The fading of the mpox outbreak among men who have sex with men: a mathematical modelling study.

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations. METHODS: We developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.

How the Disruption in Sexually Transmitted Infection Care Due to the COVID-19 Pandemic Could Lead to Increased Sexually Transmitted Infection Transmission Among Men Who Have Sex With Men in The Netherlands: A Mathematical Modeling Study.

BACKGROUND: During the COVID-19 pandemic, the disruption in care for sexually transmitted infections (STIs) and the social distancing measures have led to reductions in STI testing and sexual behavior. We assessed the impact of these COVID-19-related changes on transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among men who have sex with men (MSM) in The Netherlands. METHODS: We developed a mathematical model for CT and NG transmission among MSM, accounting for COVID-19-related changes in sexual behavior and testing in 2020 to 2021. Changes in 2020 were estimated from data from the Dutch COVID-19, Sex, and Intimacy Survey among MSM and the National Database of STI Clinics. Because of the lack of data for 2021, we examined several scenarios covering a range of changes. RESULTS: A reduction of 10% and 40% in STI testing of symptomatic and asymptomatic, respectively, individuals with a 10% to 20% reduction in numbers of casual partners (according to partner status and activity level) during the second lockdown, resulted in a 2.4% increase in CT prevalence, but a 2.8% decline in NG prevalence in 2021. A 5% and 30% reduction in STI testing of symptomatic and asymptomatic, respectively, individuals with the same reduction in casual partners resulted in a 0.6% increase in CT prevalence and a 4.9% decrease in NG prevalence in 2021. CONCLUSIONS: The disruption in STI care due to COVID-19 might have resulted in a small increase in CT prevalence, but a decrease in NG prevalence. Scaling up STI care is imperative to prevent increases in STI transmission.

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.

Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022.

In May 2022, monkeypox outbreaks have been reported in countries not endemic for monkeypox. We estimated the monkeypox incubation period, using reported exposure and symptom-onset times for 18 cases detected and confirmed in the Netherlands up to 31 May 2022. Mean incubation period was 9.0 [corrected] days (5th-95th percentiles: 4.2-17.3), underpinning the current recommendation to monitor or isolate/quarantine case contacts for 21 days. However, as the incubation period may differ between different transmission routes, further epidemiological investigations are needed.

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.

Potential effectiveness of prophylactic HPV immunization for men who have sex with men in the Netherlands: A multi-model approach.

BACKGROUND: Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands. METHODS AND FINDINGS: We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM. CONCLUSIONS: Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence.

Microscopic examination of Gram-stained smears for anogenital gonorrhoea in men who have sex with men is cost-effective: evidence from a modelling study.

OBJECTIVE: To assess the cost-effectiveness of three testing strategies with or without light microscopic Gram-stained smear (GSS) evaluation for the detection of anogenital gonorrhoea among men who have sex with men (MSM) at the Amsterdam STI clinic using a healthcare payer perspective. METHODS: Three testing strategies for MSM were compared: (1) GSS in symptomatic MSM only (currently practised strategy), (2) no GSS and (3) GSS in symptomatic and asymptomatic MSM. The three testing protocols include testing with nucleic acid amplification test to verify the GSS results in (1) and (3), or as the only test in (2). A transmission model was employed to calculate the influence of the testing strategies on the prevalence of anogenital gonorrhoea over 10 years. An economic model combined cost data on medical consultations, tests and treatment and utility data to estimate the number of epididymitis cases and quality-adjusted life years (QALY) associated with gonorrhoea. Incremental cost-effectiveness ratios (ICERs) for the testing scenarios were estimated. Uncertainty and sensitivity analyses were performed. RESULTS: No GSS testing compared with GSS in symptomatic MSM only (current strategy) resulted in nine extra epididymitis cases (95% uncertainty interval (UI): 2-22), 72 QALYs lost (95% UI: 59-187) and €7300 additional costs (95% UI: -€185 000 (i.e.cost-saving) to €407 000) over 10 years. GSS testing in both symptomatic and asymptomatic MSM compared with GSS in symptomatic MSM only resulted in one prevented epididymitis case (95% UI: 0-2), 1.1 QALY gained (95% UI: 0.1-3.3), €148 000 additional costs (95% UI: €86 000 to-€217 000) and an ICER of €177 000 (95% UI: €67 000-to €705 000) per QALY gained over 10 years. The results were robust in sensitivity analyses. CONCLUSIONS: GSS for symptomatic MSM only is cost-effective compared with no GSS for MSM and with GSS for both symptomatic and asymptomatic MSM.

Impact of point-of-care management on the transmission of anogenital gonococcal infections among men who have sex with men in Amsterdam: a mathematical modelling and cost-effectiveness study.

OBJECTIVE: Point-of-care (POC) management may avert ongoing transmissions occurring between testing and treatment or due to loss to follow-up. We modelled the impact of POC management of anogenital gonorrhoea (with light microscopic evaluation of Gram stained smears) among men who have sex with men (MSM) on gonorrhoea prevalence and testing and treatment costs. METHODS: Data concerning costs and sexual behaviour were collected from the STI clinic of Amsterdam. With a deterministic model for gonorrhoea transmission, we calculated the prevalence of gonorrhoea in MSM in Amsterdam and the numbers of consultations at our clinic over 5 years, in three testing scenarios: POC for symptomatic MSM only (currently routine), POC for all MSM and no POC for MSM. RESULTS: Among MSM, 34.7% (109/314) had sexual contacts in the period between testing and treatment, of whom 22.9% (25/109) had unprotected anal intercourse. Expanding POC testing from symptomatic MSM to all MSM could result in an 11% decrease (IQR, 8%-15%) in gonorrhoea prevalence after 5 years and a cost increase of 8.6% (€2.40) per consultation and €86 118 overall (+8.3%). Switching from POC testing of symptomatic MSM to no POC testing could save €1.83 per consultation (6.5%) and €54 044 (-5.2%) after 5 years with a 60% (IQR, 26%-127%) gonorrhoea prevalence increase. Overtreatment was 2.1% (30/1411) with POC for symptomatic MSM only and 4.1% (68/1675) with POC for all MSM. CONCLUSIONS: In the Amsterdam setting, possible abandonment of POC testing of symptomatic MSM because of budget cuts could result in a considerable increase in gonorrhoea prevalence against a reduction in costs per consultation. Expanding POC testing to all MSM could result in a modest reduction in prevalence and a cost increase. While the costs and outcomes depend on specific local characteristics, the developed framework of this study is useful to evaluate POC management in other settings.

Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among Men Who Have Sex With Men in the Netherlands.

BACKGROUND: In response to the rising threat of resistance to first-line antibiotics for gonorrhea, international guidelines recommend dual antimicrobial therapy. However, some countries continue to recommend monotherapy. We assess the cost-effectiveness of dual therapy with ceftriaxone and azithromycin compared with monotherapy with ceftriaxone, for control of gonorrhea among men who have sex with men in the Netherlands. METHODS: We developed a transmission model and calculated the numbers of new gonorrhea infections, consultations at health care specialists, tests, and antibiotic doses. With these numbers, we calculated costs and quality-adjusted life-years (QALY) with each treatment; and the incremental cost-effectiveness ratio (ICER) of dual therapy compared to monotherapy. The impact of gonorrhea on human immunodeficiency virus transmission was not included in the model. RESULTS: In the absence of initial resistance, dual therapy can delay the spread of ceftriaxone resistance by at least 15 years, compared to monotherapy. In the beginning, when there is no resistance, dual therapy results in high additional costs, without any QALY gains. When resistance spreads over time, the additional costs of dual therapy decline, the gained QALYs increase, the ICER drops off and, after 50 years, falls below &OV0556;20,000 per QALY gained. If azithromycin resistance is initially prevalent, resistance to the first-line treatment rises almost equally fast with both treatment strategies and the ICER remains extremely high. CONCLUSIONS: Compared with ceftriaxone monotherapy, dual therapy with ceftriaxone and azithromycin can considerably delay the spread of ceftriaxone resistance, but may only be cost-effective in the long run and in the absence of initial resistance.

Does online dating lead to higher sexual risk behaviour? A cross-sectional study among MSM in Amsterdam, the Netherlands.

BACKGROUND: Men having sex with men (MSM) frequently use the Internet to find sex partners. We examined the association between unprotected anal intercourse (UAI) with partners dated online and with partners dated offline (met elsewhere), and examined whether differences can be explained by self-perceived HIV status of the index and knowledge of partnership characteristics. METHODS: MSM were recruited at the Sexually Transmitted Infections Clinic in Amsterdam, in 2008-2009. Participants completed a questionnaire concerning sexual behaviour. Only men reporting both online and offline casual sex partners were included. We assessed the association between online/offline partner dating and UAI, using random-effects logistic regression analysis. RESULTS: Five hundred seventy-seven men (351 HIV-negative, 153 HIV-positive, and 73 HIV-unaware) reported UAI in 26 % of 878 online, and 23 % of 903 offline casual partnerships. The crude OR of online dating for UAI was 1.36 (95 % CI 1.03-1.81). HIV-positive men were more likely to report UAI than HIV-negative men (49 % vs. 28 % of partnerships). Adjusted for demographic characteristics, online dating had no significant effect on UAI among HIV-negative and HIV status-unaware men, but HIV-positive men were more likely to have UAI with online partners (aOR = 1.65 [95 % CI 1.05-2.57]). After correction for partner and partnership characteristics the effect of online/offline dating on UAI among HIV-positive MSM was reduced and no longer significant. CONCLUSIONS: Online dating was not significantly associated with UAI among HIV-negative MSM. HIV-positive MSM were more likely to practise UAI with partners dated online; however, after correction for partner and partnership characteristics, online partnership acquisition was not associated with a significantly increased risk of UAI.

Perceived HIV status is a key determinant of unprotected anal intercourse within partnerships of men who have sex with men in Amsterdam.

The practice of unprotected anal intercourse (UAI) involves at least two partners. We examined the associations between insertive or receptive UAI and perceived HIV seroconcordance and partnership type in self-perceived HIV-negative and self-perceived HIV-positive men who have sex with men (MSM). MSM (age ≥ 18 years) were recruited for a cross-sectional survey at the sexually transmitted infections clinic in Amsterdam, the Netherlands, in 2008-2009. Participants completed a questionnaire concerning partnerships in the preceding 6 months. Associations were quantified via multinomial logistic regression models using generalized estimating equations. The outcomes were 'no, or safe anal intercourse', 'insertive UAI', and 'receptive UAI'. We included 5,456 partnerships from 1,890 self-perceived HIV-negative men and 1,861 partnerships from 558 self-perceived HIV-positive men. Within the partnerships, perceived HIV status of the partner was an important determinant of UAI (p < 0.001). Among HIV-negative men, perceived HIV discordance was negatively associated with receptive UAI compared with no or safe UAI (OR 0.57; 95 % CI 0.36-0.92); when the partners were more familiar with each other, the risk of receptive UAI was increased relative to no or safe anal intercourse. Among HIV-positive men, perceived HIV discordance was negatively associated with insertive UAI (OR 0.05; 95 % CI 0.03-0.08). Within partnerships, perceived HIV status of the partner was one of the strongest determinants of UAI among self-perceived HIV-negative and HIV-positive MSM, and discordant serostatus was negatively associated with UAI. The findings suggest that serosorting is one of the main strategies when engaging in UAI.

A survey-based assessment of rates and covariates of mpox diagnosis and vaccination provides evidence to refine eligibility criteria for mpox vaccination among gay, bisexual and other men who have sex with men in the Netherlands.

Background: The 2022 multicountry mpox outbreaks predominantly affected gay, bisexual and other men who have sex with men (GBMSM) in non-endemic countries, including in the Netherlands. We conducted a survey-based assessment of the alignment between the risk factors associated with mpox diagnosis among GBMSM in the Netherlands and the eligibility criteria used in 2022 for vaccinating this group, with the aim to refine these criteria. Methods: An online self-report survey was conducted among adult GBMSM in the Netherlands between 29 July and 30 August 2022, corresponding to the first month of the Dutch mpox vaccination campaign. GBMSM were recruited via advertisements on social media and gay dating apps. Participants reported on their sexual behaviour, mpox diagnosis, and/or (initial) mpox vaccination since the start of the outbreak. Covariables of mpox diagnosis and vaccination were assessed using logistic regression analyses. Results: Of the 2,460 participants, 73 (3.0%, 95% CI 2.3-3.6%) were diagnosed with mpox and 485 (19.7%, 95% CI 18.1-21.3%) had received (initial) mpox vaccination. Using sample weighting, we estimated that, of the GBMSM population aged 18-80 years in the Netherlands, 1.1% (95% CI 0.7-1.6%) had been diagnosed with mpox and 7.8% (95% CI 6.8-8.9%) had received (initial) vaccination. HIV-PrEP use, living with HIV, reporting ≥20 sex partners in the past 12 months, and sex in sex venues/parties in the past 2 months were independent risk factors for mpox diagnosis. Except for sex in sex venues/parties, these variables were also independently associated with mpox vaccination. Conclusion: This study provides novel evidence regarding the degree to which the 2022 eligibility criteria for mpox vaccination align with the risk factors for mpox among GBMSM in the Netherlands. The findings contribute to a refinement of the eligibility criteria for mpox vaccination, to which sex in sex venues/parties should be added.

Hepatitis B vaccination of men who have sex with men in the Netherlands: should we vaccinate more men, younger men or high-risk men?

OBJECTIVES: The selective vaccination programme against hepatitis B virus (HBV) was introduced in the Netherlands in 2002 targeting high-risk groups, including men who have sex with men (MSM). Despite the high average age of vaccination in MSM, the number of notifications of acute HBV recently declined. We investigate whether this can be attributed to the selective vaccination programme. We examine how vaccination strategies could be improved and the impact of universal infant vaccination introduced in 2011. METHODS: We use a mathematical model for HBV transmission among MSM. The incidence of HBV was calculated from the model and from notification data of acute HBV. RESULTS: A decline was observed in the incidence of HBV since 2006, as calculated from the model; this decline was smaller than that observed in data if all MSM were equally likely to be vaccinated. Assuming that high-risk MSM were more likely to be vaccinated than low-risk MSM resulted in a steeper decline in modelled incidence and better agreement with observed incidence. Vaccinating MSM at a younger age or doubling the vaccination rate would increase the impact of selective vaccination, but is less effective than vaccinating high-risk MSM. CONCLUSIONS: Selective HBV vaccination of MSM in the Netherlands has had a substantial impact in reducing HBV incidence. The reduction suggests that vaccination rates among high-risk MSM were higher than those among low-risk MSM. Countries that have not yet reached 35-year cohorts with universal childhood vaccination should actively implement or continue selective high-risk MSM vaccination.

Modelling the impact of chlamydia screening on the transmission of HIV among men who have sex with men.

BACKGROUND: Recent studies have found high prevalences of asymptomatic rectal chlamydia among HIV-infected men who have sex with men (MSM). Chlamydia could increase the infectivity of HIV and the susceptibility to HIV infection. We investigate the role of chlamydia in the spread of HIV among MSM and the possible impact of routine chlamydia screening among HIV-infected MSM at HIV treatment centres on the incidence of chlamydia and HIV in the overall MSM population. METHODS: A mathematical model was developed to describe the transmission of HIV and chlamydia among MSM. Parameters relating to sexual behaviour were estimated from data from the Amsterdam Cohort Study among MSM. Uncertainty analysis was carried out for model parameters without confident estimates. The effects of different screening strategies for chlamydia were investigated. RESULTS: Among all new HIV infections in MSM, 15% can be attributed to chlamydia infection. Introduction of routine chlamydia screening every six months among HIV-infected MSM during regular HIV consultations can reduce the incidence of both infections among MSM: after 10 years, the relative percentage reduction in chlamydia incidence would be 15% and in HIV incidence 4%, compared to the current situation. Chlamydia screening is more effective in reducing HIV incidence with more frequent screening and with higher participation of the most risky MSM in the screening program. CONCLUSIONS: Chlamydia infection could contribute to the transmission of HIV among MSM. Preventive measures reducing chlamydia prevalence, such as routine chlamydia screening of HIV-infected MSM, can result in a decline in the incidence of chlamydia and HIV.

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study.

BACKGROUND: During the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands. METHODS: We estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence. RESULTS: With a decrease in numbers of sex partners of 15-25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred. CONCLUSIONS: Despite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.

Sex-specific immunization for sexually transmitted infections such as human papillomavirus: insights from mathematical models.

BACKGROUND: Sex-specific differences regarding the transmissibility and the course of infection are the rule rather than the exception in the epidemiology of sexually transmitted infections (STIs). Human papillomavirus (HPV) provides an example: disease outcomes differ between men and women, as does the potential for transmission to the opposite sex. HPV vaccination of preadolescent girls was recently introduced in many countries, and inclusion of boys in the vaccination programs is being discussed. Here, we address the question of whether vaccinating females only, males only, or both sexes is the most effective strategy to reduce the population prevalence of an STI like HPV. METHODS AND FINDINGS: We use a range of two-sex transmission models with varying detail to identify general criteria for allocating a prophylactic vaccine between both sexes. The most effective reduction in the population prevalence of infection is always achieved by single-sex vaccination; vaccinating the sex with the highest prevaccine prevalence is the preferred strategy in most circumstances. Exceptions arise only when the higher prevaccine prevalence is due to a substantially lower rate of natural immunity, or when natural immunity is lifelong, and a prolonged duration of infectiousness coincides with increased transmissibility. Predictions from simple models were confirmed in simulations based on an elaborate HPV transmission model. Our analysis suggests that relatively inefficient genital transmission from males to females might render male vaccination more effective in reducing overall infection levels. However, most existing HPV vaccination programs have achieved sufficient coverage to continue with female-only vaccination. CONCLUSIONS: Increasing vaccine uptake among preadolescent girls is more effective in reducing HPV infection than including boys in existing vaccination programs. As a rule, directing prophylactic immunization at the sex with the highest prevaccine prevalence results in the largest reduction of the population prevalence.

Long-term impact of human papillomavirus vaccination on infection rates, cervical abnormalities, and cancer incidence.

BACKGROUND: Vaccination against human papillomavirus (HPV) types 16/18 is being implemented in many countries. There may be indirect benefit of HPV vaccination to nonvaccinated women, who may experience a reduced risk of infection with vaccine-preventable types (herd immunity). We attempt to disentangle the direct and indirect effects of HPV vaccination, while accounting for 14 oncogenic HPV types in a dynamic modeling framework. METHODS: On the basis of vaccine uptake among preadolescent girls in the Netherlands, we calculated how heterosexual transmission of HPV-16/18 is expected to change as a result of vaccination, and used these predictions in an individual-based simulation model of cervical carcinogenesis that considers 14 high-risk HPV types. Models were parameterized to match prevaccine data on type-specific HPV infection and cervical disease. RESULTS: At 50% vaccine coverage, the estimated lifetime infection risk in nonvaccinated women dropped from 0.46 (95% credible interval = 0.35-0.54) to 0.37 (0.26-0.46) for HPV-16, and from 0.40 (0.32-0.46) to 0.31 (0.22-0.36) [corrected] for HPV-18. For the whole population, we calculated an eventual 47% reduction in cervical cancer incidence, with 1 in 4 cases prevented among nonvaccinated women. The number of indirectly averted cancer cases was highest with vaccine coverage between 50% and 70%, approximating 70 cases per 100,000 women born from 2010 onward. CONCLUSIONS: HPV-16/18 vaccination of preadolescent girls will markedly lower infection rates among nonvaccinated women. Reduced transmission of vaccine-preventable HPV becomes a prominent aspect of cervical cancer control, especially in populations with moderate vaccine coverage.

How patterns of migration can influence the heterosexual transmission of HIV in The Netherlands.

OBJECTIVES: Migrants originating from countries with a high HIV prevalence account for a large number of heterosexually acquired HIV infections in western European countries. These migrants may be infected before migrating and they may engage in unsafe sexual practices both in the country of residence and in their country of origin. This report investigates how patterns of migration may affect the heterosexual HIV epidemic in The Netherlands. METHODS: A mathematical model was used that describes the transmission of HIV in heterosexual partnerships between African migrants, Caribbean migrants and the local Dutch population. Infection of migrants before migrating to The Netherlands and during trips to their country of origin was also accounted for. RESULTS: The incidence of HIV infection among adult heterosexuals in 2010 was 1.50 new infections per 100,000 individuals per year. If the number of migrants entering the country increases, then the incidence of HIV will increase, although this change among Dutch individuals will be negligible. Moreover, if HIV prevalence among those migrating to The Netherlands (at the time of entry to the country) is higher, then incidence in the respective ethnic group will increase; among other ethnic groups, the increase will be very small. CONCLUSIONS: Heterosexual transmission of HIV in The Netherlands occurs mostly within migrant communities. Limiting migration and introducing travel restrictions would probably have no effect on HIV incidence in countries with low HIV prevalence among heterosexuals. Policy making should focus on targeted interventions, to reduce the burden of disease in migrant communities in Europe.

Ending risk-group HBV vaccination for MSM after the introduction of universal infant HBV vaccination: A mathematical modelling study.

BACKGROUND: Risk-group HBV vaccination for men who have sex with men (MSM) was introduced in the Netherlands in 2002, followed by universal infant vaccination in 2011, that will enable termination of risk-group vaccination over time. The introduction of pre-exposure prophylaxis (PrEP) for HIV prevention might result in increased HBV testing and vaccination against HBV. The aim of this study was to investigate the impact of the transition from risk-group to universal HBV vaccination, accounting for improvements in HBV testing and treatment, as well as the introduction of PrEP. METHODS: We developed a mathematical model for HBV transmission among MSM. Universal vaccination was modelled by assigning some MSM (5-15% in 2028 increasing to 80-90% in 2033 and thereafter) to be vaccinated when they become sexually active. We investigated different scenarios assuming 0.5% extra vaccination rate and 0.5% extra testing rate due to PrEP consultations; and 5% of HIV-negative MSM on PrEP, that will reduce the probability of HBV acquisition by 88%. RESULTS: Universal vaccination resulted in a reduction of 24% (interquartile range; 22-25%) of the total number of HBV infections among MSM estimated to occur from 2020 to 2070. With universal vaccination, terminating risk-group vaccination in 2030 or 2040 resulted in 30% or 10% more HBV infections over 2020-2070, respectively, compared to continuation of risk-group vaccination until 2070. With PrEP and continued risk-group vaccination, the total number of HBV infections over 2020-2070 was reduced by 13%. CONCLUSIONS: Universal HBV vaccination can lead to a major reduction in HBV incidence among MSM in the future. The reduction becomes smaller when ending risk-group HBV vaccination, but larger by PrEP use for HIV prevention. Efforts to keep high levels of HBV vaccination, testing, and treatment have to be continued in the coming decades in order to eliminate HBV as a health threat for MSM.

Offering a choice of daily and event-driven preexposure prophylaxis for men who have sex with men in the Netherlands: a cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands. METHODS: We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than €20 000 per QALY gained was considered cost-effective. RESULTS: Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP. CONCLUSIONS: A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP.