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1.
Discov Med ; 36(184): 959-970, 2024 May.
Article in English | MEDLINE | ID: mdl-38798255

ABSTRACT

BACKGROUND: Infertility is a worldwide medical issue in which infection is recognized to play a major role. Pathogens trigger various mechanisms that impact fertility, either directly by affecting the physiological indices of semen or indirectly by disrupting the process of spermatogenesis. In the current work, the effect of in-vitro cultivation of Escherichia coli (E. coli), Candida non-albicans (C. non-albicans), and Trichomonas vaginalis (T. vaginalis) (as the most frequently reported sexually transmitted infections) was assessed on the physiological functions of the spermatozoa and the chemical characteristics of the seminal fluid. METHOD: The semen samples were exposed to cultures of E. coli, C. non-albicans, and T. vaginalis. The study analyzed the changes in motility, agglutination, viability, DNA fragmentation index (DFI%), seminal pH, and biochemical parameters at 1/2, 1, 1.5, 2, 2.5, 3.5 and 4 hours. RESULTS: Incubation of the semen samples with E. coli resulted in a progressive increase in agglutination, pH, and nitrite. The seminal glucose and the sperm motility, on the other hand, were reduced. The sperm vitality and seminal protein remained unaffected. C. non-albicans induced three forms of agglutination (head-to-head, tail-to-tail, and head-to-tail), lowered pH values and decreased the sperm motility, but did not alter the seminal protein, glucose, nitrite, nor the spermatozoa viability at the different tested time intervals. T. vaginalis resulted in increased seminal protein, and reduced glucose, pH, and motility. It also induced minimal agglutination and caused unchanged nitrite and sperm viability. The DFI% was increased in all pathogens with the C. non-albicans showing the highest DNA fragmentation index. CONCLUSION: Urogenital infection with E. coli, C. non-albicans, or T. vaginalis is assumed to affect the quality of semen through DNA fragmentation, agglutination and altered seminal chemical microenvironment.


Subject(s)
Escherichia coli , Semen , Sperm Motility , Trichomonas vaginalis , Trichomonas vaginalis/physiology , Male , Humans , Semen/microbiology , Sperm Motility/drug effects , Candida/physiology , Spermatozoa/microbiology , DNA Fragmentation , Hydrogen-Ion Concentration
2.
New Microbiol ; 47(1): 103-106, 2024 May.
Article in English | MEDLINE | ID: mdl-38700890

ABSTRACT

Trichomonas vaginalis and Mycoplasma hominis, two microorganisms causing infections of the urogenital tract, are closely associated in that they establish an endosymbiosis relationship, the only case among human pathogens. As a result, the presence of one microorganism may be considered a sign that the other is present as well. Identification of the two pathogens in clinical samples is based on cultivation techniques on specific media, even though in recent years, new sensitive and rapid molecular techniques have become. Here, we demonstrate that the concomitant presence of T.vaginalis in urogenital swabs may lead to a delay in the identification of M.hominis, and thus to an underestimation of bacterial infections when cultural techniques are used.


Subject(s)
Mycoplasma Infections , Mycoplasma hominis , Trichomonas vaginalis , Mycoplasma hominis/isolation & purification , Mycoplasma hominis/genetics , Trichomonas vaginalis/isolation & purification , Trichomonas vaginalis/genetics , Humans , Mycoplasma Infections/microbiology , Female , Trichomonas Vaginitis/microbiology , Trichomonas Vaginitis/parasitology , Trichomonas Vaginitis/diagnosis , Male , Sensitivity and Specificity , Urogenital System/microbiology , Urogenital System/parasitology , Adult
3.
Biosensors (Basel) ; 14(5)2024 May 20.
Article in English | MEDLINE | ID: mdl-38785734

ABSTRACT

Sexually transmitted diseases (STDs) are a global concern because approximately 1 million new cases emerge daily. Most STDs are curable, but if left untreated, they can cause severe long-term health implications, including infertility and even death. Therefore, a test enabling rapid and accurate screening and genotyping of STD pathogens is highly awaited. Herein, we present the development of the DNA-based 6STD Genotyping 9G Membrane test, a lateral flow strip membrane assay, for the detection and genotyping of six STD pathogens, including Trichomonas vaginalis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Mycoplasma genitalium. Here, we developed a multiplex PCR primer set that allows PCR amplification of genomic materials for these six STD pathogens. We also developed the six ssDNA probes that allow highly efficient detection of the six STD pathogens. The 6STD Genotyping 9G Membrane test lets us obtain the final detection and genotyping results in less than 30 m after PCR at 25 °C. The accuracy of the 6STD Genotyping 9G membrane test in STD genotyping was confirmed by its 100% concordance with the sequencing results of 120 clinical samples. Therefore, the 6STD Genotyping 9G Membrane test emerges as a promising diagnostic tool for precise STD genotyping, facilitating informed decision-making in clinical practice.


Subject(s)
Chlamydia trachomatis , Genotype , Neisseria gonorrhoeae , Sexually Transmitted Diseases , Humans , Chlamydia trachomatis/genetics , Chlamydia trachomatis/isolation & purification , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Sexually Transmitted Diseases/microbiology , Sexually Transmitted Diseases/diagnosis , Trichomonas vaginalis/genetics , Trichomonas vaginalis/isolation & purification , Genotyping Techniques , Mycoplasma hominis/isolation & purification , Mycoplasma hominis/genetics , Ureaplasma urealyticum/genetics , Ureaplasma urealyticum/isolation & purification , DNA , Mycoplasma genitalium/genetics , Mycoplasma genitalium/isolation & purification , Biosensing Techniques , DNA, Bacterial/analysis , Multiplex Polymerase Chain Reaction/methods
4.
West J Emerg Med ; 25(3): 358-367, 2024 May.
Article in English | MEDLINE | ID: mdl-38801042

ABSTRACT

Introduction: Bacterial urinary tract infections (UTI) and some sexually transmitted infections (STI) can have overlapping signs and symptoms or nonspecific findings, such as pyuria on urinalysis. Furthermore, results from the urine culture and the nucleic acid amplification test for an STI may not be available during the clinical encounter. We sought to determine whether gonorrhea, chlamydia, and trichomoniasis are associated with bacteriuria, information that might aid in the differentiation of STIs and UTIs. Methods: We used multinomial logistic regression to analyze 9,650 encounters of female patients who were aged ≥18 years and who underwent testing for STIs. The ED encounters took place from April 18, 2014-March 7, 2017. We used a multivariable regression analysis to account for patient demographics, urinalysis findings, vaginal wet-mount results, and positive or negative (or no) findings from the urine culture and testing for Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis. Results: In multivariable analysis, infection with T vaginalis, N gonorrhoeae, or C trachomatis was not associated with having a urine culture yielding 10,000 or more colony-forming units per mililiter (CFU/mL) of bacteria compared with a urine culture yielding less than 10,000 CFU/mL or no urine culture obtained. The diagnosis of a UTI in the ED was not associated with having a urine culture yielding 10,000 or more CFU/mL compared with a urine culture yielding less than 10,000 CFU/mL. Conclusion: After adjusting for covariates, no association was observed between urine culture results and testing positive for trichomoniasis, gonorrhea, or chlamydia. Our results suggest that having a concurrent STI and bacterial UTI is unlikely.


Subject(s)
Gonorrhea , Sexually Transmitted Diseases , Urinalysis , Urinary Tract Infections , Humans , Female , Adult , Urinary Tract Infections/diagnosis , Urinary Tract Infections/microbiology , Urinary Tract Infections/urine , Sexually Transmitted Diseases/urine , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/microbiology , Gonorrhea/diagnosis , Gonorrhea/urine , Urinalysis/methods , Chlamydia Infections/urine , Chlamydia Infections/diagnosis , Middle Aged , Chlamydia trachomatis/isolation & purification , Emergency Service, Hospital , Trichomonas vaginalis/isolation & purification , Bacteriuria/diagnosis , Bacteriuria/urine , Bacteriuria/microbiology , Young Adult , Neisseria gonorrhoeae/isolation & purification , Urine/microbiology , Retrospective Studies , Adolescent , Trichomonas Infections/diagnosis , Trichomonas Infections/urine
5.
Parasit Vectors ; 17(1): 165, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38556882

ABSTRACT

BACKGROUND: Trichomonas vaginalis is the most common nonviral sexually transmitted disease (STI) worldwide. Vaccination is generally considered to be one of the most effective methods of preventing infectious diseases. Using AP65, AP33 and α-actinin proteins, this research aims to develop a protein vaccine against Trichomonas vaginalis. METHODS: Based on the B-cell and T-cell epitope prediction servers, the most antigenic epitopes were selected, and with the necessary evaluations, epitope-rich domains of three proteins, AP65, AP33, and α-actinin, were selected and linked. Subsequently, the ability of the vaccine to interact with toll-like receptors 2 and 4 (TLR2 and TLR4) was assessed. The stability of the interactions was also studied by molecular dynamics for a duration of 100 nanoseconds. RESULTS: The designed protein consists of 780 amino acids with a molecular weight of 85247.31 daltons. The results of the interaction of the vaccine candidate with TLR2 and TLR4 of the immune system also showed that there are strong interactions between the vaccine candidate protein with TLR2 (-890.7 kcal mol-1) and TLR4 (-967.3 kcal mol-1). All parameters studied to evaluate the stability of the protein structure and the protein-TLR2 and protein-TLR4 complexes showed that the structure of the vaccine candidate protein is stable alone and in complex with the immune system receptors. Investigation of the ability of the designed protein to induce an immune response using the C-ImmSim web server also showed that the designed protein is capable of stimulating B- and T-cell lymphocytes to produce the necessary cytokines and antibodies against Trichomonas vaginalis. CONCLUSIONS: Overall, our vaccine may have potential protection against Trichomonas vaginalis. However, for experimental in vivo and in vitro studies, it may be a good vaccine candidate.


Subject(s)
Parasites , Trichomonas vaginalis , Vaccines , Animals , Trichomonas vaginalis/metabolism , Actinin/metabolism , Toll-Like Receptor 2/metabolism , Protozoan Proteins/metabolism , Immunoinformatics , Toll-Like Receptor 4/metabolism , Vaccines/metabolism , Epitopes, T-Lymphocyte , Molecular Docking Simulation
6.
BMJ Open ; 14(4): e079497, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589266

ABSTRACT

OBJECTIVES: We assessed associations between intravaginal practices (IVPs) and the incidence of sexually transmitted infections (STIs) and bacterial vaginosis (BV) among women using the dapivirine vaginal ring (DVR) or placebo vaginal ring in southwestern Uganda. METHODS: This was a retrospective secondary analysis of data collected from women at risk of HIV infection recruited into the Ring Study. The latter evaluated the safety and efficacy of the DVR between 2013 and 2016. At baseline, a behavioural questionnaire was administered to obtain information on sexual activity and IVP (exposure) defined as; insertion inside the vagina of any items aimed at cleaning the vagina for any reason before, during or after sex other than practices to manage menses. Each participant self-inserted the DVR/placebo and replaced it every 4 weeks for 2 years. Outcomes were diagnosis of STIs, that is, Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis (TV), HIV and BV. The incidence rate of STI/BV was estimated, overall, by IVP and trial arm in single-event-per-participant and multiple-event-per-participant analyses. RESULTS: Of the 197 women enrolled, 66 (33.5%) were <25 years of age. Overall, 93 (47.2%) practised at least one form of IVP. During the follow-up, 172 (87.3%) women were diagnosed with an STI/BV at least once. The majority had TV (73.6%, n=145). Overall rate of STI/BV was 51.9/100 person-years, 95% CI 44.7 to 60.3 (IVP: yes, 51.0 (40.8-63.8) vs no, 52.6 (43.0-64.4)). IVPs were not statistically significantly associated with rate of individual STIs/BV. Similar results were observed when the analyses were conducted separately for each trial arm. CONCLUSIONS: IVP was not associated with risk of STIs/BV in the Ring Study. TRIAL REGISTRATION NUMBER: NCT01539226.


Subject(s)
Contraceptive Devices, Female , HIV Infections , Pyrimidines , Sexually Transmitted Diseases , Trichomonas vaginalis , Vaginosis, Bacterial , Female , Humans , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/complications , Incidence , Retrospective Studies , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Sexually Transmitted Diseases/complications , Uganda/epidemiology , Vaginosis, Bacterial/epidemiology , Young Adult , Adult
7.
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
8.
J Med Microbiol ; 73(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38591530

ABSTRACT

Sexually transmitted infections (STI) are a public health problem. Real-time PCR assays are the most sensitive test for screening and diagnosis of these infections. The aim of this study was to evaluate a new CT/NG/TV/MG Real-Time PCR (RT-PCR) kit (Vircell) for the detection of Chamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis for the diagnosis of sexual transmitted infections using the Allplex STI Essential Assay (Seegene) as the reference's method. A total of 497 samples from different anatomical sites (endocervical, urethral, rectal, pharyngeal and urine) were analysed from October 2022 to February 2023. A total of 108 (21.73 %) and 106 (21.33 %) positive samples were found for any of the assays used. The most commonly detected pathogen was N. gonorrhoeae (52 samples; 10.46 %), and the least commonly detected was T. vaginalis (three samples; 0.60 %). The anatomical site with the highest prevalence of micro-organisms was a non-urogenital site, the pharynx (26 positive samples; 5.23 %). Using the Allplex STI Essential Assay (Seegene) as the reference method, the diagnosis performance showed that the average specificity of CT/NG/TV/MG RT-PCR Kit (Vircell) was 99.84 % and the sensitivity was 99.53 %. The overall concordance was k=0.98 (CI95 %; 0.96-1). In conclusion, the CT/NG/TV/MG RT-PCR Kit (Vircell) assay shows a good sensitivity and specificity and constitutes a promising and additional alternative to routine procedures for distinct types of clinical specimen in diagnosis STI.


Subject(s)
Chlamydia Infections , Gonorrhea , Mycoplasma Infections , Mycoplasma genitalium , Sexually Transmitted Diseases , Trichomonas vaginalis , Humans , Real-Time Polymerase Chain Reaction , Chlamydia trachomatis/genetics , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , Trichomonas vaginalis/genetics , Neisseria gonorrhoeae/genetics , Mycoplasma genitalium/genetics , Mycoplasma Infections/diagnosis , Mycoplasma Infections/epidemiology , Tomography, X-Ray Computed , Chlamydia Infections/diagnosis , Gonorrhea/diagnosis , Gonorrhea/epidemiology
9.
Front Cell Infect Microbiol ; 14: 1330844, 2024.
Article in English | MEDLINE | ID: mdl-38544527

ABSTRACT

Human papillomavirus (HPV) is a sexually transmitted virus, which infects approximately 80% of all men and women at some time in their lives. Usually, the infection is resolved successfully by the body's immune system. Persistent infection with high-risk HPV (hrHPV) is necessary but not sufficient for cervical cancer development, and additional factors, such as the vaginal microbiome (vaginome), are thought to be involved. The aim of this study is to investigate whether either vaginal dysbiosis (imbalance in vaginal bacterial composition) or sexually transmitted pathogens, e.g., Chlamydia trachomatis (CT), are possible cofactors for hrHPV infection and HPV-induced cervical dysplasia in asymptomatic women attending the Dutch Cervical Cancer Screening Program. In this study, 492 hrHPV-positive and 500 hrHPV-negative cervical smears from women attending the Screening Program were included. Age and cytology were known for the hrHPV-positive samples. All cervical smears were diluted in Aptima® specimen transfer medium and tested with Aptima® transcription-mediated amplification assays targeting CT, Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), Candida spp. (CS), C. glabrata (CG), Trichomonas vaginalis (TV), and bacterial vaginosis (BV). The prevalences of CT, NG, MG, CS, CG, TV, and BV in this cohort were found to be 1.9%, 0.0%, 1.7%, 5.4%, 1.4%, 0.1%, and 27.2%, respectively. When comparing HPV groups, it was found that CT, MG, and BV had a significantly higher prevalence in hrHPV-positive smears as compared with hrHPV-negative samples (for all p < 0.001). No significant differences were found when comparing different age groups and cytology outcomes. In conclusion, vaginal dysbiosis seems associated with hrHPV infection in women attending the Dutch Cervical Cancer Screening Program.


Subject(s)
Papillomavirus Infections , Trichomonas vaginalis , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Early Detection of Cancer , Dysbiosis/diagnosis , Vaginal Smears , Neisseria gonorrhoeae , Chlamydia trachomatis , Mass Screening
10.
Int J Parasitol ; 54(6): 257-266, 2024 May.
Article in English | MEDLINE | ID: mdl-38452964

ABSTRACT

Trichomonas vaginalis is a medically important protozoan parasite, and a deep-branching, evolutionarily divergent unicellular eukaryote that has conserved several key features of eukaryotic gene expression. Trichomonas vaginalis possesses a metazoan/plant-like capping apparatus, mRNAs with a cap 1 structure and spliceosomes containing the five small nuclear RNAs (snRNAs). However, in contrast to metazoan and plant snRNAs, the structurally conserved T. vaginalis snRNAs were initially identified as lacking the canonical guanosine cap nucleotide. To explain this unusual condition, we sought to investigate transcriptional and processing features of the spliceosomal snRNAs in this protist. Here, we show that T. vaginalis spliceosomal snRNA genes mostly lack typical eukaryotic promoters. In contrast to other eukaryotes, the putative TATA box in the T. vaginalis U6 snRNA gene was found to be dispensable for transcription or RNA polymerase selectivity. Moreover, U6 transcription in T. vaginalis was virtually insensitive to tagetitoxin compared with other cellular transcripts produced by the same RNA polymerase III. Most important and unexpected, snRNA transcription in T. vaginalis appears to bypass capping as we show that these transcripts retain their original 5'-triphosphate groups. In conclusion, transcription and processing of spliceosomal snRNAs in T. vaginalis deviate considerably from the conventional rules of other eukaryotes.


Subject(s)
RNA, Small Nuclear , Spliceosomes , Transcription, Genetic , Trichomonas vaginalis , RNA, Small Nuclear/genetics , RNA, Small Nuclear/metabolism , Trichomonas vaginalis/genetics , Trichomonas vaginalis/metabolism , Spliceosomes/metabolism , Spliceosomes/genetics , RNA Processing, Post-Transcriptional , RNA, Protozoan/metabolism , RNA, Protozoan/genetics , Animals
12.
Turkiye Parazitol Derg ; 48(1): 21-26, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38449363

ABSTRACT

Objective: The aim of the current research is to evaluate the antiparasite effects of compounds isolated from marine ascidian tunicates on Trichomonas vaginalis. Methods: Ascidian tunicates after collection were cut into small pieces, freeze-dried, and powdered. The resulting material was subjected to extraction in double-distilled water, ethanol, n-hexane, and dichloromethane. To fractionate the extracts and identify the most bioactive compound, silica gel column chromatography and GC-M/S analysis were used. Results: Fraction 18 of silica gel column chromatography of ethanol extract was the most effective against T. vaginalis. The respective IC50, CC50, and SI values for fraction 18 were 28.62 µg/mL, ˃800 µg/mL, and ˃27.95. GC-M/S analysis of this fraction identified a major phenolic compound (2, 4-bis (1, 1-dimethyl ethyl), whose toxicity against vero cells was only 10.15%. Conclusion: The ethanolic fraction containing phenol-2,4-bis (1,1-dimethylethyl), which has a potent lethality effect on T. vaginalis, may be considered as an antiparasite drug candidate.


Subject(s)
Trichomonas vaginalis , Urochordata , Chlorocebus aethiops , Animals , Iran , Silica Gel , Vero Cells , Antiparasitic Agents , Ethanol , Phenols
13.
BMC Infect Dis ; 24(Suppl 1): 277, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438953

ABSTRACT

BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.


Subject(s)
Gonorrhea , Trichomonas vaginalis , Female , Humans , Trichomonas vaginalis/genetics , Chlamydia trachomatis/genetics , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Guatemala/epidemiology , Morocco/epidemiology , South Africa/epidemiology , Neisseria gonorrhoeae/genetics , Australia , Point-of-Care Testing
14.
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
15.
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
16.
Parasite Immunol ; 46(2): e13025, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38372623

ABSTRACT

Trichomonas vaginalis (Tv) is a parasite that causes trichomoniasis, a prevalent sexually-transmitted infection. Neutrophils are found at the site of infection, and can rapidly kill the parasite in vitro, using trogocytosis. However, the specific molecular players in neutrophil killing of Tv are unknown. Here, we show that complement proteins play a role in Tv killing by human neutrophil-like cells (NLCs). Using CRISPR/Cas9, we generated NLCs deficient in each of three complement receptors (CRs) known to be expressed on human neutrophils: CR1, CR3, and CR4. Using in vitro trogocytosis assays, we found that CR3, but not CR1 or CR4 is required for maximum trogocytosis of the parasite by NLCs, with NLCs lacking CR3 demonstrating ~40% reduction in trogocytosis, on average. We also observed a reduction in NLC killing of Tv in CR3 knockout, but not CR1 or CR4 knockout NLCs. On average, NLCs lacking CR3 had ~50% reduction in killing activity. We also used a parallel approach of pre-incubating NLCs with blocking antibodies against CR3, which similarly reduced NLC killing of parasites. These data support a model in which Tv is opsonized by the complement protein iC3b, and bound by neutrophil CR3 receptor, to facilitate trogocytic killing of the parasite.


Subject(s)
Parasites , Trichomonas vaginalis , Humans , Animals , Macrophage-1 Antigen , Trichomonas vaginalis/genetics , Neutrophils , CD11b Antigen
17.
Sex Transm Dis ; 51(5): 325-330, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38301630

ABSTRACT

BACKGROUND: Adolescents and young adults (AYAs) face significant barriers to screening, testing, and treatment of sexually transmitted infections (STIs). Expedited partner therapy (EPT) streamlines partner treatment of STIs, but use among adolescents is low. We aimed to increase EPT offering and provision at 2 adolescent medicine clinics (AMCs) and the emergency department (ED) in an urban children's hospital. We addressed barriers at provider, pharmacy, and patient levels. We compared EPT offering and provision for chlamydia ( Chlamydia trachomatis [CT]) and trichomonas ( Trichomonas vaginalis [TV]) infection at baseline and across 2 intervention cycles. METHODS: Baseline data were collected from July 2019 to March 2020 and our intervention time frame spanned from April 2020 to October 2021. Laboratory codes identified patients with CT or TV infections. Cycle 1 allowed providers to order EPT within a patient's chart. The second cycle targeted education and standardization for STI/EPT notification and counseling. During this cycle, notification of ED patients was centralized to the AMC nurses. RESULTS: A total of 747 CT and TV cases were identified. In the AMC, EPT offering increased from 77.3% to 87.7% ( P = 0.01). Expedited partner therapy provision increased from 32.3% to 69.9% ( P < 0.001). Expedited partner therapy offering for ED patients increased by 82.3%. Retesting rates remained consistent, with a significant drop in reinfection rates ( P = 0.003) within patients seen in the AMC. CONCLUSIONS: This quality improvement initiative successfully increased EPT offering and provision among the cases identified. Future cycles may include longer-term follow-up to confirm partner treatment and testing per guidelines.


Subject(s)
Chlamydia Infections , Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas vaginalis , Child , Humans , Young Adult , Adolescent , Chlamydia Infections/diagnosis , Chlamydia Infections/drug therapy , Chlamydia Infections/epidemiology , Quality Improvement , Sexual Partners/psychology , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/epidemiology , Chlamydia trachomatis , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology , Contact Tracing
18.
Sex Transm Dis ; 51(5): 374-379, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38346419

ABSTRACT

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.


Subject(s)
Trichomonas Infections , Trichomonas vaginalis , Vitamin D/analogs & derivatives , Adult , Humans , United States/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Trichomonas Infections/epidemiology
19.
BMC Infect Dis ; 24(Suppl 1): 203, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38418947

ABSTRACT

BACKGROUND: Sexually transmitted infections caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) remain significant global health problems. The World Health Organization (WHO) has recently conducted a multi-faceted, multi-country validation study (ProSPeRo), which included an evaluation of the Xpert CT/NG and Xpert TV assays on the GeneXpert system (Cepheid, Sunnyvale, Ca., USA) in clinic-based settings across eight countries. To support the study, a training and quality management system was implemented and evaluated. METHODS: A comprehensive training program for the study was developed. Quality control (QC) and external quality assessment (EQA) samples were provided by an accredited quality assurance provider. QC testing was conducted at 14 point-of-care testing (POCT) clinics, while EQA samples were tested by the POCT sites and a reference laboratory supporting each clinic. RESULTS: For QC testing, concordance with the expected results for CT and NG was > 99% and rates of unsuccessful tests were < 4%. For TV testing, concordance was similar (97%), but rates of unsuccessful tests were high (18%), particularly in the 'TV negative' sample. For EQA testing initially conducted in 2018, concordance was 100% for CT and NG, and 90% for TV for the reference laboratory group (which used non-GeneXpert systems). Concordance for the POCT group was also high (> 94%) for all analytes, but this cohort (which used GeneXpert systems) exhibited a high rate of unsuccessful TV tests. All but one of these unsuccessful tests was subcategorised as 'invalid'. CONCLUSIONS: The high level of concordance for QC and EQA testing confirm that the trained operators at the POC clinical sites were competent to conduct POC testing and that the training and quality systems implemented for the ProSPeRo study were effective. The quality materials used were satisfactory for CT and NG but exhibited poor performance for TV testing on the GeneXpert system. The WHO should continue to work with industry and EQA providers to provide improved materials that are reliable, stable and cost effective for quality management, as it seeks to rollout molecular-based STI POCT in non-laboratory-based settings. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee.


Subject(s)
Chlamydia Infections , Gonorrhea , Sexually Transmitted Diseases , Trichomonas vaginalis , Humans , Trichomonas vaginalis/genetics , Neisseria gonorrhoeae/genetics , Chlamydia trachomatis/genetics , Gonorrhea/diagnosis , Chlamydia Infections/diagnosis , Sexually Transmitted Diseases/diagnosis , Point-of-Care Testing
20.
Sex Transm Infect ; 100(3): 133-137, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38360847

ABSTRACT

BACKGROUND: Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach. OBJECTIVES: To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed. METHODS: Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), M. hominis (MH), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma parvum (UP), U. urealyticum (UU) and another kit to detect GU: cytomegalovirus (CMV), Haemophilus ducreyi (HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV), Treponema pallidum (TP) and varicella-zoster virus (VZV). RESULTS: In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected. CONCLUSION: This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.


Subject(s)
Coinfection , Cytomegalovirus Infections , Herpesvirus 1, Human , Sexually Transmitted Diseases , Trichomonas vaginalis , Male , Humans , Ulcer/complications , Brazil/epidemiology , Coinfection/epidemiology , Coinfection/complications , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/etiology , Chlamydia trachomatis/genetics , Herpesvirus 2, Human , Treponema pallidum , Neisseria gonorrhoeae/genetics , Genitalia , Cytomegalovirus Infections/complications
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