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.

Reproductive tract complication risks following Chlamydia trachomatis infections: a long-term prospective cohort study from 2008 to 2022.

Background: The clinical and public health relevance of widespread testing for asymptomatic Chlamydia trachomatis (chlamydia) infections is under debate. To address uncertainties in screening programs, we estimate reproductive tract complication risks following asymptomatic and symptomatic chlamydia infections in a long-term prospective cohort. Methods: A cohort of 5704 reproductive-age women recruited from a chlamydia screening study was followed for up to 14 years. Chlamydia positivity was determined using screening polymerase chain reaction test results, self-reported diagnoses (with/without symptoms), and chlamydia Immunoglobulin G antibodies. Outcome data (pregnancies, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility) were collected through self-completed questionnaires. Cox regression calculated adjusted hazard ratios (aHR) with confidence intervals (CI) to compare outcomes between time-updated chlamydia groups since sexual debut. Findings: During 104,612 person-years, 2103 (36.9%) women were chlamydia-positive and 3692 women (64.7%) had been pregnant at least once. Risks for PID, ectopic pregnancy and tubal factor infertility were 1.62 (95% CI 1.20-2.17), 1.84 (95% CI 1.14-2.95) and 2.75 (95% CI 1.53-4.94), compared to chlamydia-negatives. aHRs for PID after symptomatic and asymptomatic infections were 2.29 (95% CI 1.62-3.25) and 1.06 (95% CI 0.66-1.69), respectively. Incidence of PID, ectopic pregnancy and tubal factor infertility after symptomatic chlamydia infection remained low with rates per 1000 person-years of 5.8, 1.9, and 1.8, respectively. Interpretation: We found a significantly higher risk of PID, ectopic pregnancy and tubal factor infertility in chlamydia-positive women compared to chlamydia-negative women, although the overall incidence rates of complications remained low. Symptomatic, but not asymptomatic, chlamydia infections were associated with PID risk, suggesting the largest disease burden of complications is in this group. Funding: The Netherlands Organisation for Health Research and Development (ZonMW Netherlands) and Research Funding from the Ministry of Health, Welfare and Sports.

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.

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.

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.

Low Hepatitis C Virus Prevalence among Men Who Have Sex with Men Attending Public Health Services in The Netherlands.

The hepatitis C virus (HCV) prevalence is high among men who have sex with men (MSM) with HIV in the Netherlands. Large reductions in HCV incidence among MSM with HIV, however, have occurred since treatment with direct-acting antivirals. Over the years, a broader understanding of the HCV epidemic has shown that HCV infections are not solely restricted to MSM with HIV, but they also occur among HIV-negative MSM. Currently, HCV testing among HIV-negative MSM is only provided for PrEP users and is not part of routine sexually transmitted infection (STI) screening among HIV-negative MSM who are not using PrEP. In this study, we screened 1885 HIV-negative MSM who did not participate in a PrEP program, with over 1966 STI screening visits at four different public health clinic sites. Among the 1885 MSM, only one person had a new HCV infection, resulting in a 0.05% (95% confidence interval 0.0-0.3) incidence. Based on our findings, we can conclude that systematic HCV testing at STI clinics may not yield significant benefits for this particular population.

Evaluating the Added Value of Digital Contact Tracing Support Tools for Citizens: Framework Development.

BACKGROUND: The COVID-19 pandemic revealed that with high infection rates, health services conducting contact tracing (CT) could become overburdened, leading to limited or incomplete CT. Digital CT support (DCTS) tools are designed to mimic traditional CT, by transferring a part of or all the tasks of CT into the hands of citizens. Besides saving time for health services, these tools may help to increase the number of contacts retrieved during the contact identification process, quantity and quality of contact details, and speed of the contact notification process. The added value of DCTS tools for CT is currently unknown. OBJECTIVE: To help determine whether DCTS tools could improve the effectiveness of CT, this study aims to develop a framework for the comprehensive assessment of these tools. METHODS: A framework containing evaluation topics, research questions, accompanying study designs, and methods was developed based on consultations with CT experts from municipal public health services and national public health authorities, complemented with scientific literature. RESULTS: These efforts resulted in a framework aiming to assist with the assessment of the following aspects of CT: speed; comprehensiveness; effectiveness with regard to contact notification; positive case detection; potential workload reduction of public health professionals; demographics related to adoption and reach; and user experiences of public health professionals, index cases, and contacts. CONCLUSIONS: This framework provides guidance for researchers and policy makers in designing their own evaluation studies, the findings of which can help determine how and the extent to which DCTS tools should be implemented as a CT strategy for future infectious disease outbreaks.

Online-Mediated HIV Pre-exposure Prophylaxis Care and Reduced Monitoring Frequency for Men Who Have Sex With Men: Protocol for a Randomized Controlled Noninferiority Trial (EZI-PrEP Study).

BACKGROUND: Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. OBJECTIVE: The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. METHODS: This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, "unprotected act") as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8. RESULTS: The results of the main analysis are expected in 2024. CONCLUSIONS: This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51023.

HIV and syphilis testing for women and heterosexual men aged above 25 years in the Netherlands: possibilities for targeted testing at sexual health centres.

OBJECTIVES: Targeted testing policy for HIV/syphilis at Dutch sexual health centres (SHCs) was evaluated for its efficiency in younger heterosexuals but not for heterosexuals ≥25 years. Currently, all older heterosexuals are tested for HIV/syphilis at SHCs. To explore possibilities for increased efficiency of testing in heterosexuals aged >25 years, this study aimed to identify determinants of HIV and syphilis diagnoses that could be used in targeted testing strategies. DESIGN: An observational study using surveillance data from all Dutch SHC. PARTICIPANTS: Women and heterosexual men aged >25 years visiting SHC between 2015 and 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was HIV/syphilis diagnosis, determinants of a diagnosis were analysed. Based on these determinants and their applicability in SHC practice, different targeted testing scenarios were evaluated. For each scenario, the percentage of consultations involving HIV and syphilis testing and the total amount of missed HIV and syphilis diagnoses were calculated. RESULTS: 109 122 consultations were included among 75 718 individuals. The strongest determinants of HIV/syphilis diagnosis were HIV/syphilis-specific symptoms (adjusted OR (aOR) 34.9 (24.1-50.2)) and receiving partner notification (aOR 18.3 (13.2-25.2)), followed by low/middle education level (aOR 2.8 (2.0-4.0)), male sex (aOR 2.2 (1.6-3.0)) and age ≥30 years (aOR 1.8 (1.3-2.5)). When applying feasible determinants to targeted testing scenarios, HIV/syphilis testing would have been conducted in 54.5% of all consultations, missing 2 HIV and 3 syphilis diagnoses annually (13.4% and 11.4% of all diagnoses, respectively). In the scenario with the lowest number of missed HIV/syphilis diagnoses (0.3 HIV and 2 syphilis diagnoses annually), HIV/syphilis testing would have been conducted in 74.2% of all consultations. CONCLUSIONS: In any targeted testing scenario studied, HIV and/or syphilis diagnoses would have been missed. This raises the question whether it is acceptable to put any of these scenarios into practice. This study contributes to a discussion about the impact of targeted testing policy.

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.

Community-based HIV testing through a general health check event in a high HIV-prevalent multicultural area in Rotterdam, The Netherlands: a pilot study on feasibility and acceptance.

BACKGROUND: HIV testing is crucial for finding the remaining cases in a declining HIV epidemic in The Netherlands; providing HIV testing in non-traditional settings may be warranted. We conducted a pilot study to determine the feasibility and acceptability of a community-based HIV testing (CBHT) approach with general health checks to improve HIV test uptake. METHODS: CBHT's main conditions were low-threshold, free-of-charge, general health check, and HIV education. We interviewed 6 community leaders, 25 residents, and 12 professionals/volunteers from local organizations to outline these main conditions. Walk-in test events were piloted at community organizations, providing HIV testing along with body mass index (BMI), blood pressure, blood glucose screening, and HIV education (October 2019 to February 2020). Demographics, HIV testing history, risk perception, and sexual contact were collected via questionnaires. To evaluate the pilots' feasibility and acceptance, we utilized the RE-AIM framework and predefined goals, incorporating quantitative data from the test events and qualitative input from participants, organizations, and staff. RESULTS: A total of 140 individuals participated (74% women, 85% non-Western, median age 49 years old). The number of participants during the seven 4-h test events ranged from 10 to 31. We tested 134 participants for HIV, and one was found positive (positivity 0.75%). Almost 90% of the participants were never tested or > 1 year ago, and 90% perceived no HIV risk. One-third of the participants had one or more abnormal test results on BMI, blood pressure, or blood glucose. The pilot was well-rated and accepted by all parties. The staff had concerns about waiting time, language problems, and privacy. Participants hardly indicated these concerns. CONCLUSIONS: This CBHT approach is feasible, acceptable, and well-suited for testing not (recently) tested individuals and detecting new cases. Besides reducing HIV-associated stigma and increasing HIV test acceptance, offering multiple health tests may be appropriate as we frequently observed multiple health problems. Whether this laborious approach is sustainable in the micro-elimination of HIV and should be deployed on a large scale is questionable. CBHT like ours may be suitable as a supplement to more sustainable and cost-effective methods, e.g., proactive HIV testing by general practitioners and partner notification.

Area-based comparison of risk factors and testing rates to improve sexual health care access: cross-sectional population-based study in a Dutch multicultural area.

OBJECTIVES: Areas with high sexually transmitted infection (STI) testing rates may not require additional strategies to improve testing. However, it may be necessary to intervene in areas with elevated STI risk, but with low STI testing rates. We aimed to compare STI-related risk profiles and STI testing rates by geographical area to determine areas for improvement of sexual healthcare access. DESIGN: Cross-sectional population-based study. SETTING: Greater Rotterdam area, the Netherlands (2015-2019). PARTICIPANTS: All residents aged 15-45 years. Individual population-based register data were matched with laboratory-based STI testing data of general practitioners (GPs) and the only sexual health centre (SHC). OUTCOME MEASURES: Postal code (PC) area-specific STI risk scores (based on age, migratory background, education level and urbanisation), STI testing rates and STI positivity. RESULTS: The study area consists of approximately 500 000 residents aged 15-45 years. Strong spatial variation in STI testing, STI positivity and STI risk was observed. PC area testing rate ranged from 5.2 to 114.9 tests per 1000 residents. Three PC clusters were identified based on STI risk and testing rate: (1) high-high; (2) high-low; (3) low, independently of testing rate. Clusters 1 and 2 had comparable STI-related risk and STI positivity, but the testing rate differed greatly (75.8 vs 33.2 per 1000 residents). Multivariable logistic regression analysis with generalised estimating equation was used to compare residents in cluster 1 and cluster 2. Compared with cluster 1, residents in cluster 2 more often did not have a migratory background, lived in less urbanised areas with higher median household income, and more distant from both GP and SHC. CONCLUSION: The determinants associated with individuals living in areas with high STI-related risk scores and low testing rates provide leads for improvement of sexual healthcare access. Opportunities for further exploration include GP education, community-based testing and service (re)allocation.

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.

Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals.

In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as Imvamune, JYNNEOS or Imvanex) is a third-generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there are no data showing MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals nor vaccine efficacy against MPX. Here we show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a two-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, we conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial.

OBJECTIVES: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients. METHODS: A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were ≥50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion. RESULTS: After the enrolment of 421 patients and the transfusion in 416 patients, recruitment was discontinued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59-1.22). The OR was 0.58 (95% CI, 0.33-1.02) for patients with ≤5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28-1.34). No difference was found in viral RNA excretion or in the duration of symptoms. CONCLUSIONS: In patients with early COVID-19, CP therapy did not improve the 5-point disease severity score.

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.

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.

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.