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author:("muris, dalys")
1.  Phase IIa Study of the Immunogenicity and Safety of the Novel Staphylococcus aureus Vaccine V710 in Adults with End-Stage Renal Disease Receiving Hemodialysis 
Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 μg V710 (with or without adjuvant), 90 μg V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ≥2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ≥2.5 GMFR in anti-IsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.
PMCID: PMC3428394  PMID: 22837094
2.  Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males 
The New England journal of medicine  2011;364(5):401-411.
Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men.
We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status.
In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001).
Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; number, NCT00090285.)
PMCID: PMC3495065  PMID: 21288094
3.  Immunogenicity of the Quadrivalent Human Papillomavirus (Type 6/11/16/18) Vaccine in Males 16 to 26 Years Old 
Human papillomavirus (HPV) infection can lead to significant disease in males, including anogenital warts, intraepithelial neoplasias, and several types of oral and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to prevent persistent infection and associated disease related to vaccine HPV types in males. We report the overall immunogenicity results from a trial of the quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men who had sex with men were enrolled into a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study. Serum samples were collected prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination. Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay. Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month 7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV types, black subjects had significantly higher antibody titers at month 7 than did both Caucasian and Asian subjects. An anamnestic antibody response was seen in men seropositive before vaccination. The vaccine was highly immunogenic in males 16 to 23 years of age; responses were comparable to those observed in women. Furthermore, the immune responses were consistent with the established efficacy of the vaccine in the prevention of incident and persistent HPV infection, anogenital warts, and anal intraepithelial neoplasia.
PMCID: PMC3272915  PMID: 22155768
4.  Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults 
Human Vaccines  2011;7(7):768-775.
Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16–26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2 and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs. 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs. 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16–26 years and had a favorable safety profile.
PMCID: PMC3219080  PMID: 21712645
human papillomavirus (HPV); vaccine; safety; male; adult; adolescent
5.  External Genital Human Papillomavirus Prevalence and Associated Factors Among Heterosexual Men on 5 Continents 
Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection.
Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated.
Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence.
Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.
PMCID: PMC3086430  PMID: 21148497
6.  Prevalence of and Risk Factors for Human Papillomavirus (HPV) Infection Among HIV-Seronegative Men Who Have Sex With Men 
Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)–seronegative men who have sex with men (MSM).
Methods. Data were analyzed from 602 MSM aged 16–27 years with ≤5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA.
Results. The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence.
Conclusions. The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection.
PMCID: PMC3086446  PMID: 21148498
7.  Chickenpox Exposure and Herpes Zoster Disease Incidence in Older Adults in the U.S. 
Public Health Reports  2007;122(2):155-159.
Exposure to varicella zoster virus through close contact with people with chickenpox was suggested to boost specific immunity, reducing the risk of herpes zoster (HZ). Since the introduction of the varicella immunization program in the U.S. in 1995, varicella morbidity has decreased substantially. This article examines incidence and risk factors associated with self-reported HZ disease and whether exposure to chickenpox within the previous decade reduces the risk of shingles in this age group.
In 2004, a national random-digit dial telephone survey was used to obtain information on self-reported HZ disease, demographic characteristics, and exposure to children with chickenpox in the past decade. National estimates of the incidence of shingles disease were calculated.
Incidence rate of self-reported HZ was 19 per 1,000 population per year. White individuals were 3.5 times more likely to report shingles than Hispanic individuals (p<0.01). Previous exposure to chickenpox did not protect against HZ disease in this population. Seven percent of adults ≥65 years of age reported exposure to children with chickenpox in the past decade.
Incidence of HZ among individuals ≥65 years of age in the U.S. may be higher than previously described in the literature, with whites being at higher risk for the disease. Currently, the potential contribution of exposure to chickenpox as a mechanism for maintaining cell-mediated immunity against HZ may be limited to a small percentage of the population. Vaccination against HZ may represent the best means of decreasing this disease burden.
PMCID: PMC1820439  PMID: 17357357
8.  Genetic characterization of measles viruses isolated in Turkey during 2000 and 2001 
Virology Journal  2005;2:58.
Molecular epidemiologic studies have made significant contributions to measles surveillance activities by helping to identify source and transmission pathways of the virus. This report describes the genetic characterization of wild-type measles viruses isolated in Turkey in 2000 and 2001.
Wild-type measles viruses were isolated from 24 cases from five provinces in Turkey during 2001. The viruses were analyzed using the standard genotyping protocols. All isolates were classified as genotype D6, the same genotype that was identified in Turkey in previous outbreaks during 1998.
Turkey has begun implementation of a national program to eliminate measles by 2010. Therefore, this baseline genotype data will provide a means to monitor the success of the elimination program.
PMCID: PMC1201177  PMID: 16029506
9.  Varicella Seroprevalence and Molecular Epidemiology of Varicella-Zoster Virus in Argentina, 2002 
Journal of Clinical Microbiology  2004;42(12):5698-5704.
There is limited data on immunity against varicella-zoster virus (VZV) in adults in different parts of Argentina, and it is not known which VZV strains are circulating in Argentina. The objectives of this study were as follows: (i) to evaluate seroprevalence of varicella among adults, assessing the accuracy of clinical history and determining the sociodemographic factors associated with seropositivity; and (ii) to determine the VZV strains circulating in Argentina. A cross-sectional serological survey enrolling 2,807 women aged 15 to 49 years attending public health-care settings in four cities in Argentina (i.e., Buenos Aires, Salta, Mendoza, and Rosario) and one rural area was conducted from August to November 2002. Specimens for identification of VZV strains were obtained from vesicular lesions from 13 pediatric patients with varicella from different areas of the country. PCR amplification was used for genotyping. The overall seroprevalence of varicella antibodies was 98.5% (95% confidence interval, 98.0 to 98.9), ranging from 97.2% in central Buenos Aires to 99.3% in southern Buenos Aires and Salta. Varicella seroprevalence increased with age. Crowding and length of residence in the same place were associated with seropositivity. The positive predictive value of varicella history for immunity to varicella was 99.4%; however, the negative predictive value was 2.5%. The European genotype was identified in all viral specimens. In Argentina, seroprevalence in women more than 15 years old was high regardless of the area of residence. Negative or uncertain varicella history was not a good predictor of immunity. VZV genotype was stable in all areas of the country.
PMCID: PMC535276  PMID: 15583301
10.  Establishment of Diagnostic Cutoff Points for Levels of Serum Antibodies to Pertussis Toxin, Filamentous Hemagglutinin, and Fimbriae in Adolescents and Adults in the United States 
Numerous reports have documented that serologic methods are much more sensitive than culture for the diagnosis of pertussis in adolescents and adults. However, a standardized serologic test for pertussis is not routinely available to most clinicians, and the serologic test levels or cutoff points correlated with diseases have not been determined. The goal of the present study was to examine the distribution of immunoglobulin G (IgG) levels against three Bordetella pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], and fimbria types 2 and 3 [FIM]) and to determine population-based antibody levels for the purpose of establishing such diagnostic cutoff points. Enzyme-linked immunosorbent assays (ELISAs) were performed with sera from >6,000 U.S. residents aged 6 to 49 years who participated in the Third National Health and Nutrition Examination Survey. Mixture models were developed to identify hypothesized exposure groups and establish diagnostic cutoffs. Quantifiable (>20 ELISA units/ml [EU]) anti-FHA and anti-FIM IgG antibodies were common (65 and 62% of individuals, respectively), but quantifiable anti-PT IgG antibodies were less frequent (16%). Given the distributions of antibody levels, an anti-PT IgG level of ≥94 EU was proposed as the diagnostic cutoff point. Application of this cutoff point to culture-confirmed illness in a prior study investigating cough illness yielded a high diagnostic sensitivity (80%) and specificity (93%). A standardized ELISA for anti-PT IgG with a single serum sample appears to be useful for the identification of recent B. pertussis infection in adolescents and adults with cough illness. The PT cutoff point will be further evaluated in prospective studies of confirmed B. pertussis infection.
PMCID: PMC524757  PMID: 15539504
11.  Issues Associated with and Recommendations for Using PCR To Detect Outbreaks of Pertussis 
Journal of Clinical Microbiology  2002;40(8):2801-2805.
Two outbreaks of respiratory tract illness associated with prolonged cough occurring in 1998 and 1999 in New York State were investigated. A PCR test for Bordetella pertussis was primarily used by a private laboratory to confirm 680 pertussis cases. Several clinical specimens had positive culture results for B. pertussis during both outbreaks, which confirmed that B. pertussis was circulating during the outbreaks. However, testing by the New York State Department of Health reference laboratory suggested that some of the PCR results may have been falsely positive. In addition, features of the outbreak that suggested that B. pertussis may not have been the primary agent of infection included a low attack rate among incompletely vaccinated children and a significant amount of illness among patients testing PCR negative for B. pertussis. These investigations highlight the importance of appropriate clinical laboratory quality assurance programs, of the limitations of the PCR test, and of interpreting laboratory results in context of clinical disease.
PMCID: PMC120629  PMID: 12149333

Results 1-11 (11)