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Adults over the age of 65 are at increased risk for influenza and pneumococcal infections; particularly those residing in nursing homes (NHs). Despite the efficacy of influenza and pneumococcal vaccinations, vaccination receipt rates among NH residents remain well below federal recommendations and racial/ethnic disparities exist. Minority NH residents (non-Hispanic Blacks and Hispanics) are less likely to be offered either vaccination and are more likely to refuse them compared to their non-minority counterparts (non-Hispanic Whites). In the past decade, requirements have been implemented to increase vaccination coverage in NHs, but there is little documentation regarding current racial/ethnic disparities in vaccination receipt. Furthermore, activities important to resident care delivery and the prevention of care deficiencies such as infections are primarily dependent on the care provided by certified nursing assistants (CNAs). For these reasons, current research examining racial/ethnic disparities in vaccination receipt in NHs is needed and more attention directed towards CNAs is necessary to improve resident care delivery and outcomes related to infection prevention and control. This dissertation furthers our understanding of racial/ethnic disparities in influenza and pneumococcal vaccination coverage among minority NH residents and the role racial/ethnic diverse CNAs play in infection prevention and control. Chapter One introduces the problem of health disparities in nursing homes (NHs) related to differences in preventative vaccination receipt by racial/ethnic status and the role CNAs play in infection prevention and control. Chapter Two, an integrative literature review on racial/ethnic disparities in NHs, describes racial/ethnic disparities occurring in the NH setting in the context of infection prevention and control and influenza and pneumococcal vaccination receipt along with contributing factors and existing strategies related to policy that have been implemented to address poor care quality. In Chapter Three, facility-level factors related to the CNA’s role and the barriers and facilitators they experience that contribute to infection prevention and control are discussed. In Chapter Four, a systematic review of previous research on racial/ethnic disparities related to influenza and pneumococcal vaccination in NHs, individual, community, and facility-level factors that determine these disparities in influenza and pneumococcal vaccination receipt, along with associated strategies and practices are discussed. In Chapter Five, a national quantitative analysis of vaccination receipt practices (vaccination administered) and reasons for vaccination non-receipt (i.e., not offered versus refused) are presented. The results of this dissertation will inform clinicians and NH administrators as well as future policy and public health interventions and provide evidence needed to improve racial/ethnic minority health and eliminate health disparities.

Le peptidoglycane est un composant majeur de la paroi cellulaire bactérienne dont l'intégrité est essentielle à la survie cellulaire. La biosynthèse du peptidoglycane est un processus régulé faisant intervenir des enzymes de synthèse, les « Penicillin-Binding Proteins », et des hydrolases qui agissent, selon toute vraisemblance, de façon concertée lors de la croissance et de la division bactérienne. La comparaison des génomes bactériens a permis d'identifier un nouveau domaine protéique, probablement impliqué dans le clivage du peptidoglycane, présent uniquement chez les bactéries à Gram positif : le domaine PECACE (PEptidoglycan CArbohydrate Cleavage Enzyme). Ce domaine, prédit pour avoir un repliement tridimensionnel analogue aux domaines catalytiques de la transglycosylase lytique Slt70 d'Escherichia coli et du lysozyme de type G d'oie, pourrait participer au clivage de la liaison glycosidique β(1-4) entre les résidus acide N-acétyl-D-muramique et N-acétyl-D-glucosamine du peptidoglycane. Chez la bactérie pathogène Streptococcus pneumoniae, ce domaine est présent dans la région extracellulaire d'une protéine que nous nommons Pmp23 (Pneumococcal Membrane Protein). La forme recombinante de cette protéine membranaire bitopique de 23 kDa dégrade in vitro des extraits bactériens contenant du peptidoglycane. L'inactivation du gène pmp23 chez S. pneumoniae modifie le comportement de la bactérie en culture, accroît sa sensibilité aux antibiotiques de la famille des β-lactamines et perturbe la localisation du site de division. Ces observations indiquent que Pmp23 est une hydrolase intervenant dans le métabolisme du peptidoglycane septal.

PCR is a rapid, reproducible method for nucleic acid detection. However, this technology displays significant deficiencies when applied in clinical microbiology. This work’s aim was to improve current diagnostics and provide sensitive and quantitative real-time PCRs. Paper I describes the development of a sensitive and specific quantitative real-time PCR for the detection of Streptococcus pneumoniae, based on the Spn9802 DNA fragment. Applied to nasopharyngeal aspirates from 166 pneumonia patients, Spn9802 PCR had a sensitivity of 94% and a specificity of 98%. In Paper II the performance of a ply gene PCR for identification of pneumococcal lower respiratory tract infection (LRTI) was evaluated on bronchoalveloar lavage fluids. At the detection limit 103 genome copies/mL, 89% sensitivity but only 43% specificity was achieved. Paper III shows that S. pneumoniae DNA is detectable in plasma from acutely febrile patients. Sensitivities were low (26-42%) for detection of pneumococcal pneumonia, for bacteraemic pneumococcal pneumonia they were 60-70%. Paper IV describes evaluation of four PCR targets for Haemophilus influenzae detection. A real-time PCR based on the P6 gene was developed and applied to 166 CAP patients, using cut-off of 104 genome copies/mL the assay had a sensitivity of 97% and a specificity of 96%. In paper V, the two real-time PCRs presented in papers I and IV were combined with a PCR for detection of Neisseriae meningitidis. The analytical sensitivity of this multiplex real-time PCR was not affected by using a mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae) in single tubes. Applied to 156 LRTI patients, this PCR had sensitivities over 90% for S. pneumoniae and H. influenzae, and specificities of 89% and 96%, respectively. In conclusion, real-time PCR assays are useful for the diagnosis of S. pneumoniae and H. influenzae. They enable detection after antibiotic installation, and quantification increases the etiological specificity of pneumonia.

Streptococcus pneumoniae[italicized everytime] (S. pneumoniae) causes a spectrum of disease severity, and human host factors likely play a role in this variation. One candidate factor is macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine and upstream regulator of innate immunity. The MIF[italicized when not in parenthesis] promoter contains two functional polymorphisms, a tetranucleotide (CATT) repeat such that MIF expression increases with repeat number from 5-8 and a single nucleotide polymorphism (SNP) leading to a G-to-C transition, which results in increased MIF expression in cell line reporter assays. Emerging data suggest an association between high-expression MIF alleles and inflammatory disease. This study comprised two parts. For the in vitro portion, we hypothesized that peripheral blood monocytic cells (pBMCs) cultured from healthy individuals with low-expressing MIF genotypes (5-CATT alleles or SNP-GG) would have lower MIF content and release than those from individuals with high-expressing MIF genotypes (7-CATT or SNP-C alleles). For the in vivo study, we hypothesized that individuals with low-expressing MIF genotypes would have less severe systemic inflammatory responses than individuals with high-expressing MIF genotypes in response to S. pneumoniae infection. Blood samples and chart findings were collected prospectively at three Connecticut hospitals from 30 inpatients with documented invasive S. pneumoniae infections. Genomic DNA was isolated from host blood, amplified, and genotyped using fragment analysis (CATT repeat) and allelic discrimination (SNP) methods. Fishers exact tests were used to compare genotypes and disease severity. For the in vitro experiments, there were no differences observed in serum MIF levels or MIF content or release from pBMCs based on MIF genotype. In the cohort of patients infected with S. pneumoniae, serum MIF levels among enrolled subjects were significantly higher than the reported normal values, but levels did not vary with genotype or disease severity. The SNP genotype was not correlated with disease severity or occurrence of meningitis. The CATT genotype did not correlate significantly with disease severity or occurrence of meningitis, although there was a trend suggesting an association between the 7-CATT allele and meningitis (p = 0.1188, 8% without meningitis had a 7-CATT allele vs. 40% with meningitis). More patient samples will need to be analyzed in order to definitively elucidate the role of MIF genetics in infection with S. pneumoniae

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2010.

Title from title page of PDF (University of Missouri--St. Louis, viewed Mar. 2, 2010). Includes bibliographical references.

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Background Streptococcus pneumoniae and Staphylococcus aureus are important pathogens causing bacterial infections in children worldwide. At least 93 different serotypes have been identified and recognized in Streptococcus pneumoniae. In Hong Kong, the 7-valent-pneumococcal vaccine (PCV7) has been introduced into the childhood immunisation programme since September 2009, but widespread use of this vaccination may bring about epidemiological changes in the bacteria commonly carried by children. Objectives (i) To examine the changes in carriage, serotype distribution and antibiotic resistance of nasopharyngeal pneumococcal isolates in children before and after the introduction of PCV7 in Hong Kong. (ii) To analyse the association between S. pneumoniae and S. aureus colonisation among young children in Hong Kong following the use of pneumococcal conjugate vaccine. Methods Nasopharyngeal swabs were collected from 1978 and 2211 children aged 2 to 6 years attending day care centres (DCCs) and kindergartens (KGs) in all 18 school districts in Hong Kong in period 1 (1999-2000) and period 2 (2009-2010), respectively. Nasal samples were also collected from the participants in period 2 for detection of S. aureus. E-test and disc diffusion method were used to determine the antibiotic susceptibility. Sequential multiplex PCR and/or the quellung reactions were used for serotyping. A standardized questionnaire was also used to obtain information from children’s parents so as to study the variables associated with the carriage of these two bacteria. Results In the first part of our study, the PCV7 vaccine penetration (at least one dose) in period 2 was 28.1% (622/2211). The nasopharyngeal carriage rate of PCV7 isolates decreased from 12.8% in period 1 to 8.6% in period 2 (P < 0.001). Vaccine serotypes 14 and 18C had decreased significantly while non-vaccine serotypes 19A, 6A, 6C 23A and 15B had increased significantly from period 1 to period 2. Dual penicillin/erythromycin non-susceptibility rates for 19F, 14, 6A and 23A has also been found to increase over the two time periods. In the second part of our study, 27.6% of the children were found to carry S. aureus and the nasal MRSA carriage rate was 1.3%. Molecular typing including staphylococcal cassette chromosome mec (SCCmec), sequence type (ST) and clonal cluster (CC) showed that all the 28 MRSA isolates belonged to SCCmec IV (n = 13) or V (n = 15). Twelve of these isolates had community-associated MRSA genotypes (ST59/SCCmec IV, ST30/SCCmec IV, ST88/SCCmec V), ten isolates had healthcare-associated MRSA genotypes (ST45/SCCmec IV/V, CC5/SCCmec IV and ST630/SCCmec V) and six isolates had novel genotypes (ST10/SCCmec V, CC1/SCCmec IV). spa typing results also indicated an intra- and inter-school transmission of certain MRSA and methicillin-sensitive S. aureus strains. Significant association between S. pneumoniae and S. aureus carriage was not found in this study. Conclusion Our study found that carriage, serotype distribution and antibiotic resistance of nasopharyngeal pneumococcal isolates in children have changed after the use of PCV7 in Hong Kong while association between S. pneumoniae and S. aureus colonisation among young children in Hong Kong was not found. Further studies investigating the five increasing non-PCV7 serotypes are warranted to guide future vaccine policy. / published_or_final_version / Microbiology / Master / Master of Philosophy

BACKGROUND: Streptococcus pneumoniae is the primary causative agent of pneumonia in older adults. Vaccination is the only tool to protect against pneumococcal infection; however, vaccination rates remain far below the Healthy People 2010 objective of 90% coverage. The number one reason for such low rates is attributed to controversy over the protective efficacy of the vaccine in preventing nonbacteremic pneumonia (eg, community-acquired pneumonia [CAP]). OBJECTIVES: The primary objectives of this study were to assess the incidence of pneumonia, pneumonia requiring hospitalization, and pneumonia hospitalization costs. METHODS: In this retrospective cohort study of Medicare beneficiaries aged 65 years in 2003, subjects were selected based on exposure status. Exposure was defined as receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV23). Vaccinated persons were then matched 1:1 on gender and the presence of any comorbidity to unvaccinated persons. Subjects were followed up for 1 year (January 1, 2004 through December 31, 2004). The primary outcomes were pneumonia, pneumonia requiring hospitalization, and hospitalization costs. Mantel-Haenszel chi-square or logit was used to estimate the relative risk (RR) associated with vaccination and each outcome and Proc Ttest was used to test the difference between mean hospital costs of the vaccinated and non-vaccinated. RESULTS: During the follow-up period, 443 patients were diagnosed with pneumonia; 266 had previously been vaccinated and 177 had no documented receipt of prior vaccination. Results of the Chi-square analysis revealed a significant association between vaccination and the risk of pneumonia, as the vaccinated were 50% more likely to develop pneumonia than were the non-vaccinated (Adjusted RR: 1.50; 95% CI: 1.25, 1.81). Approximately 67% of patients diagnosed with pneumonia required hospitalization; of which, 183 were previously vaccinated and 115 had no documented receipt of prior vaccination. There was no association between vaccination and risk of pneumonia requiring hospitalization (P value 0.4001). However, the vaccine was associated with a significant reduction in hospital costs (P value 0.004). CONCLUSIONS: The results of this study suggest that use of the vaccine may be associated with cost savings due to a reduction in hospitalization.