL: To determine if patient-delivered partner treatment (PDPT) is better and more cost-effective than partner referral. STUDY DESIGN: Women attending a family planning clinic who were culture-positive and treated for TV (N = 463) were randomized to either standard partner referral (PR), booklet-enhanced partner referral (BEPR), or PDPT. At baseline and 1 month, women were interviewed and cultured for TV. Detailed cost information was also collected. RESULTS: Most women had 1 partner, were less than 24 years old, and were black. The percentage of women reporting that their partners were treated was similar for PDPT but significantly lower for BEPR compared to PR. TV follow-up rates were similar. PDPT cost less and was cost saving compared to PR and BEPR. CONCLUSION: Among women with TV, PDPT did not result in more partners taking the medicine or lower follow-up rates than PR but was less costly.

Adult↗
PubMed2006

Development of a nonhuman primate model for Trichomonas vaginalis infection.

OBJECTIVE: Trichomoniasis, caused by Trichomonas vaginalis, is a prevalent sexually transmitted infection associated with increased risk of HIV infection. An animal model of T. vaginalis infection would enable scientists to further investigate trichomoniasis. STUDY DESIGN: Seven macaques (4 test vs. 3 control) were enrolled in a 2-week pilot study. Eight additional animals participated in a 2-arm (T. vaginalis vs. sham inoculated) crossover study lasting 5 weeks before treatment. In all, 12 Macaca nemestrina monkeys were challenged with a single intravaginal inoculation of 6.6 to 7.1 x 10(5) trichomonads (ATCC 50148). Vaginal culture (InPouch TV), colposcopy, microbiology, pH, and cervical cytokines were assessed at baseline, day 2, and weekly thereafter. RESULTS: Ten of 12 challenged animals tested positive for trichomoniasis for 2 weeks or longer. One animal tested positive on days 2 and 7 but negative thereafter. Only one animal was not infected. Oral metronidazole treatment (35 mg/kg per day for 3 days) resolved infection in all animals. Trichomoniasis infection did not lead to shifts in vaginal microbiology or pH. CONCLUSIONS: A single T. vaginalis inoculation results in persistent infection in the pigtailed macaque.

Administration, Oral↗
PubMed2006

A Community-based study of risk factors for Trichomonas vaginalis infection among women and their male partners in Moshi urban district, northern Tanzania.

OBJECTIVE: The objective of this study was to determine predictors of Trichomonas vaginalis among women and their partners in Moshi, Tanzania. STUDY DESIGN: Women (N = 1440) and their partners (N = 588) were interviewed and specimens for detection of T. vaginalis and sexually transmitted infections (STIs) were collected. RESULTS: Prevalence of T. vaginalis was 10.7% in women and 6.3% in men. Having a partner with T. vaginalis was the strongest risk factor in women (adjusted odds ratio [OR], 19.44; 95% confidence interval [CI], 7.84-48.25) and men (adjusted OR, 19.01; 95% CI, 6.8-52.40). Risk of T. vaginalis infection was increased in subjects with less education. Other risk factors in women were daily alcohol consumption, being separated, reporting infertility problems, having a partner who had children with other women, and other STIs; and in men, the risk factor was having no income. T. vaginalis was not associated with HIV-1 in women and men. CONCLUSIONS: Prevention of T. vaginalis and other STIs among couples is a major priority. Reduction of alcohol consumption in women is an important intervention.

Adult↗
PubMed2007

Systemic immune response to Trichomonas vaginalis infection during pregnancy.

OBJECTIVE: The objective of this study was to characterize the systemic immune response in women with trichomoniasis in pregnancy as compared with uninfected women. STUDY DESIGN: A nested case control study was performed on 195 serum samples. Serum concentrations of cytokines, chemokines, and C-reactive protein (CRP) were compared between infected and uninfected women. Cytokines and chemokines were measured using a multiplex bead assay. The CRP concentrations were determined using a standard enzyme-linked immunosorbent assay method. RESULTS: The median serum concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in the trichomonas-infected group compared with the uninfected group (8.9 pg/mL vs. 5.7 pg/mL; P <0.001). The mean log-transformed CRP values were higher in the infected group compared with the uninfected group (1.66 vs. 1.27; P = 0.03). CONCLUSIONS: The results of this study suggest that trichomoniasis during pregnancy can lead to a systemic immune response in some women as exhibited by elevation in the serum concentrations of both GM-CSF and CRP.

Adult↗
PubMed1998

Characterization of Trichomonas vaginalis AP33 adhesin and cell surface interactive domains.

Adherence to host target cells is a critical step in establishing infection with the sexually transmitted pathogen Trichomonas vaginalis. Four parasite surface proteins mediating attachment to vaginal epithelial cells have been identified. One surface protein, termed AP33, was characterized further to identify domains interactive with previously generated antibodies and with host surface sites. N- and C-terminal deletion subclones were generated and tested for reactivity with both mAb and rabbit antiserum against AP33, and were also examined for their ability to bind to host cells. Surprisingly, the rabbit antiserum known to inhibit cytoadherence recognized an epitope(s) contained within 72 residues in the N-terminal half of the protein. However, the mAb epitope was immunoreactive with a 28-amino-acid region near the C-terminus. Subsequent mapping of this region with overlapping peptides identified a nine-amino-acid sequence reactive with the mAb. Equally surprising, two domains interactive with host cell surfaces were identified at distinct parts of AP33: one in the N-terminal half of the protein, and the other within 24 residues in the C-terminal third. Further analysis of the C-terminal binding domain revealed that a peptide representing this area could inhibit T. vaginalis cytoadherence by 40%.

Amino Acid Sequence↗
PubMed1999

Trichomonas vaginalis interactions with fibronectin and laminin.

The sexually transmitted protozoan Trichomonas vaginalis cytoadheres to vaginal epithelial cells and causes contact-dependent cytotoxicity which, when combined with the normal exfoliation process, leads to erosion of the epithelium, which may allow trichomonads into extracellular matrix and basement membrane sites. Therefore, the association of T. vaginalis with immobilized fibronectin (FN) and laminin (LM) on cover-slips was examined. Binding of live parasites to coated cover-slips was time- and parasite-density-dependent. Coincubation with an inhibitor of trichomonad cysteine proteinases resulted in an increased attachment of parasites to FN but had no effect on binding to LM, denoting that protease activity influenced optimal FN associations. Further, 20 h mid-exponential phase trichomonads placed in fresh culture medium for 3 h gave higher levels of binding to FN, suggesting that changes during growth in vitro to T. vaginalis organisms affect maximal levels of binding to FN. Extended incubation with substrates diminished the capacity of parasites to bind FN and LM. Treatment of live organisms with periodate reduced binding to LM but not FN, suggesting a role for carbohydrates. In addition, trypsinization of live parasites decreased numbers bound to both substrates. Placement of trypsinized parasites in medium for 2 h fully regenerated binding to FN but not LM. Incubation of trypsinized parasites with cycloheximide abrogated regeneration of attachment to FN, affirming a role for synthesized surface proteins in FN binding. Importantly, the T. vaginalis adhesin proteins that mediate cytoadherence, and iron, a factor that regulates adhesin synthesis, were not involved in FN and LM recognition. These results suggest a role for surface proteins and carbohydrates in trichomonal associations with FN and LM, respectively.

Animals↗
PubMed1985

Pulmonary trichomoniasis and Trichomonas tenax.

Pulmonary trichomoniasis is usually caused by aspirated Trichomonas tenax. Adult men with chronic purulent or necrotic pulmonary disease are usually affected. Sixty-eight patients were previously described. A Russian study demonstrated pulmonary trichomoniasis in 19 of 112 patients (17%), mostly in patients with lung cancer, lung abscess, or bronchiectasis. Rarely, pulmonary trichomoniasis may be caused by an intra-abdominal (T. hominis) or genitourinary (T. vaginalis) infection. T. tenax is usually regarded as a harmless commensal of the human mouth. Its prevalence ranges from 4% to 53% and may exceed that of vaginal infection with T. vaginalis in adult females. It is frequently found in patients with poor oral hygiene. Cultural identification is superior to microscopic examination of wet-smear, gram-stained and Papanicolaou-stained preparations. Aspirated pulmonary trichomoniasis is an opportunistic infection. Until the question of possible pathogenicity is resolved, metronidazole should be given. The underlying pulmonary disease should be vigorously treated.

Antibodies↗
PubMed1998

Growth and survival of Trichomonas vaginalis.

This study confirmed that Feinberg and Whittington medium was suitable for the cultivation and detailed study of the growth cycle of two clinical strains of Trichomonas vaginalis under anaerobic conditions. Both strains showed a similar growth pattern characterised by early but slow growth, extended duration of the logarithmic phase and limited survival never exceeding 144 h. Duration of survival and growth rate were inversely proportional to the inoculum density. Growth rate was pH dependent; pH values in the range 6.9-6.5 delayed the initiation of growth of T. vaginalis for at least 48 h. On the other hand, pH values of 6.4-4.5 were indifferent or slightly favourable for growth during the logarithmic and survival in the early decline phase. Normal saline and Ringer's solution exerted an early and progressively lethal effect on trichomonads and led to the disappearance of protozoa suspended in them in 150 min. In general, these in-vitro results shed light on some aspects of the biology of T. vaginalis and contribute to a better understanding of the epidemiology and clinical manifestations of the infection.

Anaerobiosis↗
PubMed1994

Antioxidant defences in the microaerophilic protozoan Trichomonas vaginalis: comparison of metronidazole-resistant and sensitive strains.

The sensitivity of the microaerophilic protozoan Trichomonas vaginalis to oxygen and products of its reduction, and the antioxidant defences employed by this organism, were investigated. Studies revealed that this amitochondrial flagellate is sensitive to oxygen tensions above those experienced in situ in the vagina (i.e. > 60 microM) and that metronidazole-resistant strains (CDC 85 and IR78) were more sensitive to elevated oxygen levels than a metronidazole-sensitive isolate (1910). In the presence of radical scavengers, inactivation of organisms at 60 microM oxygen was significantly lessened. Investigation of the antioxidant enzymes present in this organism revealed that activities of peroxide-reducing enzymes (e.g. catalase and general peroxidase) were not detectable, but that a cyanide-insensitive, azide-sensitive superoxide dismutase was present in cell extracts. Measurement of thiol-cycling enzymes indicated that NADPH could drive the reduction of oxidized glutathione (thiol reductase); however, the corresponding peroxidase activity was not detected. Analysis of thiols in whole cells of T. vaginalis indicated that glutathione was absent, but high levels of other thiols, propanethiol, methanethiol and H2S, were present. No significant differences were detected in thiol levels or antioxidant enzyme activities on comparison of metronidazole-sensitive and resistant strains. These results indicate that the sensitivity of T. vaginalis to oxygen above physiological levels is due to the lack of adequate peroxide-reducing enzymes and radical-scavenging mechanisms.

Animals↗
PubMed2004

tvcp12: a novel Trichomonas vaginalis cathepsin L-like cysteine proteinase-encoding gene.

Trichomonas vaginalis is the causative agent of trichomoniasis, one of the most common sexually transmitted diseases in humans. This protozoan has multiple proteinases that are mainly of the cysteine proteinase (CP) type, some of which are known to be involved in the parasite's virulence. Here, a novel T. vaginalis CP-encoding gene, tvcp12, was identified and characterized. tvcp12 is 948 bp long and encodes a predicted 34.4 kDa protein that has the characteristics of the papain-like CP family. TvCP12 does not appear to have a signal peptide, suggesting that this is a cytoplasmic CP. By Southern blot assays, the tvcp12 gene was found as a single copy in the T. vaginalis genome. Remarkably, Northern blot experiments showed a single transcript band of approximately 1.3 kb in the mRNA obtained from parasites grown in low iron conditions and no transcript was observed in the mRNA from parasites grown in high iron conditions. By RT-PCR assays, a 270 bp band was amplified from the cDNA of parasites grown in low iron medium, which was very faint when cDNA from parasites grown in high iron conditions was used. Transcripts of the 3' region obtained in both iron conditions presented differences in their poly(A) tail length. These data suggest that tvcp12 is another gene that is negatively regulated by iron and that the length of the poly(A) tail may be one of the factors involved in the iron-modulated protein expression.

Amino Acid Sequence↗
PubMed2003

Is there a seasonal difference in the detection of Trichomonas vaginalis by cervical cytology?

This objective of our study was to determine the prevalence of a Trichomonas vaginalis diagnosis in routine Papanicolaou smears and whether it is seasonal. We reviewed the diagnosis rendered for 93,681 Papanicolaou smears evaluated at a medical school hospital laboratory between 1992 and 1997. The occurrence of a diagnosis of T. vaginalis was analyzed by year, by quarter, and by month using a generalized linear regression model. The prevalence of a T. vaginalis diagnosis during the 6-year study period was 3.1%. The between-month and between-quarter comparisons of prevalence were not statistically different. In the population reported here, the prevalence of a Papanicolaou smear diagnosis of T. vaginalis was low and no seasonal difference in making this diagnosis was identified.

Animals↗
PubMed2004

Monoclonal antibodies against a 62 kDa proteinase of Trichomonas vaginalis decrease parasite cytoadherence to epithelial cells and confer protection in mice.

Trichomonas vaginalis infects the epithelium of the genital tract. The mechanism by which it invades the tissue leading to the disease is not thoroughly understood. However, results of several studies seem to agree that parasite adhesion to epithelium cells is the initial step leading to infection in women. T. vaginalis is associated with high levels of proteolytic activity. The role of some of these proteinases in the development of infection has been demonstrated. The current study establishes the role of a 62 kDa excretion-secretion proteinase in parasite cytoadherence. Monoclonal antibodies (MAbs) against this enzyme were tested for their ability to inhibit this process. Three stable hybrid producers of IgG(1)class MAbs (4D8, 1A8, 3C11) against the 62 kDa proteinase were obtained. Two of them (4D8 and 1A8) showed parasite recognition by immunofluorescence. Parasite cytoadherence to a monolayer of HeLa cells was inhibited by the 4D8, 1A8 and 3C11 antibodies. MAb 4D8 administered 24 h before a challenge with T. vaginalis by the intraperitoneal route was able to protect the majority of mice. Nitric oxide levels in the serum of animals inoculated with MAb 4D8 and challenged with the parasite were significantly different from those recorded in mice treated with an unrelated MAb. These studies show that an appropriate antibody against 62 kDa proteinase can help the host resist a challenge by the intraperitoneal route with T. vaginalis.

Animals↗
PubMed2004

Trichomonas vaginalis-induced apoptosis in RAW264.7 cells is regulated through Bcl-xL, but not Bcl-2.

The purpose of this study was to determine whether anti-apoptotic proteins of the Bcl-2 family such as Bcl-2 and Bcl-x(L), proteins that confer resistance to apoptotic death from some stimuli, block apoptotic cell death in RAW264.7 cells upon treatment with Trichomonas vaginalis. In this study, the expression level of Bcl-2 was unchanged throughout the course of apoptotic cell death, and overexpressed Bcl-2 did not prevent release of cytochrome c, the significant change of the membrane potential, activation of caspases, and PARP cleavage in T. vaginalis-treated RAW264.7 cells. On the other hand, Bcl-x(L)expression was decreased after T. vaginalis treatment accompanied with Bax activation. Furthermore, we showed that release of mitochondrial cytochrome c, cleavage of caspase-9 and PARP during apoptosis in T. vaginalis-treated RAW264.7 cells were considerably diminished by transfection with overexpressed Bcl-x(L), and overexpressed Bcl-x(L)could inhibit T. vaginalis-induced apoptosis in RAW264.7 cells. In addition, interestingly, pre-treatment with caspase inhibitors, Boc-D-FMK and Z-DEVD-FMK, significantly abolished T. vaginalis-induced down-regulation of Bcl-x(L), suggesting that caspase-3 may play a pivotal role in the process of apoptosis as well as the down-regulation of Bcl-x(L)by T. vaginalis. Therefore, these results suggest that T. vaginalis-induced apoptosis in RAW264.7 cells can occur via a Bcl-x(L)-dependent apoptotic mechanism.

Animals↗
PubMed1980

Effects of dextran sulfate 500 on protective responses to sublethal Trichomonas foetus infection in mice.

In order to analyze the host-parasite interactions in experimental trichomoniasis, the growth of Trichomonas foetus in the peritoneal cavity and changes in the peritoneal exudate cells were followed in mice treated with dextran sulfate 500 (DS 500), a known macrophage-toxic agent. Light microscopic observation showed that DS 500 treatment induced degeneration of peritoneal macrophages within about 48 hr after the treatment and the damaged macrophages did not phagocytize the parasites, whereas peritoneal neutrophils and lymphocytes were not affected by the drug. In the DS 500-treated mice, growth of parasites in the peritoneal cavity was accelerated and a high susceptibility of the mice to T. foetus infection was observed. These results indicate that macrophages play the most important role among the peritoneal exudate cells in resistance to T. foetus infection, especially during the early stage of infection.

Animals↗
PubMed2006

Dependence on p38 MAPK signalling in the up-regulation of TLR2, TLR4 and TLR9 gene expression in Trichomonas vaginalis-treated HeLa cells.

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that recognize conserved pathogen-associated molecular patterns (PAMPs) synthesized by micro-organisms. Despite the essential requirement for TLRs in prokaryotic infection, the pattern and regulation of TLR gene expression by Trichomonas vaginalis in the mucocutaneous barrier are still unknown. Our hypothesis is that T. vaginalis-infected epithelial cells are major effector cells in the skin barrier. These cells function as a central regulator of TLR gene expression, thus accelerating the process of barrier dysfunction via increased release of chemokines and proinflammatory cytokines. To test this hypothesis, RT-PCR was performed on TLRs, interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha. Stimulation of HeLa cells by T. vaginalis was observed to up-regulate TLR2, 4 and 9 mRNA expression as well as that of IL-8 and TNF-alpha. To further clarify the molecular mechanism of barrier devastation triggered by these up-regulatory stimuli, we examined the profiles of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB activation in HeLa cells using specific inhibitors. Interestingly, pretreatment of HeLa cells with the p38 MAPK inhibitor SB203580 demonstrated inhibition of T. vaginalis-induced up-regulation of TLR2, 4, and 9 mRNA expression. By contrast, inhibition of ERK or NF-kappaB activation failed to block T. vaginalis-induced up-regulation of TLR9 mRNA expression or TLR2 and TLR4 mRNA expression, respectively. In addition, pretreatment with SB203580 reduced epithelium-derived IL-8 and TNF-alpha release evoked by T. vaginalis. Our results show that T. vaginalis infection of the mucocutaneous barrier could up-regulate TLR2, 4 and 9 gene expression via the p38 MAPK signalling pathway in epithelial cells; this process then leads to modulation of p38 MAPK-dependent IL-8 and TNF-alpha release from the epithelium.

Animals↗
PubMed1992

In vitro nitroimidazole resistance of Trichomonas gallinae and successful therapy with an increased dosage of ronidazole in racing pigeons (Columba livia domestica).

Six out of eight different Trichomonas gallinae strains isolated from racing pigeons proved to be resistant to the nitroimidazole drugs ronidazole, carnidazole and metronidazole. The minimal cytocidal concentration of ronidazole was determined in in vitro experiments. Moreover, a therapeutic dose for ronidazole was determined for the control of trichomoniasis in pigeons from which the resistant T. gallinae strains were isolated. It was a 5-fold increase of the recommended ronidazole dosage which eliminated the infection in affected pigeons.

Animals↗
PubMed1992

Iron regulates growth of Trichomonas vaginalis and the expression of immunogenic trichomonad proteins.

Iron is an essential nutrient for Trichomonas vaginalis and is acquired via highly specific receptor-mediated mechanisms from the host. Responses of T. vaginalis to conditions of iron limitation or iron excess were analysed in order to determine whether iron levels in the growth medium regulate certain properties of the parasite. When compared with organisms grown in excess iron, iron limitation resulted in greater than or equal to 80% lower rates of protein synthesis and greater than or equal to 3-fold decreases in cell densities. These parasites also exhibited generation times of approximately 10 hours, 2.5-fold longer than organisms grown in the usual complex medium. Iron-restricted growth also resulted in increased binding of lactoferrin by trichomonads, which paralleled elevated expression of the lactoferrin-binding receptor protein having a relative molecular mass of 136,000 daltons (136 kDa). A Mr 126 kDa protein was concomitantly repressed in low-iron-grown parasites. The greater amounts of lactoferrin bound by iron-depleted T. vaginalis organisms corresponded with both the expression of additional receptors onto trichomonal surfaces and increased affinity of the receptor for the lactoferrin molecule. Finally, immunoblot analysis of parasites grown under high- and low-iron conditions using sera from patients with trichomoniasis further revealed the synthesis by T. vaginalis of at least 19 iron-regulated immunogens, and patients' sera also detected the lactoferrin receptor. These data not only show the overall importance of iron to the biology of this protozoan, but illustrate the in vivo iron modulation of gene expression of the biofunctional lactoferrin receptor and other immunogens.

Animals↗
PubMed1995

Influence of humoral immunity on leukotriene B4 production by neutrophils in response to Trichomonas vaginalis stimulation.

Neutrophils are the predominant inflammatory cells found in vaginal discharges from patients with Trichomonas vaginalis infection. In this study, we investigated the effect of humoral immunity on leukotriene B4 (LTB4) generation by neutrophils in the inflammatory response of vaginal trichomoniasis. As quantitated by a radioimmunoassay, no release of LTB4 was detected from neutrophils (5 x 10(6)/ml) interacted with trichomonads (1 x 10(6)/ml). However, specific immunoglobulin G(IgG) but not F(ab')2, at a titre of 1:256 directed against T. vaginalis, augmented LTB4 production (1.4 +/- 0.4 ng/ml, n = 5) by neutrophils, suggesting that this enhancement is Fc gamma receptor-mediated. Moreover, addition of the specific IgG (1 mg/ml) to C2-deficient serum or Factor B-deficient serum, but not C5-deficient serum, significantly increased LTB4 production by neutrophils in response to trichomonad stimulation. This indicates that the complement common pathway activation is crucial for the amplification of host defence mechanisms against T. vaginalis. An LTB4 receptor antagonist, SC-41930, completely abolished neutrophil chemotactic activity induced by LTB4. Taken together, these results indicate that humoral immunity could promote the interaction of neutrophils with T. vaginalis and augment the inflammatory response through the amplification of LTB4 production.

Animals↗