Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort.

BACKGROUND: An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. METHODS AND FINDINGS: The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals. CONCLUSIONS: In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time. TRIAL REGISTRATION: The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.

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.

Seroconversion in syphilis screening without positive confirmatory tests points at early infection.

INTRODUCTION: The chemiluminescence immunoassay (CLIA) is a widely used screening test for syphilis. A CLIA seroconversion in the absence of a positive line immunoassay (LIA) or rapid plasma reagin (RPR) could indicate either an early incubating syphilis or a false positive result. We aimed to evaluate the diagnostic value of such seroconversions. METHODS: We retrospectively analysed data of clients visiting the Centre for Sexual Health Amsterdam between July 2013 and August 2021 with a positive CLIA and a negative RPR and negative or indeterminate LIA (at time To), and a preceding visit (T-1) with a negative CLIA <6 months of To ('unconfirmed CLIA seroconversion'). If available, data of follow-up visits (T1) <2 months of To were also included. A syphilis diagnosis was confirmed if darkfield microscopy or PCR for Treponema pallidum was positive at T0 or T1, or if RPR and/or LIA were positive at T1. RESULTS: We included data of 107 clients with unconfirmed CLIA seroconversion. The value of CLIA seroconversion could not be established in 13 (12.1%) clients. In the remaining 94 clients, the unconfirmed CLIA seroconversion was confirmed as early syphilis in 72 (76.6%) clients and probable syphilis in 6 (6.4%) clients. In 16 (17.0%) clients, the unconfirmed CLIA seroconversion was regarded as a false positive reaction of whom 4 (5.3%) clients had a seroreversion of the CLIA at T1. CONCLUSION: The majority of unconfirmed CLIA seroconversions represented early syphilis infections. Therefore, additional T. pallidum PCR, a follow-up consultation or early treatment is recommended.

Minimum inhibitory concentrations of Neisseria gonorrhoeae strains in clients of the Amsterdam sexual health clinic with a Dutch versus an international sexual network.

OBJECTIVES: International travel combined with sex may contribute to dissemination of antimicrobial-resistant (AMR) Neisseria gonorrhoeae (Ng). To assess the role of travel in Ng strain susceptibility, we compared minimum inhibitory concentrations (MICs) for five antibiotics (ie, azithromycin, ceftriaxone, cefotaxime, cefixime and ciprofloxacin) in strains from clients with an exclusively Dutch sexual network and clients with an additional international sexual network. METHODS: From 2013 to 2019, we recorded recent residence of sexual partners of clients (and of their partners) with Ng at the Center for Sexual Health of Amsterdam. We categorised clients as having: (1) exclusively sexual partners residing in the Netherlands ('Dutch only') or (2) at least one partner residing outside the Netherlands. We categorised the country of residence of sexual partners by World Bank/EuroVoc regions. We analysed the difference of log-transformed MIC of Ng strains between categories using linear or hurdle regression for each antibiotic. RESULTS: We included 3367 gay and bisexual men who had sex with men (GBMSM), 516 women and 525 men who exclusively had sex with women (MSW) with Ng. Compared with GBMSM with a 'Dutch only' network, GBMSM with: (1) a Western European network had higher MICs for ceftriaxone (ß=0.19, 95% CI=0.08 to 0.29), cefotaxime (ß=0.19, 95% CI=0.08 to 0.31) and cefixime (ß=0.06, 95% CI=0.001 to 0.11); (2) a Southern European network had a higher MIC for cefixime (ß=0.10, 95% CI=0.02 to 0.17); and (3) a sub-Saharan African network had a lower MIC for ciprofloxacin (ß=-1.79, 95% CI=-2.84 to -0.74). In women and MSW, higher MICs were found for ceftriaxone in clients with a Latin American and Caribbean network (ß=0.26, 95% CI=0.02 to 0.51). CONCLUSIONS: For three cephalosporin antibiotics, we found Ng strains with slightly higher MICs in clients with partner(s) from Europe or Latin America and the Caribbean. International travel might contribute to the spread of Ng with lower susceptibility. More understanding of the emergence of AMR Ng is needed.

Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands.

BACKGROUND: Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands. METHODS: Between November 2021 and March 2022, we used a structured questionnaire containing questions about sexual behavior and factors that could have influenced compliance with sexual distancing. Variables related to sexual behavior were measured for 5 periods, before and during the pandemic, delineated by imposement and relaxation of lockdown measures. RESULTS: Eight hundred seventy participants (predominantly MSM) completed the questionnaire. We found that compliance to the sexual distancing measures decreased over time. The number of casual partners was highest after the lockdown measures were relaxed for the second time (April 2021 to March 2022), and even higher than before the first lockdown. Factors positively associated with sexual distancing compliance were: having confidence in the information provided by the government and experiencing less or similar need for physical contact compared with before the pandemic. Factors that lowered compliance over time were: previously having had COVID-19, perceiving the lockdown measures as overstated, having sex with casual partners and similar drug use during the pandemic as before. CONCLUSIONS: Our findings suggest that sexual distancing measures are difficult to maintain for a long period. Other measures, such as confinement to a small network of known partners, might be more effective for longer pandemics in minimizing the spread of infectious diseases.

Timely Diagnosis of Incubating Syphilis Infections Using Treponema pallidum Transcription-Mediated Amplification Assay.

BACKGROUND: Syphilis is a complex, multistage, sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (TP). New diagnostic tools are needed to minimize transmission. In this study, we aimed to assess the additional value of an investigational transcription-mediated amplification test for TP (TP-TMA) for routine diagnostics. METHODS: Between September 2021 and August 2022, visits by all participants of the national preexposure prophylaxis (PrEP) program at the sexual health center (SHC) in Amsterdam were included. Anal, pharyngeal, vaginal, and urine samples collected for Chlamydia trachomatis and Neisseria gonorrhoeae screening were additionally tested with the TP-TMA assay based on detection of 23S rRNA of TP. RESULTS: In total, 9974 SHC visits by 3283 participants were included. There were 191 infectious syphilis cases diagnosed: 26 (14%) primary syphilis, 54 (29%) secondary syphilis, and 111 (58%) early latent syphilis. In 79 of the 191 (41%) syphilis cases, at least 1 sample was TP-TMA-positive. For 16 participants, the positive TP-TMA result was not concordant with routine diagnostics. Of those, 2 participants were treated for syphilis within a week before the visit. Eight participants were treated for a syphilis notification at the visit or for another STI. Five participants were diagnosed with syphilis at the following visit, and 1 participant was lost to follow-up. CONCLUSIONS: By adding the TP-TMA assay to routine diagnostics, we identified 14 of 191 (7%) additional syphilis infections among participants of the national PrEP program. The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.

The impact of COVID-19-related restrictions in 2020 on sexual healthcare use, pre-exposure prophylaxis use, and sexually transmitted infection incidence among men who have sex with men in Amsterdam, the Netherlands.

OBJECTIVES: We studied the effects of restrictions related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic on the use of sexual healthcare and pre-exposure prophylaxis (PrEP) and on the incidence of sexually transmitted infections (STIs) among men who have sex with men (MSM) in a prospective, open-label PrEP demonstration study (AMPrEP) in Amsterdam, the Netherlands. METHODS: We retrieved data from 2019 to 2020 for participants with one or more study visit in 2019 (n = 305) and from two COVID-19 questionnaires (2020: n = 203; 2021: n = 160). Analyses were stratified for three periods of pandemic-related restrictions (first: 15 March 2020-15 June 2020; second: 16 June 2020-15 September 2020; third: 16 September 2020-31 December 2020 or 1 April 2021 for the COVID-19 questionnaire). Endpoints included returning for care during the pandemic, PrEP use (increased/unchanged vs. deceased/stopped, relative to 2019), and any STI/HIV. We modelled determinants of care and PrEP use via multivariable logistic regression and STI incidence using piecewise Poisson regression, comparing the 2020 and 2019 periods. RESULTS: Of the 305 MSM included in the analysis, 72.8% returned for care during the pandemic, and this was significantly more likely among daily (vs. event-driven) PrEP users (p < 0.001). Increased/unchanged PrEP use ranged from 55.2% to 58.1% across the three pandemic periods and was more likely among those reporting chemsex in the first (p = 0.001) and third (p = 0.020) periods and among those reporting an increased/unchanged number of sex partners during the second period (p = 0.010). STI incidence was significantly lower in 2020 than in 2019 during the first period (incidence rate ratio [IRR] 0.43; 95% confidence interval [CI] 0.28-0.68) and not significantly different during the second (IRR 1.38; 95% CI 0.95-2.00) and third (IRR 1.42; 95% CI 0.86-2.33) periods. No HIV was diagnosed. CONCLUSION: COVID-19-related restrictions coincided with reduced care and PrEP use. Changes in STI incidence suggest delayed diagnoses. Ways to ensure continued access to sexual healthcare during restrictions are needed.

Spontaneous clearance of asymptomatic anogenital and pharyngeal Neisseria gonorrhoeae: a secondary analysis from the NABOGO trial.

INTRODUCTION: Spontaneous clearance of asymptomatic Neisseria gonorrhoeae (NG) does occur, but data are scarce. We aimed to assess spontaneous clearance among patients with asymptomatic anal, pharyngeal, vaginal and urethral NG infections who participated in the New AntiBiotic treatment Options for uncomplicated GOnorrhoea (NABOGO) trial. In addition, we assessed the determinants associated with spontaneous clearance. METHODS: The NABOGO trial (Trial registration number: NCT03294395) was a randomised controlled, double-blind, single-centre trial assessing non-inferiority of ertapenem, gentamicin and fosfomycin to ceftriaxone for treatment of uncomplicated gonorrhoea. For asymptomatic NABOGO participants, we collected pre-enrolment and enrolment visit samples before trial medication was given. Spontaneous clearance was defined as a positive pre-enrolment nucleic acid amplification test (NAAT) result, followed by a negative NAAT at enrolment. We compared the median time between pre-enrolment and enrolment visits for patients who cleared spontaneously and for those who did not. Determinants of spontaneous clearance were assessed using logistic regression. RESULTS: Thirty-two of 221 (14.5%) anal NG infections cleared spontaneously, 17 of 91 (18.7%) pharyngeal, 3 of 13 (23.1%) vaginal and 9 of 28 (32.1%) urethral NG infections. The median time between the pre-enrolment and enrolment visit was longer for patients who cleared their pharyngeal infection spontaneously compared with those who did not (median 8 days (IQR=7-11) vs 6 days (IQR=4-8), p=0.012); no determinants of clearance at other sites were identified. Overall, patients with more days between the pre-enrolment and enrolment visit were more likely to clear spontaneously (adjusted OR=1.06 per additional day, 95% CI 1.01 to 1.12). No association between location of NG infection and spontaneous clearance was found. CONCLUSIONS: A significant proportion of asymptomatic patients cleared their NG infections spontaneously. Given these results, treatment of all NG infections after a one-time NAAT may be excessive, and more research on the natural history of NG is needed to improve antibiotic stewardship.

Developing a symptoms-based risk score for infectious syphilis among men who have sex with men.

BACKGROUND: Syphilis incidence is rising among men who have sex with men (MSM). An online tool based on a risk score identifying men with higher risk of infectious syphilis could motivate MSM to seek care. We aimed therefore to develop a symptoms-based risk score for infectious syphilis. METHODS: We included data from all consultations by MSM attending the Amsterdam Centre for Sexual Health in 2018-2019. Infectious syphilis (ie, primary, secondary or early latent syphilis) was diagnosed according to the centre's routine protocol. Associations between symptoms and infectious syphilis were expressed as odds ratios (OR), with 95% confidence intervals (CI). Based on multivariable logistic regression models, we created risk scores, combining various symptoms. We assessed the area under the curve (AUC) and cut-off based on the Youden Index. We estimated which percentage of MSM should be tested based on a positive risk score and which percentage of infectious syphilis cases would then be missed. RESULTS: We included 21,646 consultations with 11,594 unique persons. The median age was 34 years (IQR 27-45), and 14% were HIV positive (93% on antiretroviral treatment). We diagnosed 538 cases of infectious syphilis. Associations with syphilis symptoms/signs were strong and highly significant, for example, OR for a painless penile ulcer was 35.0 (CI 24.9 to 49.2) and OR for non-itching rash 57.8 (CI 36.8 to 90.9). Yet, none of the individual symptoms or signs had an AUC >0.55. The AUC of risk scores combining various symptoms varied from 0.68 to 0.69. For all risk scores using cut-offs based on Youden Index, syphilis screening would be recommended in 6% of MSM, and 59% of infectious syphilis cases would be missed. CONCLUSION: Symptoms-based risk scores for infectious syphilis perform poorly and cannot be recommended to select MSM for syphilis screening. All MSM with relevant sexual exposure should be regularly tested for syphilis.

Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study.

BACKGROUND: In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission. METHODS: Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model. RESULTS: We included 366 participants. Median follow-up was 47 months (IQR 43-50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)). CONCLUSION: Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.

Determinants of adherence to daily PrEP measured as intracellular tenofovir diphosphate concentrations over 24 months of follow-up among men who have sex with men.

OBJECTIVES: Adherence is key to the effectiveness of oral pre-exposure prophylaxis (PrEP) to prevent HIV. Therefore, we aimed to explore factors associated with adherence to daily PrEP (dPrEP). METHODS: Men who have sex with men (MSM) using dPrEP (emtricitabine/tenofovir disoproxil) within the Amsterdam PrEP demonstration project at the Public Health Service of Amsterdam, provided dried blood spots (DBS) 12 and 24 months after PrEP initiation. From DBS, we determined intracellular tenofovir diphosphate (TFV-DP) concentrations to assess adherence; TFV-DP ≥700 fmol/punch was considered adequate. We assessed associations of sociodemographic, clinical and behavioural characteristics with TFV-DP concentrations using multivariable linear regression. RESULTS: Of 263 participants who attended 12-month or 24-month study visits while on dPrEP, 257 (97.7%) provided DBS at one or both visits (492 DBS in total). Median TFV-DP concentration was 1299 (IQR 1021-1627) fmol/punch (12 months: 1332 (1087-1687); 24 months: 1248 (929-1590]). Higher TFV-DP concentrations were associated with: older age (p=0.0008), condomless anal sex with a casual partner in 6 months preceding PrEP initiation (+166 fmol/punch; 95% CI 36.5 to 296) and using a mobile application providing visualised feedback on PrEP use and sexual behaviour (+146 fmol/punch; 95% CI 28.1 to 263). Lower TFV-DP concentrations were associated with longer duration of PrEP use (24 vs 12 months; -91.5 fmol/punch; 95% CI -155 to -28.1). Time-updated number of sex partners, diagnosed STIs and chemsex were not associated with TFV-DP concentrations. CONCLUSIONS: Overall, TFV-DP concentrations were high among MSM using dPrEP, indicating excellent adherence. Especially older participants, those who reported condomless anal sex with a casual partner prior to PrEP initiation and those who used an app with visualised feedback showed higher levels of adherence. As TFV-DP concentrations had decreased slightly at 2 years of PrEP use when compared with 1 year, we emphasise the importance of adherence counselling to those who continue using PrEP. TRIAL REGISTRATION NUMBER: NL5413.

Treponema pallidum Strains Among Women and Men Who Have Sex With Women in Amsterdam, the Netherlands and Antwerp, Belgium Between 2014 and 2020.

ABSTRACT: The Treponema pallidum strain distribution among men who have sex with women were similar to the strain distribution men who have sex with men. The most prevalent strains and percentage of strains belonging to the Nichols lineage are similar to previous studies in Amsterdam focusing on men who have sex with men.

Leishmania species and clinical characteristics of Pacific and Amazon cutaneous leishmaniasis in Ecuador and determinants of health-seeking delay: a cross-sectional study.

BACKGROUND: Cutaneous Leishmaniasis (CL) affects up to 5.000 people in Ecuador each year. L. guyanensis and L. braziliensis are the most common of the eight CL-causing Leishmania species. Earlier CL research concentrated on the easily accessible Pacific region. This study aims to describe the Leishmania species in Pacific and Amazon ecoregions, to analyze regional differences in CL patient clinical presentation, and to identify determinants of health-seeking delay. METHODS: All cases in this cross-sectional study were diagnosed using smear slide microscopy, PCR, or both. Cytochrome B gene sequencing was used to identify the causative Leishmania species in qPCR-positive samples. RESULTS: This study included 245 patients, with 154 (63%) infected in the Pacific region and 91 (37%) infected in the Amazon. Causative Leishmania species were identified in 135 patients (73% of qPCR positives). L. guyanensis was identified in 76% (102/135) of the samples and L. braziliensis in 19% (26/135). The Pacific region had a low prevalence of 6% (5/89) of L. braziliensis. For the first time, we report L. guyanensis from the central Amazon, L. braziliensis from the northern Pacific, and L. lainsoni from both the central Amazon and northern Pacific. Amazon cases had a longer median health-seeking delay in months (2.0, IQR 3.0) than Pacific cases (1.0, IQR 1.5). Prolonged health-seeking delay was associated with older age, Amerindian ethnicity, infection at lower altitudes, non-ulcerative lesions, and lesions on the lower limbs. CONCLUSIONS: In the Pacific region, health-seeking delay is relatively short and L. braziliensis prevalence remains low. Limited access to health care and stigma might explain the prolonged health-seeking delay in the Amazon. We recommend larger studies on the distribution of Leishmania species in Amazon CL cases and additional regional research into diagnostic test accuracy. Furthermore, the determinants of health-seeking delay in Ecuador should be investigated further.

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.

Mpox outbreak in the Netherlands, 2022: public health response, characteristics of the first 1,000 cases and protection of the first-generation smallpox vaccine.

In early May 2022, a global outbreak of mpox started among persons without travel history to regions known to be enzootic for monkeypox virus (MPXV). On 8 August 2022, the Netherlands reported its 1,000th mpox case, representing a cumulative incidence of 55 per million population, one of the highest cumulative incidences worldwide. We describe characteristics of the first 1,000 mpox cases in the Netherlands, reported between 20 May and 8 August 2022, within the context of the public health response. These cases were predominantly men who have sex with men aged 31-45 years. The vast majority of infections were acquired through sexual contact with casual partners in private or recreational settings including LGBTQIA+ venues in the Netherlands. This indicates that, although some larger upsurges occurred from point-source and/or travel-related events, the outbreak was mainly characterised by sustained transmission within the Netherlands. In addition, we estimated the protective effect of first-generation smallpox vaccine against moderate/severe mpox and found a vaccine effectiveness of 58% (95% CI: 17-78%), suggesting moderate protection against moderate/severe mpox symptoms on top of any possible protection by this vaccine against MPXV infection and disease. Communication with and supporting the at-risk population in following mitigation measures remains essential.

Multi-sensorial perceptions of risk: the aesthetics behind (muco)cutaneous leishmaniasis-related stigma in Ecuador.

Previous research on the stigma associated with cutaneous leishmaniasis, a vector-transmitted parasitic disease, focuses on aesthetic appearance affectation as the leading cause of stigmatisation. However, Indigenous populations in the hinterland of Amazonian Ecuador trigger stigma expressions by recognising (muco)cutaneous leishmaniasis, primarily through atypical smell, followed by the odd voice sound, appearance and taste. This empirical way of recognising symptoms relies on embodied forms of identifying a disease, contrasting the Western supremacy of visuality and demanding to be understood via multi-sensorial anthropology. Through ethnographic research and data retrieved from eighty-three semistructured interviews and fifteen focus groups in seven Ecuadorian ethnic groups - including six Indigenous groups in the Amazon region - this paper analyses how the sensorium is a health thermometer. Findings reveal that differentiated cultural responses to a sense of peril, contagion and social (self)rejection, understood as stigma expressions, are linked to the holistic approach to health (or well-being) shared by Indigenous populations. In forest societies, well-being is explained through successful (non-)human relationships, and disease permeates through bodies that lack balanced relations.

Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses.

OBJECTIVES: HIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored. METHODS: This retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3-6 months. We included data of participants with ≥1 syphilis diagnosis in 2014-2019. Pearson's χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses. RESULTS: We included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032). CONCLUSIONS: In repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.

Sexual transmission of infections across Europe: appraising the present, scoping the future.

Objectives: Our journal partnered with the Europe section of the International Union against STI (IUSTI) at a workshop held at the 18th European AIDS Conference in London on 30 October 2021. The workshop reviewed epidemiological trends and discussed STI care provision within HIV services across Europe. Methods and Results: We started by highlighting trends in bacterial STIs reported to the European Centre for Disease Prevention and Control from countries in the European Union/European Economic Area. This showed that notifications of bacterial STIs reached an all-time high in 2019, but are expected to be impacted by the COVID-19 pandemic in 2020-2021. We then reviewed the evolving relationship between STIs and HIV and pointed out how antiretroviral treatment and pre-exposure prophylaxis remain highly effective against HIV transmission despite the rising incidence of STIs. Within emerging concepts in STIs, we appraised the benefits and risks of asymptomatic screening for chlamydia, and also considered the potential perils of routinely testing for agents that lack a defined role in disease. Finally, we discussed standards of STI care for people living with HIV, informed by a brief survey of IUSTI Europe country representatives and members of the Euroguidelines in Central and Eastern Europe network. Conclusions: The survey indicated substantial variability and identified key improvement targets: fighting barriers to effective service provision and access, increasing diagnostic capability and taking leadership in driving up the quality of care. We must not forget the STI-related needs of the many people who will be living with HIV for decades into the future.

Shigella is common in symptomatic and asymptomatic men who have sex with men visiting a sexual health clinic in Amsterdam.

INTRODUCTION: Shigellosis is a reportable infectious disease. It can present as a severe bloody diarrhoea but is often asymptomatic. Shigella can be sexually transmissible. We performed a study among symptomatic and asymptomatic men who have sex with men (MSM) to assess the prevalence of Shigella, Salmonella and Campylobacter. METHODS: From March to June 2020, MSM attending the Amsterdam centre for sexual health were consecutively included. Predefined minimal numbers of inclusion of 150, 100 and 50 were determined, respectively, for MSM who reported no diarrhoea, diarrhoea during last month or diarrhoea on the day of visit to clinic. Anal samples were tested for the presence of Shigella, Salmonella and Campylobacter. During the same period, the frequency of these bacteria was assessed in routinely tested samples requested by general physicians or nursing home physicians. Characteristics of included MSM were compared between the men with different diarrhoea anamnesis, and the prevalence of shigellosis was estimated in each group. RESULTS: We included 212 MSM without diarrhoea, 109 MSM who recently had diarrhoea and 68 MSM who reported diarrhoea on the day of clinic visit. Thirteen (3.3%, 95% CI 1.7% to 5.6%) MSM were infected with Shigella, none with Salmonella and 7 (1.8%, 95% CI 0.7% to 3.7%) with Campylobacter. Shigella prevalence was 2.8% (95% CI 1.0% to 6.1%) in asymptomatic men, 3.7% (95% CI 1.0% to 9.1%) in men who recently had diarrhoea and 4.4% (95% CI 0.9% to 12.4%) in men with current diarrhoea (p=0.799). Shigella was more frequently found in MSM who had used pre-exposure prophylaxis (PrEP) in the preceding 3 months (10/151), compared with those not having used PrEP (2/146) or being HIV positive (1/75) (p=0.038). Shigella was significantly more often detected among MSM compared with routinely obtained faecal samples being 11/770 (1.4%) (p=0.031). CONCLUSION: Shigella infections are relatively common in both symptomatic and asymptomatic MSM. Future studies should focus on the risk of onward transmission via asymptomatic persons. Samenvatting Introductie Shigellose is een meldingsplichtige infectieziekte. Het kan zich presenteren als een ernstige bloederige diarree, maar is vaak asymptomatisch. Shigella kan seksueel overdraagbaar zijn. We hebben een onderzoek uitgevoerd onder symptomatische en asymptomatische mannen die seks hebben met mannen (MSM) om de prevalentie van Shigella, Salmonella en Campylobacter te bepalen. Methoden Van maart tot juni 2020 werden achtereenvolgens MSM van het Amsterdamse centrum voor seksuele gezondheid opgenomen. Vooraf gedefinieerde minimale aantallen van inclusie van respectievelijk 150, 100 en 50 waren bepaald voor MSM die geen diarree, diarree in de afgelopen maand of diarree op de dag van bezoek aan de kliniek meldden. Anale monsters werden getest op de aanwezigheid van Shigella, Salmonella en Campylobacter. In dezelfde periode werd de frequentie van deze bacteriën bepaald in routinematig geteste monsters aangevraagd door huisartsen of verpleeghuisartsen. Kenmerken van geïncludeerde MSM werden vergeleken tussen mannen met verschillende diarree anamnese, en de prevalentie van shigellose werd in elke groep geschat. Resultaten We includeerden 212 MSM zonder diarree, 109 MSM die onlangs diarree hadden en 68 MSM die diarree meldden op de dag van het bezoek aan de kliniek. Dertien (3,3%, 95% CI 1,7-5,6%) MSM waren geïnfecteerd met Shigella, geen enkele met Salmonella, en 7 (1,8%, 95% CI 0,7-3,7%) met Campylobacter. De prevalentie van Shigella was 2,8% (95%CI 1,0-6,1%) bij asymptomatische mannen, 3,7% (95%CI 1,0-9,1%) bij mannen die recent diarree hadden en 4,4% (95%CI 0,9-12,4%) bij mannen met huidige diarree (P=0,799). Shigella werd vaker gevonden bij MSM die in de voorgaande drie maanden (10/151) PrEP hadden gebruikt dan bij mensen die geen PrEP hadden gebruikt (2/146) of hiv-positief waren (1/75) (p=0,038). Shigella werd significant vaker gedetecteerd bij MSM in vergelijking met routinematig verkregen fecale monsters, namelijk 11/770 (1,4%) (p=0,031). Conclusie Shigella infecties komen relatief vaak voor bij zowel symptomatische als asymptomatische MSM. Toekomstige studies moeten zich richten op het risico van verdere overdracht via asymptomatische personen.

HIV and STI positivity rates among transgender people attending two large STI clinics in the Netherlands.

BACKGROUND: Global data show that transgender people (TGP) are disproportionally affected by HIV and sexually transmitted infections (STIs); however, data are scarce for Western European countries. We assessed gender identities, sexual behaviour, HIV prevalence and STI positivity rates, and compared these outcomes between TGP who reported sex work and those who did not. METHODS: We retrospectively retrieved data from all TGP who were tested at the STI clinics of Amsterdam and The Hague, the Netherlands in 2017-2018. To identify one's gender identity, a 'two-step' methodology was used assessing, first, the assigned gender at birth (assigned male at birth (AMAB)) or assigned female at birth), and second, clients were asked to select one gender identity that currently applies: (1) transgender man/transgender woman, (2) man and woman, (3) neither man nor woman, (4) other and (5) not known yet. HIV prevalence, bacterial STI (chlamydia, gonorrhoea and/or infectious syphilis) positivity rates and sexual behaviour were studied using descriptive statistics. RESULTS: TGP reported all five categories of gender identities. In total 273 transgender people assigned male at birth (TGP-AMAB) (83.0%) and 56 transgender people assigned female at birth (TGP-AFAB) (17.0%) attended the STI clinics. Of TGP-AMAB, 14,6% (39/267, 95% CI 10.6% to 19.4%) were HIV-positive, including two new diagnoses and bacterial STI positivity was 15.0% (40/267, 95% CI 10.9% to 19.8%). Among TGP-AFAB, bacterial STI positivity was 5.6% (3/54, 95% CI 1.2% to 15.4%) and none were HIV-positive. Sex work in the past 6 months was reported by 53.3% (137/257, 95% CI 47.0% to 59.5%) of TGP-AMAB and 6.1% (3/49, 95% CI 1.3% to 16.9%) of TGP-AFAB. HIV prevalence did not differ between sex workers and non-sex workers. CONCLUSION: Of all TGP, the majority were TGP-AMAB of whom more than half engaged in sex work. HIV prevalence and STI positivity rates were substantial among TGP-AMAB and much lower among TGP-AFAB. Studies should be performed to provide insight into whether the larger population of TGP-AMAB and TGP-AFAB are at risk of HIV and STI.