Search Results (125)

Chagas disease and trichomoniasis are two neglected parasitic infections (NPIs) in need for new therapies that address both the toxicity and limited bioavailability impacting on the effectiveness of benznidazole (BZ) and nifurtimox, the only drugs available for treating the infection caused by Trypanosoma cruzi, as well as the resistance that Trichomonas vaginalis has developed to 5-nitroimidazoles. Herein, we report the outcomes of the primary screening of a series of eighteen quinoxaline-1,4-di-N-oxides (QdNOs) carried out against both protozoan parasites. Computational approaches revealed that these derivatives have adequate oral bioavailability and do not pose toxicity risks associated with their chemical structures. Meanwhile, biological studies disclosed that compounds 4b and 4m exhibit considerable activity against T. cruzi at the highest concentration tested, showing 4m a trypanocidal profile (IC₅₀ = 23.66 µM) similar to that of BZ (IC₅₀ = 21.66 µM), and a selectivity index (SI) > 5.32. Regarding the activity on T. vaginalis, derivative 4n stands out with an IC₅₀ value of 9.85 µM, showing no cytotoxicity towards mammalian cells. However, their potency decreases when tested over resistant parasites. Alterations in either the hydrogenosomal membrane potential or the production of reactive oxygen species (ROS) were also explored. The findings suggest that the trichomonacidal activity of compound 4n is not mediated by a direct disruption of hydrogenosomal bioenergetics or a pro-oxidant effect. Altogether, these preliminary results support that the QdNO scaffold could be introduced as a proper template for developing novel trypanocidal and trichomonacidal agents. Full article

Sexually transmitted diseases (STDs) continue to represent a substantial burden on public health and society worldwide. With significant implications for social, economic, and public health, STDsare a major global health concern. Despite advances in treatment, the global control of STDs is increasingly threatened by high prevalence of asymptomatic infections, delayed diagnosis and the rapid emergence of antimicrobial resistance (AMR). This emergence includes the value of asymptomatic screeningand the ensuing collateral damage resulting from the overuse of our declining potent antimicrobial resources. This review article critically examines current trends in the epidemiology, clinical significance, and laboratory diagnosis of major sexually transmitted pathogens, including Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus, herpes simplex virus, and emerging sexually transmissible infections. Major emphasis is focused on contemporary diagnostic technologies and strategies, with a major focus on nucleic acid-based and point-of-care testing and their applicability in routine testing. The review also highlights evolving AMR patterns, resistance-guided therapy, and the role of global and national surveillance systems in informing treatment guidelines, with the integration of diagnostic strategies with resistance-guided therapy and surveillance systems. Strengthening diagnostic capacity, antimicrobial stewardship, and integrated surveillance is essential to mitigate resistance, improve patient outcomes, and advance effective STD management in venereology practice. Full article

Trichomonas vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. In these cases, 5-Nitroimidazoles, particularly metronidazole (MTZ), remain the primary treatment option; however, resistance to MTZ has been increasingly reported. This study aimed to evaluate the in vitro activity of D-form synthetic antimicrobial peptides and investigate transcriptional differences associated with MTZ resistance and peptide treatment in T. vaginalis. D-form synthetic peptides (D-TN1, D-TN3, and D-TN6) developed in the R&D Laboratory of Acibadem University were tested against metronidazole-susceptible (T. vaginalis ATCC 30236) and metronidazole-resistant (T. vaginalis ATCC 50143) strains by minimum lethal concentration (MLC) assays. D-TN1 exhibited an MLC of 16 µg/mL in both strains, whereas D-TN3 and D-TN6 exhibited MLC values of 32 µg/mL and 16–32 µg/mL, respectively. Comparative transcriptomic analysis was conducted to investigate transcriptional differences. Differential gene expression analysis identified 3395 genes between the resistant and susceptible isolates and 3060 genes in the D-TN1-treated resistant isolate (FDR < 0.05, |log₂FC| ≥ 1). D-TN1 treatment in the resistant isolate was associated with downregulation of ribosomal and metabolic pathways. If confirmed with further in vivo studies, this new antimicrobial peptide may become a new therapeutic alternative in the treatment of trichomoniasis in the future. Full article

Background: Bacterial vaginosis and vaginal dysbiosis represent major causes of morbidity among women in sub-Saharan Africa, yet data from Madagascar remain scarce. This study aimed to assess the prevalence and determinants of vaginal bacterial infections among women in northern Madagascar and to explore how vaginal microflora composition reflects broader aspects of reproductive health. Methods: A cross-sectional study was conducted in April 2024 among 159 women (15–80 years) attending a rural second-referral clinic in Manerinerina, Ambatoboeny District. Sociodemographic and hygiene data were obtained through structured questionnaires. Vaginal pH was measured in situ, and Gram-stained smears were evaluated using the Nugent scoring system. The presence of Trichomonas vaginalis, Neisseria gonorrhoeae, and Candida spp. was assessed microscopically. Associations were analyzed using Chi-square or Fisher’s exact tests, with p < 0.05 considered significant. Results: Abnormal vaginal flora was observed in 68.6% of women, including 43.4% with BV (Nugent 7–10) and 25.2% with intermediate flora. Elevated vaginal pH correlated strongly with higher Nugent scores (p < 0.01). T. vaginalis and N. gonorrhoeae were detected in 10.7% and 9.4% of women, respectively, and both were significantly associated with dysbiosis (p = 0.02 and p = 0.04). Poor hygiene practices, vaginal douching (79.1% vs. 64.5%; p = 0.04), and unsafe water sources (p = 0.04) were major behavioral and environmental determinants. Conclusions: Vaginal dysbiosis is highly prevalent among women in northern Madagascar and closely linked to modifiable hygiene behaviors and environmental conditions. In resource-limited settings, Gram-stained microscopy and Nugent scoring remain cost-effective tools for surveillance and patient care. Culturally adapted education, improved water access, and integration of low-cost diagnostics are essential for reducing the burden of vaginal infections in rural Madagascar. Full article

Trichomoniasis is the most prevalent non-viral sexually transmitted infection worldwide and is caused by Trichomonas vaginalis. The development of resistance against the standard treatment, metronidazole, highlights the need for alternative therapeutic approaches. The role of innate immune cells is crucial for understanding trichomoniasis; however, the contribution of monocytes remains poorly characterized. We previously reported that the antimicrobial peptides LL-37 and its derivative KR-20 are trichomonacidal. In other systems, LL-37 displays immunomodulatory effects. Nevertheless, whether these peptides modulate monocyte responses in the presence of T. vaginalis remains unknown, which was the aim of this study. U937 monocytes were co-incubated with LL-37 or KR-20 (3 h), with or without parasite. Monocyte metabolic activity, nitric oxide production, and relative expression of innate immune genes were assessed. LL-37 decreased monocyte metabolic activity and upregulated TNF-α expression (10 and 5 μM, respectively) in parasite-challenged monocytes. Meanwhile, KR-20 (2.5–10 μM) preserved metabolic activity, bound microbial components (LPS), reduced parasite-induced nitric oxide production, and downregulated the expression of IL-8, TNF-α, IL-1β, and COX-2 in infected monocytes. This work provides initial evidence that KR-20 modulates innate immune response in monocytes during T. vaginalis infection, suggesting its potential—yet to be fully validated—as an immunomodulatory candidate for trichomoniasis. Full article

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents. Full article

Co-infection by human papillomavirus (HPV) and human immunodeficiency virus (HIV) facilitates cervical carcinogenesis, and additional cofactors such as other sexually transmitted infections (STI) further aggravate this scenario. This study aimed to validate a molecular detection strategy for Chlamydia trachomatis, Trichomonas vaginalis and Neisseria gonorrhoeae and to assess the association of these infections with cervical lesions in HPV-positive women living with HIV in Northeastern Brazil. In total, 155 samples were collected from CRIST/AIDS. After microorganism detection by conventional PCR, a multiplex PCR was standardized and validated. A prevalence of 9.03% was observed for C. trachomatis and 6.45% for T. vaginalis, with 0.64% co-infection. In addition, infection with both STIs showed a prevalence of 0.64%. Among HPV-positive women, high-risk genotypes accounted for 70.9% of cases, with HPV-16 being the most prevalent (35.5%). Overall, 18.2% of women presented cervical lesions, and 13.2% of those with co-detection of C. trachomatis and T. vaginalis were associated with high-grade squamous intraepithelial lesions (HSIL). These findings highlight the clinical relevance of screening for multiple STIs in HPV-positive women living with HIV and support the incorporation of multiplex molecular testing into public health strategies to improve early detection and targeted management. Full article

Trichomoniasis is the most common non-viral sexually transmitted infection in humans, with over 200 million people affected each year. This disease is associated with pre-term birth, low birth weight, and premature membrane rupture. Its causal pathogen, Trichomonas vaginalis (TV), is a prevalent sexually transmitted protozoan parasite that infects the urogenital tract through cytoadherence. TV infection alters TV gene expression and induces host immune responses, while TV-secreted exosomes carry RNA and protein cargoes that mediate extracellular signaling. This review summarizes recent discoveries of molecules that interact with host receptors involved in cytoadherence. We also discuss human innate and adaptive immune responses to TV infection via a variety of inflammatory mediators. Recent research on concurrent or endosymbiont relationships of TV with other urogenital microbes and cancers, is also examined. These studies not only highlight the necessity of understanding host–microbe interactions in TV pathogenesis but also provide a crucial insight into potential therapeutic targets of nitroimidazole-resistant TV strains. Full article

Background/Objectives: Transvaginal ultrasound is one of the basic diagnostic methods used during gynecological examination. Lack of care during such an examination can lead to a risk of dangerous infection for both the patient and medical staff. Therefore, a crucial part of the preparation for the test is its proper disinfection. The aim of this study was to test the effectiveness of ultraviolet (UV-C) disinfection of ultrasound probes used in transvaginal examination for the prevention of infections in patients and healthcare personnel in ambulatory care settings. Methods: The eradication of microorganisms present (as a microbiota or etiological factors of infections) in the female reproductive tract was tested. They were the following: Staphylococcus aureus, Staphylococcus haemolyticus, Streptococcus agalactiae, Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Candida albicans, and Trichomonas vaginalis. The study consisted of contaminating the ultrasound transducer with microbial strains of known density, then performing disinfection and assessing the number of surviving microbial cells. Results: Almost complete eradication of all tested pathogenic microorganisms was achieved, except T. vaginalis. But for this protozoa eradication of mobile forms reaches around 80%. Conclusions: Although the sample size in our study was limited and statistical significance was not reached, the substantial logarithmic reduction strongly indicates the effectiveness of this method. Full article

Background: Placental infections caused by Schistosoma spp. and sexually transmitted microorganisms can adversely impact pregnancy outcomes. However, the association between molecular detection of these pathogens in placental tissue and corresponding histopathological inflammation remains unclear, particularly in sub-Saharan African populations. Methods: In this cross-sectional study, placental parenchyma specimens with limited membrane sampling were collected from 103 Ivorian and Ghanaian mothers without known pregnancy or birth complications. Tissue pieces adjacent to PCR-tested samples were analyzed by real-time PCR targeting Chlamydia trachomatis, Mycoplasma hominis, Neisseria gonorrhoeae, Schistosoma spp., Streptococcus agalactiae, Trichomonas vaginalis, Ureaplasma parvum and Ureaplasma urealyticum. Corresponding adjacent tissues were examined by routine histopathology, supplemented with immunohistochemistry when higher pathogen DNA quantities were detected, to assess inflammatory changes. Results: Real-time PCR detected U. urealyticum in 15 out of 103 cases (14.6%, ±0.7%), U. parvum in 13 (12.6%, ±0.6%), S. agalactiae in 11 (10.7%, ±0.5%), the S. haematobium complex in four (3.9%, ±0.2%), M. hominis in four (3.9%, ±0.2%), confirmed N. gonorrhoeae in two (1.9%, ±0.1%) and non-confirmed N. gonorrhoeae in one (1.0%, ±0.1%), T. vaginalis in two (1.9%, ±0.1%), and C. trachomatis (non-lymphogranuloma venereum serovar) in one (1.0%, ±0.1%). Overall, pathogen DNA levels were low, with only four positive PCR results yielding cycle threshold (Ct) values below 30 and none below 25. Histopathological examination revealed no relevant inflammatory changes in any samples. Conclusions: Placental parenchyma tissues with limited membrane sampling testing positive for Schistosoma spp. or sexually transmitted pathogens by molecular methods demonstrated no corresponding histopathological inflammation. These findings warrant confirmatory studies to better characterize potential region-specific placental infection phenotypes and their clinical significance. Full article

Background: Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection. This disease is associated with an increased susceptibility to HIV and HPV infections. Currently, resistance to metronidazole (MTZ), the main drug used for treatment, has been reported in up to 9.6% of cases; additionally, the compound is also associated with adverse side effects. Therefore, it is urgent to identify new treatment options. Objective: In this study, we investigated for the first time the in vitro and in silico activity against T. vaginalis of betulin and stigmasterol isolated from Tagetes nelsonii Greenm, as well as their hemolytic activity. Methods: Plant specimen was collected in Chiapas, Mexico. Hexane and methanol extracts were prepared through sonication-assisted maceration. The antiprotozoal and hemolytic activities were evaluated in vitro against Trichomonas vaginalis trophozoites and human erythrocytes. The most active extract was fractionated using chromatographic techniques in a bioassay-guided study. The active metabolites were identified by ¹H and ¹³C-NMR spectroscopy, and their biological activity was further assessed in silico against lactate dehydrogenase (LDH), pyruvate ferredoxin oxidoreductase (PFOR) methionine gamma-lyase (MGL) and purine nucleoside phosphorylase (PNP) T. vaginalis enzymes. Results: Both triterpenes showed anti-trichomonal activity and no hemolytic activity at 100 µg/mL. Molecular docking studies predicted promising interactions of triterpenes with T. vaginalis drug target proteins, TvpFOR and TvLDH. Conclusions: Our results revealed that betulin and stigmasterol are potential molecules for the development of new trichomonacidal therapies against T. vaginalis. Full article

Piperine is an alkaloid found in plants of the genus Piper, and particularly in P. nigrum. This compound has been under extensive research lately for its antimicrobial, antiviral, and also anti-inflammatory, anti-oxidant, anticancer, and positive metabolic properties. Regarding its antibacterial applications, current data show that piperine is effective against Bacillus sphaericus, Bacterioides fragilis, Escherichia coli, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus mutans, Pseudomonas aeruginosa, and Vibrio cholerae; its antifungal potency is exerted against Candida albicans and members of the Aspergillus family; antiviral activity has been documented against MERS-CoV, SARS-CoV2, EBOV, DENV, HCV, ZKV, and HPIV; and antiparasitic activity against Leishmania spp., Plasmodium spp., Trichomonas vaginalis, and Trypanosoma spp. While such applications are promising, more research is required to elucidate the mechanisms of action and to discover new ways of administration. Full article

Sexual assault is a global public health and human rights concern, with serious physical, psychological and reproductive consequences for survivors. Among these, sexually transmitted infections are particularly relevant due to their frequently asymptomatic nature and potential for long-term complications. The detection of sexually transmitted infections in forensic settings is crucial for clinical management of victims and for evidentiary support in forensic sexual crimes investigations. This study aimed to evaluate the applicability of real-time polymerase chain reaction for detecting Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum in biological samples collected from victims of sexual assault and stored under routine forensic conditions, in some cases, for up to 18 years. A total of 231 swabs from 116 individuals collected between 2004 and 2017 were analysed using real-time PCR with pathogen-specific primers and fluorescent probes. The analysis revealed 13 positive samples of T. vaginalis (5.6%) and 11 of C. trachomatis (4.8%). No positive results were obtained for N. gonorrhoeae or T. pallidum. These findings demonstrate the usefulness of real-time polymerase chain reaction for detecting sexually transmitted infections in long-term preserved forensic samples. Moreover, the ability to identify pathogen DNA in archived samples highlights the potential role of molecular diagnostics in the retrospective investigation of sexual crimes, including cold cases. It underscores the value of molecular methods as a complementary tool in forensic proceedings and survivor care. Full article

This study was conducted in Armenia and included 32 pregnant women with TV infection and 30 healthy controls. The vaginal virome includes viruses that infect human cells and unicellular eukaryotes such as Trichomonas vaginalis (TV). Among these are Trichomonas vaginalis viruses (TVVs), double-stranded RNA viruses from the Totiviridae family, and giant DNA viruses that replicate in protozoa. This study investigated the presence of TVVs and giant protozoan viruses in pregnant women with trichomoniasis in Armenia and explored their potential associations with adverse pregnancy outcomes. Vaginal and urethral samples were collected from 32 pregnant women with confirmed TV infection and 30 healthy pregnant controls. TVVs and giant viruses (Marseilleviridae, Mimiviridae, Phycodnaviridae) were detected using qRT-PCR. Viral RNA and DNA were extracted from clinical samples and TV cultures, followed by quantification and gene expression analysis. Selected TVVs were visualized via scanning electron microscopy. All TV-positive women carried at least one TVV strain, with 94% harboring multiple TVV types and TVV4 being the most common. TV infection was significantly associated with preterm birth and premature rupture of membranes (PPROM). Giant viruses were identified in all TV-positive cases but in only 40% of controls. Marseilleviridae gene expression was observed in TV cultures, suggesting possible interactions. These findings highlight a potential role for protozoan viruses in reproductive complications and warrant further investigation. Full article

Trichomonas vaginalis infection (TVI) is the most common curable sexually transmitted infection (STI). In this study, we aimed to assess the performances of different tests for TVI diagnosis in symptomatic Greek women, evaluating the TVI prevalence rate (PR) in Greece and comparing the latter with TVI-PR estimates from Europe. A laboratory-based cross-sectional analysis and a meta-analysis were conducted. Of 399 symptomatic Greek women, 17 had TVI, corresponding to a TVI-PR of 4.3%. The commercial nucleic acid amplification test (NAAT) achieved a sensitivity of 94.1%, which was 6% higher than the sensitivity of the culture method, 35% higher than that of the wet mount test, and 59% higher than that of the Giemsa stain test. The wet mount test achieved the lowest positive predictive value of 76.9%. All the tests had high specificity levels and negative predictive values. Data from 34 European TVI-PR studies in symptomatic women were pooled. The TVI-PR established in our study was similar to the TVI-PR estimates of 4.8% in Europe and 4.5% in Greece, with the second being higher than those of 2.1% in Northwestern Europe and 1.5% in Southern Europe but closer to that of 6.7% in Türkiye. In Greece, a European country with a relatively high TVI-PR among symptomatic women, the highly sensitive and specific, automated, point-of-care NAAT would facilitate rapid, accurate TVI diagnosis and the treatment of this target population to meet the WHO’s goal of ending STI epidemics by 2030. Full article