Use of Home-Based Self-Collected Dried Blood Spots to Test for Syphilis, Human Immunodeficiency Virus, Hepatitis C and B Virus Infections and Measuring Creatinine Concentration.

INTRODUCTION: Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration. METHODS: We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing. RESULTS: In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 µmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3-5). DISCUSSION: Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low.

Characteristics of mpox positive, versus mpox negative, and mpox unsuspected clients from the Centre of Sexual Health, Public Health Service of Amsterdam, 20 May to 15 September 2022.

BACKGROUND: In May 2022, an outbreak of mpox (monkeypox) in men-who-have-sex-with-men (MSM) emerged and quickly affected over 100 countries. In the early stages of the outbreak, overlap in symptoms with sexually transmitted infections (STI) made triage for mpox testing challenging. More information was needed on whom to screen and the main route of transmission. OBJECTIVES: We aimed to identify characteristics of mpox cases to further strengthen case definitions. We also compared Cycle threshold (Ct) values of the DNA positive mpox samples as a proxy for viral load by body location. METHODS: From 20 May 2022 to 15 September 2022, we tested all MSM who presented with malaise, and/or ulcerative lesions, and/or proctitis and/or a papular-vesicular-pustular eruption attending the Centre of Sexual Health in Amsterdam, the Netherlands, for mpox, with a PCR test. In the same period, 6932 MSM mpox unsuspected clients were not tested. We compared those tested positive for mpox with those tested negative and those unsuspected for mpox. RESULTS: Of the 374 MSM tested, 135 (36%) were positive for mpox. The mpox-positive MSM were older (median age, respectively, 36, 34 and 34 years, p = 0.019) and more often lived with HIV (30% vs. 16% and 7%, p < 0.001). Furthermore, mpox-positive patients more often reported receptive anal sex without a condom, sexualized drug use, more sex partners, and were more often diagnosed with bacterial STI (p < 0.001). Systemic symptoms and anogenital lesions were associated with mpox infection. For mpox-positive patients, anal samples (p = 0.009) and lesional samples (p = 0.006) showed significantly lower median mpox Ct values compared to throat samples. CONCLUSIONS: Mpox-positive patients more often reported receptive anal sex without a condom, had more sex partners and more often lived with HIV. Our results suggest that in the current mpox outbreak among MSM, sexual transmission is the main route.

Treponema pallidum Subspecies Pallidum Intrapatient Homogeneity at Various Body Locations in Men with Infectious Syphilis.

Syphilis, caused by Treponema pallidum subspecies pallidum (TP), is a complex multistage infectious disease. Systematic dissemination occurs within a few hours of transmission. We determined the molecular variation of TP at various body locations and peripheral blood within patients in different stages of syphilis to assess the distribution of TP strains at these locations. We included 162 men who have sex with men (MSM) with syphilis visiting the Sexual Health Center in Amsterdam between 2018 to 2019, who had TP DNA detected in at least one sample type (anal swab, urine sample, peripheral blood, pharyngeal swab, and/or ulcer swab). TP DNA was detected in 287 samples using a qPCR targeting the polA gene. With multilocus sequence typing (TP-MLST) based on partial sequence analysis of three genetic regions (tp0136, tp0548, tp0705), we characterized all TP DNA positive samples. Samples could be typed (119/287) from at least one anatomical location or peripheral blood from 93/162 (57%) patients in the following stages: 48 (52%) primary, 35 (38%) secondary, and 10 (11%) early latent stage syphilis. The TP-MLST type was identical within each of the 12 patients with typed samples at ≥2 different body locations. The most prevalent TP strains were 1.3.1 (39/93, 42%) and 1.1.1 (17/93, 18%) belonging to the SS14 lineage; 80% (74/93) of the patients carried a SS14 lineage TP strain and 20% (19/93) Nichols lineage. The distribution of TP-MLST types did not differ between patients by syphilis stage. We found intrapatient TP strain homogeneity and no TP strain variation between anatomical location or syphilis stages. More early latent samples should be typed and added in future studies to investigate this in more detail. IMPORTANCE Syphilis, caused by Treponema pallidum subspecies pallidum, is a complex multistage infectious disease. Systematic dissemination is known to occur within a few hours of transmission. Despite the effective antibiotic penicillin, syphilis remains prevalent worldwide. Men who have sex with men are disproportionally affected in high income countries like the Netherlands where 96% of the syphilis cases in 2020 were among this population. The inability to in vitro culture T. pallidum directly from patient samples limits whole-genome sequencing efforts. Fortunately, in 2018 a multilocus sequence typing technique was developed for T. pallidum allowing the monitoring of circulating strains. The significance of our research is in the investigation of T. pallidum molecular variation at various body locations and blood within patients in different stages of syphilis in order to assess the distribution of strains at these locations.

Detection of Treponema pallidum DNA During Early Syphilis Stages in Peripheral Blood, Oropharynx, Ano-Rectum and Urine as a Proxy for Transmissibility.

BACKGROUND: Syphilis diagnosis may be challenging, especially in the asymptomatic and early clinical stages. We evaluated the presence of Treponema pallidum DNA (TP-DNA) in various sample types to elucidate transmissibility during various syphilis stages. METHODS: The study was conducted at the Amsterdam Centre for Sexual Health. We included adult men who have sex with men (MSM), who were suspected of having syphilis. The 2020 European guidelines definitions were followed for the diagnosis and staging of syphilis. Using a polymerase chain reaction (PCR) targeting the polA gene of Treponema pallidum (TP-PCR), we tested the following study samples on TP-DNA: peripheral blood, oropharyngeal swab, ano-rectal swab, and urine. RESULTS: From November 2018 to December 2019 we included 293 MSM. Seventy clients had primary syphilis, 73 secondary syphilis, 86 early latent syphilis, 14 late latent syphilis, 23 treated syphilis, and 27 had no syphilis. TP-DNA was detected in at least 1 study sample in 35/70 clients with primary syphilis (2/70 peripheral blood, 7/70 oropharynx, 13/70 ano-rectum, and 24/70 urine); in 62/73 clients with secondary syphilis (15/73 peripheral blood, 47/73 oropharynx, 37/73 ano-rectum, and 26/73 urine); and in 29/86 clients with early latent syphilis (5/86 peripheral blood, 21/86 oropharynx, 11/86 ano-rectum, and 6/86 urine). TP-DNA was not detected in clients with late latent syphilis or treated syphilis, nor in clients without syphilis. CONCLUSIONS: TP-DNA was frequently detected in various sample types in the absence of lesions. This is in line with the high transmission rate of syphilis and opens diagnostic opportunities for early presymptomatic syphilis stages.

Current evidence on the adoption of indicator condition guided testing for HIV in western countries: A systematic review and meta-analysis.

BACKGROUND: Indicator condition (IC) guided testing for HIV is an effective way to identify undiagnosed people living with HIV, but studies suggest its implementation is lacking. This systematic review provides an overview of the adoption of IC-guided testing in Western countries. METHODS: Seven ICs were selected: tuberculosis (TB), malignant lymphoma, hepatitis B, hepatitis C, cervical/vulvar carcinoma/intraepithelial neoplasia grade 2+ (CC/CIN2+, VC/VIN2+), and peripheral neuropathy (PN). Embase and Ovid MEDLINE were searched up to November 20th, 2020. Publications of all types, using data from ≥2009, reporting on HIV test ratios in patients ≥18 years in all settings in Western countries were eligible. HIV test ratios and positivity were reported per IC. A random effects-model for proportions was used to calculate estimated proportions (ES) with 95% CIs. This study was registered at PROSPERO, registration number CRD42020160243. FINDINGS: Fifty-seven references, including 23 full-text articles and 34 other publications were included. Most (28/57) reported on HIV testing in TB. No reports on HIV testing in VC/VIN2+ or PN patients were eligible for inclusion. Large variation in HIV test ratios was observed between and within ICs, resulting from different testing approaches. Highest HIV test ratios (pooled ratio: 0·72, 95%CI 0·63-0·80) and positivity (0·05, 95% CI 0·03-0·06) were observed among TB patients, and lowest among CC/CIN2+ patients (pooled ES test ratio: 0·12, 95%CI 0·01-0·31, positivity: 0·00, 95%CI 0·00-0·00). INTERPRETATION: IC-guided HIV testing is insufficiently implemented in Western countries. The large variation in test ratios provides insight into priority areas for implementing routine IC-guided HIV testing in the future. FUNDING: HIV Transmission Elimination in Amsterdam (H-TEAM) consortium and Aidsfonds (grant number P-42,702).

Changes in mental health and drug use among men who have sex with men using daily and event-driven pre-exposure prophylaxis: Results from a prospective demonstration project in Amsterdam, the Netherlands.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are at increased risk of mental health disorders and drug use. In GBMSM taking pre-exposure prophylaxis (PrEP) for HIV, the proportion engaging in risk behaviors could increase due to decreased perception in HIV risk. In turn, this could leave them further susceptible to mental health disorders. METHODS: The AMsterdam PrEP study (AMPrEP) is a demonstration project offering a choice of daily PrEP or event-driven PrEP regimen at the STI clinic of the Public Health Service of Amsterdam. Eligible participants were HIV-negative GBMSM and transgender people at risk of HIV, aged ≥18 years. We assessed anxiety and depressive mood disorders (Mental Health Inventory 5), sexual compulsivity (Sexual Compulsivity Scale), alcohol use disorder (Alcohol Use Disorder Identification Test), and drug use disorder (Drug Use Disorder Identification Test) using yearly self-administered assessments (August 2015-September 2018). The proportion of mental health problems were analyzed and changes over time and between regimen were assessed using a logistic regression model. Variables associated with the development or recovery of disorders were assessed using a multistate Markov model. OUTCOMES: Of 376 enrolled, we analyzed 341 participants with data at baseline and at least one follow-up visit. During a median follow-up of 2.5 years (IQR=2.3-2.7), the proportion assessed with sexual compulsivity decreased from 23% at baseline to 10% at the last visit (p<0.001) and drug use disorder decreased from 38% at baseline to 31% at the last visit (p = 0.004). No changes occurred in proportion assessed with anxiety/depressive mood disorders (20% at baseline, 18% at last visit, p = 0.358) or alcohol use disorder (28% at baseline, 22% at the last visit, p = 0.106). During follow-up, participants reported significant less use of alcohol (p<0.001), nitrites (p<0.001) and ecstasy (p<0.001). We found no differences between daily and event-driven PrEP users. The development and recovery of disorders during follow-up were highly interrelated. INTERPRETATION: Mental health disorders are prevalent among those initiating PrEP. We did not find increases in mental health disorders during PrEP use, but rather a decrease in sexual compulsivity and drug use disorders. The initial prevalence of mental health disorders in our study point at the continuous need to address mental health disorders within PrEP programs. FUNDING: ZonMw, H-TEAM, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Grading immunohistochemical markers p16INK4a and HPV E4 identifies productive and transforming lesions caused by low- and high-risk HPV within high-grade anal squamous intraepithelial lesions.

OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.

Anal Squamous Intraepithelial Lesions (SILs) in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men: Incidence and Risk Factors of SIL and of Progression and Clearance of Low-Grade SILs.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs). METHODS: HIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level. RESULTS: Of 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs. CONCLUSION: Incident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.

Hepatitis E virus seroprevalence and determinants in various study populations in the Netherlands.

BACKGROUND: The epidemiology of hepatitis E virus (HEV) is not fully understood. In this study, we assessed putative risk factors for HEV seropositivity in various study populations in the Netherlands. METHODS: Data and samples from five different study populations were analysed: (A) blood donors (n = 5,239), (B) adults reporting a vegetarian life style since the age of 12 years (n = 231), (C) residents of Amsterdam, the Netherlands, with different ethnic backgrounds (n = 1,198), (D) men who have sex with men (MSM) (HIV positive and HIV negative) (n = 197), and (E) persons who use drugs (PWUD) (HIV positive and HIV negative) (n = 200). Anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG) testing was performed using ELISA test (Wantai). RESULTS: HEV IgM seroprevalence was low across all study populations (<1% to 8%). The age and gender-adjusted HEV IgG seroprevalence was 24% among blood donors (reference group) and 9% among the vegetarian group (adjusted Relative Risk [aRR]:0.36, 95%CI:0.23-0.57). Among participants of different ethnic backgrounds, the adjusted HEV IgG seroprevalence was 16% among participants with a Dutch origin (aRR:0.64, 95%CI:0.40-1.02), 2% among South-Asian Surinamese (aRR:0.07, 95%CI:0.02-0.29), 3% among African Surinamese (aRR:0.11, 95%CI:0.04-0.34), 34% among Ghanaian (aRR:1.53, 95%CI:1.15-2.03), 19% among Moroccan (aRR:0.75, 95%CI:0.49-1.14), and 5% among Turkish (aRR:0.18, 95%CI:0.08-0.44) origin participants. First generation Moroccans had a higher risk for being IgG HEV seropositive compared to second generation Moroccan migrants. The statistical power to perform these analyses in the other ethnic groups was too low. In the MSM group the IgG HEV seroprevalence was 24% (aRR:0.99, 95%CI:0.76-1.29), and among PWUD it was 28% (aRR:1.19, 95%CI:0.90-1.58). The number of sexual partners in the preceding six months was not significantly associated with IgG HEV seropositivity in MSM. The association between HIV status and HEV seropositivity was significant in PWUD, yet absent in MSM. HIV viral load and CD4 cell count were not associated with HEV seropositivity in HIV positive MSM and PWUD. CONCLUSIONS: Vegetarians were significantly less often HEV seropositive. Ethnic origin influenced the risk for being IgG HEV seropositive. MSM and PWUD were not at higher risk for being IgG HEV seropositive than blood donors.

Vaginal and anal human papillomavirus infection and seropositivity among female sex workers in Amsterdam, the Netherlands: Prevalence, concordance and risk factors.

BACKGROUND: We studied prevalence, risk factors and concordance of vaginal and anal HPV infection and L1 seropositivity among female sex workers (FSW) in Amsterdam. METHODS: In 2016, FSW aged ≥18 years having a sexually transmitted infections (STI) consultation were invited to participate. Participation entailed taking vaginal and anal self-swabs. Demographics and sexual behaviour data were collected. HPV DNA was analysed using the SPF10-PCR-DEIA-LiPA25-system-v1. Serum was tested for HPV L1 antibodies using multiplex serology assays. Determinants of vaginal and anal high risk HPV (hrHPV) infection and L1 seropositivity were assessed with logistic regression analyses. RESULTS: We included 304 FSW; median age was 29 years (IQR 25-37). Vaginal and anal hrHPV prevalence were 46% and 55%, respectively. HrHPV L1 seropositivity was 37%. Vaginal-anal hrHPV concordance was strong, but no significant association between vaginal or anal hrHPV infection and seropositivity was found. Having had anal sexual contact was not associated with anal hrHPV infection (P = 0.119). DISCUSSION: Vaginal and anal hrHPV prevalence is high among FSW in Amsterdam, the Netherlands. Promotion of HPV vaccination, preferably at the beginning of the sex (work) career, may be a useful prevention method against hrHPV infection and disease.

High-risk human papillomavirus seroprevalence in men and women of six different ethnicities in Amsterdam, the Netherlands: The HELIUS study.

BACKGROUND: Ethnic variations in the (sero)prevalence of Human Papillomavirus (HPV) and HPV related diseases have been observed previously. We explored if high-risk HPV (hrHPV) seropositivity indeed differs among 6 ethnic groups in Amsterdam the Netherlands and assessed if hrHPV seroprevalence is higher among women than men within each ethnic group, both after adjustment for confounders. METHODS: From the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) study in Amsterdam (the Netherlands) we randomly selected 4637 men and women aged 18-44 years with a Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, or Turkish ethnicity. Blood samples were tested for HPV-16,-18,-31,-33,-45,-52, and -58 antibodies using a validated Luminex-based multiplex serology assay. We assessed the association of both ethnicity and gender with hrHPV seropositivity using logistic regression models with generalised estimating equations. RESULTS: The hrHPV seroprevalence in Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, and Turkish participants was 18%, 12%, 23%, 19%, 17%, and 15% in men, and 30%, 22%, 34%, 31%, 14%, and 15% in women, respectively. HrHPV seroprevalence of non-Dutch men did not differ significantly from Dutch men. HrHPV seroprevalence was significantly higher among African Surinamese women, and significantly lower among Moroccan and Turkish women when compared to Dutch women. These differences were not significant anymore after adjustment for demographic, health, and sexual behavioural differences between ethnicities. HrHPV seroprevalence varied by age, age of sexual debut, and lifetime sexual partners among women but not among men. Seroprevalence of hrHPV was higher among women than among men, except in the Turkish group. CONCLUSION: Among women hrHPV seroprevalence differed by ethnicity, yet among men no pronounced differences were observed across ethnicities.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

HPV vaccination intention among male clients of a large STI outpatient clinic in Amsterdam, the Netherlands.

We explored HPV vaccination intention and its determinants among male clients of the sexually transmitted infections (STI) clinic in Amsterdam. In 2015, male clients aged ≥18 years were invited to complete a web-based questionnaire regarding HPV vaccination intention and socio-psychological determinants. Determinants (scale -3 to +3) were assessed with linear regression, stratified for men who have sex with men (MSM) (including men who have sex with men and women) and men who only have sex with women (MSW). Additionally, we explored the effect of out-of-pocket payment on intention. Of 1490 participants (median age 33 years [IQR:25-44]), 1,053(71%) were MSM. HPV vaccination intention was high (mean 1.68, 95%CI:1.55-1.81 among MSW; mean 2.35, 95%CI:2.29-2.42 among MSM). In multivariable analyses, socio-psychological determinants had similar effects on intention in both groups (R2=0.70 among MSW; R2=0.68 among MSM), except for subjective norms, self-efficacy, and HPV knowledge (significantly stronger associations among MSW). HPV vaccination intention decreased significantly when vaccination would require out-of-pocket payment; intention was negative at the current list price (€350). HPV vaccination intention among male clients of the Amsterdam STI-clinic is high and variance in intention was mostly be explained by socio-psychological factors. Out-of-pocket payment had a strong negative effect on HPV vaccination intention.

The Accelerating Access Initiative: experience with a multinational workplace programme in Africa.

PROBLEM: A multinational company with operations in several African countries was committed to offer antiretroviral treatment to its employees and their dependants. APPROACH: The Accelerating Access Initiative (AAI), an initiative of six pharmaceutical companies and five United Nations' agencies, offered the possibility of obtaining brand antiretroviral drugs (ARVs) at 10% of the commercial price. PharmAccess, a foundation aimed at removing barriers to AIDS treatment in Africa, helped to establish an HIV policy and treatment guidelines, and a workplace programme was rolled out from September 2001. LOCAL SETTING: Private sector employers in Africa are keen to take more responsibility in HIV prevention and AIDS care. An important hurdle for African employers remains the price and availability of ARVs. RELEVANT CHANGES: The programme encountered various hurdles, among them the need for multiple contracts with multiple companies, complex importation procedures, taxes levied on ARVs, lack of support from pharmaceutical companies in importation and transportation, slow delivery of the drugs, lack of institutional memory in pharmaceutical companies and government policies excluding the company from access to ARVs under the AAI. LESSONS LEARNED: The launch of the AAI enabled this multinational company to offer access to ARVs to its employees and dependants. The private sector should have access to these discounted drugs under the AAI. A network of local AAI offices should be created to assist in logistics of drugs ordering, purchase and clearance. No taxes should be levied on ARVs.

Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands.

Antimicrobial resistance is an increasing problem in Neisseria gonorrhoeae (NG) treatment. Presently, third-generation parenteral cephalosporins, like ceftriaxone and cefotaxime, are the first option. Resistance to oral, but not to parenteral, third-generation cephalosporins has been reported previously. We analysed the microbial susceptibility (as minimum inhibitory concentration - MIC) of NG cultures obtained from high-risk visitors of the largest Dutch outpatient clinic for sexually transmitted infections (STI) in Amsterdam, the Netherlands. Among 1,596 visitors, we identified 102 patients with at least one NG isolate with reduced susceptibility to cefotaxime (0.125 microg/ml < MIC < or = 0.5 microg/ml). The percentage of NG isolates with reduced susceptibility to cefotaxime rose from 4.8% in 2006 to 12.1% in 2008 (chi2 17.5, p<0.001). With multivariate logistic regression, being a man who has sex with men (MSM) was significantly associated with reduced susceptibility to cefotaxime (p<0.001). Compared to susceptible NG isolates, those with decreased susceptiblity to cefotaxime were more often resistant also to penicillin (16.5% vs. 43.3%), tetracycline (21.5% vs. 68.9%) and ciprofloxacin (44.4% vs. 90.0%, all p<0.001). The increased prevalence of NG strains with reduced susceptibility to cefotaxime among MSM may herald resistance to third-generation parenteral cephalosporins. A considerable proportion of these strains show resistance to multiple antibiotics which could limit future NG treatment options.

Population-based study on the seroprevalence of parvovirus B19 in Amsterdam.

A study was undertaken to estimate the seroprevalence of parvovirus B19 infection in the general adult population of Amsterdam, The Netherlands. To our knowledge this is the first study testing parvovirus B19 in a random sample of the Dutch adult population. The study was a cross-sectional survey, and the study sample was stratified by age and ethnicity, with deliberate oversampling of minority ethnic groups. Serum samples obtained from 1,323 residents in 2004 were tested for antibodies to parvovirus B19. Basic demographic data (gender, age, country of birth, and number of children) were also available. Sixty-two percent of the participants were seropositive; corrected for the oversampling the estimated prevalence in the Amsterdam adult population was 61%. No specific predictors or risk groups for seropositivity were identified. In our urban adult study population no positive correlation with increasing neither age, nor significant differences between age groups were found. These results imply that almost 40% of the adult Amsterdam population is susceptible to infection. J. Med. Virol. 81:1305-1309, 2009. (c) 2009 Wiley-Liss, Inc.

Sudden deaths following influenza vaccination: can this be expected?

BACKGROUND: In November 2006, four Dutch people, aged 53, 58, 80 and 88, died unexpectedly on the day they had received their influenza vaccination. A rapid epidemiological assessment was needed to quantify the risk of a causal association. METHODS: Using routinely available data on age-stratified population size, cardiovascular mortality, and vaccination coverage, a daily rate and daily risk of sudden death per 5-year age-group was calculated. A cumulative probability that at least one person in four specific age-groups would die on the day of vaccination was calculated using a binomial distribution. No assumptions on deaths in other age groups were included. RESULTS: The overall likelihood that at least one person in each of the four age categories 50-54, 55-59, 80-84 and 85-89 would die suddenly on the day of influenza vaccination in the Netherlands was calculated to be 0.016. This was 330 times more likely than nobody dying in each of these categories, and 45 times less likely than the most probable outcome. CONCLUSION: We concluded that there was a small but real chance of the four deaths occurring without a causal link to the vaccination. Policy decisions regarding unexpected deaths following vaccination can benefit from a rapid epidemiological evaluation.

A template for improved prevention and control of cardiovascular disease in sub-Saharan Africa.

Cardiovascular disease (CVD) is rapidly becoming an important public health problem in sub-Saharan Africa, yet the response so far is often minimal and inadequate. While there is, undoubtedly, a 'double burden of disease' (persisting infectious diseases co-existing with emerging non-communicable disease), this is hardly reflected in current health planning, possibly due to a limited appreciation of the changing pattern of CVD and CVD risk factor exposure. In a situation where there are also considerable budget constraints and well-established infectious disease priorities, it is difficult to implement effective interventions for prevention or treatment of CVD. Yet such planning is urgently needed and a template for a comprehensive programme, adaptable to local situations, is presented here. The first step is to raise awareness and create evidence-based commitment among policy-makers, which could lead to the establishment of a multi-sectoral CVD unit at national level. Programmes need to focus on prevention of modifiable risk factors at population level, involving a wide range of institutions and individuals. Recommended strategies include decentralizing the design and implementation of programmes, with appropriate standardized surveillance of major risk factors, all complemented by operational, epidemiological and basic research.

HIV-2 does not protect against HIV-1 infection in a rural community in Guinea-Bissau.

OBJECTIVE: To examine the putative protective effect of HIV-2 infection against subsequent HIV-1 infection. DESIGN: Retrospective analysis of data from two cross-sectional surveys in the same community. METHODS: Two surveys between 1989 and 1998 in a rural area in northwestern Guinea-Bissau provided data from residents aged 15-59 years. HIV testing was done in the first survey. In the second survey, tests were made for both HIV and syphilis, and data on sociodemographic factors and sexual behaviour, including commercial sex work, were gathered. Qualitative polymerase chain reaction amplification of HIV-1 and HIV-2 viral DNA was performed on serologically dually reactive samples. RESULTS: Of the 2276 eligible adult villagers initially tested, 60% (1360) provided a second sample. Of 110 HIV-2-infected subjects, 17 became additionally infected with HIV-1 [incidence rate (IR), 26.3/1000 person-years observation]. Of the 1250 HIV-seronegative subjects, 24 became infected with HIV-1 (IR, 2.8/1000 person-years observation). The incidence rate ratio (IRR), comparing the incidence rate in HIV-2-infected people with the rate in HIV-seronegative subjects, was > 1 in all three "risk groups": men, female commercial sex workers, and other women. The overall estimate of the IRR, adjusted for age group and risk group, was 3.24 (confidence interval, 1.5-7.1). CONCLUSIONS: There was no protective effect of HIV-2 in this population. HIV-2 cannot be regarded as a vaccine, but, instead, may be a risk factor for HIV-1 infection.