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OBJECTIVES: Antimicrobial resistance in Mycoplasma genitalium (MG) is a poorly surveyed and controlled global health concern. We evaluated the first commercial dual resistance assay, AmpliSens M. genitalium-ML/FQ-Resist-FL assay, for detection of potential macrolide and quinolone resistance-associated mutations (MRAMs and QRAMs, respectively) and estimated the prevalence of these mutations in MG in St. Petersburg, Russia. METHODS: Urogenital samples positive (n=145 from 2007 to 2020) and negative (n=56 from 2021) for MG in routine diagnostics were retrospectively analysed using the AmpliSens M. genitalium-ML/FQ-Resist-FL assay (Central Research Institute of Epidemiology, Moscow, Russia) and Sanger sequencing for validation. RESULTS: The AmpliSens M. genitalium-ML/FQ-Resist-FL assay detected potential MRAMs and QRAMs with sensitivities of 100% (CI95% 83.9 to 100) and 92.3% (CI95% 66.7 to 99.6) and specificities of 99.2% (CI95% 95.6 to 100) and 100% (CI95% 97.2 to 100), respectively, in clinical specimens with ≥1000 MG geq/mL. In total, MRAMs were detected in 13.8% (CI95% 9.1 to 20.3) of samples, with 23S rRNA A2058G being the most prevalent mutation (45.0% (CI95% 25.8 to 65.8)). QRAMs were found in 9.0% (CI95% 5.3 to 14.7) of samples, with S83I the most frequent mutation (53.8% (CI95% 29.1 to 76.8)). Dual resistance was observed in 5.5% (CI95% 2.8 to 10.5) of samples. Potential MRAM and dual resistance rates significantly increased over time: from 0% in 2007-2008 to 25% (p trend =0.0009) and 10% (p trend =0.0447), respectively, in 2018-2020. QRAM rate appeared to increase (from 0% to 13%), but significance was not reached (p trend =0.0605). CONCLUSIONS: The rapid increase in MG antimicrobial resistance in St. Petersburg, especially prominent for MRAMs, necessitates implementation of macrolide resistance-guided therapy in Russia. The first commercial dual resistance assay, AmpliSens M. genitalium-ML/FQ-Resist-FL assay, was sensitive and specific for detection of poten, Funding agency:Ministry of Science, ICT & Future Planning, Republic of Korea A19--119--021290030--0

BackgroundMycoplasma genitalium (MG) is associated with urethritis in men and weakly associated with pelvic inflammatory disease in women. Mycoplasma genitalium coinfections with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are commonly reported; however, little is known about their interaction. One study suggested that MG/NG coinfections might increase the bacterial load of NG, which has been shown to have a higher transmission potential. As even less is known about the impact of a simultaneous MG/CT infection, we assessed whether patients with urogenital MG/CT coinfections have a higher bacterial load than patients with a single infection.MethodsThere were 1673 urogenital samples from patients from a population-based chlamydia study, and our sexually transmitted infection clinic tested for both CT and MG. When positive, the load was quantified. Nonparametric tests compared the CT and MG load, and linear regression analyses tested the association of the CT and MG load within a patient.ResultsIn 60 MG-positive patients, MG load ranged from 1.7 to 6.0 log10 copies/ml, similar to the CT load distribution. Only 6 patients were MG-positive and CT-negative, but the MG load distribution was similar to that of CT-positive patients (n.s.). The MG and CT load was unrelated in coinfected persons (n.s.).ConclusionsWe found no correlation between the CT and MG load in urogenital samples, and the MG load distribution was similar in CT-positive and CT-negative patients. These results could have implications for the transmission risk of these infections.

This article provides information on the course, origin, prevention, treatment and treatment of urethritis. There is also information on the treatment of urethritis with tinctures. In the treatment of the urinary tract, patients are usually treated in an outpatient setting, the drugs are selected according to the etiology of the patient. The article also provides information about acute urethritis. There is also enough information about the symptoms of urethritis in men and women. I hope you will like this article.

Objective: This study aimed to investigate the prevalence of sexually transmitted infections (STIs) and colonizing bacteria in relation to urogenital symptoms. Materials and Methods: In this cross-sectional study, patients visiting the STI clinic at Umeå University Hospital were asked for symptoms and condom use. Samples from 759 patients (465 male and 294 female) were analyzed for 4 STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) and 3 colonizing bacteria (Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum). Results: Chlamydia trachomatis prevalence was 11% among women and 9.5% among men. Neisseria gonorrhoeae prevalence was 0.7% among women and 0.9% among men. Mycoplasma genitalium was found in 11% and 5.6% of women and men, respectively. Asymptomatic men and women had similar distribution patterns of microorganisms as those with urogenital symptoms, with the exceptions of Neisseria gonorrhoeae- and Mycoplasma genitalium-infected men who declared symptoms more frequently. Of 158 men with urogenital symptoms, 55% were test-negative. Of 129 women with urogenital symptoms, 12% were test-negative. Conclusions: This study reveals a complex picture, where a large number of multi-positive tests made it complicated to correlate urogenital symptoms with microorganisms. A high number of test-negative but symptomatic patients indicate a need of searching for additional pathogens.

Introduction: Sexually transmitted infections are a public health problem worldwide. Their inadequate antimicrobial management has been associated with a higher risk of recurrence.Objective: To characterize the main sexually transmitted infections, the adherence to clinical practice guidelines, and the factors associated with recurrence in Colombia.Materials and methods: We conducted an observational study to identify the main sexually transmitted infections, the sociodemographic variables, and the pharmacological management in a patient cohort from a population database of 6.5 million people affiliated with the Colombian health system. We made a multivariate analysis to identify the variables associated with recurrence.Results: We detected 3,158 patients with a mean age of 41.8 ± 14.5 years, of whom 63.1% were men. We found 4.030 episodes of sexually transmitted infections, predominantly urethral syndrome (27.5%). Only 13.6% of patients with urethral syndrome, ulcerative syndrome, or genital warts were managed in compliance with clinical practice guidelines and 20.6% were dispensed condoms; 16.7% of patients had recurrences and being male (OR=1.32; 95%CI 1.08-1.63), <30 years old (OR=1.72; 95%CI 1.40-2.13), being treated in municipalities other than capital cities (OR=1.43; 95%CI 1.06-1.94), and having received inadequate treatment for the first episode (OR=1.93; 95%CI 1.52-2.39) were associated with recurrence.Conclusions: The majority of patients with sexually transmitted infections were not treated in compliance with clinical practice guidelines and those who did not have adequate management had a higher risk of recurrence., Introducción. Las infecciones de transmisión sexual constituyen actualmente un problema de salud pública en el mundo. Su inadecuado tratamiento antimicrobiano se ha relacionado con un mayor riesgo de recurrencias.Objetivo. Caracterizar las principales infecciones de transmisión sexual, el cumplimiento de las guías de práctica clínica de Colombia y los factores asociados con las recurrencias.Materiales y métodos. Se hizo un estudio observacional para determinar las principales infecciones de transmisión sexual, las variables sociodemográficas y el tratamiento farmacológico en una cohorte de pacientes registrados en una base de datos poblacional de 6,5 millones de personas afiliadas al Sistema de Salud de Colombia. Se hizo un análisis multivariado para establecer las variables asociadas con las recurrencias.Resultados. Se detectaron 3.158 pacientes; su edad media era de 41,8 ±14,5 años y 63,1 % de ellos correspondía a hombres; se encontraron 4.030 episodios de infecciones de transmisión sexual con predominio del síndrome uretral (27,5 %). El 13,6 % de los pacientes con síndrome uretral, ulceroso o con verrugas genitales se manejó según las guías de práctica clínica. El 20,6 % tenía acceso a condones y el 16,7 % presentó recurrencias. Ser hombre (OR=1,32; IC95% 1,08-1,63), tener <30 años (OR=1,72; IC95% 1,40-2,13), ser tratado en municipios distintos a ciudades capitales (OR=1,43; IC95% 1,06-1,94) y haber recibido un tratamiento inadecuado en el primer episodio (OR=1,93; IC95% 1,52-2,39) fueron factores asociados con las recurrencias.Conclusiones. La mayoría de los pacientes con infecciones de transmisión sexual no fueron tratados según las guías de práctica clínica y quienes no tuvieron un manejo adecuado presentaban mayor riesgo de recurrencias.

Background. Most oropharyngeal Neisseria gonorrhoeae infections are asymptomatic, and many infections remain undetected, creating a reservoir for ongoing transmission and potential drug resistance. It is unclear what the optimal testing policy is in men who have sex with men (MSM), as routine universal testing data are lacking.Methods. Surveillance data from all Dutch sexually transmitted infection (STI) clinics between 2008 and 2017 were used (N = 271 242 consultations). Oropharyngeal testing policy was defined as routine universal testing when >= 85% of consultations included oropharyngeal testing or as selective testing (Results. Routine universal testing was performed in 90% (238 619/265 127) of consultations. Prevalence was higher using routine universal testing (5.5%; 95% CI, 5.4-5.6; 12 769/233 476) than with selective testing (4.7%; 95% CI, 4.4-5.0; 799/17 079; P < .001). Proportions of oropharyngeal-only infections were 55% and 47%, respectively. Independent risk factors were age 43 years), being notified for any STI (OR, 2.0; 95% CI, 1.9-2.1), concurrent urogenital N. gonorrhoeae (OR, 2.4; 95% CI, 2.1-2.7), and concurrent anorectal N. gonorrhoeae (OR, 11.4; 95% CI, 10.6-12.3). When using any of the risk factors age, notified, or oral sex as testing indicators, 98.4% (81 022/82 332) of MSM would be tested, finding 99.5% (4814/4838) of infections.Conclusions. Routine universal testing detected more oropharyngeal N. gonorrhoeae infections than selective testing, of which more than half would be oropharyngeal only. Using independent risk factors as testing indicator is not specific. Therefore, routine universal oropharyngeal testing in MSM is feasible and warranted, as currently advised in most guidelines.

Data from a large prospective multicenter clinical validation study of a nucleic acid amplification in vitro diagnostic test for Mycoplasma genitalium were analyzed to describe the prevalence of M. genitalium infection, risk factors, and disease associations in female and male patients seeking care in diverse geographic regions of the United States. Among 1,737 female and 1,563 male participants, the overall prevalence of M. genitalium infection was 10.3% and was significantly higher in persons ages 15 to 24 years than in persons ages 35 to 39 years (for females, 19.8% versus 4.7% [odds ratio {OR} = 5.05; 95% confidence interval {CI} = 3.01 to 8.46]; for males, 16.5% versus 9.4% [OR = 1.91; 95% CI = 1.20 to 3.02]). The risk for M. genitalium infection was higher in black than in white participants (for females, 12.0% versus 6.8% [OR = 1.88; 95% CI = 1.30 to 2.72]; for males, 12.9% versus 6.9% [OR = 2.02; 95% CI = 1.38 to 2.96]) and higher in non-Hispanic than in Hispanic participants (for females, 11.2% versus 6.0% [OR = 1.97; 95% CI = 1.25 to 3.10]; for males, 11.6% versus 6.8% [OR = 1.80; 95% CI = 1.14 to 2.85]). Participants reporting urogenital symptoms had a significantly elevated risk of M. genitalium infection compared to that for asymptomatic individuals (for females, OR = 1.53 [95% CI = 1.09 to 2.14]; for males, OR = 1.42 [95% CI = 1.02 to 1.99]). Women diagnosed with vaginitis and cervicitis had a higher prevalence of M. genitalium infection than women without those diagnoses, although this was statistically significant only for vaginitis (for vaginitis, OR = 1.88 [95% CI = 1.37 to 2.58]; for cervicitis, OR = 1.42 [95% CI = 0.61 to 2.96]). A diagnosis of urethritis in men was also significantly associated with M. genitalium infection (OR = 2.97; 95% CI = 2.14 to 4.13). Few characteristics distinguished asymptomatic from symptomatic M. genitalium infections. These results from persons seeking care in the United States suggest that M. genitalium infection sh

BackgroundAntimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the United States or about its associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and posttreatment symptom persistence.MethodsWe enrolled men presenting with urethritis symptoms to 6 US sexually transmitted disease (STD) clinics during June 2017-July 2018; men with urethritis were eligible for follow-up contact and, if they had persistent symptoms or MG, a chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S ribosomal ribonucleic acid (rRNA) loci (macrolide resistance-associated mutations [MRMs]) and in parC and gyrA (quinolone-associated mutations) were detected by targeted amplification/Sanger sequencing.ResultsAmong 914 evaluable participants, 28.7% (95% confidence interval [CI], 23.8-33.6) had MG. Men with MG were more often Black (79.8% vs 66%, respectively), <30 years (72.9% vs 56.1%, respectively), and reported only female partners (83.7% vs 74.2%, respectively) than men without MG. Among MG-positive participants, 64.4% (95% CI, 58.2-70.3%) had MRM, 11.5% (95% CI, 7.9-16.0%) had parC mutations, and 0% had gyrA mutations. Among participants treated with azithromycin-based therapy at enrollment and who completed the follow-up survey, persistent symptoms were reported by 25.8% of MG-positive/MRM-positive men, 13% of MG-positive/MRM-negative men, and 17.2% of MG-negative men.ConclusionsMG infection was common among men with urethritis; the MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men both with and without MG.

INTRODUCTION: (MG) causes frequently asymptomatic STIs. MG prevalence figures are lacking and management is complicated by the lack of etiological diagnostics and high antimicrobial resistance in many countries. Appropriately validated, quality-assured, and FDA-approved MG diagnostic assays have been lacking. AREAS COVERED: The clinical and analytical performance characteristics of the Aptima® MG assay, the first FDA-approved MG nucleic acid amplification test (NAAT), are summarized. Key priorities in the management and control of MG infections are also discussed. EXPERT OPINION: Highly sensitive, specific, and quality-assured MG NAATs, e.g. the Aptima MG assay on the automated and flexible Panther® platform, are imperative to improve the management and control of MG infections internationally. This testing, combined with macrolide resistance testing (not yet available on the Panther platform), offers a rapid, high-throughput, and appropriate diagnosis of MG. Macrolide resistance-guided sequential treatment needs to be implemented for MG infections. Dual antimicrobial therapy, novel antimicrobials and, ideally, a vaccine may become essential.

Background: Gonorrhoea is usually managed in community sexual health or general practice, but a proportion of cases present to hospital settings. In this study, we examined how gonorrhoea was managed through a large hospital network and what the implications may be for public health management. Method(s): A retrospective chart review was performed of the management of patients with Neisseria gonorrhoeae infection diagnosed at a large Australian healthcare network from January 2015 to May 2018. Documentation rates of five parameters of care were assessed: (1) the presence (or absence) of previous sexually transmissible infections (STIs); (2) recent travel; (3) discussion of HIV testing; (4) contact tracing; and (5) public health notification. Result(s): In all, 110 cases (48 male, 62 female) were analysed. Most cases were in the 15-39 years age group; 98 cases (89%) were symptomatic, and 12 (11%) were screening tests. The most common presenting syndromes were pelvic inflammatory disease (32%; 31/98 symptomatic cases), urethritis (26%; 25/98) and epididymo-orchitis (13%; 13/98). None of the five parameters assessed were documented in most cases. Documentation was most likely to occur in patients admitted to hospital. When HIV testing was performed, no new cases of HIV were identified. Conclusion(s): Infections with gonorrhoea present on a regular basis to hospital practice, but overall management is suboptimal. Automated prompts for other recommended tests, including HIV testing when testing for other sexually transmissible diseases is ordered, may improve management. Better awareness of best practice is needed, which can be facilitated with ongoing education. However, the greatest benefit is likely achieved by linking patients back to community-based services, which are best placed to provide ongoing long-term care.Copyright © CSIRO 2019 Open Access.

Objectives Most international STI guidelines recommend Chlamydia trachomatis anorectal testing in women after self-reported sexual exposure or symptoms in women. However, it has been shown that the prevalence of anorectal C. trachomatis is as high (7%-17 %) in women who do not report anorectal intercourse (AI) as in women who do. This study assessed the correlation between the genital and anorectal C. trachomatis load in concurrently infected women for increased microbiological insight. Methods A convenience sample of 105 women with a concurrent (genital and anorectal) C. trachomatis infection was included from the STI clinic in South Limburg, the Netherlands. Women provided self-collected vaginal and anorectal swabs. The C. trachomatis load was quantified with qPCR and the human cell load was assessed to ensure sample adequacy. Genital and anorectal C. trachomatis loads were divided into tertiles for comparison. The chi(2) test and linear regression were used to compare genital and anorectal C. trachomatis loads and identify determinants associated with load. Results The overall median C. trachomatis load was higher in genital (median 5.3 log(10)C. trachomatis/ml) than anorectal samples (median 3.4, p

BackgroundProliferative urethritis (PU) is a lower urinary tract disease of dogs characterized by frond-like lesions in the urethra. The etiology of PU is unknown, although an association with bacterial cystitis is reported.ObjectivesDeep-seated bacterial cystitis is associated with PU, particularly in dogs with neutrophilic or granulomatous inflammation.AnimalsTwenty-two client-owned dogs with PU and 5 control dogs euthanized for non-urinary disease.MethodsIn retrospective analysis, medical records of dogs with PU from 1986 to 2016 were reviewed. Signalment, clinical signs, cystoscopic findings, antimicrobial use, and results of urine, bladder, or urethral tissue cultures, if available, were recorded. Histopathology was reviewed and classified as lymphocytic-plasmacytic (LP), neutrophilic, LP-neutrophilic (LPN), granulomatous, or pleocellular. Eubacterial fluorescence in situ hybridization (FISH) was performed on 18 tissue samples (13 cases, 5 controls), with subsequent evaluation of bacterial species.ResultsOf the 22 dogs, 9 had LP urethritis, 6 had LPN, 4 had pleocellular, and 3 had neutrophilic urethritis. Of note, 7 of 13 PU samples were FISH+ for adherent or invasive bacteria; 1 of 5 controls were FISH+ for adherent bacteria. Five dogs had negative urine and tissue cultures when FISH was positive. There was no association detected between the type of urethral inflammation and the results of urine and tissue culture or FISH.Conclusions and clinical importanceThe type of inflammation varied widely in these 22 PU cases. Deep-seated bacterial urethritis could be contributing to the inflammatory process in some dogs, regardless of the inflammation type. Urine and tissue cultures likely underestimate bacterial colonization of the urethra in dogs.

At present, we have no evidence that we are doing more good than harm detecting and subsequently treating Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum colonisations/infections. Consequently, routine testing and treatment of asymptomatic or symptomatic men and women for M. hominis, U. urealyticum, and U. parvum is not recommended. Asymptomatic carriage of these bacteria is common and the majority of individuals do not develop disease. Although U. urealyticum has been associated with urethritis in men, it is probably not causal unless a high load is present (likely carriage in 40-80% of detected cases). The extensive testing, detection and subsequent antimicrobial treatment of these bacteria performed in some settings may result in selection of antimicrobial resistance, in these bacteria, "true" STI agents, as well as in the general microbiota, and substantial economic cost for society and individuals, particularly women. The commercialisation of many particularly multiplex PCR assays detecting traditional non-viral STIs together with M. hominis, U. parvum and/or U. urealyticum have worsened this situation. Thus, routine screening of asymptomatic men and women or routine testing of symptomatic individuals for M. hominis, U. urealyticum, and U. parvum is not recommended. If testing of men with symptomatic urethritis is undertaken, traditional STI urethritis agents such as Neisseria gonorrhoeae, Chlamydia trachomatis, M. genitalium and, in settings where relevant, Trichomonas vaginalis should be excluded prior to U. urealyticum testing and quantitative species-specific molecular diagnostic tests should be used. Only men with high U. urealyticum load should be considered for treatment, however, appropriate evidence for effective treatment regimens is lacking. In symptomatic women, bacterial vaginosis (BV) should always be tested for and treated if detected., Funding Agencies:NIHR Health Protection Research Unit in Evaluation of Interventions at University of Bristol Public Health England (PHE) Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden WHO ECDC Örebro County Council Research Committee, Örebro, Sweden

Purpose: To evaluate topical treatment with clobetasol propionate and lidocaine in women with urethral pain syndrome (UPS) in a retrospective pilot study. Materials and Methods: Urethral instillations of two ml clobetasol propionate cream and two ml lidocaine gel in 30 Caucasian women age 15-74 years with UPS between 1999 and 2006 were evaluated retrospectively. Instillations were given approximately once a week until the patient improved. Between one and 15 (median three) instillations were given. In substudy I a review was undertaken of the medical records to register the treatment effect at the end of the treatment (the last instillation) and any relapses six months thereafter. Substudy II was a follow-up at least five years after last instillation based on medical records and a written questionnaire. Results: Substudy I (n=30): By the end of the treatment 18 women had no symptoms and 12 were improved. Five patients had relapsed within six months. Substudy II (n=28): Twenty-eight women responded to the questionnaire. Four women remained with no symptoms, 18 remained improved, and six had the same symptoms as before treatment. Twenty women thought the treatment was very effective, five rather effective, and three women reported poor effect. Twenty-six women would ask for retreatment if a relapse occurred, two patients would not. No side effects, except transient pain, were reported. Conclusions: This retrospective study and long-term follow-up suggests that urethral instillation of clobetasol propionate and lidocaine is effective in treating women with UPS. Randomized control studies are warranted.

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Medical Science, Griffith Health, Urinary tract infections (UTI) are a major source of morbidity, affecting 50% of women at least once, and sometimes with recurrent episodes. These infections can be localised as cystitis or urethritis, and sometimes develop more severely as pyelonephritis or urosepsis. UTI also affects the elderly and catheterised patients in large numbers. The burden on the health care system arises from more than 8 million UTI-related consultations per year; with health care costs estimated in excess of $3.5 billion, in the USA alone. While UTI is caused by a range of different microbes, the predominant infectious organism is uropathogenic Escherichia coli (UPEC), which accounts for 55 to 85% of UTI cases. UPEC has multiple virulence factors that confer motility, adhesion, invasion, immune evasion, nutrient acquisition and biofilm formation. These virulence traits contribute to the development of UTI to various degrees. The human response to UTI has been characterised in many studies to date that have defined a complex series of biochemical and immunological signalling interactions, incorporating lymphocytes, granulocytes, mononuclear and uroepithelial cells. The research literature on UPEC UTI has focused mainly on discrete virulence factors of the bacteria and specific components of the host response to infection. Some features of UTI such as localisation of infection, severity, persistence, and chronic re-recrudescence are partially understood. However, there are many elements that require further study and there have been few broad-based approaches to deciphering the overall pathogenesis of UPEC UTI. Research projects using wider approaches to document events that occur at specific points during infection can offer insight into previously unknown aspects of critical UTI stages.

Urinary tract infections (UTI) are a major source of morbidity, affecting 50% of women at least once, and sometimes with recurrent episodes. These infections can be localised as cystitis or urethritis, and sometimes develop more severely as pyelonephritis or urosepsis. UTI also affects the elderly and catheterised patients in large numbers. The burden on the health care system arises from more than 8 million UTI-related consultations per year; with health care costs estimated in excess of $3.5 billion, in the USA alone. While UTI is caused by a range of different microbes, the predominant infectious organism is uropathogenic Escherichia coli (UPEC), which accounts for 55 to 85% of UTI cases. UPEC has multiple virulence factors that confer motility, adhesion, invasion, immune evasion, nutrient acquisition and biofilm formation. These virulence traits contribute to the development of UTI to various degrees. The human response to UTI has been characterised in many studies to date that have defined a complex series of biochemical and immunological signalling interactions, incorporating lymphocytes, granulocytes, mononuclear and uroepithelial cells. The research literature on UPEC UTI has focused mainly on discrete virulence factors of the bacteria and specific components of the host response to infection. Some features of UTI such as localisation of infection, severity, persistence, and chronic re-recrudescence are partially understood. However, there are many elements that require further study and there have been few broad-based approaches to deciphering the overall pathogenesis of UPEC UTI. Research projects using wider approaches to document events that occur at specific points during infection can offer insight into previously unknown aspects of critical UTI stages., Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Medical Science, Griffith Health, Full Text

Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pili, opacity proteins, IgA1 protease, and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea., Published in Frontiers in Microbiology, v2 article 123 p1-12, 31 May 2011. The original document contains color images.

The overall agreement between different criteria for cervicitis in women infected with Chlamydia trachomatis and/or Mycoplasma genitalium, and in women who tested negative was examined. Women attending a clinic for sexually transmitted diseases were enrolled because of sexual partners’ suspected chlamydia infection. M. genitalium was tested in a sample of first-catch urine and an endocervical specimen, whereas specimens from four different sites were used for detection of C. trachomatis. Signs of friability and purulent endocervical discharge were documented at gynaecological examination. Specimens for microscopy were taken from the endocervix and urethra as well as the vaginal discharge, and bacterial vaginosis was examined for. The criteria being evaluated included cervical friability and/or pus; polymorphonuclear leukocytes (PMNL)/epithelium cell ratio in the vaginal discharge; and more than 30 PMNL per high-power field in the endocervical smear. The overall agreement of the indicators of cervicitis in women infected with C. trachomatis and/or M. genitalium was 40.5% (15/37), and for those women with negative tests 35.3% (12/34). The criteria for cervicitis require further evaluation, including study of a control group of women at low risk of having a sexually transmitted infection.

Objective: To determine the association of Mycoplasma genitalium and Ureaplasma urealyticum in symptomatic male patients presenting with non-gonococcal urethritis in a sexually transmitted infection clinic in Hong Kong. Design: Cross-sectional study. Setting: A sexually transmitted infection clinic, Department of Health, Centre for Health Protection, Hong Kong. Patients: A cohort of consecutive new male patients attending the government sexually transmitted infection clinic. Main outcome measures: Prevalence of Mycoplasma genitalium and Ureaplasma urealyticum among symptomatic male patients with non-gonococcal urethritis and asymptomatic patients without non-gonococcal urethritis. Results: Specimens of 22 and 10 patients tested positive by polymerase chain reaction for Ureaplasma urealyticum and Mycoplasma genitalium respectively, among the symptomatic non-gonococcal urethritis group (n=98). In the asymptomatic control group (n=236), corresponding patient numbers whose specimens tested positive were 47 and 5. There was no statistically significant difference between the two groups, in terms of the proportion of patients infected with Mycoplasma genitalium (P=0.799) or Ureaplasma urealyticum (P=0.535). Conclusions: In our study, demonstration of Mycoplasma genitalium and Ureaplasma urealyticum by polymerase chain reaction was not associated with symptomatic non-gonococcal urethritis in male patients attending a Hong Kong government clinic for sexually transmitted infections.

Introduction Around 92 million urogenital infections are caused yearly by Chlamydia trachomatis worldwide .The overall incidence of sexually transmitted diseases is increasing, as shown by the increases in the number of reported cases of syphilis and gonorrhea . Chlamydia trachomatis infections are associated with various serious diseases in women, men and newborns, which could be, at least partially, avoided by means of early diagnosis and therapy. The Federal Joint Committee - responsible for decision-making concerning the benefit package of the German Social Health Insurance - has publicly announced the starting of deliberations on the issue of screening for Chlamydia trachomatis . Research Questions The leading question to be answered is whether screening for Chlamydia trachomatis should be included in the German benefit basket. The aim of this report is to provide a summary of the available evidence concerning the issue of screening for Chlamydia trachomatis . Methods The summary of published scientific evidence, including HTA reports, systematic reviews, guidelines and primary research is represented. The synthesis follows the structure given by the criteria of Wilson and Jungner for the introduction of screening in a population: relevance of the condition, availability of an adequate test, effectiveness of screening, acceptance of the programme, and economical issues. A literature search was conducted for each aspect of the synthesis and the evidence has been summarised in evidence tables. Results We identified five HTA reports from three European agencies , , , and one from the USA . In addition, we identified four guidelines from Northamerica, , , and one from Europe . A total of 56 primary research publications were included: relevance of the disease (n=26), availability of test (n=1), effectiveness of screening (n=11), acceptance of the programme (n=11), economical issues (n=7). Discussion The main limitation of this report is that we relied only on publi, Einleitung Urogenitale Chlamydia trachomatis -Infektionen gehören mit jährlich ca. 92 Millionen Neuerkrankungen zu den häufigsten sexuell übertragbaren Infektionen weltweit . Der in den letzten Jahren zu beobachtende Anstieg meldepflichtiger Infektionen wie Syphilis und Gonorrhö weist auf eine allgemeine Zunahme sexuell übertragbarer Infektionen hin, einschließlich Chlamydia trachomatis . Chlamydia trachomatis -Infektionen stehen im Zusammenhang mit einer ganzen Reihe teils schwerwiegender Erkrankungen bei Frauen, Neugeborenen und auch Männern, die durch eine frühzeitige Diagnose und Therapie zumindest teilweise verhindert werden könnten. Der Gemeinsame Bundesausschuss (G-BA) hat, entsprechend den gesetzlichen Bestimmungen im SGB V (SGB = Sozialgesetzbuch), im März 2004 das "Screening auf genitale Chlamydia trachomatis-Infektionen bei Frauen" als Beratungsthema zur Überprüfung festgesetzt . Fragestellung Ziel dieses Berichts ist es, die wissenschaftliche Evidenz zusammenzufassen und zu diskutieren, ob es sinnvoll ist, ein Screening für Frauen auf urogenitale Chlamydia trachomatis -Infektionen im Rahmen der präventiven Leistungen der Gesetzlichen Krankenversicherung (GKV) in Deutschland einzuführen. Methodik Bei der Zusammenfassung der veröffentlichten wissenschaftlichen Evidenz werden zunächst HTA-Berichte und Leitlinien anderer Institutionen betrachtet (Kontextdokumente). Die Fragestellung wird in Teilfragen/-aspekte unterteilt, um die Erfüllung der modifizierten Kriterien von Wilson und Jungner zu überprüfen: Relevanz der Zielkondition, Verfügbarkeit von adäquaten Testverfahren, Effektivität eines Screenings, Akzeptanz eines Screenings, ökonomische Aspekte. Für diese unterschiedlichen Teilaspekte werden spezifische Recherchen sowie unterschiedliche Selektions- und Bewertungskriterien der Literatur verwendet. Die Evidenz wird narrativ und tabellarisch zusammengefasst. Ergebnisse Es wurden insgesamt fünf Health Technology Assessment (HTA)-Berichte von drei europäisc

Lipid-associated membrane proteins (LAMPs) exposed externally on the surface of mycoplasmas are responsible for inducing antibody responses during infections. We showed mycoplasmal LAMPs are species-specific. Antibodies to M. genitalium LAMPs detected by ELISA can be confirmed by Western Blotting and consistent with PCR results of patients' urines. We tested more than 1400 serum samples from patients with various diseases.

The investigations described in this thesis can be divided into two parts. In the first part, the clinical efficacies of enoxacin (a new qninolone), cefodizime (a third generation parenteral cephalosporin) and ceftetrame (a new oral cephalosporin) were assessed in patients with gonococcal urethritis. In the second part, the therapeutic effectiveness of ciprofloxacin (a new quinolone) and roxithromycin (a new macrolide) were assessed in patients with NGU. Susceptibilities of N. gonorrhoeae and C. trachomatis to different antibiotics were also assessed. N. gonorrhoeae and C. rrachomatis strains that were isolated from patients before and after treatment were also tested for possible resistance formation to the particular antibiotic used for treatment. These strains were also typed wherever possible. Side-effects and laboratory abnormalities caused by these trial drugs were also strictly monitored and critically evaluated.

Surveillance studies to determine the etiologic agents of acute respiratory disease (ARD) in basic combat trainees (BCT's) were accomplished during FY 77. A special influenza surveillance program was also conducted at Forts Wood, Jackson and Bliss, to signal an early warning of a probable A/Swine flu epidemic. Virus isolations and Serological Studies indicated that 19.9% of ARD hospitalizations were caused by Adenoviruses, 4.5% by Influenza A and B, Mycoplasma, Coxsackie A 21 and Polio; and 74.7% by agents that were not determined. Field studies to determine the immunogenicity of Adenovirus Vaccines were conducted utilizing 360 serum pairs collected from 6 Training Forts. Accummulative results indicated the type 4 vaccine to be 69% immunogenic, and the type 7 was 63.6% immunogenic. A preliminary study to determine the effectiveness of Charcoal Viral Transport Media (CVTM), and bentonite media for transporting virus specimens was conducted using Tryptose Phosphate Broth (TPB) as a control. The recovery of Vaccinia, ECHO 9, Coxsackievirus, Polio, Adenovirus, Herpes, Mumps, and Influenza were similar, but neither media maintained virus titers as adequately as TPB. Studies to determine whether Coxsackievirus is a significant cause of upper-respiratory infections revealed that this agent represented 25%, 36/144, of the total number of viruses isolated during the period July thru December. Serological data confirms Coxsackievirus A21 as a significant cause of ARD., Report on Communicable Diseases and Immunology.

This thesis takes a closer look at three aspects of human chlamydial infections. With regard to diagnosis the influence of logistics on the sensitivity of the culture method is discussed, along with optimalization of the culture itself and an evaluation of new diagnostic methods. Next, epidemiological data are discussed with regard to the prevalence and role of Chlamydia, on the one hand in asymptomatic persons from low-risk groups and on the other hand in women with postinflammatory tubal infertility. Finally the therapeutic problems are considered with reference to measurements of the in-vitro sensitivity of various chlamydial strains to tetracycline and some recently developed chemotherapeutic agents. The significance of Chlamydia for some of the sexually transmitted nongonococcal oculogeni tal infections was not generally recognised until relatively recently. One of the reasons for this was undou~tedly the lack of a culture method to isolate the organism for study of its biological characteristics. Even after the introduction of a technique to culture Chlamydia on cell lines, large scale epidemiological research was impeded by lack of adequately equipped laboratories where the complicated method might be employed. The manner of collecting patient material for culture, transport from outpatient clinic to laboratory, and the culture method employed are critical parameters which determine the ultimate result. A disadvantage of the culture method is the relatively long time required (6 days). Rapid diagnosis and if necessary treatment, especially of asymptomatic persons, is of great epidemiological importance. Chlamydial antigen-detecting methods have recently been developed which can present results within a few hours. They are based on the immunofluorescence (IF) technique and on the enzyme immunoassay (EIA). Both techniques employ monoclonal antibodies against genus-specific epitopes of the Major Outer Membrane Protein (IF technique) or of the lipopolysaccharide

These studies were undertaken in preparation for an extensive investigation of the association of cell-mediated immunity to chlamydial agents to clinical nongonococcal urethritis. Spleen cells from guinea pigs immunized with the meningopneumonitis strain of Chlamydia psittaci (MN) derived from infected chicken embryos were made to react with MN antigen derived from cell cultures. Lymphocytic blastogenic transformation, production of lymphotoxin, and of migration inhibition factor were demonstrated. The results indicate that these tests can be performed with considerable simplicity with chlamydial antigens. These studies were not applied to nongonococcal urethritis because of the untimely death of Dr. Gordon. (Author)

Isolation of T strain mycoplasmas was found to be directly related to sexual activity in three groups of women. Metabolic inhibition titers followed the same pattern, the number of titers increased with sexual activity. The rate of mycoplasma isolations from the urine of asymptomatic males was lower in statistically significant levels than the rate of mycoplasma isolations from patients attending the genitoinfectious disease clinic. Nonspecific urethritis due to T strain mycoplasmas is a discrete entity which can be diagnosed in the initial office visit. Normal sexually active controls without prior history of urethritis have only an 18% incidence of positive T strain cultures, whereas patients with nonspecific urethritis range from 60%-70% positive T strain mycoplasma cultures in a urethral washout urine specimen. (Author)

Method for measuring uroflow and void duration in the mouse, Objective: Genetically engineered mice may improve understanding of a variety of human bladder diseases. We developed a non-invasive method to measure urinary flow rate in the mouse. This could be useful for the study of bladder outlet obstruction as well as processes affecting detrusor function in the awake animal. Methods: A metabolic cage without a fecal separation screen was placed above a precision balance that reported the mass of the excreta pan every 100 msec. A computational algorithm identified voids suitable for assessment of uroflow from other excretory events. These algorithms were verified by comparison with series of images obtained automatically before and during excretory events. Intraurethral acetic acid was used to induce urethritis and to verify the sensitivity of the measurement technique. Results: Automatic categorization and characterization of uroflow was successful. Brief exposures of the urethra of the female C57BL6/J mouse to 2% acetic acid decreased uroflow and increased void duration without a change in void volume. Conclusions: This method will enable studies of urologic function in mice of differing age, sex, strain, and genetic constitution. Murine urethritis can be differentiated from cystitis, known to be associated with a decrease in void volume. The observed changes are consistent with urethral obstruction induced by local swelling and inflammation.

Method for measuring uroflow and void duration in the mouse, Objective: Genetically engineered mice may improve understanding of a variety of human bladder diseases. We developed a non-invasive method to measure urinary flow rate in the mouse. This could be useful for the study of bladder outlet obstruction as well as processes affecting detrusor function in the awake animal. Methods: A metabolic cage without a fecal separation screen was placed above a precision balance that reported the mass of the excreta pan every 100 msec. A computational algorithm identified voids suitable for assessment of uroflow from other excretory events. These algorithms were verified by comparison with series of images obtained automatically before and during excretory events. Intraurethral acetic acid was used to induce urethritis and to verify the sensitivity of the measurement technique. Results: Automatic categorization and characterization of uroflow was successful. Brief exposures of the urethra of the female C57BL6/J mouse to 2% acetic acid decreased uroflow and increased void duration without a change in void volume. Conclusions: This method will enable studies of urologic function in mice of differing age, sex, strain, and genetic constitution. Murine urethritis can be differentiated from cystitis, known to be associated with a decrease in void volume. The observed changes are consistent with urethral obstruction induced by local swelling and inflammation.