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Berlin Brandenburg

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  • 2010  (12)
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  • 2010  (12)
  • 1
    Language: English
    In: The Journal of infectious diseases, 01 January 2010, Vol.201(1), pp.42-51
    Description: Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.
    Keywords: Anti-Bacterial Agents -- Therapeutic Use ; Azithromycin -- Therapeutic Use ; Chlamydia Infections -- Drug Therapy
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: The Journal of infectious diseases, 15 June 2010, Vol.201(12), pp.1839-48
    Description: Haemophilus ducreyi causes chancroid, a genital ulcer disease. Among human volunteers, the majority of experimentally infected individuals fail to clear the infection and form pustules. Here, we investigated the role played by CD4(+)FOXP3(+) regulatory T (T(reg)) cells in the formation of pustules. In pustules, there was a significant enrichment of CD4(+)FOXP3(+) T cells, compared with that in peripheral blood. The majority of lesional FOXP3(+) T cells were CD4(+), CD25(+), CD127(lo/-), and CTLA-4(+). FOXP3(+) T cells were found throughout pustules but were most abundant at their base. Significantly fewer lesional CD4(+)FOXP3(+) T cells expressed interferon gamma, compared with lesional CD4(+)FOXP3(-) effector T cells. Depletion of CD4(+)CD25(+) T cells from the peripheral blood of infected and uninfected volunteers significantly enhanced proliferation of H. ducreyi-reactive CD4(+) T cells. Our results indicate that the population of CD4(+)CD25(+)CD127(lo/-)FOXP3(+) T(reg) cells are expanded at H. ducreyi-infected sites and that these cells may play a role in suppressing the host immune response to the bacterium.
    Keywords: Immune Tolerance ; Cd4-Positive T-Lymphocytes -- Immunology ; Forkhead Transcription Factors -- Analysis ; Haemophilus Infections -- Immunology ; Haemophilus Ducreyi -- Immunology ; T-Lymphocytes, Regulatory -- Immunology
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 3
    In: Infection and Immunity, 2010, Vol. 78(9), p.3898
    ISSN: 0019-9567
    ISSN: 00199567
    Source: American Society of Microbiology
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  • 4
    Language: English
    In: Infection and immunity, September 2010, Vol.78(9), pp.3898-904
    Description: Haemophilus ducreyi must adapt to the environment of the human host to establish and maintain infection in the skin. Bacteria generally utilize stress response systems, such as the CpxRA two-component system, to adapt to hostile environments. CpxRA is the only obvious two-component system contained in the H. ducreyi genome and negatively regulates the lspB-lspA2 operon, which encodes proteins that enable the organism to resist phagocytosis. We constructed an unmarked, in-frame H. ducreyi cpxA deletion mutant, 35000HPDeltacpxA. In human inoculation experiments, 35000HPDeltacpxA formed papules at a rate and size that were significantly less than its parent and was unable to form pustules compared to the parent. CpxA usually has kinase and phosphatase activities for CpxR, and the deletion of CpxA leads to the accumulation of activated CpxR due to the loss of phosphatase activity and the ability of CpxR to accept phosphate groups from other donors. Using a reporter construct, the lspB-lspA2 promoter was downregulated in 35000HPDeltacpxA, confirming that CpxR was activated. Deletion of cpxA downregulated DsrA, the major determinant of serum resistance in the organism, causing the mutant to become serum susceptible. Complementation in trans restored parental phenotypes. 35000HPDeltacpxA is the first H. ducreyi mutant that is impaired in its ability to form both papules and pustules in humans. Since a major function of CpxRA is to control the flow of protein traffic across the periplasm, uncontrolled activation of this system likely causes dysregulated expression of multiple virulence determinants and cripples the ability of the organism to adapt to the host.
    Keywords: Bacterial Proteins -- Physiology ; Haemophilus Ducreyi -- Pathogenicity ; Protein Kinases -- Physiology
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 5
    In: Infection and Immunity, 2010, Vol. 78(3), p.1176
    Description: Haemophilus ducreyi is an extracellular pathogen of human epithelial surfaces that resists human antimicrobial peptides (APs). The organism's genome contains homologs of genes sensitive to antimicrobial peptides (sap operon) in nontypeable Haemophilus influenzae. In this study, we characterized the sap-containing loci of H. ducreyi 35000HP and demonstrated that sapA is expressed in broth cultures and H. ducreyi-infected tissue; sapA is also conserved among both class I and class II H. ducreyi strains. We constructed a nonpolar sapA mutant of H. ducreyi 35000HP, designated 35000HPsapA, and compared the percent survival of wild-type 35000HP and 35000HPsapA exposed to several human APs, including alpha-defensins, beta-defensins, and the cathelicidin LL-37. Unlike an H. influenzae sapA mutant, strain 35000HPsapA was not more susceptible to defensins than strain 35000HP was. However, we observed a significant decrease in the survival of strain 35000HPsapA after exposure to LL-37, which was complemented by introducing sapA in trans. Thus, the Sap transporter plays a role in resistance of H. ducreyi to LL-37. We next compared mutant strain 35000HPsapA with strain 35000HP for their ability to cause disease in human volunteers. Although both strains caused papules to form at similar rates, the pustule formation rate at sites inoculated with 35000HPsapA was significantly lower than that of sites inoculated with 35000HP (33.3% versus 66.7%; P = 0.007). Together, these data establish that SapA acts as a virulence factor and as one mechanism for H. ducreyi to resist killing by antimicrobial peptides. To our knowledge, this is the first demonstration that an antimicrobial peptide resistance mechanism contributes to bacterial virulence in humans.
    Keywords: Medicine ; Biology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 6
    In: Perspectives on Sexual and Reproductive Health, March 2010, Vol.42(1), pp.43-48
    Description: CONTEXT: Adolescent pregnancy prevention is difficult because adolescent sex is intermittent. Understanding why sexually experienced adolescents have sex after a period of abstinence will help clinicians to tailor counseling. METHODS: For up to 4.5 years between 1999 and 2006, a sample of 354 adolescent women recruited at urban primary care clinics were interviewed and tested for STDs every three months, and were asked to complete three months of daily diaries twice a year. Survival analyses were used to estimate associations between intrapersonal, relationship and STD‐related characteristics and the risk of ending an abstinence period with sex. RESULTS: Participants reported 9,236 abstinence periods, which averaged 31 days. The risk that an abstinence period ended with sex increased steeply for periods of fewer than 17 days (short), rose less steeply for 17–39‐day (intermediate) periods and was fairly steady for longer periods. For short periods, the risk increased with age, sexual interest, positive mood, partner support, relationship quality and history of STD diagnosis more than three months ago (hazard ratios, 1.02–1.2); it decreased as negative mood increased (0.98) and was reduced among adolescents with a recent STD diagnosis (0.9). For intermediate periods, the association with a recent STD diagnosis became positive (1.4). For long periods, sex was associated only with age, sexual interest and relationship quality. CONCLUSIONS: To provide targeted and timely sexual health counseling, clinicians may want to ask adolescents not only whether they are sexually active but also when they last had sex.
    Keywords: Sexual Abstinence -- Research ; Teenage Sexual Behavior -- Research ; Sexual Intercourse -- Research;
    ISSN: 1538-6341
    E-ISSN: 1931-2393
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  • 7
    Language: English
    In: Sexually Transmitted Diseases, April, 2010, Vol.37(4), p.248(5)
    Description: Background: Population-based studies suggest that acquisition of herpes simplex virus 2 (HSV 2) is most common between ages 20 and 29, especially in minority women. We examined HSV 2 infection and viral shedding in a cohort of young women. Methods: Women. age 18 to 24 (median 21), who were part of an observational cohort enrolled between ages 14 to 17, had blood obtained for HSV 2 antibody. Intensive diary collections on sexual behavior and genital symptoms and weekly vaginal swabs were obtained at regular intervals. Results: HSV 2 antibodies were detected in 43 of 127 participants (33.9%), only 4 of whom were previously known to be positive. Factors associated with a positive test included older age, years of sexual activity, and number of lifetime partners. Testing for HSV 2 DNA by polymerase chain reaction on weekly vaginal swabs from a 13-week sampling period for each HSV 2 antibody positive participant showed 32 of 43 (74.4%) were positive at least once. The positive predictive value of pain for viral shedding was poor. Conclusions: HSV 2 infection is very common among young adult women, but symptomatic genital herpes is not. Shedding of HSV 2 DNA can be detected in most antibody positive persons. Early intervention strategies will be needed to control HSV 2 infection. DOI: 10.1097/OLQ.0b013e3181d4f866
    Keywords: Herpes Simplex -- Risk Factors ; Herpes Simplex -- Development And Progression ; Herpes Simplex -- Diagnosis ; Herpes Simplex Virus -- Health Aspects
    ISSN: 0148-5717
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  • 8
    Language: English
    In: Population health management, December 2010, Vol.13(6), pp.325-30
    Description: Capacity constraints and efficiency considerations require that disease management programs identify patients most likely to benefit from intervention. Predictive modeling with available administrative data has been used as a strategy to match patients with appropriate interventions. Administrative data, however, can be plagued by problems of incompleteness and delays in processing. In this article, we examine the effects of these problems on the effectiveness of using administrative data to identify suitable candidates for disease management, and we evaluate various proposed solutions. We build prospective models using regression analysis and evaluate the resulting stratification algorithms using R² statistics, areas under receiver operator characteristic curves, and cost concentration ratios. We find delays in receipt of data reduce the effectiveness of the stratification algorithm, but the degree of compromise depends on what proportion of the population is targeted for intervention. Surprisingly, we find that supplementing partial data with a longer panel of more outdated data produces algorithms that are inferior to algorithms based on a shorter window of more recent data. Demographic data add little to algorithms that include prior claims data, and are an inadequate substitute when claims data are unavailable. Supplementing demographic data with additional information on self-reported health status improves the stratification performance only slightly and only when disease management is targeted to the highest risk patients. We conclude that the extra costs associated with surveying patients for health status information or retrieving older claims data cannot be justified given the lack of evidence that either improves the effectiveness of the stratification algorithm.
    Keywords: Health Promotion ; Models, Statistical ; Information Management -- Organization & Administration
    ISSN: 19427891
    E-ISSN: 1942-7905
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  • 9
    In: Sexually Transmitted Diseases, 2010, Vol.37(4), pp.248-252
    Description: BACKGROUND:: Population-based studies suggest that acquisition of herpes simplex virus 2 (HSV 2) is most common between ages 20 and 29, especially in minority women. We examined HSV 2 infection and viral shedding in a cohort of young women. METHODS:: Women, age 18 to 24 (median 21), who were part of an observational cohort enrolled between ages 14 to 17, had blood obtained for HSV 2 antibody. Intensive diary collections on sexual behavior and genital symptoms and weekly vaginal swabs were obtained at regular intervals. RESULTS:: HSV 2 antibodies were detected in 43 of 127 participants (33.9%), only 4 of whom were previously known to be positive. Factors associated with a positive test included older age, years of sexual activity, and number of lifetime partners. Testing for HSV 2 DNA by polymerase chain reaction on weekly vaginal swabs from a 13-week sampling period for each HSV 2 antibody positive participant showed 32 of 43 (74.4%) were positive at least once. The positive predictive value of pain for viral shedding was poor. CONCLUSIONS:: HSV 2 infection is very common among young adult women, but symptomatic genital herpes is not. Shedding of HSV 2 DNA can be detected in most antibody positive persons. Early intervention strategies will be needed to control HSV 2 infection.
    Keywords: Herpes Simplex ; Risk Factors ; Development and Progression ; Diagnosis ; Herpes Simplex Virus ; Health Aspects ; Medicine;
    ISSN: 0148-5717
    E-ISSN: 15374521
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  • 10
    Language: English
    In: Chronic Illness, June 2010, Vol.6(2), pp.83-88
    Description: In 2003, the Indiana Office of Medicaid Policy and Planning launched the Indiana Chronic Disease Management Program (ICDMP), a programme intended to improve the health and healthcare utilization of 15,000 Aged, Blind and Disabled Medicaid members living with diabetes and/or congestive heart failure in Indiana. Within ICDMP, programme components derived from the Chronic Care Model and education based on an integrated theoretical framework were utilized to create a telephonic care management intervention that was delivered by trained, non-clinical Care Managers (CMs) working under the supervision of a Registered Nurse. CMs utilized computer-assisted health education scripts to address clinically important topics, including medication adherence, diet, exercise and prevention of disease-specific complications. Employing reflective listening techniques, barriers to optimal self-management were assessed and members were encouraged to engage in health-improving actions. ICDMP evaluation results suggest that this low-intensity telephonic intervention shifted utilization and lowered costs. We discuss this patient-centred method for motivating behaviour change, the theoretical constructs underlying the scripts and the branched-logic format that makes them suitable to use as a computer-based application. Our aim is to share these public-domain materials with other programmes.
    Keywords: Brief Intervention ; Chronic Disease Management ; Health Belief Model ; Stages of Change ; Telephonic Education ; Public Health
    ISSN: 1742-3953
    E-ISSN: 1745-9206
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