Pneumococcal Vaccines and Flu Preparedness

Emory University, Atlanta, Georgia, United States
Science (Impact Factor: 33.61). 05/2007; 316(5821):49-50. DOI: 10.1126/science.316.5821.49c
Source: PubMed
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    • "Influenza virus is a major cause of respiratory disease and bacterial infection associated with influenza often increases morbidity and mortality [1,2]. Viral and bacterial co-infection is a common cause of death in seasonal [3-8] and pandemic influenza [9-13]. "
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    ABSTRACT: Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear. In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined. The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation. Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous down-regulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important co-infection.
    BMC Infectious Diseases 07/2011; 11(1):201. DOI:10.1186/1471-2334-11-201 · 2.61 Impact Factor
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    • "In adults from industrialized countries, pneumococcal pneumonia accounts for at least 30% of all cases of community-acquired pneumonia admitted to hospital, with a fatality rate of 11% to 44% [4]. In addition, co-infection of influenza patients with S. pneumoniae is known to exacerbate their clinical outcome [4]: for example, 50% or more of the flu-associated mortality in the 1918-1919 Spanish Flu epidemic is believed to have resulted from pneumococcal superinfections [8,9], and S. pneumoniae co-infection has been specifically correlated with the severity of the recent H1N1 pandemic influenza [10]. The rate of antibiotic resistance in S. pneumoniae has escalated dramatically since penicillin-resistant strains were first detected in the 1970s [11-15]. "
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    ABSTRACT: Streptococcus pneumoniae is a globally important pathogen. The Gram-positive diplococcus is a leading cause of pneumonia, otitis media, bacteremia, and meningitis, and antibiotic resistant strains have become increasingly common over recent years. Alanine racemase is a ubiquitous enzyme among bacteria and provides the essential cell wall precursor, D-alanine. Since it is absent in humans, this enzyme is an attractive target for the development of drugs against S. pneumoniae and other bacterial pathogens. Here we report the crystal structure of alanine racemase from S. pneumoniae (AlrSP). Crystals diffracted to a resolution of 2.0 Å and belong to the space group P3121 with the unit cell parameters a = b = 119.97 Å, c = 118.10 Å, α = β = 90° and γ = 120°. Structural comparisons show that AlrSP shares both an overall fold and key active site residues with other bacterial alanine racemases. The active site cavity is similar to other Gram positive alanine racemases, featuring a restricted but conserved entryway. We have solved the structure of AlrSP, an essential step towards the development of an accurate pharmacophore model of the enzyme, and an important contribution towards our on-going alanine racemase structure-based drug design project. We have identified three regions on the enzyme that could be targeted for inhibitor design, the active site, the dimer interface, and the active site entryway.
    BMC Microbiology 05/2011; 11(1):116. DOI:10.1186/1471-2180-11-116 · 2.73 Impact Factor
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    • "To estimate age-specific influenza and pneumonia incidence, we applied estimates of age-specific excess population mortality in 13 countries, and scaled the pneumonia and influenza incidence in proportion to the observed excess pneumococcal and influenza-related mortality in the US (0.39%), assuming 30% of persons had influenza [57]. When performing the calibration, we also assumed that 30% of pneumonia cases were bacteremic in a severe pandemic [55]. The largest increase in incidence was observed among influenza cases in the 18 - 49 year age group (4-fold). "
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    ABSTRACT: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.
    BMC Infectious Diseases 01/2010; 10(1):14. DOI:10.1186/1471-2334-10-14 · 2.61 Impact Factor
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