Global Type-Specific Genital Human Papillomavirus Prevalence in Men, by Sexual Orientation: A Systematic Review and Meta-Analysis.

BACKGROUND: Knowledge on genital type-specific human papillomavirus (HPV) prevalence among men is important for prevention of HPV-related cancers and other diseases. Men who have sex with men (MSM) have higher anal prevalence than men who have sex with women only (MSW) but for genital HPV this is unclear. We performed a systematic review and meta-analysis of type-specific genital HPV prevalence among men, by sexual orientation. METHODS: MEDLINE and Embase were used for searching publications reporting on male genital HPV prevalence with data from November 2011 onwards. A random-effects meta-analysis was conducted estimating pooled type-specific and grouped external genital and urethral HPV prevalence. Subgroup analyses were conducted for sexual orientation. RESULTS: Twenty-nine studies were eligible. Of those, 13 studies reported prevalence among MSM, 5 among MSW, and 13 studies did not stratify by sexual orientation. The most common genotypes were HPV-6 and HPV-16 for both anatomical locations, although heterogeneity was high. HPV prevalence was similar among studies reporting on MSW, MSM, and men with unknown sexual orientation. CONCLUSIONS: Genital HPV is common among men, with HPV-6 and HPV-16 being the most common genotypes. Type-specific HPV genital prevalence appears to be similar among MSM and MSW, which contrasts with earlier findings on anal HPV.

Substantial impact of the COVID-19 pandemic on the reported number of diagnosed chronic hepatitis C virus infections in the Netherlands, 2019-2021.

BACKGROUND: The COVID-19 pandemic has widespread consequences for health facilities, social contacts, and health-seeking behaviour, affecting the incidence, diagnosis and reporting of other infectious diseases. We examined trends in reported chronic hepatitis C virus (HCV) infections and associated transmission routes in the Netherlands to identify the potential impact of COVID-19 on access to healthcare (testing) services. METHODS: We analysed notification data of patients with chronic HCV reported to the National Notifiable Disease Surveillance System from January 2019 until December 2021 in the Netherlands. Rates of newly reported chronic cases per 100,000 population with 95% confidence intervals (CI) were calculated, and we compared proportional changes in transmission routes for chronic HCV between 2019, 2020 and 2021. RESULTS: During the study period, a total of 1,521 chronic HCV infections were reported, 72% males, median age 52 years, and an overall rate of 8.8 (95%CI 8.4-9.2) per 100,000 population. We observed an overall decline (-41.9%) in the number of reported chronic HCV in 2020 compared to 2019, with the sharpest decline in men who have sex with men (MSM)-related transmission (-57.9% in 2020, p = 0.005). CONCLUSIONS: Reported cases of chronic HCV strongly declined during the COVID-19 pandemic when healthcare services were scaled down. Between February and June 2021, reported chronic HCV cases increased again, indicating a recovery of healthcare services. MSM showed the largest decline compared to other groups. Further research is needed to fully understand the impact of access to healthcare, health seeking behaviour, and (sexual) transmission risks of HCV during the COVID-19 pandemic.

Eligibility criteria vs. need for pre-exposure prophylaxis: a reappraisal among men who have sex with men in Amsterdam, the Netherlands.

To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011-2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs (n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0-17.0); PAF = 55.3% (95% CI 43.3-83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3-8.7); PAF = 38.0% (95% CI 18.3-93.6)) and anal STI (RR = 5.3 (95% CI 1.7-16.7); PAF = 22.0 (95% CI -16.8 to 100.0)) were significantly (P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6-2.4); PAF = 19.5 (95% CI 10.6-30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0-3.0); PAF = 28.0 (95% CI 21.0-36.4)) were also significantly associated with anal STI, as was younger age (16-34/≥35; RR = 1.7 (95% CI 1.4-2.1); PAF = 15.5 (95% CI 6.4-27.6)) and group sex (RR = 1.3 (95% CI 1.1-1.6); PAF = 9.0 (95% CI -2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.

Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects.

BACKGROUND: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. METHODS: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. RESULTS: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women). CONCLUSIONS: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.

Partial Protective Effect of Bivalent Human Papillomavirus 16/18 Vaccination Against Anogenital Warts in a Large Cohort of Dutch Primary Care Patients.

BACKGROUND: There is ongoing debate about the possible protective effect of the bivalent human papillomavirus (2vHPV) vaccine, targeting oncogenic types HPV-16/18, against anogenital warts (AGWs), commonly attributed to HPV-6/11. We performed a retrospective registry-based open cohort study to assess the effect of 2vHPV vaccination on AGWs. METHODS: We linked general practice (ie, primary care) data from women born between 1993 and 2002, who had been eligible for HPV vaccination in the Netherlands, to the Dutch national immunization registry on an individual level. Women were followed until their first AGW diagnosis or end of follow-up. Adjusted incidence rate ratios (aIRRs) were estimated using Poisson regression with vaccination status as a time-dependent exposure. RESULTS: We linked data of 96 468 women with a total of 328 019 years observation time and 613 AGW diagnoses (incidence: 1.87/1000 person-years). At the end of follow-up, 61% were 2vHPV vaccinated (≥ 1 dose) of whom 91% were fully vaccinated. The AGW incidence was lower among those with ≥ 1 dose vs 0 doses (aIRR, 0.75 [95% confidence interval {CI}, .64-.88]). The effect of vaccination was stronger after full vaccination (aIRR, 0.72 [95% CI, .61-.86]) and for women who were offered vaccination at 12-13 years of age (aIRR, 0.69 [95% CI, .51-.93]) vs those at 13-16 years of age (aIRR, 0.77 [95% CI, .64-.93]). CONCLUSIONS: This is the largest population-based study so far to examine the effect of 2vHPV vaccination on AGWs, with reliable individual information on AGW diagnoses and vaccination status. The results indicate that 2vHPV vaccination partially protects against AGWs, especially when administered in early adolescence.

Where to go to in chlamydia control? From infection control towards infectious disease control.

OBJECTIVES: The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites. METHODS: We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands. RESULTS: Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost-effectiveness analysis. CONCLUSION: The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of 'test and treat' and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.

Bivalent Vaccine Effectiveness Against Anal Human Papillomavirus Positivity Among Female Sexually Transmitted Infection Clinic Visitors in the Netherlands.

Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for vaccine effectiveness (VE) against anal HPV infections among women is limited. We estimated the VE (≥1 dose) against anal HPV positivity of the bivalent vaccine, whose target types HPV-16/18 are associated with approximately 90% of HPV-related anal cancers. Among 548 female STI clinic visitors 16-24 years old who provided an anal swab sample as part of a repeated cross-sectional survey, VE against HPV-16/18 was 89.9% (95% confidence interval, 63.0%-97.2%). Type-specific VE correlated well with VE against cervicovaginal HPV (Spearman ρ = 0.76), suggesting comparable effectiveness of HPV-16/18 vaccination against genital and anal infections.

Low gonorrhoea antimicrobial resistance and culture positivity rates in general practice: a pilot study.

OBJECTIVE: In the Netherlands, the Gonococcal Resistance to Antimicrobials Surveillance (GRAS) programme is carried out at Centres for Sexual Health (CSH), which provide care for sexual high-risk populations. However, half of gonorrhoea infections are diagnosed in general practice (GP). We performed a pilot study to explore expanding GRAS to GPs using laboratory-based surveillance. Additionally, antimicrobial resistance patterns of GP and CSH patients were compared. METHODS: Three laboratories from different regions were included, which all perform gonorrhoea diagnostics for GPs and used ESwab for patient sampling. Additional culturing for all GP patients with gonorrhoea took place from February to July 2018. After positive PCR-nucleic acid amplification test, residual ESwab material was used for culture. In positive cultures, susceptibility testing was performed for azithromycin, ciprofloxacin, cefotaxime and ceftriaxone using Etest. RESULTS: During the study period, 484 samples were put in culture. 16.5% of cultures were positive (n=80). Antimicrobial resistance levels were low, with 2.6% resistance to azithromycin, 21.5% to ciprofloxacin and 0.0% to cefotaxime and ceftriaxone. Resistance levels in CSH GRAS data (first half of 2018) were 19.2% for azithromycin, 31.5% for ciprofloxacin, 1.9% for cefotaxime and 0.0% for ceftriaxone. CONCLUSIONS: Culture positivity rates for GP patients were low, probably due to long transportation times and awaiting PCR test results before attempting culture. Positivity rates might be improved by making changes in sampling and/or transportation methods, but that would require involvement of GPs and patients instead of keeping the surveillance lab based. Resistance levels appeared to be lower at GPs than at the CSH, indicating that resistance might emerge first in more high-risk populations. It is important to consider all potentially relevant patient populations when establishing a gonococcal antimicrobial resistance surveillance programme. However, based on the findings from this study the current GRAS programme will not be extended to GPs.

Latent classes of sexual risk and corresponding STI and HIV positivity among MSM attending centres for sexual health in the Netherlands.

OBJECTIVES: Continuing high STI positivity among men who have sex with men (MSM) attending centres for sexual health (CSH) indicates that high-risk behaviour is ongoing. The objective of this study was to gain a better insight into risk behaviours among MSM attending CSH and to explore STI and HIV positivity by subgroups. METHODS: We used national data routinely collected during CSH consultations for this study. From September to December 2017, questions on group sex, substance use and sex with HIV-positive partners were asked at each CSH consultation. We analysed latent classes of client-related factors and sexual risk behaviour among MSM attending CSH in this period. We examined STI positivity and prevalence ratios by latent classes. RESULTS: A total of six classes were identified in order of increasing risk: 'overall low-risk behaviour' (n=2974; 22.0%), 'Western origin and multiple sex partners' (MSP) (n=4182; 30.9%), 'Non-Western origin and MSP' (n=2496; 18.5%), 'living with HIV' (n=827; 6.1%), 'group sex and HIV-positive partners' (n=1798; 13.3%) and 'group sex and chemsex' (n=1239; 9.2%). The any STI positivity ranged from 14.0% in the overall low-risk behaviour class to 35.5% in the group sex and chemsex class. HIV positivity did not differ significantly between classes. The Western origin and MSP class was largest and accounted for the majority of STI and HIV infections. CONCLUSIONS: Although STI positivity increased with increased risky behaviours, considerable STI positivity was found in all six latent classes. Comparable HIV positivity between classes indicates risk reduction strategies among subgroups engaged in risky behaviours. The differences in risk behaviour and STI positivity require preventive strategies tailored to each subgroup.

Impact of frequent testing on the transmission of HIV and N. gonorrhoeae among men who have sex with men: a mathematical modelling study.

OBJECTIVES: To investigate the impact and efficiency of combined testing for HIV and other STIs on HIV and STI transmission among men who have sex with men (MSM) and to assess what subgroups of MSM should be targeted for frequent testing. METHODS: We developed an agent-based transmission model that simulates infection with HIV or Neisseria gonorrhoeae (NG) among MSM. We examined scenarios with increased percentages of MSM getting tested six monthly, among all MSM or only specific subgroups of MSM (defined according to recent gonorrhoea, number of partners and engagement in condomless anal intercourse (CAI)) and scenarios with reduced intervals between HIV/STI tests. RESULTS: The most efficient strategies were those with increased percentage of MSM getting tested every 6 months among MSM with a recent gonorrhoea diagnosis; or among MSM who had CAI and ≥10 partners; or MSM who had ≥10 partners. Over 10 years, these strategies resulted in 387-718 averted HIV infections and required 29-164 additional HIV tests per averted HIV infection or one to seven additional gonorrhoea tests per averted NG infection. The most effective strategy in reducing HIV transmission was the one where the intervals between tests were reduced by half, followed by the strategy with increased percentage of MSM getting tested every 6 months among all MSM. Over 10 years, these strategies resulted in 1362 and 1319 averted HIV infections, but required 663 and 584 additional HIV tests per averted HIV infection, respectively. CONCLUSIONS: Targeting MSM with recent gonorrhoea diagnosis or MSM with many partners is efficient in terms of HIV/STI tests needed to prevent new HIV or NG infections. Major reductions in HIV incidence can be achieved with consistent HIV/STI testing every 6 months among larger groups, including low-risk MSM. To impede HIV transmission, frequent testing should be combined with other prevention measures.

Pregnancies and Time to Pregnancy in Women With and Without a Previous Chlamydia trachomatis Infection.

BACKGROUND: A Chlamydia trachomatis infection (chlamydia) can result in tubal factor infertility in women. To assess if this association results in fewer pregnant women, we aimed to assess pregnancy incidences and time to pregnancy among women with a previous chlamydia infection compared with women without one and who were participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: The NECCST is a cohort of women of reproductive age tested for chlamydia in a chlamydia screening trial between 2008 and 2011 and reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative) was defined using chlamydia screening trial-nucleic acid amplification test results, chlamydia immunoglobulin G presence in serum, or self-reported chlamydia infections. Data on pregnancies were collected via questionnaires in 2015-2016 and 2017-2018. Overall pregnancies (i.e., planned and unplanned) and time to pregnancy (among women with a pregnancy intention) were compared between chlamydia-positive and chlamydia-negative women using Cox regressions. RESULTS: Of 5704 women enrolled, 1717 (30.1%; 95% confidence interval [CI], 28.9-31.3) women was chlamydia positive. Overall pregnancy proportions were similar in chlamydia-positive and chlamydia-negative women (49.0% [95% CI, 46.5-51.4] versus 50.5% [95% CI, 48.9-52.0]). Pregnancies per 1000 person-years were 53.2 (95% CI, 51.5-55.0) for chlamydia negatives and 83.0 (95% CI, 78.5-87.9) for chlamydia positives. Among women with a pregnancy intention, 12% of chlamydia-positive women had a time to pregnancy of >12 months compared with 8% of chlamydia negatives (P < 0.01). CONCLUSIONS: Overall pregnancy rates were not lower in chlamydia-positive women compared with chlamydia-negative women, but among women with a pregnancy intention, time to pregnancy was longer and pregnancy rates were lower in chlamydia-positive women. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR-5597.

Placing sexually transmitted infection surveillance data in perspective by using national probability sample surveys.

BACKGROUND: Many European countries do not have comprehensive sexually transmitted infection (STI) surveillance in place. The objective was to investigate whether national probability sample surveys are useful in placing STI surveillance into perspective. METHODS: We used data from the Dutch national cross-sectional probability sample survey on sexual health 2016 (18-34-year-old sexually active individuals). Descriptive analyses were performed regarding STI testing (last year). Test numbers were extrapolated from the survey and compared with surveillance data from sexual health centres (SHCs) (complete) and general practitioners (GPs) (representative estimates from 7% of all GPs). Statistical differences in characteristics between SHC attendees and general population (according to weighted survey participants) were determined using χ2 statistic. Predictors of recent testing at GPs or SHCs were determined using multinomial multivariable logistic regression. RESULTS: Of the 17 222 survey invitees, 3217 (19%) were eligible for analyses. Testing uptake was higher in women (17.2%, 14.8-20.0%) than men (11.5%, 9.1-14.3%). The majority of tests were conducted by GPs followed by SHCs and hospitals. Number of tests extrapolated from the survey was similar to SHC surveillance data, but higher than GP surveillance data (women only). Testing at SHCs was associated with high-risk behaviour and with living in highly urbanized areas. Low education level and older age were, next to high-risk behaviour factors, determinants of testing at GPs. CONCLUSIONS: National probability sample surveys are useful for placing STI surveillance data into perspective by providing insights in testing patterns in the general population and identifying strengths and weaknesses of national surveillance systems.

Bivalent Human Papillomavirus (HPV) Vaccine Effectiveness Correlates With Phylogenetic Distance From HPV Vaccine Types 16 and 18.

To substantiate cross-protection reported across AS04-adjuvanted bivalent human papillomavirus (HPV) vaccine (2vHPV) studies, we reevaluated vaccine effectiveness against type-specific HPV positivity as a function of phylogenetic distance to vaccine target types HPV-16 and -18. We provide evidence of sustained cross-protection up to 8 years postvaccination in a high-risk population in the Netherlands. Moreover, our findings suggest that genomic distance better explains cross-protection than distance measures based on capsid antigens only. Taken together, 2vHPV is predicted to provide partial cross-protection against HPV-31, -33, -35, -45, -52, and possibly -58, that is, acknowledged oncogenic types with close phylogenetic relationships to HPV-16 or -18.

National prevalence estimates of chlamydia and gonorrhoea in the Netherlands.

OBJECTIVES: National prevalence estimates of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) are important for providing insights in the occurrence and control of these STIs. The aim was to obtain national prevalence estimates for chlamydia and gonorrhoea and to investigate risk factors associated with infection. METHODS: Between November 2016 and January 2017, we performed a national population-based cross-sectional probability sample survey among men and women aged 18-34 years in the Netherlands. Individuals were invited to complete a questionnaire about sexual health. At the end of the questionnaire, sexually active individuals could request a home-based sampling kit. Samples were tested for chlamydia and gonorrhoea using nucleic acid amplification test (NAAT). Logistic regression analyses were performed for predictors of participation and chlamydia infection. RESULTS: Of the 17 222 invited individuals, 4447 (26%) participated. Of these, 3255 were eligible for prevalence survey participation and 550 (17%) returned a sample. Participation in the prevalence survey was associated with age (20+) and risk factors for STI. We did not detect any gonorrhoea. The overall weighted prevalence of chlamydia was 2.8% (95% CI 1.5% to 5.2%); 1.1% (0.1% to 7.2%) in men and 5.6% (3.3% to 9.5%) in women. Risk factors for chlamydia infections in women aged 18-24 years were low/medium education level, not having a relationship with the person you had most recent sex with and age at first sex older than 16. CONCLUSIONS: Chlamydia and gonorrhoea prevalence were low in the general Dutch population, as was the participation rate. Repeated prevalence surveys are needed to analyse trends in STI prevalences and to evaluate control policies.

Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial.

OBJECTIVES: A better understanding of Chlamydia trachomatis infection (chlamydia)-related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: Women who participated in the CSI 2008-2011 (n=13 498) were invited in 2015-2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders. RESULTS: Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8). CONCLUSION: We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low. TRIAL REGISTRATION: NTR-5597.

Evaluating progress towards triple elimination of mother-to-child transmission of HIV, syphilis and hepatitis B in the Netherlands.

BACKGROUND: In 2014 the World Health Organisation (WHO) established validation criteria for elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. Additionally, the WHO set targets to eliminate hepatitis, including hepatitis B (HBV). We evaluated to what extent the Netherlands has achieved the combined WHO criteria for EMTCT of HIV, syphilis and HBV. METHODS: Data of HIV, syphilis and HBV infections among pregnant women and children (born in the Netherlands with congenital infection) for 2009-2015, and data required to validate the WHO criteria were collected from multiple sources: the antenatal screening registry, the HIV monitoring foundation database, the Perinatal Registry of the Netherlands, the national reference laboratory for congenital syphilis, and national HBV notification data. RESULTS: Screening coverage among pregnant women was > 99% for all years, and prevalence of HIV, syphilis and HBV was very low. In 2015, prevalence of HIV, syphilis and HBV was 0.06, 0.06 and 0.29%, respectively. No infections among children born in the Netherlands were reported in 2015 for all three diseases, and in previous years only sporadic cases were observed In 2015, treatment of HIV positive pregnant women was 100% and HBV vaccination of children from HBV positive mothers was > 99%. For syphilis, comprehensive data was lacking to validate WHO criteria. CONCLUSIONS: In the Netherlands, prevalence of maternal HIV, syphilis and HBV is low and congenital infections are extremely rare. All minimum WHO criteria for validation of EMTCT are met for HIV and HBV, but for syphilis more data are needed to prove elimination.

Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

Background: Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results: We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination <5 years ago (83% and 33%, respectively). Conclusion: We demonstrated high VE of the bivalent vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands.

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed.

STIs in sex partners notified for chlamydia exposure: implications for expedited partner therapy.

OBJECTIVES: Expedited partner therapy (EPT) may reduce chlamydia reinfection rates. However, the disadvantages of EPT for chlamydia include missing the opportunity to test for other STIs and unnecessary use of antibiotics among non-infected partners. As part of a larger study that investigated the feasibility of EPT in the Netherlands, we explored the frequency of STI among a potential EPT target population of chlamydia-notified heterosexual men and women attending STI clinics for testing. METHODS: Cross-sectional national STI/HIV surveillance data, which contain information on all consultations at STI clinics, were used to calculate STI positivity rates stratified by chlamydia notification and gender, and proportions of STI that were attributable to clients notified for chlamydia. RESULTS: Of all consultations in 2015 (n=101 710), 14 445 (14.4%) clients reported to be notified exclusively for chlamydia. Among chlamydia-notified clients, the chlamydia positivity rate was 34.2% (n=4947), and consequently 65.8% (n=9488) of them tested negative for chlamydia. Chlamydia-notified clients contributed to 10.2% of all gonorrhoea infections (n=174/1702) and 10.9% of all infectious syphilis, HIV and/or infectious hepatitis B infections (n=15/173). CONCLUSION: Implementing EPT without additional STI testing for all partners of chlamydia-infected index patients implies that STIs other than chlamydia will be missed. Although the chlamydia positivity rate was high among chlamydia-notified partners, two-thirds would unnecessarily use azithromycin. An evaluation of EPT against the current partner treatment strategy is needed to carefully weigh the potential health gains against the potential health losses and to explore the characteristics of EPT-eligible partners.

What explains anorectal chlamydia infection in women? Implications of a mathematical model for test and treatment strategies.

OBJECTIVES: Female anorectal Chlamydia trachomatis (chlamydia) infections are common irrespective of recent anal sex. We explored the role of anorectal infections in chlamydia transmission and estimated the impact of interventions aimed at improved detection and treatment of anorectal infections. METHODS: We developed a pair compartmental model of heterosexuals aged 15-29 years attending STI clinics, in which women can be susceptible to or infected with chlamydia urogenitally and/or anorectally and men urogenitally. Transmission probabilities per vaginal and anal sex act, together with an autoinoculation probability, were estimated by fitting to anatomic site-specific prevalence data (14% urogenital; 11% anorectal prevalence). We investigated the 10-year reduction in female chlamydia prevalence of interventions (universal anorectal testing of female STI clinic attendees or doxycycline use for urogenital chlamydia) relative to continued current care (anorectal testing on indication and doxycycline for anorectal and azithromycin for urogenital chlamydia). RESULTS: The transmission probability per anal sex act was 5.8% (IQR 3.0-8.3%), per vaginal sex act 2.0% (IQR 1.7-2.2%) and the daily autoinoculation probability was 0.7% (IQR 0.5-1.0%). More anorectal chlamydia infections were caused by autoinoculation than by recent anal sex. Universal anorectal testing reduced population prevalence modestly with 8.7% (IQR 7.6-9.7%), yet the reduction was double that of doxycycline use for urogenital infections (4.3% (IQR 3.5-5.3%)) relative to continued current care. CONCLUSIONS: Autoinoculation between anatomic sites in women might play a role in sustaining high chlamydia prevalence. A shift to more anorectal testing of female STI clinic attendees may be considered for its (albeit modest) impact on reducing prevalence.