Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis.

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

In vitro anti-Trichomonas gallinae effects of Ziziphus vulgaris L. and Camellia sinensis (L.) Kuntze extracts.

BACKGROUND: Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating avian trichomoniasis. Due to drug resistance, non-chemical alternatives, such as medicinal plant extracts, are also considered possible therapies for this disease. OBJECTIVES: This study compares the antitrichomonal effects of MTZ with extracts of Camellia sinensis and Ziziphus vulgaris on T. gallinae in vitro. METHODS: Samples of T. gallinae were taken from infected pigeons. Multi-well plates with different concentrations (5, 10, 25, 50 and 100 µg/mL) of plant extracts were used for the in vitro study. RESULTS: The minimum inhibitory concentration (MIC) of C. sinensis extract was 25 µg/mL over 24 h, compared to 50 µg/mL for MTZ. The MIC value of the Z. vulgaris extracts was 50 µg/mL. CONCLUSIONS: The results suggest that the extracts of Z. vulgaris and C. sinensis, as potential natural agents, could have anti-avian trichomoniasis properties. This study also shows that MTZ, C. sinensis and Z. vulgaris are equally effective in preventing the growth of T. gallinae trophozoites in the culture.

Reducing Barriers for Expedited Partner Treatment in Adolescents and Young Adults: A Quality Improvement Initiative.

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

Phenolic chalcones as agents against Trichomonas vaginalis.

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

Efficacy of single-dose oral secnidazole for the treatment of trichomoniasis in women co-infected with trichomoniasis and bacterial vaginosis: a post hoc subgroup analysis of phase 3 clinical trial data.

OBJECTIVES: Bacterial vaginosis (BV) and trichomoniasis are the most common causes of vaginitis. Both infections are associated with increased risk of acquisition and transmission of HIV and other sexually transmitted infections as well as adverse reproductive health outcomes. Co-infection is common, with rates ranging from 60% to 80%. We evaluated the efficacy of single-dose oral secnidazole 2 g for the treatment of trichomoniasis in a subgroup of women co-infected with BV and trichomoniasis. DESIGN: Post hoc analysis of data from a phase 3 randomised, double-blind, placebo-controlled, delayed-treatment study. SETTING: 10 centres in the USA. PARTICIPANTS: Subgroup of women (aged ≥12 years) with a confirmed diagnosis of Trichomonas vaginalis and co-infection with BV clinically diagnosed using Amsel's criteria. INTERVENTION: Single dose of secnidazole 2 g or placebo. OUTCOME MEASURES: The primary efficacy outcome was the microbiological cure (negative culture for T. vaginalis) at the test of cure (TOC) visit 6-12 days after dosing in the modified intent-to-treat population (mITT). At TOC, participants received the opposite treatment. RESULTS: Of the 131 T. vaginalis-infected participants in the mITT, 79 (60.3%) met ≥3 Amsel's criteria for BV at enrolment. Microbiological cure rates for trichomoniasis at TOC among this subgroup of women were 97.7% (42/43) for secnidazole and 0% (0/36) for placebo. CONCLUSION: Single-dose oral secnidazole 2 g was highly efficacious in curing trichomoniasis in women co-infected with BV. Appropriate and effective treatment options for co-infection are essential for reducing transmission and reinfection. Secnidazole is the only single-dose medication approved by the Food and Drug Administration for the treatment of BV in women and trichomoniasis in women and men. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03935217; post-results.

Identification of new drug candidates against Trichomonas gallinae using high-throughput screening.

Trichomonas gallinae is a protozoan parasite that is the causative agent of trichomoniasis, and infects captive and wild bird species throughout the world. Although metronidazole has been the drug of choice against trichomoniasis for decades, most Trichomonas gallinae strains have developed resistance. Therefore, drugs with new modes of action or targets are urgently needed. Here, we report the development and application of a cell-based CCK-8 method for the high-throughput screening and identification of new inhibitors of Trichomonas gallinae as a beginning point for the development of new treatments for trichomoniasis. We performed the high-throughput screening of 173 anti-parasitic compounds, and found 16 compounds that were potentially effective against Trichomonas gallinae. By measuring the median inhibitory concentration (IC50) and median cytotoxic concentration (CC50), we identified 3 potentially safe and effective compounds against Trichomonas gallinae: anisomycin, fumagillin, and MG132. In conclusion, this research successfully established a high-throughput screening method for compounds and identified 3 new safe and effective compounds against Trichomonas gallinae, providing a new treatment scheme for trichomoniasis.

Effects of SQ109 on Trichomonas vaginalis.

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.

Novel therapeutic opportunities for Toxoplasma gondii, Trichomonas vaginalis, and Giardia intestinalis infections.

INTRODUCTION: Toxoplasma gondii, Trichomonas vaginalis, and Giardia intestinalis are the causative agents of toxoplasmosis, trichomoniasis, and giardiasis, three important infections threatening human health and affecting millions of people worldwide. Although drugs and treatment are available to fight these protozoan parasites, side effects and increasing drug resistance require continuous efforts for the development of novel effective drugs. AREAS COVERED: The patents search was carried out in September/October 2022 with four official scientific databases (Espacenet, Scifinder, Reaxys, Google Patents). Treatments for toxoplasmosis, trichomoniasis, and giardiasis (2015-2022) have been grouped according to their chemotypes. In particular, novel chemical entities have been reported and investigated for their structure-activity relationship, when accessible. On the other hand, drug repurposing, extensively exploited to obtain novel antiprotozoal treatment, has been in-depth described. Finally, natural metabolites and extracts have also been reported. EXPERT OPINION: T. gondii, T. vaginalis, and G. intestinalis are protozoan infections usually controlled by immune system in immunocompetent patients; however, they could represent a threatening health for immunocompromised people. The needs of novel effective drugs, endowed with new mechanisms of actions, arises from the increasing drug resistance affecting antibiotic as well as antiprotozoal therapies. In this review different therapeutic approaches to treat protozoan infections have been reported.

Trichomoniasis.

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.

Trichomonas tenax induces barrier defects and modulates the inflammatory cytotoxicity of gingival and pulmonary epithelial cells.

BACKGROUND: Trichomonas tenax is a single-cell flagellated anaerobic organism, commensal in the human oral cavity. Although a previous study indicated that T. tenax could cause cell damage and phagocytose host epithelial cells, its pathological effects on gum cells remain unknown. Furthermore, several case reports have detected T. tenax in several patients with empyema and/or pleural effusion, which may have been aspirated from the oral cavity. However, the cytotoxic effects and immune responses of alveolar cells are unknown. Therefore, we aimed to determine the cytotoxic and immune effects of T. tenax on gums and pulmonary cell lines. The cytopathic effect and lactate dehydrogenase (LDH) cytotoxicity assays were used to determine the level of cell damage in gum and lung epithelial cells. Western blot was used to determine the disruption of cell junctions. Finally, epithelial cell cytokines were measured using ELISA to elucidate the immune response to T. tenax. RESULTS: We found that T. tenax induced a cytotoxic effect on gum epithelial cells by disrupting cell junctions; however, it hardly triggered cellular damage in alveolar A549 cells and mucoepidermoid NCI-H292 cells. Furthermore, T. tenax induced the production of IL-6 at a low multiplicity of infection (MOI) in gum, A549, and NCI-H292 cells. CONCLUSIONS: Our results suggest that T. tenax can trigger gingival cell cytotoxicity, disrupt cell junctions, and induce IL-6 production in gingival and pulmonary cell lines.

Title: Trichomonas tenax induit des défauts de barrière et module la cytotoxicité inflammatoire des cellules épithéliales gingivales et pulmonaires. Abstract: Contexte : Trichomonas tenax est un organisme anaérobie unicellulaire flagellé, commensal dans la cavité buccale humaine. Bien qu'une étude précédente ait indiqué que T. tenax pouvait endommager les cellules et phagocyter les cellules épithéliales de l'hôte, ses effets pathogènes sur les cellules gingivales restent inconnus. En outre, plusieurs rapports ont détecté T. tenax chez des patients présentant un empyème et/ou un épanchement pleural, qui peut avoir été aspiré de la cavité buccale. Cependant, les effets cytotoxiques et les réponses immunitaires des cellules alvéolaires sont inconnus. Par conséquent, nous avons cherché à déterminer les effets cytotoxiques et immunitaires de T. tenax sur des lignées cellulaires de gencives et de poumons. Les tests d'effet cytopathique et de cytotoxicité de la lactate déshydrogénase (LDH) ont été utilisés pour déterminer le niveau de dommages cellulaires dans les cellules. Le Western Blot a été utilisé pour déterminer la perturbation des jonctions cellulaires. Enfin, les cytokines des cellules épithéliales ont été mesurées par ELISA pour élucider la réponse immunitaire à T. tenax. Résultats : Nous avons constaté que T. tenax induisait un effet cytotoxique sur les cellules épithéliales gingivales en perturbant les jonctions cellulaires. Cependant, T. tenax a déclenché des dommages cellulaires seulement mineurs dans les cellules alvéolaires A549 et les cellules mucoépidermoïdes NCI-H292. De plus, T. tenax a induit la production d'IL-6 à une faible multiplicité d'infection (MOI) dans les cellules de gencives, A549 et NCI-H292. Conclusions : Nos résultats suggèrent que T. tenax peut déclencher la cytotoxicité des cellules gingivales, perturber les jonctions cellulaires et induire la production d'IL-6 dans les lignées cellulaires gingivales et pulmonaires.

Successful Treatment of Persistent 5-Nitroimidazole-Resistant Trichomoniasis With an Extended Course of Oral Secnidazole Plus Intravaginal Boric Acid.

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.

In Vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentrations for Metronidazole and Tinidazole That Correspond With Treatment Failure.

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.

Drug susceptibility testing for oxygen-dependent and oxygen-independent resistance phenotypes in trichomonads.

Trichomonas vaginalis is the most prevalent, non-viral sexually transmitted human infection, causing 170 million cases of trichomoniasis annually. Since the 1950s, treatment has relied on 5-nitroimidazoles (5NIs), leading to increasing drug resistance. A similar drug resistance problem is present in the veterinary pathogen, Tritrichomonas foetus. There are currently no agreed standards for defining 5NI resistance, due in part to two distinct oxygen-dependent ("aerobic") and oxygen-independent ("anaerobic") resistance phenotypes. Diagnostic tools to detect 5NI resistance are lacking, and current assays used to phenotypically assess 5NI resistance in vitro are complicated by these two resistance phenotypes. We demonstrate that microaerophilic conditions support sufficient parasite growth to interrogate oxygen-dependent resistance of 5NIs against known resistant and susceptible isolates of T. vaginalis and T. foetus. We further demonstrate that microaerophilic conditions allow sufficient growth for compatibility with existing growth assays, including our TriTOX assay. Adopting microaerophilic conditions eliminates traditional 'by-eye' estimates of minimum inhibitory concentrations and opens up options for increased throughput and automation, scalable to higher-throughput analyses of 5NI resistance. This would further allow the development of quantitative phenotypic standards to benchmark oxygen-dependent or oxygen-independent trichomonad 5NI resistance towards standardised surveillance programs to combat drug resistance.

In vitro and in silico trichomonacidal activity of 2,8-bis(trifluoromethyl) quinoline analogs against Trichomonas vaginalis.

Trichomoniasis is a great public health burden worldwide and the increase in treatment failures has led to a need for finding alternative molecules to treat this disease. In this study, we present in vitro and in silico analyses of two 2,8-bis(trifluoromethyl) quinolines (QDA-1 and QDA-2) against Trichomonas vaginalis. For in vitro trichomonacidal activity, up to seven different concentrations of these drugs were tested. Molecular docking, biochemical, and cytotoxicity analyses were performed to evaluate the selectivity profile. QDA-1 displayed a significant effect, completely reducing trophozoites viability at 160 µM, with an IC50 of 113.8 µM, while QDA-2 at the highest concentration reduced viability by 76.9%. QDA-1 completely inhibited T. vaginalis growth and increased reactive oxygen species production and lipid peroxidation after 24 h of treatment, but nitric oxide accumulation was not observed. In addition, molecular docking studies showed that QDA-1 has a favorable binding mode in the active site of the T. vaginalis enzymes purine nucleoside phosphorylase, lactate dehydrogenase, triosephosphate isomerase, and thioredoxin reductase. Moreover, QDA-1 presented a level of cytotoxicity by reducing 36.7% of Vero cells' viability at 200 µM with a CC50 of 247.4 µM and a modest selectivity index. In summary, the results revealed that QDA-1 had a significant anti-T. vaginalis activity. Although QDA-1 had detectable cytotoxicity, the concentration needed to eliminate T. vaginalis trophozoites is lower than the CC50 encouraging further studies of this compound as a trichomonacidal agent.

In vitro activity of amixicile against T. vaginalis from clinical isolates.

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.

British Association for Sexual Health and HIV (BASHH) United Kingdom national guideline on the management of Trichomonas vaginalis 2021.

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).

Detection of metronidazole resistance in Trichomonas vaginalis using uncultured vaginal swabs.

Trichomonas vaginalis (T. vaginalis) is the most prevalent sexually transmitted infection (STI) globally. Metronidazole is the drug of choice for treating T. vaginalis infections although metronidazole-resistant T. vaginalis has been reported in clinical isolates. The purpose of this study was to determine the presence of mutations in nitroreductase genes associated with metronidazole resistance in vaginal swabs testing positive for T. vaginalis. This study included 385 human immunodeficiency virus (HIV)-positive pregnant women. Vaginal swabs were collected from consenting pregnant women and used for the detection of T. vaginalis using the TaqMan assay. From the vaginal swabs, nitroreductase genes ntr4 and ntr6 containing mutations associated with metronidazole resistance were amplified using a quantitative polymerase chain reaction (PCR) assay. To validate the PCR assay, T. vaginalis cultured isolates with known metronidazole resistance profiles were used as controls in the mutation detection assays. The prevalence of T. vaginalis in the study population was 12.2% (47/385). Mutations associated with resistance to metronidazole were detected in more than 40% of the samples tested, i.e. 21/47 (45%) and 24/47 (51%) for ntr4 and ntr6, respectively. A total of 19 samples (40%) carried mutations for both ntr4 and ntr6 genes associated with metronidazole resistance. The validation assays showed a positive correlation between phenotypic and genotypic resistance profiles. This study found a high prevalence of mutations associated with metronidazole resistance. This is concerning since metronidazole is currently used in the syndromic management of STIs in South Africa. Molecular-based assays for monitoring metronidazole resistance profiles using nitroreductase genes may serve as a feasible method for antimicrobial surveillance studies for T. vaginalis.

Secnidazole: a treatment for trichomoniasis in adolescents and adults.

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.

Diagnosis and Management of Trichomonas vaginalis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

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.