Basil Donovan

ACUTE AIDS RETROVIRUS INFECTION: Definition of a Clinical Illness Associated with Seroconversion

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.

Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data

BACKGROUND Quadrivalent human papillomavirus (HPV) vaccine has high efficacy in clinical trials but no reports describe its effects at a population level. From July, 2007, Australia was the first country to fund a vaccination programme for all women aged 12-26 years. We established a national surveillance network in Australia and aimed to identify trends in diagnoses of genital warts in 2004-09. METHODS We obtained standardised data for demographic factors, frequency of genital warts, HPV vaccination status, and sexual behaviour for new patients attending eight sexual health services in Australia between January, 2004, and December, 2009. We used χ² analysis to identify significant trends in proportions of patients diagnosed with warts in periods before and after vaccination began. Our primary group of interest was female Australian residents who were eligible for free vaccination, although data were assessed for patients ineligible for free vaccination, including women older than 26 years of age, non-resident women, and men. FINDINGS Among 112 083 new patients attending sexual health services, we identified 9867 (9%) cases of genital warts. Before the vaccine programme started, there was no change in proportion of women or heterosexual men diagnosed with genital warts. After vaccination began, a decline in number of diagnoses of genital warts was noted for young female residents (59%, p(trend)<0·0001). No significant decline was noted in female non-residents, women older than 26 years in July, 2007, or in men who have sex with men. However, proportionally fewer heterosexual men were diagnosed with genital warts during the vaccine period (28%, p(trend)<0·0001), and this effect was more pronounced in young men. By 2009, 65·1% of female Australian residents who were eligible for free vaccine reported receipt of quadrivalent or unknown HPV vaccine. INTERPRETATION The decrease in frequency of genital warts in young Australian women resulting from the high coverage of HPV vaccination might provide protective effects in heterosexual men through herd immunity. FUNDING CSL Biotherapies.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING The Canadian Institutes of Health Research.

Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data

Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Design Trend analysis of national surveillance data. Setting Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Participants Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Main outcome measure Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Results Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period—from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period—from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. Conclusions The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.

The many faces of sex work

Objective: To compile a global typography of commercial sex work. Methods: A Medline search and review of 681 “prostitution” articles was conducted. In addition, the investigators pooled their 20 years of collected papers and monographs, and their observations in more than 15 countries. Arbitrary categories were developed to compile a workable typology of sex work. Results: At least 25 types of sex work were identified according to worksite, principal mode of soliciting clients, or sexual practices. These types of work are often grouped under the headings of “direct” and “indirect” prostitution, with the latter group less likely to be perceived or to perceive themselves as sex workers. In general, policing sex work can change its typology and location but its prevalence is rarely affected. The public health implications of sex work vary widely. Conclusion: Developing comprehensive sexual health promotion programmes requires a complete understanding of the types of sex work in a particular area. This study provides a checklist for developing appropriate and targeted programmes.

Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women.

Objective: This study aimed to determine if the Australian human papillomavirus (HPV) vaccination programme has had a population impact on presentations of genital warts. Methods: Retrospective study comparing the proportion of new clients with genital warts attending Melbourne Sexual Health Centre (MSHC) from January 2004 to December 2008. Australia provided free quadrivalent HPV vaccine to 12–18-year-old girls in a school-based programme from April 2007, and to women 26 years and younger through general practices from July 2007. Results: 36 055 new clients attended MSHC between 2004 and 2008 and genital warts were diagnosed in 3826 (10.6%; 95% CI 10.3 to 10.9). The proportion of women under 28 years with warts diagnosed decreased by 25.1% (95% CI 30.5% to 19.3%) per quarter in 2008. Comparing this to a negligible increase of 1.8% (95% CI 0.2% to 3.4%) per quarter from the start of 2004 to the end of 2007 also in women under 28 years generates strong evidence of a difference in these two trends (p<0.001). There was no evidence of a difference in trend for the quarterly proportions before and after the end of 2007 for any other subgroup, and on only one occasion was there strong evidence of a trend different to zero, for heterosexual men in 2008 in whom the average quarterly change was a decrease of 5% (95% CI 0.5% to 9.4%; p = 0.031). Conclusions: The data suggest that a rapid and marked reduction in the incidence of genital warts among vaccinated women may be achievable through an HPV vaccination programme targeting women, and supports some benefit being conferred to heterosexual men.

The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme

Background Australia provided free quadrivalent human papillomavirus vaccines to 12–18-year-old girls and women aged ≤26 years from mid-2007 until the end of 2009. After this time, only girls aged 12–13 years had access to free vaccines. Methods Before and after the study, of the proportion of new patients attending Melbourne Sexual Health Centre from mid-2004 to mid-2011, diagnosed with genital warts (GW) by risk group. Results From July 2004 to June 2011, 52 454 new patients were seen at Melbourne Sexual Health Centre and 5021 (9.6%, 95% CI 9.3% to 9.8%) were diagnosed with GW. From July 2004 to June 2007, the proportions with GW either increased or did not change in all groups. Comparing the two 12-month periods of 2007/2008 and 2010/2011, GW declined in women under 21 years from 18.6% to 1.9% and in heterosexual men under 21 years from 22.9% to 2.9%. The ORs per year for diagnosis of GW adjusted for number of sexual partners from July 2007 until June 2011 in women and heterosexual men <21 years were 0.44 (95% CI 0.32 to 0.58) and 0.42 (95% CI 0.31 to 0.60), respectively. There was no significant change in GW in women ≥30 years (OR 0.97, 95% CI 0.84 to 1.12), heterosexual men ≥30 years (OR 0.97, 95% CI 0.89 to 1.06) or in homosexual men (OR 0.95, 95% CI 0.85 to 1.07). Conclusion The dramatic decline and near disappearance of GW in women and men under 21 years of age, 4 years after commencing this programme, suggest that the basic reproductive rate has fallen below one.

Incidence and risk factors for urethral and anal gonorrhoea and chlamydia in a cohort of HIV-negative homosexual men: the Health in Men Study

Background: Early detection and treatment of bacterial sexually transmitted infections has been advocated as an HIV prevention strategy. Aim: To inform screening guidelines, the incidence and risk factors for urethral and anal gonorrhoea and chlamydia were studied in a prospective cohort of community-based HIV negative homosexual men in Sydney, New South Wales, Australia. Methods: All participants were offered annual screening for gonorrhoea and chlamydia (study-visit diagnoses) on urine and anal swabs using nucleic acid amplification. Participants also reported diagnoses of gonorrhoea and chlamydia made elsewhere between interviews (interval diagnoses). All diagnoses were summed to create a combined incidence rate, and detailed data on specific sexual practices with casual and regular partners were collected. Results: Among 1427 men enrolled, the combined incidence rates were 3.49 and 2.96 per 100 person-years for urethral and anal gonorrhoea, respectively; and 7.43 and 4.98 per 100 person-years for urethral and anal chlamydia, respectively. Urethral infections were associated with unprotected anal intercourse (UAI) with HIV-positive partners (hazard ratio (HR) = 2.58, 95% CI 1.10 to 6.05 for urethral gonorrhoea) and with frequent insertive oral sex (p for trend 0.007 for urethral chlamydia). Anal infections were associated with receptive UAI (p for trend 0.001 for both anal gonorrhoea and chlamydia) and other receptive anal sexual practices. Stratified analyses showed the independence of the associations of insertive oral sex with urethral infections and of non-intercourse receptive anal practices with anal infections. Conclusion: Incident gonorrhoea and chlamydia were common. Risk behaviours for both urethral and anal infections were not restricted to UAI. Screening that includes tests for anal and urethral infections should be considered for all sexually active homosexual men, not just for those who report UAI.

Chlamydia trachomatis Incidence and Re-Infection among Young Women – Behavioural and Microbiological Characteristics

Background This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women. Methods 1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR. Results There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01). Conclusions Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia.

Response to hepatitis B vaccination in a primary care setting : Influence of HIV infection, CD4+ lymphocyte count and vaccination schedule

Factors affecting the response to hepatitis B vaccination in a primary care setting were examined by means of a review of case notes of patients attending 22 sexually transmissible disease services. Where not available from the notes, presence of antibody to hepatitis B surface antigen (anti-HBs) was determined by testing available stored serum. One hundred and ninety-five patients completed a course of 3 injections and had an anti-HBs assay performed. The highest response rate (anti-HBs > or = 10 IU/L) was found in human immunodeficiency virus (HIV)-negative heterosexual women (16 of 17, 94.1%) followed by HIV-negative heterosexual men (11 of 12, 91.7%); HIV-negative homosexual men (105 of 120, 87.5%); and HIV-positive homosexual men (6 of 14, 42.9%). (For HIV-positive vs HIV-negative homosexual men, P = 0.0003). Eleven of 14 (78.6%) homosexual men of unknown HIV status responded to vaccination. There was a trend to lower CD4+ lymphocyte counts among HIV-infected patients who responded to hepatitis B vaccination (mean 482 cells/cm2) when compared to those that did not respond (632 cells) but this difference was not statistically significant (P = 0.330). Neither the type of vaccine (recombinant, plasma-derived or mixed) nor the length of vaccination course (mean 6.2 months; range 2 to 18) affected response. This study confirmed that vaccination against hepatitis B is much less effective in HIV-infected homosexual men and marginally less effective for HIV-negative homosexual men, though the mechanism for this reduced response is uncertain. Reassuringly vaccine response was not affected by common variables in primary care settings such as vaccine type or delays in the vaccine schedule.