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1.
Sex Transm Dis ; 51(5): 325-330, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38301630

ABSTRACT

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


Subject(s)
Chlamydia Infections , Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas vaginalis , Child , Humans , Young Adult , Adolescent , Chlamydia Infections/diagnosis , Chlamydia Infections/drug therapy , Chlamydia Infections/epidemiology , Quality Improvement , Sexual Partners/psychology , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/epidemiology , Chlamydia trachomatis , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology , Contact Tracing
2.
Bioorg Med Chem ; 102: 117679, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38461555

ABSTRACT

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


Subject(s)
Antiprotozoal Agents , Nitroimidazoles , Trichomonas Infections , Trichomonas vaginalis , Humans , Nitroimidazoles/pharmacology , Metronidazole/pharmacology , HeLa Cells , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Trichomonas Infections/drug therapy , Pyrazoles/pharmacology , Pyrazoles/therapeutic use
3.
Altern Ther Health Med ; 30(3): 6-8, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38518169

ABSTRACT

Trichomonas tenax is an oral protozoan with an estimated global pooled prevalence of 17% in the human population.1 Observational studies have demonstrated a significant statistical correlation between oral colonization by T. tenax and the progression of periodontal disease.2 Proposed pathogenic mechanisms for this protozoan include the production of tissue-damaging enzymes, induction of apoptosis in human cells, and dysbiosis of the oral microbiome.3 In patients for whom metronidazole (MTZ) is contraindicated, phytochemicals may offer a viable alternative for controlling T. tenax. Various plant extracts have shown promising in vitro activity against other trichomonads, such as T. vaginalis and Tritrichomonas foetus, as reviewed by Friedman et al.4.


Subject(s)
Phytochemicals , Trichomonas , Humans , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Trichomonas/drug effects , Trichomonas Infections/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use
4.
Sex Transm Dis ; 50(4): 243-246, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36730040

ABSTRACT

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.


Subject(s)
Trichomonas Infections , Trichomonas Vaginitis , Female , Humans , Metronidazole/therapeutic use , Trichomonas Infections/drug therapy , Tinidazole/pharmacology , Tinidazole/therapeutic use , Trichomonas Vaginitis/drug therapy
5.
Sex Transm Dis ; 50(6): 370-373, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36849257

ABSTRACT

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.


Subject(s)
Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Female , Humans , Metronidazole/pharmacology , Metronidazole/therapeutic use , Tinidazole/therapeutic use , Trichomonas Vaginitis/drug therapy , Pharmaceutical Preparations , Drug Resistance , Trichomonas Infections/drug therapy , Treatment Failure , In Vitro Techniques
6.
Bioorg Chem ; 141: 106888, 2023 12.
Article in English | MEDLINE | ID: mdl-37839143

ABSTRACT

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


Subject(s)
Antiprotozoal Agents , Chalcones , Trichomonas Infections , Trichomonas vaginalis , Humans , Trichomonas vaginalis/metabolism , Chalcones/metabolism , Reactive Oxygen Species/metabolism , Trichomonas Infections/drug therapy , Trichomonas Infections/parasitology , Antiprotozoal Agents/metabolism , Phenols/metabolism
7.
Exp Parasitol ; 250: 108549, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37196704

ABSTRACT

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.


Subject(s)
Antiprotozoal Agents , Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Female , Humans , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Trichomonas Vaginitis/drug therapy , Metronidazole/pharmacology , Metronidazole/therapeutic use , Trichomonas Infections/drug therapy
8.
Clin Infect Dis ; 74(Suppl_2): S152-S161, 2022 04 13.
Article in English | MEDLINE | ID: mdl-35416973

ABSTRACT

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.


Subject(s)
HIV Infections , Premature Birth , Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Centers for Disease Control and Prevention, U.S. , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Infant, Newborn , Male , Metronidazole/therapeutic use , Pregnancy , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/epidemiology , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology , Trichomonas Vaginitis/diagnosis , Trichomonas Vaginitis/drug therapy , Trichomonas Vaginitis/epidemiology , United States/epidemiology
9.
Sex Transm Dis ; 49(4): 262-267, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34813579

ABSTRACT

BACKGROUND: Accurate same-day sexually transmitted infection (STI) diagnostic testing is generally unavailable, leading to syndromic management with high rates of overtreatment and undertreatment. We analyzed the ease of integration of the Visby STI Panel into clinical practice, studied acceptance by patients and clinic personnel, and assessed the potential to inform accurate treatment decisions. METHODS: In a cross-sectional single-visit study of 55 women aged 18 to 56 years, women self-collected vaginal swab samples that were analyzed using the Visby STI Panel for Chlamydia trachomatis, Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Results were compared with standard-of-care clinic results from send-out laboratory polymerase chain reaction tests. Surveys assessed patient and device operator experiences with the Visby STI Panel and clinicians' perceived need for and acceptance of the device. Time parameters were measured to evaluate the impact on clinical workflow, and syndromic treatment decisions were compared with anticipated treatment based on the Visby STI Panel results. RESULTS: Patients strongly agreed that sample self-collection was easy, and operators reported the device easy to use. Clinicians valued the rapid return of results, and patients were comfortable waiting up to 30 minutes to receive them. In 13 of 15 cases, the Visby STI Panel correctly identified undertreated patients as infected and correctly identified all 33 incidences of overtreatment. CONCLUSIONS: Clinical adoption of the Visby STI Panel into primary care clinics and doctors' offices could reduce overtreatment and undertreatment of STIs. If integrated efficiently into the clinical workflow, the test would have minimal impact on staff time and visit duration for patients.


Subject(s)
Chlamydia Infections , Gonorrhea , Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas vaginalis , Trichomonas , Chlamydia Infections/diagnosis , Chlamydia Infections/drug therapy , Chlamydia Infections/epidemiology , Chlamydia trachomatis/genetics , Cross-Sectional Studies , Female , Gonorrhea/diagnosis , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Humans , Male , Neisseria gonorrhoeae/genetics , Point-of-Care Testing , Polymerase Chain Reaction , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/epidemiology , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology , Trichomonas vaginalis/genetics
10.
Parasitol Res ; 121(8): 2421-2432, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35657426

ABSTRACT

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.


Subject(s)
Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Drug Resistance , Female , Humans , Metronidazole/pharmacology , Metronidazole/therapeutic use , Polymerase Chain Reaction , Pregnancy , Trichomonas Infections/drug therapy , Trichomonas Vaginitis/diagnosis
11.
Parasitol Res ; 121(9): 2697-2711, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35857093

ABSTRACT

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.


Subject(s)
Quinolines , Trichomonas Infections , Trichomonas vaginalis , Animals , Chlorocebus aethiops , Humans , Molecular Docking Simulation , Quinolines/pharmacology , Quinolines/therapeutic use , Trichomonas Infections/drug therapy , Trophozoites , Vero Cells
12.
Parasitol Res ; 121(3): 981-989, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35113221

ABSTRACT

Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and it may have serious consequences, especially for women. Currently, 5-nitroimidazole drugs are the treatment of choice for trichomoniasis, although presenting adverse effects and reported cases of drug resistance. Metabolites isolated from marine fungi have attracted considerable attention due to their unique chemical structures with diverse biological activities, including antiprotozoal activity. In this study, we showed the anti-Trichomonas vaginalis activity of fractions obtained from marine fungi and the chemical composition of the most active fraction was determined. Ethyl acetate fractions of the fungus Aspergillus niger (EAE03) and Trichoderma harzianum/Hypocrea lixii complex (EAE09) were active against T. vaginalis. These samples, EAE03 and EAE09, were also effective against the fresh clinical isolate metronidazole-resistant TV-LACM2R, presenting MIC values of 2.0 mg/mL and 1.0 mg/mL, respectively. The same MIC values were found against ATCC 30,236 T. vaginalis isolate. In vitro cytotoxicity revealed only the fraction named EAE03 with no cytotoxic effect; however, the active fractions did not promote a significant hemolytic effect after 1-h incubation. Already, the in vivo toxicity evaluation using Galleria mellonella larvae demonstrated that none of the tested samples caused a reduction in animal survival. The fraction EAE03 was followed for purification steps and analyzed by LC-DAD-MS. Eleven compounds were annotated, including butyrolactone, butanolide, and atromentin. Overall, the range of activities reported confirms the potential of marine fungi to produce bioactive molecules.


Subject(s)
Antiprotozoal Agents , Trichomonas Infections , Trichomonas vaginalis , Animals , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Female , Fungi , Humans , Metronidazole/pharmacology , Trichomonas Infections/drug therapy
13.
Parasitol Res ; 121(8): 2453-2455, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35676563

ABSTRACT

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.


Subject(s)
Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Benzamides , Drug Resistance , Female , Humans , Male , Metronidazole/pharmacology , Metronidazole/therapeutic use , Thiazoles , Trichomonas Infections/drug therapy , Trichomonas Vaginitis/drug therapy
14.
Arch Pharm (Weinheim) ; 355(6): e2200046, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35332589

ABSTRACT

The development of new drugs is continuous in the world; currently, saving resources (both economic ones and time) and preventing secondary effects have become a necessity for drug developers. Trichomoniasis is the most common nonviral sexually transmitted infection affecting more than 270 million people around the world. In our research group, we focussed on developing a selective and more effective drug against Trichomonas vaginalis, and we previously reported on a compound, called A4, which had a trichomonacidal effect. Later, we determined another compound, called D4, which also had a trichomonacidal effect together with favorable toxicity results. Both A4 and D4 are directed at the enzyme triosephosphate isomerase. Thus, we made combinations between the two compounds, in which we determined a synergistic effect against T. vaginalis, determining the IC50 and the toxicity of the best relationship to obtain the trichomonacidal effect. With these results, we can propose a combination of compounds that represents a promising alternative for the development of a new therapeutic strategy against trichomoniasis.


Subject(s)
Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas vaginalis , Humans , Sexually Transmitted Diseases/complications , Sexually Transmitted Diseases/drug therapy , Structure-Activity Relationship , Trichomonas Infections/complications , Trichomonas Infections/drug therapy , Triose-Phosphate Isomerase/pharmacology
15.
Clin Infect Dis ; 73(6): e1282-e1289, 2021 09 15.
Article in English | MEDLINE | ID: mdl-33768237

ABSTRACT

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.


Subject(s)
Trichomonas Infections , Vaginosis, Bacterial , Double-Blind Method , Female , Humans , Metronidazole/adverse effects , Metronidazole/analogs & derivatives , Treatment Outcome , Trichomonas Infections/drug therapy
16.
Clin Infect Dis ; 73(6): 1119-1124, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34079999

ABSTRACT

Trichomonas vaginalis infections in men are traditionally considered to be benign and consequently have been overlooked. However, men with this common sexually transmitted infection can experience urethritis, prostatitis, reduced fertility, and amplified human immunodeficiency virus risk. In addition, men are often asymptomatic and can unknowingly spread the infection to their female sexual partners. With advances in T. vaginalis diagnostics, more men are being diagnosed, yet the optimal method of treatment in men remains unknown. The purpose of this review is to discuss the epidemiology, natural history, diagnosis, and treatment of T. vaginalis among men.


Subject(s)
Sexually Transmitted Diseases , Trichomonas Infections , Trichomonas vaginalis , Urethritis , Humans , Male , Prevalence , Sexual Partners , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/drug therapy , Sexually Transmitted Diseases/epidemiology , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology
17.
Sex Transm Dis ; 48(8): e111-e115, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33137011

ABSTRACT

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.


Subject(s)
Nitroimidazoles , Trichomonas Infections , Trichomonas Vaginitis , Trichomonas vaginalis , Female , Humans , Metronidazole/adverse effects , Nitroimidazoles/adverse effects , Trichomonas Infections/drug therapy , Trichomonas Vaginitis/drug therapy
18.
Sex Transm Dis ; 48(3): e45-e47, 2021 03 01.
Article in English | MEDLINE | ID: mdl-32810026

ABSTRACT

ABSTRACT: We used 2016-2018 outpatient claims data to calculate direct outpatient medical costs per case of trichomoniasis in 2019 US dollars. The outpatient, drug, and total costs per treated case of trichomoniasis were $174, $39, and $213, respectively. Total costs were higher for female patients ($220) than for male patients ($158).


Subject(s)
Outpatients , Trichomonas Infections , Ambulatory Care , Databases, Factual , Female , Health Care Costs , Humans , Male , Retrospective Studies , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy , Trichomonas Infections/epidemiology , United States/epidemiology
19.
Bioorg Med Chem Lett ; 37: 127843, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33556576

ABSTRACT

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated.


Subject(s)
Antiparasitic Agents/pharmacology , Indazoles/pharmacology , Trichomonas Infections/drug therapy , Trichomonas vaginalis/drug effects , Antiparasitic Agents/chemical synthesis , Antiparasitic Agents/chemistry , Dose-Response Relationship, Drug , Drug Resistance/drug effects , Indazoles/chemical synthesis , Indazoles/chemistry , Molecular Structure , Structure-Activity Relationship , Trichomonas Infections/parasitology
20.
BMC Infect Dis ; 21(1): 842, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34416850

ABSTRACT

BACKGROUND: Trichomonas tenax may appear in the oral cavity of humans due to poor dentition or oral hygiene. Pyopneumothorax is a serious complication of lower respiratory tract infections that very rarely can be caused by a trichomonad species in predisposed individuals. We report a rare case of pleurisy due to T. tenax with coinfection by a fungus. CASE PRESENTATION: We describe a 16-year-old patient with cerebral palsy who presented with severe pyopneumothorax. T. tenax was identified by microscopic examination of the pleural effusion and next-generation sequencing. We also identified Geotrichum capitatum in the pleural effusion and bronchoalveolar lavage fluid cultures. Treatment with voriconazole and metronidazole successfully eliminated these pathogens and relieved the clinical symptoms. A literature review indicated this is the first reported case of pleurisy due to T. tenax with coinfection by a fungus. CONCLUSION: The rarity of pyopneumothorax caused by T. tenax coinfection with a fungus should not be overlooked in the clinic. These patients should be and treated in a timely manner.


Subject(s)
Coinfection , Trichomonas Infections , Trichomonas , Adolescent , Coinfection/drug therapy , Humans , Mouth , Saccharomycetales , Trichomonas Infections/complications , Trichomonas Infections/diagnosis , Trichomonas Infections/drug therapy
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