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  • 1
    Publication Date: 2013-05-03
    Description: In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000–2002) and The Gambia (2001–2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true "gold standard" diagnostic test for C. trachomatis . Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the postelimination setting.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 2
    Publication Date: 2015-02-07
    Description: Background.  Circumcision and lower human papillomavirus (HPV) viral loads in men are possibly associated with a reduced risk of HPV transmission to women. However, the association between male circumcision and HPV viral load remains unclear. Methods.  Swab specimens from the glans and shaft of the penis were collected from men enrolled in a circumcision trial in Kisumu, Kenya. GP5+/6+ polymerase chain reaction (PCR) was used to identify HPV DNA types. HPV-16 and HPV-18 loads were measured with a LightCycler real-time PCR and classified as high (〉250 copies/scrape) or low (≤250 copies/scrape). Results.  A total of 1159 men were randomly assigned to undergo immediate circumcision, and 1140 men were randomly assigned to the control arm (these individuals were asked to remain uncircumcised until the study ended). The hazard of acquisition of high-viral load infections in the glans was lower in the circumcision arm, compared with the control arm, for HPV-16 (hazard ratio [HR], 0.32 [95% confidence interval {CI}, .20–.49]) and HPV-18 (HR, 0.34 [95% CI, .21–.54]). The 6-month risk of HPV persistence among men with high-viral load infections in the glans at baseline was lower in the circumcision arm, compared with the control arm, for HPV-16 (risk ratio [RR], 0.36 [95% CI, .18–.72]) and HPV-18 (RR 0.34 [95% CI, .13–.86]). Weaker and less precise results were obtained for shaft samples. Conclusions.  Male circumcision could potentially reduce the risk of HPV transmission to women by reducing the hazard of acquisition, and the risk of persistence of high-HPV viral load infections in the glans in men.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 3
    Publication Date: 2013-11-02
    Description: Background.  We estimated the 72-month efficacy of medical male circumcision (MMC) against herpes simplex virus 2 (HSV-2) incidence among men in the Kisumu MMC randomized trial. Methods.  From 2002 to 2005, 2784 men aged 18–24 were enrolled and randomized 1:1 to immediate circumcision or control. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling was used to estimate the efficacy of MMC on HSV-2 risk. Conventional conditional Cox regression identified multivariable risks for HSV-2 seroconversion. Results.  Among 2044 HSV-2 seronegative men at baseline, the cumulative 72-month HSV-2 incidence was 33.5% (32.7% among circumcised men, 34.6% among uncircumcised men). In weight-adjusted Cox regression, the hazard ratio was 0.88 (95% confidence interval, .77–1.10). In multivariable analyses, risks for HSV-2 included human immunodeficiency virus (HIV) infection, genital ulcer disease (GUD), penile epithelial trauma, multiple recent sex partners, and being married /cohabiting. Conclusions.  MMC had no effect on acquisition of HSV-2 during 72 months of follow-up. The temporal sequence and limited correlation between HSV-2, GUD, and penile epithelial trauma suggests that these are distinct phenomena rather than misclassification of HSV-2 symptoms. Determining the etiology of non–sexually transmitted infection GUD and penile epithelial trauma is needed, as both are commonly occurring risks for HSV-2 and HIV acquisition. Clinical Trials Registration.  NCT0005937.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 4
    Publication Date: 2012-08-09
    Description: Background. Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. Methods. Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. Results. Among 1097 human immunodeficiency virus–negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. Conclusions. These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 5
    Publication Date: 2014-11-25
    Description: We define three types of neighbour-balanced designs for experiments where the units are arranged in a circle or single line in space or time. The designs are balanced with respect to neighbours at distance one and at distance two. The variants come from allowing or forbidding self-neighbours, and from considering neighbours to be directed or undirected. For two of the variants, we give a method of constructing a design for all values of the number of treatments, except for some small values where it is impossible. In the third case, we give a partial solution that covers all sizes likely to be used in practice.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
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