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Sample records for 23-valent pneumococcal polysaccharide

  1. Effectiveness of 23-valent pneumococcal polysaccharide vaccine on diabetic elderly

    PubMed Central

    Kuo, Chia-Sheng; Lu, Chia-Wen; Chang, Yu-Kang; Yang, Kuen-Cheh; Hung, Shou-Hung; Yang, Ming-Ching; Chang, Hao-Hsiang; Huang, Chi-Ting; Hsu, Chih-Cheng; Huang, Kuo-Chin

    2016-01-01

    Abstract Diabetes mellitus is associated with increased risk of pneumonia, and 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for prevention of pneumonia. However, the effectiveness of PPV23 remains unclear in the older diabetic patients who usually have compromised immune function. We used data extracted from the Taiwanese National Health Insurance Research Database (NHIRD) from 2000 to 2009 to conduct a population-based retrospective cohort study, comparing the incidence of pneumococcal diseases among PPV23-vaccinated and propensity-score matched PPV23-unvaccinated groups in diabetic elderly. The primary outcome was invasive pneumococcal diseases (IPDs), and the secondary outcomes were medical utilization. PPV23-vaccinated group had reduced risks of IPD (adjusted OR: 0.86, 95% CI: 0.78–0.94), respiratory failure (0.84, 0.77–0.93), and shorter length of hospitalization (−1.27 ± 0.19 days, P value: 0.0012). In flu-vaccinated group, subjects who received PPV23 had reduced risks of IPD, hospitalization, and respiratory failure; had shorter lengths of hospitalization; and less medical costs, than those without receiving PPV23. In not flu-vaccinated group, PPV23 vaccination was associated with reduced risks of IPD and respiratory failure. Receiving both vaccines could bring better protection in IPD, hospitalization, visits of emergency department, and respiratory failure. PPV23 vaccination was effective in prevention of pneumococcal diseases and reduction of medical utilization in diabetic elderly aged 75 and more. Receiving both vaccines resulted in better outcomes than PPV vaccination alone. PMID:27368047

  2. Effectiveness of the 23-valent polysaccharide vaccine against invasive pneumococcal disease in Navajo adults.

    PubMed

    Benin, Andrea L; O'Brien, Katherine L; Watt, James P; Reid, Raymond; Zell, Elizabeth R; Katz, Scott; Donaldson, Connie; Parkinson, Alan; Schuchat, Anne; Santosham, Mathuram; Whitney, Cynthia G

    2003-07-01

    Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population. PMID:12825175

  3. 23-Valent Pneumococcal Polysaccharide Vaccine Uptake in the United States Air Force HIV Program.

    PubMed

    Ocampo, Thad F; Le, Tuan; Matthews, Peter E; Okulicz, Jason F

    2016-07-01

    Streptococcus pneumoniae infection is a predominant cause of bacterial infection in HIV-infected individuals. However, reported rates of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) are variable. We evaluated uptake of PPV23 in patients diagnosed with HIV between 1996 and 2012 (n = 507) in the United States Air Force, a centralized HIV program with free access to care including vaccines and medications. A total of 411 (81.1%) patients received at least 1 PPV23 dose. The PPV23 vaccination within 1 year of diagnosis was greater for those diagnosed between 2004 and 2012 (n = 184, 86%) compared with 1996 to 2003 (n = 104, 56.5%; P < .001). For those with ≥6 years of follow-up, receipt of a second recommended PPV23 dose was greater for those diagnosed between 1996 and 2003 (n = 52, 57.8%) compared with 2004 to 2012 (n = 9, 28.1%; P = .004). Although first PPV23 vaccination was high in recent years, process improvement efforts are underway to overcome barriers and improve uptake of pneumococcal vaccines in our program. PMID:27215560

  4. Cost-effectiveness of vaccinating adults with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany.

    PubMed

    Jiang, Yiling; Gauthier, Aline; Annemans, Lieven; van der Linden, Mark; Nicolas-Spony, Laurence; Bresse, Xavier

    2012-10-01

    The introduction of routine infant vaccination against pneumococcal disease has resulted in a decreased overall invasive pneumococcal disease incidence in adults but also a change in invasive pneumococcal disease serotypes. This study aimed to assess the cost-effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany in this context. A population-based Markov model was developed. A cohort of adults currently eligible for vaccination was followed until death. Adult vaccination with PPV23 was associated with an incremental cost-effectiveness ratio of €17,065/quality-adjusted life years gained from the third-party payer's perspective. Univariate sensitivity analyses showed that the incremental cost-effectiveness ratio was below €50,000/quality-adjusted life years gained in most test scenarios. The model suggests that adult PPV23 vaccination is cost effective in Germany, due to its broad serotype coverage. This is despite epidemiological changes in Streptococcus pneumoniae serotypes caused by wider use of pneumococcal conjugate vaccines during childhood. PMID:23025422

  5. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study

    PubMed Central

    Lombardi, Francesca; Belmonti, Simone; Fabbiani, Massimiliano; Morandi, Matteo; Rossetti, Barbara; Tordini, Giacinta; Cauda, Roberto; De Luca, Andrea; Di Giambenedetto, Simona; Montagnani, Francesca

    2016-01-01

    Objectives Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) versus the 23-valent polysaccharide vaccine (PPSV23) in HIV-infected adults. Methods We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18–65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50) received two doses of PCV13 eight weeks apart, and group 2 (n = 50) received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100) were also enrolled as baseline controls. Results Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group. Conclusions In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated. Trial Registration ClinicalTrials.gov NCT02123433 PMID:27258647

  6. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years: A randomized, double-blinded, active control, phase III trial.

    PubMed

    Kong, Yujia; Zhang, Wei; Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Li, Yanping; Xia, Jielai

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to -10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was -10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9 V, 10A, 11A, 15 B, 18C, 19 A, 22 F and 33 F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and

  7. Effectiveness of 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and over in the Region of Madrid, Spain, 2008-2011.

    PubMed

    Gutierrez Rodriguez, M A; Ordobas Gavin, M A; Garcia-Comas, L; Sanz Moreno, J C; Cordoba Deorador, E; Lasheras Carbajo, M D; Taveira Jimenez, J A; Martin Martinez, F; Iniesta Fornies, D; Arce Arnaez, A

    2014-01-01

    Invasive pneumococcal disease (IPD) is a notifiable disease in the Region of Madrid. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for children and adults aged two years or over with a high risk of disease, and for all adults aged 60 and over. We describe the evolution of IPD incidence from 2008 to 2011 in people aged 60 years and over and PPV23 vaccine effectiveness (VE). VE is estimated using both the screening method and indirect cohort method. The incidence of IPD varied from 20.0 in 2008 to 15.2 per 100,000 inhabitants in 2011 (RR: 0.8; 95% CI: 0.6–0.9). Adjusted VE estimated with the screening method was 68.2% (95% CI: 56.2–76.9). VE with the Broome method was 44.5% (95% CI: 23.8–59.6) for all PPV23 serotypes, and 64.4% (95% CI: 45.2–76.8) for PPV23 serotypes not included in conjugate vaccines. VE was lower in patients aged 80 years and older (25.5%; 95% CI:-23.2 to 55.0) and those with highrisk medical conditions (31.7%; 95% CI: -2.2 to -54.4). Adjusted VE was 44.5% (95% CI: 19.4-61.8) within 5 years of vaccination and 32.5% (95% CI: -5.6 to 56.9) after 5 years. These results are compatible with current recommendations for PPV23. PMID:25323079

  8. Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs.

    PubMed

    Kapetanovic, Meliha Crnkic; Roseman, Carmen; Jönsson, Göran; Truedsson, Lennart

    2011-12-01

    The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR. PMID:21956234

  9. Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

    PubMed Central

    Hayward, Starla; Thompson, Lou Ann; McEachern, Andrea

    2016-01-01

    Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against S. pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults 65 years and older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials which evaluate the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. The two studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo. PMID:27376105

  10. Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study

    PubMed Central

    Cordonnier, Catherine; Ljungman, Per; Juergens, Christine; Maertens, Johan; Selleslag, Dominik; Sundaraiyer, Vani; Giardina, Peter C.; Clarke, Keri; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2015-01-01

    Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention. Methods. In an open-label study, patients (n = 251) 3–6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed. Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99–23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00–6.97), and little change after PPSV23 (GMFR range, 0.86–1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines. Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable. Clinical Trials Registration. NCT00980655. PMID:25870329

  11. Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults

    PubMed Central

    Juergens, Christine; de Villiers, Pierre JT; Moodley, Keymanthri; Jayawardene, Deepthi; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2014-01-01

    This randomized open-label trial was designed to provide preliminary immunogenicity and safety data to support development of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) for adults. The aims were to: identify an age-appropriate PCV13 formulation, i.e., with (n = 309) or without (n = 304) aluminum phosphate (AlPO4); compare the selected PCV13 formulation (n = 309) with 23-valent pneumococcal polysaccharide vaccine (PPSV23; n = 301); and, together with an extension study, assess sequential use of pneumococcal vaccines at 1-year intervals in adults aged ≥65 years (n = 105) not pre-vaccinated with PPSV23. Immune responses were measured by ELISA and opsonophagocytic activity assays 1 month postvaccination. Immunoglobulin G responses elicited by PCV13 with AlPO4 and PCV13 without AlPO4 were similar for the majority, and noninferior for all PCV13 serotypes. PCV13 with AlPO4 was generally more reactogenic, with reactions mainly mild or moderate. Thus, PCV13 with AlPO4 (hereafter PCV13) became the selected formulation. Immune responses to PCV13 were noninferior for all but one serotype and for most PCV13 serotypes superior to PPSV23. Vaccine sequence assessments showed that for PCV13/PPSV23, the initial PCV13 dose generally enhanced responses to a subsequent PPSV23 dose, compared with PPSV23 alone. For PCV13/PCV13, a second dose did not enhance the first dose response when given after 1 year. For PCV13/PPSV23/PCV13, priming with PCV13 (vaccination 1) did not protect against lower responses induced by PPSV23 to subsequent PCV13 (vaccination 3). In conclusion, the pediatric PCV13 formulation with AlPO4 is well tolerated and immunogenic in adults, is generally more immunogenic than PPSV23, and subsequent vaccination with PPSV23 is possible if required. PMID:24576885

  12. Effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine in preventing hospitalization with laboratory confirmed influenza during the 2009-2010 and 2010-2011 seasons

    PubMed Central

    Domínguez, Angela; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Saez, Marc; Soldevila, Núria; Astray, Jenaro; Mayoral, José María; Martín, Vicente; Quintana, José María; González-Candelas, Fernando; Galán, Juan Carlos; Tamames, Sonia; Castro, Ady; Baricot, Maretva; Garín, Olatz; Pumarola, Tomas; Working Group (Spain), CIBERESP Cases and Controls in Pandemic Influenza

    2013-01-01

    Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009–2010 pandemic wave and 2010–2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged ≥ 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8–62) in all patients and 43% (95% CI 2–78) in patients aged ≥ 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65–90) in all patients and 76% (95% CI 46–90) in patients aged ≥ 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38–72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza. PMID:23563516

  13. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

    PubMed Central

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2015-01-01

    Background Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot. Methods We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%. Results Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45

  14. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    Pneumococcal polysaccharide vaccine (PPSV)Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. But ... the disease, through vaccination, even more important. Pneumococcal polysaccharide vaccine (PPSV) protects against 23 types of pneumococcal ...

  15. Comparative reactogenicity and immunogenicity of 23 valent pneumococcal vaccine administered by intramuscular or subcutaneous injection in elderly adults.

    PubMed

    Cook, Ian F; Pond, Dimity; Hartel, Gunter

    2007-06-15

    23 Valent pneumococcal vaccine is provided to the elderly through public health programs in many countries. However there is no clear recommendation regarding its route of administration (subcutaneous or intramuscular). In a randomised, observer blind study of 254 elderly subjects, the immunogenicity of a 23 valent pneumococcal vaccine was not influenced by its route of administration. A low rate of systemic adverse reactions was observed with the vaccine (subcutaneous and intramuscular both 6.3%). Local adverse reaction rates were; intramuscular 7.1% and subcutaneous 18.9% and these were predicted by: * Pre-vaccination antibody titres>1 microg/ml, odds ratio 22.4 (8.06-74.84) compared with pre-vaccination antibody titre<1 microg/ml. * Female gender, odds ratio 5.0 (1.85-14.83) compared with male gender. * Subcutaneous injection route, odds ratio 3.20 (1.13-9.13) compared with intramuscular injection route. * Female gender subcutaneous injection route, odds ratio 2.99 (1.10-8.70) compared with female gender intramuscular injection route. These data support the intramuscular injection of 23 valent pneumococcal vaccine, especially in elderly females. PMID:17512098

  16. In-Hospital Pneumococcal Polysaccharide Vaccination Is Associated With Detection of Pneumococcal Vaccine Serotypes in Adults Hospitalized for Community-Acquired Pneumonia.

    PubMed

    Grijalva, Carlos G; Wunderink, Richard G; Zhu, Yuwei; Williams, Derek J; Balk, Robert; Fakhran, Sherene; Courtney, D Mark; Anderson, Evan J; Qi, Chao; Trabue, Christopher; Pavia, Andrew T; Moore, Matthew R; Jain, Seema; Edwards, Kathryn M; Self, Wesley H

    2015-12-01

    During an etiology study of adults hospitalized for pneumonia, in which urine specimens were examined for serotype-specific pneumococcal antigen detection, we observed that some patients received 23-valent pneumococcal polysaccharide vaccine before urine collection. Some urine samples became positive for specific vaccine pneumococcal serotypes shortly after vaccination, suggesting false-positive test results. PMID:26512357

  17. In-Hospital Pneumococcal Polysaccharide Vaccination Is Associated With Detection of Pneumococcal Vaccine Serotypes in Adults Hospitalized for Community-Acquired Pneumonia

    PubMed Central

    Grijalva, Carlos G.; Wunderink, Richard G.; Zhu, Yuwei; Williams, Derek J.; Balk, Robert; Fakhran, Sherene; Courtney, D. Mark; Anderson, Evan J.; Qi, Chao; Trabue, Christopher; Pavia, Andrew T.; Moore, Matthew R.; Jain, Seema; Edwards, Kathryn M.; Self, Wesley H.

    2015-01-01

    During an etiology study of adults hospitalized for pneumonia, in which urine specimens were examined for serotype-specific pneumococcal antigen detection, we observed that some patients received 23-valent pneumococcal polysaccharide vaccine before urine collection. Some urine samples became positive for specific vaccine pneumococcal serotypes shortly after vaccination, suggesting false-positive test results. PMID:26512357

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

    PubMed Central

    Daniels, Calvin C.; Rogers, P. David

    2016-01-01

    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. PMID:26997927

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

    PubMed

    Daniels, Calvin C; Rogers, P David; Shelton, Chasity M

    2016-01-01

    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. PMID:26997927

  20. Pneumococcal polysaccharide vaccine - what you need to know

    MedlinePlus

    ... taken in its entirety from the CDC Pneumococcal Polysaccharide Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ppv.html CDC review information for Pneumococcal Polysaccharide VIS: Page last reviewed: April 24, 2015 Page ...

  1. Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil

    PubMed Central

    Neto, Joao Tonolio; Gagliardi, Anna; Pinho, Amanda; Durand, Laure; Fonseca, Marcelo

    2011-01-01

    Vaccination of adults aged 60 years and older against Streptococcus pneumonia is not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine (PPV23) is only available for institutionalized persons or with underlying diseases despite the substantial medical and economic burden related to pneumococcal infections in adults over than 59 years. The study aimed at evaluating the cost effectiveness of implementing a large PPV program in this population. This analysis was performed using a static decision tree model. Demographic and epidemiological data were obtained from Brazilian official sources and international literature. Economic data were obtained from a study performed in 2007 in a public and a private hospital located in Sao Paulo. Vaccination was assumed to protect for 5 years with 60% effectiveness against bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses were performed. The pneumococcal polysaccharide vaccination saved 5,218 life year gained (LYG). The vaccination program was found to be cost effective in the social security and public health care perspectives with a mean incremental cost-effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were sensitive to the vaccine effectiveness against NBPP, the incidence and case-fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60 and older was found to be cost-saving. Pneumococcal polysaccharide vaccination is clinically and economically favored over the present vaccination strategy, in which persons aged over 59 years in Sao Paulo have not been vaccinated. PMID:21941088

  2. [PNEUMOCOCCAL VACCINE IN ADULTS REDUCES THE RISK OF INFECTIONS CAUSED BY STREPTOCOCCUS PNEUMONIAE].

    PubMed

    Belocerkovskaja, Ju G; Romanovskih, A G; Styrt, E A

    2016-01-01

    Streptococcus pneumoniae is a major cause of severe disease worldwide, particularly in the risk population. Two pneumococcal vaccines are currently available for specific prevention of pneumococcal infections among adults in Russia: a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). The article describes modern views on the effectiveness and safety of two pneumococcal vaccines in adults with underlying medical conditions and adults aged ≥ 65 years and provides current recommendations for routine use of PPSV23 and PCV13 among persons included in the risk group. PMID:27172726

  3. Pneumococcal Vaccination Strategies. An Update and Perspective.

    PubMed

    Berical, Andrew C; Harris, Drew; Dela Cruz, Charles S; Possick, Jennifer D

    2016-06-01

    Streptococcus pneumoniae is an important global pathogen that causes a wide range of clinical disease in children and adults. Pneumococcal pneumonia is by far the common presentation of noninvasive and invasive pneumococcal disease and affects the young, the elderly, and the immunocompromised disproportionately. Patients with chronic pulmonary diseases are also at higher risk for pneumococcal infections. Substantial progress over the century has been made in the understanding of pneumococcal immunobiology and the prevention of invasive pneumococcal disease through vaccination. Currently, two pneumococcal vaccines are available for individuals at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal protein-conjugate vaccine (PCV13). The goal of pneumococcal vaccination is to stimulate effective antipneumococcal antibody and mucosal immunity response and immunological memory. Vaccination of infants and young children with pneumococcal conjugate vaccine has led to significant decrease in nasal carriage rates and pneumococcal disease in all age groups. Recent pneumococcal vaccine indication and schedule recommendations on the basis of age and risk factors are outlined in this Focused Review. As new pneumococcal vaccine recommendations are being followed, continued efforts are needed to address the vaccine efficacy in the waning immunity of the ever-aging population, the implementation of vaccines using two different vaccines under very specific schedules and their real world clinical and cost effectiveness, and the development of next generation pneumococcal vaccines. PMID:27088424

  4. Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

    2012-01-01

    Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

  5. Theory and strategy for Pneumococcal vaccines in the elderly.

    PubMed

    Namkoong, Ho; Ishii, Makoto; Funatsu, Yohei; Kimizuka, Yoshifumi; Yagi, Kazuma; Asami, Takahiro; Asakura, Takanori; Suzuki, Shoji; Kamo, Testuro; Fujiwara, Hiroshi; Tasaka, Sadatomo; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. Because the incidence of pneumococcal diseases is likely to increase with the aging society, we should determine an optimal strategy for pneumococcal vaccination. While consensus indicates that 23-valent pneumococcal polysaccharide vaccine prevents invasive pneumococcal diseases (IPD), its effects on community-acquired pneumonia (CAP) remain controversial. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was released. The latest clinical study (CAPiTA study) showed that PCV13 reduced vaccine-type CAP and IPD. Based on these results, the Advisory Committee on Immunization Practices recommended initial vaccination with PCV13 for the elderly. Scientific evidence regarding immunosenescence is needed to determine a more ideal vaccination strategy for the elderly with impaired innate and adaptive immunity. Continuing research on the cost effectiveness of new vaccine strategies considering constantly changing epidemiology is also warranted. PMID:26406267

  6. Effect of previous vaccination with pneumococcal conjugate vaccine on pneumococcal polysaccharide vaccine antibody responses.

    PubMed

    Schaballie, H; Wuyts, G; Dillaerts, D; Frans, G; Moens, L; Proesmans, M; Vermeulen, F; De Boeck, K; Meyts, I; Bossuyt, X

    2016-08-01

    During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced. PMID:26939935

  7. A novel chemistry for conjugating pneumococcal polysaccharides to Luminex microspheres.

    PubMed

    Schlottmann, Sonela A; Jain, Neil; Chirmule, Narendra; Esser, Mark T

    2006-02-20

    Here we describe a novel method to conjugate pneumococcal polysaccharides (PnPS) to Luminex microspheres for use in serological assays. 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium (DMTMM) modification of PnPS and conjugation to carboxyl functional groups on Luminex microspheres (COOH-DMTMM method) was shown to be a reproducible chemistry that efficiently conjugated PnPS to Luminex microspheres without affecting the antigenicity of a broad set of PnPS. The COOH-DMTMM method was compared to three other methods for robustness, reproducibility and effect on PnPS antigenicity in a multiplexed assay format. The other methods examined included adsorption of the unmodified PnPS to Luminex microspheres, oxidation of the PnPS to conjugate them to amino-modified microspheres using carbodiimide chemistry and poly-l-lysine modification of the PnPS before conjugating to carboxy Luminex microspheres using carbodiimide chemistry. Of the four methods, the COOH-DMTMM chemistry was shown to be a robust methodology, producing stable PnPS coupled microspheres with a 4-log dynamic range and low cross-reactivity when used in a PnPS-specific IgG serology assay. This novel chemistry should be useful for developing serological assays to measure antibodies to polysaccharides for use in vaccine and epidemiology studies. PMID:16448665

  8. Pneumococcal Polysaccharide Vaccine: What You Need to Know

    MedlinePlus

    ... children and younger adults) from pneumococcal disease . Pneumococcal disease is caused by bacteria that can spread from person to person through close contact. It can cause ear infections, and it can also lead to more serious infections of ... can get pneumococcal disease, but children under 2 years of age, people ...

  9. Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

    PubMed

    Papadatou, Ioanna; Spoulou, Vana

    2016-05-01

    Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals. PMID:27009210

  10. Pneumococcal Vaccines: Understanding Centers for Disease Control and Prevention Recommendations

    PubMed Central

    Schraufnagel, Dean E.

    2014-01-01

    Streptococcus pneumoniae infection is a common and serious health problem that is best prevented by the pneumococcal vaccine. The first vaccine approved by the U.S. Federal Drug Administration in 1977 contained 14 polysaccharide antigens. An improved vaccine introduced in 1983 included 23 polysaccharide antigens. Both vaccines were effective for immunocompetent adults; however, young children and immunocompromised adults remained susceptible. A pediatric vaccine was developed consisting of the capsular antigens of seven pneumococcal serotypes commonly found in children. The antigens in this preparation are covalently conjugated to diphtheria protein to make them more antigenic. The conjugate vaccine was expanded to include 13 serotypes by 2010. Although more immunogenic, the conjugate vaccine has fewer serotypes than the older 23-valent vaccine. The U.S. Centers for Disease Control and Prevention recommend that children at risk for pneumococcal pneumonia as defined by the presence of chronic disease should receive the 13-valent conjugated vaccine. Adults at risk for pneumococcal pneumonia, which includes those over 65 years of age and those who have a chronic disease, should receive the 23-polysaccharide vaccine. Immunosuppressed patients of any age should receive both vaccines. Adults should be revaccinated once at age 65 years or older with the 23-polysaccharide vaccine provided that at least 5 years have elapsed since the previous vaccination. PMID:25032872

  11. Benefits and Effectiveness of Administering Pneumococcal Polysaccharide Vaccine With Seasonal Influenza Vaccine: An Approach for Policymakers

    PubMed Central

    Nanni, Angeline; Levine, Orin

    2012-01-01

    For the influenza pandemic of 2009–2010, countries responded to the direct threat of influenza but may have missed opportunities and strategies to limit secondary pneumococcal infections. Delivering both vaccines together can potentially increase pneumococcal polysaccharide vaccine (PPV23) immunization rates and prevent additional hospitalizations and mortality in the elderly and other high-risk groups. We used PubMed to review the literature on the concomitant use of PPV23 with seasonal influenza vaccines. Eight of 9 clinical studies found that a concomitant program conferred clinical benefits. The 2 studies that compared the cost-effectiveness of different strategies found concomitant immunization to be more cost-effective than either vaccine given alone. Policymakers should consider a stepwise strategy to reduce the burden of secondary pneumococcal infections during seasonal and pandemic influenza outbreaks. PMID:22397339

  12. Cost-effectiveness analysis of pneumococcal conjugate vaccine 13-valent in older adults in Colombia

    PubMed Central

    2014-01-01

    Background Nowadays, there are two vaccination strategies in Colombia to prevent pneumococcal diseases in people over 50 years. Our aim is to estimate cost-effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal diseases and their related mortality in people over 50 years old in Colombia. Methods A Markov model was developed with national data, including pneumococcal serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort was simulated and a five year time horizon was assumed. Analysis was done from a perspective of a third party payer. Direct costs were provided by a national insurance company; sensitive univariate and probabilistic analysis were done for epidemiological and clinical effectiveness parameters and costs. Results PCV13 avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would save U.S. $ 145,196,578 versus no vaccine. Conclusion PCV13 would be a cost-saving strategy in the context of a mass vaccination program in Colombia to people over 50 years old because it would reduce burden of disease and specific mortality by pneumococcal diseases, besides, it saves money versus PPSV23. PMID:24679135

  13. Impact of the Hajj on pneumococcal transmission.

    PubMed

    Memish, Z A; Assiri, A; Almasri, M; Alhakeem, R F; Turkestani, A; Al Rabeeah, A A; Akkad, N; Yezli, S; Klugman, K P; O'Brien, K L; van der Linden, M; Gessner, B D

    2015-01-01

    Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-Hajj (Mina) during 2011 and 2012. A questionnaire was administered and a nasopharyngeal swab was collected. The swab was tested for pneumococcus, serotype and antibiotic resistance. A total of 3203 subjects (1590 at beginning-Hajj and 1613 at end-Hajj) originating from 18 countries in Africa or Asia were enrolled. The overall pneumococcal carriage prevalence was 6.0%. There was an increase in carriage between beginning-Hajj and end-Hajj cohorts for: overall carriage (4.4% versus 7.5%, prevalence ratio (PR) 1.7, 95% CI 1.3-2.3), and carriage of 23-valent pneumococcal polysaccharide vaccine serotypes (2.3% versus 4.1%, PR 1.8, 95% CI 1.2-2.7), 13-valent pneumococcal conjugate vaccine (PCV) serotypes (1.1% versus 3.6%, PR 3.2, 95% CI 1.9-5.6), 10-valent PCV serotypes (0.6% versus 1.6%, PR 2.6, 95% CI 1.2-5.3), antibiotic non-susceptible isolates (2.5% versus 6.1%, PR 2.5, 95% CI 1.7-3.6) and multiple non-susceptible isolates (0.6% versus 2.2%, PR 3.8, 95% CI 1.8-7.9). Fifty-two different serotypes were identified, most commonly serotypes 3 (17%), 19F (5%) and 34 (5%). These results suggest that the Hajj may increase pneumococcal carriage-particularly conjugate vaccine serotypes and antibiotic non-susceptible strains, although the exact mechanism remains unknown. The Hajj may therefore provide a mechanism for the global distribution of pneumococci. PMID:25636939

  14. Differences in Homing Potentials of Streptococcus pneumoniae–Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations

    PubMed Central

    Palkola, Nina V.; Pakkanen, Sari H.; Kantele, Jussi M.; Pakarinen, Laura; Puohiniemi, Ritvaleena; Kantele, Anu

    2015-01-01

    Background. Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae–specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia. Methods. The expression of α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae–specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11). Results. In patients with pneumonia, the proportion of S. pneumoniae–specific plasmablasts expressing L-selectin was high, the proportion expressing α4β7 was moderate, and the proportion expressing CLA was low. The homing receptor α4β7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001). Conclusions. The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia. PMID:25838267

  15. Pneumococcal vaccination: what have we learnt so far and what can we expect in the future?

    PubMed

    Torres, A; Bonanni, P; Hryniewicz, W; Moutschen, M; Reinert, R R; Welte, T

    2015-01-01

    Individuals <2 years and ≥ 50 years of age, as well as those with other specific risk factors, are especially vulnerable to invasive pneumococcal disease (IPD). Conjugate vaccines have been developed against encapsulated bacteria such as Streptococcus pneumoniae to provide improved immune responses. The 7-valent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of vaccine-type pneumococcal diseases in children, including invasive disease and pneumonia and acute otitis media. There have also been significant declines in antimicrobial resistance in 7-valent vaccine serotypes and carriage of S. pneumoniae in the post-PCV7 era. Two to three years after the introduction of PCV13, there is emerging, global evidence of a reduced burden of pneumococcal diseases in children, including declines in IPD (UK and Germany) and nasopharyngeal carriage of PCV13 serotypes (Portugal and France). The functional immunogenicity of PCV13 in individuals ≥ 50 years of age has been demonstrated in clinical trials in comparison with the 23-valent pneumococcal polysaccharide vaccine and for children and adults 6 to 49 years of age. Between 2011 and 2013, PCV13 received market authorisation by the European Medicines Agency (EMA) for these additional age groups and is now available in Europe for the prevention of pneumococcal disease in all age groups. PMID:25149825

  16. Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

    PubMed

    Jakobsen, H; Schulz, D; Pizza, M; Rappuoli, R; Jónsdóttir, I

    1999-11-01

    Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans. PMID:10531245

  17. [Prophylaxis of Community-Acquired Pneumonia Outbreaks with Pneumococcal Polysaccharide Vaccine. Prospects Analysis for Russian Military Community].

    PubMed

    Guchev, I A; Klochkov, O I; Sinopalnikov, A I

    2016-01-01

    Pneumococcal pneumonia and other diseases caused by pneumococci still remain the main factors of high morbidity and mortality rates throughout the world. Pneumococci as the leading pathogens of community-acquired pneumonia (CAP), acute otitis media and sinusitis also cause a number of other serious systemic disorders including invasive infections with high mortality in spite of the antimicrobial resistance status and adequate antimicrobials choice. Pneumococcal infections are responsible for 5-35% or more of community-acquired pneumonias. The burden of pneumonia (up to 100-200 per thousand) is recorded among military recruits in training centers. Since the specific environment of the soldiers could be carrected, their health protection requires medical surveillance. For these reasons, polysaccharide and more immunogenic conjugated pneumococcal vaccines were developed. There is now an urgent need to understand whether such vaccines are effective in military conscripts. Controversy about the effectiveness and value of the polysaccharide (PPV-23) vaccine as a CAP morbidity restriction measure still persists. There were implemented plenty of metaanalyses of pneumococcal vaccines in adults. Some of them showed that the vaccine was effective against bacteremic pneumococcal pneumonia in 'low risk' healthy adults and elders. There have been a number of poor quality observational studies in Russia where 'all pneumonia cases' were considered as an endpoint. It remains controversial whether these observational studies provide adequate evidence to justify the use of the polysaccharide vaccine in the groups of healthy young men for whom it is being advocated. In our analysis we found weak evidence supporting pneumococcal vaccination with PPV-23 for this group. Nevertheless, favorable tendency was found to immunize. It is the reason for a trail to find pharmacoepidemiological support for vaccination by novel conjugated vaccines with better immunogenicity. PMID:27337866

  18. Invasive pneumococcal disease in Australia, 2009 and 2010.

    PubMed

    Bareja, Chritina; Toms, Cindy; Lodo, Kerryn; de Kluyver, Rachel

    2015-06-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was conducted in all Australian states and territories in 2009 and 2010 with comprehensive comparative data available since 2002. There were 1,556 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2009, a notification rate of 7.2 cases per 100,000 population. In 2010 there were 1,640 cases, a notification rate of 7.4 cases per 100,000. The overall rate of IPD in Indigenous Australians was almost 6 times the rate in non-Indigenous Australians in both 2009 and 2010. In 2009 and 2010, notification rates of IPD caused by serotypes included in the 7-valent pneumococcal conjugate vaccine (7vPCV) continued to decrease across all age groups. Rates of IPD caused by non-7vPCV serotypes continued to show an increasing trend in both Indigenous and non-Indigenous children aged less than 5 years. In Indigenous adults (≥50 years), rates of IPD caused by both 23-valent pneumococcal polysaccharide vaccine (23vPPV) serotypes and non-23vPPV serotypes continued to show an overall increase, particularly in 2010. There were 110 deaths attributed to IPD in 2009 and 137 in 2010, although it should be noted that deaths may be under-reported. The number of invasive pneumococcal isolates with reduced penicillin susceptibility remained low and reduced susceptibility to third generation cephalosporins was rare. PMID:26234260

  19. [Pneumococcal vaccines: different types and their use in practice].

    PubMed

    Van Steenkiste, M

    2013-03-01

    Streptococcus pneumoniae is responsible for a large number of invasive infections and upper respiratory tract infections in infants, elderly and patients with high complication risk. Currently, two types of vaccine are available on the Belgian market. In the context of pharmaceutical care, it is important for pharmacists to know their specific characteristics and differences. In this article we try to explain these and to motivate their use in different patient populations. The 23-valent vaccine is different from the 13-valent vaccine, not only in number of serotypes, but also in its presentation as respectively polysaccharide- and conjugated vaccine which affects the immunogenicity. Moreover, their indication and use are also different. Finally we take a closer look at the specific use in infants and children at risk at one hand, and vaccination of eldery and adults with increased risk for severe pneumococcal infection on the other hand. PMID:23638606

  20. Evaluation and Optimization of an ELISA Procedure to Quantify Antibodies Against Pneumococcal Polysaccharides Included in the 13-Valent Conjugate Vaccine.

    PubMed

    Belmonti, Simone; Lombardi, Francesca; Morandi, Matteo; Fabbiani, Massimiliano; Tordini, Giacinta; Cauda, Roberto; De Luca, Andrea; Di Giambenedetto, Simona; Montagnani, Francesca

    2016-01-01

    The 13-valent pneumococcal conjugate vaccine (PCV-13) is recommended for HIV-infected people, although its effectiveness in this population remains under evaluation. In this study, we describe the development, optimization, and analytical validation of an ELISA procedure to measure specific antibodies for the pneumococcal polysaccharide serotypes included in PCV13 vaccine, testing sera obtained from HIV-infected outpatients (n = 30) who received the vaccine. The protocol followed the last version of WHO guidelines, based on the new standard 007sp, with the modification of employing Statens Serum Institut (SSI) antigens. We supplied the assay performance validation in terms of sensitivity, reproducibility, precision and accuracy. In addition we detailed optimal antigen-coating concentrations and ELISA conditions common to all 13 serotypes, suitable for laboratories performing these assays in order to standardize the method. Our procedure showed reproducibility and reliability, making it a valid alternative for evaluating the response to pneumococcal serotypes included in PCV13 vaccine. PMID:26506438

  1. [Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural empyema and bacteremia].

    PubMed

    Kanık Yüksek, Saliha; Gülhan, Belgin; Tezer, Hasan; Özkaya Parlakay, Aslınur; Uzun Kenan, Bahriye; Sayed Oskovi, Hülya; Nar Ötgün, Selin

    2015-07-01

    Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and <2 years or >65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections

  2. Recurrent Invasive Pneumococcal Disease Serotype 12F in a Vaccinated Splenectomized Patient

    PubMed Central

    Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn; Kristensen, Lena Hagelskjær; Schumacher, Helga

    2016-01-01

    This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded that she had responded sufficiently to vaccination. Still, she had a fulminate recurrent infection with PPV23 serotype 12F. We investigated the anti-pneumococcal IgG test, and it turned out that it is based on the geometric mean value of only 12 of the serotypes included in PPV23; 12F is none of them. The reason is that there are no titer cut-offs available for 11 of the PPV23 serotypes, including 12F, neither nationally nor internationally. Yet, this is not specified in the answer to the clinicians. This case illustrates the need for titer cut-offs for the remaining pneumococcal serotypes in available vaccines, in order to get a more accurate estimation of the vaccination coverage for the individual patient. Therefore, more research on this area is warranted, along with a discussion of whether the laboratory answers to the clinicians should be more detailed. PMID:27141317

  3. Assignment of Weight-Based Antibody Units for Seven Additional Serotypes to a Human Pneumococcal Standard Reference Serum, 007sp

    PubMed Central

    Tan, C. Y.; Burbidge, P.; McElhiney, S.; McLaughlin, L.; Tucker, R.; Rauh, M.; Sidhu, M.; Giardina, P. C.

    2015-01-01

    The pneumococcal enzyme-linked immunosorbent assay (ELISA) reference standard serum, lot 89SF, has been in use since 1990 and was replaced in 2013 with a new reference standard, 007sp, that is projected to be available for the next 25 years. 007sp was generated under an FDA-approved clinical protocol; 278 adult volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice from each immunized subject within 120 days following immunization. Pooled serum was prepared from the plasma of 262 subjects, filled at 6 ml per vial, and lyophilized. Five independent laboratories participated in bridging the serotype-specific IgG assignments for 89SF to the new reference standard, 007sp, to establish equivalent reference values for 13 pneumococcal capsular serotypes (1,3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) by using the WHO reference ELISA. In a second study involving three laboratories, a similar protocol was used to assign weight-based IgG concentrations in micrograms per ml to 007sp of seven serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) also present in the 23-valent pneumococcal unconjugated polysaccharide vaccine. In addition, the IgG assignments for a 12-member WHO quality control (QC) serum panel were also extended to cover these seven serotypes. Agreement was excellent, with a concordance correlation coefficient (rc) of >0.996 when each laboratory was compared to the assigned values for the 12 WHO QC serum samples. There are four remaining pneumococcal serotypes (2, 9N, 17F, and 20) found in Pneumovax II for which IgG assignments exist for 89SF and remain to be bridged. PMID:26354860

  4. A review of the evidence to inform pneumococcal vaccine recommendations for risk groups aged 2 years and older.

    PubMed

    Steens, A; Vestrheim, D F; Aaberge, I S; Wiklund, B S; Storsaeter, J; Riise Bergsaker, M A; Rønning, K; Furuseth, E

    2014-12-01

    For decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine (PPV23) has been available for risk groups aged ⩾2 years to prevent invasive pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine (PCV13) has been licensed for use in all age groups. PCV13 may induce better protection than PPV23 because of different immunogenic properties. This called for a revision of vaccine recommendations for risk groups. We therefore reviewed literature on risk groups for IPD, and effectiveness and safety of pneumococcal vaccines and supplemented that with information from public health institutes, expert consultations and data on IPD epidemiology. We included 187 articles. We discuss the implications of the heterogenic vulnerability for IPD within and between risk groups, large indirect effects of childhood immunization, and limited knowledge on additional clinical benefits of PCV13 in combination with PPV23 for the Norwegian recommendations. These are now step-wise and consider the need for vaccination, choice of pneumococcal vaccines, and re-vaccination interval by risk group. PMID:24932959

  5. Call to action on pneumococcal disease: review of vaccination evidence and outcomes of webcast programs.

    PubMed

    Grogg, Stanley E; Schultz, Jan

    2015-06-01

    In 2015, the Advisory Committee on Immunization Practices issued updated recommendations for the use of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to immunize adults aged 19 to 64 years with risk factors and all adults aged 65 years or older. Despite these recommendations, rates of vaccination among adults remain low. Federal and state initiatives have been launched to encourage health care providers to incorporate vaccination screening and recommendations in practice. Several resources are available to improve vaccination rates, including implementing electronic medical records; engaging non-physician staff in assessing vaccination history and administering immunizations; adopting standing order protocols; and implementing strong recommendations to patients regarding needed immunizations. However, even in the face of compelling evidence-based research, implementing changes in practice is challenging. The American Osteopathic Association implemented a 2-part Web program called the Call to Action on Pneumococcal Disease. Although some changes in attitudes and intent to change were demonstrated by this initiative, there were no statistically significant increases in self-reported actual adoption of standing order protocols or increases in adult pneumococcal immunization. Nonetheless, some lessons were learned, and these results support the need for ongoing efforts in this area of medicine. PMID:26000904

  6. Why the recent ACIP recommendations regarding conjugate pneumococcal vaccine in adults may be irrelevant.

    PubMed

    Musher, Daniel M; Rodriguez-Barradas, Maria B

    2016-02-01

    The Advisory Committee on Immunization Practices of the US Centers for Disease Control (ACIP) has recently recommended the 13-valent protein-conjugate pneumococcal vaccine (PCV13) for routine use in adults age 18-65 who have immunocompromising conditions as well as in all adults over the age of 65. By comparison to 23-valent pneumococcal polysaccharide vaccine (PPSV23), antibody responses to PCV13 are similar or modestly better one month after vaccination. The implication that PCV13 will provide more persistent immunity has been disproven; 12 months later, recipients of PPSV23 or PCV13 have identical anti-pneumococcal activity. The theoretical concept that a protein-based vaccine will be followed by a booster effect when pure polysaccharide antigens are administered is based on remarkably little evidence. The strongest objection to the current recommendations is that, since PCVs stimulate mucosal antibodies, the widespread use of these PCVs has led to a near-disappearance of vaccine serotypes from the population. This phenomenon has been amply documented for PCV7, and PCV13 is well on its way to doing the same. Thus, as US physicians are convincing their adult patients to receive 2 "pneumonia shots" instead of one, the use of PCV13 in the USA is rapidly becoming irrelevant. PMID:26606172

  7. The Efficacy of Pneumococcal Capsular Polysaccharide-specific Antibodies to Serotype 3 Streptococcus pneumoniae requires Macrophages

    PubMed Central

    Fabrizio, Kevin; Manix, Catherine; Tian, Haijun; van Rooijen, Nico; Pirofski, Liise-anne

    2010-01-01

    The efficacy of antibody immunity against Streptococcus pneumoniae stems from the ability of opsonic, serotype (ST)-specific antibodies to pneumococcal capsular polysaccharide (PPS) to facilitate killing of the homologous ST by host phagocytes. However, PPS-specific antibodies have been identified that are protective in mice, but do not promote opsonic killing in vitro, raising the question of how they mediate protection in vivo. To probe this question, we investigated the dependence of antibody efficacy against lethal systemic (intraperitoneal, i.p.) infection with Streptococcus pneumoniae serotype 3 (ST3) on macrophages and neutrophils for the following PPS3-specific monoclonal antibodies (MAbs) in survival experiments in mice using a non-opsonic human IgM (A7), a non-opsonic mouse IgG1 (1E2) and an opsonic mouse IgG1 (5F6). The survival of A7- and PPS3-specific and isotype control-MAb-treated neutrophil-depleted and neutrophil-sufficient and macrophage-depleted and macrophage-sufficient mice were determined after i.p. challenge with ST3 strains 6303 and WU2. Neutrophils were dispensable for A7 and the mouse MAbs to mediate protection in this model, but macrophages were required for the efficacy of A7 and optimal mouse MAb-mediated protection. For A7-treated mice, macrophage-depleted mice had higher blood CFU, cytokines and peripheral neutrophil levels than macrophage-sufficient mice, and macrophage-sufficient mice had lower tissue bacterial burdens than control MAb-treated mice. These findings demonstrate that macrophages contribute to opsonic and non-opsonic PPS3-specific MAb-mediated protection against ST3 infection by enhancing bacterial clearance and suggest that neutrophils do not compensate for the absence of macrophages in the model used in this study. PMID:20800700

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

    PubMed Central

    Sadlier, C.; O’Dea, S.; Bennett, K.; Dunne, J.; Conlon, N.; Bergin, C.

    2016-01-01

    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. PMID:27580688

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

    PubMed

    Sadlier, C; O'Dea, S; Bennett, K; Dunne, J; Conlon, N; Bergin, C

    2016-01-01

    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. PMID:27580688

  10. Serotype Changes and Drug Resistance in Invasive Pneumococcal Diseases in Adults after Vaccinations in Children, Japan, 2010-2013.

    PubMed

    Ubukata, Kimiko; Chiba, Naoko; Hanada, Shigeo; Morozumi, Miyuki; Wajima, Takeaki; Shouji, Michi; Iwata, Satoshi

    2015-11-01

    After 7-valent pneumococcal conjugate vaccine (PCV) for children was introduced in Japan in November 2010, we examined changes in Streptococcus pneumoniae serotypes and in genetic antimicrobial drug resistance of isolates from adults with invasive pneumococcal diseases. During April 2010-March 2013, a total of 715 isolates were collected from adults with invasive pneumococcal diseases. Seven-valent PCV serotypes in adults decreased from 43.3% to 23.8%, most noticeably for serotype 6B. Concomitantly, 23-valent pneumococcal polysaccharide vaccine (PPSV23) serotypes decreased from 82.2% to 72.2%; non-PPSV23 serotypes increased from 13.8% to 25.1%. Parallel with serotype changes, genotypic penicillin-resistant S. pneumoniae decreased from 32.4% to 21.1%, and 6 non-PPSV23 serotypes emerged (6D, 15A, 15C, 16F, 23A, and 35B). Respective vaccine coverage rates for 13-valent PCV and PPSV23 differed by disease: 73.9% and 84.3% for patients with pneumonia, 56.4% and 69.2% for patients with bacteremia and sepsis, and 45.7% and 69.3% for patients with meningitis. PMID:26485679

  11. Serotype Changes and Drug Resistance in Invasive Pneumococcal Diseases in Adults after Vaccinations in Children, Japan, 2010–2013

    PubMed Central

    Chiba, Naoko; Hanada, Shigeo; Morozumi, Miyuki; Wajima, Takeaki; Shouji, Michi; Iwata, Satoshi

    2015-01-01

    After 7-valent pneumococcal conjugate vaccine (PCV) for children was introduced in Japan in November 2010, we examined changes in Streptococcus pneumoniae serotypes and in genetic antimicrobial drug resistance of isolates from adults with invasive pneumococcal diseases. During April 2010–March 2013, a total of 715 isolates were collected from adults with invasive pneumococcal diseases. Seven-valent PCV serotypes in adults decreased from 43.3% to 23.8%, most noticeably for serotype 6B. Concomitantly, 23-valent pneumococcal polysaccharide vaccine (PPSV23) serotypes decreased from 82.2% to 72.2%; non-PPSV23 serotypes increased from 13.8% to 25.1%. Parallel with serotype changes, genotypic penicillin-resistant S. pneumoniae decreased from 32.4% to 21.1%, and 6 non-PPSV23 serotypes emerged (6D, 15A, 15C, 16F, 23A, and 35B). Respective vaccine coverage rates for 13-valent PCV and PPSV23 differed by disease: 73.9% and 84.3% for patients with pneumonia, 56.4% and 69.2% for patients with bacteremia and sepsis, and 45.7% and 69.3% for patients with meningitis. PMID:26485679

  12. Invasive pneumococcal disease in Australia, 2011 and 2012.

    PubMed

    Toms, Cindy; de Kluyver, Rachel

    2016-01-01

    In Australia, there were 1,883 cases (8.3 per 100,000 population) of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System (NNDSS) in 2011 and 1,823 cases (8.0 per 100,000) in 2012. The overall rate of IPD in Indigenous Australians was 9 times the rate of IPD in non-Indigenous Australians in 2011 and 7 times in 2012. Following the July 2011 introduction of the 13-valent pneumococcal conjugate vaccine (13vPCV) to the National Immunisation Program, rates of IPD in children aged less than 5 years decreased from 19.5 per 100,000 in 2011 to 12.6 per 100,000 in 2012. In Indigenous adults aged 50 years or over the rates of IPD caused by serotypes included in the 23-valent pneumococcal polysaccharide vaccine (23vPPV) continued to increase in both 2011 (47.2 per 100,000) and 2012 (51.2 per 100,000). The rates of IPD in non-Indigenous adults aged 65 years or over caused by serotypes included in the 23vPPV also increased in 2011 (10.1 per 100,000) and 2012 (11.2 per 100,000). There were 134 deaths attributable to IPD in 2011 and 126 in 2012, although it should be noted that deaths may be under-reported. The number of invasive pneumococcal isolates with reduced penicillin susceptibility remained low and reduced susceptibility to ceftriaxone/cefotaxime continued to be rare. PMID:27522138

  13. A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany.

    PubMed

    Jiang, Yiling; Gauthier, Aline; Annemans, Lieven; van der Linden, Mark; Nicolas-Spony, Laurence; Bresse, Xavier

    2012-10-01

    To assess the comparative public health and budget impact over 5 years of several pneumococcal vaccination strategies (23-valent pneumococcal polysaccharide vaccine [PPV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]) in Germany, within the context of changing invasive pneumococcal disease (IPD) incidence over time. A multi-cohort, population-based Markov model was developed. Uncertainty around vaccine effectiveness, costs and IPD incidence change was handled through scenario analyses. Between 2012 and 2016, the introduction of PCV13 in adults, compared with the use of PPV23, would be associated with a net estimated budget increase of €59.7 million (+6.7%) to €151.6 million (+13.7%). Impact on IPD incidence ranged from -113 cases (-0.8%) to +298 cases (+2.8%). Introducing PCV13 in adults is expected to significantly affect healthcare budgets. Adult vaccination with PPV23 remains the optimal vaccination strategy from public health and budget perspectives. PMID:23025421

  14. Effects of solution conditions on characteristics and size exclusion chromatography of pneumococcal polysaccharides and conjugate vaccines.

    PubMed

    Hadidi, Mahsa; Buckley, John J; Zydney, Andrew L

    2016-11-01

    Molecular properties of bacterial polysaccharides and protein-polysaccharide conjugates play an important role in the efficiency and immunogenicity of the final vaccine product. Size exclusion chromatography (SEC) is commonly used to analyze and characterize biopolymers, including capsular polysaccharides. The objective of this work was to determine the effects of solution ionic strength and pH on the SEC retention of several capsular polysaccharides from S. pneumoniae bacteria in their native and conjugated forms. The retention time of the charged polysaccharides increased with increasing ionic strength and decreasing pH due to compaction of the polysaccharides associated with a reduction in the intramolecular electrostatic interactions. The calculated radius of gyration was in good agreement with model calculations based on the worm-like chain model accounting for the increase in chain stiffness and excluded volume of the charged polysaccharide at low ionic strength. These results provide important insights into the effects of solution ionic strength on physical properties and SEC behavior of capsular polysaccharides and their corresponding conjugates. PMID:27516244

  15. Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in children vaccinated with conjugated polysaccharide pneumococcal vaccines

    PubMed Central

    Wyllie, Anne L.; Wijmenga-Monsuur, Alienke J.; van Houten, Marlies A.; Bosch, Astrid A. T. M.; Groot, James A.; van Engelsdorp Gastelaars, Jody; Bruin, Jacob P.; Bogaert, Debby; Rots, Nynke Y.; Sanders, Elisabeth A. M.; Trzciński, Krzysztof

    2016-01-01

    Following the introduction of pneumococcal conjugate vaccines (PCVs) for infants, surveillance studies on Streptococcus pneumoniae carriage have proven valuable for monitoring vaccine effects. Here, we compared molecular versus conventional diagnostic methods in prospective cross-sectional surveillances in vaccinated infants in the Netherlands. Nasopharyngeal samples (n = 1169) from 11- and 24-month-old children, collected during autumn/winter 2010/2011 and 2012/2013, were tested by conventional culture for S. pneumoniae. DNA extracted from all culture-plate growth was tested by qPCR for pneumococcal-specific genes (lytA/piaB) and selected serotypes (including PCV13-serotypes). qPCR significantly increased the number of carriers detected compared to culture (69% vs. 57%, p < 0.0001). qPCR assays targeting vaccine-serotypes 4 and 5 proved non-specific (results excluded). For serotypes reliably targeted by qPCR, the number of serotype-carriage events detected by qPCR (n = 709) was 1.68× higher compared to culture (n = 422). There was a strong correlation (rho = 0.980; p < 0.0001) between the number of serotypes detected using qPCR and by culture. This study demonstrates the high potential of molecular methods in pneumococcal surveillances, particularly for enhanced serotype detection. We found no evidence of a hidden circulation of vaccine-targeted serotypes, despite vaccine-serotypes still significantly contributing to invasive pneumococcal disease in unvaccinated individuals, supporting the presence of a substantial S. pneumoniae reservoir outside vaccinated children. PMID:27046258

  16. Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in children vaccinated with conjugated polysaccharide pneumococcal vaccines.

    PubMed

    Wyllie, Anne L; Wijmenga-Monsuur, Alienke J; van Houten, Marlies A; Bosch, Astrid A T M; Groot, James A; van Engelsdorp Gastelaars, Jody; Bruin, Jacob P; Bogaert, Debby; Rots, Nynke Y; Sanders, Elisabeth A M; Trzciński, Krzysztof

    2016-01-01

    Following the introduction of pneumococcal conjugate vaccines (PCVs) for infants, surveillance studies on Streptococcus pneumoniae carriage have proven valuable for monitoring vaccine effects. Here, we compared molecular versus conventional diagnostic methods in prospective cross-sectional surveillances in vaccinated infants in the Netherlands. Nasopharyngeal samples (n = 1169) from 11- and 24-month-old children, collected during autumn/winter 2010/2011 and 2012/2013, were tested by conventional culture for S. pneumoniae. DNA extracted from all culture-plate growth was tested by qPCR for pneumococcal-specific genes (lytA/piaB) and selected serotypes (including PCV13-serotypes). qPCR significantly increased the number of carriers detected compared to culture (69% vs. 57%, p < 0.0001). qPCR assays targeting vaccine-serotypes 4 and 5 proved non-specific (results excluded). For serotypes reliably targeted by qPCR, the number of serotype-carriage events detected by qPCR (n = 709) was 1.68× higher compared to culture (n = 422). There was a strong correlation (rho = 0.980; p < 0.0001) between the number of serotypes detected using qPCR and by culture. This study demonstrates the high potential of molecular methods in pneumococcal surveillances, particularly for enhanced serotype detection. We found no evidence of a hidden circulation of vaccine-targeted serotypes, despite vaccine-serotypes still significantly contributing to invasive pneumococcal disease in unvaccinated individuals, supporting the presence of a substantial S. pneumoniae reservoir outside vaccinated children. PMID:27046258

  17. Interlaboratory Comparison of Three Multiplexed Bead-Based Immunoassays for Measuring Serum Antibodies to Pneumococcal Polysaccharides

    PubMed Central

    Whaley, Melissa J.; Rose, Charles; Martinez, Joseph; Laher, Gouri; Sammons, Deborah L.; Smith, Jerry P.; Snawder, John E.; Borrow, Ray; Biagini, Raymond E.; Plikaytis, Brian; Carlone, George M.; Romero-Steiner, Sandra

    2010-01-01

    Serotype-specific IgG, as quantified by a standardized WHO enzyme-linked immunosorbent assay (ELISA), is a serologic end point used to evaluate pneumococcal polysaccharide-based vaccine immunogenicity. Antibodies to each vaccine polysaccharide in licensed multivalent vaccines are quantified separately; this is laborious and consumes serum. We compared three bead-based immunoassays: a commercial assay (xMAP Pneumo14; Luminex) and two in-house assays (of the Health Protection Agency [HPA] and Centers for Disease Control and Prevention [CDC]), using the WHO-recommended standard reference and reference sera (n = 11) from vaccinated adults. Multiple comparisons of the IgG concentrations for seven conjugate vaccine serotypes were performed by sample (percent error), serotype (equivalency testing), and laboratory (concordance correlation coefficient [CCC]). When comparing concentrations by sample, bead-based immunoassays generally yielded higher antibody concentrations than the ELISA and had higher variability for serotypes 6B, 18C, and 23F. None of the three assays met the current WHO recommendation of 75% of sera falling within 40% of the assigned antibody concentrations for all seven serotypes. When compared by serotype, the CDC and HPA tests were equivalent for five of seven serotypes, whereas the Luminex assay was equivalent for four of seven serotypes. When overall mean IgG concentrations were compared by laboratory, a higher level of agreement (CCC close to 1) was found among bead-based immunoassays than between the assays and WHO assignments. When compared to WHO assignments, the HPA assay outperformed the other assays (r = 0.920; CCC = 0.894; coefficient of accuracy = 0.972). Additional testing with sera from immunogenicity studies should demonstrate the applicability of this methodology for vaccine evaluation. PMID:20335434

  18. Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2.

    PubMed Central

    Griffioen, A W; Rijkers, G T; Janssens-Korpela, P; Zegers, B J

    1991-01-01

    The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a split product of C3 that is generated after degradation of iC3b, can be bound to PS antigens. The binding of C3d to PS can occur in the absence of specific antibodies. Subsequently, we showed that PS complexed with C3d can be recognized by complement receptor type 2 that is expressed on B cells. Treatment of B cells with a monoclonal antibody recognizing the C3d-binding site of complement receptor type 2 reduces the binding of PS-C3d to the cells. In addition, we showed that PS4 complexed with C3d exerted an increased immunogenicity compared with free PS4. Our results show that the complement system plays a role in the activation of PS-specific B cells, carrying membrane receptors for C3d. Consequently, the complement system plays a regulatory role in the antibody response to T-cell-independent type 2 antigens such as PS. PMID:1826897

  19. Further Studies on the Immunogenicity of Haemophilus influenzae Type b and Pneumococcal Type 6A Polysaccharide-Protein Conjugates

    PubMed Central

    Chu, Chiayung; Schneerson, Rachel; Robbins, John B.; Rastogi, Suresh C.

    1983-01-01

    Conjugates were prepared by carbodiimide-mediated coupling of adipic acid hydrazide derivatives of Haemophilus influenzae type b (Hib), Escherichia coli K100, and pneumococcal 6A (Pn6A) polysaccharides with tetanus toxoid (TT), as an example of a “useful” carrier, and horseshoe crab hemocyanin (HCH), as an example of a “nonsense” carrier. These conjugates were injected into NIH mice, and their serum antibody responses to the polysaccharides and proteins were characterized. As originally reported, Hib conjugates increased the immunogenicity of the capsular polysaccharide and elicited greater than the estimated protective levels of anti-Hib antibodies in most recipients after one injection and in all after the third injection (Schneerson et al., J. Exp. Med. 152:361-376, 1980). Both Hib conjugates induced similar anti-Hib responses. The K100-HCH conjugate was more immunogenic than the K100-TT conjugate and elicited anti-Hib responses similar to the Hib conjugates after the third injection. Simultaneous injection of the K100 and the Hib conjugates did not enhance the anti-Hib response. The Pn6A-TT conjugate induced low levels of anti-Hib antibodies; when injected simultaneously with the Hib conjugates, the anti-Hib response was enhanced, as all mice responded after the first injection and with higher levels of anti-Hib than observed with the Hib conjugates alone (P < 0.05). The Pn6A conjugates were not as immunogenic as the Hib conjugates. Pn6A-TT was more effective than was Pn6A-HCH; it elicited anti-Pn6A (>100 ng of antibody nitrogen per ml) in 6 of 10 mice after the third injection. The addition of the Hib-HCH conjugate to the Pn6A-TT conjugate increased the anti-Pn6A response with a higher geometric mean antibody titer, and 9 of 10 mice responded after the third injection. A preparation of diphtheria toxoid, TT, and pertussis vaccine increased the anti-Hib antibody levels after the first injection only in mice receiving Hib-TT, but not in mice receiving

  20. Open-Label Trial of Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine in Adults ≥50 Years of Age in Mexico

    PubMed Central

    Juergens, Christine; Ruiz Palacios, Guillermo M.; Vazquez-Narvaez, Jorge; Enkerlin-Pauwells, Hermann Leo; Sundaraiyer, Vani; Pathirana, Sudam; Kalinina, Elena; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2014-01-01

    This open-label multicenter clinical trial conducted in Mexico assessed the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥50 years of age not previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). The PCV13 elicited a robust immune response in this study population, as reflected by the magnitude of fold rises in functional antibody levels measured by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination. Although the prevaccination OPA geometric mean titers (GMTs) for the majority of the serotypes were significantly lower in the 50- to 64-year age group than those in the ≥65-year age group, the postvaccination immune responses were generally similar. The overall immune responses were higher for the majority of the serotypes in the Mexican study population than those in similar adult study populations who received the PCV13 in Europe and the United States. PCV13 was well tolerated, and there were no vaccine-related serious adverse events. In conclusion, PCV13 is safe and immunogenic when administered to adults ≥50 years of age in Mexico and has the potential to protect against vaccine-type pneumococcal disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT01432262.) PMID:25499011

  1. Functional anti-polysaccharide IgG titres induced by unadjuvanted pneumococcal-conjugate vaccine when delivered by microprojection-based skin patch.

    PubMed

    Pearson, Frances E; Muller, David A; Roalfe, Lucy; Zancolli, Marta; Goldblatt, David; Kendall, Mark A F

    2015-11-27

    Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia--a consequence of Streptococcus pneumoniae infection--is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine. PMID:26518398

  2. [Pneumococcal vaccines. New conjugate vaccines for adults].

    PubMed

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. PMID:26474708

  3. Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

    PubMed Central

    Perciani, Catia T.; Barazzone, Giovana C.; Goulart, Cibelly; Carvalho, Eneas; Cabrera-Crespo, Joaquin; Gonçalves, Viviane M.; Leite, Luciana C. C.

    2013-01-01

    Despite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface protein A (rPspA), a well-known protective antigen from Streptococcus pneumoniae, were covalently attached by two conjugation methods. The conjugation methodology developed by our laboratory, employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an activating agent through carboxamide formation, was compared with reductive amination, a classical methodology. DMT-MM-mediated conjugation was shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate fraction with reductive amination. The influence of the conjugation process on the rPspA1 structure was assessed by circular dichroism. According to our results, both conjugation processes reduced the alpha-helical content of rPspA; reduction was more pronounced when the reaction between the polysaccharide capsule and rPspA1 was promoted between the carboxyl groups than the amine groups (46% and 13%, respectively). Regarding the immune response, both conjugates induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest that the secondary structure of PspA1, as well as its reactive groups (amine or carboxyl) involved in the linkage to PS6B, may not play an important role in eliciting a protective immune response to the antigens. PMID:23554468

  4. Pneumococcal Disease

    MedlinePlus

    ... pneumococcal disease. Quick Facts About Pneumococcal Disease and Vaccination According to WHO, pneumococcal pneumonia and meningitis are ... of antibiotic treatment. (9, 10, 11) Conjugate pneumococcal vaccination is safe and effective for preventing severe childhood ...

  5. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Coalition; Centers for Disease Control and Prevention Pneumococcal Polysaccharide Vaccine (PPV23) English 肺炎球菌多糖疫苗 - 繁體中文 (Chinese - Traditional) PDF ... Coalition; Centers for Disease Control and Prevention Pneumococcal Polysaccharide Vaccine (PPV23) English Русский (Russian) PDF Immunization Action ...

  6. Development of a conjugate vaccine against invasive pneumococcal disease based on capsular polysaccharides coupled with PspA/family 1 protein of Streptococcus pneumoniae.

    PubMed

    Lin, Haiying; Peng, Yonghui; Lin, ZiLin; Zhang, Shuangling; Guo, Yanghao

    2015-01-01

    The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. Our strategy involved the use of the carrier protein, pneumococcal surface protein A (PspA), conjugated with capsular polysaccharides (CPS), to provide effective and non-serotype-dependent protection. In this study, we generated a stable Escherichia coli construct expressing functional PspA from a capsular serotype 6B strain and confirmed it belonging to family 1, which was conjugated with CPS. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, but that of anti-PspA IgG subclass antibodies was almost equal IgG1 and IgG2a subclasses. Though PspA was less conspicuous on the surface of pneumococci than the capsule, the antibodies induced with CPS-rPspA conjugate possessed more accessibility to the surface of Streptococcus pneumoniae serotype 6B and 19F (the same family 1 PspA). By survival experiment, the result suggested that the level of cross-protection after immunized with the conjugate was more measurable within the same family 1. The CPS-rPspA conjugate not only induced CPS-specific protection but also provided PspA specific cross-protection. PMID:25959527

  7. Non-invasive pneumococcal pneumonia in Portugal--serotype distribution and antimicrobial resistance.

    PubMed

    Horácio, Andreia N; Lopes, Joana P; Ramirez, Mário; Melo-Cristino, José

    2014-01-01

    There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999-2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009-2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999-2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009-2011 - serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD. PMID:25075961

  8. Meningitis - pneumococcal

    MedlinePlus

    ... and older People at high risk for pneumococcus infection Alternative Names Pneumococcal meningitis Images Pneumococci organism Pneumococcal pneumonia References Swartz MN. Meningitis: bacterial, ...

  9. Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2012-01-01

    We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years. PMID:22100892

  10. Antibody Persistence and Immunologic Memory after Sequential Pneumococcal Conjugate and Polysaccharide Vaccination in HIV-Infected Children on Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Song, Lin Ye; Levin, Myron J.; Nachman, Sharon A.; Borkowsky, William; Pelton, Stephen I.

    2013-01-01

    Background The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. Methods HIV-infected children 2–<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized four-five years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5 mcg/mL of serotype-specific antibody on day 0 or change from <0.5 mcg/mL to ≥0.5 mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Results Prior to boosting, four to five years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL (serotype 14), with concentrations ≥0.5 mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5 mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42–61% for serotype 1 and 87–94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3–13%; serotype 6B, 13–31%; serotype 14, 29–53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5–0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Conclusions Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present four-five years after PCV7-PCV7-PPV in HIV-infected children on HAART. PMID:23954381

  11. Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

    PubMed Central

    Restori, Katherine H.; Kennett, Mary J.

    2013-01-01

    Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positive Streptococcus pneumoniae serotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum. PMID:23389932

  12. Role of complement receptor type 2 and endogenous complement in the humoral immune response to conjugates of complement C3d and pneumococcal serotype 14 capsular polysaccharide.

    PubMed

    Mitsuyoshi, Joyce K; Hu, Yong; Test, Samuel T

    2005-11-01

    Conjugation of the complement fragment C3d to both T-cell-dependent (TD) protein and T-cell-independent type 2 (TI-2) polysaccharide antigens enhances the humoral immune response in mice immunized with either type of antigen. However, the ability of C3d-protein conjugates to enhance the antibody response in mice deficient in complement receptor types 1 and 2 (CR1 and CR2) has raised questions about the role of C3d-CR2 interactions in the adjuvant effect of C3d. In this study, we examined the role of CR2 binding and endogenous complement activation in the antibody response to conjugates of C3d and serotype 14 pneumococcal capsular polysaccharide (PPS14). To block binding of PPS14-C3d conjugates to CR2, mice were immunized with a mixture of vaccine and (CR2)2-immunoglobulin G1 (IgG1). Mice receiving (CR2)2-IgG1 at the time of primary immunization had a marked reduction in the primary anti-PPS14 antibody response but an enhanced secondary anti-PPS14 response, suggesting that C3d-CR2 interactions are required for the primary response but can have negative effects on the memory response. Further, compared with mice receiving PPS14-C3d having a high C3d/PPS14 ratio, mice immunized with PPS14-C3d with low C3d/PPS14 ratios had an enhanced secondary antibody response. Treatment of mice with cobra venom factor to deplete complement had insignificant effects on the antibody response to PPS14-C3d. Experiments with CBA/N xid mice confirmed that PPS14-C3d conjugates retain the characteristics of TI-2 rather than TD antigens. Thus, the adjuvant effect of C3d conjugated to PPS14 requires C3d-CR2 interactions, does not require activation of endogenous complement, and is not mediated by TD carrier effects. PMID:16239528

  13. The majority of adult pneumococcal invasive infections in Portugal are still potentially vaccine preventable in spite of significant declines of serotypes 1 and 5.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2013-01-01

    In Portugal, pneumococcal conjugate vaccines have been administered to children outside of the national immunization plan since 2001. We determined the serotype and antimicrobial susceptibility of 1265 isolates responsible for adult invasive pneumococcal infections (IPD) between 2009 and 2011 and compared the results with previously published data from 1999 to 2008. Serotypes 3 (12.6%), 7F (10.0%), 19A (9.1%), 14 (8.4%), 1 (6.9%) and 8 (6.2%) were the most frequent and together accounted for 53.2% of adult IPD. Serotypes 1 and 5 declined significantly while serotype 34, not included in any vaccine, increased. Taken together, the serotypes included in the 13-valent conjugate vaccine (PCV13) peaked among adult IPD isolates in 2008 (70.2%) and declined since then reaching 53.5% in 2011. The decline in the serotypes included in the 23-valent polysaccharide vaccine since 2007 was also significant but much more modest with 79.2% of the isolates causing IPD in 2011 expressing these serotypes. Since the changes in serotypes causing IPD in adults coincided with the 10-valent and PCV13 introduction in children, it is unlikely that vaccination triggered these changes although it may have accelerated them. The proportion of IPD caused by serotypes included in the 7-valent conjugate vaccine remained stable (19.0%). Both penicillin non-susceptibility and erythromycin resistance increased in the study period, with serotypes 14 and 19A accounting for the majority of resistant isolates. PMID:24066064

  14. Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide.

    PubMed

    Test, S T; Mitsuyoshi, J; Connolly, C C; Lucas, A H

    2001-05-01

    Previous studies have demonstrated an adjuvant effect for the C3d fragment of complement C3 when coupled to T-dependent protein antigens. In this study, we examined the antibody response to covalent conjugates of C3d and a T-independent antigen, the capsular polysaccharide of serotype 14 Streptococcus pneumoniae (PPS14). We prepared a conjugate of mouse C3d and PPS14 and compared its immunogenicity with that of a conjugate of PPS14 and ovalbumin (OVA). When BALB/c mice were immunized with PPS14-C3d, there was a significant increase in serum anti-PPS14 concentrations compared with either native PPS14 or control PPS14-glycine conjugates. This was accompanied by a switch in anti-PPS14 from predominantly immunoglobulin M (IgM) to IgG1 by day 25 following primary immunization. Following secondary immunization with PPS14-C3d, there was a marked booster response and a further increase in the ratio of IgG1 to IgM anti-PPS14. Although the primary antibody response to the PPS14-OVA conjugate exceeded that induced by immunization with PPS14-C3d, serum anti-PPS14 concentrations after a second injection of PPS14-C3d were nearly identical to those induced by secondary immunization with PPS14-OVA. Experiments with athymic nude mice suggested that T cells were not required for the adjuvant effect of C3d on the primary immune response to PPS14 but were necessary for enhancement of the memory response after a second injection of PPS14-C3d. These studies show that the adjuvant effects of C3d extend to T-independent antigens as well as T-dependent antigens. As a means of harnessing the adjuvant potential of the innate immune system, C3d conjugates may prove useful as a component of vaccines against encapsulated bacteria. PMID:11292721

  15. Increased Immunogenicity and Induction of Class Switching by Conjugation of Complement C3d to Pneumococcal Serotype 14 Capsular Polysaccharide

    PubMed Central

    Test, Samuel T.; Mitsuyoshi, Joyce; Connolly, Charles C.; Lucas, Alexander H.

    2001-01-01

    Previous studies have demonstrated an adjuvant effect for the C3d fragment of complement C3 when coupled to T-dependent protein antigens. In this study, we examined the antibody response to covalent conjugates of C3d and a T-independent antigen, the capsular polysaccharide of serotype 14 Streptococcus pneumoniae (PPS14). We prepared a conjugate of mouse C3d and PPS14 and compared its immunogenicity with that of a conjugate of PPS14 and ovalbumin (OVA). When BALB/c mice were immunized with PPS14-C3d, there was a significant increase in serum anti-PPS14 concentrations compared with either native PPS14 or control PPS14-glycine conjugates. This was accompanied by a switch in anti-PPS14 from predominantly immunoglobulin M (IgM) to IgG1 by day 25 following primary immunization. Following secondary immunization with PPS14-C3d, there was a marked booster response and a further increase in the ratio of IgG1 to IgM anti-PPS14. Although the primary antibody response to the PPS14-OVA conjugate exceeded that induced by immunization with PPS14-C3d, serum anti-PPS14 concentrations after a second injection of PPS14-C3d were nearly identical to those induced by secondary immunization with PPS14-OVA. Experiments with athymic nude mice suggested that T cells were not required for the adjuvant effect of C3d on the primary immune response to PPS14 but were necessary for enhancement of the memory response after a second injection of PPS14-C3d. These studies show that the adjuvant effects of C3d extend to T-independent antigens as well as T-dependent antigens. As a means of harnessing the adjuvant potential of the innate immune system, C3d conjugates may prove useful as a component of vaccines against encapsulated bacteria. PMID:11292721

  16. Efficacy of PPV23 in Preventing Pneumococcal Pneumonia in Adults at Increased Risk – A Systematic Review and Meta-Analysis

    PubMed Central

    Schiffner-Rohe, Julia; Witt, Annika; Hemmerling, Jana; von Eiff, Christof; Leverkus, Friedrich-Wilhelm

    2016-01-01

    Background Pneumococcal community-acquired pneumonia (pCAP) is the most frequent form of pneumonia. The elderly and adults with underlying diseases are at an increased risk of developing pCAP. The 23-valent pneumococcal polysaccharide vaccine (PPV23) was licensed over 30 years ago and is recommended as the standard intervention in many countries across the globe, although its efficacy continues to be debated. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the effect of PPV23 for preventing pCAP in adults ≥60 years of age. Methods An existing Cochrane Review was updated to Oct 2014 using a systematic literature search to select appropriate RCTs. DerSimonian and Laird random-effects meta-analyses were performed and odd ratios (OR) with 95%-confidence intervals (CI) and p-values were calculated for the descriptive analyses. Reasons for heterogeneity were explored by subgroup analyses. Results Meta-analysis of PPV23 efficacy included four studies. Three of them did not demonstrate efficacy for PPV23. The body of evidence indicated statistically significant heterogeneity (I2 = 78%, p = 0.004) that could be explained by subgroup analysis by “study setting”. Further effect modifiers for pCAP were “continent of trial” (p<0.01), and “method of pneumococcal diagnostics” (p = 0.001). Subgroup analyses revealed that the only study showing efficacy for PPV23 was an outlier. Overall, the validity of the meta-analytic PPV23 efficacy assessment was confirmed by the meta-analysis of all-cause CAP including six studies. Discussion Inconsistencies in PPV23 treatment effects to prevent pCAP could solely be explained by one outlier study that was performed in nursing homes in Japan. The effect modifier “method of pneumococcal diagnostics” should be interpreted carefully, since methodological weaknesses are not restricted to one special method only, which would justify the exclusion of certain studies. Overall, we conclude from our

  17. Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England

    PubMed Central

    van Hoek, Albert Jan; Miller, Elizabeth

    2016-01-01

    Background Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. Method A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. Results The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust

  18. Pneumococcal vaccination in older adults in the era of childhood vaccination: Public health insights from a Norwegian statistical prediction study.

    PubMed

    Steens, Anneke; Vestrheim, Didrik F; de Blasio, Birgitte Freiesleben

    2015-06-01

    Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13 + PPV23 in 2014-2019. Quasi-Poisson regression models were fitted to 2004-2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in 2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity. PMID:25979279

  19. Pneumococcal Infections

    MedlinePlus

    ... blood, imaging, or lab tests. Treatment is with antibiotics. Vaccines can prevent pneumococcal infections. There are two vaccines. One is for infants and young children. The other is for people ...

  20. Pneumococcal Disease

    MedlinePlus

    ... is a very serious infection that causes pneumonia, meningitis, and bloodstream infection (sepsis). About one million US ... will die from it. Fewer will get pneumococcal meningitis or sepsis, but the mortality rate in this ...

  1. Increase in Invasive Streptococcus pneumoniae Infections in Children with Sickle Cell Disease since Pneumococcal Conjugate Vaccine Licensure

    PubMed Central

    McCavit, Timothy L.; Quinn, Charles T.; Techasaensiri, Chonnamet; Rogers, Zora R.

    2010-01-01

    Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine (PCV7) usage. We report 10 IPD cases since PCV7 licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in SCD. PMID:21193205

  2. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults.

    PubMed

    Offersen, Rasmus; Melchjorsen, Jesper; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Søgaard, Ole S

    2012-08-01

    HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/- a TLR9 agonist (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group had significantly higher relative cytokine responses than the placebo group for IL-1β, IL-2R, IL-6, IFN-γ and MIP-β, which, did not correlate with IgG antibody responses. These findings suggests that CPG 7909 as adjuvant to pneumococcal conjugate vaccine induces cellular memory to pneumococcal polysaccharides in HIV-patients, independently of the humoral response. PMID:22854665

  3. Binding of Klebsiella K/sub 2/ LPS to specific antibody and cross-reactivity with pneumococcal group 19 polysaccharides (PS)

    SciTech Connect

    Li, J.P.; Ching, E.D.; Lee, C.J.

    1987-05-01

    The authors have studied the chemical basis of the antigen-antibody reaction between Klebsiella K/sub 2/ LPS and specific antiserum, and cross-reactivity with pneumococcal group 19 PSs. K/sub 2/ LPS was isolated and purified from Klebsiella K/sub 2/ strain by the methods of hot phenol-water extraction, ultracentrifugation, treatment with enzymes and gel filtration. K/sub 2/ LPS was hydrolyzed with 1% acetic acid to produce 2 fractions, separated by Sephadex G-50 column. Fraction G-I was passed through Sepharose 4B column to separate into 3 peaks (4B-I, -II, and -III). Peak 4B-II showed a molecular size of Kd, 0.35 and 4B-III had Kd, 0.79. When K/sub 2/ LPS was injected to mice, IgM and IgG antibody responses were induced, as determined by ELISA. In contrast, with the 19F and 19A PSs, the K/sub 2/ LPS induced antibody was mostly IgM. They have studied the ability of PS fractions (4B-II, 4B-III and G-I) to inhibit the binding of K/sub 2/ LPS to specific IgM and IgG antibodies. Among these fractions, 4B-II PS showed a highest inhibition to the binding activity; approximately 1000-fold greater inhibiting ability than 4B-III and G-I PS. These results indicate that 4B-II PS may serve as an immunologic determinant of K/sub 2/ LPS. Pneumococcal 19F and 19A PSs induced low inhibition of the binding activity between K/sub 2/ LPS and specific IgM antibody. The fraction 4B-II as immunologic determinant of K/sub 2/ LPS was further characterized by /sup 125/I-K/sub 2/ LPS anti-serum and Western blotting electrophoresis.

  4. Clinical effectiveness of pneumococcal vaccine. Meta-analysis.

    PubMed Central

    Hutchison, B. G.; Oxman, A. D.; Shannon, H. S.; Lloyd, S.; Altmayer, C. A.; Thomas, K.

    1999-01-01

    OBJECTIVE: To determine the clinical effectiveness of pneumococcal vaccine. DATA SOURCES: Computerized searches of MEDLINE, EMBASE, and SCISEARCH databases were performed, reference lists of retrieved articles were reviewed, and first authors of published studies were contacted. STUDY SELECTION: Studies of use of pneumococcal vaccines in adults were included if the study design was a randomized or quasi-randomized controlled trial and at least one of the following clinical outcomes was reported: vaccine-type systemic pneumococcal infection, systemic pneumococcal infection, vaccine-type pneumococcal pneumonia, pneumococcal pneumonia, non-vaccine-type pneumococcal pneumonia. SYNTHESIS: Study quality was assessed and descriptive information concerning the study populations, interventions, and outcome measurements was extracted for 13 trials involving more than 65,000 patients. Estimates of vaccine efficacy, based on a meta-analysis of randomized and quasi-randomized trials, were determined for clinical outcomes. CONCLUSIONS: Vaccination with pneumococcal polysaccharide vaccine can be expected to reduce the risk of systemic infection due to pneumococcal types included in the vaccine by 83% and systemic infection due to all pneumococci by 73%. We found no evidence that the vaccine was less efficacious for the elderly, institutionalized people, or those with chronic disease. PMID:10540698

  5. Depletion of complement has distinct effects on the primary and secondary antibody responses to a conjugate of pneumococcal serotype 14 capsular polysaccharide and a T-cell-dependent protein carrier.

    PubMed

    Test, Samuel T; Mitsuyoshi, Joyce K; Hu, Yong

    2005-01-01

    Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 mug of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines. PMID:15618164

  6. Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination

    PubMed Central

    Fay, Emily E.; Hoppe, Kara K.; Schulkin, Jay; Eckert, Linda O.

    2016-01-01

    Objective. The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. Methods. We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. Results. 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed. PMID:26949324

  7. Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination.

    PubMed

    Fay, Emily E; Hoppe, Kara K; Schulkin, Jay; Eckert, Linda O

    2016-01-01

    Objective. The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. Methods. We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. Results. 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed. PMID:26949324

  8. The contribution of naturally occurring IgM antibodies, IgM cross-reactivity and complement dependency in murine humoral responses to pneumococcal capsular polysaccharides.

    PubMed

    Jones, Hannah E; Taylor, Philip R; McGreal, Eamon; Zamze, Susanne; Wong, Simon Y C

    2009-09-25

    Immunogenicity of 12 capsular polysaccharides (CPS) from Streptococcus pneumoniae did not correlate with pre-existing levels of natural IgM anti-CPS antibodies in mice. Immunization of mice with individual CPS, with the exception of type 14 (the only neutral CPS tested), increased serum IgM that also bound other CPS serotypes independent of structural similarity or commonly known contaminants. Surprisingly only IgM response to type 4 (which has a small immunodominant epitope) was dependent on either complement C3 or complement receptors CD35/CD21. IgG anti-CPS responses were infrequently induced, but critically dependent on complement. Our results have clarified the role of complement in the induction of IgM and IgG anti-CPS antibody responses in mice and have implications for CPS vaccine development. PMID:19660585

  9. Pneumococcal conjugate vaccine use in adults.

    PubMed

    Isturiz, Raul E; Schmoele-Thoma, Beate; Scott, Daniel A; Jodar, Luis; Webber, Chris; Sings, Heather L; Paradiso, Peter

    2016-03-01

    Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell-dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need. PCV13 efficacy against vaccine-type pneumococcal community-acquired pneumonia was confirmed in a large randomized controlled trial in older adults and its use is now increasingly recommended globally. PMID:26651847

  10. Pneumococcal vaccine (image)

    MedlinePlus

    Pneumococcal vaccine is an immunization against Streptococcus pneumoniae , a bacterium that frequently causes meningitis and pneumonia in the elderly, and people with chronic illnesses. Pneumococcal pneumonia accounts for 10 ...

  11. Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid.

    PubMed Central

    Fattom, A; Lue, C; Szu, S C; Mestecky, J; Schiffman, G; Bryla, D; Vann, W F; Watson, D; Kimzey, L M; Robbins, J B

    1990-01-01

    Conjugates of an uronic acid-containing capsular polysaccharide (CP), pneumococcous type 12F (Pn12F) bound to diphtheria toxoid (DT), were studied for safety and immunogenicity in adult volunteers. In mice, these conjugates, prepared with the same lot of DT and Pn12F-40234-006, a homogenous CP of high molecular weight, or Pn12-812408, a polydisperse CP with lower-molecular-weight material, were more immunogenic than the Pn12F alone and had T-cell dependent properties (A. Fattom, W. F. Vann, S.C. Szu, A. Sutton, X. Li, B. Bryla, G. Schiffman, J. B. Robbins, and R. Schneerson, Infect. Immun. 56:2292-2298, 1988). Adult volunteers, randomized into three groups, were injected either with one of these two conjugates or with Pnu-Imune, the 23 valent pneumococcus vaccine containing 25 micrograms of Pn12F as one of its components. Volunteers were injected two times, 4 weeks apart, with the Pn12F-DT conjugates and once with the Pnu-Imune. Side reactions following injection of the conjugates of Pnu-Imune were mild and short-lived. At 4 weeks and at 7 months after the first injection, higher levels of Pn12F antibodies were found in the volunteers injected with the conjugates than in the Pnu-Imune group (P less than 0.001). The conjugate prepared with the higher-molecular-weight Pn12F elicited higher levels of antibodies than the conjugate prepared with a lower-molecular-weight Pn12F preparation (P = 0.05). Both conjugates elicited about a 13-fold rise in DT antibodies. PMID:2365462

  12. Rationale and prospects for novel pneumococcal vaccines.

    PubMed

    Moffitt, Kristin; Malley, Richard

    2016-01-01

    Streptococcus pneumoniae remains one of the most frequent bacterial causes of morbidity and mortality worldwide. National immunization programs implementing pneumococcal polysaccharide conjugate vaccines (PCVs) have successfully reduced rates of vaccine-type invasive disease and colonization both via direct effects in immunized children and, in some settings, indirect effects in unimmunized individuals. Limitations of the current PCV approach include the emergence of non-vaccine serotypes contributing to carriage and invasive disease in high-PCV coverage settings and the high cost of goods of PCVs which limits their accessibility in developing countries where the burden of disease remains highest. Furthermore, the distribution of serotypes causing disease varies geographically and includes more serotypes than are currently covered in a single PCV formulation. Researchers have long been exploring the potential of genetically conserved non-capsular pneumococcal antigens as vaccine candidates that might overcome such limitations. To better evaluate the rationale of such approaches, an understanding of the mechanisms of immunity to the various phases of pneumococcal infection is of paramount importance. Herein we will review the evolving understanding of both vaccine-induced and naturally acquired immunity to pneumococcal colonization and infection and discuss how this informs current approaches using serotype-independent pneumococcal vaccine candidates. We will then review the alternative vaccine candidates that have been or are currently under evaluation in clinical trials. PMID:26535755

  13. [Pneumococcal vaccine recommendations in chronic respiratory diseases].

    PubMed

    Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

    2014-09-01

    Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD. PMID:25107494

  14. Pneumococcal Capsules and Their Types: Past, Present, and Future.

    PubMed

    Geno, K Aaron; Gilbert, Gwendolyn L; Song, Joon Young; Skovsted, Ian C; Klugman, Keith P; Jones, Christopher; Konradsen, Helle B; Nahm, Moon H

    2015-07-01

    Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules. PMID:26085553

  15. Pneumococcal Capsules and Their Types: Past, Present, and Future

    PubMed Central

    Geno, K. Aaron; Gilbert, Gwendolyn L.; Song, Joon Young; Skovsted, Ian C.; Klugman, Keith P.; Jones, Christopher; Konradsen, Helle B.

    2015-01-01

    SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules. PMID:26085553

  16. Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.

    PubMed Central

    Alonso de Velasco, E; Verheul, A F; van Steijn, A M; Dekker, H A; Feldman, R G; Fernández, I M; Kamerling, J P; Vliegenthart, J F; Verhoef, J; Snippe, H

    1994-01-01

    Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes. PMID:7509318

  17. [Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].

    PubMed

    Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam

    2014-02-01

    Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD

  18. Effective management in clusters of pneumococcal disease: a systematic review.

    PubMed

    Basarab, Marina; Ihekweazu, Chikwe; George, Robert; Pebody, Richard

    2011-02-01

    Outbreaks of serious pneumococcal disease can occur with high attack rates in certain settings. We systematically reviewed studies of interventions implemented in pneumococcal clusters and those reporting the effect of antibiotics on carriage reduction to assess the effectiveness of interventions. Evidence was graded according to the Scottish Intercollegiate Guidelines Network system. Of 28 identified cluster reports, one showed that administration of antibiotics to close contacts reduced risk of pneumococcal disease. In three of four clusters where rifampicin chemoprophylaxis was used and in four of five clusters where penicillin was used no further cases were seen after intervention. In clusters where pneumococcal polysaccharide vaccine was used, subsequent cases occurred, all within around 2 weeks of vaccination, which suggests delayed benefit with this approach (evidence grade D). Use of infection control measures alone was reported in eight clusters, with no further cases being reported in seven (grade D). From 21 selected carriage studies, large carriage reductions were observed consistently with use of penicillin and azithromycin, with median values being 90% and 73%, respectively (grade C). The findings were presented to a working group for pneumococcal cluster guidelines and used to develop key recommendations on the management of clusters that supported prompt use of amoxicillin or azithromycin chemoprophylaxis, pneumococcal vaccination for close contacts, and implementation of infection control measures. PMID:21272792

  19. Fulminant pneumococcal infection

    PubMed Central

    Naito, Ryo; Miyazaki, Tetsuro; Kajino, Kazunori; Daida, Hiroyuki

    2014-01-01

    Summary Fulminant pneumococcal infection is a fatal pneumococcal infection that tends to occur in immunocompromised hosts, such as patients who are asplenic or on immunosuppressant therapy. We experienced a case of a 73-year-old Japanese man with a medical history of coronary stent implantation and catheter ablation for atrial flutter who presented with dyspnoea at rest. The patient was diagnosed with streptococcal pneumonia based on a urine antigen test and CT. Despite the use of effective antibiotics and systemic therapies, his clinical course was rapidly progressive and he died 18 h after admission. This case of fulminant pneumococcal infection is reported along with the autopsy findings. PMID:25150240

  20. Alcoholic leukopenic pneumococcal sepsis.

    PubMed

    Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi

    2013-04-01

    Alcohol abuse has been associated with an increased mortality and morbidity due to increased aspiration, delirium tremens, and seizures. The association of pneumococcal lung infections and leukopenia in the setting of alcohol abuse are rarely reported; however, when present, severe lung infections can happen with severe lung injury and poor response to conventional therapy and ultimately, death. We are reporting a case of 55-year-old-man presented with shortness of breath, cough and altered mental status and eventually found with severe pneumococcal lung infection in the setting of leukopenia and long-term alcohol abuse representing alcoholic leukopenic pneumococcal sepsis syndrome. PMID:23930244

  1. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... Know About Zika & Pregnancy Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...

  2. Pneumococcal Conjugate Vaccine (PCV13)

    MedlinePlus

    ... to protect infants and toddlers, and some older children and adults with certain health conditions, from pneumococcal disease.Pneumococcal disease is caused by infection with Streptococcus pneumoniae bacteria. These bacteria can spread from person ...

  3. MedlinePlus: Pneumococcal Infections

    MedlinePlus

    ... infections are Ear infections Sinus infections Pneumonia Sepsis Meningitis How the diagnosis is made depends upon where ... Article: The Earliest Success of Penicillin. Article: Pneumococcal meningitis outbreaks in sub-Saharan Africa. Pneumococcal Infections -- see ...

  4. Pneumococcal conjugate vaccine in adults: Let's see what happens.

    PubMed

    Paradiso, Peter R

    2016-07-01

    The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population. PMID:26901618

  5. Lactococcus lactis as an adjuvant and delivery vehicle of antigens against pneumococcal respiratory infections

    PubMed Central

    Vintiñi, Elisa; Villena, Julio; Raya, Raul

    2010-01-01

    Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent a definitive solution. Novel, safe and inexpensive vaccines are necessary, especially in developing countries. Probiotic microorganisms such as lactic acid bacteria (LAB) are an interesting alternative for their use as vehicles in pneumococcal vaccines due to their GRAS (Generally Recognized As Safe) status. Thus, the adjuvanticity of Lactococcus lactis by itself represents added value over the use of other bacteria, a question dealt with in this review. In addition, the expression of different pneumococcal antigens as well as the use of oral and nasal mucosal routes of administration of lactococcal vaccines is considered. The advantages of nasal live vaccines are evident; nonetheless, oral vaccines can be a good alternative when the adequate dose is used. Another point addressed here is the use of live versus inactivated vaccines. In this sense, few researchers have focused on inactivated strains to be used as vaccines against pneumoccoccus. The immunogenicity of live vaccines is better than the one afforded by inactivated ones; however, the probiotic-inactivated vaccine combination has improved this matter considerably. The progress made so far in the protective immune response induced by recombinant vaccines, the successful trials in animal models and the safety considerations of their application in humans suggest that the use of recombinant vaccines represents a good short-term option in the control of pneumococcal diseases. PMID:21326831

  6. Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine.

    PubMed

    Yildirim, Inci; Shea, Kimberly M; Pelton, Stephen I

    2015-12-01

    Universal immunization of infants and toddlers with pneumococcal conjugate vaccines over the last 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in invasive pneumococcal disease, all-cause pneumonia, empyema, mastoiditis, acute otitis media, and complicated otitis media have been reported from multiple countries in which universal immunization has been implemented. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared with otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed. PMID:26610421

  7. [Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

    PubMed

    Pletz, Mathias W

    2011-06-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones. PMID:21812250

  8. Functional Antibodies Elicited by Two Heptavalent Pneumococcal Conjugate Vaccines in the Finnish Otitis Media Vaccine Trial▿

    PubMed Central

    Ekström, Nina; Väkeväinen, Merja; Verho, Jouko; Kilpi, Terhi; Käyhty, Helena

    2007-01-01

    In the Finnish Otitis Media Vaccine Trial, the now-licensed pneumococcal conjugate vaccine containing polysaccharides conjugated to protein CRM197 (PncCRM) and the experimental pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC), showed similar efficacy profiles against acute otitis media despite different antibody concentrations in sera. We now report the opsonophagocytic activities (OPA) in these sera. OPA, antibody concentration, and avidity for serotypes 6B, 19F, and 23F were determined in sera of infants who received either pneumococcal conjugate (PCV) or control vaccine at 2, 4, and 6 months of age and either the homologous or pneumococcal polysaccharide vaccine at 12 months of age. OPA varied by vaccine and serotype. The majority of PCV recipients had positive OPA after the fourth dose, while OPA was undetectable in the control group. Coinciding with the efficacy data, the concentration of antibodies required for 50% killing was low for 6B and high for 19F for both PCVs. Contradictory to the efficacy data, PncOMPC induced lower functional capacity to 23F than PncCRM. OPA correlated with antibody concentration, while avidity and functional capacity of antibodies showed no correlation. The OPA data provide valuable additional information for serotype-specific differences in protection and when evaluating serotype-specific immunogenicity and should thus be considered when defining serological correlates of protection. PMID:17261612

  9. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    NASA Astrophysics Data System (ADS)

    May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

    2004-09-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  10. Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers

    PubMed Central

    Rogers, Kara; Cotte, Christina; Adami, Alexander J.; Bracken, Sonali J.; Salmon, Sharon; Secor, Eric R.; Thrall, Roger S.; Andemariam, Biree; Metzger, Dennis W.

    2016-01-01

    Background One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. Methods Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. Results Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. Conclusion Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population. PMID:26910228

  11. Pneumococcal Vaccination: Who Needs It?

    MedlinePlus

    ... News and Media Resources News Newsletters Events Pneumococcal Vaccination: Who Needs It? Recommend on Facebook Tweet Share ... doses will depend on the child's age when vaccination begins. Ask your healthcare provider for details. Children ...

  12. A pneumococcal pilus influences virulence and host inflammatory responses.

    PubMed

    Barocchi, M A; Ries, J; Zogaj, X; Hemsley, C; Albiger, B; Kanth, A; Dahlberg, S; Fernebro, J; Moschioni, M; Masignani, V; Hultenby, K; Taddei, A R; Beiter, K; Wartha, F; von Euler, A; Covacci, A; Holden, D W; Normark, S; Rappuoli, R; Henriques-Normark, B

    2006-02-21

    Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response. PMID:16481624

  13. A pneumococcal pilus influences virulence and host inflammatory responses

    PubMed Central

    Barocchi, M. A.; Ries, J.; Zogaj, X.; Hemsley, C.; Albiger, B.; Kanth, A.; Dahlberg, S.; Fernebro, J.; Moschioni, M.; Masignani, V.; Hultenby, K.; Taddei, A. R.; Beiter, K.; Wartha, F.; von Euler, A.; Covacci, A.; Holden, D. W.; Normark, S.; Rappuoli, R.; Henriques-Normark, B.

    2006-01-01

    Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response. PMID:16481624

  14. Preclinical Evaluation of the Pht Proteins as Potential Cross-Protective Pneumococcal Vaccine Antigens▿

    PubMed Central

    Godfroid, Fabrice; Hermand, Philippe; Verlant, Vincent; Denoël, Philippe; Poolman, Jan T.

    2011-01-01

    Current pneumococcal vaccines are composed of capsular polysaccharides (PS) of various serotypes, either as free PS or as protein-PS conjugates. The use of pneumococcus protein antigens that are able to afford protection across the majority of serotypes is envisaged as a relevant alternative and/or complement to the polysaccharides. In this context, based on several studies, the Pht protein family emerged as relevant vaccine candidates. The purpose of the present study was to evaluate the Pht protein family in several preclinical mouse models. Immunization with these antigens was compared with immunization with other pneumococcal antigens, such as CbpA, PspA, and PsaA. In a nasopharyngeal colonization model and in a lung colonization model, the Phts were found to be superior to the other candidates in terms of efficacy of protection and serotype coverage. Likewise, vaccination with PhtD allowed higher animal survival rates after lethal intranasal challenge. Finally, a passive transfer model in which natural anti-PhtD human antibodies were transferred into mice demonstrated significant protection against lethal intranasal challenge. This indicates that natural anti-PhtD human antibodies are able to protect against pneumococcal infection. Our findings, together with the serotype-independent occurrence of the Phts, designate this protein family as valid candidate antigens to be incorporated in protein-based pneumococcal vaccines. PMID:20956575

  15. Anatomical site-specific contributions of pneumococcal virulence determinants

    PubMed Central

    Shenoy, Anukul T.; Orihuela, Carlos J.

    2016-01-01

    Streptococcus pneumoniae is an opportunistic pathogen globally associated with significant morbidity and mortality. It is capable of causing a wide range of diseases including sinusitis, conjunctivitis, otitis media, pneumonia, bacteraemia, sepsis, and meningitis. While its capsular polysaccharide is indispensible for invasive disease, and opsonising antibodies against the capsule are the basis for the current vaccines, a long history of biomedical research indicates that other components of this Gram-positive bacterium are also critical for virulence. Herein we review the contribution of pneumococcal virulence determinants to survival and persistence in the context of distinct anatomical sites. We discuss how these determinants allow the pneumococcus to evade mucociliary clearance during colonisation, establish lower respiratory tract infection, resist complement deposition and opsonophagocytosis in the bloodstream, and invade secondary tissues such as the central nervous system leading to meningitis. We do so in a manner that highlights both the critical role of the capsular polysaccharide and the accompanying and necessary protein determinants. Understanding the complex interplay between host and pathogen is necessary to find new ways to prevent pneumococcal infection. This review is an attempt to do so with consideration for the latest research findings.

  16. IMMUNOCHEMISTRY OF PNEUMOCOCCAL TYPES II, V, AND VI. II.

    PubMed Central

    Rebers, Paul A.; Hurwitz, Esther; Heidelberger, Michael

    1961-01-01

    Rebers, Paul A. (Rutgers University, New Brunswick, N. J.), Esther Hurwitz, and Michael Heidelberger. Immunochemistry of pneumococcal types II, V, and VI. II. Inhibition tests in the type VI precipitating system. J. Bacteriol. 82:920–926. 1961.—As in other immune systems involving polysaccharides, rabbit antibodies but not those engendered in the horse were found sensitive to degradation of type VI pneumococcal (Pn) polysaccharide (SVI), and were readily inhibited by fragments of SVI. Large amounts, 30 to 111 μmoles, of most sugars gave up to 15% inhibition, while sugar and polyol phosphates inhibited as much as 25%, with little relation to their presence or absence in SVI. The phosphate-free repeating unit of SVI was a good inhibitor, its phosphate monoester was better, and the “trimer” still better. The “trimer” precipitated most of the antibodies from horse anti-Pn VI. Although inhibition of precipitation of SVI anti-Pn horse sera could not be demonstrated with fragments of SVI, cross-reactions of antibodies in the horse sera could be inhibited. Precipitation of SII was inhibited by low concentrations of l-rhamnose, while even high concentrations of the other sugar components of SII and SVI were ineffective. Precipitation by guar gum was inhibited by galactose and α- and β-methyl-galactopyranosides, also by rhamnose, although guar gum does not contain this sugar, while SVI, the antigenic determinant, does. PMID:14490831

  17. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    PubMed Central

    Swiatlo, Edwin

    2016-01-01

    ABSTRACT  Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal vaccines is developed. PMID:27222469

  18. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    PubMed

    McDaniel, Larry S; Swiatlo, Edwin

    2016-01-01

    Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal vaccines is developed. PMID:27222469

  19. A comparative public health and budget impact analysis of pneumococcal vaccines: The French case

    PubMed Central

    Jiang, Yiling; Gervais, Frédéric; Gauthier, Aline; Baptiste, Charles; Martinon, Prescilla; Bresse, Xavier

    2015-01-01

    In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy. PMID:26267239

  20. A comparative public health and budget impact analysis of pneumococcal vaccines: The French case.

    PubMed

    Jiang, Yiling; Gervais, Frédéric; Gauthier, Aline; Baptiste, Charles; Martinon, Prescilla; Bresse, Xavier

    2015-01-01

    In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy. PMID:26267239

  1. Antibiofilm polysaccharides

    PubMed Central

    Rendueles, Olaya; Kaplan, Jeffrey B.; Ghigo, Jean-Marc

    2012-01-01

    Summary Bacterial extracellular polysaccharides have been shown to mediate many of the cell-to cell and cell-to-surface interactions that are required for the formation, cohesion and stabilization of bacterial biofilms. However, recent studies have identified several bacterial polysaccharides that inhibit biofilm formation by a wide-spectrum of bacteria and fungi both in vitro and in vivo. This review discusses the composition, modes of action, and potential biological roles of antibiofilm polysaccharides recently identified in bacteria and eukaria. Some of these molecules may have technological applications as antibiofilm agents in industry and medicine. PMID:22730907

  2. Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli.

    PubMed

    Kay, Emily J; Yates, Laura E; Terra, Vanessa S; Cuccui, Jon; Wren, Brendan W

    2016-04-01

    Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology. PMID:27110302

  3. Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli

    PubMed Central

    Kay, Emily J.; Yates, Laura E.; Terra, Vanessa S.; Cuccui, Jon; Wren, Brendan W.

    2016-01-01

    Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology. PMID:27110302

  4. Pneumococcal Disease: Symptoms and Complications

    MedlinePlus

    ... bacteremia and sepsis are blood infections. Symptoms include: Fever Chills Low alertness Pneumococcus bacteria causes up to half of middle ear infections (otitis media). Symptoms include: Ear pain A red, swollen ear drum Fever Sleepiness  Top of Page Complications Some pneumococcal ...

  5. Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease

    PubMed Central

    Baxendale, H E; Johnson, M; Stephens, R C M; Yuste, J; Klein, N; Brown, J S; Goldblatt, D

    2008-01-01

    The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18·4 (±4·2) and selective use of IGHD6 (P < 0·001) and IGHJ6 (P < 0·01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo. PMID:17983446

  6. Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia

    PubMed Central

    Alpkvist, Helena; Athlin, Simon; Nauclér, Pontus; Herrmann, Björn; Abdeldaim, Guma; Slotved, Hans-Christian; Hedlund, Jonas; Strålin, Kristoffer

    2015-01-01

    Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log10 DNA copies/mL (range 1.79–9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration ≥2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient’s own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54–82% and positive predictive values of 37–56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration ≥2 days, and a medium/high serum immunoglobulin titer against the patient

  7. Polysaccharide Degradation

    NASA Astrophysics Data System (ADS)

    Stone, Bruce A.; Svensson, Birte; Collins, Michelle E.; Rastall, Robert A.

    An overview of current and potential enzymes used to degrade polysaccharides is presented. Such depolymerases are comprised of glycoside hydrolases, glycosyl transferases, phosphorylases and lyases, and their classification, active sites and action patterns are discussed. Additionally, the mechanisms that these enzymes use to cleave glycosidic linkages is reviewed as are inhibitors of depolymerase activity; reagents which react with amino acid residues, glycoside derivatives, transition state inhibitors and proteinaceous inhibitors. The characterization of various enzymes of microbial, animal or plant origin has led to their widespread use in the production of important oligosaccharides which can be incorporated into food stuffs. Sources of polysaccharides of particular interest in this chapter are those from plants and include inulin, dextran, xylan and pectin, as their hydrolysis products are purported to be functional foods in the context of gastrointestinal health. An alternative use of degraded polysaccharides is in the treatment of disease. The possibility exists to treat bacterial exopolysaccharide with lyases from bacteriophage to produce oligosaccharides exhibiting bioactive sequences. Although this area is currently in its infancy the knowledge is available to investigate further.

  8. Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland.

    PubMed Central

    Sankilampi, U.; Herva, E.; Haikala, R.; Liimatainen, O.; Renkonen, O. V.; Leinonen, M.

    1997-01-01

    Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05). PMID:9042030

  9. PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease.

    PubMed

    Ramos-Sevillano, Elisa; Urzainqui, Ana; de Andrés, Belén; González-Tajuelo, Rafael; Domenech, Mirian; González-Camacho, Fernando; Sánchez-Madrid, Francisco; Brown, Jeremy S; García, Ernesto; Yuste, Jose

    2016-03-01

    Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium--the amidase LytA--were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1-/- mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1-/- mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease. PMID:26975045

  10. PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease

    PubMed Central

    Ramos-Sevillano, Elisa; Urzainqui, Ana; de Andrés, Belén; González-Tajuelo, Rafael; Domenech, Mirian; González-Camacho, Fernando; Sánchez-Madrid, Francisco; Brown, Jeremy S.; García, Ernesto; Yuste, Jose

    2016-01-01

    Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium ―the amidase LytA― were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1−/− mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1−/− mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1−/− mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease. PMID:26975045

  11. [Pneumococcal vaccination for children and adults].

    PubMed

    Albrich, Werner

    2016-01-01

    Pneumococci are the leading bacterial causes of respiratory tract infections, bacteremia and meningitis. Pneumococcal conjugate vaccines (PCV) are effective and safe in young children. Their introduction led to significant reductions of invasive pneumococcal disease (IPD), pneumonia, otitis media and antibiotic-resistant pneumococcal infections. Beyond these effects in the vaccinated age groups, there is a reduction in nasopharyngeal pneumococcal carriage and therefore in transmission. This in turn led to marked reductions in IPD and pneumonia in non-vaccinated age groups, particularly elderly adults as evidence of herd protection. Recently it was shown that the 13-valent PCV13 is effective and safe in adults leading to the age-independent recommendation of PCV13 in all persons with risk factors. PMID:27268445

  12. Pneumococcal Disease: Risk Factors and Transmission

    MedlinePlus

    ... Foundation for Infectious Diseases Sepsis Risk Factors and Transmission Recommend on Facebook Tweet Share Compartir On this ... the brain and spinal cord) Who smoke cigarettes Transmission Pneumococcal bacteria spread from person-to-person by ...

  13. Pneumococcal Vaccine in Diabetes: Relevance in India.

    PubMed

    Shashank, R Joshi; Samika, S Joshi; Siddharth, N Shah

    2015-04-01

    Currently we have more than 65 million Diabetes patients in India with estimated 80 million prediabetics. Diabetes is a immunologically vulnerable population to develop all types of microbial infections. Pneumoccocal infections do have a substantial morbidity and mortality burden in the community. India has a large geriatric pool now which has substantially increased pneumococcal disease burden. Diabetes is a well-known risk factor for pneumococcal infection and predisposes individuals to nasopharyngeal colonization with the pneumococcus which is associated with invasive infection. In diabetics who are elderly, with chronic kidney or pulmonary disease and long standing duration of the disease with poor glycemic control are the highest risk group susceptible to invasive pneumococcal disease. With now availibilty of Pneumoccal vaccine in India, now it may be an preventive option which can be offered. Most global organisations recommend pneumococcal vaccination to diabetics. PMID:26562963

  14. A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

    PubMed Central

    Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

    2015-01-01

    We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

  15. Pneumococcal conjugate vaccine (PCV13) - What you need to know

    MedlinePlus

    ... www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html CDC review information for Pneumococcal Conjugate VIS: ... the disease, through vaccination, even more important. 2. PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against ...

  16. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets.

    PubMed

    Tunjungputri, Rahajeng N; de Jonge, Marien I; de Greeff, Astrid; van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T; de Groot, Phillip G; Smith, Hilde E; van der Ven, Andre J; de Mast, Quirijn

    2016-08-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection. PMID:27322088

  17. Directed vaccination against pneumococcal disease.

    PubMed

    Li, Yi; Hill, Andrew; Beitelshees, Marie; Shao, Shuai; Lovell, Jonathan F; Davidson, Bruce A; Knight, Paul R; Hakansson, Anders P; Pfeifer, Blaine A; Jones, Charles H

    2016-06-21

    Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens. PMID:27274071

  18. Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization.

    PubMed

    Greene, Christopher J; Marks, Laura R; Hu, John C; Reddinger, Ryan; Mandell, Lorrie; Roche-Hakansson, Hazeline; King-Lyons, Natalie D; Connell, Terry D; Hakansson, Anders P

    2016-06-01

    Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx. PMID:27001538

  19. Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation.

    PubMed Central

    Lortan, J E; Vellodi, A; Jurges, E S; Hugh-Jones, K

    1992-01-01

    Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period. PMID:1606736

  20. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  1. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  2. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  3. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  4. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  5. Enzymatic Modifications of Polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polysaccharides are often modified chemically in order to improve its properties or to impart specific characteristics. Indeed quite a few commercial products are based on modified polysaccharides. In this talk, I shall describe a new set of modified polysaccharides based on enzymatic reactions. ...

  6. Pathogenesis and pathophysiology of pneumococcal meningitis.

    PubMed

    Mook-Kanamori, Barry B; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-07-01

    Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  7. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

    PubMed Central

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-01-01

    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  8. Selective and Genetic Constraints on Pneumococcal Serotype Switching

    PubMed Central

    Croucher, Nicholas J.; Kagedan, Lisa; Thompson, Claudette M.; Parkhill, Julian; Bentley, Stephen D.; Finkelstein, Jonathan A.; Lipsitch, Marc; Hanage, William P.

    2015-01-01

    Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes), which can be classified into “serogroups” based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps) locus. Twenty such “serotype switching” events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001) enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β–lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern. PMID:25826208

  9. Conserved Surface Accessible Nucleoside ABC Transporter Component SP0845 Is Essential for Pneumococcal Virulence and Confers Protection In Vivo

    PubMed Central

    Saxena, Sneha; Khan, Naeem; Dehinwal, Ruchika; Kumar, Ajay; Sehgal, Devinder

    2015-01-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia, sepsis and meningitis. Surface accessible proteins of S. pneumoniae are being explored for the development of a protein-based vaccine in order to overcome the limitations of existing polysaccharide-based pneumococcal vaccines. To identify a potential vaccine candidate, we resolved surface-associated proteins of S. pneumoniae TIGR4 strain using two-dimensional gel electrophoresis followed by immunoblotting with antisera generated against whole heat-killed TIGR4. Ten immunoreactive spots were identified by mass spectrometric analysis that included a putative lipoprotein SP0845. Analysis of the inferred amino acid sequence of sp0845 homologues from 36 pneumococcal strains indicated that SP0845 was highly conserved (>98% identity) and showed less than 11% identity with any human protein. Our bioinformatic and functional analyses demonstrated that SP0845 is the substrate-binding protein of an ATP-binding cassette (ABC) transporter that is involved in nucleoside uptake with cytidine, uridine, guanosine and inosine as the preferred substrates. Deletion of the gene encoding SP0845 renders pneumococci avirulent suggesting that it is essential for virulence. Immunoblot analysis suggested that SP0845 is expressed in in vitro grown pneumococci and during mice infection. Immunofluorescence microscopy and flow cytometry data indicated that SP0845 is surface exposed in encapsulated strains and accessible to antibodies. Subcutaneous immunization with recombinant SP0845 induced high titer antibodies in mice. Hyperimmune sera raised against SP0845 promoted killing of encapsulated pneumococcal strains in a blood bactericidal assay. Immunization with SP0845 protected mice from intraperitoneal challenge with heterologous pneumococcal serotypes. Based on its surface accessibility, role in virulence and ability to elicit protective immunity, we propose that SP0845 may be a potential candidate for a protein

  10. Predictors of pneumococcal vaccination among older adults with pneumonia: findings from the Community Acquired Pneumonia Impact Study

    PubMed Central

    2010-01-01

    Background The incidence of community-acquired pneumonia (CAP) almost triples for older adults aged 65 years or older. In Canada, CAP is a leading cause of hospital admissions and mortality. Although CAP is very prevalent, complications due to CAP may be reduced with the pneumococcal polysaccharide vaccine (PPV). The purpose of this study was to identify predictors of pneumococcal vaccination among community-dwelling older adults with clinically diagnosed CAP. Methods A telephone survey was used to collect detailed information from adults aged 60 years and older with clinically diagnosed CAP. This was a community wide study with participants being recruited from all radiology clinics in one Ontario community. Results The most important predictors of pneumococcal vaccination among older adults included: getting an influenza vaccine within the past year (OR 14.5, 95% CI 4.27 to 49.0); at least weekly contact with a friend (OR 3.97, 95% CI 1.71 to 9.24); having one or more co-morbidities/chronic conditions (OR 3.64, 95% CI 1.60 to 8.28); being 70 years of age or older (OR 2.56, 95% CI 1.21 to 5.40); having health problems that limited physical activities (OR 5.37, 95% CI 1.49 to 19.3); having little or no bodily pain (OR 2.90, 95% CI 1.25 to 6.73); and reporting having spiritual values or religious faith (OR 3.47, 95% CI 1.03 to 11.67). Conclusions A wide range of factors, including demographic, co-morbidity, quality of life, social support and lifestyle were found to be associated with pneumococcal vaccination status among older adults with clinically diagnosed CAP. The findings from this study could inform future pneumococcal immunization strategies by identifying individuals who are least likely to receive the PPV. PMID:20591180

  11. [Pneumococcal vaccination for persons 65 years of age and older].

    PubMed

    van den Bosch, W J H M

    2002-05-01

    In the Netherlands, in contrast to other countries, pneumococcal vaccination for older people and people at risk is not routine, except for patients under special circumstances, such as after a splenectomy. Although pneumococcal vaccination is an effective way to prevent invasive pneumococcal disease in young healthy persons, there is no conclusive evidence that it is effective in older people and people at risk without a good immune response. Pneumococcal disease can be an important complication of an ordinary flu. Because there is a high level of vaccination against influenza in the Netherlands, the risk of pneumococcal disease is low compared to other countries in the world. Adding a pneumococcal vaccine to the influenza vaccination could decrease the degree of protection against influenza. The experimental introduction of pneumococcal vaccination does not seem to lead to an increase in the number of patients that refuse vaccination against influenza. PMID:12038219

  12. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  13. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  14. Unveiling Unexpected Immune Activities Induced by Your Pneumococcal Vaccine

    PubMed Central

    Hurwitz, Julia L.

    2016-01-01

    ABSTRACT In modern-day vaccine design, a good pneumococcal capsular polysaccharide vaccine is measured by its ability to induce opsonic antibodies. These antibodies label bacteria for phagocytosis by neutrophils and thereby overcome the capsule’s barrier function. Doyle and Pirofski have raised a serious challenge to the current paradigm by describing anti-capsular antibodies that are highly protective but nonopsonic [C.R. Doyle and L. Pirofski, mBio 7(1):e02260-15, 2016, doi:10.1128/mBio.02260-15]. In fact, some functions are not related to neutrophils or phagocytosis at all. An increased awareness of these activities is critical not only for accurate comparisons of vaccine candidates but also for improvements in vaccination outcomes in settings of neutropenia. When vaccine developers select a single gatekeeper assay (e.g., an opsonophagocytic assay for bacteria or a neutralization assay for viruses), promising vaccine candidates may be missed. Doyle and Pirofski stress that multiple functions, not just one, should be investigated to enhance discovery of antibody mechanisms and to best assess vaccine-induced correlates of immune protection. PMID:26908576

  15. Hearing loss in adults surviving pneumococcal meningitis is associated with otitis and pneumococcal serotype.

    PubMed

    Heckenberg, S G B; Brouwer, M C; van der Ende, A; Hensen, E F; van de Beek, D

    2012-09-01

    We assessed the incidence of hearing loss and its relationship with clinical characteristics and pneumococcal serotypes in adults surviving pneumococcal meningitis. We analysed hearing loss in 531 adults surviving pneumococcal meningitis included in two prospective nationwide cohort studies performed from April 1998 through to October 2002 and March 2006 through to January 2009. Hearing loss was evaluated on admission and discharge for all patients. Severe hearing loss was assessed by pure tone average on audiology and corrected for age, or by the combination of hearing loss on discharge and a score on the Glasgow Outcome Scale below 5, which could not be explained by other neurological sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal outcome were included. Predisposing conditions for pneumococcal meningitis were present in the majority of patients (64%), most commonly otitis (36%). Hearing loss was present at discharge in 116 patients (22%) and was classified as mild in 53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.66-4.02; p < 0.001) and inversely related to serotype 23 F infection (OR, 0.36; 95% CI, 0.13-0.98; p = 0.025), but not with parameters of disease severity or indicators of cerebrospinal fluid inflammation severity. Meningitis due to pneumococcal serotype 3 was associated with the highest rate of hearing loss. Hearing loss frequently complicates pneumococcal meningitis. Risk factors for hearing loss were infection with pneumococcal serotype 23 F and otitis, but not disease severity. Otitis and resulting perilympathic inflammation contribute to meningitis-associated hearing loss. PMID:21958295

  16. Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children

    PubMed Central

    Fortunato, Francesca; Martinelli, Domenico; Cappelli, Maria Giovanna; Cozza, Vanessa; Prato, Rosa

    2015-01-01

    In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6%) in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE) of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP) between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs) with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%); it was 69% (95% CI: 30%–88%) against IPD and 77% (95% CI: 61%–87%) against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage. PMID:26351644

  17. Maternal Immunization with Pneumococcal Surface Protein A Protects against Pneumococcal Infections among Derived Offspring

    PubMed Central

    Hollingshead, Susan K.; Briles, David E.; Yamanaka, Noboru

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. (191 words) PMID:22073127

  18. Maternal immunization with pneumococcal surface protein A protects against pneumococcal infections among derived offspring.

    PubMed

    Kono, Masamitsu; Hotomi, Muneki; Hollingshead, Susan K; Briles, David E; Yamanaka, Noboru

    2011-01-01

    Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. PMID:22073127

  19. Pneumococcal Vaccination Recommendations for Children and Adults by Age and/or Risk Factor

    MedlinePlus

    Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate ... X X X X X 1 For PCV13 vaccination of healthy children, see “Recommen- dations for Pneumococcal ...

  20. Method for producing capsular polysaccharides

    NASA Technical Reports Server (NTRS)

    Kern, Roger G. (Inventor); Petersen, Gene R. (Inventor); Richards, Gil F. (Inventor)

    1994-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  1. Prevention of pneumococcal infections during mass gathering.

    PubMed

    Al-Tawfiq, Jaffar A; Memish, Ziad A

    2016-01-01

    The interest in mass gathering and its implications has been increasing due to globalization and international travel. The potential occurrence of infectious disease outbreaks during mass gathering is most feared. In this context, respiratory tract infections are of great concern due to crowding in a limited space which facilitates and magnifies the potential of disease spread among attendees. Pneumococcal disease is best described among pilgrims to Makkah and vaccination is one of the methods for the prevention of this disease. Pneumonia was described in a mass gathering with a prevalence of 4.8/100,000 pilgrims and contributes to 15-39% of hospitalizations. Various studies showed that 7-37% of pilgrims are 65 y of age or older. The uptake of pneumococcal vaccine among pilgrims is low at 5%. There is no available data to make strong recommendations for S. pneumoniae vaccination of all pilgrims, it is important that a high risk population receive the indicated vaccination. We reviewed the available literature on the burden of pneumococcal infections during mass gathering and evaluate the available literature on pneumococcal vaccinations for attendees of mass gathering. PMID:26176306

  2. Chemical Modification of Polysaccharides

    PubMed Central

    Cumpstey, Ian

    2013-01-01

    This review covers methods for modifying the structures of polysaccharides. The introduction of hydrophobic, acidic, basic, or other functionality into polysaccharide structures can alter the properties of materials based on these substances. The development of chemical methods to achieve this aim is an ongoing area of research that is expected to become more important as the emphasis on using renewable starting materials and sustainable processes increases in the future. The methods covered in this review include ester and ether formation using saccharide oxygen nucleophiles, including enzymatic reactions and aspects of regioselectivity; the introduction of heteroatomic nucleophiles into polysaccharide chains; the oxidation of polysaccharides, including oxidative glycol cleavage, chemical oxidation of primary alcohols to carboxylic acids, and enzymatic oxidation of primary alcohols to aldehydes; reactions of uronic-acid-based polysaccharides; nucleophilic reactions of the amines of chitosan; and the formation of unsaturated polysaccharide derivatives. PMID:24151557

  3. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

    PubMed

    Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

    2016-02-01

    Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic. PMID:26618243

  4. A physico-chemical assessment of the thermal stability of pneumococcal conjugate vaccine components

    PubMed Central

    Gao, Fang; Lockyer, Kay; Burkin, Karena; Crane, Dennis T; Bolgiano, Barbara

    2014-01-01

    Physico-chemical analysis of pneumococcal polysaccharide (PS)-protein conjugate vaccine components used for two commercially licensed vaccines was performed to compare the serotype- and carrier protein-specific stabilities of these vaccines. Nineteen different monovalent pneumococcal conjugates from commercial vaccines utilizing CRM197, diphtheria toxoid (DT), Protein D (PD) or tetanus toxoid (TT) as carrier proteins were incubated at temperatures up to 56°C for up to eight weeks or were subjected to freeze-thawing (F/T). Structural stability was evaluated by monitoring their size, integrity and carrier protein conformation. The molecular size of the vaccine components was well maintained for Protein D, TT and DT conjugates at -20°C, 4°C and F/T, and for CRM197 conjugates at 4°C and F/T. It was observed that four of the eight serotypes of Protein D conjugates tended to form high molecular weight complexes at 37°C or above. The other conjugated carrier proteins also appeared to form oligomers or ‘aggregates’ at elevated temperatures, but rarely when frozen and thawed. There was evidence of degradation in some of the conjugates as evidenced by the formation of lower molecular weight materials which correlated with measured free saccharide. In conclusion, pneumococcal-Protein D/TT/DT and most CRM197 bulk conjugate vaccines were stable when stored at 2–8°C, the recommended temperature. In common between the conjugates produced by the two manufacturers, serotypes 1, 5, and 19F were relatively less stable and 6B was the most stable, with types 7F and 23F also showing good stability. PMID:25483488

  5. Polysaccharide-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  6. Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore.

    PubMed

    Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita

    2014-01-01

    The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults. PMID:24729726

  7. Delivering pneumococcal vaccine to a high risk population: the Navajo experience.

    PubMed

    Benin, Andrea L; Watt, James P; O'Brien, Katherine L; Reid, Raymond; Zell, Elizabeth R; Katz, Scott; Donaldson, Connie; Schuchat, Anne; Santosham, Mathuram; Whitney, Cynthia G

    2005-01-01

    High rates of preventable diseases such as pneumococcal disease occur among the Navajo despite their universal health insurance through the Indian Health Service. The objective of this study was to determine the proportion of Navajo adults vaccinated with pneumococcal polysaccharide vaccine and to examine key features of vaccination programs of the Navajo Indian Health Service. For this cross-sectional study, medical charts of Navajo patients with vaccine indications were randomly selected and reviewed to determine who had been vaccinated as of January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95% confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs utilized extensive public health nursing, home visits, standing orders, and "express lane" clinics. In spite of excellent delivery systems and universal healthcare, the proportion of Navajo persons vaccinated was still below the goals for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and 60% of high-risk persons 18-64 years old vaccinated. PMID:17038821

  8. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV: brief report.

    PubMed

    Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B; Schønheyder, Henrik C

    2012-04-01

    HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patients (23%) were colonized, 11 at baseline only, four at both baseline and 9 months, and seven at 9 months only. Compared to non-colonized patients, more colonized patients were smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization, antiretroviral treatment and the CPG adjuvant had no impact on colonization. These results suggest preventive strategies in addition to pneumococcal immunization. PMID:22384845

  9. Incidence of Pneumococcal Pneumonia among Adults in Rural Thailand, 2006–2011: Implications for Pneumococcal Vaccine Considerations

    PubMed Central

    Piralam, Barameht; Tomczyk, Sara M.; Rhodes, Julia C.; Thamthitiwat, Somsak; Gregory, Christopher J.; Olsen, Sonja J.; Praphasiri, Prabda; Sawatwong, Pongpun; Naorat, Sathapana; Chantra, Somrak; Areerat, Peera; Hurst, Cameron P.; Moore, Matthew R.; Muangchana, Charung; Baggett, Henry C.

    2015-01-01

    The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)–related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 persons per year (2.2 and 28.3 cases per 100,000 persons per year by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 persons per year among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/409) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions. PMID:26503277

  10. Incidence of Pneumococcal Pneumonia Among Adults in Rural Thailand, 2006-2011: Implications for Pneumococcal Vaccine Considerations.

    PubMed

    Piralam, Barameht; Tomczyk, Sara M; Rhodes, Julia C; Thamthitiwat, Somsak; Gregory, Christopher J; Olsen, Sonja J; Praphasiri, Prabda; Sawatwong, Pongpun; Naorat, Sathapana; Chantra, Somrak; Areerat, Peera; Hurst, Cameron P; Moore, Matthew R; Muangchana, Charung; Baggett, Henry C

    2015-12-01

    The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)-related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 persons per year (2.2 and 28.3 cases per 100,000 persons per year by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 persons per year among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/409) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions. PMID:26503277

  11. The phosphocholine-binding pocket on C-reactive protein is necessary for initial protection of mice against pneumococcal infection.

    PubMed

    Gang, Toh B; Hammond, David J; Singh, Sanjay K; Ferguson, Donald A; Mishra, Vinod K; Agrawal, Alok

    2012-12-14

    Human C-reactive protein (CRP) protects mice from lethal Streptococcus pneumoniae infection when injected into mice within the range of 6 h before to 2 h after the administration of pneumococci. Because CRP binds to phosphocholine-containing substances and subsequently activates the complement system, it has been proposed that the antipneumococcal function of CRP requires the binding of CRP to phosphocholine moieties present in pneumococcal cell wall C-polysaccharide. To test this proposal experimentally, in this study, we utilized a new CRP mutant incapable of binding to phosphocholine. Based on the structure of CRP-phosphocholine complexes, which showed that Phe(66), Thr(76), and Glu(81) formed the phosphocholine-binding pocket, we constructed a CRP mutant F66A/T76Y/E81A in which the pocket was blocked by substituting Tyr for Thr(76). When compared with wild-type CRP, mutant CRP bound more avidly to phosphoethanolamine and could be purified by affinity chromatography using phosphoethanolamine-conjugated Sepharose. Mutant CRP did not bind to phosphocholine, C-polysaccharide, or pneumococci. Mutant CRP was free in the mouse serum, and its rate of clearance in vivo was not faster than that of wild-type CRP. When either 25 μg or 150 μg of CRP was administered into mice, unlike wild-type CRP, mutant CRP did not protect mice from lethal pneumococcal infection. Mice injected with mutant CRP had higher mortality rates than mice that received wild-type CRP. Decreased survival was due to the increased bacteremia in mice treated with mutant CRP. We conclude that the phosphocholine-binding pocket on CRP is necessary for CRP-mediated initial protection of mice against lethal pneumococcal infection. PMID:23139417

  12. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... please enable JavaScript. Chinese - Traditional (繁體中文) Farsi (فارسی) Russian (Русский) Spanish (español) Tagalog (Tagalog) Thai (ภาษาไทย) Vietnamese ( ... Action Coalition; Centers for Disease Control and Prevention Russian (Русский) Pneumococcal Conjugate Vaccine English Русский (Russian) PDF ...

  13. Overwhelming pneumococcal infection in a hyposplenic adult.

    PubMed Central

    Hatch, J. P.; Sibbald, W. J.; Austin, T. W.

    1983-01-01

    In a woman with an atrophic, apparently nonfunctioning spleen pneumococcal septicemia led to death within 72 hours of admission. As in five previously described adults, the patient's presentation and subsequent clinical course were identical to those of the syndrome of overwhelming postsplenectomy infection, except that there was no history of splenectomy. Patients without spleens may be given penicillin prophylaxis for an indefinite period, vaccinated against pneumococci or both. PMID:6616391

  14. A case of necrotizing fasciitis due to Streptococcus pneumoniae serotype 5 in Saskatchewan

    PubMed Central

    Dawar, Meenakshi; Russell, Bob; McClean, Karen; Levett, Paul N; Tyrrell, Gregory J; Irvine, James

    2008-01-01

    Necrotizing fasciitis due to Streptococcus pneumoniae is a rare and grave condition, and only a few cases have been reported. Suggested risk factors include minor trauma, systemic lupus erythematosus, immunosuppression secondary to medication, use of intramuscular anti-inflammatories and alcoholism. A fatal case of pneumococcal necrotizing fasciitis that occurred in a 51-year-old woman with a history of alcohol abuse and oral anti-inflammatory use is presented. Her condition was caused by a multi-etiology outbreak of community-acquired pneumonia, from which S pneumoniae serotype 5 was also isolated. The case description outlines the subtle presentation and rapid clinical progression of this condition. Because serotype 5 antigen is included in the polysaccharide 23-valent pneumococcal vaccine, the present case highlights the importance of pneumococcal immunization programs in Canada. PMID:19145265

  15. Protease Inhibitors Do Not Affect Antibody Responses to Pneumococcal Vaccination.

    PubMed

    De La Rosa, Indhira; Munjal, Iona M; Rodriguez-Barradas, Maria; Yu, Xiaoying; Pirofski, Liise-Anne; Mendoza, Daniel

    2016-06-01

    HIV(+) subjects on optimal antiretroviral therapy have persistently impaired antibody responses to pneumococcal vaccination. We explored the possibility that this effect may be due to HIV protease inhibitors (PIs). We found that in humans and mice, PIs do not affect antibody production in response to pneumococcal vaccination. PMID:27074938

  16. Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event

    PubMed Central

    Johnson, Tamara M; Chitturi, Chandrika; Lange, Michael; Suh, Jin S; Slim, Jihad

    2016-01-01

    Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation. PMID:27621563

  17. Density and duration of experimental human pneumococcal carriage

    PubMed Central

    Gritzfeld, J F; Cremers, A J H; Ferwerda, G; Ferreira, D M; Kadioglu, A; Hermans, P W M; Gordon, S B

    2014-01-01

    The density and duration of pneumococcal carriage are considered to affect the likelihood of transmission and invasive disease. Because of its importance in both spreading and causing disease, carriage has been suggested as an endpoint in future vaccine studies. Culture is the current gold standard for detection, but may not be sensitive enough to detect changes at low density. Healthy adult volunteers received an intranasal inoculation of Streptococcus pneumoniae serotype 6B. Pneumococcal density in nasal washes collected at six time-points post-inoculation was determined by culture and quantitative PCR (qPCR). Natural pneumococcal carriers detected at initial screening were followed in parallel. In 331 nasal washes from 79 volunteers, the sensitivity and specificity of pneumococcal detection by qPCR, as compared with culture, were 92.3% and 75.9%. The estimation of pneumococcal density by culture and qPCR was highly correlated (rs = 0.73, p <0.0001), although qPCR had a lower detection limit. Pneumococcal density fluctuated within a carriage episode, and occasionally fell below the detection limit of both methods. The duration of carriage episodes was underestimated when only one method was used. Similar fluctuations in density were observed in natural carriers. Pneumococcal carriage is a dynamic event. Culture and qPCR are complementary for surveying the density and duration of pneumococcal carriage episodes. PMID:24995531

  18. Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event.

    PubMed

    Johnson, Tamara M; Chitturi, Chandrika; Lange, Michael; Suh, Jin S; Slim, Jihad

    2016-01-01

    Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation. PMID:27621563

  19. Lactate dehydrogenase is the key enzyme for pneumococcal pyruvate metabolism and pneumococcal survival in blood.

    PubMed

    Gaspar, Paula; Al-Bayati, Firas A Y; Andrew, Peter W; Neves, Ana Rute; Yesilkaya, Hasan

    2014-12-01

    Streptococcus pneumoniae is a fermentative microorganism and causes serious diseases in humans, including otitis media, bacteremia, meningitis, and pneumonia. However, the mechanisms enabling pneumococcal survival in the host and causing disease in different tissues are incompletely understood. The available evidence indicates a strong link between the central metabolism and pneumococcal virulence. To further our knowledge on pneumococcal virulence, we investigated the role of lactate dehydrogenase (LDH), which converts pyruvate to lactate and is an essential enzyme for redox balance, in the pneumococcal central metabolism and virulence using an isogenic ldh mutant. Loss of LDH led to a dramatic reduction of the growth rate, pinpointing the key role of this enzyme in fermentative metabolism. The pattern of end products was altered, and lactate production was totally blocked. The fermentation profile was confirmed by in vivo nuclear magnetic resonance (NMR) measurements of glucose metabolism in nongrowing cell suspensions of the ldh mutant. In this strain, a bottleneck in the fermentative steps is evident from the accumulation of pyruvate, revealing LDH as the most efficient enzyme in pyruvate conversion. An increase in ethanol production was also observed, indicating that in the absence of LDH the redox balance is maintained through alcohol dehydrogenase activity. We also found that the absence of LDH renders the pneumococci avirulent after intravenous infection and leads to a significant reduction in virulence in a model of pneumonia that develops after intranasal infection, likely due to a decrease in energy generation and virulence gene expression. PMID:25245810

  20. Lactate Dehydrogenase Is the Key Enzyme for Pneumococcal Pyruvate Metabolism and Pneumococcal Survival in Blood

    PubMed Central

    Gaspar, Paula; Al-Bayati, Firas A. Y.; Andrew, Peter W.; Neves, Ana Rute

    2014-01-01

    Streptococcus pneumoniae is a fermentative microorganism and causes serious diseases in humans, including otitis media, bacteremia, meningitis, and pneumonia. However, the mechanisms enabling pneumococcal survival in the host and causing disease in different tissues are incompletely understood. The available evidence indicates a strong link between the central metabolism and pneumococcal virulence. To further our knowledge on pneumococcal virulence, we investigated the role of lactate dehydrogenase (LDH), which converts pyruvate to lactate and is an essential enzyme for redox balance, in the pneumococcal central metabolism and virulence using an isogenic ldh mutant. Loss of LDH led to a dramatic reduction of the growth rate, pinpointing the key role of this enzyme in fermentative metabolism. The pattern of end products was altered, and lactate production was totally blocked. The fermentation profile was confirmed by in vivo nuclear magnetic resonance (NMR) measurements of glucose metabolism in nongrowing cell suspensions of the ldh mutant. In this strain, a bottleneck in the fermentative steps is evident from the accumulation of pyruvate, revealing LDH as the most efficient enzyme in pyruvate conversion. An increase in ethanol production was also observed, indicating that in the absence of LDH the redox balance is maintained through alcohol dehydrogenase activity. We also found that the absence of LDH renders the pneumococci avirulent after intravenous infection and leads to a significant reduction in virulence in a model of pneumonia that develops after intranasal infection, likely due to a decrease in energy generation and virulence gene expression. PMID:25245810

  1. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia

    PubMed Central

    Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P.J.

    2015-01-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  2. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia.

    PubMed

    Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P J

    2015-11-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  3. Profiling pneumococcal type 3-derived oligosaccharides by high resolution liquid chromatography-tandem mass spectrometry

    PubMed Central

    Li, Guoyun; Li, Lingyun; Xue, Changhu; Middleton, Dustin; Linhardt, Robert J.; Avci, Fikri Y.

    2015-01-01

    Pneumococcal type-3 polysaccharide (Pn3P) is considered a major target for the development of a human vaccine to protect against Streptococcus pneumonia infection. Thus, it is critical to develop methods for the preparation and analysis of Pn3P-derived oligosaccharides to better understand its immunological properties. In this paper, we profile oligosaccharides, generated by the free radical depolymerization of Pn3P, using liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Hydrophilic liquid interaction chromatography (HILIC)-mass spectrometry (MS) revealed a series of oligosaccharides with an even- and odd-number of saccharide residues, ranging from monosaccharide, degree of polymerization (dp1) to large oligosaccharides up to dp 20, generated by free radical depolymerization. Isomers of oligosaccharides with an even number of sugar residues were easily separated on a HILIC column, and their sequences could be distinguished by comparing MS/MS of these oligosaccharides and their reduced alditols. Fluorescent labeling with 2-aminoacridone (AMAC) followed by reversed phase (RP)-LC-MS/MS was applied to analyze and sequence poorly separated product mixtures, as RP-LC affords higher resolution of AMAC-labeled oligosaccharides than does HILIC-based separation. The present methodology can be potentially applied to profiling other capsular polysaccharides. PMID:25913329

  4. Many radiologic facies of pneumococcal pneumonia

    SciTech Connect

    Kantor, H.G.

    1981-12-01

    In 1978, 89 patients were treated for (S. pneumoniae) pneumonia at New York Hospital-Cornell Medical Center. Only 40 cases met rather strict diagnostic criteria. Of these, 12 demonstrated the classical consolidative (air space) pattern usually ascribed to this disease. A bronchopneumonic (patch) pattern was demonstrated in an equal number of patients; interstitial (irregular linear) infiltrates were manifest in nine cases and a mixed interstitial and patchy presentation shown in seven cases. Absence of the consolidative pattern does not exclude pneumococcal pneumonia. Bacteriologic investigation is required to determine the proper diagnosis and course of therapy.

  5. Surveillance of pneumococcal diseases in Central and Eastern Europe

    PubMed Central

    Ceyhan, Mehmet; Dagan, Ron; Sayiner, Abdullah; Chernyshova, Liudmyla; Dinleyici, Ener Çağrı; Hryniewicz, Waleria; Kulcsár, Andrea; Mad'arová, Lucia; Pazdiora, Petr; Sidorenko, Sergey; Streinu-Cercel, Anca; Tambić-Andrašević, Arjana; Yeraliyeva, Lyazzat

    2016-01-01

    ABSTRACT Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine vaccination. Pneumococcal conjugate vaccines (e.g. PCV7, PCV13) provide protection from invasive pneumococcal disease as well as non-invasive infection (pneumonia, acute otitis media), and decrease vaccine-type nasopharyngeal colonisation, thus reducing transmission to unvaccinated individuals. PCVs have also been shown to reduce the incidence of antibiotic-resistant pneumococcal disease. Surveillance for pneumococcal disease is important to understand local epidemiology, serotype distribution and antibiotic resistance rates. Surveillance systems also help to inform policy development, including vaccine recommendations, and monitor the impact of pneumococcal vaccination. National pneumococcal surveillance systems exist in a number of countries in Central and Eastern Europe (such as Croatia, Czech Republic, Hungary, Poland, Romania and Slovakia), and some have introduced PCVs (Czech Republic, Hungary, Kazakhstan, Russia, Slovakia and Turkey). Those countries without established programs (such as Kazakhstan, Russia and Ukraine) may be able to learn from the experiences of those with national surveillance systems. The serotype distributions and impact of PCV13 on pediatric pneumococcal diseases are relatively similar in different parts of the world, suggesting that approaches to vaccination used elsewhere are also likely to be effective in Central and Eastern Europe. This article briefly reviews the epidemiology of pneumococcal disease, presents the latest surveillance data from Central and Eastern Europe, and discusses any similarities and differences in these data as well the potential implications for vaccination policies in the region. PMID:27096714

  6. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome.

    PubMed

    Groves, Andrew P; Reich, Patrick; Sigdel, Binayak; Davis, T Keefe

    2016-08-01

    Pneumococcal-associated hemolytic uremic syndrome (pHUS) is a rare but severe complication of invasive Streptococcus pneumoniae infection. We report the case of a 12-year-old female with steroid-resistant nephrotic syndrome treated with adrenocorticotrophic hormone (H.P. Acthar(®) Gel), who developed pneumococcal pneumonia and subsequent pHUS. While nephrotic syndrome is a well-known risk factor for invasive pneumococcal disease, this is the first reported case of pHUS in an adolescent patient with nephrotic syndrome, and reveals novel challenges in the diagnosis, treatment and potential prevention of this complication. PMID:27478599

  7. Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.

    PubMed

    Pride, Michael W; Huijts, Susanne M; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C; Bonten, Marc J M; Jansen, Kathrin U

    2012-08-01

    To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID:22675155

  8. Validation of an Immunodiagnostic Assay for Detection of 13 Streptococcus pneumoniae Serotype-Specific Polysaccharides in Human Urine

    PubMed Central

    Huijts, Susanne M.; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C.; Bonten, Marc J. M.; Jansen, Kathrin U.

    2012-01-01

    To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID:22675155

  9. Humoral Immune Responses to Streptococcus pneumoniae in the Setting of HIV-1 Infection

    PubMed Central

    Zhang, Lumin; Li, Zihai; Wan, Zhuang; Kilby, Andrew; Kilby, J Michael; Jiang, Wei

    2015-01-01

    Streptococcus pneumonia (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold higher in HIV-infected individuals. Both innate and adaptive host immune responses to pneumococcal infection are important against pathogen invasion. Pneumococcal-specific IgA antibody (Ab) is key to control infection at the mucosal sites. Ab responses against pneumococcal infection by B cells can be generated through T cell-dependent or T cell-independent pathways. Depletion of CD4+ T cells is a hallmark of immunodeficiency in HIV infection and this defect also contributes to B cell dysfunction, which predisposes to infections such as the pneumococcus. Two pneumococcal vaccines have been demonstrated to have potential benefits for HIV-infected patients. One is a T cell dependent 13-valent pneumococcal conjugate vaccine (PCV13); the other is a T cell independent 23-valent pneumococcal polysaccharide vaccine (PPV23). However, many questions remain unknown regarding these two vaccines in the clinical setting in HIV disease. Here we review the latest research regarding B cell immune responses against pneumococcal antigens, whether derived from potentially invading pathogens or vaccinations, in the setting of HIV-1 infection. PMID:26141012

  10. Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

    PubMed Central

    Kasirye, Yusuf; Epperla, Narendranath; Manne, Janaki Ram; Bapani, Sowjanya; Garcia-Montilla, Romel J

    2012-01-01

    Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy. PMID:22634540

  11. The Saudi Thoracic Society pneumococcal vaccination guidelines-2016

    PubMed Central

    Alharbi, N. S.; Al-Barrak, A. M.; Al-Moamary, M. S.; Zeitouni, M. O.; Idrees, M. M.; Al-Ghobain, M. O.; Al-Shimemeri, A. A.; Al-Hajjaj, Mohamed S.

    2016-01-01

    Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well. PMID:27168856

  12. The Saudi Thoracic Society pneumococcal vaccination guidelines-2016.

    PubMed

    Alharbi, N S; Al-Barrak, A M; Al-Moamary, M S; Zeitouni, M O; Idrees, M M; Al-Ghobain, M O; Al-Shimemeri, A A; Al-Hajjaj, Mohamed S

    2016-01-01

    Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well. PMID:27168856

  13. Systemic lupus erythematosus presenting as pneumococcal septicaemia and septic arthritis.

    PubMed Central

    Webster, J; Williams, B D; Smith, A P; Hall, M; Jessop, J D

    1990-01-01

    A 50 year old woman presented with pneumococcal septicaemia, septic arthritis, and a lobar pneumonia and was subsequently diagnosed as having systemic lupus erythematosus. The blood film and splenic 99mTc sulphur colloid uptake were normal, although selective functional hyposplenism was shown by the impaired clearance of immunoglobulin coated erythrocytes. Systemic lupus erythematosus presenting with fulminating pneumococcal sepsis in the presence of selective defects in spleen function is previously unreported. PMID:2322028

  14. Factors predicting mortality in invasive pneumococcal disease in adults in Alberta.

    PubMed

    Marrie, Thomas James; Tyrrell, Gregory J; Garg, Sipi; Vanderkooi, Otto G

    2011-05-01

    To define the factors associated with 30-day mortality among adult patients with invasive pneumococcal disease (IPD), we conducted a retrospective review of all cases of IPD in Alberta from 2000 to 2004. We hypothesized that multiple factors would be predictive of such mortality. We also examined the factors predictive of early (within 5 days of admission) mortality. We identified 1154 patients who met our inclusion criteria, 163 (14.1%) of whom died within 30 days. Over half (62.6%) of the deaths occurred within 5 days of admission. Ten factors were independently associated with increased 30-day mortality: 3 comorbidity factors-cancer within 5 years of diagnosis of IPD, diabetes, and cirrhosis; 4 complications-requirement for supplemental oxygen, mechanical ventilation, alteration of mental status, and cardiac arrest; 2 microorganism-related factors-infection with high- or infection with intermediate-mortality serotypes; and 1 treatment-related factor-treatment with a single antibiotic. Age 18-40 years and treatment with 2 antibiotics concurrently were associated with lower 30-day mortality. Comorbid illnesses were not contributory to early mortality (within 5 days of admission); instead, complications (alteration of mental status, requirement for supplemental oxygen, mechanical ventilation, and cardiac arrest) as well as infection with high-mortality serotypes and treatment with a single antibiotic were important. Age 18-40 years, infection with serotypes in the polysaccharide vaccine, and treatment with 2 or more than 2 antibiotics were associated with decreased early mortality. Early mortality accounted for 62.6% of the deaths. In conclusion, we found that mortality in IPD is multifactorial, the factors differ for 5- and 30-day mortality, and mortality is associated with host (age and complications), microorganism (pneumococcal serotypes), and therapeutic factors. Our data indicate that treatment with 2 or more antibiotics effective against Streptococcus

  15. Influenza-induced inflammation drives pneumococcal otitis media.

    PubMed

    Short, Kirsty R; Reading, Patrick C; Brown, Lorena E; Pedersen, John; Gilbertson, Brad; Job, Emma R; Edenborough, Kathryn M; Habets, Marrit N; Zomer, Aldert; Hermans, Peter W M; Diavatopoulos, Dimitri A; Wijburg, Odilia L

    2013-03-01

    Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM. PMID:23319557

  16. Inflammatory Markers and Immune Response to Pneumococcal Vaccination in HIV-Positive and -Negative Adults

    PubMed Central

    Leggat, David J.; Ohtola, Jennifer A.; Saul-McBeth, Jessica L.; Khuder, Sadik A.; Westerink, M. A. Julie

    2016-01-01

    Background Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated. Objective To investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization. Methods Markers of inflammation, C-reactive protein (CRP), IL-6, sCD27 and sCD30, were assessed in HIV-positive and -negative individuals as potential predictors of PPV23 response. Serum levels of B cell activating factor (BAFF), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B cell maturation antigen (BCMA) and B cell expression of BAFF-R, TACI, BCMA, CD40 and CD21 were assessed in total (unselected) and PPS23F (antigen)-specific B cells of PPV23 immunized HIV-positive and -negative individuals. Results CRP, sCD27, sCD30 and BAFF were significantly elevated in the serum of HIV-positive individuals but did not adversely affect PPV23 response. Assessment of PPS-specific B cells revealed enhanced TACI and reduced BAFF-R expression compared to unselected B cells in HIV-positive and -negative individuals. Surface TACI was similar but soluble TACI was significantly lower in HIV-positive compared to HIV-negative individuals. Conclusion Current studies highlight a potential role for TACI in PPV23 response based on its enhanced expression on PPS-specific B cells. Although surface levels of TACI were similar, diminished soluble TACI (sTACI) in HIV-positive compared to HIV-negative individuals could potentially decrease BAFF responsiveness and Ig response. A better understanding of the role of TNF receptors

  17. Climate induces seasonality in pneumococcal transmission

    PubMed Central

    Numminen, Elina; Chewapreecha, Claire; Turner, Claudia; Goldblatt, David; Nosten, Francois; Bentley, Stephen D.; Turner, Paul; Corander, Jukka

    2015-01-01

    Streptococcus pneumoniae is a significant human pathogen and a leading cause of infant mortality in developing countries. Considerable global variation in the pneumococcal carriage prevalence has been observed and the ecological factors contributing to it are not yet fully understood. We use data from a cohort of infants in Asia to study the effects of climatic conditions on both acquisition and clearance rates of the bacterium, finding significantly higher transmissibility during the cooler and drier months. Conversely, the length of a colonization period is unaffected by the season. Independent carriage data from studies conducted on the African and North American continents suggest similar effects of the climate on the prevalence of this bacterium, which further validates the obtained results. Further studies could be important to replicate the findings and explain the mechanistic role of cooler and dry air in the physiological response to nasopharyngeal acquisition of the pneumococcus. PMID:26067932

  18. Climate induces seasonality in pneumococcal transmission.

    PubMed

    Numminen, Elina; Chewapreecha, Claire; Turner, Claudia; Goldblatt, David; Nosten, Francois; Bentley, Stephen D; Turner, Paul; Corander, Jukka

    2015-01-01

    Streptococcus pneumoniae is a significant human pathogen and a leading cause of infant mortality in developing countries. Considerable global variation in the pneumococcal carriage prevalence has been observed and the ecological factors contributing to it are not yet fully understood. We use data from a cohort of infants in Asia to study the effects of climatic conditions on both acquisition and clearance rates of the bacterium, finding significantly higher transmissibility during the cooler and drier months. Conversely, the length of a colonization period is unaffected by the season. Independent carriage data from studies conducted on the African and North American continents suggest similar effects of the climate on the prevalence of this bacterium, which further validates the obtained results. Further studies could be important to replicate the findings and explain the mechanistic role of cooler and dry air in the physiological response to nasopharyngeal acquisition of the pneumococcus. PMID:26067932

  19. Silver polyvinyl pyrrolidone nanoparticles exhibit a capsular polysaccharide influenced bactericidal effect against Streptococcus pneumoniae

    PubMed Central

    Bibbs, Ronda K.; Harris, Rhonda D.; Peoples, Veolanda A.; Barnett, Cleon; Singh, Shree R.; Dennis, Vida A.; Coats, Mamie T.

    2014-01-01

    Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide. The highly adaptive nature of S. pneumoniae exemplifies the need for next generation antimicrobials designed to avoid high level resistance. Metal based nanomaterials fit this criterion. Our study examined the antimicrobial activity of gold nanospheres, silver coated polyvinyl pyrrolidone (AgPVP), and titanium dioxide (TiO2) against various serotypes of S. pneumoniae. Twenty nanometer spherical AgPVP demonstrated the highest level of killing among the tested materials. AgPVP (0.6 mg/mL) was able to kill pneumococcal serotypes 2, 3, 4, and 19F within 4 h of exposure. Detailed analysis of cultures during exposure to AgPVP showed that both the metal ions and the solid nanoparticles participate in the killing of the pneumococcus. The bactericidal effect of AgPVP was lessened in the absence of the pneumococcal capsular polysaccharide. Capsule negative strains, JD908 and RX1, were only susceptible to AgPVP at concentrations at least 33% higher than their respective capsule expressing counterparts. These findings suggest that mechanisms of killing used by nanomaterials are not serotype dependent and that the capsular polysaccharide participates in the inhibition. In the near future these mechanisms will be examined as targets for novel antimicrobials. PMID:25520713

  20. Reduction of Streptococcus pneumoniae Colonization and Dissemination by a Nonopsonic Capsular Polysaccharide Antibody

    PubMed Central

    Doyle, Christopher R.

    2016-01-01

    ABSTRACT Streptococcus pneumoniae colonization of the nasopharynx (NP) is a prerequisite for invasive pneumococcal disease (IPD). The marked reduction in IPD that followed the routine use of pneumococcal polysaccharide conjugate vaccines (PCVs) has been linked to reduced NP colonization with vaccine-included serotypes (STs), with the caveat that PCVs are less effective against pneumonia than against IPD. Although PCV-elicited opsonic antibodies that enhance phagocytic killing of the homologous ST are considered a key correlate of PCV-mediated protection, recent studies question this relationship for some STs, including ST3. Studies with monoclonal antibodies (MAbs) to the pneumococcal capsular polysaccharide (PPS) of ST3 (PPS3) have shown that nonopsonic, as well as opsonic, antibodies can each protect mice against pneumonia and sepsis, but the effect of these types of MAbs on NP colonization is unknown. In this study, we determined the effects of protective opsonic and nonopsonic PPS3 MAbs on ST3 NP colonization in mice. Our results show that a nonopsonic MAb reduced early NP colonization and prevented ST3 dissemination to the lungs and blood, but an opsonic MAb did not. Moreover, the opsonic MAb induced a proinflammatory NP cytokine response, but the nonopsonic MAb had an antiinflammatory effect. The effect of the nonopsonic MAb on colonization did not require its Fc region, but its antiinflammatory effect did. Our findings challenge the paradigm that opsonic MAbs are required to prevent NP colonization and suggest that further studies of the activity of nonopsonic antibodies could advance our understanding of mechanisms of PCV efficacy and provide novel correlates of protection. PMID:26838726

  1. Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices

    PubMed Central

    Pennant, Keyana N.; Costa, John J.; Fuhlbrigge, Anne L.; Sax, Paul E.; Szent-Gyorgyi, Lara E.; Coblyn, Jonathan; Desai, Sonali P.

    2015-01-01

    Background. Influenza and pneumococcal vaccinations are recommended for elderly and high-risk patients; however, rates of adherence are low. We sought to implement influenza and pneumococcal vaccine initiatives in 4 different ambulatory specialty practices, using 3 unique approaches. Methods. Four specialties with high-risk patient populations were selected for intervention: allergy (asthma), infectious disease (ID) (human immunodeficiency virus), pulmonary (chronic lung disease), and rheumatology (immunocompromised). Allergy and ID focused on influenza vaccination, and pulmonary and rheumatology focused on pneumococcal vaccination. We used 3 strategies for quality improvement: physician reminders, patient letters, and a nurse-driven model. Physicians were provided their performance data on a monthly basis and presented trended data on a quarterly basis at staff meetings. Results. All 4 specialties developed processes for improving vaccination rates with all showing some increase. Higher rates were achieved with pneumococcal vaccine than influenza. Pneumococcal vaccine rates showed steady improvement from year to year while influenza vaccine rates remained relatively constant. Allergy's influenza rate was 59% in 2011 and 64% in the 2014 flu season. Infectious disease influenza rates moved from 74% in the 2011 flu season to 86% for the 2014 season. Pneumococcal vaccine in pulmonary patients' rate was 52% at the start of intervention in February 2009 and 79% as of January 2015. Rheumatology rates rose from 50% in February 2009 to 87% in January 2015. Conclusions. Integrated routine workflow and performance data sharing can effectively engage specialists and staff in vaccine adherence improvement. Influenza vaccination may require other approaches to achieve the rates seen with pneumococcal vaccine. PMID:26430697

  2. Evolving pneumococcal serotypes and sequence types in relation to high antibiotic stress and conditional pneumococcal immunization

    PubMed Central

    Su, Lin-Hui; Kuo, An-Jing; Chia, Ju-Hsin; Li, Hsin-Chieh; Wu, Tsu-Lan; Feng, Ye; Chiu, Cheng-Hsun

    2015-01-01

    In Taiwan, beginning in 2013, the 13-valent pneumococcal conjugate vaccine (PCV13) was provided free of charge to children 2–5 years of age. In 2014, this was extended to children 1–5 years old. During 2012–2014, 953 cases of culture-confirmed pneumococcal disease (CCPD), including 104 invasive pneumococcal disease (IPD), were prospectively identified and analyzed at a 3,700-bed hospital in Taiwan. From 2012 to 2014, the incidence per 10,000 admissions decreased from 26.7 to 20.4 for CCPD (P < 0.001) and from 3.2 to 1.9 for IPD (P < 0.05). Significant reduction of PCV13 serotypes was firstly noted in children in 2013 and extended to both paediatric and adult populations in 2014. Simultaneously, the incidence per 10,000 admissions of non-PCV13 serotypes increased from 6.1 in 2012 to 9.3 in 2014 (P < 0.005). The most prevalent non-PCV13 serotypes were 15A, 15B, and 23A, each containing a predominant clone, ST6315A, ST8315B, and ST33823A. From 2012 to 2014, isolates with penicillin minimum inhibitory concentrations >2 mg/L decreased from 27.8% to 8.1% (P < 0.001) among all isolates. PCV13 immunization in young children demonstrated an early protective effect in all ages. However, in the elderly, the effect was compromised by an emergence of non-PCV13 serotypes. PMID:26522920

  3. Amine treatment of polysaccharide solution

    SciTech Connect

    Shay, L. K.; Reiter, S. E.

    1984-11-27

    A thermostable, viscous xanthan polysaccharide solution prepared by the process of heating a xanthan polysaccharide solution in the presence of at least one C/sub 1/ to C/sub 10/ alkyl or C/sub 3/ to C/sub 10/ cycloalkyl substituted primary or secondary mono- or diamine having an upper limit of a total of 15 carbon atoms under conditions sufficient to form a thermostable, viscous xanthan polysaccharide solution. The thermostable, viscous xanthan polysaccharide solution may be used as a mobility buffer in a process for the enhanced recovery of oil.

  4. Seasonality of Pneumococcal Nasopharyngeal Carriage in Rural Gambia Determined within the Context of a Cluster Randomized Pneumococcal Vaccine Trial

    PubMed Central

    Bojang, Abdoulie; Jafali, James; Egere, Uzochukwu E.; Hill, Phillip C.; Antonio, Martin; Jeffries, David; Greenwood, Brian M.; Roca, Anna

    2015-01-01

    Background We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. Methods 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. Results Prevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis. Conclusions In areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data. PMID:26132206

  5. CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae

    PubMed Central

    Wu, Kaifeng; Xu, Hongmei; Zheng, Yuqiang; Wang, Libin; Zhang, Xuemei; Yin, Yibing

    2016-01-01

    Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region −146 to −114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis. PMID:27386955

  6. Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient

    PubMed Central

    Morand, Philippe C; Veuillez, Veronique; Poyart, Claire; Abachin, Eric; Quesne, Gilles; Dupont, Bertrand; Berche, Patrick; Viard, Jean-Paul

    2003-01-01

    Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case. PMID:14613586

  7. Pneumococcal meningitis in an adolescent with fever and foot ache.

    PubMed

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  8. The importance of splenic blood flow in clearing pneumococcal organisms.

    PubMed Central

    Horton, J; Ogden, M E; Williams, S; Coln, D

    1982-01-01

    Overwhelming infection from encapsulated bacteria occurs after splenectomy. Decreases in IgM, tufsin, and serum opsonin are known to occur in animals and humans after splenectomy. A substantial immunologic advantage exists if some splenic tissue remains, but this may not offer sufficient protection from encapsulated bacteria if splenic arterial blood flow is reduced. This experiment was designed to examine the rate of pneumococcal clearance by the spleen and to determine the relationship between splenic blood flow and splenic tissue mass in bacterial clearance from the blood. Pneumococcal clearance, splenic blood flow, and residual splenic weight were measured in 171 rabbits with normal spleens, ligated splenic arteries, splenic autotransplants, hemisplenectomies, and splenectomies. Interruption of the splenic artery results in delayed pneumococcal clearance that is due to reduced blood flow and not to a decrease in splenic tissue mass. Splenic artery ligation to preserve an injured spleen cannot be assumed to give protection from sepsis. PMID:7055394

  9. Pneumococcal Meningitis in an Adolescent with Fever and Foot Ache

    PubMed Central

    Dias, Catarina; Pedrosa, Cláudia; Romariz, Jorge; Santos, Mafalda; Rodrigues, Lúcia

    2013-01-01

    Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement. PMID:23956909

  10. Pediatric Pneumococcal Serotypes in 4 European Countries

    PubMed Central

    Kissling, Esther; Fenoll, Asuncion; George, Robert; Lepoutre, Agnes; Lernout, Tinne; Tarragó, David; Varon, Emmanuelle; Verhaegen, Jan

    2010-01-01

    After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999–2002 (prevaccine) and 2005–2006 (postmarketing). Vaccine coverage increased to ≈32%–48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3–4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9–16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends. PMID:20735928

  11. Iodine-Catalyzed Polysaccharide Esterification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A review is provided of the recent reports to use iodine-catalyzed esterification reaction to produce esters from polysaccharides. The process entails reaction of the polysaccharide with an acid anhydride in the presence of a catalytic level of iodine, and in the absence of additional solvents. T...

  12. Characterization of Brucella polysaccharide B.

    PubMed Central

    Bundle, D R; Cherwonogrodzky, J W; Perry, M B

    1988-01-01

    Polysaccharide B was extracted from Brucella melitensis 16M and from a rough strain of Brucella abortus 45/20 by autoclaving or trichloroacetic acid extraction of whole cells and by a new method involving mild leaching of cells. The material obtained by either of the established procedures was contaminated by O polysaccharide. The new leaching protocol eliminated this impurity and provided a pure glucan, which was regarded as polysaccharide B. This polysaccharide was found by high-performance liquid chromatography separations, chemical composition, methylation, and two-dimensional homo- and heteronuclear magnetic resonance experiments to be a family of nonreducing cyclic 1,2-linked polymers of beta-D-glucopyranosyl residues. The degree of polymerization varied between 17 and 24. Polysaccharide B was essentially identical to cyclic D-glucans produced by Rhizobia, Agrobacteria, and other bacterial species. Pure polysaccharide B did not precipitate with Brucella anti-A or anti-M serum and did not inhibit the serological reaction of Brucella A or M antigen with either bovine or murine monoclonal Brucella anti-A or anti-M serum. Previously described serological reactions of polysaccharide B preparations with Brucella anti-A and anti-M sera are related in this study to the presence in crude extracts of contaminants with the antigenic properties of Brucella lipopolysaccharide O polysaccharides. PMID:3356461

  13. Polysaccharides of Type 6 Klebsiella

    PubMed Central

    Gormus, B. J.; Wheat, R. W.

    1971-01-01

    Water-extractable type 6 Klebsiella antigens were separated into a type 6-specific acidic polysaccharide and a neutral polysaccharide. The neutral polymer was devoid of type 6 activity although it was serologically active. The type 6-specific polymer contained fucose, glucose, and mannose, and pyruvic, galacturonic, and possibly glucuronic acids. The neutral polymer contained glucose, galactose, and mannose. PMID:5003178

  14. Polysaccharides and bacterial plugging

    SciTech Connect

    Fogler, H.S.

    1991-11-01

    Before any successful application of Microbial Enhanced Oil Recovery process can be realized, an understanding of the cells' transport and retentive mechanisms in porous media is needed. Cell transport differs from particle transport in their ability to produce polysaccharides, which are used by cells to adhere to surfaces. Cell injection experiments have been conducted using Leuconostoc cells to illustrate the importance of cellular polysaccharide production as a transport mechanism that hinders cell movement and plugs porous media. Kinetic studies of the Leuconostoc cells, carried out to further understand the plugging rates of porous media, have shown that the cells' growth rates are approximately equal when provided with monosaccharide (glucose and fructose) or sucrose. The only difference in cell metabolism is the production of dextran when sucrose is supplied as a carbon source. Experimentally it has also been shown that the cells' growth rate is weakly dependent upon the sucrose concentration in the media, and strongly dependent upon the concentration of yeast extract. The synthesis of cellular dextran has been found to lag behind cell generation, thus indicating that the cells need to reach maturity before they are capable of expressing the detransucrase enzyme and synthesizing insoluble dextran. Dextran yields were found to be dependent upon the sucrose concentration in the media. 10 refs., 9 figs., 9 tabs.

  15. Why Were Polysaccharides Necessary?

    NASA Astrophysics Data System (ADS)

    Tolstoguzov, Vladimir

    2004-12-01

    The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, `compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

  16. The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases.

    PubMed

    Frandsen, Kristian E H; Simmons, Thomas J; Dupree, Paul; Poulsen, Jens-Christian N; Hemsworth, Glyn R; Ciano, Luisa; Johnston, Esther M; Tovborg, Morten; Johansen, Katja S; von Freiesleben, Pernille; Marmuse, Laurence; Fort, Sébastien; Cottaz, Sylvain; Driguez, Hugues; Henrissat, Bernard; Lenfant, Nicolas; Tuna, Floriana; Baldansuren, Amgalanbaatar; Davies, Gideon J; Lo Leggio, Leila; Walton, Paul H

    2016-04-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that oxidatively break down recalcitrant polysaccharides such as cellulose and chitin. Since their discovery, LPMOs have become integral factors in the industrial utilization of biomass, especially in the sustainable generation of cellulosic bioethanol. We report here a structural determination of an LPMO-oligosaccharide complex, yielding detailed insights into the mechanism of action of these enzymes. Using a combination of structure and electron paramagnetic resonance spectroscopy, we reveal the means by which LPMOs interact with saccharide substrates. We further uncover electronic and structural features of the enzyme active site, showing how LPMOs orchestrate the reaction of oxygen with polysaccharide chains. PMID:26928935

  17. Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path).

    PubMed

    Engelen-Lee, Joo-Yeon; Brouwer, Matthijs C; Aronica, Eleonora; van de Beek, Diederik

    2016-01-01

    Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path). PMID:27001057

  18. Sialic Acid Transport Contributes to Pneumococcal Colonization ▿

    PubMed Central

    Marion, Carolyn; Burnaugh, Amanda M.; Woodiga, Shireen A.; King, Samantha J.

    2011-01-01

    Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Airway colonization is a necessary precursor to disease, but little is known about how the bacteria establish and maintain colonization. Carbohydrates are required as a carbon source for pneumococcal growth and, therefore, for colonization. Free carbohydrates are not readily available in the naso-oropharynx; however, N- and O-linked glycans are common in the airway. Sialic acid is the most common terminal modification on N- and O-linked glycans and is likely encountered frequently by S. pneumoniae in the airway. Here we demonstrate that sialic acid supports pneumococcal growth when provided as a sole carbon source. Growth on sialic acid requires import into the bacterium. Three genetic regions have been proposed to encode pneumococcal sialic acid transporters: one sodium solute symporter and two ATP binding cassette (ABC) transporters. Data demonstrate that one of these, satABC, is required for transport of sialic acid. A satABC mutant displayed significantly reduced growth on both sialic acid and the human glycoprotein alpha-1. The importance of satABC for growth on human glycoprotein suggests that sialic acid transport may be important in vivo. Indeed, the satABC mutant was significantly reduced in colonization of the murine upper respiratory tract. This work demonstrates that S. pneumoniae is able to use sialic acid as a sole carbon source and that utilization of sialic acid is likely important during pneumococcal colonization. PMID:21189320

  19. What are the latest recommendations for pneumococcal vaccines?

    PubMed

    Fabel, Patricia H; Horton, Emily C; Shealy, Kayce

    2016-04-01

    The Advisory Committee on Immunization Practices recently updated its guidelines on pneumococcal pneumonia vaccines for older adults. The new guidelines recommend that patients age 65 years and older receive the PCV13 vaccine in a series along with the PPSV23 vaccine. This article summarizes these changes along with a review of when to vaccinate other key adult populations. PMID:27023652

  20. Impact of the 13-valent pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in children.

    PubMed

    Chapoutot, A G; Dessein, R; Guilluy, O; Lagrée, M; Wallet, F; Varon, E; Martinot, A; Dubos, F

    2016-02-01

    The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of pneumococcal meningitis (PM) in children is unknown. To determine this impact, a descriptive multicentre retrospective cohort study was conducted from 2008 to 2013 in northern France. All laboratory-confirmed PM in children aged <18 years in all hospitals of the area with paediatric units were included. Two independent databases were used for exhaustive identification of cases: medical plus laboratory records at each hospital and discharge codes. The corrected incidence of PM was determined by a capture-recapture analysis using these two databases. Sixty-two cases were found over the 6-year period. A decrease of the PM corrected incidence was observed in the global population (P = 0·07), significant only for children aged <2 years, from 11·9/100 000 in 2008 in 1·9/100 000 in 2013 [6·4 fold-decrease, 95% confidence interval (CI) 1·4-41, P = 0·01] between years 2008 and 2013. When comparing the pre- and post-PCV13 periods, this decrease was still statistically significant for children aged <2 years [7·32/100 000 (95% CI 4·39-10·25) to 2·78/100 000 (95% CI 0·96-4·60), P = 0·01]. Only three (5%) cases of PM caused by vaccine serotypes could have been prevented. After the introduction of the PCV13 vaccine, a decrease in the incidence of PM cases in children in northern France was observed. PMID:26234410

  1. T-cell modulation of the antibody response to bacterial polysaccharide antigens.

    PubMed Central

    Taylor, C E; Bright, R

    1989-01-01

    Pretreatment of mice with subimmunogenic doses of meningococcal polysaccharide (MP), Pseudomonas aeruginosa lipopolysaccharide (PA), or Streptococcus mutans polysaccharide (SM) resulted in suppression of antibody response. The transfer of putative suppressor T cells (Ts cells) from donor mice primed with a subimmunogenic dose of MP to naive recipients at the time of immunization with MP substantially reduced the magnitude of the antibody response. Also, the infusion of B cells taken from animals immunized with either MP or PA suppressed the antibody response of naive recipients to MP or PA, respectively, relative to controls, suggesting that Ts cells respond to determinants on immune B cells. We observed that the injection of concanavalin A or phytohemagglutinin (two lectins known to augment the activity of amplifier T cells [Ta cells]) 2 days postimmunization enhanced the antibody response to MP and SM. In addition, Ta-cell activity was transferred to naive animals by using spleen cells. Although the administration of phytohemagglutinin at the time of immunization with MP also resulted in increased antibody response, the injection of concanavalin A simultaneous with immunization resulted in a suppression of the antibody response to MP. Although Ts cells generated in response to pneumococcal polysaccharide type III were found to respond to monoclonal antibody Ly-m22, Ta cells responded to monoclonal antibodies L3T4 and Ia but not to Ly-m22. These studies suggest that Ta and Ts cells can modulate the antibody response to MP, SM, and PA in a positive and negative manner, respectively. PMID:2462536

  2. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis.

    PubMed

    Kloek, Anne T; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L; Asselbergs, Folkert W; Valls Serón, Mercedes; Brouwer, Matthijs C; van de Beek, Diederik; Ferwerda, Bart

    2016-01-01

    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10(-7)). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10(-6); G allele OR 3.21 [95% CI 2.05-5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10(-5); G allele OR 0.66 [95% CI 0.54-0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10(-7)). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

  3. Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

    PubMed Central

    Kloek, Anne T.; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L.; Asselbergs, Folkert W.; Serón, Mercedes Valls; Brouwer, Matthijs C.; van de Beek, Diederik; Ferwerda, Bart

    2016-01-01

    Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

  4. Unravelling the structure of the pneumococcal autolytic lysozyme

    PubMed Central

    Monterroso, Begoña; López-Zumel, Consuelo; García, José L.; Sáiz, José L.; García, Pedro; Campillo, Nuria E.; Menéndez, Margarita

    2005-01-01

    The LytC lysozyme of Streptococcus pneumoniae forms part of the autolytic system of this important pathogen. This enzyme is composed of a C-terminal CM (catalytic module), belonging to the GH25 family of glycosyl hydrolases, and an N-terminal CBM (choline-binding module), made of eleven homologous repeats, that specifically recognizes the choline residues that are present in pneumococcal teichoic and lipoteichoic acids. This arrangement inverts the general assembly pattern of the major pneumococcal autolysin, LytA, and the lytic enzymes encoded by pneumococcal bacteriophages that place the CBM (made of six repeats) at the C-terminus. In the present paper, a three-dimensional model of LytC built by homology modelling of each module and consistent with spectroscopic and hydrodynamic studies is shown. In addition, the putative catalytic-pair residues are identified. Despite the inversion in the modular arrangement, LytC and the bacteriophage-encoded Cpl-1 lysozyme most probably adopt a similar global fold. However, the distinct choline-binding ability and their substrate-binding surfaces may reflect a divergent evolution directed by the different roles played by them in the host (LytC) or in the bacteriophage (Cpl-1). The tight binding of LytC to the pneumococcal envelope, mediated by the acquisition of additional choline-binding repeats, could facilitate the regulation of the potentially suicidal activity of this autolysin. In contrast, a looser attachment of Cpl-1 to the cell wall and the establishment of more favourable interactions between its highly negatively charged catalytic surface and the positively charged chains of pneumococcal murein could enhance the lytic activity of the parasite-encoded enzyme and therefore liberation of the phage progeny. PMID:15943581

  5. Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

    PubMed

    Ingels, Helene Andrea Sinclair

    2015-07-01

    the rIPD. Most common was immune deficiency due to transplantation. In 19% the episode of rIPD was the clinical manifestation that subsequently led to a diagnosis of an underlying disease. Finally, in 31% of the children no underlying disease was detected. Paper 2 covers data from a follow-up of the cohort of children described in Paper 1. Of this unselected cohort of rIPD, all children without an obvious underlying disease predisposing to pneumococcal disease (such as malignancy, HIV or cerebrospinal-fluid leakage) were invited to participate in the study by undergoing a thorough immunological evaluation. Basic immunological parameters including activity of complement-pathways and T-, B-, NK-cell count were examined in the children and their families. Furthermore, B-cell function including antibody response to polysaccharide-based pneumococcal vaccination and somatic hypermutation was evaluated. Toll like receptor (TLR) signalling function was evaluated in a functional assay. When children with classical risk factors for IPD were excluded, 15 individuals were eligible. Of whom, sex (40%) children with complement C2 deficiency were identified. Moreover, impaired vaccination response was found in six children: three with concurrent C2 deficiency and three with no other immune abnormality. One patient with a severe TLR signalling dysfunction was diagnosed. In Paper 3, we aimed to assess the impact of PCV7 in Denmark following the first three years of infant immunization. By comparing age-specific disease incidences of IPD in the pre-PCV7 (years 2000-2007) and the PCV7 periods (years 2008-2010) we sought to assess direct and indirect effects on incidence of IPD. In addition, changes in pneumococcal serotype distribution and IPD-related mortality were assessed. We documented a marked decline in the incidence of IPD in both vaccinated and non-vaccinated age groups. The overall incidence of IPD among children aged 0-5 years declined from 26.7 to 16.3 cases per 100,000 (IRR

  6. A threading receptor for polysaccharides

    NASA Astrophysics Data System (ADS)

    Mooibroek, Tiddo J.; Casas-Solvas, Juan M.; Harniman, Robert L.; Renney, Charles M.; Carter, Tom S.; Crump, Matthew P.; Davis, Anthony P.

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (Ka up to 19,000 M-1), and is shown—by nuclear Overhauser effect spectroscopy—to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules.

  7. A threading receptor for polysaccharides.

    PubMed

    Mooibroek, Tiddo J; Casas-Solvas, Juan M; Harniman, Robert L; Renney, Charles M; Carter, Tom S; Crump, Matthew P; Davis, Anthony P

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (K(a) up to 19,000 M(-1)), and is shown--by nuclear Overhauser effect spectroscopy--to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules. PMID:26673266

  8. Computer simulation and experimental study of the polysaccharide-polysaccharide interaction in the bacteria Azospirillum brasilense Sp245

    NASA Astrophysics Data System (ADS)

    Arefeva, Oksana A.; Kuznetsov, Pavel E.; Tolmachev, Sergey A.; Kupadze, Machammad S.; Khlebtsov, Boris N.; Rogacheva, Svetlana M.

    2003-09-01

    We have studied the conformational properties and molecular dynamics of polysaccharides by using molecular modeling methods. Theoretical and experimental results of polysaccharide-polysaccharide interactions are described.

  9. Incidence of Hospitalized Pneumococcal Pneumonia among Adults in Guatemala, 2008-2012

    PubMed Central

    Contreras, Carmen Lucía; Verani, Jennifer R.; Lopez, María Renee; Paredes, Antonio; Bernart, Chris; Moscoso, Fabiola; Roldan, Aleida; Arvelo, Wences; Lindblade, Kim A.; McCracken, John P.

    2015-01-01

    Background Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. Methods Data from 2008–2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). Results Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18–24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. Conclusions An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala. PMID:26488871

  10. Streptococcus pneumoniae Serotype Distribution and Pneumococcal Conjugate Vaccine Serotype Coverage among Pediatric Patients in East and Southeast Asia, 2000-2014: a Pooled Data Analysis.

    PubMed

    Tai, Stanley S

    2016-01-01

    Pneumococcal infection is one of the leading causes of death worldwide, especially in children of developing and underdeveloped countries. Capsular polysaccharide-based vaccines are available for the prevention of this disease. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for use in children less than two years of age. Subsequently, to broaden the protection, 10-valent (PCV10) and 13-valent (PCV13) vaccines were licensed in 2009 and 2010, respectively. All of these conjugate vaccines elicit an immune response that only provides protection against the infection of S. pneumoniae serotypes included in the formulation. Profiles of S. pneumoniae serotype distribution and serotype coverage for both PCV7 and PCV13 have been reported in some Asian countries/territories. But the published results cannot provide conclusive information due to the difference in studied population and geographic areas. The goals of this review are to obtain an accurate estimate of serotype coverage for PCV7, PCV10, and PCV13 and examine the change in the S. pneumoniae serotype distribution after PCV7 use among pediatric patients in East and Southeast Asia through the analysis of pooled data that were published in the English literature between 2000 and 2014. PMID:26907356

  11. Streptococcus pneumoniae Serotype Distribution and Pneumococcal Conjugate Vaccine Serotype Coverage among Pediatric Patients in East and Southeast Asia, 2000–2014: a Pooled Data Analysis

    PubMed Central

    Tai, Stanley S.

    2016-01-01

    Pneumococcal infection is one of the leading causes of death worldwide, especially in children of developing and underdeveloped countries. Capsular polysaccharide-based vaccines are available for the prevention of this disease. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for use in children less than two years of age. Subsequently, to broaden the protection, 10-valent (PCV10) and 13-valent (PCV13) vaccines were licensed in 2009 and 2010, respectively. All of these conjugate vaccines elicit an immune response that only provides protection against the infection of S. pneumoniae serotypes included in the formulation. Profiles of S. pneumoniae serotype distribution and serotype coverage for both PCV7 and PCV13 have been reported in some Asian countries/territories. But the published results cannot provide conclusive information due to the difference in studied population and geographic areas. The goals of this review are to obtain an accurate estimate of serotype coverage for PCV7, PCV10, and PCV13 and examine the change in the S. pneumoniae serotype distribution after PCV7 use among pediatric patients in East and Southeast Asia through the analysis of pooled data that were published in the English literature between 2000 and 2014. PMID:26907356

  12. Biochemical And Genetic Modification Of Polysaccharides

    NASA Technical Reports Server (NTRS)

    Kern, Roger G.; Petersen, Gene R.; Richards, Gil F.

    1993-01-01

    Bacteriophages producing endopolysaccharase-type enzymes used to produce, isolate, and purify high yields of modified polysaccharides from polysaccharides produced by, and incorporated into capsules of, certain bacteria. Bacteriophages used in conversion of native polysaccharide materials into polymers of nearly uniform high molecular weight or, alternatively, into highly pure oligosaccharides. Also used in genetic selection of families of polysaccharides structurally related to native polysaccharide materials, but having altered properties. Resulting new polysaccharides and oligosaccharides prove useful in variety of products, including pharmaceutical chemicals, coating materials, biologically active carbohydrates, and drag-reducing additives for fluids.

  13. Pneumococcal Hydrogen Peroxide–Induced Stress Signaling Regulates Inflammatory Genes

    PubMed Central

    Loose, Maria; Hudel, Martina; Zimmer, Klaus-Peter; Garcia, Ernesto; Hammerschmidt, Sven; Lucas, Rudolf; Chakraborty, Trinad; Pillich, Helena

    2015-01-01

    Microbial infections can induce aberrant responses in cellular stress pathways, leading to translational attenuation, metabolic restriction, and activation of oxidative stress, with detrimental effects on cell survival. Here we show that infection of human airway epithelial cells with Streptococcus pneumoniae leads to induction of endoplasmic reticulum (ER) and oxidative stress, activation of mitogen-associated protein kinase (MAPK) signaling pathways, and regulation of their respective target genes. We identify pneumococcal H2O2 as the causative agent for these responses, as both catalase-treated and pyruvate oxidase-deficient bacteria lacked these activities. Pneumococcal H2O2 induced nuclear NF-κB translocation and transcription of proinflammatory cytokines. Inhibition of translational arrest and ER stress by salubrinal or of MAPK signaling pathways attenuate cytokine transcription. These results provide strong evidence for the notion that inhibition of translation is an important host pathway in monitoring harmful pathogen-associated activities, thereby enabling differentiation between pathogenic and nonpathogenic bacteria. PMID:25183769

  14. Risk Factors for Death from Invasive Pneumococcal Disease, Europe, 2010

    PubMed Central

    Dias, Joana Gomes; Hruba, Frantiska; Lopalco, Pier Luigi; Pastore-Celentano, Lucia; Gauci, Andrew J. Amato

    2015-01-01

    We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were significantly associated with death. Non–pneumococcal conjugate vaccine (PCV) serotypes among children <5 years of age and 7-valent PCV serotypes among persons 5–64 years of age were associated with increased risk for death; among adults >65 years of age, risk did not differ by serotype. These findings highlight differences in case-fatality rates between serotypes and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs. PMID:25693604

  15. Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers.

    PubMed

    Zhao, Xiaoran; Li, Hongen; Wang, Jianfeng; Guo, Yan; Liu, Bowen; Deng, Xuming; Niu, Xiaodi

    2016-03-01

    Pneumolysin (PLY), an essential virulence factor of Streptococcus pneumoniae (pneumococcus), can penetrate the physical defenses of the host and possesses inflammatory properties. The vital role PLY plays in pneumococcus pathogenesis makes this virulence factor one of the most promising targets for the treatment of pneumococcal infection. Verbascoside (VBS) is an agent that does not exhibit bacteriostatic activity but has been shown to inhibit PLY-mediated cytotoxicity. The results from molecular dynamics simulations and mutational analysis indicated that VBS binds to the cleft between domains 3 and 4 of PLY, thereby blocking PLY's oligomerization and counteracting its hemolytic activity. Moreover, VBS can effectively alleviate PLY-mediated human alveolar epithelial (A549) cell injury, and treatment with VBS provides significant protection against lung damage and reduces mortality in a pneumococcal pneumonia murine model. Our results demonstrate that VBS is a strong candidate as a novel therapeutic in the treatment of Streptococcus pneumoniae infection. PMID:26700563

  16. Microarray Analysis of Pneumococcal Gene Expression during Invasive Disease

    PubMed Central

    Orihuela, Carlos J.; Radin, Jana N.; Sublett, Jack E.; Gao, Geli; Kaushal, Deepak; Tuomanen, Elaine I.

    2004-01-01

    Streptococcus pneumoniae is a leading cause of invasive bacterial disease. This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research. Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro. Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function. Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants. Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease. PMID:15385455

  17. Impact of Preceding Flu-Like Illness on the Serotype Distribution of Pneumococcal Pneumonia

    PubMed Central

    Song, Joon Young; Nahm, Moon H.; Cheong, Hee Jin; Kim, Woo Joo

    2014-01-01

    Background Even though the pathogenicity and invasiveness of pneumococcus largely depend on capsular types, the impact of serotypes on post-viral pneumococcal pneumonia is unknown. Methods and Findings This study was performed to evaluate the impact of capsular serotypes on the development of pneumococcal pneumonia after preceding respiratory viral infections. Patients with a diagnosis of pneumococcal pneumonia were identified. Pneumonia patients were divided into two groups (post-viral pneumococcal pneumonia versus primary pneumococcal pneumonia), and then their pneumococcal serotypes were compared. Nine hundred and nineteen patients with pneumococcal pneumonia were identified during the study period, including 327 (35.6%) cases with post-viral pneumococcal pneumonia and 592 (64.4%) cases with primary pneumococcal pneumonia. Overall, serotypes 3 and 19A were the most prevalent, followed by serotypes 19F, 6A, and 11A/11E. Although relatively uncommon (33 cases, 3.6%), infrequently colonizing invasive serotypes (4, 5, 7F/7A, 8, 9V/9A, 12F, and 18C) were significantly associated with preceding respiratory viral infections (69.7%, P<0.01). Multivariate analysis revealed several statistically significant risk factors for post-viral pneumococcal pneumonia: immunodeficiency (OR 1.66; 95% CI, 1.10–2.53), chronic lung diseases (OR 1.43; 95% CI, 1.09–1.93) and ICI serotypes (OR 4.66; 95% CI, 2.07–10.47). Conclusions Infrequently colonizing invasive serotypes would be more likely to cause pneumococcal pneumonia after preceding respiratory viral illness, particularly in patients with immunodeficiency or chronic lung diseases. PMID:24691515

  18. Evolving role of 13-valent pneumococcal conjugate vaccine in clinical practice.

    PubMed

    Azzari, Chiara; Martinón-Torres, Federico; Schmitt, Heinz-Josef; Dagan, Ron

    2014-08-01

    Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), PCVs with extended coverage have become available, and there is emerging global evidence that these vaccines, in particular PCV13, have further reduced rates of invasive pneumococcal disease compared with PCV7. The present article aims to address emerging topics related to PCV13 use in routine clinical practice; specifically: (1) the potential role of high-valent PCVs in reducing pneumococcal disease burden; (2) the impact of PCVs on nasopharyngeal carriage and how this may contribute to reductions in otitis media and pneumonia, as well as the prevalence of resistant pneumococcal strains; (3) new PCV13 indications and (4) importance of schedule adherence for PCV in the prevention of cases of vaccine serotype-specific invasive pneumococcal disease. The beneficial effects of PCVs in protecting individuals from a wide spectrum of pneumococcal diseases can be increased by improving the vaccine coverage and adhering to the recommended vaccination schedules. There is increasing evidence that PCV13 has reduced much of the post-PCV7 burden of pneumococcal diseases in the pediatric community, including reducing pneumococcal colonization and the incidence of invasive pneumococcal disease and mucosal diseases. This has also led to a reduction in antibiotic-resistant pneumococcal diseases. The role of PCV13 in clinical practice is evolving, with PCV13 now available for children and adolescents between the ages of 6 weeks and 17 years, thus ensuring that children in all age groups can be protected against vaccine-serotype pneumococcal diseases. Continued surveillance is warranted to monitor the impact of PCV13 on disease burden. PMID:24618937

  19. Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

    PubMed

    Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T

    2015-09-01

    The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia. PMID:26059041

  20. Dense genomic sampling identifies highways of pneumococcal recombination.

    PubMed

    Chewapreecha, Claire; Harris, Simon R; Croucher, Nicholas J; Turner, Claudia; Marttinen, Pekka; Cheng, Lu; Pessia, Alberto; Aanensen, David M; Mather, Alison E; Page, Andrew J; Salter, Susannah J; Harris, David; Nosten, Francois; Goldblatt, David; Corander, Jukka; Parkhill, Julian; Turner, Paul; Bentley, Stephen D

    2014-03-01

    Evasion of clinical interventions by Streptococcus pneumoniae occurs through selection of non-susceptible genomic variants. We report whole-genome sequencing of 3,085 pneumococcal carriage isolates from a 2.4-km(2) refugee camp. This sequencing provides unprecedented resolution of the process of recombination and its impact on population evolution. Genomic recombination hotspots show remarkable consistency between lineages, indicating common selective pressures acting at certain loci, particularly those associated with antibiotic resistance. Temporal changes in antibiotic consumption are reflected in changes in recombination trends, demonstrating rapid spread of resistance when selective pressure is high. The highest frequencies of receipt and donation of recombined DNA fragments were observed in non-encapsulated lineages, implying that this largely overlooked pneumococcal group, which is beyond the reach of current vaccines, may have a major role in genetic exchange and the adaptation of the species as a whole. These findings advance understanding of pneumococcal population dynamics and provide information for the design of future intervention strategies. PMID:24509479

  1. Investigational new drugs for the treatment of resistant pneumococcal infections.

    PubMed

    Hoffman-Roberts, Holly L; C Babcock, Emily; Mitropoulos, Isaac F

    2005-08-01

    Antibiotic resistance in Streptococcus pneumoniae is not only increasing with penicillin but also with other antimicrobial classes including the macrolides, tetracyclines and sulfonamides. This trend with antibiotic resistance has highlighted the need for the further development of new anti-infectives for the treatment of pneumococcal infections, particularly against multi-drug resistant pneumococci. Several new drugs with anti-pneumococcal activity are at various stages of development and will be discussed in this review. Two new cephalosporins with activity against S. pneumoniae include ceftobiprole and RWJ-54428. Faropenem is in a new class of beta-lactam antibiotics called the penems. Structurally, the penems are a hybrid between the penicillins and cephalosporins. Sitafloxacin and garenoxacin are two new quinolones that are likely to have a role in treating pneumococcal infections. Oritavancin and dalbavancin are glycopeptides with activity against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus spp. as well as multi-drug resistant pneumococci. Tigecycline is the first drug in a new class of anti-infectives called the glycycyclines that has activity against penicillin-resistant pneumococci. PMID:16050791

  2. Dense genomic sampling identifies highways of pneumococcal recombination

    PubMed Central

    Chewapreecha, Claire; Harris, Simon R; Croucher, Nicholas J; Turner, Claudia; Marttinen, Pekka; Cheng, Lu; Pessia, Alberto; Aanensen, David M; Mather, Alison E; Page, Andrew J; Salter, Susannah J.; Harris, David; Nosten, Francois; Goldblatt, David; Corander, Jukka; Parkhill, Julian

    2014-01-01

    Evasion of clinical interventions by Streptococcus pneumoniae occurs through selection of non-susceptible genomic variants. Here we use genome sequencing of 3,085 pneumococcal carriage isolates from a 2.4 km2 refugee camp to enable unprecedented resolution of the process of recombination, and highlight its impact on population evolution. Genomic recombination hotspots show remarkable consistency between lineages, indicating common selective pressures acting at certain loci, particularly those associated with antibiotic resistance. Temporal changes in antibiotic consumption are reflected in changes in recombination trends demonstrating rapid spread of resistance when selective pressure is high. The highest frequencies of receipt and donation of recombined DNA fragments were observed in non-encapsulated lineages, implying that this largely overlooked pneumococcal group, which is beyond the reach of current vaccines, may play a major role in genetic exchange and adaptation of the species as a whole. These findings advance our understanding of pneumococcal population dynamics and provide important information for the design of future intervention strategies. PMID:24509479

  3. Rheologically interesting polysaccharides from yeasts

    NASA Technical Reports Server (NTRS)

    Petersen, G. R.; Nelson, G. A.; Cathey, C. A.; Fuller, G. G.

    1989-01-01

    We have examined the relationships between primary, secondary, and tertiary structures of polysaccharides exhibiting the rheological property of friction (drag) reduction in turbulent flows. We found an example of an exopolysaccharide from the yeast Cryptococcus laurentii that possessed high molecular weight but exhibited lower than expected drag reducing activity. Earlier correlations by Hoyt showing that beta 1 --> 3, beta 2 --> 4, and alpha 1 --> 3 linkages in polysaccharides favored drag reduction were expanded to include correlations to secondary structure. The effect of sidechains in a series of gellan gums was shown to be related to sidechain length and position. Disruption of secondary structure in drag reducing polysaccharides reduced drag reducing activity for some but not all exopolysaccharides. The polymer from C. laurentii was shown to be more stable than xanthan gum and other exopolysaccharides under the most vigorous of denaturing conditions. We also showed a direct relationship between extensional viscosity measurements and the drag reducing coefficient for four exopolysaccharides.

  4. The economic burden of childhood invasive pneumococcal diseases and pneumonia in Taiwan: Implications for a pneumococcal vaccination program

    PubMed Central

    Ho, Yi-Chien; Lee, Pei-Lun; Wang, Yu-Chiao; Chen, Shiou-Chien; Chen, Kow-Tong

    2015-01-01

    Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children <5 y of age between January 2008 and December 2008. A prospective survey was administered to the families of patients to obtain detailed personal costs. All costs are presented in US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%–81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection. PMID:25874476

  5. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... these materials is included in a December 17, 1999 Federal Register notice (64 FR 70914). Proposed... Vaccine: What You Need to Know 1. Pneumococcal Disease Infection with Streptococcus pneumoniae bacteria... risk for serious disease than older children. Pneumococcal bacteria are spread from person to...

  6. Pneumococcal meningitis: development of a new animal model

    PubMed Central

    Wei, Benjamin P.C.; Shepherd, Robert K.; Robins-Browne, Roy M.; Clark, Graeme M.; O’Leary, Stephen J.

    2007-01-01

    Hypothesis The rat is a suitable animal to establish a model for the study of pneumococcal meningitis post cochlear implantation Background There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis post implantation and are based on relatively small animal numbers, making it difficult to assess the cause and effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods Eighteen non-implanted rats were infected with 1× 106 and 1 × 108 colony forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear and intraperitoneal) to examine for evidence of meningitis over 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU intraperitoneal, 3 × 108CFU middle ear, 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. Histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system either via the cochlear aqueduct or canaliculi perforantes of osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal

  7. Invasive pneumococcal disease in patients with haematological malignancies before routine use of conjugate vaccines in Finland.

    PubMed

    Lindström, Vesa; Aittoniemi, Janne; Lyytikäinen, Outi; Klemets, Peter; Ollgren, Jukka; Silvennoinen, Raija; Nuorti, J Pekka; Sinisalo, Marjatta

    2016-05-01

    The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups. PMID:26635103

  8. Identification of potential new protein vaccine candidates through pan-surfomic analysis of pneumococcal clinical isolates from adults.

    PubMed

    Olaya-Abril, Alfonso; Jiménez-Munguía, Irene; Gómez-Gascón, Lidia; Obando, Ignacio; Rodríguez-Ortega, Manuel J

    2013-01-01

    Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141), whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms. PMID:23894641

  9. Identification of Potential New Protein Vaccine Candidates through Pan-Surfomic Analysis of Pneumococcal Clinical Isolates from Adults

    PubMed Central

    Olaya-Abril, Alfonso; Jiménez-Munguía, Irene; Gómez-Gascón, Lidia; Obando, Ignacio; Rodríguez-Ortega, Manuel J.

    2013-01-01

    Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the “shaving” proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called “pan-surfome”, consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141), whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms. PMID:23894641

  10. Polysaccharide-modified synthetic polymeric biomaterials.

    PubMed

    Baldwin, Aaron D; Kiick, Kristi L

    2010-01-01

    This review presents an overview of polysaccharide-conjugated synthetic polymers and their use in tissue-engineered scaffolds and drug-delivery applications. This topic will be divided into four categories: (1) polymeric materials modified with non-mammalian polysaccharides such as alginate, chitin, and dextran; (2) polymers modified with mammalian polysaccharides such as hyaluronan, chondroitin sulfate, and heparin; (3) multi-polysaccharide-derivatized polymer conjugate systems; and (4) polymers containing polysaccharide-mimetic molecules. Each section will discuss relevant conjugation techniques, analysis, and the impact of these materials as micelles, particles, or hydrogels used in in-vitro and in-vivo biomaterial applications. PMID:20091875