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Trichomonas vaginalis is the causative agent of the common sexually transmitted disease, trichomoniasis, which affects more than a hundred million people worldwide. Metronidazole and tinidazole, agents belonging to the 5-nitroheterocyclic class of antimicrobials, are most often used to treat infection, but increased resistance has been reported and adverse effects of these drugs can be significant. Consequently, an urgent need exists for the development of novel drug entities against trichomoniasis. Critical for antimicrobial drug development is the demonstration of in vivo efficacy. Murine models of vaginal T. vaginalis infection are unreliable for unknown reasons. Meanwhile, murine infections with the related bovine pathogen, Tritrichomonas foetus, tend to be more robust, although susceptibility to different antimicrobials might differ from T. vaginalis. Here, we explored the utility of T. foetus infection as a surrogate model for drug development against T. vaginalis. Four different T. foetus strains caused robust vaginal infection in young mice, while none of four diverse T. vaginalis strains did. Comparison of drug susceptibility profiles revealed that T. foetus and T. vaginalis were similarly susceptible to a range of 5-nitroheterocyclic and gold(I) compounds. By comparison, proteasome inhibitors were 10- to 15-fold less active against T. foetus than T. vaginalis, although one of the proteasome inhibitors, bortezomib, had low micromolar activity or better against multiple strains of both trichomonads. Different strains of T. foetus were used to demonstrate the utility of the murine vaginal infection models for in vivo efficacy testing, including for bortezomib and a gold(I) compound. The differences in susceptibility to proteasome inhibitors may be partially explained by differences in the proteasome subunit sequences between the two trichomonads, although the functional relevance of the proteasome was similar in both organisms. These findings indicate that T. foetus can serve as a reliable surrogate model for T. vaginalis in vitro and in murine infections in vivo, but caution must be exercised for specific drug classes with targets, such as the proteasome, that may display genetic divergence between the trichomonads., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nieskens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Treatment options for recalcitrant Trichomonas vaginalis (TV), when very high dose systemic 5-nitroimidazole plus intravaginal therapy for over 14 days has failed, are very limited. They have poor efficacy, unpleasant side effects, and are difficult and expensive to acquire. We report successful treatment with 24 weeks of daily dequalinium chloride vaginal tablets. Dequalinium is licensed in Europe where it is readily available and cheap. It offers a safe and pragmatic alternative for recalcitrant TV., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: State: Dr Janet Wilson is the Chief Investigator of an NIHR funded trial ‘Dequalinium versus usual care antibiotics for the treatment of bacterial vaginosis (DEVA): a multicentre, randomised, open label, non-inferiority trial’.

Background: Women living with HIV (WLWH) are often coinfected with Trichomonas vaginalis (TV), and annual screening is recommended. Our goal was to assess differences in TV prevalence at study entry and over time in enrollment cohorts of the Women's Interagency HIV Study. Methods: In a multisite study, TV was diagnosed by wet mount microscopy. Prevalence was determined across four enrollment waves: 1994-1995, 2001-2002, 2011-2012, and 2013-2015. Generalized estimating equation multivariable logistic regression models assessed changes in visit prevalence across waves after controlling for HIV disease severity and other risks. Results: At 63,824 person-visits (3,508 WLWH and 1,262 women without HIV), TV was diagnosed by wet mount at 1979 visits (3.1%). After multivariable adjustment, HIV status was not associated with TV detection, which was more common among younger women, women with multiple partners, and irregular condom use. All enrollment waves showed a decline in TV detection over time, although p -value for trend did not reach significance for most recent waves. To explore the potential utility of screening among WLWH, we assessed rates of TV detection among women without appreciable vaginal discharge on examination. Initial TV prevalence among asymptomatic women was 3.5%, and prevalence decreased to 0.5%-1% in the most recent wave (2013-2015) ( p -trend <0.0001). Conclusions: In this cohort, TV rates are low among WLWH, and HIV does not increase TV risk. Screening may benefit newly diagnosed WLWH, women with risk factors, or those receiving care sporadically but is unlikely to further reduce the low rate of TV among women in care, especially older women without multiple partners. The clinical trials registration number for WIHS is NCT00000797.

Background: Trichomonas vaginalis (TV) is a common sexually transmitted infection. High rates of repeated infections have been observed, particularly among women living with human immunodeficiency virus (HIV). Trichomonas vaginalis frequently cooccurs with bacterial vaginosis (BV). The purpose of this study was to determine if coinfections with TV, BV, and HIV could lead to differential treatment failure outcomes., Methods: Data were pooled from 2 prior randomized control trials comparing 2 g oral single-dose versus 500-mg twice daily oral 7-day dose metronidazole for the treatment of TV in HIV infected and HIV uninfected women. Trichomonas vaginalis rates 1-month postcompletion of treatment were compared by arm, HIV and BV status after removing those who had sexual reexposure, and/or did not complete their treatment., Results: Data for 795 subjects were included in the study, of which 76 (9.6%) experienced treatment failure. In the final multivariable model, which included treatment dose, HIV status, and BV status, odds of treatment failure infection in the 7-day dose group were lower than the odds in the single dose group (odds ratio, 040; 95% confidence interval, 0.23-0.68). Treatment failure was lower in the multidose arm compared with single dose for both HIV-infected (4.0% vs 10.3%; P = 0.0568) and HIV-uninfected (7.3% vs 15.4%; P = 0.0037). Neither HIV nor BV was associated with higher treatment failure., Conclusions: Human immunodeficiency virus infection and BV status did not significantly alter the rate of repeat infection for either single dose or 7-day dose metronidazole. Among all women, 7-day metronidazole lowered the odds of treatment failure., Competing Interests: Conflict of Interest: None declared., (Copyright © 2023 American Sexually Transmitted Diseases Association. All rights reserved.)

Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. has received research grant support from Lupin Pharmaceuticals, Gilead Sciences, Inc, and Abbott Molecular; is a consultant for Lupin Pharmaceuticals, BioNTech, and BioFire Diagnostics; and has received honoraria from Elsevier, Abbott Molecular, Cepheid, Becton Dickinson, Roche Diagnostics, and Lupin Pharmaceuticals. P.J.K. does not have any conflicts to declare. C.A.M. and P.J.K. did not receive funding to develop this article.

Trichomoniasis is a sexually transmitted parasitic infection caused by Trichomonas vaginalis. In the diagnosis of trichomoniasis, direct microscopy (DM) is preferred, which is a cheap and fast method, although it has low sensitivity. Culture methods, which are accepted as the gold standard, can only be applied in certain centers due to the need for experienced personnel and the ability to get results within 2-7 days, despite their high sensitivity. In this study, it was aimed to compare conventional microscopic and culture methods used in the routine diagnosis of T.vaginalis with polymerase chain reaction (PCR) method and to investigate ntr4 and/or ntr6 gene polymorphism in the nitroreductase gene region, which are thought to be associated with metronidazole resistance in T.vaginalis strains isolated from clinical specimens. Vaginal swab specimens were collected from the posterior fornix of the vagina with two sterile ecuvion sticks during the gynecological examinations of 200 patients who applied to the Balıkesir University Health Practice and Research Hospital, Obstetrics and Gynecology Polyclinic between March 2019 and August 2021. The first swab sample was used for direct microscopic examination, Giemsa staining and conventional PCR analysis, while the second swab specimen was taken into trypticase-yeast-extract-maltose (TYM) medium for T.vaginalis culture and followed for eight days at 37 °C. All specimens were screened for the presence of T.vaginalis using primers specific to the β-tubulin (btub1) gene region and clinical isolates grown in TYM medium were examined for metronidazole resistance using primers specific for the nitroreductase gene region by using conventional PCR. Drug resistance test was also performed for the isolates in which polymorphism associated with metronidazole resistance was detected. Eight (4%) of 200 patient specimens were found positive by both culture/staining and PCR methods. The mean age of the patients included in the study was 39.9, while the mean age of the patients with positive T.vaginalis was 41.8. The most common clinical findings in the patients were foul-smelling vaginal discharge (36%), groin pain (21%), vaginal itching (19%), and burning sensation during urination (18%). In three out of eight T.vaginalis strains isolated from clinical samples, the presence of polymorphism in the ntr6 gene, which is thought to be associated with metronidazole resistance, was demonstrated by PCR. It was observed that three isolates with ntr6 gene polymorphism were phenotypically resistant to metronidazole (MLK= 390 µM). In this study, the fact that three of eight clinical isolates that were resistant to metronidazole by the broth microdilution method and as well as showing ntr6 gene polymorphism supported the thesis that there might be a close relationship between metronidazole resistance and ntr6 gene polymorphism. As a result, the use of culture and molecular methods in the diagnosis of T.vaginalis, in addition to the microscopy method, may contribute to a more accurate laboratory diagnosis of the agent, to detect metronidazole resistance molecularly and phenotypically, to determine metronidazole resistance rates in our country and to update treatment protocols within the framework of these data.

Purpose: Nonspecific vaginitis is a distinct clinical entity with particular microscopic and immunologic features. There is currently no standard of care for women with nonspecific vaginitis. The aim of our study was to assess the change in vaginal symptoms score after 3 months of treatment with an intravaginal medical device in participants with abnormal vaginal discharge and specific signs and symptoms. As secondary objectives, the study analyzed other clinical and microscopic features, such as vaginal discharge aspect, change in vaginal pH, change in vaginal microbiome, and vaginal inflammation., Methods: The study population included 47 participants with symptomatic vulvovaginitis, distinct from candidiasis, trichomoniasis, or bacterial vaginosis. The study design included 2 research sites from Romania. The treatment protocol consisted of 1 ovule per day inserted intravaginally during 15 consecutive days. The total study duration was 3 months., Findings: The intravaginal medical device had a positive impact on the vaginal symptoms score for 72.34% of the study participants. Topical administration of the ovules balanced vaginal pH values and significantly reduced signs of inflammation between study visits., Implications: This intravaginal medical device had curative effects that support its use as a stand-alone treatment in women with nonspecific vaginitis. A second clinical investigation is ongoing to evaluate the clinical efficacy of the device in postoperative care of cervical and vaginal wounds traumatic or secondary to surgical interventions., Clinicaltrials: gov identifier: NCT04735705., Competing Interests: Declaration of Competing Interest MDX Research was involved in the study design, site selection, collection, statistical analysis, and preparation of the manuscript. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2023. Published by Elsevier Inc.)

Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as Metronidazole (MTZ). Although effective in eliminating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5'-nitroimidazoles, prompting the development of alternative drugs for trichomoniasis. Here we show that SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa- 2,6-dienyl)-ethane-1,2-diamine], a drug under development (antitubercular drug candidate that completed Phase IIb/III) for the treatment of tuberculosis, and previously tested in Trypanosoma cruzi and Leishmania. SQ109 inhibited T.vaginalis growth with an IC50 of 3.15 μM. We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by SQ109. The microscopy analysis showed morphological changes on the protozoan surface, where the cells became rounded with increasing surface projections. In addition, the hydrogenosomes increased their size and area occupied in the cell. Furthermore, the volume and a significant association of glycogen particles with the organelle were seen to be altered. A bioinformatics search was done about the compound to find its possible targets and mechanisms of action. Our observations identify SQ109 as a promising compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Trichomoniasis is the most common nonviral sexually transmitted infection. 1 For patients with resistance to standard treatment with 5-nitroimidazoles, alternative therapies are limited. We present a case of a 34-year-old woman with multidrug-resistant trichomoniasis who was successfully treated with 600 mg intravaginal boric acid twice daily for 3 months., Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. has received research grant support from the National Institutes of Health/National Institute of Allergy and Infectious Disease, Lupin Pharmaceuticals, Gilead Sciences, Inc, Visby Medical, and Abbot Molecular; is a consultant for Lupin Pharmaceuticals, BioTechN, Scynexis, and Cepheid; and has received honoraria from Visby Medical, Elsevier, Abbot Molecular, Cepheid, Roche Diagnostics, and Lupin Pharmaceuticals. The other authors have no conflicts of interest to declare., (Copyright © 2023 American Sexually Transmitted Diseases Association. All rights reserved.)

Trichomoniasis (TV), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are the most common causes of vaginitis. This study investigated the prevalence of these diagnoses, their associated factors, and the appropriateness of the empirical treatment. From March 25, 2019, to June 17, 2022, 429 women with symptoms or signs of vaginitis were enrolled in a hospital in northern Taiwan with 438 episodes of vaginitis. Vaginal swabs were collected for Gram's staining, in vitro cultures for Trichomonas vaginalis, bacteria, and yeasts, and multiplex PCR assay for TV, BV, and VVC. Their empirical treatments were recorded. Factors associated with different etiologies of vaginitis were sought in multivariable logistic regression models. The prevalence of TV, BV, and VVC were 2.1%, 22.8%, and 21.7%, respectively, while coinfections of BV and VVC, TV and BV, TV and VVC, and triple infection occurred in 5.0%, 0.2%, 0.2%, and 0.7%, respectively. Multivariable analyses revealed that having multiple sexual partners was associated with TV and BV (adjusted odds ratio [aOR] 9.756 and 3.246, respectively), while menopausal women were less likely to have VVC (aOR 0.184). Moreover, dysuria was associated with TV (aOR 4.981), vaginal itch and pelvic pain with VVC (aOR 3.223 and 0.425, respectively), and discharge pH > 4.5 with BV (aOR 1.767). Other clinical symptoms and pelvic examination features had limited value for differential diagnosis. Among the 78 empirical antifungal and metronidazole prescriptions, 55.2% were ineffective or unnecessary. Our study highlights the importance to integrate appropriate diagnostic tools into the clinical care of women with vaginitis. IMPORTANCE Vaginal complaints are widespread among women and are associated with emotional, physical, and economic burdens with challenges in their diagnosis and management. In this survey, we identified that 40% of vaginitis in Taiwan was caused by either trichomoniasis, bacterial vaginosis, vulvovaginal candidiasis, or a combination of these infections. Our data suggested that typical physical findings appeared infrequently among women with these infections and their empirical treatments were frequently inappropriate. Our findings highlighted the importance of integrating proper diagnostic tools into clinical practice to improve the diagnosis and management of vaginitis, as recommended by national and international guidelines., Competing Interests: The authors declare no conflict of interest.

Trichomoniasis is the most common nonviral sexually transmitted infection worldwide. It has been associated with a variety of adverse sexual and reproductive health outcomes for both men and women. In this review, the authors discuss updates in its epidemiology, pathophysiology, clinical significance, diagnosis, and treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The only drugs approved by the US Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined. We conducted a study using T. vaginalis isolates from women with reported treatment success or failure to determine these values., Methods: We measured MLCs of 47 isolates obtained from women who had failed metronidazole treatment, 33 isolates from women who had failed tinidazole treatment, and 48 isolates from women successfully cured with metronidazole. The cutoff was calculated as the 95th percentile of MLCs of susceptible isolates for each drug., Results: Our data confirmed that the MLC previously associated with metronidazole treatment failure is ≥50 μg/mL and identified the MLC associated with tinidazole treatment failure as ≥6.3 μg/mL. For metronidazole, the agreement between laboratory result and treatment outcome was 93.7%; for tinidazole, this agreement was 88.9%., Conclusions: The T. vaginalis susceptibility assay is useful for determining whether 5-nitroimidazole treatment failure in persons with trichomoniasis can be attributed to drug resistance. These results are useful for establishing interpretive guidance of test results, and MLC levels can help guide appropriate patient treatment., Competing Interests: Conflict of Interest and Sources of Funding: All authors declare no conflicts of interest. This project was supported by the Centers for Disease Control and Prevention operating budget and involved no external funding., (Copyright © 2023 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

The aim of this paper is to describe the prevalence of Mycoplasma genitalium and Trichomonas vaginalis in patients who visited general practitioners in the Netherlands. Additionally, we describe the prevalence of M. genitalium resistance to azithromycin and moxifloxacin. We used data from 7,411 consecutive female patients who were screened for Chlamydia trachomatis , Neisseria gonorrhoeae , M. genitalium , and T. vaginalis and data from 5,732 consecutive male patients screened for C. trachomatis , N. gonorrhoeae , and M. genitalium . The prevalence of M. genitalium and T. vaginalis in female patients was 6.7% (95% CI: 6.2 to 7.4) and 1.9% (95%CI: 1.6 to 2.2%), respectively. M. genitalium prevalence in male patients was 3.7% (3.3 to 4.3). M. genitalium co-occurred with C. trachomatis in 1.4% (0.3 to 0.6%) of female and in 0.7% (0.5 to 0.9) of male patients. Macrolide resistance gene mutations and fluoroquinolone resistance gene mutations were detected in 73.8% and 9.9%, respectively. We concluded that M.genitalium is relatively infrequently found in a large general practitioner population in the Netherlands. It can co-occur with C. trachomatis , and is often resistant to azithromycin. Therefore, when treating sexually transmitted infections, these prevalence and resistance data should be taken into account.

Abstract: We describe a case of persistent 5-nitroimidazole-resistant trichomoniasis cured after 14 days of oral secnidazole and intravaginal boric acid. Secnidazole may be an important treatment option for resistant trichomoniasis, particularly in women who fail other regimens, including higher doses of oral metronidazole and tinidazole for longer durations of time., Competing Interests: Conflict of Interest and Sources of Funding: C.J.M. has received grants or contracts from Biomedical Advanced Research and Development Authority/GlaxoSmithKline, Becton Dickinson, Binx, Cepheid, the Centers for Disease Control and Prevention, Gilead, Hologic, the National Association of County and City Health Officials, and the National Institutes of Health, paid to her employer, the Wake Forest University School of Medicine. J.C.W. has no conflicts of interest to declare. C.A.M. has received research grant support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, Lupin Pharmaceuticals, Gilead Sciences, Inc, Visby Medical, and Abbott Molecular; is a consultant for Lupin Pharmaceuticals, BioNTech, Scynexis, and Cepheid; and has received honoraria from Visby Medical, Elsevier, Abbott Molecular, Cepheid, Roche Diagnostics, and Lupin Pharmaceuticals., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Vaginal symptoms are one of the most common reasons women consult with physicians and can significantly impact quality of life. The differential diagnosis of vaginal discharge includes physiologic discharge, vaginitis, cervicitis, and pelvic inflammatory disease (PID). Vaginitis is inflammation of the vagina, most commonly caused by bacterial vaginosis (BV), vulvovaginal candidiasis, and trichomoniasis infections. Cervicitis is an inflammation of the cervix and typically caused by Chlamydia trachomatis and Neisseria gonorrhoeae. PID is infection of the female upper genital tract, involving the uterus, fallopian tubes, ovaries, and/or pelvic peritoneum and usually caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis-associated pathogens. A pelvic exam should be performed for any woman presenting with vaginal discharge to confirm the diagnosis and rule out an upper tract infection. BV and vulvovaginal candidal infections only require treatment if symptomatic and do not require partner therapy, whereas treatment and partner therapy is recommended for sexually transmitted illnesses, such as trichomoniasis, chlamydia and gonorrhea. Vaginitis may be uncomfortable, but rarely leads to serious long-term consequence, but pelvic inflammatory disease can lead to serious long-term sequelae, including increased risk for ectopic pregnancy, infertility, and chronic pelvic pain., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) occurring worldwide and the majority of infected persons (70-85%) have mild or no genital symptoms. Symptoms in women may include a vaginal discharge which may be associated with vulval irritation and most infections can be effectively treated with metronidazole 500mg bd for seven days. Trichomoniasis unresponsive to 5-nitroimidazole therapy is uncommon but results in substantial therapeutic challenges, especially in resource limited countries. We present such a case which was eventually treated with a low-cost intravaginal combination of boric acid and clotrimazole cream.

For the treatment of trichomonas vaginitis, a combination therapy of metronidazole vaginal effervescent tablet combined with Flavescentis Sophora suppository is proposed. The patients diagnosed with trichomonas vaginitis are divided into the conventional treatment group and the joint group. The conventional group is treated with metronidazole vaginal effervescent tablets, and the joint group is treated with metronidazole vaginal effervescent tablets combined with sophora bolt. Both groups are treated for 3 months to observe the therapeutic effect of the two treatment methods. The expressions of IL-2 and IL-13 in serum of patients are detected by the ELISA. The changes in the vaginal pH value and cleanliness at each time point are observed. The patients are followed up for 6 months after treatment in order to observe the recurrence of trichomonas vaginitis in both groups. Experimental results show that the combination of the two tablets can further improve the clinical efficacy and reduce the inflammatory response and effectively improve the PH value and cleanliness of the vagina, and the recurrence rate is lower, which is worthy of clinical application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Lingjia Shi et al.)

Introduction: Single-dose 2-g oral secnidazole (SEC), newly approved by the U.S. Food and Drug administration (FDA) for treatment of trichomoniasis, is a potent 5-nitroimidazole with selective toxicity against various micro-organisms. It has been used internationally to treat trichomoniasis, bacterial vaginosis, and other infections for decades. Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and is associated with significant morbidity. In comparison to the only other FDA-approved treatments for trichomoniasis in the United States - metronidazole and tinidazole - SEC has favorable pharmacokinetics, including a longer half-life and a lower minimal lethal concentration., Areas Covered: This work summarizes the chemistry and pharmacology of SEC and reviews the evidence on its efficacy, tolerability, and safety for the treatment of trichomoniasis., Expert Opinion: SEC is an efficacious, well tolerated, and safe treatment for patients aged ≥12 years with trichomoniasis. Single-dose administration makes it a favorable treatment option, especially in cases where adherence to multi-dose treatment regimens may be low.

Trichomoniasis is a sexually transmitted infection in humans caused by the protozoan Trichomonas vaginalis, the leading causative agent of vaginitis in women and urethritis in men worldwide. Metronidazole is the standard treatment for trichomoniasis, with tinidazole as the second line. There are currently no FDA-approved non-nitroimidazole alternative treatments for resistant strains. This study compares the efficacy of a newly synthesized non-nitroimidazole oral drug, amixicile, to that of both metronidazole and the synthetic precursor of amixicile, nitazoxanide with in vitro sensitivity testing. One standard strain from ATCC and three patient-isolated strains of T. vaginalis were used to compare treatments under anaerobic conditions. The minimum inhibitory concentration for metronidazole, nitazoxanide, and amixicile were 12.5 μM, 100 μM, and 6.25 μM, respectively. These results suggest that amixicile may be highly active against T. vaginalis and warrants further investigation as a potential alternative to metronidazole in the treatment of trichomoniasis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The main objective of this guideline is to assist practitioners in managing individuals diagnosed with Trichomonas vaginalis (TV). It offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of TV. It covers the management of the initial presentation, as well as how to prevent transmission and future re-infection. It is aimed primarily at people aged 16 years or older presenting to health care professionals, working in departments offering specialist care in sexually transmitted infection (STI) management within the United Kingdom. However, the principles of the recommendations are applicable across all levels of STI care providers (N.B. non-specialist services may need to develop, where appropriate, local care pathways).

Trichomonas vaginalis is a protozoan that causes human trichomoniasis, the most common non-viral sexually transmitted infection (STI) affecting approximately 278 million people worldwide. The current treatment for trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as metronidazole (MTZ). Although effective in clearing the parasite infection, MTZ is related to provoking severe side effects, and it is not recommended during pregnancy. In addition, some strains present resistance to 5'-nitroimidazoles, making urgent the development of alternative drugs for trichomoniasis. Amiodarone, an antiarrhythmic drug, exerts a significant anti-parasite effect, mainly due to its interference with calcium homeostasis and the biosynthesis of sterols. Therefore, we decided to test the effect of amiodarone and two other related compounds (amioder and dronedarone) on T. vaginalis. Our observations show that amiodarone stimulated, rather than inhibited, parasite growth, induced cell aggregation, and glycogen accumulation. Furthermore, the other two compounds displayed anti-parasite activity with IC50 of 3.15 and 11 µM, respectively, and the apoptosis-like process killed the cells. In addition, cells exhibited morphological changes, including an effect on hydrogenosomes structure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In a randomized controlled trial of 2 g (single-dose) metronidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trichomonas vaginalis treatment, multidose was superior. We examined if the effect was similar by select clinical factors to determine if treatment recommendations could be targeted., Methods: The primary outcome was T. vaginalis repeat infection at test-of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified by T. vaginalis history, baseline genital symptoms, and concurrent diagnosis of bacterial vaginosis (BV) per Nugent score at baseline., Results: Women who returned for TOC (n = 540) were included. At baseline, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symptoms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up, 97.4% took all MTZ as instructed and 34.5% had interval condomless sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis. In stratified analysis, women randomized to single-dose MTZ had a higher rate of TOC T. vaginalis positivity than those randomized to multidose if they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a reported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T. vaginalis positivity was higher for women receiving a single dose (18.9%) versus multidose (10.8%), irrespective of baseline BV status (P > 0.06). In multivariable analysis, only a history of T. vaginalis and single-dose MTZ were independently associated with a positive TOC for T. vaginalis., Conclusions: Although multidose MTZ is recommended for all women with T. vaginalis, it is especially important for women with a T. vaginalis history and, given high posttreatment infection rates, a TOC should be performed., Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. is a consultant for Lupin Pharmaceuticals, BioFire Diagnostics, Cepheid, and PhagoMed. She has also received research funding support from Lupin Pharmaceuticals and Abbott Molecular as well as speaker honoraria from Abbott Molecular, Cepheid, Roche Diagnostics, and Becton Dickinson. L.A.M. has received honoraria for his role as a consultant to Gilead Sciences, ViiV Healthcare, Roche, and Merck. He has received research grants from Gilead Sciences, ViiV Healthcare/GSK, Janssen, Binx Health (Atlas Genetics), Becton Dickinson, Rheonix, Click Diagnostics, Roche, Evofem, Westat, and Lupin Pharmaceuticals. R.A.L. has conducted clinical trials for Cepheid and Hologic and is a consultant for Roche and Merck. N.S., D.H.M., and P.K. have nothing to disclose., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Competing Interests: Competing interests: Vanessa Poliquin reports receiving consulting fees from GSK and SearchLight Pharma, and an honorarium from Sanofi Pasteur. No other competing interests were declared.

Importance: Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes., Observations: From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception., Conclusions and Relevance: Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.

In the late 90s, a sharp increase of treatment failures of Trichomonas vaginalis (TV) infections with metronidazole (MTZ) was reported, representing a problem due to limited treatment options. We proposed to review the available evidence on the frequency of MTZ resistance by TV isolates and the relationship between treatment failure and in vitro resistance to MTZ. A systematic review based on the PRISMA guidelines was conducted by searching published studies in three different databases (PubMed, Scopus and Web of Science) up to December 2020. The extracted studies were uploaded to Covidence software; screening was guided based on inclusion and exclusion criteria. Additionally, different articles were included through other sources. For each article, study design, objectives, study population and key outcomes were summarized. We found 403 references from the databases and four extra studies. After duplicate removal and screening of title, abstract and full text, 27 studies were included. The selected studies were published between 1983 and 2019; all except one addressed only vaginal TV infection. We identified four major populations in vitro MTZ resistance: two studies evaluated female adolescents; other two assessed HIV-positive women. Fifteen studies considered MTZ resistance in newly diagnosed vaginal TV infection. Finally, eight articles studied in vitro susceptibility of isolates from women with clinical resistant trichomoniasis. High level of in vitro MTZ resistance was rare; low-moderate level was described in most of the cases. Although clinical resistance to MTZ of trichomoniasis was widely reported, there was a paucity of prospective controlled studies. Our review unveiled the need to standardize susceptibility testing, to define breakpoints for detection of MTZ-resistant isolates and to correlate with clinical outcome. It is important to establish criteria to define clinical resistance to MTZ. Such a consensus would foster the development of surveillance studies about clinical and microbiological response to MTZ treatment., (© 2021 European Academy of Dermatology and Venereology.)

Abstract: Metronidazole and other 5-nitroimidazoles are the mainstay of Trichomonas vaginalis treatment, with few efficacious and safe treatment options available outside of this class. Patients with trichomoniasis and a history of a clinically confirmed hypersensitivity reaction to 5-nitroimidazoles present a management challenge for clinicians. The first step in managing such patients is metronidazole desensitization. In situations where this cannot be performed or tolerated, treatment with alternative regimens outside of the 5-nitroimidazole class, such as intravaginal boric acid or paromomycin, may be possible., Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. has received research grant support from Lupin Pharmaceuticals, is a consultant for Lupin Pharmaceuticals and BioFire Diagnostics, and has received honoraria from Elsevier, Abbott Molecular, Cepheid, Becton Dickinson, Roche Diagnostics, and Lupin Pharmaceuticals. All other authors have no relevant conflicts of interest to disclose., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Although vaginal symptoms are common, diagnosis of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis (TV) is not standardized. Diagnostic approaches and appropriateness of treatment were evaluated for women with symptoms of vaginitis who were seeking care at community practice sites., Methods: Three hundred three symptomatic women, across 8 University of Pittsburgh Medical Center-affiliated clinics, were evaluated per standard office-based practice. Four of 5 vaginal swabs (1 cryopreserved) were collected for a US Food and Drug Administration-authorized nucleic acid amplification test (NAAT) for vaginitis/vaginosis diagnosis; Nugent scoring (BV); yeast culture (VVC); and a second NAAT (for TV). Two hundred ninety women had evaluable samples. Medical record extraction facilitated verification of treatments prescribed within 7 days of the index visit and return visit frequency within 90 days., Results: Women had a mean age of 29.4 ± 6.5 years, 90% were not pregnant, 79% were of white race, and 38% reported vaginitis treatment within the past month. Point-of-care tests, including vaginal pH (15%), potassium hydroxide/whiff (21%), and wet mount microscopy (17%), were rarely performed. Of the 170 women having a laboratory-diagnosed cause of vaginitis, 81 (47%) received 1 or more inappropriate prescriptions. Of the 120 women without BV, TV, or VVC, 41 (34%) were prescribed antibiotics and/or antifungals. Among women without infectious vaginitis, return visits for vaginitis symptoms were more common among women treated empirically compared to those not receiving treatment (9/41 vs 5/79, P = .02)., Conclusions: Within a community practice setting, 42% of women having vaginitis symptoms received inappropriate treatment. Women without infections who received empiric treatment were more likely have recurrent visits within 90 days., Clinical Trials Registration: NCT03151928., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl- and HCO3-. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl- and HCO3- secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl- transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl- signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment., Competing Interests: The authors have declared that no competing interests exist.

This study investigated the effect of nano-Ag/TiO₂ composite antibacterial agent on bacterial vaginosis and trichomonas vaginitis. Bacterial vaginosis and trichomonas vaginitis were treated with nano-Ag/TiO₂ composite antibacterial agent (composite treatment group) and ornidazole suppository (traditional treatment group). Vaginal secretions from both treatment groups were analyzed to determine the effectiveness of the methods. The effective rate of the nano-Ag/TiO₂ composite antibacterial agent was 97.0% for bacterial vaginosis and 94.4% for trichomonas vaginitis. The traditional treatment method, ornidazole suppository, showed an effective rate of 79.5% for bacterial vaginitis and 88.9% for trichomonas vaginitis. Therefore, the nano-Ag/TiO₂ composite antibacterial agent was determined to be an effective treatment method for bacterial vaginosis and trichomonas vaginitis.

The protozoan pathogen Trichomonas vaginalis encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the β-class. One of these enzymes, T. vaginalis carbonic anhydrase 1 (TvaCA1), was recently cloned and characterized by our group, and its X-ray crystal structure reported. No inhibitors of this enzyme were reported up until now. Here we investigated the inhibition of TvaCA1 with inorganic anions and small molecules and observed that thiocyanate, cyanide, selenite, selenocyanate and divanadate are sub-millimolar inhibitors, whereas sulfamide, sulfate, phenylboronic acid and phenylarsonic acid are micromolar inhibitors. Finding effective TvaCA1 inhibitors may be useful for developing new antiprotozoan drugs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Current pelvic inflammatory disease (PID) treatment effectively treats Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). However, coverage may be inadequate for Mycoplasma genitalium (MG)/Trichomonas vaginalis (TV) infections. We compared the longitudinal MG and TV outcomes with NG/CT outcomes for women enrolled in a longitudinal randomized controlled trial to optimize outcomes after PID. The prevalences of CT and NG were lower at 30- and 90-day follow-up compared with the prevalence at the time of diagnosis. No significant difference was observed for MG (odds ratio, 0.95; 0.86-1.04; P = 0.265) and TV (odds ratio, 0.89; 0.75-1.04; P = 0.146) over time for both treatment groups, showing that persistence and/or reinfection with MG and TV occurs more frequently than with CT or NG after treatment of PID using current national treatment guidelines.

Human trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.

After the incidental observation of an almost complete resolution of maculopapular eruption in a patient having simultaneously secondary syphilis and trichomonas vaginalis infection, we extended the treatment with tinidazole (500 mg 4 times daily for 7 days) to 10 other early syphilis patients before the start of the conventional penicillin treatment. All patients showed marked improvement of their lesions in a few days. After the introduction of the conventional penicillin regimen, the lesions further improved and VDRL titers declined at least 4-fold within 6 months in all patients. Tinidazole is a 5-nitroimidazole derivative as well as metronidazole but with a longer plasma half-life. It is activated intracellularly by bacterial/parasitic enzymes to a redox cytotoxic intermediate that damages large protein molecules and inhibits repair and transcription of DNA affecting also the cell wall. With this action, tinidazole might also have a synergic action with penicillin and doxycycline, facilitating the entry of such drugs. It is possible that tinidazole has the same bactericidal action on spirochetes other than Borrelia, such as Treponema pallidum, explaining its rapid therapeutic action on the lesions of early syphilis. Whether this action could be confirmed by studies on larger series of patients, tinidazole might be considered in case of allergy to penicillin or other antibiotics usually prescribed in syphilis., (© 2020, The American College of Clinical Pharmacology.)

Objectives: In 2016, WHO estimated 376 million new cases of the four main curable STIs: gonorrhoea, chlamydia, trichomoniasis and syphilis. Further, an estimated 290 million women are infected with human papillomavirus. STIs may lead to severe reproductive health sequelae. Low-income and middle-income countries carry the highest global burden of STIs. A large proportion of urogenital and the vast majority of extragenital non-viral STI cases are asymptomatic. Screening key populations and early and accurate diagnosis are important to provide correct treatment and to control the spread of STIs. This article paints a picture of the state of technology of STI point-of-care testing (POCT) and its implications for health system integration., Methods: The material for the STI POCT landscape was gathered from publicly available information, published and unpublished reports and prospectuses, and interviews with developers and manufacturers., Results: The development of STI POCT is moving rapidly, and there are much more tests in the pipeline than in 2014, when the first STI POCT landscape analysis was published on the website of WHO. Several of the available tests need to be evaluated independently both in the laboratory and, of particular importance, in different points of care., Conclusion: This article reiterates the importance of accurate, rapid and affordable POCT to reach universal health coverage. While highlighting the rapid technical advances in this area, we argue that insufficient attention is being paid to health systems capacity and conditions to ensure the swift and rapid integration of current and future STI POCT. Unless the complexity of health systems, including context, institutions, adoption systems and problem perception, are recognised and mapped, simplistic approaches to policy design and programme implementation will result in poor realisation of intended outcomes and impact., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Mycoplasma genitalium (M. genitalium) and Trichomonas vaginalis (T. vaginalis), sexually transmitted infections that remain non-reportable in the United States, may lead to pelvic inflammatory disease (PID) and adverse pregnancy outcomes if left untreated. Prevalence estimates have highlighted socioeconomic and racial/ethnic disparities in rates of infection. This review summarizes the recent literature on M. genitalium and T. vaginalis with a focus on the epidemiology, screening, and treatment of M. genitalium and T. vaginalis., Recent Findings: The burden of T. vaginalis testing remains on women. Antimicrobial resistance is of great concern for M. genitalium. Comprehensive screening and treatment guidelines present an opportunity to address these public health concerns., Summary: M. genitalium and T. vaginalis infections disproportionately affect sexual and racial/ethnic minorities and those facing socioeconomic disparities. The availability of nucleic acid amplification test testing has facilitated accurate diagnosis of both disorders. Safe and efficacious treatments are available for treatment of both disorders. Integrating macrolide resistance testing into treatment algorithms for M. genitalium and dual antibiotic therapy may prove a useful strategy for future US-based guidance. Public health reporting and increased public awareness campaigns are key next steps to addressing the observed reproductive health disparities.

Background: Trichomonas vaginalis is a common treatable sexually transmitted infection among older women. Persistent T. vaginalis infection after treatment is common among women with human immunodeficiency virus (HIV). We sought to determine if HIV-negative women were as likely as women with HIV to have persistent T. vaginalis infection., Methods: We performed a retrospective cohort study of women 45 years or older with T. vaginalis infection. We evaluated differences in persistent T. vaginalis infection according to HIV status using χ analysis. We performed regression analyses to describe factors associated with persistent and recurrent infection in older women., Results: Over a 10-year study period, we identified 282 women with T. vaginalis, 46 with HIV. Most women (240, 86%) were treated in accordance with 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases treatment guidelines. Half of the women (144, 53%) had a repeat T. vaginalis test 90 to 365 days after treatment, and one third had persistent infection (39/125, 31%). Persistent infection was similar between women with HIV and HIV-negative women treated according to Centers for Disease Control recommendations (17% vs 33%, P = 0.3). When adjusting for age and incidental diagnosis, tobacco use was associated with an increased risk of more than 1 or recurrent T. vaginalis infection during the study period (adjusted odds ratio, 2.8; 95% confidence interval, 1.5-4.9)., Conclusions: The HIV status did not affect persistent T. vaginalis infection in women 45 years or older. Given over one third of women have a positive test within a year after the recommended treatment, our data support repeat testing in women 45 years and older treated for T. vaginalis.

The purpose was to evaluate whether probiotics can increase the effectiveness of antimicrobial therapy. Ninety women with Trichomonas vaginalis (TV) in the presence BV were included in the study of regimens for therapy combination with metronidazole and vaginal probiotics. For 7 days, the probiotics group patients received metronidazole at 500 mg twice a day and 1 capsule of probiotic Gynophilus® vaginally twice a day; the placebo group patients in addition to metronidazole received a placebo instead of a probiotic. For the next 7 days, patients in both groups in order restore normal microflora were given the probiotics vaginally. Before the treatment, on the 4th, 8th, and 15th day of therapy complaints, pH and redox potential of the vaginal fluid were recorded, TV detection culturally, microflora of the vagina with the qPCR-RT and microscopically. Adding probiotics to traditional therapy of TV in the presence of BV increased the likelihood of cure from TV (88.6 and 42.9% in the probiotic and placebo groups, respectively) and from BV (63.6 and 11.9%, respectively). We have found that the addition of probiotics to antimicrobial therapy causes the decrease in the inflammatory response and significant changes in the vagina's physicochemical parameters (decreased of the pH values, increased of the redox potential) already on the fourth day of the therapy. The changes in the metronidazole's antimicrobial action implementation when a probiotic is added are the reason of increasing the TV therapy's effectiveness in the BV presence.

Background: Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high., Objectives: To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure., Study Design: HIV-negative, nonpregnant women aged 18-45 years with bacterial vaginosis and/or Trichomonas vaginalis (N=68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7-10 and a valid posttreatment Nugent score (N=55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4-10., Results: The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log 10 /μL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log 10 /μL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log 10 /μL (P=.017), with L. iners being the most common species pre- and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log 10 /μL pretreatment to 2.01 log 10 /μL posttreatment (P=.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P=.044 and P=.084, respectively)., Conclusions: Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Trichomonas vaginalis (T. vaginalis) is a common sexually transmitted infection, affecting the urogenital tract. Trichomoniasis is customarily treated with metronidazole (MTZ). MTZ is known to cause undesirable side effects and there is several reports on MTZ resistant T. vaginalis. Thus, the present study aimed to in-vitro evaluate the activity of DNA minor groove binder drug ''Netropsin dihydrochloride'' against metronidazole-sensitive T. vaginalis isolates (G and U isolates) and resistant T. vaginalis isolate (ATCC50138) (R isolate). Netropsin was tested at concentrations ranging from 3.5 to 200 μg/ml. It showed effectiveness against all isolates with MLC of 12.5 μg/ml for G and U isolates and of 25 μg/ml for R isolate. Cytotoxicity assay of isolates exposed to the respective MLC of netropsin for 42 h showed a highly significant reduction in the death percentage of MCDK cell line as compared to the effect elicited by drug free controls. The hemolytic activity was evaluated by hemolytic assay and by monitoring the interaction of T. vaginalis isolates with human erythrocytes by inverted microscopy and scanning electron microscopy. The hemolytic assay showed (0%) hemolysis of RBCs incubated with T. vaginalis isolates treated with the corresponding MLC of netropsin for 24 h. Scanning electron microscopy revealed cytoskeletal deformities of netropsin treated isolates. Taken together, these observations suggest that netropsin is a promising therapy for T. vaginalis infection affecting its viability, virulence, cytopathogenic and hemolytic activity with a mechanism of action that might overcome T. vaginalis resistance to metronidazole., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kilo-base pair (kbp), double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine the TVV prevalence in US Trichomonas vaginalis isolates and TVV's associations with patient demographics, clinical outcomes, and metronidazole resistance., Methods: Archived T. vaginalis isolates from the enrollment visits of 355 women participating in a T. vaginalis treatment trial in Birmingham, Alabama, were thawed and grown in culture. Their total RNA was extracted using a Trizol reagent. Contaminating, single-stranded RNA was precipitated using 4.0 M Lithium Chloride and centrifugation. The samples were analyzed by gel electrophoresis to visualize a 4.5 kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates obtained from the women's test of cure visits., Results: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV-positive (TVV+) isolates were significantly older (P = .01), more likely to smoke (P = .04), and less likely to report a history of gonorrhea (P = .04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infections with TVV+ isolates (P = .14 and P = .44, respectively). Of 25 test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance, while 2/15 TVV-negative isolates demonstrated mild to moderate resistance (P = .23)., Conclusions: Of 355 T. vaginalis isolates tested for TVV, T. vaginalis isolates tested for TVV, the prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be commensal to T. vaginalis., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Trichomoniasis is a sexually transmitted disease with hundreds of millions of annual cases worldwide. Approved treatment options are limited to two related nitro-heterocyclic compounds, yet resistance to these drugs is an increasing concern. New antimicrobials against the causative agent, Trichomonas vaginalis , are urgently needed. We show here that clinically approved anticancer drugs that inhibit the proteasome, a large protease complex with a critical role in degrading intracellular proteins in eukaryotes, have submicromolar activity against the parasite in vitro and on-target activity against the enriched T. vaginalis proteasome in cell-free assays. Proteomic analysis confirmed that the parasite has all seven α and seven β subunits of the eukaryotic proteasome although they have only modest sequence identities, ranging from 28 to 52%, relative to the respective human proteasome subunits. A screen of proteasome inhibitors derived from a marine natural product, carmaphycin, revealed one derivative, carmaphycin-17, with greater activity against T. vaginalis than the reference drug metronidazole, the ability to overcome metronidazole resistance, and reduced human cytotoxicity compared to that of the anticancer proteasome inhibitors. The increased selectivity of carmaphycin-17 for T. vaginalis was related to its >5-fold greater potency against the β1 and β5 catalytic subunits of the T. vaginalis proteasome than against the human proteasome subunits. In a murine model of vaginal trichomonad infection, proteasome inhibitors eliminated or significantly reduced parasite burden upon topical treatment without any apparent adverse effects. Together, these findings validate the proteasome of T. vaginalis as a therapeutic target for development of a novel class of trichomonacidal agents., (Copyright © 2019 American Society for Microbiology.)

It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world's population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T. vaginalis : anthraquinones, xanthone-anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A ( 51 ) exhibiting potent activity against the parasite (EC 50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.

Rationale: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate., Patient Concerns: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp., Diagnoses: The patient was diagnosed based on clinical findings for MTX toxic reactions., Interventions: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed., Outcomes: The vulvar edema and oral cavity ulceration and scalp ulceration healed., Lessons: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

Sexually transmitted diseases (STDs) continue to be underrecognized leading to devastating health and economic consequences. Emergency clinicians play an important role in diagnosing and managing STDs and in improving health care outcomes for both the patient and their partners. In addition, antibiotic resistance and emerging infections continue to challenge providers in clinical practice. This review focuses on the cause, history, physical examination, diagnostic studies, and treatment strategies for bacterial vaginosis, chlamydia, genital herpes, gonorrhea, human papillomavirus, granuloma inguinale, Lymphogranuloma Venereum, Mycoplasma genitalium, syphilis, and trichomoniasis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Because of its increasing prevalence worldwide, its sexual transmissibility and its facilitation of human immunodeficiency virus transmission, Trichomonas vaginalis (TV) infection constitutes an important public health concern., The Aim of the Study: While searching for possible resistant TV cases, adequacy of management of TV-infected women was assessed., Methods: Cervical cytology between July 2007 and July 2014 was tested with TV polymerase chain reaction, and 304 women expressed repeatedly positive results, 718 in total. For each of these positive results, a questionnaire about treatment decisions was sent to the 182 Belgian physicians treating these women., Results: From the 346 returned questionnaires by their physician it was evident that 58.1% of women with repeatedly positive TV had received no treatment. TV was overlooked in 31.5%, and in 17.6% the test result was seen but ignored. Upon seeing the positive result, 23.9% of physicians decided that this finding was not important enough to institute treatment, and/or requested confirmatory tests. Adequate treatment was prescribed in 38.4%. Retreatment after failed therapy was given in only 29.3% of the cases. And 60% of the partners of women with persistent TV infection were not traced, nor treated., Conclusion: Most of the repeatedly positive TV infection may not be due to antibiotics resistance. The low awareness, poor attention, failure of contact tracing, and low rates of proper treatment provided by treating physicians question the adequacy of the current management of TV infection and requires renewed education campaigns and increased surveillance., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)