Position statement for the diagnosis and management of anogenital warts.

BACKGROUND: Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. OBJECTIVE: To provide guidance to physicians on the diagnosis and management of AGW. METHODS: Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. RESULTS: A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. CONCLUSION: The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW.

2015 European guideline on the management of Chlamydia trachomatis infections.

Chlamydia trachomatis infections, which most frequently are asymptomatic, are major public health concerns globally. The 2015 European C. trachomatis guideline provides: up-to-date guidance regarding broader indications for testing and treatment of C. trachomatis infections; a clearer recommendation of using exclusively-validated nucleic acid amplification tests for diagnosis; advice on (repeated) C. trachomatis testing; the recommendation of increased testing to reduce the incidence of pelvic inflammatory disease and prevent exposure to infection; and recommendations to identify, verify and report C. trachomatis variants. Improvement of access to testing, test performance, diagnostics, antimicrobial treatment and follow-up of C. trachomatis patients are crucial to control its spread. For detailed background, evidence base and discussions, see the background review for the present 2015 European guideline on the management of Chlamydia trachomatis infections (Lanjouw E, et al. Int J STD AIDS. 2015).

Background review for the '2015 European guideline on the management of Chlamydia trachomatis infections'.

SummaryChlamydia trachomatis infections are major public health concerns globally. Of particular grave concern is that the majority of persons with anogenital Chlamydia trachomatis infections are asymptomatic and accordingly not aware of their infection, and this silent infection can subsequently result in severe reproductive tract complications and sequelae. The current review paper provides all background, evidence base and discussions for the 2015 European guideline on the management of Chlamydia trachomatis infections (Lanjouw E, et al. Int J STD AIDS 2015). Comprehensive information and recommendations are included regarding the diagnosis, treatment and prevention of anogenital, pharyngeal and conjunctival Chlamydia trachomatis infections in European countries. However, Chlamydia trachomatis also causes the eye infection trachoma, which is not a sexually transmitted infection. The 2015 European Chlamydia trachomatis guideline provides up-to-date guidance regarding broader indications for testing and treatment of Chlamydia trachomatis infections; clearer recommendation of using validated nucleic acid amplification tests only for diagnosis; advice on (repeated) Chlamydia trachomatis testing; recommendation of increased testing to reduce the incidence of pelvic inflammatory disease and prevent exposure to infection and recommendations to identify, verify and report Chlamydia trachomatis variants. Improvement of access to testing, test performance, diagnostics, antimicrobial treatment and follow-up of Chlamydia trachomatis patients are crucial to control its spread.

First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhoea treatment failure in Austria, 2011.

We describe the first cefixime-resistant Neisseria gonorrhoeae strain in Austria that caused treatment failure.It follows the first five cases in Europe of cefixime treatment failure, reported in Norway in 2010 and the United Kingdom in 2011. Effective treatment of gonorrhoea is crucial for public health control and, at present, requires substantially enhanced awareness, more frequent test-of-cure, interaction with experts after therapeutic failure, tracing and therapy of contacts, and surveillance of gonococcal antimicrobial resistance and treatment failures worldwide.

2010 European guideline for the management of Chlamydia trachomatis infections.

This guideline aims to provide comprehensive information regarding the management of infections caused by Chlamydia trachomatis in European countries. The recommendations contain important information for physicians and laboratory staff working with sexually transmitted infections (STIs) and/or STI-related issues. Individual European countries may be required to make minor national adjustments to this guideline as some of the tests or specific local data may not be accessible, or because of specific laws.

The anti-protozoal drug pentamidine blocks KIR2.x-mediated inward rectifier current by entering the cytoplasmic pore region of the channel.

BACKGROUND AND PURPOSE: Pentamidine is a drug used in treatment of protozoal infections. Pentamidine treatment may cause sudden cardiac death by provoking cardiac arrhythmias associated with QTc prolongation and U-wave alterations. This proarrhythmic effect was linked to inhibition of hERG trafficking, but not to acute block of ion channels contributing to the action potential. Because the U-wave has been linked to the cardiac inward rectifier current (I(K1)), we examined the action and mechanism of pentamidine-mediated I(K1) block. EXPERIMENTAL APPROACH: Patch clamp measurements of I(K1) were made on cultured adult canine ventricular cardiomyocytes, K(IR)2.1-HEK293 cells and K(IR)2.x inside-out patches. Pentamidine binding to cytoplasmic amino acid residues of K(IR)2.1 channels was studied by molecular modelling. KEY RESULTS: Pentamidine application (24 h) decreased I(K1) in cultured canine cardiomyocytes and K(IR)2.1-HEK293 cells under whole cell clamp conditions. Pentamidine inhibited I(K1) in K(IR)2.1-HEK293 cells 10 min after application. When applied to the cytoplasmic side under inside-out patch clamp conditions, pentamidine block of I(K1) was acute (IC(50)= 0.17 microM). Molecular modelling predicted pentamidine-channel interactions in the cytoplasmic pore region of K(IR)2.1 at amino acids E224, D259 and E299. Mutation of these conserved residues to alanine reduced pentamidine block of I(K1). Block was independent of the presence of spermine. K(IR)2.2, and K(IR)2.3 based I(K1) was also sensitive to pentamidine blockade. CONCLUSIONS AND IMPLICATIONS: Pentamidine inhibits cardiac I(K1) by interacting with three negatively charged amino acids in the cytoplasmic pore region. Our findings may provide new insights for development of specific I(K1) blocking compounds.

Improvement of trochanteric bone quality in an osteoporosis model after short-term treatment with parathyroid hormone: a new mechanical test for trochanteric region of rat femur.

UNLABELLED: We have examined the changes induced in the trochanteric region of femur of ovariectomized rat after administration of estradiol and parathyroid hormone. We have developed a reproducible biomechanical test and produced trochanteric fractures to evaluate stiffness and strength of this region in addition to histomorphometry. INTRODUCTION: We investigated the short-term effects of parathyroid hormone (PTH) and estrogen (E) on the strength of the rat trochanteric region in a new mechanical test. METHODS: Forty-four 3-month-old female Sprague-Dawley rats were ovariectomized and 8 weeks later treated with soy-free diet (C), daily applications of orally supplied E (0.5 mg/kg food) or subcutaneously injected PTH (0.014 mg/kg), for 5 weeks, and an additional untreated group was added as sham-operated. The femurs were examined for biomechanical and histomorphometric changes. RESULTS: Our new mechanical test was validated in a right-left comparison. The PTH treatment induced significantly superior biomechanical results (F (max) = 225.3 N, stiffness = 314.9 N/mm) compared to E (F (max) = 182.9 N, stiffness = 237.2 N/mm), C (F (max) = 166.03 N, stiffness = 235.56 N/mm), and sham (F (max) = 192.1 N, stiffness = 267.2 N/mm). Animals of the PTH group demonstrated a significantly improved trabecular bone structure and area (75.67%) in comparison to the E (61.04%) and C (57.18%) groups. CONCLUSION: Our new biomechanical test is valid and produces trochanteric fracture. Our results show that the short-term antiosteoporotic effects of PTH are in the trochanteric region of ovariectomized rat superior to E.

Xeroderma pigmentosum variant and error-prone DNA polymerases.

Replicative DNA synthesis is a faithful event which requires undamaged DNA and high fidelity DNA polymerases. If unrepaired damage remains in the template DNA during replication, specialised low fidelity DNA polymerases synthesises DNA past lesions (translesion synthesis, TLS). Current evidence suggests that the polymerase switch from replicative to translesion polymerases might be mediated by post-translational modifications involving ubiquitination processes. One of these TLS polymerases, polymerase eta carries out TLS past UV photoproducts and is deficient in the variant form of xeroderma pigmentosum (XP-V). The dramatic proneness to skin cancer of XP-V individuals highlights the importance of this DNA polymerase in cancer avoidance. The UV hypermutability of XP-V cells suggests that, in the absence of a functional poleta, UV-induced lesions are bypassed by inaccurate DNA polymerase(s) which remain to be identified.

Cost effectiveness of screening for Chlamydia trachomatis: a review of published studies.

OBJECTIVE: Screening for Chlamydia trachomatis in the lower genital tract may contribute to the prevention of pelvic inflammatory disease in women. The purpose of this review was to critically appraise, and summarise studies of the cost effectiveness of screening for C trachomatis. METHODS: A literature search was conducted on Medline and in Health Star from 1990-2000. Keywords were C trachomatis, screening, cost effectiveness. Bibliographies of reviewed articles were also searched. The population studied was asymptomatic sexually active women under 30 years of age in a primary care setting. The intervention assessed was screening for lower genital tract infection with C trachomatis and the outcomes studied were cases of C trachomatis detected, cases of PID prevented, and associated costs. Studies were assessed using the Drummond criteria for economic evaluations. They were assessed qualitatively as they were too heterogeneous to allow quantitative analysis. RESULTS: 10 studies were included. All were modelled scenarios and all found screening to be more cost effective than simply testing symptomatic women, although all were based on probabilities that were assumed. Six of the studies focused on DNA based testing, three of them using urine. The models showed screening to be cost effective at prevalences of 3.1-10.0%, and cost saving (overtesting symptomatic women) at a prevalence as low as 1.1%, if age was used as a selection factor and DNA based tests were used in urine samples. CONCLUSIONS: At the prevalence of infection expected in the target population, all studies suggest screening is cost effective. However, the assumptions used in the models have been difficult to confirm and there is a need for more data, particularly on the risk of complications in women with asymptomatic lower tract infection.

Sexually transmitted infections and human immunodeficiency virus infection in Europe: the way ahead?

The incidence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) infection is increasing in Europe. The reasons for this are multifactorial but ease of travel is one of them. This is worrying in view of the established role of STIs in facilitating HIV transmission. Care of this group of infections is provided by a variety of doctors, often not following agreed guidelines. It is vital that doctors and their specialist societies engage in setting standards, in ensuring that STIs and HIV infection are moved up the healthcare agendas of all European countries and in making sure that access to care is rapid. Surveillance should be enhanced, interventions evaluated and the media engaged.

Correct samples for diagnostic tests in sexually transmitted diseases: which sample for which test?

Amplified DNA technology such as the polymerase chain reaction (PCR) and ligase chain reaction (LCR) are new techniques for the diagnosis of genital chlamydial infections in both men and women. These tests are highly sensitive and specific in detecting chlamydial genes in different specimen types such as genital samples as well as in non-invasive specimens such as urine and vulval smears. Due to the advantage of a high reliability of these techniques even when they are performed on non-invasive specimen types, amplification tests allow chlamydial diagnosis for screening especially high risk persons as the basis of chlamydia control programs.

The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes.

The human XPB DNA helicase is a subunit of the DNA repair/basal transcription factor TFIIH, involved in early steps of the nucleotide excision repair pathway. Two distinct clinical phenotypes, xeroderma pigmentosum associated with Cockayne's syndrome (XP/CS) and trichothiodystrophy (TTD), can be due to mutations in the XPB gene. In the present work, we studied cellular DNA repair properties of skin fibro-blasts from two patients mutated in the XPB gene: an XP/CS patient cell (XPCS2BA) with a T296C (F99S) transition and a TTD patient cell (TTD6VI) exhibiting an A355C (T119P) transversion. Both cells are clearly associated with different levels of alterations in their response to UV light. To establish the relationship between the relative expression level of these two alleles and DNA repair properties, we transfected SV40-transformed XPCS2BA (XPCS2BASV) cells with a plasmid (pTTD6VI) carrying the XPB-A355C cDNA and examined DNA repair properties after UV irradiation (cell survival, unscheduled DNA synthesis and kinetics of photoproduct removal) in stable transfectants. We isolated three clones, which express the XPB-A355C gene (Cl-5) or the XPB-T296C gene (Cl-14) or both genes (Cl-19). This con-stitutes a model system allowing us to correlate the relative expression levels of the XPB-A355C (TTD) and XPB-T296C (XP/CS) genes with various DNA repair properties. Overexpression of the XPB-A355C (TTD) gene in an XP/CS cell gives rise to a cellular phenotype of increased repair similar to that of TTD6VI cells, while equal expression of the two mutated genes leads to an intermediate cellular phenotype between XP/CS and TTD.

Performance of transcription-mediated amplification and ligase chain reaction assays for detection of chlamydial infection in urogenital samples obtained by invasive and noninvasive methods.

Based on the amplification of chlamydia-specific rRNA sequences and the ligase chain reaction (LCR), the performance characteristics of the Gen-Probe Chlamydia trachomatis transcription-mediated amplification (TMA) assay were evaluated with endocervical, urine, and vulval specimens from women and urethral and urine specimens from men and were compared with those for cultures on endocervical, vulval, and urethral swabs. Of the 308 women and 240 men tested, 25 (8.1%) and 44 (18.3%), respectively, were shown to be infected. By using the infected individual as the expanded "gold standard" for calculations, the TMA assay and LCR gave similar performances for the sensitivity of male urethral (93.2%) and urine (88.6 and 86.4%) samples, while culture detected only half of the 44 infected men. In women, the sensitivities of the TMA assay for endocervical and vulval samples were 88 and 92%, respectively, compared to values of 92% for the LCR on both sample types and of 52 and 8%, respectively, for culture. By using first-void urine for chlamydial diagnosis in women, LCR detected 24 (96%) and TMA assay detected 19 (76%) infected individuals, showing a significantly lower sensitivity for urine in women (P = 0.0253). The results indicate a high overall agreement for both amplifying techniques for all examined specimen types, except for female urine. Furthermore, they confirm the previous observation that vulval swabs are an effective alternative noninvasive sample type for the detection of C. trachomatis infection in women by nucleic acid-based amplification technologies.

Fluconazole in the treatment of tinea corporis and tinea cruris.

BACKGROUND: Results of topical dermatomycosis treatment are often unsatisfactory, particularly in patients with extended or multiple infection sites. OBJECTIVE: Given the high fluconazole concentrations attainable in the stratum corneum and the long elimination half-life of fluconazole, we investigated whether efficacy is satisfactory when using fluconazole at once weekly doses of 150 mg. METHODS: In an open, noncomparative study, tinea corporis and cruris patients were treated with once weekly fluconazole 150 mg over 2-4 weeks. Clinical (pruritus, erythema, scaling, burning/pain, vesiculation) and mycologic (culture and microscopy) assessments were performed before treatment, at weekly intervals until the end of treatment and 3 weeks after treatment. All adverse events were recorded. RESULTS: The total severity scores of clinical symptoms were reduced from 7.1 before to 1.5 after treatment (p = 0.001, n = 100 patients). Seven patients experienced adverse events. CONCLUSIONS: Fluconazole 150 mg once weekly for 2-4 weeks is an efficacious and safe regimen in the treatment of tinea corporis and cruris.

Cyclobutane pyrimidine dimers are the main mutagenic DNA photoproducts in DNA repair-deficient trichothiodystrophy cells.

We have used the replicating shuttle vector pR2 to determine the role of ultraviolet C (UVC)-induced cyclobutane pyrimidine dimers (CPDs) and nondimer photoproducts in mutagenesis in human trichothiodystrophy (TTD) cells and in their repair-proficient counterparts obtained after complementation with the wild-type XPD/ERCC2 repair gene (TTD + ERCC2 cells). Before transfection in human cells, the UVC-irradiated vector DNA was treated with Anacystis nidulans photolyase [photoreactivation (PR) procedure] that selectively removed CPDs, leaving nondimer photoproducts intact. The mutant frequency of the UV-irradiated pR2 plasmid treated by PR was similar after replication in TTD or in TTD + ERCC2 cells. This result indicates that TTD cells were able to repair nondimer photoproducts as efficiently as TTD cells complemented with the wild-type repair gene and that in TTD cells, CPDs were the major photoproducts generating an increased mutant frequency after UVC irradiation. Sequence analysis of > 300 mutant plasmids indicated that PR of the DNA increased the relative level of tandem mutations and decreased the relative level of multiple mutations in TTD cells. In both cell lines, we observed that CPDs mostly led to GC-AT transitions; whereas only nondimer photoproducts were responsible for the induction of GC-TA transversions in TTD and TTD + ERCC2 cells.

Urethritis. Diagnosis of nongonococcal urethritis.

Nongonococcal urethritis (NGU) frequently occurs in men after infection of the lower genital tract with a genital pathogen and is mostly associate with complaint of a scanty, thin discharge and urinary symptoms. Management of NGU includes clinical examination, microbiological diagnosis of genital pathogens, and efficient treatment as well as contact tracing. Diagnosis, especially of the Chlamydia trachomatis, the most frequent cause of NGU, has improved by using amplification assays for the detection of DNA or rRNA. These new methods have the advantage of a higher sensitivity especially for specimens with a low number of infectious agents. In addition, they enable the use of urine as a noninvasive specimen type.

Mycoplasma hominis and Ureaplasma urealyticum in patients with sexually transmitted diseases.

Mycoplasma hominis and Ureaplasma urealyticum can be isolated with considerable frequency from the human urogenital tract and are thought to cause various syndromes such as nongonococcal urethritis, pelvic inflammatory disease, pyelonephritis or infertility. The aim of this study was the evaluation of the presence of different genital pathogens in patients with sexually transmitted diseases (STD) and, in particular, the detection of mycoplasmas in individuals infected with genital microbes and an assessment of the presence of genital microorganisms in patients harbouring Mycoplasma hominis or Ureaplasma urealyticum. Furthermore, the occurrence of mycoplasmas in women with bacterial vaginosis was established. Specimens were collected from a total of 41,980 persons attending the Outpatients' Centre for Infectious Venero-Dermatological Diseases in Vienna from 1994 to 1996. Of all genital pathogens, Ureaplasma urealyticum was cultured most frequently in men and women. Mycoplasma hominis and Ureaplasma urealyticum were detected more often in the vaginal fluid than in the male urethra. By contrast, infection rates with Neisseria gonorrhoeae and Chlamydia trachomatis were higher in men than in women. In both men and women, trichomoniasis increased colonisation with Mycoplasma hominis, while mycoplasmas occurred less frequently together with genital candidiasis. Mycoplasma hominis was cultivated significantly more often in women with bacterial vaginosis than in those without. In contrast to urethral infections in men, cervical infections with Neisseria gonorrhoeae or Chlamydia trachomatis raised the incidence of Mycoplasma hominis in the vaginal fluid.