Positive hepatitis B virus core antibody in HIV infection--false positive or evidence of previous infection?

Isolated HBV core antibody (anti-HBc) is defined as the presence of anti-HBc with a negative HBV surface antigen (HBsAg) and HBV surface antibody (anti-HBs <10 IU/l). In patients infected with HIV with isolated anti-HBc, the aim was to determine: The prevalence of isolated positive anti-HBc; The most effective method of identifying which patients have had previous Hepatitis B Virus (HBV) infection; The prevalence of false positive anti-HBc. HBV serology results were identified from 539 patients infected with HIV sampled between January 2010 and December 2012. In those with an isolated anti-HBc and negative anti-HBe, a second anti-HBc test was carried out using a different assay. Samples were also screened for HBV DNA. The anti-retroviral regimens at time of screening were documented. 101/539 had an isolated anti-HBc. Of these, 32 (32%) had a positive anti-HBe (including 1 equivocal) and 69(68%) were anti-HBe negative. Of those negative for anti-HBe, 32 were tested for both DNA and a second anti-HBc. Of these 26 (81%) were on cART at time of HBV testing, with 25 (78%) on ART with anti-HBV activity. The prevalence of isolated anti-HBc was 19%. Only 32% were also anti-HBe positive, whereas 97% of those anti-HBe negative were positive on a second anti-HBc assay suggesting lack of utility of anti-HBe in resolving serological quandaries. One subject (3%) had a false positive anti-HBc. There was no evidence of chronic HBV but 78% patients were on HBV-suppressive combination anti-retroviral therapy.

Providing a genitourinary medicine colposcopy service.

Between 15 and 30 years ago, the management of women with abnormal cervical cytology fell within the remit of GU Medicine. This involved performing colposcopy. With the introduction of certification for colposcopists in 1998, most GU Medicine clinicians stopped providing a colposcopy service. As certification is not required for using the colposcope to diagnose and manage other ano-genital conditions, a GU Medicine-based colposcopy service was introduced at Addenbrooke's Hospital, Cambridge, UK, to assess young women with post-coital bleeding (PCB). One of the objectives of this study was to review this service. In 2011, local guidelines were implemented advising referral to the department of GU Medicine for women under the age of 40 years presenting with PCB with or without inter-menstrual bleeding (IMB) and with no history of previous cervical pathology. A case note review was undertaken for 357 consecutive patients to document clinical findings and management and to determine whether this was an appropriate route of referral. Cervical pathology was found to be uncommon and easily treated within the GU Medicine setting. The provision of a colposcopy service by GU Medicine nurse practitioners or doctors is achievable but requires appropriate training. Importantly, once obtained, these skills can be easily and usefully transferred to examining the vulva, penis, anus and anal canal.

Prevalence, clinical features and quantification of genital non-viral infections.

We conducted a study of the prevalence, clinical features and microscopy findings, by retrospective case-notes survey, of six non-viral organisms, among 1718 attendees at a genitourinary (GU) medicine clinic in England. An in-house assay for six non-viral infections was used and quantitation of ureaplasmas performed. The prevalences of the six organisms were: Chlamydia trachomatis (CT), 7.1%; Neisseria gonorrhoeae (NG), 0.6%; Mycoplasma genitalium (MG), 1.0%; Trichomonas vaginalis, 0.2%; Ureaplasma urealyticum, 16.1%; Ureaplasma parvum, 35.6%. Among men (but not women) there were significantly raised odds ratios compared with that for U. parvum, for the symptom of discharge with CT, 7.30; MG, 6.43; NG 19.29; dysuria with CT, 5.89 and MG, 5.95; and the microscopy finding of >4 pus cells per high power field with: CT, 7.22; MG, 4.58 and NG 22.31. Evaluation of a possible link between quantitation of U. urealyticum and urethritis did not confirm research findings elsewhere.

Genital streptococcal infection in non-pregnant women: a case-note review.

The purpose of this case-note review was to examine the clinical features and management of women with either vulval or vaginal swabs culturing positive for streptococci. Group B haemolytic streptococcus was isolated in all cases. The majority of women with vulval streptococci presented with irritation or soreness. Candidal infection was found in 43% and a dermatosis in 27%. All women with positive vaginal culture had vaginal soreness and/or discharge. Candida was isolated in 27% and there were features of desquamative vaginitis in 20%. Women treated with erythromycin failed to improve symptomatically. The findings of this study suggest that streptococci mostly play a secondary role and colonize an already damaged genital epithelium.

A surgical approach to anogenital disease: guidance on providing a minor surgery service in sexual health and genitourinary medicine.

Certain anogenital conditions require surgical intervention and although the specialty training curriculum for genitourinary (GU) medicine mentions skin biopsy as the only surgical skill required for training, most practitioners could usefully provide a more extensive surgical or 'minor ops' service. The purpose of this paper is to provide guidance for practitioners considering starting a minor surgery service, outlines the equipment required and describes commonly used techniques such as skin biopsy, cryotherapy, excision, electrosurgery and laser ablation.

Toll-like receptors and genital tract infection.

Our knowledge of the immune response to genital tract infection has progressed appreciably in recent years. This review focuses on the innate immune system, in particular the role of Toll-like receptors (TLRs), in controlling genital tract infection. Research into the role of TLRs in recognizing 'pathogen-associated molecular patterns' (PAMPS) has provided an important insight into the host's early immune response. TLRs are activated following binding of microbial components leading to cytokine production, which, in turn, stimulate phagocytic and natural killer cells and mobilize T and B lymphocytes of the antigen-specific acquired immune system. The therapeutic use of TLR agonists as topical agents or for improving CD4+ and CD8+ T-cell responses to microbial vaccines is an important area of ongoing research, particularly with respect to genital mucosal infection.

Post-coital bleeding in young women: the role of genitourinary medicine.

Recently published Department of Health (DoH) guidelines and National Health Service Cervical Screening Programme guidelines recommend referral to a genitourinary (GU) medicine or sexual health clinic as part of the management pathway for young women with post-coital bleeding (PCB). The objectives of this questionnaire study were to ascertain whether GU medicine practitioners agreed with these recommendations and to assess which skills were considered necessary regarding the diagnosis and management of cervical pathology in departments of GU medicine and sexual health and also, therefore, in training in the specialty. The majority of respondents considered it important to check for cervical infection in determining the cause of PCB, but few GU medicine practitioners now perform colposcopy and many consider themselves insufficiently trained to assess the cervix in more detail. Since the colposcope is the optimal tool for examining the anogenital tract, we suggest that colposcopy, in its broadest sense, should be reconsidered as an essential part of GU medicine training.

Destigmatizing genitourinary medicine and sexually transmitted infections in the UK.

Sexually transmitted infections (STIs) and the clinics patients attend for STI management remain stigmatized. Although emphasizing sexual intercourse rather than sexual behaviour as an important factor in STI acquisition may help to destigmatize STIs, this will require a change in the national mindset. A different approach entails destigmatizing genitourinary (GU) medicine/sexual health thereby normalizing the conditions managed in these settings. This may be helped by emphasizing the non-STI-related aspect of GU medicine and by considering a change in terminology that removes the focus from STIs and attempts to absorb the term into the broader category of genital infection.

A multicentre, randomised, double-blind, placebo controlled study of cryotherapy versus cryotherapy and podophyllotoxin cream as treatment for external anogenital warts.

OBJECTIVES: To compare the efficacy and safety of combination therapy with cryotherapy and podophyllotoxin 0.15% cream versus cryotherapy alone in the treatment of anogenital warts. METHODS: A randomised, double-blind, multicentre controlled trial. Patients received podophyllotoxin cream or placebo twice daily for 3 days/week for up to 4 weeks, with weekly cryotherapy continued to week 12 if required. Further treatment from week 12 to 24 was discretionary. Patients were stratified by sex and history of warts. HIV positivity, warts treated in the past 4 months, or warts with a combined area of less than 10 mm(2) were exclusion criteria. Primary endpoints were clearance at weeks 4 and 12. RESULTS: 70 patients per group were randomly assigned and started treatment; 101 first-episode warts, 91 male. No treatment-related serious adverse events were reported. Follow-up at week 12 was 85%. By intention-to-treat analysis, clearances at 4 and 12 weeks were higher in the combination group (60.0% and 60.0%, respectively) than with cryotherapy alone (45.7%, 45.7%) although not statistically significant (RR 1.31, 95% CI 0.95 to 1.81). By week 24 there was no difference between the groups (68.6% and 64.3%, respectively; RR 1.07, CI 0.84 to 1.35). At week 4, wart clearance was higher in men (p = 0.001) and those with a past history of warts (p = 0.009), but these differences were not detected at week 12. There was some evidence for a higher relapse rate in the group receiving cryotherapy alone. CONCLUSIONS: Initial combination therapy with podophyllotoxin/cryotherapy was well tolerated and may have resulted in earlier clearance in some patients, compared with cryotherapy alone; however, overall differences in clearance rates were not statistically significant.

Frequently asked questions about genital warts in the genitourinary medicine clinic: an update and review of recent literature.

Genital warts are the commonest viral STI in the UK, and the incidence continues to rise. Diagnosing, treating and advising patients about this infection remain a large part of the work in any department of GU Medicine. This article reviews and provides the levels of evidence currently available on data about genital warts, and is primarily to advise and guide clinicians when faced with commonly asked questions in the clinic.

Molecular epidemiology of genital human papillomavirus and Chlamydia trachomatis among patients attending a genitourinary medicine clinic - will vaccines protect?

High-risk subtypes of human papillomavirus (HPV) are the main causative agents of cervical cancer, for which Chlamydia trachomatis (CT) may sometimes be a co-factor. Vaccines have been developed against some subtypes of human papillomavirus and a vaccine against CT is in development. The objective of this study was to determine the prevalence of the subtypes of HPV and CT in genitourinary (GU) medicine clinic attenders. In total, 1000 consecutive patients attending the GU clinic participated in this anonymized point-prevalence study. Urethral swabs from 437 men and urethral plus cervical swabs as a single specimen from 563 women were tested for the subtypes of both organisms. Nested major outer membrane protein (MOMP) polymerase chain reaction detected CT chromosomal DNA in 44/437 (10%) of the men and 73/563 (13%) of the women. Genotypes E, F, and D were the most common. In all, 55/437 (13%) of men and 244/563 (43%) of women were infected with at least one high-risk HPV type. In conclusion, the new HPV vaccines, Gardasil and Cervarix, would have protected against 58% and 45%, respectively, of the high-risk subtypes found in women in this population. The rate of high-risk HPV infection (43%) found in women in this study raises concern.

Treatment of ano-genital warts: the effect of an educational event on practitioner choice.

To determine whether an educational event can affect treatment choice for ano-genital warts, genitourinary medicine clinicians attending a wart management lecture were shown 14 photographs of genital warts of differing morphology at different sites and asked to choose their preferred method of treatment. Study questionnaires were completed pre-lecture and repeated after the lecture and discussion. Podophyllin was chosen significantly less frequently and cryotherapy more frequently post-lecture for certain wart types. Podophyllotoxin was favoured for multiple small penile and posterior fourchette warts, whereas imiquimod was chosen predominantly for large or bulky lesions. Trichloracetic acid was infrequently chosen as a treatment option (<6% of respondents). This study has shown that clinicians attending a lecture on the management of ano-genital warts do change their treatment choice for certain clinical scenarios. Whether opting for a particular treatment in a lecture setting translates to altered practice in the clinical setting requires further study.

Local and systemic human papillomavirus type 6b-specific cellular immune responses in patients with recurrent genital warts.

Anogenital warts are a common clinical manifestation of genital infection with human papillomavirus type 6b (HPV-6b). Accumulating data indicate that an effective cellular immune response is required for the control of HPV infections. However, in a minority of patients there is a high rate of recurrence of wart lesions. We report the characterization of both local and systemic HPV-specific cellular immune responses in three patients with a history of recurrent genital warts. Although the patients had chronic recurrent wart lesions, we have shown that each had both detectable intralesional and peripheral HPV-specific T lymphocytes. Interestingly, the lesion-infiltrating T cells were specific for only one HPV antigen, focusing on only a few epitopes. Conversely, the T cells derived from peripheral blood recognized a broader range of HPV antigens. The characteristics of the HPV-specific cellular immunity that we have shown in these patients may be indicative of a failure to mount an effective response against the virus. This would be consistent with the chronic nature of the disease in these specific individuals. These observations could be relevant to the design and immunomonitoring of immunotherapeutic vaccines for persistent HPV infections.

The superiority of polymerase chain reaction over an amplified enzyme immunoassay for the detection of genital chlamydial infections.

BACKGROUND/OBJECTIVES: The polymer conjugate enhanced enzyme immunoassay (IDEIA) and Cobas Amplicor polymerase chain reaction Chlamydia trachomatis (CT) (Amplicor PCR) are two commonly used assays for the diagnosis of CT infection. The performance of these assays was compared for the diagnosis of genital CT infection among 1000 consecutive patients attending a genitourinary medicine (GUM) clinic. Confirmation of positive results and the clinical significance of the absence of cryptic plasmid in chlamydia on the diagnosis of infection by Amplicor PCR were also investigated. METHODS: IDEIA, Amplicor PCR, and two nested in-house PCR assays targeting cryptic plasmid and omp1 gene were performed on all samples. DNA from Amplicor PCR negative samples was pooled for in-house PCR assays. Each pool contained DNA from seven Amplicor PCR negative samples. RESULTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and efficiency of IDEIA in the diagnosis of genital CT infection were 80%, 97%, 80%, 97%, and 95%, respectively. Sensitivity, specificity, PPV, NPV and efficiency of Amplicor PCR were 99%, 98%, 89%, 100%, and 98%, respectively. 16 (11%) of 144 Amplicor PCR positive results were identified as false positive by in-house PCR assays. No isolate of plasmid free CT was detected among the study population. CONCLUSIONS: IDEIA should not be used for the diagnosis of CT infection because of its poor sensitivity. Although the analytic specificity of Amplicor PCR was 98%, because of the adverse medical, social, and psychological impact of false positive results for patients, confirmation of Amplicor PCR positive results by a different assay with comparable sensitivity is essential. Amplification assays targeting cryptic plasmid are appropriate for the diagnosis of genital CT infections.

Genital allergy.

Genital allergy should be considered as a possible diagnosis in all patients with genital soreness or irritation for which no infection or dermatosis can be identified and in whom symptoms remain unchanged or worsen with treatment. Type I and IV hypersensitivity reactions are most commonly encountered and can be assessed by performing skin prick testing/radioallergosorbent test (RAST) or patch testing, respectively. Type IV reactions (contact dermatitis) may sometimes prove difficult to distinguish clinically from an irritant dermatitis. This clinical review attempts to summarise key features of genital allergy for the practicing clinician.

Contamination of environmental surfaces by genital human papillomaviruses.

OBJECTIVE: To investigate contamination of environmental surfaces with human papillomaviruses (HPV) DNA in two genitourinary medicine (GUM) clinics and in an on-site staff leisure and fitness centre. METHODS: Samples were collected from the treatment rooms and patients' toilets of two GUM clinics situated at two hospital sites and from the toilets of the staff leisure and fitness centre on one of the sites. Samples were tested for the presence of HPV DNA by nested polymerase chain reaction (PCR), and HPV amplicons were typed by reverse line hybridisation using HPV type specific oligonucleotide probes complementary to 35 HPV types. All samples were also tested for beta globin DNA by PCR in order to assess their quality. RESULTS: HPV DNA was found to be present at more than 50% of the sites sampled in one of the GUM clinics, but was absent in the second, and also from the staff leisure and fitness centre. All HPV DNA detected was found to be cell associated. The most commonly found HPV types were 6, 11, and 16, respectively. HPV infected cells were found to be localised mainly to surfaces used predominantly by medical staff. CONCLUSIONS: This study has identified contamination of the environment of a GUM clinic. Possible sources for the contamination of the clinic toilets were from genital sites via hands to the environment. Within the treatment rooms the most likely route of HPV DNA contamination of the environment was via the doctor's gloved hands.

The treatment of human papillomavirus lesions of the lower genital tract.

Anogenital warts are caused by human papillomavirus types 6 and 11 infection, and are the most common clinical manifestation of lower genital tract human papillomavirus infection. They are the most frequently recognized sexually transmitted disease in the developed world, occurring at an incidence rate of 0.5-1.2% in young men and women aged 18-25 years. Many therapies for genital warts have been described, none being ideal in that all therapeutic modalities fail to clear the warts in a proportion of patients, and the recurrence of warts after successful treatment is seen with all treatments. The current knowledge base of the therapy of genital warts is flawed by a lack of good natural history data either with treatment or without treatment over longer periods of time, in that most trials report comparisons of monotherapies over a short time and there is a lack of structured trials addressing consecutive therapies over longer durations, as occurs in real-life clinical situations.