Risk factors for hepatitis E virus seropositivity in Dutch blood donors

Background: A marked increase of hepatitis E cases has recently been observed in the Netherlands. Causes of the (re-)emergence of hepatitis E virus (HEV) and exact sources and routes of transmission of HEV infection are currently unknown. We aimed to identify risk factors for HEV seropositivity. Methods: Using the Wantai EIA, 2100 plasma samples of blood donors from all over the Netherlands aged 18-70 years were tested for anti-HEV IgG antibodies. A questionnaire on socio-demographic characteristics, health, and potential risk factors for HEV exposure was sent to these participants. Results: The overall IgG-seroprevalence was 31% (648/2100) and increased with age. Several food products were independently associated with IgG-seropositivity in a multivariate analysis adjusting for age and gender among 1562 participants who completed the questionnaire: traditional Dutch dry raw sausages called "cervelaat", "fijnkost", "salami" and "salametti" which are generally made from raw pork and beef (aOR 1.5; 95%CI 1.2-1.9), frequent consumption of bovine steak (aOR 1.3; 95%CI 1.0-1.7), and frequent consumption of smoked beef (aOR 1.3 95%CI 1.0-1.7). Although not frequently reported, contact with contaminated water was also a risk factor for seropositivity (aOR 2.5; 95%CI 1.5-4.4). Lower seroprevalence was associated with eating raspberries, going out for dinner, and contact with wild animals and dogs. Conclusion: Several pork food products, mainly dry raw sausages, and contact with contaminated water were associated with past HEV infection in the Netherlands. Further investigation is needed into the prevalence and infectivity of HEV in these risk factor food products, as well as investigation of the production methods and possible origin of HEV-contamination within these sausages, e.g. very small amounts of pork liver, pig-derived blood products as food additive, or the pork muscle tissue

Potential effectiveness of prophylactic HPV immunization for men who have sex with men in the Netherlands: A multi-model approach.

Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands. We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM. Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence

HPV and anal cancer in HIV-infected individuals: a review

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long ru

HPV and anal cancer in HIV-infected individuals: a review

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long ru

Risk factors for hepatitis E virus seropositivity in Dutch blood donors

Background: A marked increase of hepatitis E cases has recently been observed in the Netherlands. Causes of the (re-)emergence of hepatitis E virus (HEV) and exact sources and routes of transmission of HEV infection are currently unknown. We aimed to identify risk factors for HEV seropositivity. Methods: Using the Wantai EIA, 2100 plasma samples of blood donors from all over the Netherlands aged 18-70 years were tested for anti-HEV IgG antibodies. A questionnaire on socio-demographic characteristics, health, and potential risk factors for HEV exposure was sent to these participants. Results: The overall IgG-seroprevalence was 31% (648/2100) and increased with age. Several food products were independently associated with IgG-seropositivity in a multivariate analysis adjusting for age and gender among 1562 participants who completed the questionnaire: traditional Dutch dry raw sausages called "cervelaat", "fijnkost", "salami" and "salametti" which are generally made from raw pork and beef (aOR 1.5; 95%CI 1.2-1.9), frequent consumption of bovine steak (aOR 1.3; 95%CI 1.0-1.7), and frequent consumption of smoked beef (aOR 1.3 95%CI 1.0-1.7). Although not frequently reported, contact with contaminated water was also a risk factor for seropositivity (aOR 2.5; 95%CI 1.5-4.4). Lower seroprevalence was associated with eating raspberries, going out for dinner, and contact with wild animals and dogs. Conclusion: Several pork food products, mainly dry raw sausages, and contact with contaminated water were associated with past HEV infection in the Netherlands. Further investigation is needed into the prevalence and infectivity of HEV in these risk factor food products, as well as investigation of the production methods and possible origin of HEV-contamination within these sausages, e.g. very small amounts of pork liver, pig-derived blood products as food additive, or the pork muscle tissue

Comparison of different assays to assess human papillomavirus (HPV) type 16- and 18-specific antibodies after HPV infection and vaccination

We compared the measurement of human papillomavirus (HPV)-specific serum antibody levels with the virus-like-particle multiplex immunoassay (VLP-MIA), competitive Luminex immunoassay (cLIA), and glutathione S-transferase (GST) L1-based MIA. Using a large panel of serum samples, these assays showed mutually good correlations for both naturally induced and vaccine-derived HPV-specific antibody levels. However, an adaptation of the GST L1-based MIA resulted in an improved correlation with both cLIA and VLP-MI

Association of HIV Infection With Anal and Penile Low-Risk Human Papillomavirus Infections Among Men Who Have Sex With Men in Amsterdam: The HIV & HPV in MSM Study

This study among men who have sex with men (MSM) aimed to (1) assess prevalence of anogenital low-risk human papillomavirus (lrHPV) infections, (2) evaluate associations with HIV infection, and (3) investigate lrHPV concordance. In 2010 to 2011, MSM 18 years or older were recruited in Amsterdam, the Netherlands, and provided anal and penile self-swabs (HIV & HPV in MSM study). Using the HPV SPF10-PCR/DEIA/LiPA25 system, the presence of lrHPV types 6, 11, 34, 40, 42, 43, 44, 53, 54, 66, 68/73, 70, and 74 could be detected. Logistic regression with generalized estimating equations was used to assess the independent effect of HIV on lrHPV infections. The model was repeated for lrHPV subcategories (nononcogenic and weakly oncogenic infections separately). Concordance was defined as detection of the same lrHPV type in both self-swabs of one individual. A total of 778 MSM were included, of whom 317 (41%) were HIV positive (median CD4 count at enrollment, 530 cells/mm). Prevalence of anal lrHPV was 45% (95% confidence interval [CI], 41%-50%) in HIV-negative MSM and 69% (95% CI, 64%-74%) in HIV-positive MSM. Prevalence of penile lrHPV was 20% (95% CI, 16%-24%) and 37% (95% CI, 31%-42%), respectively. In multivariable analysis, HIV infection was independently associated with anal (adjusted odds ratio [aOR], 1.9; 95% CI, 1.5-2.3) and penile lrHPV (aOR, 2.0; 95% CI, 1.4-2.7). Nononcogenic and weakly oncogenic lrHPV subcategories showed a similar pattern of association. Anal lrHPV infections were strongly associated with the presence of a type-concordant penile infection (aOR, 5.8; 95% CI, 4.4-7.5) and vice versa (aOR, 5.7; 95% CI, 4.4-7.5). Anal and penile infections with lrHPV are common in MSM. HIV infection was an independent determinant for lrHPV infection

Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive MSM and association with persistence

Does anal HPV viral load explain the difference in anal HPV persistence between HIV-negative and -positive men who have sex with men (MSM)? MSM 18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped (SPF10-PCR-DEIA-LIPA(25)-system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV-negative and -positive men using ranksum test. Persistence was defined as 3 positive samples for the same HPV-type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18 8.6 (95%CI 2.7-27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ significantly between HIV-negative and -positive MSM (P=0.7; P=0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). No difference in anal HPV viral load was found between HIV-positive and HIV-negative MSM. HPV 16/18 viral load is an independent determinant of type-specific persistenc

Association of HIV Infection With Anal and Penile Low-Risk Human Papillomavirus Infections Among Men Who Have Sex With Men in Amsterdam: The HIV & HPV in MSM Study

This study among men who have sex with men (MSM) aimed to (1) assess prevalence of anogenital low-risk human papillomavirus (lrHPV) infections, (2) evaluate associations with HIV infection, and (3) investigate lrHPV concordance. In 2010 to 2011, MSM 18 years or older were recruited in Amsterdam, the Netherlands, and provided anal and penile self-swabs (HIV & HPV in MSM study). Using the HPV SPF10-PCR/DEIA/LiPA25 system, the presence of lrHPV types 6, 11, 34, 40, 42, 43, 44, 53, 54, 66, 68/73, 70, and 74 could be detected. Logistic regression with generalized estimating equations was used to assess the independent effect of HIV on lrHPV infections. The model was repeated for lrHPV subcategories (nononcogenic and weakly oncogenic infections separately). Concordance was defined as detection of the same lrHPV type in both self-swabs of one individual. A total of 778 MSM were included, of whom 317 (41%) were HIV positive (median CD4 count at enrollment, 530 cells/mm). Prevalence of anal lrHPV was 45% (95% confidence interval [CI], 41%-50%) in HIV-negative MSM and 69% (95% CI, 64%-74%) in HIV-positive MSM. Prevalence of penile lrHPV was 20% (95% CI, 16%-24%) and 37% (95% CI, 31%-42%), respectively. In multivariable analysis, HIV infection was independently associated with anal (adjusted odds ratio [aOR], 1.9; 95% CI, 1.5-2.3) and penile lrHPV (aOR, 2.0; 95% CI, 1.4-2.7). Nononcogenic and weakly oncogenic lrHPV subcategories showed a similar pattern of association. Anal lrHPV infections were strongly associated with the presence of a type-concordant penile infection (aOR, 5.8; 95% CI, 4.4-7.5) and vice versa (aOR, 5.7; 95% CI, 4.4-7.5). Anal and penile infections with lrHPV are common in MSM. HIV infection was an independent determinant for lrHPV infection