Circulation, viral diversity and genomic rearrangement in mpox virus in the Netherlands during the 2022 outbreak and beyond.

Mpox is an emerging zoonotic disease which has now spread to over 113 countries as of August 2023, with over 89,500 confirmed human cases. The Netherlands had one of the highest incidence rates in Europe during the peak of the outbreak. In this study, we generated 158 near-complete mpox virus (MPXV) genomes (12.4% of nationwide cases) that were collected throughout the Netherlands from the start of the outbreak in May 2022 to August 2023 to track viral evolution and investigate outbreak dynamics. We detected 14 different viral lineages, suggesting multiple introductions followed by rapid initial spread within the country. The estimated evolutionary rate was relatively high compared to previously described in orthopoxvirus literature, with an estimated 11.58 mutations per year. Genomic rearrangement events occurred at a rate of 0.63% and featured a large deletion event. In addition, based on phylogenetics, we identified multiple potential transmission clusters which could be supported by direct source- and contact tracing data. This led to the identification of at least two main transmission locations at the beginning of the outbreak. We conclude that whole genome sequencing of MPXV is essential to enhance our understanding of outbreak dynamics and evolution of a relatively understudied and emerging zoonotic pathogen.

Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022.

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.

Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023.

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.

Testing for sexually transmitted infection: who and where? A data linkage study using population and provider data in the Rotterdam area, the Netherlands.

BACKGROUND: In the Netherlands, insight into sexually transmitted infection (STI) testing and characteristics of those tested by general practitioners (GPs) and sexual health centres (SHC) is limited. This is partly due to lacking registration of socio-demographics at GPs. We aimed to fill this gap by linking different registers. METHODS: Individual STI testing data of GPs and SHC were linked to population register data (aged ≥15 years, Rotterdam area, 2015-2019). We reported population-specific STI positivity, proportion STI tested, and GP-SHC testing rate comparison using negative binomial generalised additive models. Factors associated with STI testing were determined by the provider using logistic regression analyses with generalised estimating equations. RESULTS: The proportion of STI tested was 2.8% for all residents and up to 9.8% for younger and defined migrant groups. STI positivity differed greatly by subgroup and provider (3.0-35.3%). Overall, GPs performed 3 times more STI tests than the SHC. The smallest difference in GP-SHC testing rate was for 20-24-year-olds (SHC key group). Younger age, non-western migratory background, lower household income, living more urbanised, and closer to a testing site were associated with STI testing by either GP or SHC. GPs and SHC partly test different groups: GPs test women and lower-educated more often, the SHC men and middle/higher educated. CONCLUSIONS: This study highlights GPs' important role in STI testing. The GPs' role in the prevention, diagnosis, and treatment of STIs needs continued support and strengthening. Inter-professional exchange and collaboration between GP and SHC is warranted to reach vulnerable groups.

The roles of the general practitioner and sexual health centre in HIV testing: comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study.

BACKGROUND: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. METHODS: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015-2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015-2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. RESULTS: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56-1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74-0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs' contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25-29-year-olds. CONCLUSIONS: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.

Mpox outbreak among men who have sex with men in Amsterdam and Rotterdam, the Netherlands: no evidence for undetected transmission prior to May 2022, a retrospective study.

Since May 2022, over 21,000 mpox cases have been reported from 29 EU/EEA countries, predominantly among men who have sex with men (MSM). The Netherlands was the fourth most affected country in Europe, with more than 1,200 cases and a crude notification rate of 70.7 per million population. The first national case was reported on 10 May, yet potential prior transmission remains unknown. Insight into prolonged undetected transmission can help to understand the current outbreak dynamics and aid future public health interventions. We performed a retrospective study and phylogenetic analysis to elucidate whether undetected transmission of human mpox virus (hMPXV) occurred before the first reported cases in Amsterdam and Rotterdam. In 401 anorectal and ulcer samples from visitors to centres for sexual health in Amsterdam or Rotterdam dating back to 14 February 2022, we identified two new cases, the earliest from 6 May. This coincides with the first cases reported in the United Kingdom, Spain and Portugal. We found no evidence of widespread hMPXV transmission in Dutch sexual networks of MSM before May 2022. Likely, the mpox outbreak expanded across Europe within a short period in the spring of 2022 through an international highly intertwined network of sexually active MSM.

Confirmatory testing of Neisseria gonorrhoeae in a sexual health clinic: implications for epidemiology and treatment policy.

OBJECTIVES: European guidelines advise the use of dual nucleic acid amplification tests (NAAT) in order to minimise the inappropriate diagnosis of Neisseria gonorrhoeae (Ng) in urogenital samples from low prevalence areas and in extragenital specimens. In this cross-sectional study, we investigated the effect of confirmatory testing and confirmation policy on the Ng-positivity in a population visiting the sexual health clinic in Rotterdam, the Netherlands. METHODS: Apart from urogenital testing, extragenital (oropharyngeal/anorectal) testing was performed for men who have sex with men (MSM) and according to sexual exposure for women and heterosexual men. Ng detection using NAAT was performed using BD Viper and for confirmatory testing BD MAX. Sexual transmitted infection consultation data were merged with diagnostic data from August 2015 through May 2016. RESULTS: In women (n=4175), oral testing was performed in 84% and 22% were tested anally. In MSM (n=1828), these percentages were 97% and 96%, respectively. Heterosexual men (n=3089) were tested urogenitally. After confirmatory testing, oropharyngeal positivity rates decreased from 7.3% (95% CI 6.5 to 8.2) to 1.5% (95% CI 1.1 to 1.8) in women and from 13.9% (95% CI 12.3 to 15.5) to 5.4% (95% CI 4.3 to 6.4) in MSM. Anorectal positivity rates decreased from 2.6% (95% CI 1.6 to 3.7) to 1.8% (95% CI 0.9 to 2.6) in women and from 9.3% (95% CI 7.9 to 10.7) to 7.2% (95% CI 6.0 to 8.5) in MSM. Urogenital Ng-positivity rate ranged between 3.0% and 4.4% and after confirmation between 2.3% and 3.9%. When confirming oropharyngeal samples, Ng-positivity was 3.8% in women, 3.0% in heterosexual men and 12.5% in MSM. Additional confirmation of urogenital and anorectal samples led to 3.0% Ng positivity in women, 2.7% in heterosexual men and 11.4% in MSM. CONCLUSIONS: Confirmation of urogenital and anorectal samples reduced the Ng-positivity rates, especially for women. However, as there is no gold standard for the confirmation of Ng infection, the dilemma within public health settings is to choose between two evils: missing diagnoses or overtreatment. In view of the large decrease in oropharyngeal positivity, confirmation Ng-positivity in oropharyngeal samples remains essential to avoid unnecessary treatment.

Incident urogenital and anorectal Chlamydia trachomatis in women: the role of sexual exposure and autoinoculation: a multicentre observational study (FemCure).

BACKGROUND: Anorectal infections with Chlamydia trachomatis (CT) are common in women visiting STI outpatient clinics. We here evaluated the risk posed by sexual exposure and by alternate anatomical site infection for incident anorectal and urogenital CT. METHODS: Prospective multicentre cohort study, FemCure. Participants were treated for CT, and after 4, 6, 8, 10 and 12 weeks, they self-collected anorectal and urogenital samples (swabs) for CT-DNA testing. We calculated the proportion with incident CT, that is, CT incidence (at weeks 6-12) by 2-week time-periods. Compared with no exposure (A), we estimated the risk of incident CT for (B) sexual exposure, (C) alternate site anatomic site infection and (D) both, adjusted for confounders and expressed as adjusted ORs with 95% CIs. RESULTS: We analysed data of 385 participants contributing 1540 2-week periods. The anorectal CT incidence was 2.9% (39/1343) (95 CI 1.8 to 3.6); 1.3% (A), 1.3% (B), 27.8% (C) and 36.7% (D). The ORs were: 0.91 (95% CI 0.32 to 2.60) (B), 26.0 (95% CI 7.16 to 94.34) (C), 44.26 (95% CI 14.38 to 136.21) (D).The urogenital CT incidence was 3.3% (47/1428) (95% CI 2.4 to 4.4); 0.7% (A), 1.9% (B), 13.9% (C) and 25.4% (D). The ORs were: 2.73 (95% CI 0.87 to 8.61) (B), 21.77 (95% CI 6.70 to 70 71) (C) and 49.66 (95% CI 15.37 to 160.41) (D). CONCLUSIONS: After initial treatment, an alternate anatomical site CT infection increased the risk for an incident CT in women, especially when also sex was reported. This may suggest a key role for autoinoculation in the re-establishment or persistence of urogenital and anorectal chlamydia infections.

Determinants associated with viable genital or rectal Chlamydia trachomatis bacterial load (FemCure).

BACKGROUND: Chlamydia trachomatis (CT) is routinely diagnosed by nucleic acid amplification tests (NAATs), which are unable to distinguish between nucleic acids from viable and non-viable CT organisms. OBJECTIVES: We applied our recently developed sensitive PCR (viability PCR) technique to measure viable bacterial CT load and explore associated determinants in 524 women attending Dutch sexual health centres (STI clinics), and who had genital or rectal CT. METHODS: We included women participating in the FemCure study (Netherlands, 2016-2017). At the enrolment visit (pre-treatment), 524 were NAAT positive (n=411 had genital and rectal CT, n=88 had genital CT only and n=25 had rectal CT only). We assessed viable rectal and viable genital load using V-PCR. We presented mean load (range 0 (non-viable) to 6.5 log10 CT/mL) and explored potential associations with urogenital symptoms (coital lower abdominal pain, coital blood loss, intermenstrual bleeding, altered vaginal discharge, painful or frequent micturition), rectal symptoms (discharge, pain, blood loss), other anatomical site infection and sociodemographics using multivariable regression analyses. RESULTS: In genital (n=499) CT NAAT-positive women, the mean viable load was 3.5 log10 CT/mL (SD 1.6). Genital viable load was independently associated with urogenital symptoms-especially altered vaginal discharge (Beta=0.35, p=0.012) and with concurrent rectal CT (aBeta=1.79; p<0.001). Urogenital symptoms were reported by 50.3% of women; their mean genital viable load was 3.6 log10 CT/mL (vs 3.3 in women without symptoms). Of 436 rectal CT NAAT-positive women, the mean rectal viable load was 2.2 log10 CT/mL (SD 2.0); rectal symptoms were reported by 2.5% (n=11) and not associated with rectal viable load. CONCLUSION: Among women diagnosed with CT in an outpatient clinical setting, viable genital CT load was higher in those reporting urogenital symptoms, but the difference was small. Viable genital load was substantially higher when women also had a concurrent rectal CT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02694497.

Who is providing HIV diagnostic testing? Comparing HIV testing by general practitioners and sexual health centres in five regions in the Netherlands, 2011-2018.

OBJECTIVES: General practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections. METHODS: Laboratory data (2011-2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15-29 years, 30-44 years, 45-59 years, ≥60 years). χ2 tests were used to compare positivity percentage between the two groups of providers. RESULTS: In the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15-29 years old, GPs' testing rates were lower than SHCs', while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs. CONCLUSIONS: This retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs' HIV testing practices.

Trends and regional variations of gonococcal antimicrobial resistance in the Netherlands, 2013 to 2019.

BackgroundGonococcal antimicrobial resistance is emerging worldwide and is monitored in the Netherlands in 18 of 24 Sexual Health Centres (SHC).AimTo report trends, predictors and regional variation of gonococcal azithromycin resistance (AZI-R, minimum inhibitory concentration (MIC) > 1 mg/L) and ceftriaxone decreased susceptibility (CEF-DS, MIC > 0.032 mg/L) in 2013-2019.MethodsSHC reported data on individual characteristics, sexually transmitted infection diagnoses, and susceptibility testing (MIC, measured by Etest). We used multilevel logistic regression analysis to identify AZI-R/CEF-DS predictors, correcting for SHC region. Population differences' effect on regional variance of AZI-R and CEF-DS was assessed with a separate multilevel model.ResultsThe study included 13,172 isolates, predominantly (n = 9,751; 74%) from men who have sex with men (MSM). Between 2013 and 2019, annual proportions of AZI-R isolates appeared to increase from 2.8% (37/1,304) to 9.3% (210/2,264), while those of CEF-DS seemed to decrease from 7.0% (91/1,306) to 2.9% (65/2,276). Among SHC regions, 0.0‒16.9% isolates were AZI-R and 0.0-7.0% CEF-DS; population characteristics could not explain regional variance. Pharyngeal strain origin and consultation year were significantly associated with AZI-R and CEF-DS for MSM, women, and heterosexual men. Among women and heterosexual men ≥ 4 partners was associated with CEF-DS, and ≥ 10 with AZI-R.ConclusionsNo resistance or decreasing susceptibility was found for CEF, the first line gonorrhoea treatment in the Netherlands. Similar to trends worldwide, AZI-R appeared to increase. Regional differences between SHC support nationwide surveillance with regional-level reporting. The increased risk of resistance/decreased susceptibility in pharyngeal strains underlines the importance of including extragenital infections in gonococcal resistance surveillance.

From more testing to smart testing: data-guided SARS-CoV-2 testing choices, the Netherlands, May to September 2020.

BackgroundSARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness.AimWe assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing.MethodsSensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases.ResultsThe distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65-99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30-99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55-99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection.ConclusionThe most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing.

Oropharyngeal Chlamydia trachomatis in women; spontaneous clearance and cure after treatment (FemCure).

OBJECTIVES: Women attending STI clinics are not routinely tested for oropharyngeal Chlamydia trachomatis (CT) infections. We aimed to assess spontaneous clearance of oropharyngeal CT and cure after antibiotic treatment in women. METHODS: Women with vaginal or rectal CT (n=560) were recruited at STI clinics in 2016-2017, as part of the FemCure study (prospective cohort study). We included participants' data from week -1, that is, the diagnosis at initial visit, when clinics applied selective oropharyngeal testing. At week -1, a total of 241 women were oropharyngeally tested (30 positive) and 319 were untested. All FemCure participants provided nurse-collected oropharyngeal samples at study enrolment, that is, week 0, just prior to treatment (n=560), and after treatment at weeks 4 (n=449), 8 (n=433) and 12 (n=427). Samples were tested by nucleic acid amplification test, and at week 0 also by viability testing by viability PCR. Proportions of oropharyngeal CT test results were presented to represent spontaneous clearance and cure. RESULTS: Of 30 women diagnosed with oropharyngeal CT at week -1, fifteen (50%) were negative at week 0 after a median of 9 days, that is, 'spontaneous clearance'. At week 0, a total of 560 participants were tested, and 46 (8.8%) were oropharyngeal CT positive; 12 of them (26.1%) had viable CT. Of the 46 positive, 36 women had an oropharyngeal test after treatment; 97.2% (35/36) were negative at week 4, that is, 'cure'. Of all women with follow-up visits, the proportion of oropharyngeal CT positive was between 0.5% and 1.6% between weeks 4 and 12. Of those not tested at week -1 (n=319), 8.5% (n=27) were oropharyngeal positive at week 0. CONCLUSIONS: The clinical importance of oropharyngeal CT in women is debated. We demonstrated that spontaneous clearance of oropharyngeal CT among women is common; of those who did not clear for CT, three-quarters had non-viable CT. After regular treatment with azithromycin or doxycycline, cure rate (97%) of oropharyngeal CT is excellent. TRIAL REGISTRATION NUMBER: NCT02694497.

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.

Distance as explanatory factor for sexual health centre utilization: an urban population-based study in the Netherlands.

BACKGROUND: The central sexual health centre (SHC) in the greater Rotterdam area in the Netherlands helps finding people unaware of their STI/HIV status. We aimed to determine a possible association between SHC utilization and travel distance in this urban and infrastructure-rich area. Insight in area-specific utilization helps adjust outreach policies to enhance STI testing. METHODS: The study population consists of all residents aged 15-45 years in the greater Rotterdam area (2015-17). We linked SHC consultation data from STI tested heterosexual clients to the population registry. The association between SHC utilization and distance was investigated by multilevel modelling, adjusting for sociodemographic and area-specific determinants. The data were also stratified by age (aged < 25 years) and migratory background (non-Western), since SHC triage may affect their utilization. We used straight-line distance between postal code area centroid and SHC address as a proxy for travel distance. RESULTS: We found large area variation in SHC utilization (range: 1.13-48.76 per 1000 residents). Both individual- and area-level determinants determine utilization. Travel distance explained most area variation and was inversely associated with SHC utilization when adjusted for other sociodemographic and area-specific determinants [odds ratio (OR) per kilometre: 0.95; 95% confidence interval (CI): 0.93-0.96]. Similar results were obtained for residents <25 years (OR: 0.95; 95% CI: 0.94-0.96), but not for non-Western residents (OR: 0.99; 95% CI: 0.99-1.00). CONCLUSIONS: Living further away from a central SHC shows a distance decline effect in utilization. We recommend to enhance STI testing by offering STI testing services closer to the population.

What Is the Optimal Testing Strategy for Oropharyngeal Neisseria gonorrhoeae in Men Who Have Sex With Men? Comparing Selective Testing Versus Routine Universal Testing From Dutch Sexually Transmitted Infection Clinic Data (2008-2017).

BACKGROUND: Most oropharyngeal Neisseria gonorrhoeae infections are asymptomatic, and many infections remain undetected, creating a reservoir for ongoing transmission and potential drug resistance. It is unclear what the optimal testing policy is in men who have sex with men (MSM), as routine universal testing data are lacking. METHODS: Surveillance data from all Dutch sexually transmitted infection (STI) clinics between 2008 and 2017 were used (N = 271 242 consultations). Oropharyngeal testing policy was defined as routine universal testing when ≥85% of consultations included oropharyngeal testing or as selective testing (<85% tested). Independent risk factors for oropharyngeal N. gonorrhoeae were assessed among MSM routinely universally screened using backward multivariable logistic regression analyses. RESULTS: Routine universal testing was performed in 90% (238 619/265 127) of consultations. Prevalence was higher using routine universal testing (5.5%; 95% CI, 5.4-5.6; 12 769/233 476) than with selective testing (4.7%; 95% CI, 4.4-5.0; 799/17 079; P < .001). Proportions of oropharyngeal-only infections were 55% and 47%, respectively. Independent risk factors were age <31 years (OR, 2.1; 95% CI, 1.9-2.3), age 31-43 years (OR, 1.7; 95% CI, 1.6-1.9, compared with >43 years), being notified for any STI (OR, 2.0; 95% CI, 1.9-2.1), concurrent urogenital N. gonorrhoeae (OR, 2.4; 95% CI, 2.1-2.7), and concurrent anorectal N. gonorrhoeae (OR, 11.4; 95% CI, 10.6-12.3). When using any of the risk factors age, notified, or oral sex as testing indicators, 98.4% (81 022/82 332) of MSM would be tested, finding 99.5% (4814/4838) of infections. CONCLUSIONS: Routine universal testing detected more oropharyngeal N. gonorrhoeae infections than selective testing, of which more than half would be oropharyngeal only. Using independent risk factors as testing indicator is not specific. Therefore, routine universal oropharyngeal testing in MSM is feasible and warranted, as currently advised in most guidelines.

Spontaneous clearance of Chlamydia trachomatis accounting for bacterial viability in vaginally or rectally infected women (FemCure).

OBJECTIVES: Spontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patients to assess clearance using a conventional definition (no total CT-DNA, assessed by routine quantitative PCR methods) and a definition accounting for viability, assessed by viability PCR testing. METHODS: Three outpatient STI clinics included CT-diagnosed women (The Netherlands, 2016-2017, FemCure study); participants had vaginal CT (vCT) and rectal CT (rCT) (group A: n=155), vCT and were rectally untested (group B: n=351), single vCT (group C: n=25) or single rCT (group D: n=29). Follow-up (median interval 9 days) vaginal and rectal samples underwent quantitative PCR testing (detecting total CT-DNA). When PCR positive, samples underwent V-PCR testing to detect 'viable CT' (CT-DNA from intact CT organisms; V-PCR positive). 'Clearance' was the proportion PCR-negative patients and 'clearance of viable CT' was the proportion of patients testing PCR negative or PCR positive but V-PCR negative. We used multivariable logistic regression analyses to assess diagnosis group (A-D), age, days since initial CT test (diagnosis) and study site (STI clinic) in relation to clearance and clearance of viable CT. RESULTS: Clearance and clearance of viable CT at both anatomic sites were for (A) 0.6% and 3.9%; (B) 5.4% and 9.4%; (C) 32.0% and 52.0% and (D) 27.6% and 41.4%, respectively. In multivariate analyses, women with single infections (groups C and D) had higher likelihood of clearance than women concurrently infected with vCT and rCT (p<0.001).Of rectally untested women (group B), 76.9% had total CT-DNA and 46.7% had viable CT (V-PCR positive) at the rectal site. CONCLUSIONS: Of untreated female vCT patients who had CT also at the rectal site, or who were rectally untested, only a small proportion cleared CT (in fact many had viable CT) at their follow-up visit (median 9 days). Among single site infected women clearance was much higher. TRIAL REGISTRATION NUMBER: NCT02694497.

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.

Increasing trends of lymphogranuloma venereum among HIV-negative and asymptomatic men who have sex with men, the Netherlands, 2011 to 2017.

IntroductionLymphogranuloma venereum (LGV), an invasive form of Chlamydia trachomatis infection, has been reported among (mainly HIV-positive) men who have sex with men (MSM) since 2003. In the Netherlands, LGV testing recommendations changed from selective to universal testing in 2015. Changes in tested populations could have led to incomparable LGV positivity rates over time.AimWe investigated LGV trends among MSM attending Centres for Sexual Health using surveillance data between 2011 and 2017.MethodsLGV positivity was calculated among MSM tested for rectal Chlamydia infection and MSM tested specifically for LGV. With multivariable logistic regression analysis, the association between years and LGV was adjusted for testing indicators and determinants.ResultsWe included 224,194 consultations. LGV increased from 86 in 2011 to 270 in 2017. Among LGV-positives, proportions of HIV-negative and asymptomatic MSM increased from 17.4% to 45.6% and from 31.4% to 49.3%, respectively, between 2011 and 2017. Among MSM tested for rectal chlamydia, LGV positivity increased from 0.12% to 0.33% among HIV-negatives and remained stable around 2.5% among HIV-positives. Among LGV-tested MSM, LGV positivity increased from 2.1% to 5.7% among HIV-negatives and from 15.1% to 22.1% among HIV-positives. Multivariable models showed increased odds ratios and significant positive associations between years and LGV.ConclusionsAlthough increased testing and changes in LGV incidence are difficult to disentangle, we found increasing LGV trends, especially when corrected for confounding. LGV was increasingly attributed to HIV-negative and asymptomatic MSM, among whom testing was previously limited. This stresses the importance of universal testing and continuous surveillance.

Treatment Effectiveness of Azithromycin and Doxycycline in Uncomplicated Rectal and Vaginal Chlamydia trachomatis Infections in Women: A Multicenter Observational Study (FemCure).

BACKGROUND: Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a sexually transmitted infection outpatient clinic, but it remains unclear what the most effective treatment is. We assessed the effectiveness of doxycycline and azithromycin for the treatment of rectal and vaginal chlamydia in women. METHODS: This study is part of a prospective multicenter cohort study (FemCure). Treatment consisted of doxycycline (100 mg twice daily for 7 days) in rectal CT-positive women, and of azithromycin (1 g single dose) in vaginally positive women who were rectally untested or rectally negative. Participants self-collected rectal and vaginal samples at enrollment (treatment time-point) and during 4 weeks of follow-up. The endpoint was microbiological cure by a negative nucleic acid amplification test at 4 weeks. Differences between cure proportions and 95% confidence intervals (CIs) were calculated. RESULTS: We analyzed 416 patients, of whom 319 had both rectal and vaginal chlamydia at enrollment, 22 had rectal chlamydia only, and 75 had vaginal chlamydia only. In 341 rectal infections, microbiological cure in azithromycin-treated women was 78.5% (95% CI, 72.6%-83.7%; n = 164/209) and 95.5% (95% CI, 91.0%-98.2%; n = 126/132) in doxycycline-treated women (difference, 17.0% [95% CI, 9.6%-24.7%]; P < .001). In 394 vaginal infections, cure was 93.5% (95% CI, 90.1%-96.1%; n = 246/263) in azithromycin-treated women and 95.4% (95% CI, 90.9%-98.2%; n = 125/131) in doxycycline-treated women (difference, 1.9% [95% CI, -3.6% to 6.7%]; P = .504). CONCLUSIONS: The effectiveness of doxycycline is high and exceeds that of azithromycin for the treatment of rectal CT infections in women. CLINICAL TRIALS REGISTRATION: NCT02694497.