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1.
Lancet Reg Health West Pac ; 48: 101110, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38952441

ABSTRACT

Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. Interpretation: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. Funding: This work was supported by an Australian National Health and Medical Research Council Partnership Grant (APP1092503), the Australian Government Department of Health, Western Australia and Queensland Departments of Health.

2.
Molecules ; 29(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38893461

ABSTRACT

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.


Subject(s)
Carbamates , Imidazoles , Trichomonas vaginalis , Trichomonas vaginalis/drug effects , Trichomonas vaginalis/genetics , Trichomonas vaginalis/growth & development , Imidazoles/pharmacology , Imidazoles/chemistry , Humans , Carbamates/pharmacology , Carbamates/chemistry , Metronidazole/pharmacology , Metronidazole/chemistry , Gene Expression Regulation/drug effects , Trophozoites/drug effects
3.
Int J STD AIDS ; : 9564624241248674, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709824

ABSTRACT

BACKGROUND: Sexually transmitted infections (STIs) are a major public health concern worldwide. Untreated STIs may have serious sequelae, particularly in pregnant women. The objective of this study was to assess the feasibility and acceptability of screening and treating common STIs in women during pregnancy in Bangladesh. METHODS: Women were enrolled from four maternity clinics/hospitals serving the lower-middle class population in Dhaka, Bangladesh. The participants were interviewed, and vaginal swab samples were collected by clinical staff. Specimens were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and high-risk Human Papilloma Viruses (HPVs) using GeneXpert (Cepheid, Sunnyvale, California). Women were informed of their test results and were provided treatment for curable infections. A test of cure was performed. RESULTS: Out of 1157 pregnant women approached, 1000 (86.4%) participated. Ninety-one percent women learned of their test results on the same day of testing. Out of the 996 valid results, 7 (0.7%) tested positive for Chlamydia trachomatis and 1 (0.1%) for Trichomonas vaginalis. There were no gonorrhoea cases. Out of the 971 women with valid results for high-risk HPVs, 46 (4.7%) tested positive. CONCLUSIONS: Screening women for STIs during antenatal care was highly feasible and well-accepted in Bangladesh. While the prevalence of common curable STIs was very low, hrHPV infection prevalence was moderately high. Our findings support period monitoring of STIs and continued prevention efforts for cervical cancer in Bangladesh.

4.
Int J Mol Sci ; 25(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674152

ABSTRACT

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.


Subject(s)
Benzimidazoles , Trichomonas vaginalis , Trichomonas vaginalis/drug effects , Trichomonas vaginalis/genetics , Trichomonas vaginalis/metabolism , Benzimidazoles/pharmacology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Gene Expression Regulation/drug effects , Humans , Antiprotozoal Agents/pharmacology , Antitrichomonal Agents/pharmacology
6.
Trop Anim Health Prod ; 56(2): 96, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38441747

ABSTRACT

Bovine genital campylobacteriosis, caused by the gram-negative bacteria Campylobacter fetus venerealis, and bovine trichomonosis, caused by the parasite protozoan Tritrichomonas foetus, are venereal diseases that occur with long intercalving periods and abortion. The control of both diseases relies on microbiological testing and culling infected bulls. Vaccination and antibiotic treatment may help in controlling campylobacteriosis but are not recommended for trichomonosis control. Several regions of the world have active control programs for trichomonosis, not campylobacteriosis. In Argentina, the state of La Pampa aims to eradicate trichomonosis and campylobacteriosis by imposing annual diagnostic testing of every bull and slaughtering positive animals. Prior studies indicated a declining trend in the prevalence of campylobacteriosis and trichomonosis in La Pampa. It was also proposed that the prevalence of one disease could be estimated from the prevalence of the other. The purpose of this retrospective analysis of data gathered from 2008 to 2021 was to determine the La Pampa program's efficacy. Descriptive statistics were employed to determine the reason behind the correlation between tricomonosis and campylobacteriosis diagnostic results. The outcomes refute the notion that this program of venereal eradication was a success. Furthermore, an excess of false positives in both diagnoses may have contributed to the correlation between the prevalences of campylobactriosis and trichomonosis. The practice of killing animals without verifying positive results hinders the determination of disease prevalence and results in the death of numerous healthy animals.


Subject(s)
Campylobacter Infections , Cattle Diseases , Tritrichomonas foetus , Female , Pregnancy , Cattle , Animals , Male , Campylobacter Infections/drug therapy , Campylobacter Infections/epidemiology , Campylobacter Infections/prevention & control , Campylobacter Infections/veterinary , Argentina/epidemiology , Retrospective Studies , Genitalia , Cattle Diseases/drug therapy , Cattle Diseases/epidemiology , Cattle Diseases/prevention & control
7.
Bioorg Med Chem ; 102: 117679, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38461555

ABSTRACT

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.


Subject(s)
Antiprotozoal Agents , Nitroimidazoles , Trichomonas Infections , Trichomonas vaginalis , Humans , Nitroimidazoles/pharmacology , Metronidazole/pharmacology , HeLa Cells , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Trichomonas Infections/drug therapy , Pyrazoles/pharmacology , Pyrazoles/therapeutic use
8.
Exp Parasitol ; 259: 108722, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38395187

ABSTRACT

Trichomonas vaginalis is an extracellular flagellate protozoan and the etiological agent of human trichomoniasis, a sexually transmitted infection (STI) with a high incidence. Several reports have shown that this protozoan releases microvesicles into the culture medium, which show high potential in modulating cell-to-cell communication and the host response to infections. However, the biogenesis of these vesicles has not been analyzed in detail. In the present study, high-resolution ion scanning microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze the surface of control cells and cells incubated in the presence of Ca2+ alone or with A 23187 calcium ionophore. Two different strains of T. vaginalis were analyzed. Most control cells displayed relatively smooth surfaces, whereas cells incubated with Ca2+ had many surface projections of variable shape and size (from 40 nm to around 1 µm). Quantitative analyses were performed directly in the scanning electron microscope and showed a significant increase in the number of cells with surface projections after incubation in the presence of calcium. TEM showed that treated cells presented several cytoplasmic multivesicular structures, suggesting membrane fusion and exosomes in the extracellular medium. The amount and size of the released vesicles were quantitatively analyzed using light scattering and TEM on negatively stained samples. The observations show that incubation of both parasite strains in the presence of Ca2+ significantly increased the release of microvesicles into the extracellular medium in a time-dependent process. Sequential incubation in the presence of Ca2+ and the calcium ionophore A23187 increases the presence of vesicles on the parasite surface only at a short incubation time (5 min). Transmission electron microscopy showed that at least part of the vesicles are originated from cytoplasmic multivesicular structures. This information contributes to a better understanding of the biogenesis of extracellular vesicles secreted by T. vaginalis.


Subject(s)
Extracellular Vesicles , Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Female , Humans , Calcium Ionophores , Microscopy, Electron, Transmission , Trichomonas Vaginitis/parasitology
9.
Front Cell Infect Microbiol ; 14: 1289231, 2024.
Article in English | MEDLINE | ID: mdl-38318165

ABSTRACT

Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.


Subject(s)
High-Throughput Nucleotide Sequencing , Trichomonas Infections , Female , Male , Humans , Retrospective Studies , Bronchoalveolar Lavage Fluid , Risk Factors , Metagenomics , Trichomonas Infections/diagnosis , Sensitivity and Specificity
10.
Pathogens ; 13(2)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38392864

ABSTRACT

More than one million curable sexually transmitted infections occur every day. Trichomonas vaginalis is one of the main infections responsible for these epidemiological data; however, the diagnosis of this protozoan is still mainly based on microscopic and culture identification. The commercialization of immunological tests and the development of molecular techniques have improved the sensitivity of classical methods. Nevertheless, the fact that trichomoniasis is a neglected parasitic infection hinders the development of novel techniques and their implementation in routine diagnosis. This review article shows the different methods developed to identify T. vaginalis in population and the difficulties in diagnosing male and asymptomatic patients. The importance of including this parasite in routine gynecological screening, especially in pregnant women, and the importance of considering T. vaginalis as an indicator of high-risk sexual behavior are also discussed.

11.
Int J STD AIDS ; 35(6): 412-417, 2024 May.
Article in English | MEDLINE | ID: mdl-38225875

ABSTRACT

BACKGROUND: The Centers for Disease Control and Prevention recommends universal retesting within 3 months after treatment of Trichomonas vaginalis infection given high rates of persistent infection or reinfection, or if this is not possible, within 12 months following treatment. Data is lacking on how often this is actually done. METHODS: We analyzed the demographic and clinical characteristics, rate of return for the recommended retesting, concordance between wet prep and nucleic acid amplification testing, and percent positivity for T. vaginalis on repeat vaginal specimens at a local public health department in Durham, North Carolina, United States. RESULTS: Of 193 females treated for trichomoniasis between March 1, 2021 - May 31, 2022, 83% were Black or African American and 44% between the ages of 20 and 29 years. Of these individuals, 32% had retesting performed within 3 months and 50% within 365 days after treatment. Females between the ages of 20 and 29 years were more likely to return for retesting than those between the ages of 30 and 39 years. Of those who returned for retesting, 10% were positive on repeat testing. CONCLUSION: In this study, 50% of females diagnosed with trichomoniasis completed retesting within 365 days. Improved scheduling of clients at the time of trichomoniasis treatment and improved identification in our electronic health record of individuals diagnosed with trichomoniasis within the prior year would likely improve retesting rates. Given the high prevalence of trichomoniasis, expanded screening of asymptomatic females in settings where this is feasible may be warranted.


Subject(s)
Trichomonas Infections , Trichomonas vaginalis , Humans , Female , North Carolina/epidemiology , Adult , Trichomonas vaginalis/isolation & purification , Young Adult , Trichomonas Infections/epidemiology , Trichomonas Infections/diagnosis , Trichomonas Vaginitis/diagnosis , Trichomonas Vaginitis/epidemiology , Middle Aged , Prevalence , Nucleic Acid Amplification Techniques , Vagina/parasitology , Adolescent
12.
Vet Res Commun ; 48(2): 865-875, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37968413

ABSTRACT

The protozoan parasite Tritrichomonas foetus (T. foetus) is the causative organism of bovine trichomonosis (also referred to as trichomoniasis), a sexually-transmitted infection that reduces fertility in cattle. Efforts to control trichomonosis on cattle farms are hindered by the discouragement of antibiotic use in agriculture, and the incomplete, short-lived protection conferred by the current vaccines. A more complete mechanistic understanding of what effective immunity to T. foetus entails could enable the development of more robust infection control strategies. While neutrophils, the primary responders to infection, are present in infected tissues and have been shown to kill the parasite in vitro, the mechanism they use for parasite killing has not been established. Here, we show that primary bovine neutrophils isolated from peripheral blood rapidly kill T. foetus in vitro in a dose-dependent manner, and that optimal parasite killing is reduced by inhibitors of trogocytosis. We also use imaging to show that bovine neutrophils surround T. foetus and trogocytose its membrane. These findings are consistent with killing via trogocytosis, a recently described novel neutrophil antimicrobial mechanism.


Subject(s)
Cattle Diseases , Parasites , Protozoan Infections, Animal , Tritrichomonas foetus , Cattle , Animals , Neutrophils , Trogocytosis , Cattle Diseases/parasitology , Protozoan Infections, Animal/parasitology , Protozoan Infections, Animal/prevention & control
13.
BMC Womens Health ; 23(1): 677, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38114988

ABSTRACT

BACKGROUND: Infectious vaginitis is one of the most prevalent conditions affecting women of reproductive age with significant clinical consequences. Bacterial vaginosis (BV), vulvo-vaginal candidiasis (VVC), and trichomoniasis (TV) are the main etiologies. Unfortunately, there is limited data on the prevalence and associated risk factors, especially in sub-saharan Africa. This study, thus, determined the prevalence and risk factors of infectious vaginitis among women seeking reproductive health services at a Marie-stopes health facility in urban areas of Kampala, Uganda. METHODS: A cross-sectional study with 361 participants was conducted from July to October 2021. Data on risk factors and infection were collected via a structured questionnaire and laboratory analysis of vaginal swabs, respectively, with data analysis performed using Stata version 14.0 college station, Texas 77,845 US. RESULTS: The ages of participants ranged from 18 to 49 years, with a mean age of 29.53 years. Overall, 58.45% were infected, of whom 33.24% had VVC, 24.93% had BV, and 0.28% had TV. Bivariate analysis revealed that women with pruritus (COR: 3.057, 95% CI: 1.940-4.819), pregnancy (COR: 4.914, 95% CI: 1.248-19.36), antibiotic use (COR: 1.592, 95% CI: 1.016-2.494), douching (COR: 1.719, 95% CI: 1.079-2.740), and multiple partners (COR: 1.844, 95% CI: 1.079-2.904) were more likely to have VVC, whereas having higher education status (University; Vocational) (COR: 0.325, 95% CI: 0.134-0.890; COR: 0.345, 95% CI: 0.116-0.905) reduced the risk. On the other hand, women with a smelly discharge (COR: 1.796, 95% CI: 1.036-3.110), IUD use (COR: 1.868, 95% CI: 1.039-3.358), and antibiotic use (COR: 1.731, 95% CI: 1.066-2.811) were more likely to have BV. Multivariable analysis identified pruritus (AOR: 2.861, 95% CI: 1.684-4.863) as the only independent predictor for VVC. CONCLUSION: Results indicate a high prevalence of infection among these women; therefore regular screening and treatment is recommended to curb the high rate of infection. More studies on risk factors of infection are recommended.


Subject(s)
Candidiasis, Vulvovaginal , Reproductive Health Services , Trichomonas Vaginitis , Vaginosis, Bacterial , Pregnancy , Female , Humans , Adult , Reproductive Health , Cross-Sectional Studies , Uganda/epidemiology , Trichomonas Vaginitis/epidemiology , Trichomonas Vaginitis/diagnosis , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/diagnosis , Candidiasis, Vulvovaginal/epidemiology , Candidiasis, Vulvovaginal/drug therapy , Prevalence , Health Facilities , Anti-Bacterial Agents/therapeutic use , Pruritus/drug therapy
14.
Cancers (Basel) ; 15(21)2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37958367

ABSTRACT

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case-control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82-2.64; adjusted OR = 1.31, 95% CI 0.67-2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63-3.01; adjusted OR = 1.20, 95% CI 0.46-3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer.

15.
Bioorg Chem ; 141: 106888, 2023 12.
Article in English | MEDLINE | ID: mdl-37839143

ABSTRACT

Trichomonas vaginalis, a flagellated and anaerobic protozoan, is a causative agent of trichomoniasis. This disease is among the world's most common non-viral sexually transmitted infection. A single class drug, nitroimidazoles, is currently available for the trichomoniasis treatment. However, resistant isolates have been identified from unsuccessfully treated patients. Thus, there is a great challenge for a discovery of innovative anti-T. vaginalis agents. As part of our ongoing search for antiprotozoal chalcones, we designed and synthesized a series of 21 phenolic chalcones, which were evaluated against T. vaginalis trophozoites. Structure-activity relationship indicated hydroxyl group plays a role key in antiprotozoal activity. 4'-Hydroxychalcone (4HC) was the most active compound (IC50 = 27.5 µM) and selected for detailed bioassays. In vitro and in vivo evaluations demonstrated 4HC was not toxic against human erythrocytes and Galleria mellonella larvae. Trophozoites of T. vaginalis were treated with 4HC and did not present significant reactive oxygen species (ROS) accumulation. However, compound 4HC was able to increase ROS accumulation in neutrophils coincubated with T. vaginalis. qRT-PCR Experiments indicated that 4HC did not affect the expression of pyruvate:ferredoxin oxidoreductase (PFOR) and ß-tubulin genes. In silico simulations, using purine nucleoside phosphorylase of T. vaginalis (TvPNP), corroborated 4HC as a promising ligand. Compound 4HC was able to establish interactions with residues D21, G20, M180, R28, R87 and T90 through hydrophobic interactions, π-donor hydrogen bond and hydrogen bonds. Altogether, these results open new avenues for phenolic chalcones to combat trichomoniasis, a parasitic neglected infection.


Subject(s)
Antiprotozoal Agents , Chalcones , Trichomonas Infections , Trichomonas vaginalis , Humans , Trichomonas vaginalis/metabolism , Chalcones/metabolism , Reactive Oxygen Species/metabolism , Trichomonas Infections/drug therapy , Trichomonas Infections/parasitology , Antiprotozoal Agents/metabolism , Phenols/metabolism
16.
J Infect Dev Ctries ; 17(8): 1160-1167, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37699101

ABSTRACT

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.


Subject(s)
Trichomonas vaginalis , Uterine Cervical Neoplasms , Animals , Female , Humans , Epithelial Cells , HeLa Cells , Interleukin-1 Receptor-Associated Kinases , NF-kappa B , Toll-Like Receptor 5 , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/parasitology
17.
Pathogens ; 12(9)2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37764891

ABSTRACT

Trichomonas vaginalis is a pathogenic protozoan diffused worldwide capable of infecting the urogenital tract in humans, causing trichomoniasis. One of its most intriguing aspects is the ability to establish a close relationship with endosymbiotic microorganisms: the unique association of T. vaginalis with the bacterium Mycoplasma hominis represents, to date, the only example of an endosymbiosis involving two true human pathogens. Since its discovery, several aspects of the symbiosis between T. vaginalis and M. hominis have been characterized, demonstrating that the presence of the intracellular guest strongly influences the pathogenic characteristics of the protozoon, making it more aggressive towards host cells and capable of stimulating a stronger proinflammatory response. The recent description of a further symbiont of the protozoon, the newly discovered non-cultivable mycoplasma Candidatus Mycoplasma girerdii, makes the picture even more complex. This review provides an overview of the main aspects of this complex microbial consortium, with particular emphasis on its effect on protozoan pathobiology and on the interplays among the symbionts.

18.
Exp Parasitol ; 253: 108601, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37625643

ABSTRACT

Trichomoniasis is a sexually transmitted infection caused by the protozoan Trichomonas vaginalis. Currently, trichomoniasis is treated with the class of nitroimidazoles, namely, metronidazole; however, resistant isolates and strains have been reported. The compounds derived from benzofuroxan are biologically active heterocycles. This study evaluated the in vitro antiparasitic activity of these compounds in trophozoites of T. vaginalis and determined the mean inhibitory concentration (IC50), minimum inhibitory concentration (MIC), mortality curve, and cytotoxicity. The compounds were named EH1, EH2, EH3, and EA2 and tested in various concentrations: 100 to 15 µM (EH1 and EH2); 100 to 5 µM (EH3); and 100 to 25 µM (EA2), respectively. The greatest efficacy was observed in the highest concentrations in 24 h, with inhibition of approximately 100% of trophozoites. Compounds EH2 and EH3 had the lowest MIC: EH2 (35 µM) and EH3 (45 µM), with IC50 of 11.33 µM and 6.83 µM, respectively. Compound EA2 was effective at the highest concentrations. The activity of the compounds in T. vaginalis started in the first hour of incubation with 90% inhibition; after 12 h, inhibition >95% was observed. Compound EH1 showed the lowest activity, with the highest activity between 12 and 24 h after incubation. These results demonstrate that benzofuroxan derivatives are promising compounds for the in vitro treatment of T. vaginalis.


Subject(s)
Nitroimidazoles , Trichomonas Infections , Animals , Antiparasitic Agents , Microbial Sensitivity Tests , Trophozoites
19.
Indian J Sex Transm Dis AIDS ; 44(1): 40-44, 2023.
Article in English | MEDLINE | ID: mdl-37457518

ABSTRACT

Introduction: Trichomoniasis remains one of the most common sexually transmitted infections, which is curable. To prevent complications and transmission, prompt and correct diagnosis is essential to treat Trichomonas vaginalis. The present study was done to evaluate polymerase chain reaction (PCR) with other conventional techniques for the diagnosis of T. vaginalis infection and determine the prevalence of T. vaginalis in women with vaginal discharge based on PCR assay. Methods: Vaginal swabs were collected by the trained health-care professional using FLOQSwabs™ (Copan, Italy) during routine pelvic examinations among 1974 symptomatic females. The wet microscopy, culture, and PCR were performed. Results: The sensitivity of wet mount and culture in comparison to PCR was 60.87% and 56.52%, respectively. The kappa inter-rater agreement of T. vaginalis PCR showed substantial agreement with wet mount microscopy (κ = 0.742) and culture (κ = 0.707). The PCR detected an additional 17 cases that were missed by conventional techniques. Discussion: The study highlights the importance of PCR for T. vaginalis screening among symptomatic females.

20.
Indian J Sex Transm Dis AIDS ; 44(1): 1-5, 2023.
Article in English | MEDLINE | ID: mdl-37457531

ABSTRACT

Background: Vaginal discharge is a common complaint among women attending the sexually transmissible infections (STIs) clinic and is a cause for concern and mental distress. It can be attributed to physiological or pathological causes. This study aims to understand the prevalence of various etiologies of vaginal discharge, which would help frame health policies based on local needs. Objectives: (1) To estimate the prevalence of discharge per vaginum among sexually active women attending the STI clinic at a tertiary care center during a 1-year period, (2) To identify the organisms causing vaginal discharge, (3) To have a clinicoetiological correlation of the cases, and (4) To identify the subspecies of Candida causing vaginal candidiasis. Materials and Methods: A total of 126 patients with vaginal discharge attending the STI clinic at a tertiary care center were included in the study. A detailed clinical history, physical examination of the external genitalia, and vaginal examination were done on each patient. Five swabs were taken from the posterior fornix and lateral vaginal wall for evaluation of the organisms. Results: The mean age of the study population was 31.51 ± 7.9 years. Vulvovaginal candidiasis (VVC) was found to be the most common cause of vaginal discharge, followed by bacterial vaginosis, mucopurulent cervicitis, herpes genitalis, and trichomoniasis. The most common species of Candida was found to be Candida albicans. Conclusion: Even though VVC still remains the major cause, other viral infections like herpes significantly contribute. Vaginal discharge is an important indicator of women's reproductive health and its detailed evaluation helps identify the prevalence of various STIs in the community.

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