Influenza-like illness symptoms due to endemic human coronavirus reinfections are not influenced by the length of the interval separating reinfections.

After 3 years of its introduction to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as endemic. Little is known about the severity of the disease manifestation that future infections may cause, especially when reinfections occur after humoral immunity from a previous infection or vaccination has waned. Such knowledge could inform policymakers regarding the frequency of vaccination. Reinfections by endemic human coronaviruses (HCoVs) can serve as a model system for SARS-CoV-2 endemicity. We monitored 44 immunocompetent male adults with blood sampling every 6 months (for 17 years), for the frequency of HCoV (re-)infections, using rises in N-antibodies of HCoV-NL63, HCoV-29E, HCoV-OC43, and HCoV-HKU1 as markers of infection. Disease associations during (re-)infections were examined by comparison of self-reporting records of influenza-like illness (ILI) symptoms, every 6 months, by all participants. During 8,549 follow-up months, we found 364 infections by any HCoV with a median of eight infections per person. Symptoms more frequently reported during HCoV infection were cough, sore throat, and myalgia. Two hundred fifty-one of the 364 infections were species-specific HCoV-reinfections, with a median interval of 3.58 (interquartile range 1.92-5.67) years. The length of the interval between reinfections-being either short or long-had no influence on the frequency of reporting ILI symptoms. All HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1 (re-)infections are associated with the reporting of ILIs. Importantly, in immunocompetent males, these symptoms are not influenced by the length of the interval between reinfections. IMPORTANCE: Little is known about the disease following human coronavirus (HCoV) reinfection occurring years after the previous infection, once humoral immunity has waned. We monitored endemic HCoV reinfection in immunocompetent male adults for up to 17 years. We found no influence of reinfection interval length in the disease manifestation, suggesting that immunocompetent male adults are adequately protected against future HCoV infections.

Determinants of epidemic size and the impacts of lulls in seasonal influenza virus circulation.

During the COVID-19 pandemic, levels of seasonal influenza virus circulation were unprecedentedly low, leading to concerns that a lack of exposure to influenza viruses, combined with waning antibody titres, could result in larger and/or more severe post-pandemic seasonal influenza epidemics. However, in most countries the first post-pandemic influenza season was not unusually large and/or severe. Here, based on an analysis of historical influenza virus epidemic patterns from 2002 to 2019, we show that historic lulls in influenza virus circulation had relatively minor impacts on subsequent epidemic size and that epidemic size was more substantially impacted by season-specific effects unrelated to the magnitude of circulation in prior seasons. From measurements of antibody levels from serum samples collected each year from 2017 to 2021, we show that the rate of waning of antibody titres against influenza virus during the pandemic was smaller than assumed in predictive models. Taken together, these results partially explain why the re-emergence of seasonal influenza virus epidemics was less dramatic than anticipated and suggest that influenza virus epidemic dynamics are not currently amenable to multi-season prediction.

What determines mpox vaccination uptake? Assessing the effect of intent-to-vaccinate versus other determinants among men who have sex with men.

BACKGROUND: In response to the mpox outbreak, vaccination was offered in the Netherlands to men who have sex with men (MSM) at increased risk for mpox. Successful vaccination campaigns are leveraged by high intent-to-vaccinate, yet intent might not always lead to uptake. Therefore, we assessed the impact of intent-to-vaccinate and other factors on vaccination uptake among participants of the Amsterdam Cohort Studies (ACS). METHOD: In July 2022, prior to the mpox vaccination campaign, we distributed an online survey regarding mpox intent-to-vaccinate, as well as e.g. beliefs, attitude, subjective norms, and perception of risk among ACS participants (all MSM). Vaccination uptake was self-reported during study visits after August 2022. The association between vaccination intent and uptake, and determinants of intent, was jointly assessed using a structural equation model (SEM) based on components of the Theory of Planned Behavior (TPB). In a second SEM, determinants of intent were allowed to have a direct effect on vaccination uptake. RESULTS: 492 MSM (median age = 46 years) were included in analyses. 380 (77%) had high intent-to-vaccinate and 238 (48%) received at least one vaccine dose. In the first model with a direct relation between intent and uptake only, TBP components predicted intent as expected, and high intent-to-vaccinate was significantly associated with getting vaccinated (ß = 1.1, 95%CI = 0.6-1.5). However, 175/380 (46%) participants with high intent-to-vaccinate did not get vaccinated. The second model had an improved model fit compared to the first model. The effect of intent on uptake was non-significant, and only perceiving to be at higher risk of infection significantly increased vaccination uptake later on (ß = 0.42, 95%CI = 0.26-0.59). Having a steady relationship decreased the probability of vaccination (ß = -0.59, 95%CI = -1.0- -0.18). CONCLUSIONS: While intent-to-vaccinate for mpox was high among MSM, high intent did not necessarily result in vaccine uptake. Mpox risk perception might have played a more pivotal role in getting vaccinated, which may be related to the evolution of vaccination eligibility criteria and accessibility to the vaccine.

The epidemiological impact of digital and manual contact tracing on the SARS-CoV-2 epidemic in the Netherlands: Empirical evidence.

The Dutch government introduced the CoronaMelder smartphone application for digital contact tracing (DCT) to complement manual contact tracing (MCT) by Public Health Services (PHS) during the 2020-2022 SARS-CoV-2 epidemic. Modelling studies showed great potential but empirical evidence of DCT and MCT impact is scarce. We determined reasons for testing, and mean exposure-testing intervals by reason for testing, using routine data from PHS Amsterdam (1 December 2020 to 31 May 2021) and data from two SARS-CoV-2 rapid diagnostic test accuracy studies at other PHS sites in the Netherlands (14 December 2020 to 18 June 2021). Throughout the study periods, notification of DCT-identified contacts was via PHS contact-tracers, and self-testing was not yet widely available. The most commonly reported reason for testing was having symptoms. In asymptomatic individuals, it was having been warned by an index case. Only around 2% and 2-5% of all tests took place after DCT or MCT notification, respectively. About 20-36% of those who had received a DCT or MCT notification had symptoms at the time of test request. Test positivity after a DCT notification was significantly lower, and exposure-test intervals after a DCT or MCT notification were longer, than for the above-mentioned other reasons for testing. Our data suggest that the impact of DCT and MCT on the SARS-CoV-2 epidemic in the Netherlands was limited. However, DCT impact might be enlarged if app use coverage is improved, contact-tracers are eliminated from the digital notification process to minimise delays, and DCT is combined with self-testing.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.

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.

Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV: Results from a Case-Control Diagnostic Validation Study.

We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63-0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8-86.2%) and specificity was 59.2% (95%CI: 47.3-70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4-65.1) and specificity of 71.2% (95%CI = 61.8-79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection.

A psychosocial network approach studying biomedical HIV prevention uptake between 2017 and 2019.

Biomedical HIV-prevention strategies (BmPS) among men who have sex with men (MSM), such as pre-exposure prophylaxis (PrEP) and viral load sorting (VLS), are essential but relatively new and their uptake gradual. Using an extension of the causal attitude network approach, we investigated which beliefs are related to uptake of PrEP and VLS at each time-point. We included 632 HIV-negative MSM from the Amsterdam Cohort Studies from four data-waves between 2017 and 2019. We estimated weighted, undirected networks for each time-point, where we included pairwise interactions of PrEP and VLS uptake and related beliefs. PrEP use increased from 10 to 31% (p < 0.001), while VLS was reported by 7-10% at each time-point. Uptake of both BmPS was directly related to the perceived positive impact of the strategy on one's quality of sex life and perceived supportive social norms. Overall network structure differed between time points, specifically in regard to PrEP. At earlier time points, perceptions of efficacy and affordability played an important role for PrEP uptake, while more recently social and health-related concerns became increasingly important.The network structure differed across data-waves, suggesting specific time changes in uptake motives. These findings may be used in communication to increase prevention uptake.

Putative transmission of extended-spectrum ß-lactamase-producing Escherichia coli among men who have sex with men in Amsterdam, the Netherlands.

OBJECTIVES: A previous study showed higher prevalence of Escherichia coli (E. coli) expressing extended-spectrum ß-lactamases (ESBL-Ec) among men who have sex with men (MSM) in Amsterdam, the Netherlands, compared with the general Dutch population. This study genetically characterised the ESBL-Ec isolates and investigated whether the increased prevalence could be explained by transmission between participants. METHODS: Whole-genome sequences were obtained from 93 unique ESBL-Ec isolates that were cultured from rectal swabs of 79 participants. Isolates were typed according to the Achtman MLST scheme and ESBL and virulence genes were identified. Pairwise SNP distances were determined between isolates. Isolate pairs with ≤ 25 SNPs were considered part of a putative transmission event, and events between multiple participants formed putative transmission clusters. To investigate whether putatively transmitted isolates belonged to globally expanded lineages, the level of hierarchical clustering with international isolates was assessed using core genome MLST (cgMLST) implemented on the Enterobase platform. RESULTS: The most frequently detected E. coli types were ST131:blaCTX-M-15 (16 of 117, 13.5%), ST131:blaCTX-M-27, ST3075:blaCTX-M-15 and ST14:blaSHV-12 (all six of 117, 6.5%). Fourteen putative transmission events were identified, forming four putative transmission clusters. The largest putative transmission cluster contained ST131 isolates, which clustered with multiple international isolates in SNP and cgMLST analysis. One other transmission cluster (ST14:blaSHV-12) and two transmission events (ST14:blaSHV-12 and ST394:blaCTX-M-15) contained very rarely reported strains. CONCLUSIONS: The identification of unique ESBL-Ec strains involved in putative transmission and carried by multiple participants demonstrated a high probability of ESBL-Ec transmission between MSM in Amsterdam; therefore, ESBL-Ec infection should be considered in cases of sexually active MSM having associated symptoms.

Evaluating interventions to reduce behaviour associated with HCV reinfection in men who have sex with men: study protocol for a non-blinded, phase 2, randomised trial.

BACKGROUND: As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM. METHODS: The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate. DISCUSSION: The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04156945. Registered on November 8, 2019.

Improving web-based respondent-driven sampling performance among men who have sex with men in the Netherlands.

Respondent-driven sampling (RDS) uses the social network of participants to sample people of populations that can be challenging to engage. While in this context RDS offers improvements on standard sampling methods, it does not always generate a sufficiently large sample. In this study we aimed to identify preferences of men who have sex with men (MSM) in the Netherlands regarding surveys and recruitment to studies with the subsequent goal of improving the performance of web-based RDS in MSM. A questionnaire about preferences with respect to various aspects of an web-based RDS study was circulated among participants of the Amsterdam Cohort Studies, a study among MSM. The duration of a survey and the type and amount of participation reward were explored. Participants were also asked about their preferences regarding invitation and recruitment methods. We used multi-level and rank-ordered logistic regression to analyze the data and identify the preferences. The majority of the 98 participants were older than 45 years (59.2%), were born in the Netherlands (84.7%), and had a university degree (77.6%). Participants did not have a preference regarding the type of participation reward, but they preferred to spend less time on a survey and to get a higher monetary reward. Sending a personal email was the preferred option to getting invited or inviting someone to a study, while using Facebook messenger was the least preferred option. There are differences between age groups: monetary rewards were less important to older participants (45+) and younger participants (18-34) more often preferred SMS/WhatsApp to recruit others. When designing a web-based RDS study for MSM, it is important to balance the duration of the survey and the monetary reward. If the study takes more of a participants time, it might be beneficial to provide a higher incentive. To optimize expected participation, the recruitment method should be selected based on the targeted population group.

Dengue, chikungunya and Zika virus infections among Dutch travellers to Suriname: a prospective study during the introduction of chikungunya and Zika virus, 2014 to 2017.

BackgroundSuriname, a country endemic for dengue virus (DENV), is a popular destination for Dutch travellers visiting friends and relatives and tourist travellers. Chikungunya and Zika virus (CHIKV, ZIKV) were introduced in 2014 and 2015, respectively. Data on infection risks among travellers are limited.AimWe aimed to prospectively study incidence rate (IR) and determinants for DENV, ZIKV and CHIKV infection in adult travellers to Suriname from 2014 through 2017.MethodsParticipants kept a travel diary and were tested for anti-DENV, anti-ZIKV and anti-CHIKV IgG antibodies (Euroimmun). Selected samples were subjected to an in-house DENV and ZIKV PRNT50. The IR (infections/1,000 person-months of travel) and IR ratio and determinants for infection were calculated.ResultsTravel-acquired infections were found in 21 of 481 participants: 18 DENV, four ZIKV and two CHIKV, yielding an IRDENV of 47.0 (95% CI: 29.6-74.6), IRZIKV of 11.6 (95% CI: 4.4-31.0) and IRCHIKV of 5.6 (95% CI: 1.4-22.2)/1,000 person-months. In nine DENV and three ZIKV infected participants, infections were PRNT50-confirmed, yielding a lower IRDENV of 23.3 (95% CI: 12.1-44.8) and an IRZIKV of 8.4 (95% CI: 2.7-26.1) per 1,000 person-months. Tourist travel was associated with DENV infection. ZIKV and CHIKV infections occurred soon after their reported introductions.ConclusionsDespite an overestimation of serologically confirmed infections, Dutch travellers to Suriname, especially tourists, are at substantial risk of DENV infection. As expected, the risk of contracting ZIKV and CHIKV was highest during outbreaks. Cross-reaction and potential cross-protection of anti-DENV and -ZIKV antibodies should be further explored.

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.

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

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

Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics.

Background: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics. Methods: We analyzed historical influenza virus epidemiological data from 2003-2019 to assess the historical frequency of near-absence of seasonal influenza virus circulation and its impact on the size and severity of subsequent epidemics. Additionally, we measured haemagglutination inhibition-based antibody titres against seasonal influenza viruses using longitudinal serum samples from 165 healthy adults, collected before and during the COVID-19 pandemic, and estimated how antibody titres against seasonal influenza waned during the first two years of the pandemic. Findings: Low country-level prevalence of influenza virus (sub)types over one or more years occurred frequently before the COVID-19 pandemic and had relatively small impacts on subsequent epidemic size and severity. Additionally, antibody titres against seasonal influenza viruses waned negligibly during the first two years of the pandemic. Interpretation: The commonly held notion that lulls in influenza virus circulation, as observed during the COVID-19 pandemic, will lead to larger and/or more severe subsequent epidemics might not be fully warranted, and it is likely that post-lull seasons will be similar in size and severity to pre-lull seasons. Funding: European Research Council, Netherlands Organization for Scientific Research, Royal Dutch Academy of Sciences, Public Health Service of Amsterdam. Research in context: Evidence before this study: During the first years of the COVID-19 pandemic, the incidence of seasonal influenza was unusually low, leading to widespread concerns of exceptionally large and/or severe influenza epidemics in the coming years. We searched PubMed and Google Scholar using a combination of search terms (i.e., "seasonal influenza", "SARS-CoV-2", "COVID-19", "low incidence", "waning rates", "immune protection") and critically considered published articles and preprints that studied or reviewed the low incidence of seasonal influenza viruses since the start of the COVID-19 pandemic and its potential impact on future seasonal influenza epidemics. We found a substantial body of work describing how influenza virus circulation was reduced during the COVID-19 pandemic, and a number of studies projecting the size of future epidemics, each positing that post-pandemic epidemics are likely to be larger than those observed pre-pandemic. However, it remains unclear to what extent the assumed relationship between accumulated susceptibility and subsequent epidemic size holds, and it remains unknown to what extent antibody levels have waned during the COVID-19 pandemic. Both are potentially crucial for accurate prediction of post-pandemic epidemic sizes.Added value of this study: We find that the relationship between epidemic size and severity and the magnitude of circulation in the preceding season(s) is decidedly more complex than assumed, with the magnitude of influenza circulation in preceding seasons having only limited effects on subsequent epidemic size and severity. Rather, epidemic size and severity are dominated by season-specific effects unrelated to the magnitude of circulation in the preceding season(s). Similarly, we find that antibody levels waned only modestly during the COVID-19 pandemic.Implications of all the available evidence: The lack of changes observed in the patterns of measured antibody titres against seasonal influenza viruses in adults and nearly two decades of epidemiological data suggest that post-pandemic epidemic sizes will likely be similar to those observed pre-pandemic, and challenge the commonly held notion that the widespread concern that the near-absence of seasonal influenza virus circulation during the COVID-19 pandemic, or potential future lulls, are likely to result in larger influenza epidemics in subsequent years.

Malaria in long-term travelers: Infection risks and adherence to preventive measures - A prospective cohort study.

BACKGROUND: Chemoprophylaxis and anti-mosquito measures are key to preventing malaria in travelers. Long-term travelers are at higher risk than short-term travelers, but their adherence to preventive measures is lower. Our aim was to determine malaria exposure risks and predictors for adherence to malaria-preventive measures in long-term travelers. METHODS: Long-term travelers (>12 weeks) completed a weekly questionnaire about preventive measures, symptoms, and malaria treatment abroad. Blood samples were tested for seroconversion to Plasmodium falciparum anti-circumsporozoite (PfCSP) antibody. Adherence to preventive measures was defined as number of weeks of their usage divided by number of weeks in malaria-endemic areas. RESULTS: Of 561 travelers, the median travel time was 20 weeks (IQR 16-25). Eighteen were treated for malaria, all in sub-Saharan Africa. Sixteen PfCSP seroconversions were found, of whom only 3 had traveled to high-endemic areas. Of the 18 travelers treated for malaria, only one seroconverted. No associations were found between covariates and seroconversion. Neither treatment abroad nor seroconversion were reliable predictors for exposure. 'Full adherence' to chemoprophylaxis was reported by 52% (218/417) and was associated with travel to Africa, use of mefloquine, lack of prior travel history, shorter duration of travel, and use of DEET. CONCLUSIONS: The risk of malaria in this long-term travelers cohort was low. Our data confirm that anti-PfCSP seroconversion is not a reliable method to retrospectively identify incident infection, or probably exposure. Prevention efforts should focus on more experienced travellers and longer travel duration, for whom mefloquine should be considered as the first-choice chemoprophylaxis.

Factors Associated With Using the COVID-19 Mobile Contact-Tracing App Among Individuals Diagnosed With SARS-CoV-2 in Amsterdam, the Netherlands: Observational Study.

BACKGROUND: Worldwide, efforts are being made to stop the COVID-19 pandemic caused by SARS-CoV-2. Contact tracing and quarantining are key in limiting SARS-CoV-2 transmission. Mathematical models have shown that the time between infection, isolation of cases, and quarantining of contacts are the most important components that determine whether the pandemic can be controlled. Mobile contact-tracing apps could accelerate the tracing and quarantining of contacts, including anonymous contacts. However, real-world observational data on the uptake and determinants of contact-tracing apps are limited. OBJECTIVE: The aim of this paper is to assess the use of a national Dutch contact-tracing app among notified cases diagnosed with SARS-CoV-2 infection and investigate which characteristics are associated with the use of the app. METHODS: Due to privacy regulations, data from the app could not be used. Instead, we used anonymized SARS-CoV-2 routine contact-tracing data collected between October 28, 2020, and February 26, 2021, in the region of Amsterdam, the Netherlands. Complete case logistic regression analysis was performed to identify which factors (age, gender, country of birth, municipality, number of close contacts, and employment in either health care or education) were associated with using the app. Age and number of close contacts were modelled as B-splines due to their nonlinear relationship. RESULTS: Of 29,766 SARS-CoV-2 positive cases, 4824 (16.2%) reported app use. Median age of cases was 41 (IQR 29-55) years, and 46.7% (n=13,898) were male. In multivariable analysis, males (adjusted odds ratio [AOR] 1.11, 95% CI 1.04-1.18) and residents of municipalities surrounding Amsterdam were more likely to use the app (Aalsmeer AOR 1.34, 95% CI 1.13-1.58; Ouder-Amstel AOR 1.96, 95% CI 1.54-2.50), while people born outside the Netherlands, particularly those born in non-Western countries (AOR 0.33, 95% CI 0.30-0.36), were less likely to use the app. Odds of app use increased with age until the age of 58 years and decreased sharply thereafter (P<.001). Odds of app use increased with number of contacts, peaked at 8 contacts, and then decreased (P<.001). Individuals working in day care, home care, and elderly nursing homes were less likely to use the app. CONCLUSIONS: Contact-tracing app use among people with confirmed SARS-CoV-2 infection was low in the region of Amsterdam. This diminishes the potential impact of the app by hampering the ability to warn contacts. Use was particularly low among older people, people born outside the Netherlands, and people with many contacts. Use of the app was also relatively low compared to those from some other European countries, some of which had additional features beyond contact tracing, making them potentially more appealing. For the Dutch contact-tracing app to have an impact, uptake needs to be higher; therefore, investing more into promotional efforts and additional features could be considered.

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

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

Trends in Sexual Behavior and Sexually Transmitted Infections After Initiating Human Immunodeficiency Virus Pre-Exposure Prophylaxis in Men Who Have Sex with Men from Amsterdam, the Netherlands: A Longitudinal Exposure-Matched Study.

Men who have sex with men (MSM) initiating human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) may increase condomless anal sex (CAS) and number of partners, and, consequently, more often acquire sexually transmitted infections (STIs). Using data from the Amsterdam Cohort Studies, we compared sexual behavior and STI among MSM after PrEP-initiation with controls not initiating PrEP. The MSM reported on sexual behavior and were tested for HIV, chlamydia, gonorrhea, and syphilis semi-annually. We matched MSM who initiated PrEP between January 1, 2015 and December 31, 2019 1:1 to MSM who did not use time-dependent propensity scores based on age, sexual behavior, and STI. Primary end-points were number of casual partners, and proportion with CAS and receptive CAS (rCAS) with casual partners, sexualized drug use (SDU), any STI, and anal STI. We modeled end-points during the 4 years before and 2 years after PrEP-initiation or matched PrEP-initiation timepoint by using logistic regression (dichotomous end-points) or negative binomial regression (count end-point), adjusted for calendar year. Two hundred twenty-eight out of the 858 (26.6%) MSM initiated PrEP. We matched 198 out of 228 (86.8%) to a control. Before PrEP-initiation, end-points increased over time in both groups, with no statistically significant difference. The odds of CAS, rCAS, and anal STI were on average higher after than before PrEP-initiation in PrEP initiators, whereas after versus before differences were not observed in controls. After PrEP-initiation, PrEP initiators had statistically significantly more casual partners, and higher odds of CAS, rCAS, SDU, any STI, and anal STI than controls. These findings support frequent STI screening and counseling in MSM using PrEP.

Factors Associated With the Intention to Use HIV Preexposure Prophylaxis for Young and Older Men Who Have Sex With Men.

BACKGROUND: The uptake of preexposure prophylaxis (PrEP) against HIV is low among young men who have sex with men (MSM) in the Netherlands. Studying the intention to use PrEP among non-PrEP using young and older MSM can guide health authorities in developing new prevention campaigns to optimize PrEP uptake. METHODS: We investigated the sociodemographic, behavioral, and psychosocial factors associated with a high PrEP use intention in the coming 6 months among 93 young MSM (aged ≤25 years), participating in an online survey, and 290 older MSM (aged ≥26 years), participating in an open, prospective cohort in 2019 to 2020. RESULTS: Perceiving PrEP as an important prevention tool was associated with a high PrEP use intention among young and older MSM. Among young MSM, a high level of PrEP knowledge and believing that PrEP users take good care of themselves and others were associated with a high PrEP use intention. Among older MSM, 2 or more anal sex partners, chemsex, high HIV risk perception, and believing PrEP increases sexual pleasure were associated with a high PrEP use intention. Believing PrEP leads to adverse effects was associated with a low intention to use PrEP among older MSM. CONCLUSIONS: To conclude, we showed that both behavioral and psychosocial factors were associated with a high PrEP use intention among young and older MSM. In addition to focusing on sexual behavior and HIV risk, future prevention campaigns and counseling on PrEP could incorporate education, endorsing positive beliefs, and disarming negative beliefs to improve the uptake of PrEP in young and older MSM.