Anti-Trichomonas vaginalis activity of 1,10-phenanthroline-5,6-dione-based metallodrugs and synergistic effect with metronidazole

Parasitology ◽  
2018 ◽  
Vol 146 (9) ◽  
pp. 1179-1183 ◽  
Author(s):  
Graziela Vargas Rigo ◽  
Brenda Petro-Silveira ◽  
Michael Devereux ◽  
Malachy McCann ◽  
André Luis Souza dos Santos ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Trichomonas Vaginalis ◽  
Treatment Options ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Low Cytotoxicity ◽  
New Treatment ◽  
Clinical Drug ◽  
Increased Susceptibility

AbstractTrichomonas vaginalis is responsible for the most common non-viral, sexually transmitted infection, human trichomoniasis, and is associated with an increased susceptibility to HIV. An escalation in resistance (2.5–10%) to the clinical drug, metronidazole (MTZ), has been detected and this compound also has adverse side-effects. Therefore, new treatment options are urgently required. Herein, we investigate the possible anti-T. vaginalis activity of 1,10-phenanthroline-5,6-dione (phendione) and its metal complexes, [Ag(phendione)2]ClO4 and [Cu(phendione)3](ClO4)2·4H2O. Minimum inhibitory concentration (MIC) against T. vaginalis ATCC 30236 and three fresh clinical isolates and mammalian cells were performed using serial dilution generating IC50 and CC50 values. Drugs combinations with MTZ were evaluated by chequerboard assay. A strong anti-T. vaginalis activity was found for all test compounds. IC50 values obtained for [Cu(phendione)3](ClO4)2·4H2O were similar or lower than those obtained for MTZ. In vitro assays with normal cells showed low cytotoxicity and [Cu(phendione)3](ClO4)2·4H2O presented a high selectivity index (SI) for fibroblasts (SI = 11.39) and erythrocytes (SI > 57.47). Chequerboard assay demonstrated that the combination of [Cu(phendione)3](ClO4)2·4H2O with MTZ leads to synergistic interaction, which suggests distinct mechanisms of action of the copper–phendione complex and avoiding the MTZ resistance pathways. Our results highlight the importance of phendione-based drugs as potential molecules of pharmaceutical interest.

scholarly journals Trichomonas vaginalis AND HIV INFECTION: RELATION AND PREVALENCE AMONG WOMEN IN SOUTHERN BRAZIL

2019 ◽  
Vol 48 (1) ◽  
pp. 15-24
Author(s):  
Mirian Pinheiro Bruni ◽  
Carolina Caetano dos Santos ◽  
Dulce Stauffert ◽  
Nilton Da Cunha Filho ◽  
Guilherme De Oliveira Bicca ◽  
...  
Keyword(s):  
Viral Load ◽  
Low Income ◽  
Trichomonas Vaginalis ◽  
Hiv Positive ◽  
Hiv Status ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Cell Counts ◽  
Hiv Negative

Trichomoniasis is a curable sexually transmitted infection (STI) that has been reported to be linked to exposure to human immunodeficiency virus (HIV), although few studies have described this association. The purpose of this study was to focus on the incidence of trichomoniasis in low-income women, its relation to HIV status, viral load levels and TCD4+ cell counts, among other risk factors, using an in vitro culture as a diagnostic test. A crosssectional study among 267 women (103 HIV-positive and 164 HIV-negative) was conducted in 2015. The overall prevalence of Trichomonas vaginalis (TV) infection was 6.4%. Among HIVpositive and HIV-negative women, the prevalence was 3.9% and 7.9%, respectively, yet these results were not statistically different (p=0.1878). The factors associated with TV infection were cigarette smoking (OR= 3.52), vaginal itching (OR=4.43) and bacterial vaginosis (BV) (OR= 5.29). HIV status, TCD4+ cell count and viral load were not associated with TV infection in this group. The prevalence rates found, lower than those observed in other studies, may be due to the fact that the women evaluated in the present study are part of a low-risk populationas well as the limited sample size of HIV positive women.

scholarly journals Neutrophil interactions with the sexually transmitted parasite Trichomonas vaginalis: implications for immunity and pathogenesis

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200192 ◽  
Author(s):  
Suhani B. Bhakta ◽  
Jose A. Moran ◽  
Frances Mercer
Keyword(s):  
Trichomonas Vaginalis ◽  
Mycoplasma Hominis ◽  
Protozoan Parasite ◽  
Parasite Clearance ◽  
Infectious Agents ◽  
Transmitted Infection ◽  
Innate And Adaptive Immunity ◽  
Sexually Transmitted ◽  
Microbial Symbionts

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.

scholarly journals The protozoanTrichomonas vaginalistargets bacteria with laterally-acquired NlpC/P60 peptidoglycan hydrolases

2018 ◽  
Author(s):  
Jully Pinheiro ◽  
Jacob Biboy ◽  
Waldemar Vollmer ◽  
Robert P. Hirt ◽  
Jeremy R. Keown ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Close Association ◽  
Transmitted Disease ◽  
Protozoan Parasite ◽  
Mixed Cultures ◽  
Vaginal Mucosa ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Peptidoglycan Hydrolases

AbstractTrichomonas vaginalisis a human eukaryotic pathogen and the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. This extracellular protozoan parasite is intimately associated with the human vaginal mucosa and microbiota but key aspects of the complex interactions between the parasite and the vaginal bacteria remain elusive. We report thatT. vaginalishas acquired, by lateral gene transfer from bacteria, genes encoding peptidoglycan hydrolases of the NlpC/P60 family. Two of theT. vaginalisenzymes were active against bacterial peptidoglycan, retaining the active site fold and specificity as DL-endopeptidases. The endogenous NlpC/P60 genes are transcriptionally up regulated inT. vaginaliswhen in the presence of bacteria. The over-expression of an exogenous copy produces a remarkable phenotype where the parasite is capable of competing out bacteria from mixed cultures, consistent with the biochemical activity of the enzymein vitro. Our study highlights the relevance of the interactions of this eukaryotic pathogen with bacteria, a poorly understood aspect on the biology of this important human parasite.Author summaryTrichomonas vaginalisis a protozoan parasite that causes a very common sexually transmitted disease known as trichomoniasis. This extracellular parasite resides in the vagina where it is in close association with the mucosa and the local microbiota. Very little is known about the nature of the parasite-bacteria interactions. Here, we report that this parasite had acquired genes from bacteria which retained their original function producing active enzymes capable of degrading peptidoglycan, a polymer that is chemically unique to the cell envelope of bacteria. Our results indicate that these enzymes help the parasite compete out bacteria in mixed cultures. These observations suggest that these enzymes may be critical for the parasite to establish infection in the vagina, a body site that is densely colonised with bacteria. Our study further highlights the importance of understanding the interactions between pathogens and microbiota, as the outcomes of these interactions are increasingly understood to have important implications on health and disease.

In vitro trichomonacidal activity and preliminary in silico chemometric studies of 5-nitroindazolin-3-one and 3-alkoxy-5-nitroindazole derivatives

Parasitology ◽  
2015 ◽  
Vol 143 (1) ◽  
pp. 34-40 ◽  
Author(s):  
ALEXANDRA IBÁÑEZ-ESCRIBANO ◽  
JUAN JOSÉ NOGAL-RUIZ ◽  
ALICIA GÓMEZ-BARRIO ◽  
VICENTE J. ARÁN ◽  
JOSÉ ANTONIO ESCARIO
Keyword(s):  
In Silico ◽  
Mammalian Cells ◽  
Trichomonas Vaginalis ◽  
Specific Activity ◽  
Parasite Growth ◽  
Significant Activity ◽  
Sexually Transmitted ◽  
Pharmacokinetic Properties ◽  
Specific Cytotoxicity

SUMMARYA selection of 1,2-disubstituted 5-nitroindazolin-3-ones (1–19) and 3-alkoxy-5-nitroindazoles substituted at positions 1 (20–24) or 2 (25–39) from our in-house compound library were screened in vitro against the most common curable sexually transmitted pathogen, Trichomonas vaginalis. A total of 41% of the studied molecules (16/39) achieved a significant activity of more than 85% growth inhibition at the highest concentration assayed (100 µg mL−1). Among these compounds, 3-alkoxy-5-nitroindazole derivatives 23, 24, 25 and 27 inhibited parasite growth by more than 50% at 10 µg mL−1. In addition, the first two compounds (23, 24) still showed remarkable activity at the lowest dose tested (1 µg mL−1), inhibiting parasite growth by nearly 40%. Their specific activity towards the parasite was corroborated by the determination of their non-specific cytotoxicity against mammalian cells. The four mentioned compounds exhibited non-cytotoxic profiles at all of the concentrations assayed, showing a fair antiparasitic selectivity index (SI > 7·5). In silico studies were performed to predict pharmacokinetic properties, toxicity and drug-score using Molinspiration and OSIRIS computational tools. The current in vitro results supported by the virtual screening suggest 2-substituted and, especially, 1-substituted 3-alkoxy-5-nitroindazoles as promising starting scaffolds for further development of novel chemical compounds with the main aim of promoting highly selective trichomonacidal lead-like drugs with adequate pharmacokinetic and toxicological profiles.

Optimization of Coumarins Extraction from Pterocaulon balansae by Box-Behnken Design and Anti-Trichomonas vaginalis Activity

Planta Medica ◽  
2021 ◽  
Author(s):  
Nathalya Tesch Brazil ◽  
Bruna Medeiros-Neves ◽  
Flávia Nathiely Silveira Fachel ◽  
Vanessa Pittol ◽  
Roselena Silvestri Schuh ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Extraction Time ◽  
Vaginal Mucosa ◽  
Solvent Ratio ◽  
Transmitted Infection ◽  
Box Behnken Design ◽  
Sexually Transmitted ◽  
Drug Of Choice ◽  
Receptor Compartment ◽  
Low Cytotoxicity

Abstract Trichomonas vaginalis causes trichomoniasis, a nonviral sexually transmitted infection with a high prevalence worldwide. Oral metronidazole is the drug of choice for the treatment of this disease, although high levels of T. vaginalis resistance to this agent are well documented in the literature. This study describes the anti-T. vaginalis activity of an optimized coumarin-rich extract from Pterocaulon balansae. Optimization was performed to maximize extraction of total coumarins by means of a 3-level Box-Behnken design, evaluating the effect of three factors: extraction time, plant : solvent ratio, and ethanol concentration. Optimum conditions were found to be 5 h extraction time and a plant : solvent ratio of 1% (w/v) and 60% (v/v) ethanol, which resulted in approximately 30 mg of total coumarins/g of dry plant. The coumarin-enriched extract exhibited a minimum inhibitory concentration of 30 µg/mL and an IC50 of 3.2 µg/mL against T. vaginalis, a low cytotoxicity, and a high selectivity index (18 for vaginal epithelial cells and 16 for erythrocytes). The coumarins permeation/retention profile through porcine vaginal mucosa was evaluated in Franz-type diffusion cells. After 8 h of kinetics, coumarins were detected in the tissue (4.93 µg/g) without detecting them in the receptor compartment. A significant increase of coumarins in the mucosa layers (8.18 µg/g) and receptor compartment (0.26 µg/g) was detected when a T. vaginalis suspension (2 × 105 trophozoites/mL) was previously added onto the mucosa. No alterations were visualized in the stratified squamous non-keratinized epithelium of the porcine vaginal mucosa after contact with the extract. Overall, these results suggest that the P. balansae coumarin-rich extract may have potential as a treatment for trichomoniasis.

Prevalence of Trichomonas Vaginalis and its Correlation with Socio-demographic Variables in Pregnant Women in Al-Diwaniya,Iraq

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Shiren Ali Al Hamzawi
Keyword(s):  
Pregnant Women ◽  
Rural Areas ◽  
Trichomonas Vaginalis ◽  
Cross Sectional Study ◽  
Demographic Variables ◽  
Transmitted Infection ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Vaginal Swabs ◽  
Low Education

Estimates of Trichomonas vaginalis prevalence in pregnant women are variable with few studies in Iraq.T. vaginalis is a worldwide prevalent sexually transmitted infection,but fortunately,it is very treatable. Researchers believed that pregnancy is one of the effective factors for T. vaginalis infection in women.A cross-sectional study performed in Obstetrics and Gynecology Department at Maternity and Children Teaching Hospital in Al-Diwaniya city on two hundred female pregnant patients between the ages of 16-45 years. These females had no intercourse for 2–3 days,not using drugs (antibiotics,antiprotozoal or steroids) for the last 15 days. Vaginal discharges of any type with or without itching,burning sensation or both were their main complaints. Vaginal swabs were taken from all participating patients for direct wet mount microscopy and culture for the detection of Trichomonas vaginalis infection. The study showed that twelve out of two hundred examined pregnant women (6%) presented with T. vaginalis infection. The infection was more in those with mothers’ age (26-35) years,housewives,low education,higher parity,and of rural residents. Other maternal variables were not significantly associated with T. vaginalis infection. The study showed a prevalence of (6%) of T. vaginalis infection in pregnant female attendees. Infection was more in those with mothers ’age (26-35) years,housewives,low educational level,higher parity,and living in rural areas.

scholarly journals Improved molecular laboratory productivity by consolidation of testing on the new random-access analyzer Alinity m

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin Obermeier ◽  
Monia Pacenti ◽  
Robert Ehret ◽  
Francesco Onelia ◽  
Rory Gunson ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Random Access ◽  
Mycoplasma Genitalium ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
International Multicenter Study ◽  
Laboratory Productivity ◽  
Laboratory Workflow

AbstractObjectivesAutomated molecular analyzers have accelerated diagnosis, allowing earlier intervention and better patient follow-up. A recently developed completely automated molecular analyzer, Alinity™ m (Abbott), offers consolidated, continuous, and random-access testing that may improve molecular laboratory workflow.MethodsAn international, multicenter study compared laboratory workflow metrics across various routine analyzers and Alinity m utilizing assays for human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), high-risk human papillomavirus (HR HPV), and sexually transmitted infection (STI) (Chlamydia trachomatis [CT]/Neisseria gonorrhoeae [NG]/Trichomonas vaginalis [TV]/Mycoplasma genitalium [MG]). Three turnaround times (TATs) were assessed: total TAT (sample arrival to result), sample onboard TAT (sample loading and test starting to result), and processing TAT (sample aspiration to result).ResultsTotal TAT was reduced from days with routine analyzers to hours with Alinity m, independent of requested assays. Sample onboard TATs for standard workflow using routine analyzers ranged from 7 to 32.5 h compared to 2.75–6 h for Alinity m. The mean sample onboard TAT for STAT samples on Alinity m was 2.36 h (±0.19 h). Processing TATs for Alinity m were independent of the combination of assays, with 100% of results reported within 117 min.ConclusionsThe consolidated, continuous, random-access workflow of Alinity m reduces TATs across various assays and is expected to improve both laboratory operational efficiency and patient care.

A Review on Diagnostic Methods for Trichomonas Vaginalis

2021 ◽  
Author(s):  
Fatemeh Rahmani ◽  
Yahya Ehteshaminia ◽  
Hamid Mohammadi ◽  
Seif Ali Mahdavi
Keyword(s):  
Trichomonas Vaginalis ◽  
Pap Smear ◽  
High Sensitivity ◽  
Protozoan Parasite ◽  
Signs And Symptoms ◽  
Diagnostic Methods ◽  
Culture Methods ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Asymptomatic Individuals

Introduction: Trichomoniasis is the most common non-viral sexually transmitted infection in the world, caused by the protozoan parasite Trichomonas vaginalis, which infects the urogenital tract of men and women. Approximately, 250 million new cases of Trichomonas vaginalis Infection are reported worldwide each year. Trichomoniasis is also considered an important HIV co-infection. The infection is often asymptomatic but can be accompanied by symptoms such as severe inflammation, itching and irritation, foamy discharge, and malodorous smell mucus, but the signs and symptoms of the disease are not sufficient for specific diagnosis. Material and Methods: In this study, the websites of PubMed, Google Scholar, SID, and Margiran were searched and related articles were reviewed. Results: Only screening and the use of highly sensitive and specific diagnostic methods can identify asymptomatic individuals. Today, the most common way to diagnose the infection is to use wet slide, Pap smear and culture methods that do not have high sensitivity and specificity. Also, due to the increase in infection and its complications, finding an efficient, rapid, and easy test to detect the parasite and differentiate Trichomoniasis vaginitis from other sexually transmitted diseases is considered important and necessary. Conclusion: Nowadays, there are several diagnostic methods that differentiate trichomoniasis infection from other sexually transmitted infections with high accuracy and sensitivity. Of course, existing diagnostic methods mostly use women's urine and vaginal samples for diagnosis, and methods that specifically diagnose the infection in men are more limited.

scholarly journals Medicinal Plants with Anti-Trichomonas vaginalis Activity in Iran: A Systematic Review

2019 ◽  
Author(s):  
Hajar ZIAEI HEZARJARIBI ◽  
Najmeh NADEALI ◽  
Mahdi FAKHAR ◽  
Masoud SOOSARAEI
Keyword(s):  
Systematic Review ◽  
Medicinal Plants ◽  
Trichomonas Vaginalis ◽  
Scientific Information ◽  
Medicinal Herbs ◽  
In Vivo Studies ◽  
Eligibility Criteria ◽  
Sexually Transmitted

Background: Trichomoniasis, due to Trichomonas vaginalis, is one of the most common sexually transmitted parasitic diseases in the world such as Iran. This systematic review aimed to explore the studies evaluating the medicinal herbs with anti- T. vaginalis activity which used in Iran. Methods: Articles published in 4 Persian and 4 English databases were obtained between 2000 and 2015 including Google Scholar, PubMed, Science Direct, Scopus, Magiran, Barakatkns (formerly IranMedex), Elm net, and SID (Scientific Information Database). Studies out of Iran, studies on animal models and articles on other parasite species than T. vaginalis were excluded from this review. Results: Twenty-one articles including in vitro experiments, met our eligibility criteria. Thoroughly, 26 types of plants were examined against T. vaginalis. Medicinal herbs such as Artemisia, Zataria multiflora, and Lavandula angustifolia are remarkably effective on T. vaginalis. As such, use of other parts of these plants in different concentrations and timelines is recommended for future in vivo studies. Conclusion: The present systematic review provides comprehensive and useful information about Iranian medicinal plants with anti-T. vaginalis activity, which would be examined in the future experimental and clinical trials and herbal combination therapy.

scholarly journals Therapeutical aspect of trichomoniasis

2003 ◽  
Vol 131 (3-4) ◽  
pp. 156-162 ◽  
Author(s):  
Jelica Vukicevic ◽  
Jasmina Jankicevic
Keyword(s):  
Trichomonas Vaginalis ◽  
Communicable Disease ◽  
Repeated Administration ◽  
Transmitted Infection ◽  
Microbiological Test ◽  
Clinical Forms ◽  
Short Period ◽  
Significant Difference

Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole) according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center) [19]. The resistance of Trichomonas vaginalis (TV) strains to metronidazole (MND) was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001) 612 patients (244 females and 368 males) suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects). Trichomonas infection was found in 90 (36.88 %) out of 244 tested females and in 126 (32.34 %) of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases). The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05). The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three phases proceeding in succession, in so far TV had not been eliminated by previous one. The number of cured patients, according to therapeutical phases, was shown in Table 4. Three patients (1.39 %, 2 males and 1 female) were not cured in spite of all three completed phases of therapeutical protocol. In all three cases, TV was eliminated by MND application in dose of 3 g/daily, during two days. The failure of minute MND treatment was analyzed in relation to clinical forms of the infection (manifested or asymptomatic), as well as in relation to types of infection (single- or associated infection). The incidence of refractory trichomoniasis treated by a single metronidazole dose of 2 g was significantly higher in the group of patients with polyinfection (c2=18.270 p<0.01). There was no significant difference of resistance to a single MND dose between the groups with manifested and asymptomatic trichomoniasis (c2=0.321; p<0.01). The prevalence of TV in vaginal and urethral smears indicates the significant incidence of trichomoniasis in STD. TV was more frequently isolated in patients with clinically manifested infection. TV susceptibility to MND was tested in vitro in aerobic and anaerobic conditions. The resistance of strains under in vitro conditions did not correlate with refractory feature of trichomoniasis to MND application [7 17, 18]. The success of trichomoniasis treatment depends upon multiple factors, including: a) TV susceptibility to drug, b) intravaginal redox potential, c) drug concentration in situ, d) associated microorganisms that may modify the amount of the drug available in situ [7, 18, 21]. The results of our investigation argue for the latter item, verifying that TV resistance to MND is higher in patients with polyinfection in relation to those with monoinfection (significant difference, c2=18.270; p<0.01). Repeated administration of low metronidazole doses may prolong the therapy of trichomonas infections, while application of high doses (over 3 g/day) may result in undesired complications. Given the well-known fact that repeated sublethal doses induce the resistance, would it be more beneficial to begin with slightly higher metronidazole dose (3 g/day) during short period of time (3-5 days)? This will be the subject of our further investigation.

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