application s abstract): A K24 award would afford the candidate the opportunity to attain the following objectives: 1) Short-term Objectives: Determine the epidemiology of Streptococcus pneumoniae infections in HIV-infected patients and establish the optimum clinical conditions necessary to facilitate utilization of an innovative, tailored, immunogenic and safe vaccine. 2) Long-term Objectives: The candidate has become proficient at pulse field gel electrophoresis (PFGE) and computer assisted gel analysis. This award will allow her to increase her current technical ability while realizing her aspiration of performing clinical trials. She will obtain her MPH in Epidemiology at the University of Pittsburgh School of Medicine s Program in Clinical Effectiveness/Evaluation Sciences and the Graduate School of Public Health with a focus on epidemiological methods, design of clinical trials, data management and analyses. The candidate will be able to synthesize her technical expertise in bacterial subtyping with her desire to prevent bacterial disease in high risk populations. S. pneumoniae disease is associated with more deaths than any other vaccine- preventable bacterial pathogen. While the 23-valent pneumococcal polysaccharide vaccine covers the majority of invasive serotypes, this vaccine has inferior immunogenicity in HIV-infected patients with CD4 lymphocyte counts <500/mm3. Although the efficacy of one conjugate vaccine has been demonstrated among healthy infants, no efficacy data are available for high- risk populations. The candidate proposes a three tiered approach to preventing pneumococcal disease in HIV infected patients: 1) Using a regional database of over 2000 patients with invasive S. pneumoniae, the candidate will compare serotypes, antibiograms, and case fatality rates between HIV-infected and uninfected individuals. The effect of viral load, and CD4 count on the incidence of recurrent invasive disease will be assessed. The molecular epidemiology of recurrent disease will be performed by comparing PFGE subtypes with dendrograms of genetic relatedness. The HIV-infected patients she sees in the Pittsburgh Aids Center for Treatment (PACT) clinic will be the subjects for two randomized, double-blind vaccine trials. The effect of viral load and HAART on the immunogenicity of the pneumococcal polysaccharide and conjugate vaccines will be assessed. Pneumococcal antibody concentrations will be analyzed by logistic regression to assess the effect of initial viral load and CD4 lymphocyte count. All patients who exhibit a greater that 3-fold transient rise in HIV-1 RNA levels 2 and 4 weeks postimmunization will be evaluated by Fisher's Exact and McNemar's Tests.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23AI001788-01
Application #
6147584
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Sager, Polly R
Project Start
2000-09-30
Project End
2005-05-31
Budget Start
2000-09-30
Budget End
2001-05-31
Support Year
1
Fiscal Year
2000
Total Cost
$124,686
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Pandya, Gagan A; McEllistrem, M Catherine; Venepally, Pratap et al. (2011) Monitoring the long-term molecular epidemiology of the pneumococcus and detection of potential 'vaccine escape' strains. PLoS One 6:e15950
McEllistrem, M Catherine; Ransford, Jennifer V; Khan, Saleem A (2007) Characterization of in vitro biofilm-associated pneumococcal phase variants of a clinically relevant serotype 3 clone. J Clin Microbiol 45:97-101
Noller, Anna C; McEllistrem, M Catherine; Shutt, Kathleen A et al. (2006) Locus-specific mutational events in a multilocus variable-number tandem repeat analysis of Escherichia coli O157:H7. J Clin Microbiol 44:374-7
McEllistrem, M Catherine; Adams, Jennifer M; Shutt, Kathleen et al. (2005) Erythromycin-nonsusceptible Streptococcus pneumoniae in children, 1999-2001. Emerg Infect Dis 11:969-72
McEllistrem, M Catherine; Adams, Jennifer M; Patel, Kartik et al. (2005) Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 40:1738-44
McEllistrem, M Catherine; Carman, Robert J; Gerding, Dale N et al. (2005) A hospital outbreak of Clostridium difficile disease associated with isolates carrying binary toxin genes. Clin Infect Dis 40:265-72
McEllistrem, M Catherine; Noller, Anna C; Visweswaran, Shyam et al. (2004) Serotype 14 variants of the France 9V(-3) clone from Baltimore, Maryland, can be differentiated by the cpsB gene. J Clin Microbiol 42:250-6
McEllistrem, M Catherine; Kolano, John A; Pass, Margaret A et al. (2004) Correlating epidemiologic trends with the genotypes causing meningococcal disease, Maryland. Emerg Infect Dis 10:451-6
McEllistrem, M Catherine; Adams, Jennifer; Mason, Edward O et al. (2003) Epidemiology of acute otitis media caused by Streptococcus pneumoniae before and after licensure of the 7-valent pneumococcal protein conjugate vaccine. J Infect Dis 188:1679-84
McEllistrem, M Catherine; Mendelsohn, Aaron B; Pass, Margaret A et al. (2002) Recurrent invasive pneumococcal disease in individuals with human immunodeficiency virus infection. J Infect Dis 185:1364-8

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