Current Pneumococcal Vaccines Research Articles

Improving Pneumococcal Vaccination Rates in a Community-Based Internal Medicine Resident Clinic

CONTEXTDespite proven benefits of vaccination such as reduced morbidity and mortality, many patients remain out of date on their recommended vaccines. The goal of this pilot project was to develop and test a systematic vaccination review and ordering protocol aimed to increase the percentage of patients who were assessed under current pneumococcal vaccine recommendations by 5%.METHODSThe study location was set in a community-based internal medicine resident clinic in Muskegon, Michigan, with the patient population coming from the same setting. Data from 50 patients who had completed office visit appointments at a resident clinic from January 2016 through April 7th, 2017 were randomly extracted before implementation of the protocol. Two months post-implementation, the authors obtained office visit data from another randomly selected 50 clinic patients for comparison. The nurses and medical assistants in the office had been educated on the pneumonia vaccine protocol based on CDC (United States Centers for Disease Control and Prevention) vaccination guidelines and state registry records. They were also provided copies of the seven-step vaccine assessment and ordering protocol that included obtaining MCIR (Michigan Care Improvement Registry) data to update the patient’s chart for a possible provider order set. Clinic residents were also educated on CDC pneumonia vaccine guidelines, and the authors posted several guideline related posters on clinic walls.RESULTSThe authors initially compared the percentage of patients who providers had assessed regarding their vaccination status before protocol implementation to the percentage of patients after protocol implementation. There was a 10% post-implementation increase in pneumonia vaccination assessment.CONCLUSIONSAlthough the results of this pilot project are obviously limited by methodological and sample size characteristics, the initially measured improvements in vaccination status suggests that this type of systematic protocol approach may warrant further testing in similar settings.

Triptych of the Hermit Saints: pneumococcal polysaccharide vaccines for the elderly.

Pneumococcal pneumonia is a serious disease with considerable morbidity and mortality in the elderly. Despite adequate antibiotic treatment, the long-term mortality of pneumococcal pneumonia remains high. Preventive measures in the form of vaccination, therefore, are warranted. Twenty-three-valent polysaccharide vaccines have a broad coverage but limited efficacy. Pneumococcal conjugate vaccines have been shown in children to be able to prevent invasive and mucosal pneumococcal diseases. It should be realized that the serotype composition of current pneumococcal conjugate vaccines is not tailored for the elderly, and that replacement disease can occur. Yet, the current 13-valent conjugate vaccine has been shown to protect against infections with vaccine serotypes. Long-term mortality of pneumococcal pneumonia should be included in policy making about the introduction of these vaccines for the elderly.

Primary Care Physicians' Struggle with Current Adult Pneumococcal Vaccine Recommendations.

In 2012, the Advisory Committee on Immunization Practices recommended 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for at-risk adults ≥19; in 2014, it expanded this recommendation to adults ≥65. Primary care physicians' practice, knowledge, attitudes, and beliefs regarding these recommendations are unknown. Primary care physicians throughout the U.S. were surveyed by E-mail and post from December 2015 to January 2016. Response rate was 66% (617 of 935). Over 95% of respondents reported routinely assessing adults' vaccination status and recommending both vaccines. A majority found the current recommendations to be clear (50% "very clear," 38% "somewhat clear"). Twenty percent found the upfront cost of purchasing PCV13, lack of insurance coverage, inadequate reimbursement, and difficulty determining vaccination history to be "major barriers" to giving these vaccines. Knowledge of recommendations varied, with 83% identifying the PCV13 recommendation for adults ≥65 and only 21% identifying the recommended interval between PCV13 and PPSV23 in an individual <65 at increased risk. Almost all surveyed physicians reported recommending both pneumococcal vaccines, but a disconnect seems to exist between perceived clarity and knowledge of the recommendations. Optimal implementation of these recommendations will require addressing knowledge gaps and reported barriers.

The profile of invasive pneumococcal disease in a tertiary care PICU

Background : Streptococcus pneumoniae, or pneumococcus, is an encapsulated Gram-positive bacterium that is the major cause of bacteremia and upper respiratory infections (eg, otitis media and sinusitis) in children and a common cause of serious invasive infections. Invasive pneumococcal disease (IPD) refers to disease in which the bacterium enters a sterile site such as blood, cerebrospinal fluid (CSF), pleural fluid, joint fluid or pericardial fluid and causes significant morbidity and mortality. Despite availability of an effective vaccine against this disease, we see a significant number of cases of IPD. Methods : All patients Results : 10 patients were diagnosed with bacteremia caused by Strep. Pneumonia and were confirmed by PCR method and identifying Lyt A gene. Two patients died (20%). Among survivors, the diseases spectrum extends from mild illness to life threatening illness. Two children had pneumococci isolated from other body fluids (CSF/ Pleural Fluids). One child had Meningitis with brain abscess. Four children had pneumonia with ARDS requiring prolonged ventilation support. Majority of children (60%) had milder version of the disease. Conclusion : Bacteremia in children is a serious condition associated. The limitations of the current polysaccharide pneumococcal vaccine in Indian population warrant the prevention against the disease. We suggest that the virulence of pneumococcal serotypes should be considered by identifying the the serotype and developing novel vaccines specific to our Indian population

Intranasal Immunization With an Attenuated pep27 Mutant Provides Protection From Influenza Virus and Secondary Pneumococcal Infections.

During influenza pandemics, secondary pneumococcal infections cause excessive mortality. However, the current 13-valent pneumococcal conjugate vaccine, PCV13, provides only limited protection against secondary infection. Therefore, a more effective pneumococcal vaccine is required to protect against secondary pneumococcal infections. Here, intranasal immunization with an attenuated pneumococcal pep27 mutant provides protection from influenza virus infection, and also from secondary pneumococcal challenge. These results indicate that mucosal immunity might be an effective way to reduce the morbidity and mortality due to secondary pneumococcal infections during influenza pandemics.

The scope for pneumococcal vaccines that do not prevent transmission.

The pneumococcal vaccine pipeline holds candidates developed with the aim to prevent the majority if not all pneumococcal disease. Herd protection is a critical component of the overall impact of current pneumococcal conjugate vaccines (PCVs) and is a prerequisite for disease elimination through an infant vaccination programme. We assessed the scope of a hypothetical pneumococcal vaccine candidate (HPVC) with high clinical efficacy against all pneumococci but that fails to induce such indirect protection. We found that, despite a lack of impact on unvaccinated individuals, HPVC use in infancy may offer similar or superior impact among young children if compared to current PCVs. Hence, it could provide a more affordable alternative to PCVs in particular in settings where most pneumococcal disease is concentrated in children.

Conjugation of PspA4Pro with Capsular Streptococcus pneumoniae Polysaccharide Serotype 14 Does Not Reduce the Induction of Cross-Reactive Antibodies.

Current pneumococcal vaccines are composed of bacterial polysaccharides as antigens, plain or conjugated to carrier proteins. While efficacious against vaccine serotypes, epidemiologic data show an increasing incidence of infections caused by nonvaccine serotypes of Streptococcus pneumoniae The use of pneumococcal surface protein A (PspA) as a carrier protein in a conjugate vaccine could help prevent serotype replacement by increasing vaccine coverage and reducing selective pressure of S. pneumoniae serotypes. PspA is present in all pneumococcal strains, is highly immunogenic, and is known to induce protective antibodies. Based on its sequence, PspA has been classified into three families and six clades. A PspA fragment derived from family 2, clade 4 (PspA4Pro), was shown to generate antibodies with a broad range of cross-reactivity, across clades and families. Here, PspA4Pro was modified and conjugated to capsular polysaccharide serotype 14 (PS14). We investigated the impact of conjugation on the immune response induced to PspA4Pro and PS14. Mice immunized with the PS14-mPspA4Pro conjugate produced higher titers of anti-PS14 antibodies than the animals that received coadministered antigens. The conjugate induced antibodies with opsonophagocytic activity against PS14-carrying strains, as well as against a panel of strains bearing PspAs from five clades (encompassing families 1 and 2) bearing a non-PS14 serotype. Furthermore, mice immunized with PS14-mPspA4Pro were protected against nasal colonization with a nonrelated S. pneumoniae strain bearing PspA from clade 1, serotype 6B. These results demonstrate that the cross-reactivity mediated by PspA4Pro is retained following conjugation, supporting the use of PspA4 as a carrier protein in order to enhance pneumococcal vaccine coverage and encourage its further investigation as a candidate in future vaccine designs.

Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study

The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population. For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design. 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia. PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated. Pfizer and Nagasaki University.

Preclinical evaluation of a chemically detoxified pneumolysin as pneumococcal vaccine antigen

ABSTRACTThe use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sequence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment. Detoxi-fication was confirmed by dPly challenge in mice and histological analysis of the injection site in rats. Immunization with dPly elicited Ply-specific functional antibodies that were able to inhibit Ply activity in a hemolysis assay. In addition, immunization with dPly protected mice against lethal intranasal challenge with Ply, and intranasal immunization inhibited nasopharyngeal colonization after intranasal challenge with homologous or heterologous pneumococcal strain. Our findings supported dPly as a valid candidate antigen for further pneumococcal vaccine development.

A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection

The identification of immunogenic glycotopes thatrender glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to theheterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose theleast-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.

Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial.

The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22–2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15–2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals.

Pneumococcal vaccination coverages among low-, intermediate-, and high-risk adults in Catalonia

ABSTRACTThere is scarce data about pneumococcal vaccination coverages among adults in recent years. We investigated current pneumococcal vaccination coverages in Catalonia, Spain, with a cross-sectional population-based study including 2,033,465 individuals aged 50 y or older assigned to the Catalonian Health Institute at 01/01/2015 (date of survey). A previously validated institutional research clinical Database was used to classify study subjects by their vaccination status for both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), to identify comorbidities and underlying conditions, and establish the risk stratum of each individual: High risk stratum: functional or anatomic asplenia, cochlear implants, CSF leaks, or immunocompromising conditions; medium risk stratum: immunocompetent persons with history of chronic cardiac or respiratory disease, liver disease, diabetes mellitus, alcoholism and/or smoking; low risk stratum: persons without high or medium risk conditions. Of the total 2,033,465 study population, an amount of 789,098 (38.8%) had received PPVS23, whereas 5031 (0.2%) had received PCV13. PPSV23 coverages increased largely with increasing age: 4.8% in 50–59 y vs 35.5% in 60–69 y vs 71.9% in 70–79 y vs 79.5% in 80 y or older; p < 0.001). PCV13 coverages also increased with age, although they were very low in all age groups. PPSV23 coverages were 59.2% in high risk stratum, 48.3% in medium risk stratum and 28.1% in low risk stratum (p < 0.001). For the PCV13, uptakes were 1.2%, 0.3% and 0.1% in high, medium and low stratum, respectively (p < 0.001). In conclusion, pneumococcal vaccination coverages in Catalonian adults are not optimal, being especially small for the PCV13 (even in high-risk subjects).

Genomic analysis of nontypeable pneumococci causing invasive pneumococcal disease in South Africa, 2003-2013.

BackgroundThe capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa.ResultsIsolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003–2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae.ConclusionsNTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2808-x) contains supplementary material, which is available to authorized users.

Innovative Strategies Designed to Improve Adult Pneumococcal Immunizations in Safety Net Patient-Centered Medical Homes.

Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247).

A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens.

This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.

Molecular epidemiology of nonencapsulated Streptococcus pneumoniae among Japanese children with acute otitis media.

The introduction of pneumococcal conjugate vaccine may change the epidemiology of Streptococcus pneumoniae. The increased prevalence of non-vaccine serotypes as the cause of pneumococcal diseases has already reported in the United States and Europe. However, little attention has been focused on the S. pneumoniae. In this study, nonencapsulated S. pneumoniae were identified in 15 isolates (6.4%) out of 236 pneumococcal strains obtained from the nasopharynges of children with acute otitis media (AOM), in 3 isolates (14.3%) out of 21 strains from acute rhinosinusitis, and in 2 isolates (12.5%) out of 16 nasopharyngeal carriage strains obtained from normal healthy children. Among the 20 nonencapsulated S. pneumoniae isolates, 15 (75.0%) isolates had the pspK gene. Seven sequence types (STs) were identified: ST7502 (5 strains), ST1106 (2 strains), ST7803 (2 strains), ST7786 (1 strain), ST6741 (1 strain), ST7496 (1 strain), and ST8642 (1 strain). Because nonencapsulated S. pneumoniae strains are not targeted by the current available pneumococcal vaccines, these strains will gradually become more common in nasopharyngeal carriage. The increase in colonization and dissemination of these strains would increase the risk of AOM and other systemic pneumococcal diseases against which current vaccines cannot provide protection. Nonencapsulated S. pneumoniae may thus become more prevalent as human pathogen.

Review of Current Pneumococcal Vaccine Guidelines

Pneumococcal vaccination has been associated with a decline in the infectious disease burden caused by Streptococcus pneumoniae since it was incorporated into routine vaccination schedules for adults and children. In 2014, the Centers for Disease Control and Prevention updated its recommendations to include a single dose of a 13-valent pneumococcal conjugate vaccine for adults ≥65 years. The pediatric recommendations remain unchanged. This paper reviews the current vaccine recommendations for adults and children.

Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012.

Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria.

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

ObjectiveDue to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. MethodsC57BL/6J infant mice were intramuscularly vaccinated at age 1–3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3–4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. ResultsPPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6–24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. ConclusionTrivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation and tissue damage.

Colorectal cancer screening in an academic center compared to the national average.

To investigate if the increased emphases on training and education on current colorectal cancer (CRC) screening guidelines has resulted in improved national CRC screening rates in an internal medicine training program, and to determine if the doctor's post graduate year (PGY) level of training affected CRC screening rates. We conducted a cross sectional study of every patient who presented to the outpatient clinic of New York Methodist Hospital, Brooklyn, NY, over the span of six continuous weeks in 2011. A questionnaire was integrated into every patient's medical interview that helped determine that patient's current CRC screening status, screening mammography status if applicable, Papanicolaou smear status if applicable, and current pneumococcal vaccination status. At the same time, patient demographics were also obtained. All of the questionnaire data was collected at the end of each medical visit and was compiled by a designated researcher. After all the data points were collected, it was ensured that the patient has been seen by his or her continuity care resident at least twice in the past. Data was then compiled into a secure, encrypted database to then be analyzed by our statistician. Data from 547 consecutive clinic visits were obtained. Of these, we reviewed 483 charts that met all of the inclusion criteria and did not meet the exclusion criteria. The data was then analyzed for differences between PGY levels, patient's sex, race, and educational level. The study population consisted of 138 men and 345 women. 35 patients were white (7.40%), 174 were black (39.79%) and 264 were Hispanic (55.81%). Our CRC screening rates were: 66% for PGY-1's, 72% for PGY-2's and 77% for PGY-3's. There was no statistical difference noted between the three groups (P ≤ 0.05) or was there any difference sex, insurance status or educational level. Overall CRC screening rate was 72% which was not different from the New York State average (P < 0.05). There was a statistically significant higher rate of CRC screening amongst Hispanics 76% (P = 0.034) and in people within the ages of 70-79, 82% (P = 0.015). Patients that are followed by internal medicine residents at our urban outpatient teaching clinic did not receive higher rates of CRC screening nor did rates of screening vary with their PGY level.