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.

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.

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.

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.

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.

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.

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.

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.

Transmission of HIV to heterosexual partners of infected men and women.

Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission.

Human papillomavirus infection with particular reference to genital disease.

HPV is the commonest sexually transmitted viral infection in the United Kingdom and as such poses a major public health problem. In addition to the potential physical morbidity associated with genital warts, abnormal cervical cytology, and anogenital dysplasia and neoplasia, the associated psychological morbidity should not be forgotten. Although our knowledge of viral function and disease pathogenesis has advanced appreciably in recent years, we are still some way from developing an in vitro method of viral propagation. Vaccination against HPV infection will hopefully be achieved within the next 10 years, but a prevention and treatment strategy which is appropriate for both developed and developing nations must be our major long term goal.

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.

The management of chlamydial infection: setting standards at a regional level.

Between 1993 and 1997, clinicians from 9 departments of genitourinary medicine (GUM) and one department of sexual health in East Anglia met to audit the process of contact tracing in chlamydial infection. After defining the target group, standards were set for discussion of the diagnosis with the index patient, appropriate treatment of the condition and documented notification of partners. Data were collected for all patients with confirmed chlamydial infection during the periods January to March 1995 and 1996. Considering the combined data for both years, overall 97% of patients were informed of the diagnosis and 100% received appropriate treatment. Notification of partners was addressed at the initial consultation in 99% of cases and again at follow-up in 87%. Where contacts were traceable, there was confirmation that assessment had occurred in 65%, and the index cases reported that 66% had undergone assessment. The achievements and also the problems associated with this audit are discussed.

Pearly penile papules: a common cause of concern.

This study of two hundred men attending a department of genitourinary medicine documented a prevalence of pearly penile papules of 48%. Most men with papules had only a few lesions of less than 1 mm in size (73%). Nineteen per cent had papules of less than 1 mm in size extending around the corona and 8% had lesions greater than 1 mm in size extending around the corona. Over one-third of men with papules had previously been concerned or worried by their presence and approximately one-quarter had experienced embarrassment. Fourteen per cent of men with small lesions and 75% with larger lesions wished to have them removed. Two men with large and extensive papules underwent treatment by CO2 laser ablation with excellent cosmetic results.

Testing for HIV antibody: a comparison of two services offered in a genitourinary medicine clinic.

Rates of screening for sexually transmissible infections in patients using different services provided by a genitourinary medicine clinic for testing for HIV antibodies are presented. Those patients whose primary reason for attending the clinic was HIV antibody testing and used the same day result (SDR) service were significantly less likely to be screened for other infections than those using the normal waiting time (NWT) service, (P < 0.00001). This was true for both males and females. Of those patients screened for other infections in the SDR and NWT groups 29% and 35% respectively were found to have a sexually transmitted infection. It would appear that an SDR service offers little benefit for the majority of patients as only a few patients would not have had an HIV antibody test had the SDR not been available.

Risk behaviours for HIV infection among injecting drug users attending a drug dependency clinic.

To study a range of possible risk factors for HIV among injecting drug user patients attending a clinic in London were interviewed from November 1986 to November 1987. Serum samples were tested for viral markers. Of 116 patients, 101 had shared injecting equipment, 75 on the first occasion of injecting and 76 during the past year. Seventy said that sharing was because equipment was not available. In the past year 102 had been sexually active, a third having two to 20 partners; a quarter of the women had exchanged sexual intercourse for money. The four patients who were positive for antibody to HIV antigen had shared equipment or had intercourse with drug users from areas with a high prevalence of HIV. Eleven patients had injected drugs while in prison. Despite a low prevalence of HIV infection this infection remains a threat to drug users in London; strenuous efforts are still needed to prevent its further transmission.

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.

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.

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.