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PubMed1998

Activity of disulfiram (bis(diethylthiocarbamoyl)disulphide) and ditiocarb (diethyldithiocarbamate) against metronidazole-sensitive and -resistant Trichomonas vaginalis and Tritrichomonas foetus.

Clinical resistance of Trichomonas vaginalis to metronidazole is best correlated with MIC values measured under aerobic conditions. Under these conditions both disulfiram (bis(diethylthiocarbamoyl)disulphide), and its first mammalian metabolite, ditiocarb (diethyldithiocarbamate), showed high levels of activity against metronidazole-sensitive (disulfiram MIC, 0.1-0.7 microM; ditiocarb MIC, 0.3-9 microM) and -resistant (MICs 0.2-1.3 microM and 1.2-9 microM respectively) isolates. Tritrichomonas foetus was also sensitive-the MICs for seven metronidazole-sensitive isolates were 0.1-1.0 microM for disulfiram and 1.0-6.9 microM for ditiocarb; those for two highly metronidazole-resistant strains were 0.3-1.3 microM and 0.6-6 microM respectively. Under anerobic conditions most strains became highly resistant to both compounds. Surprisingly, disulfiram was consistently more active than ditiocarb.

Aerobiosis↗
PubMed2002

In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis.

The activities of the N-(nitrothiazolyl) salicylamide nitazoxanide and its metabolite tizoxanide were compared with metronidazole in vitro in microplates against six axenic isolates of Giardia intestinalis. Tizoxanide was eight times more active than metronidazole against metronidazole-susceptible isolates and twice as active against a resistant isolate. In 10 axenic isolates of Entamoeba histolytica, while tizoxanide was almost twice as active as metronidazole against more susceptible isolates, it was more than twice as active against less susceptible isolates. Fourteen metronidazole-susceptible isolates of Trichomonas vaginalis were 1.5 times more susceptible to tizoxanide, which was nearly five times as active against resistant isolates. Two highly metronidazole-resistant isolates retained complete susceptibility to tizoxanide, and one moderately resistant isolate showed reduced susceptibility. In all three organisms, nitazoxanide results paralleled those of tizoxanide. Analogues lacking the reducible nitro-group had similar low activities against susceptible G. intestinalis, E. histolytica and T. vaginalis, indicating that nitro-reduction and free radical production was a probable mode of action. Nitazoxanide and its metabolite tizoxanide are more active in vitro than metronidazole against G. intestinalis, E. histolytica and T. vaginalis. Although, like metronidazole, they depend on the presence of a nitro-group for activity, they retain some activity against metronidazole-resistant strains, particularly of T. vaginalis. The results suggest that resistance mechanisms for metronidazole can be bypassed by nitazoxanide and tizoxanide.

Amebicides↗
PubMed2003

In vitro susceptibility of Trichomonas vaginalis to AT-specific minor groove binding drugs.

Trichomoniasis is one of the most common sexually transmitted diseases, with around 120 million world-wide suffering from Trichomonas vaginalis-induced vaginitis every year. Although trichomoniasis can be treated with metronidazole, the prevalence of metronidazole-resistant T. vaginalis seems to be increasing. Since the percentage of AT base pairs in T. vaginalis DNA (71%) is very much higher than in human cells, in this study a series of bisquaternary quinolinium salt compounds with high AT-binding specificity were tested for their antitrichomonal activities. Minimum inhibitory concentrations (MICs) were determined for these compounds against a local strain of T. vaginalis in culture. Among 14 bisquaternary quinolinium compounds tested, an N-ethyl derivative was the most effective drug against T. vaginalis, being nearly as potent (MIC = 0.16 microM) as metronidazole (MIC = 0.096 microM), and with low toxicity towards human cells. The nature of the substitution at the quinolinium quaternary centre appears to be important in terms of effectiveness of bisquaternary compounds against the parasite. In contrast, no clear relationships could be seen for substituents on the quinolinium ring; Me and Cl substituted analogues showed higher activity against trichomonads, whereas OMe, NHMe and NH2 substituents decreased activity.

Animals↗
PubMed2005

In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis.

OBJECTIVES: Trichomonas vaginalis is the causative agent of trichomoniasis, a sexually transmitted disease with worldwide significance. Trichomoniasis can be treated with metronidazole; however, resistant strains of T. vaginalis have been isolated and there is a lack of useful alternative drugs. The aim of the present study was to examine the activity of hexadecylphosphocholine (HePC; miltefosine), a membrane-active alkylphospholipid, that is licensed as an antileishmanial agent against T. vaginalis. METHODS: The efficacy of HePC after 30 min, 1 h, 16 h and 24 h against four different T. vaginalis strains (with varying resistance to metronidazole) was evaluated. RESULTS: It was shown that all isolates, including the metronidazole-resistant strains, were susceptible to HePC, with EC50s of between 8 and 40 microM and EC90s of between 8 and 80 microM depending on time and on the medium used for the experiments. Treatment of trichomonads with HePC resulted in rounding up and, at concentrations of >or=40 microM, in subsequent total lysis of the organisms. CONCLUSIONS: HePC may be a promising new candidate for the treatment of trichomoniasis.

Animals↗
PubMed2004

A potentially functional mariner transposable element in the protist Trichomonas vaginalis.

Mariner transposable elements encoding a D,D34D motif-bearing transposase are characterized by their pervasiveness among, and exclusivity to, animal phyla. To date, several hundred sequences have been obtained from taxa ranging from cnidarians to humans, only two of which are known to be functional. Related transposons have been identified in plants and fungi, but their absence among protists is noticeable. Here, we identify and characterize Tvmar1, the first representative of the mariner family to be found in a species of protist, the human parasite Trichomonas vaginalis. This is the first D,D34D element to be found outside the animal kingdom, and its inclusion in the mariner family is supported by both structural and phylogenetic analyses. Remarkably, Tvmar1 has all the hallmarks of a functional element and has recently expanded to several hundred copies in the genome of T. vaginalis. Our results show that a new potentially active mariner has been found that belongs to a distinct mariner lineage and has successfully invaded a nonanimal, single-celled organism. The considerable genetic distance between Tvmar1 and other mariners may have valuable implications for the design of new, high-efficiency vectors to be used in transfection studies in protists.

Amino Acid Sequence↗
PubMedDate not supplied

Measuring the in vitro susceptibility of Trichomonas vaginalis to metronidazole: a disk broth method.

Strains of Trichomonas vaginalis were evaluated for their in vitro responses to metronidazole. A serial twofold dilution method that measured minimal inhibitory concentrations (MICs) by cessation of trophozoite motility was compared with the disk broth method, in which both cessation of motility and inhibition of trophozoite proliferation were used for measurement of MICs. These methods gave comparable results in distinguishing a metronidazole-resistant and two metronidazole-susceptible strains of T. vaginalis under conditions of both aerobic and anaerobic incubation. However, anaerobic test conditions significantly lowered the MIC of metronidazole against a metronidazole-resistant strain. Clinical isolates of T. vaginalis and strain ATCC 30001 from the American Type Culture Collection (Rockville, Md.) were also tested. Two of 12 clinical isolates were resistant to metronidazole in vitro. It is concluded that the disk broth method is a simple and reliable screening method for detection of metronidazole-resistant strains of T. vaginalis.

Drug Resistance, Microbial↗
PubMedDate not supplied

Isoenzyme patterns of isolates of Trichomonas vaginalis from Vancouver.

Isoenzyme patterns of 63 isolates of Trichomonas vaginalis obtained in Vancouver were evaluated by use of thin-layer starch-gel electrophoresis. We attempted to use eight enzymes, but only four gave reproducible and interpretable results. There were four patterns with malic enzyme, two with malate dehydrogenase, one with hexokinase, and four with lactate dehydrogenase. The isoenzyme patterns of the 63 isolates were classified into 15 groups, but 49 (78%) fell into five groups and 14 (22%) fell into ten groups. There was no obvious correlation between groups and magnitude of symptoms and signs, past history of trichomoniasis, or likelihood of treatment failure. Results were consistent for isolates obtained from the same patient on different days. This system will allow differentiation of isolates into groups, a procedure that could be useful. However, groups do not appear to correlate with clinical or historical features or with outcome of treatment.

Animals↗
PubMedDate not supplied

Epidemiology of trichomonas vaginalis. A prospective study in China.

BACKGROUND AND OBJECTIVES: Trichomonas vaginalis infection is probably one of the most common sexually transmitted diseases. The epidemiology of this disease has long been ignored, and not much is known about its natural history and risk factors. GOALS: The authors conducted this study to define the incidence rates of T. vaginalis infection and to investigate risk factors for the infection. STUDY DESIGN: A prospective study was carried out on a cohort of 16,797 women followed up from 1974 to 1985 within the framework of a cervical screening program in Jingan, China. Personal interviews were conducted by trained interviewers. RESULTS: A total of 1489 new cases of T. vaginalis infection were diagnosed with 132,946 person-years of observation. In a multivariate analysis, the increased risk was associated with multiple sexual partners (P = 0.0124) and greater number of induced abortions (P = 0.0028). The relative risks were 1.3 (95% confidence interval [CI], 1.1 to 1.5) for smokers and 1.5 (95% CI, 1.2 to 2.0) for those who drink alcohol. An inverse relationship was observed in older women and in women with cervical atrophy. CONCLUSIONS: This study confirmed the relationship between T. vaginalis and multiple sexual partners and suggests that the risk for T. vaginalis also may be related to life-style risk factors.

Adult↗
PubMed1997

Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group.

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 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.

Adult↗
PubMed1998

A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.

BACKGROUND: Trichomonas vaginalis is a common sexually transmitted pathogen. In the United States, oral metronidazole is the only officially sanctioned treatment option. OBJECTIVE: This study was undertaken to compare the efficacy and safety of 0.75% metronidazole vaginal gel with that of oral metronidazole for the treatment of trichomonal vaginitis. STUDY DESIGN: Women with trichomoniasis were enrolled in this randomized, open-label pilot study of 0.75% metronidazole vaginal gel twice daily for 7 days compared with 7 days of generic oral metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits 5 to 7 days and 21 to 28 days after the last dose of medication. RESULTS: Using culture for test of cure, trichomonal infection was eliminated in all 15 women treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal metronidazole. Adverse events were similar, except that there were more taste-related adverse events in the oral metronidazole group. Significant reductions in genitourinary symptoms were seen in both the oral and intravaginal groups. CONCLUSION: This study has shown that 0.75% metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. Future studies may define a role for metronidazole gel for symptomatic relief in patients intolerant of oral medication or as adjunctive treatment with oral metronidazole for the management of patients infected with metronidazole-resistant strains of T. vaginalis.

Administration, Intravaginal↗
PubMed2000

Effect of chlorhexidine on genital microflora, Neisseria gonorrhoeae, and Trichomonas vaginalis in vitro.

BACKGROUND: Chlorhexidine is a disinfectant that has been used in skin and mouth washes and as a preservative in some vaginal lubricants. A gel containing 0.25% chlorhexidine gluconate has been found to be effective against Chlamydia trachomatis in vitro and in animal models. Applied vaginally, 5 g of this gel could achieve vaginal fluid concentrations of < or = 1250 microg/ml. GOAL: To test the in vitro activity of chlorhexidine in a gel over a pH range of 4 to 8 in the presence or absence of blood. STUDY DESIGN: Organisms were exposed to chlorhexidine for 30 minutes to 2 hours, and the minimum cidal concentration (MCC) was calculated. RESULTS: The MCC for Neisseria gonorrhoeae was 25 microg/ml at 30 minutes and 12.5 microg/ml at 1 to 2 hours of exposure, whereas the MCC for Trichomonas vaginalis was 1250 microg/ml. Chlorhexidine was more active at pH 8 than pH 4, and less active in the presence of blood. The MCC for Lactobacillus crispatus was 1250 microg/ml at pH 4 and only 125 microg/ml at pH 8. CONCLUSIONS: Based on its in vitro activity, chlorhexidine may be an appropriate topical microbicide for prevention of gonorrhea, but not for prevention of trichomoniasis. This study suggests that the presence of blood and pH affect the activity of chlorhexidine against genital pathogens and commensals.

Animals↗
PubMed2005

Detection of bacterial vaginosis, Trichomonas vaginalis infection, and vaginal Candida infection: a comparative study of methods of extracting exudates, with and without a speculum, during pregnancy.

PURPOSE: To compare the collection of vaginal exudates with and without the use of a speculum to diagnose vaginal infections. MATERIAL AND METHODS: We examined 45 patients with vaginal discharge. Two vaginal swabs were taken, one with and the other without a speculum. Both were examined by wet mount microscopy to detect bacterial vaginosis (BV), Trichomonas vaginalis, and the presence of blastospores with or without pseudomycelium. RESULTS: A total of 90.9% of patients whose vaginal exudates were negative for BV when extracted with a speculum were also negative in the swab taken without a speculum. In the case of BV-positive exudates using a speculum, the correspondence was 90.5% with the swabs taken without a speculum. Among those exudates obtained with a speculum that were negative for Candida, 92.6% of those obtained without a speculum tested negative. In patients with pseudomycelium, when a speculum was used, 100% also presented a diagnosis of pseudomycelium from the swabs taken without a speculum. A concordance test between the techniques involving the use or nonuse of a speculum was performed for each of the diagnoses showed a good agreement according to the observed Kappa statistics (0.8467 and 0.8396 for BV and Candida, respectively). CONCLUSIONS: A very good agreement between the results obtained with and without the use of a speculum was observed. Swabbing without the use of a speculum is especially convenient for pregnant women who require frequent testing for these types of infections during their pregnancies.

Candidiasis, Vulvovaginal↗
PubMed2006

The associations between pelvic inflammatory disease, Trichomonas vaginalis infection, and positive herpes simplex virus type 2 serology.

OBJECTIVE: Roles for Chlamydia trachomatis and Neisseria gonorrhoeae infections in pelvic inflammatory disease pathogenesis are well delineated; however, the etiologic contributions of herpes simplex virus type 2 (HSV-2) and Trichomonas vaginalis have been underexplored. GOAL: The goal of this study was to investigate the association between acute and plasma cell endometritis, fallopian tube obstruction, HSV-2 serology, and T. vaginalis infection. STUDY DESIGN: The authors conducted a cross-sectional secondary analysis of 736 women at risk for bacterial sexually transmitted diseases that used endometrial biopsy data obtained at enrollment as well as hysterosalpingography results obtained 12 weeks after enrollment. RESULTS: Women diagnosed with T. vaginalis at enrollment were more likely to have histologic evidence of acute endometritis. Both plasma cell and acute endometritis were significantly more common among women with positive serology HSV-2; furthermore, women coinfected with HSV-2 and C. trachomatis, N. gonorrhoeae, T. vaginalis, or bacterial vaginosis were much more likely to be diagnosed with acute endometritis than were women infected with HSV-2 or one of these pathogens alone. Among women with available HSV-2 serology and hysterosalpingogram results, HSV-2 was the only genital tract pathogen infection associated with fallopian tube obstruction. CONCLUSIONS: Our analyses demonstrate that T. vaginalis infection and positive HSV-2 serology are associated with endometritis. Further work will be needed to determine the specific roles these pathogens may play in pelvic inflammatory disease pathogenesis.

Adult↗
PubMed1985

Metronidazole radical anion generation in vivo in Trichomonas vaginalis: oxygen quenching is enhanced in a drug-resistant strain.

The nitro radical-anion of metronidazole has been detected in vivo in the sexually transmitted human parasite, Trichomonas vaginalis, under anaerobic conditions by electron spin resonance spectrometry. Exposure of organisms to oxygen decreased the intensity of the radical signal in both metronidazole-sensitive ATCC strain 30001 and in the metronidazole-resistant strain 85. The sensitive strain still gave radical signals at partial pressures of oxygen (greater than 6 kPa) sufficient to remove all detectable radicals from the resistant strain. This evidence suggests that the resistant strain has defective oxygen scavenging system(s).

Aerobiosis↗
PubMed1985

Energy-dispersive X-ray microanalysis of membrane-associated inclusions in hydrogenosomes isolated from Trichomonas vaginalis.

Energy-dispersive X-ray microprobe analysis of electron-dense inclusions in hydrogenosomes isolated from the aerotolerant anaerobic protozoal human parasite Trichomonas vaginalis, Bushby strain, indicated the presence of high levels of Mg, P and Ca. This suggested that divalent cation (e.g. Ca2+ or Mg2+) accumulation by hydrogenosomes may be important in the regulation of intracellular ion concentrations.

Calcium↗
PubMed1985

Metronidazole inhibition of hydrogen production in vivo in drug-sensitive and resistant strains of Trichomonas vaginalis.

H2 production by the human protozoan parasite Trichomonas vaginalis was monitored continuously under a mobile gas phase using a membrane-inlet mass spectrometer. Simultaneous and continuous measurement of dissolved H2, O2 and CO2 indicated that H2 evolution was inhibited at levels of O2 (less than 0.25 microM) undetectable by the technique, whereas CO2 production was stimulated. Respiration was not stimulated by admitting H2 to the gas phase. Metronidazole inhibited both H2 and CO2 production. Values of K1 for inhibition of H2 formation in strain ATCC 30001 (metronidazole sensitive) of 0.16 mM and in strain 85 (metronidazole resistant) of 1.0 mM were obtained. These data suggest that metronidazole not only competes with protons as electron acceptor but that the drug itself or a product of reduction actively inhibits some hydrogenosomal enzyme or electron carrier involved in H2 production. Under these conditions metronidazole inhibition leads to irreversible loss of cell motility.

Carbon Dioxide↗
PubMed1985

The generation of metronidazole radicals in hydrogenosomes isolated from Trichomonas vaginalis.

The nitro radical-anion of the anti-trichomonal drug metronidazole has been detected by electron spin resonance spectrometry under anaerobic conditions in suspensions of intact hydrogenosomes isolated from the parasitic protozoon Trichomonas vaginalis. Metronidazole reduction was driven by pyruvate, but progressive damage to the radical generating system was observed. Quenching of signals due to metronidazole radicals by chromium oxalate suggests that the radicals generated within the organelle can cross the hydrogenosomal membrane into the external medium. Even if a similar process of radical migration occurs in vivo, it seems likely that intrahydrogenosomal damage may explain drug action.

Electron Spin Resonance Spectroscopy↗
PubMed1988

The effect of hormones on Trichomonas vaginalis.

The hormonal milieu can alter susceptibility to infection. The effect of hormones on Trichomonas vaginalis was studied utilizing axenically cultured clinical isolates. Oestrogens, in physiological concentrations, decreased the growth of the organisms and their attachment to mammalian cells in vitro, and acted as a chemorepellent. The specificity of these effects was verified by their being blocked with anti-oestrogens, by the dose- and time-dependency of the responses, and by the lack of effect with other hormones. These results suggest that oestrogens may decrease the virulence of T. vaginalis; however, interactions between oestrogens and mammalian cells may promote the development of infection. Thus complicated interactions between hormones, micro-organisms and mammalian cells must determine whether exposure to oestrogens predisposes to or prevents the development of infection.

Animals↗