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Sample records for 23-valent pneumococcal polysaccharide

  1. Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

    PubMed

    Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

    2016-08-02

    Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD.

  2. 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.

  3. Expression of hBD-2 induced by 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine.

    PubMed

    Shen, Zhenwei; Lei, Han

    2012-10-01

    Human β-defensin-2 (hBD-2) is an antimicrobial peptide with high activity and broad spectrum activity. hBD-2 expression may be highly elevated by microorganisms and inflammation. We reported that the majority of common vaccines used, including 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine, could induce the expression of hBD-2 in epithelial cells. Among them, the 23-valent pneumococcal polysaccharide vaccine was effective at a lower concentration (0.5 µg/ml), while Haemophilus influenzae type b vaccine and split influenza virus vaccine were effective at the concentration of 1 µg/ml. However, bacteriostatic experiments revealed that the split influenza virus vaccine was capable of inducing the highest antimicrobial activity. The medium of the 23-valent pneumococcal polysaccharide vaccine treatment group had a higher antimicrobial activity than the medium of the Haemophilus influenzae type b vaccine treatment group. The transcriptional regulator of hBD-2, that is, the NF-κB subunit, had a high level of activity, while the normal epithelial cells showed barely detectable activity, indicating that these vaccines have potential for clinical application.

  4. Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes

    PubMed Central

    Ciprero, Karen L.; Marchese, Rocio D.; Richard, Patrick; Baudin, Martine; Sterling, Tina M.; Manoff, Susan B.; Radley, David; Stek, Jon E.; Soubeyrand, Benoît; Grabenstein, John D.; Samson, Sandrine I.; Musey, Luwy K.

    2016-01-01

    ABSTRACT PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 µg/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre-vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates. PMID:27002793

  5. Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis

    PubMed Central

    Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian

    2017-01-01

    Background Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. Methods We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. Results We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10–92%) in four clinical trials, 45% (95%CI: 15–65%) in three cohort studies, and 59% (95%CI: 35–74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35–80%) in two clinical trials and 48% (95%CI: 25–63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Conclusions Our meta

  6. Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil

    PubMed Central

    de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

    2015-01-01

    Objective To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. Methods Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. Results The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. Conclusion The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil. PMID:26114297

  7. Elderly-onset neuromyelitis optica which developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination.

    PubMed

    Kitazawa, Yu; Warabi, Yoko; Bandoh, Mitsuaki; Takahashi, Toshiyuki; Matsubara, Shiro

    2012-01-01

    We report a case of elderly-onset neuromyelitis optica (NMO) positive for the anti-aquaporin-4 (AQP-4) antibody; symptoms developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination. We suggest that activation of CD4-positive T cells and secretion of interferon-gamma induced by adenocarcinoma and complement activation induced by vaccination are responsible for the onset and relapse of NMO, even if a patient is positive for the anti-AQP-4 antibody. This case supports the previous experimental finding that the anti-AQP-4 antibody does not cause NMO-like lesions when injected alone, but does so after the induction of T cell-mediated experimental autoimmune encephalomyelitis or when co-injected with human complement.

  8. Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine.

    PubMed

    Thisyakorn, Usa; Chokephaibulkit, Kulkanya; Kosalaraksa, Pope; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate

    2014-01-01

    The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23(®) [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar(®), Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7.

  9. Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine

    PubMed Central

    Thisyakorn, Usa; Chokephaibulkit, Kulkanya; Kosalaraksa, Pope; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate

    2014-01-01

    The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23® [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar®, Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7. PMID:25424793

  10. Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

    PubMed Central

    2017-01-01

    Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly. PMID:28168172

  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. Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

    PubMed Central

    Zielen, S.; Bühring, I.; Strnad, N.; Reichenbach, J.; Hofmann, D.

    2000-01-01

    There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 μg/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 μg/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients. PMID:10678957

  14. Effectiveness of 23-valent pneumococcal polysaccharide vaccination in preventing community-acquired pneumonia hospitalization and severe outcomes in the elderly in Spain.

    PubMed

    Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Torner, Núria; Force, Luis; Pérez, María José; Martín, Vicente; Rodríguez-Rojas, Lourdes; Astray, Jenaro; Egurrola, Mikel; Sanz, Francisco; Castilla, Jesús

    2017-01-01

    Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013-2014 and 2014-2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1-30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3-56.9) in all patients, 30.9% (95% CI -32.2-67.4) in immunocompetent patients and 26.9% (95% CI -38.6-64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP.

  15. Effectiveness of 23-valent pneumococcal polysaccharide vaccination in preventing community-acquired pneumonia hospitalization and severe outcomes in the elderly in Spain

    PubMed Central

    Soldevila, Núria; Toledo, Diana; Torner, Núria; Force, Luis; Pérez, María José; Martín, Vicente; Rodríguez-Rojas, Lourdes; Astray, Jenaro; Egurrola, Mikel; Sanz, Francisco; Castilla, Jesús

    2017-01-01

    Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013–2014 and 2014–2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1–30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3–56.9) in all patients, 30.9% (95% CI -32.2–67.4) in immunocompetent patients and 26.9% (95% CI -38.6–64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP. PMID:28187206

  16. 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 Central

    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, 9V, 10A, 11A, 15B, 18C, 19A, 22F and 33F. 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

  17. Anaphylaxis to the 23-valent pneumococcal vaccine: a second explored case by means of immediate-reading skin tests with pneumococcal vaccines.

    PubMed

    Ponvert, C; Scheinmann, P; de Blic, J

    2010-12-06

    Anaphylaxis to pneumococcal vaccines is rare. In the only one child with anaphylaxis to a first injection of the 23-valent pneumococcal vaccine that has been explored, skin tests and specific IgE determination diagnosed immediate-type hypersensitivity to pneumococcal antigens. We report the case of a child who tolerated three injections of the 7-valent pneumococcal vaccine, but experienced anaphylaxis to a fourth injection of the 23-valent vaccine. Immediate responses in skin tests diagnosed immediate-type hypersensitivity to the two vaccines. Immunizations with the 7-valent pneumococcal vaccine may induce IgE-dependent sensitization to pneumococcal antigens, responsible for anaphylaxis to subsequent injections of pneumococcal vaccines.

  18. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    ... the United States.Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. Anyone who has a severe allergy to any component of PPSV should not receive ...

  19. Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults.

    PubMed

    Durando, P; Faust, S N; Fletcher, M; Krizova, P; Torres, A; Welte, T

    2013-10-01

    Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain

  20. Increased Invasive Pneumococcal Disease, North East England, UK

    PubMed Central

    Houseman, Catherine; Hughes, Gareth J.; Chapman, Kaye E.; Wilson, Deborah

    2017-01-01

    Since April 2014, invasive pneumococcal disease incidence has increased substantially across North East England, United Kingdom, reversing the decline that followed the 2006 introduction of pneumococcal conjugate vaccines. Significant increases occurred in 23-valent polysaccharide vaccine serotypes and nonvaccine serotypes. Trends in other regions and long-term effects of multivalent vaccines require further investigation. PMID:27983490

  1. Relationship between public subsidies and vaccination rates with the 23-valent pneumococcal vaccine in elderly persons, including the influence of the free vaccination campaign after the Great East Japan Earthquake.

    PubMed

    Naito, Toshio; Matsuda, Naoto; Tanei, Mika; Watanabe, Yukiko; Watanabe, Akira

    2014-07-01

    Low vaccination rates with pneumococcal vaccine in elderly persons in Japan are thought to be related to low levels of public subsidy. To identify strategies to increase future pneumococcal vaccination rates, we examined the relationship between public subsidies and vaccination rates. We also investigated the influence of free vaccinations after the 2011 Great East Japan Earthquake on vaccination rates in the three Tohoku prefectures of Japan. We surveyed a total of 1742 municipalities in Japan about whether public subsidies were available and their monetary amount. Vaccination rates with the 23-valent pneumococcal vaccine were calculated as the "cumulative amount shipped to each municipality divided by the population aged ≥65 years." There were no subsidies in 773 municipalities (44.4%). In those municipalities with public subsidies, larger subsidies were significantly associated with elevated vaccination rates (p < 0.0001). Compared to a mean vaccination rate of 25.4% throughout Japan, the vaccination rate was 52.1% in municipalities where the full cost was subsidized. The three prefectures (Iwate, Miyagi, and Fukushima) most affected by the Great East Japan Earthquake ranked as the top three prefectures for vaccination rates in Japan, presumably as a result of the free vaccination campaign for disaster victims. Our findings show that public subsidies play an important role in increasing the vaccination rate. The free vaccinations given to disaster victims after the Great East Japan Earthquake helped to achieve extremely high vaccination rates in the three Tohoku prefectures. We suggest that such public subsidies should be promoted throughout Japan.

  2. A comparison of multiple regimens of pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers.

    PubMed

    Blum, M D; Dagan, R; Mendelman, P M; Pinsk, V; Giordani, M; Li, S; Bohidar, N; McNeely, T B

    2000-05-08

    Children who had been randomized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PCV) or 23-valent pneumococcal polysaccharide vaccine (PN23) at 12, 15, or 18 months of age were subsequently randomized to receive a booster injection of either PCV or PN23 12 months later. For those children who received a priming dose of PCV (N=75) compared to PN23 (N=48) at 12, 15, or 18 months of age, higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested (p<0.001). Within the group of children receiving a priming dose of PCV, those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B, yet more frequent erythema (p=0.030) and pain or soreness (p=0.024) at the injection site compared to those boosted with PCV. In conclusion, a single dose of PCV at 12-18 months of age primed for responses to booster doses of either PCV or PN23 12 months later. For those children who received a priming dose of PCV, boosting with PN23 resulted in more frequent injection site pain and erythema than boosting with PCV, yet higher antibody concentrations for most of the serotypes tested.

  3. 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

  4. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults.

    PubMed

    Peñaranda, Maria; Payeras, Antoni; Cambra, Ana; Mila, Joan; Riera, Melcior

    2010-05-15

    This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy.

  5. Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial

    PubMed Central

    Rodriguez-Barradas, Maria C.; Serpa, Jose A.; Munjal, Iona; Mendoza, Daniel; Rueda, Adriana M.; Mushtaq, Mahwish; Pirofski, Liise-anne

    2015-01-01

    Background. Pneumococcal vaccination is recommended for human immunodeficiency virus-infected (HIV+) persons; the best timing for immunization with respect to initiation of antiretroviral therapy (ART) is unknown. Methods. Double-blind, placebo-controlled trial in HIV+ with CD4+ T cells/µL (CD4) ≥ 200 randomized to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23) or placebo at enrollment, followed by placebo or PPV23, respectively, 9–12 months later (after ≥6 months of ART). Capsular polysaccharide-specific immunoglobin (Ig) G and IgM levels to serotypes 1, 3, 4, 6B, and 23F, and opsonophagocytic killing activity (OPA) to serotypes 6B and 23F were evaluated 1 month postvaccination. Results. One hundred seven subjects were enrolled, 72 (67.3%) were evaluable (36/group). Both groups had significant increases in pre- to 1-month postvaccination IgG levels, but negligible to IgM, and significant increases in OPA titers to serotype 6B but not to 23F. There were no significant differences between groups in serotype-specific IgM or IgG levels or OPA titers. For the combined groups, there was a significant correlation between serotype-specific IgG and OPA titers to 23F but not to 6B. There was no correlation between CD4, viral load and IgG responses. Conclusions. In HIV+ with CD4 ≥ 200, delaying PPV23 until ≥6 months of ART does not improve responses and may lead to missed opportunities for immunization. PMID:25538270

  6. Factors associated with pneumococcal polysaccharide vaccination of the elderly in Spain: A cross-sectional study.

    PubMed

    Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Torner, Núria; Force, Luis; Castilla, Jesús; Mayoral, José María; Tamames, Sonia; Martín, Vicente; Egurrola, Mikel; Sanz, Francisco; Astray, Jenaro; Project Pi12/02079 Working Group

    2016-07-02

    Vaccination of the elderly is an important factor in limiting the impact of pneumonia in the community. The aim of this study was to investigate the factors associated with pneumococcal polysaccharide vaccination in patients aged ≥ 65 years hospitalized for causes unrelated to pneumonia, acute respiratory disease, or influenza-like illness in Spain. We made a cross-sectional study during 2013-2014. A bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking into account sociodemographic variables and risk medical conditions. A multivariate analysis was performed using multilevel regression models. 921 patients were included; 403 (43.8%) had received the pneumococcal vaccine (394 received the polysaccharide vaccine). Visiting the general practitioner ≥ 3 times during the last year (OR = 1.79; 95% CI 1.25-2.57); having received the influenza vaccination in the 2013-14 season (OR = 2.57; 95% CI 1.72-3.84) or in any of the 3 previous seasons (OR = 11.70; 95% CI 7.42-18.45) were associated with receiving the pneumococcal polysaccharide vaccine. Pneumococcal vaccination coverage of hospitalized elderly people is low. The elderly need to be targeted about pneumococcal vaccination and activities that encourage healthcare workers to proactively propose vaccination might be useful. Educational campaigns aimed at the elderly could also help to increase vaccination coverages and reduce the burden of pneumococcal disease in the community.

  7. 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.

  8. Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

    PubMed Central

    Moore, R Andrew; Wiffen, Philip J; Lipsky, Benjamin A

    2000-01-01

    The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit. PMID:11038265

  9. Pneumococcal polysaccharide vaccine - what you need to know

    MedlinePlus

    ... the Unites States. Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. Anyone who has a severe allergy to any component of PPSV should not receive ...

  10. Pneumococcal Polysaccharide Vaccine: What You Need to Know

    MedlinePlus

    ... Unite d States. Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. • Anyone who has a severe allergy to any component of PPSV should not receive ...

  11. Conjugation of PEG-hexadecane markedly increases the immunogenicity of pneumococcal polysaccharide conjugate vaccine.

    PubMed

    Chang, Xin; Yu, Weili; Ji, Shaoyang; Shen, Lijuan; Tan, Aijuan; Hu, Tao

    2017-02-24

    Streptococcus pneumoniae is a serious Gram-positive pathogen that can lead to an invasive pneumococcal disease with high mortality rate. Pneumococcal capsular polysaccharide (PS) is a key virulence determinant and its immunogenicity can be increased by conjugation with a carrier protein. However, the PS-specific cellular and humoral immunity of pneumococcal conjugate vaccine needs further improvement. Hexadecane (HD) is an element of lipid that decorates the surface of nearly all microbial classes. Polyethylene glycol (PEG)-HD conjugate (PEG-HD) is soluble and can act as an adjuvant. In the present study, a novel pneumococcal polysaccharide conjugate vaccine was prepared by conjugation of tetanus toxoid (TT) portion of PS-TT conjugate (PS-TT) with PEG-HD. As compared with PS-TT, conjugation with PEG-HD led to an 8.0-fold increase in the PS-specific IgG titers. Conjugation with PEG-HD also gave rise to 34.9-, 3.6- and 7.7-fold increase in the IFN-γ, TNF-α and IL-5 levels, respectively. Thus, the conjugated PEG-HD has a stimulatory adjuvant activity to potentiate a robust humoral and cellular immunity. Our proposed conjugate was expected to act as an effective pneumococcal conjugate vaccine for prevention of S. pneumoniae infections.

  12. Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides

    PubMed Central

    Wiertsema, Selma P.; Corscadden, Karli J.; Mateus, Tulia; Mullaney, Gemma L.; Zhang, Guicheng; Richmond, Peter C.; Thornton, Ruth B.

    2016-01-01

    ABSTRACT The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group (P < 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. PMID:28031178

  13. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  14. Pneumococcal Vaccine to Counter Emerging Infectious Disease Threat in the Military

    DTIC Science & Technology

    2001-12-01

    clinical trial of the currently In 1945, the first successful trial of a polyvalent polysaccha- available 23- valent pneumococcal vaccine . The purpose...December 2001 1088 Pneumococcal Vaccine bers are affected by pneumococcal disease; however, because of Board 35 recommended that the 23- valent ...pnoeumococcal vaccines years studied to date. The efficacy of the conjugate 7- valent Athe bi-oeti peuis cc vacspcilcone, witvaccine in children appears to also

  15. 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.

  16. 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

  17. Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage.

    PubMed

    Licciardi, Paul V; Russell, Fiona M; Balloch, Anne; Burton, Robert L; Nahm, Moon H; Gilbert, Gwendolyn; Tang, Mimi L K; Mulholland, Edward K

    2014-04-25

    The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunization with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunization. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses. The most frequently carried serotypes were 6B (N=11), 19F (N=14) and 23F (N=23). Significantly lower serotype-specific IgG for 19F, 23F but not 6B post-PPS were detected in infants with homologous serotype carriage prior to PPS compared with non-carriers (N=230). However, OPA levels for 6B and 23F were lower in infants that carried these serotypes. Pneumococcal carriage with 19F or 23F at any time prior to PPS immunization in infants at 12 months of age who were previously primed with PCV resulted in serotype-specific hyporesponsiveness that persisted until 17 months of age. These results may have implications for the timing of infant vaccine schedules, particularly in high disease burden settings.

  18. Immunosuppression in murine malaria. I. Response to type III pneumococcal polysaccharide.

    PubMed Central

    McBride, J S; Micklem, H S; Ure, J M

    1977-01-01

    Acute Plasmodium yoelii yoelii and chronic Plasmodium berghei malaria infections of CBA mice were accompanied by a reduced capacity to give an antibody response to type III pneumococcal polysaccharide (SIII). The depression of response initiated by acute malaria persisted for several weeks after recovery from clinical infection. During chronic infection, and at the peak of acute parasitaemia, virtually no response to SIII was detected. A substance which crossreacted serologically with SIII was found in blood cells of infected mice. The results suggest that antigen-specific, as well as non-specific, factors may contribute to the depression of the response to this antigen. PMID:67996

  19. Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

    PubMed

    Zon, G; Szu, S C; Egan, W; Robbins, J D; Robbins, J B

    1982-07-01

    The hydrolyses of the immunologically cross-reactive and constitutionally isomeric group 6 pneumococcal polysaccharides, types 6A and 6B, were investigated by 31P nuclear magnetic resonance spectroscopy, gel filtration through Sepharose 4B, reducing-sugar analysis, and rocket immunoelectrophoresis. Phosphorus nuclear magnetic resonance spectroscopy showed that cleavage of the repeating-unit phosphodiester linkages at pH 10, 60 degrees C was considerably faster (greater than 10(3) ) for the type 6A than the type 6B polysaccharide. Under these reaction conditions, 31P nuclear magnetic resonance kinetic measurements showed that the Na+ form of the type 6A polysaccharide underwent phosphodiester-linkage hydrolysis two times slower than the corresponding Ca+2 form; a stoichiometrically excess amount of Ca+2 caused a 30-fold enhancement of the latter hydrolysis rate. The spectroscopic characterization of phosphorus-containing end groups resulting from hydrolysis of the type 6A polymer provided additional mechanistic information. Heating the type 6A and 6B polysaccharides at 56 degrees C for various times led to gel filtration coefficients of distribution (Kd values) which indicated that the type 6A material underwent size reductions considerably faster than did the type 6B antigen; these increased Kd values qualitatively correlated with the loss of immunochemical reactivity measured by rocket immunoelectrophoresis. The application of a statistical theory to the depolymerization of the type 6A and 6B polysaccharides was consistent with random bond cleavage, as evidenced by the calculated versus measured gel filtration patterns. Although the molecular changes causing the size reductions were not fully elaborated, it was established that the acetal linkages of the type 6A and 6B polysaccharides were comparatively resistant to hydrolysis and that depolymerization by hydrolysis of the phosphodiester linkage was a major factor only in the type 6A structure. It was concluded

  20. Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

    PubMed Central

    Zon, G; Szu, S C; Egan, W; Robbins, J D; Robbins, J B

    1982-01-01

    The hydrolyses of the immunologically cross-reactive and constitutionally isomeric group 6 pneumococcal polysaccharides, types 6A and 6B, were investigated by 31P nuclear magnetic resonance spectroscopy, gel filtration through Sepharose 4B, reducing-sugar analysis, and rocket immunoelectrophoresis. Phosphorus nuclear magnetic resonance spectroscopy showed that cleavage of the repeating-unit phosphodiester linkages at pH 10, 60 degrees C was considerably faster (greater than 10(3) ) for the type 6A than the type 6B polysaccharide. Under these reaction conditions, 31P nuclear magnetic resonance kinetic measurements showed that the Na+ form of the type 6A polysaccharide underwent phosphodiester-linkage hydrolysis two times slower than the corresponding Ca+2 form; a stoichiometrically excess amount of Ca+2 caused a 30-fold enhancement of the latter hydrolysis rate. The spectroscopic characterization of phosphorus-containing end groups resulting from hydrolysis of the type 6A polymer provided additional mechanistic information. Heating the type 6A and 6B polysaccharides at 56 degrees C for various times led to gel filtration coefficients of distribution (Kd values) which indicated that the type 6A material underwent size reductions considerably faster than did the type 6B antigen; these increased Kd values qualitatively correlated with the loss of immunochemical reactivity measured by rocket immunoelectrophoresis. The application of a statistical theory to the depolymerization of the type 6A and 6B polysaccharides was consistent with random bond cleavage, as evidenced by the calculated versus measured gel filtration patterns. Although the molecular changes causing the size reductions were not fully elaborated, it was established that the acetal linkages of the type 6A and 6B polysaccharides were comparatively resistant to hydrolysis and that depolymerization by hydrolysis of the phosphodiester linkage was a major factor only in the type 6A structure. It was concluded

  1. A peptide mimotope of type 8 pneumococcal capsular polysaccharide induces a protective immune response in mice.

    PubMed

    Buchwald, Ulrike K; Lees, Andrew; Steinitz, Michael; Pirofski, Liise-Anne

    2005-01-01

    Increasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci. However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease. The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci. We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8 Streptococcus pneumoniae capsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning. Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS. PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS. The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls. The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization. The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci.

  2. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis.

    PubMed

    Overturf, G D

    2000-08-01

    Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15

  3. Preparation of pneumococcal capsular polysaccharide-protein conjugate vaccines utilizing new fragmentation and conjugation technologies.

    PubMed

    Pawlowski, A; Källenius, G; Svenson, S B

    2000-03-17

    There is a global urgent need for a new efficient and inexpensive vaccine to combat pneumococcal disease, which should also be affordable in developing countries. In view of this need a simple low-cost technique to prepare such a vaccine was developed. The preparation of serotype 14 and 23F pneumococcal capsular polysaccharide (PnPS)-protein conjugates to be included in a forthcoming multivalent PnPS conjugate vaccine is described. Commercial lots of PnPSs produced according to Good Manufacturing Practice from Streptococcus pneumoniae serotype 14 (PS14) and 23F (PS23F) were partially depolymerized by sonication or irradiation in an electron beam accelerator. The PnPS fragments were conjugated to tetanus toxoid (TT) using a recently developed conjugation chemistry. The application of these new simple, efficient and inexpensive fragmentation and conjugation technologies allowed the synthesis of several PnPS-protein conjugates containing PnPS fragments of preselected sizes and differing in the degree of substitution. The PS14TT and PS23FTT conjugate vaccine candidates were characterized chemically and their immunogenicity was evaluated in rabbits and mice. All PnPS conjugate vaccines, unlike the corresponding plain polysaccharides, produced high IgG titres in both animal species. The PS14TT conjugates tended to be more immunogenic than the PS23FTT conjugates. The immune response to the PS14TT conjugates, but not to the PS23FTT conjugates, was related to the size of the conjugated polysaccharide hapten. Both types of conjugates elicited strong booster effects upon secondary immunizations, resulting in high IgG1, IgG2a and IgG2b titres.

  4. Lack of Effectiveness of the 23-Valent Polysaccharide Pneumococcal Vaccine in Reducing All-Cause Pneumonias Among Healthy Young Military Recruits: A Randomized, Double-Blind, Placebo-Controlled Trial

    DTIC Science & Technology

    2015-01-08

    his pathogen [14]. Civilian cost-benefit and cost-effectiveness studies performed rior to this study suggested that vaccination against pneumococ- al...pneumonia would create net health improvements in every ge group and that vaccination programs for those considered at igh risk were economically...justified [22,23]. Beutels and Postma emonstrated that vaccination of those between 65 and 75 years f age, immunocompromised individuals, and military

  5. Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage

    PubMed Central

    Reiné, J; Zangari, T; Owugha, JT; Pennington, SH; Gritzfeld, JF; Wright, AD; Collins, AM; van Selm, S; de Jonge, MI; Gordon, SB; Weiser, JN; Ferreira, DM

    2016-01-01

    The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal IgG to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow-cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model samples were collected from PCV and control vaccinated adults. In PCV-vaccinated subjects IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared to pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity. PMID:27579859

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

    PubMed

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

    2015-11-01

    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 (r(c)) 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.

  7. [Pneumococcal disease in adults: Risk levels and vaccine recommendations].

    PubMed

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga

    2017-02-01

    There are currently two anti-pneumococcal vaccines available for use in adults: the classical 23-valent polysaccharide pneumococcal vaccine (PPV23) and the new 13-valent pneumococcal conjugate vaccine (PCV13). The main advantage of the PCV13 is the potentially better immunogenicity, with its major disadvantages being the higher cost and the lower serotype-coverage than the PPV23. The currently available scientific evidence supports the following basic recommendations: (i)among adults with greatest risk (basically asplenia and immunocompromised), a dual vaccination (PCV13+PPV23) is recommended; (ii)among adults with increased risk (basically persons >65years-old and patients 15-64years with chronic pulmonary or heart disease, diabetes and/or alcoholism), a single vaccination with PPV23 is recommended (single dose in primo-vaccinated >65years; re-vaccination at 5-10years in those primo-vaccinated <65years-old); and (iii) in the rest of adults (risk normal/low) vaccination is not recommended.

  8. Education does pay off: pneumococcal vaccine screening and administration in hospitalized adult patients with pneumonia.

    PubMed

    Kruspe, Rachel; Lillis, Rebecca; Daberkow, Dayton W; Blais, Christopher M; Wilbright, Wayne; Gupta, Shaminder; Gould, Cynthia A; Sun, Tony; Martinez, Jorge A; deBoisblanc, Ben; Ladabaum, Uri; Sanders, Charles V; Lopez, Fred A

    2003-01-01

    Streptococcus pneumoniae-associated infections are an important cause of hospitalization and mortality in high-risk and elderly patients. Even in the setting of appropriate therapy, the case fatality rate of invasive pneumococcal disease in the elderly may approach 40%. Since approximately 40,000 people die annually from pneumococcal-associated disease, it represents a substantial target for vaccine-preventable, bacterial fatalities. The 23-valent pneumococcal polysaccharide vaccine has proven consistently effective in preventing invasive pneumococcal disease. Despite its endorsement by numerous specialty societies, the pneumococcal vaccine is underutilized in the inpatient setting. In a recent report of quality indicators for Medicare beneficiaries, the percentage of Medicare beneficiaries in Louisiana admitted with pneumonia who were screened or received the pneumococcal vaccination prior to discharge was only 4%, the lowest percentage in the United States. The Louisiana State University-New Orleans Internal Medicine Department and its house staff embarked upon a retrospective study to determine its baseline pneumococcal vaccination or screening rates for all patients with pneumonia on its inpatient services at the The Medical Center of Louisiana in New Orleans from July 2000 through June 2001. From July 2001 through June 2002 an intensive educational intervention concentrating on the indications and benefits of pneumococcal vaccination was directed toward the Louisiana State University Internal Medicine house staff assigned to the inpatient service. Retrospective analysis for pneumococcal vaccine screening and administration of charts of all patients with pneumonia on the LSU Medicine service from July 2001 through June 2002 was performed in order to determine the effects of the intervention. Data from the pre-educational intervention period revealed a baseline pneumococcal vaccine screening or administration rate of 11% for all patients with pneumonia on the

  9. Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.

    PubMed

    Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine

    2015-10-13

    Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23v

  10. The efficacy of pneumococcal capsular polysaccharide-specific antibodies to serotype 3 Streptococcus pneumoniae requires macrophages.

    PubMed

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

    2010-11-03

    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.

  11. 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

    2016-09-01

    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.

  12. Polysaccharide Responsiveness Is Not Biased by Prior Pneumococcal-Conjugate Vaccination

    PubMed Central

    Bernth-Jensen, Jens Magnus; Søgaard, Ole Schmeltz

    2013-01-01

    Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes. To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness. HIV-infected adults (n = 47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies. Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P = 0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P = 0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted responseś number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R2 = 0.59, P<0.0001). We found that polysaccharide responsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in

  13. Invasive pneumococcal disease in Australia, 2006.

    PubMed

    Roche, Paul W; Krause, Vicki; Cook, Heather; Barralet, Jenny; Coleman, David; Sweeny, Amy; Fielding, James; Giele, Carolien; Gilmour, Robin; Holland, Ros; Kampen, Riemke; Brown, Mitchell; Gilbert, Lyn; Hogg, Geoff; Murphy, Denise

    2008-03-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in all Australian states and territories in 2006 with comprehensive comparative data available since 2002. There were 1,445 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2006; a notification rate of 7 cases per 100,000 population. The rates varied between states and territories and by geographical region with the highest rates in the Northern Territory, the jurisdiction with the largest proportion of Indigenous people. Invasive pneumococcal disease was reported most frequently in those aged 85 years or over (30.8 cases per 100,000 population) and in children aged one year (26.5 cases per 100,000 population). There were 130 deaths attributed to IPD resulting in an overall case fatality rate of 9%. The overall rate of IPD in Indigenous Australians was 4.3 times the rate in non-indigenous Australians. The rate of IPD in the under two years population continued to fall in 2006, but the rate in Indigenous children (73 cases per 100,000 population) was significantly greater than in non-Indigenous children (21 cases per 100,000 population). The rates of disease caused by serotypes in the 7-valent pneumococcal conjugate vaccine (7vPCV) decreased between 2002 and 2006 by 78% in children aged under two years as a result of the introduction of a universal childhood 7vPCV immunisation program. Significant decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65 years or over age groups. Rates of disease caused by non-7vPCV in the same periods were little changed. Serotypes were identified in 94% of all notified cases, with 43% of disease caused by serotypes in the 7vPCV and 85% caused by serotypes in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). The number of invasive pneumococcal isolates with reduced penicillin susceptibility remains low and reduced susceptibility to third generation cephalosporins is rare.

  14. Humoral immune response of a pneumococcal conjugate vaccine: capsular polysaccharide serotype 14-Lysine modified PspA.

    PubMed

    Santamaria, Raquel; Goulart, Cibelly; Perciani, Catia T; Barazzone, Giovana C; Carvalho, Rimenys; Gonçalves, Viviane M; Leite, Luciana C C; Tanizaki, Martha M

    2011-11-03

    Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens.

  15. Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine.

    PubMed

    Lai, Zengzu; Schreiber, John R

    2011-05-01

    Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.

  16. Invasive pneumococcal disease in Australia, 2005.

    PubMed

    Roche, Paul; Krause, Vicki; Cook, Heather; Bartlett, Mark; Coleman, David; Davis, Craig; Fielding, James; Giele, Carolien; Gilmour, Robin; Holland, Ros; Kampen, Riemke

    2007-03-01

    Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in all Australian states and territories in 2005 with comparative data available since 2001. There were 1,680 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2005; a notification rate of 8.3 cases per 100,000 population. The rates varied between states and territories and by geographical region with the highest rates in the Northern Territory, the jurisdiction with the largest proportion of Indigenous people. Invasive pneumococcal disease was reported most frequently in those aged 85 years or over (41 cases per 100,000 population) and in 1-year-old children (36.5 cases per 100,000 population). Enhanced data provided additional information on 1,015 (60%) of all notified cases. The overall rate of IPD in Indigenous Australians was 8.6 times the rate in non-Indigenous Australians. There were 126 deaths attributed to IPD resulting in an overall case fatality rate of 7.5%. While the rate of IPD in the Indigenous under 2-year-old population decreased from 219 cases per 100,000 population since targeted introduction of the 7-valent conjugate pneumococcal vaccine (7vPCV) in 2001, the rate in 2005 (94 cases per 100,000 population) was significantly greater than in non-Indigenous children (20.4 cases per 100,000 population). Rates of disease in all children aged less than 2 years, caused by serotypes in the 7vPCV decreased by 75% between 2004 and 2005 as a result of the introduction of a universal childhood 7vPCV immunisation program. Significant decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65 years or over age groups. There is no evidence of replacement disease with non-vaccine serotypes. Serotypes were identified in 90% of all notified cases, with 61% of disease caused by serotypes in the 7vPCV and 88% caused by serotypes in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Reduced penicillin susceptibility

  17. Population-Based Surveillance for Invasive Pneumococcal Disease in Homeless Adults in Toronto

    PubMed Central

    Plevneshi, Agron; Svoboda, Tomislav; Armstrong, Irene; Tyrrell, Gregory J.; Miranda, Anna; Green, Karen; Low, Donald; McGeer, Allison

    2009-01-01

    Background Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs. Methods We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006. Results We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001), and more likely than other adults to be smokers (95% vs. 31%, P<.001), to abuse alcohol (62% vs 15%, P<.001), and to use intravenous drugs (42% vs 4%, P<.001). Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006), but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73). The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001). In homeless adults, 28 (32%) of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48%) of serotypes included in the 13-valent conjugate vaccine, and 72 (83%) of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population. Conclusions Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes or

  18. The epidemiology of invasive pneumococcal disease in older adults from 2007 to 2014 in Ontario, Canada: a population-based study

    PubMed Central

    Desai, Shalini; Policarpio, Michelle E.; Wong, Kenney; Gubbay, Jonathan; Fediurek, Jill; Deeks, Shelley

    2016-01-01

    Background: In Ontario, pneumococcal conjugate vaccines (PCVs) have been sequentially introduced into the publicly funded childhood vaccination program since 2005. A 23-valent polysaccharide pneumococcal vaccine (PPV23) has been routinely recommended for adults aged 65 years and older since 1996. To determine the effect of herd immunity, we examined the epidemiology of invasive pneumococcal disease in adults aged 65 years and older. Methods: Invasive pneumococcal disease is a provincially reportable disease. We were therefore able to conduct a descriptive epidemiologic analysis that included assessing time trends for patients aged 65 years and older using surveillance data from 2007 to 2014. Using serotype information within the surveillance data, cases were grouped into categories according to vaccine type and periods and then compared using Poisson regression. Results: A total of 3825 cases of invasive pneumococcal disease were reported among adults aged 65 years and older, for an overall annualized incidence of 25.4 cases per 100 000 population. There was a decrease in incidence due to serotypes included in 7-valent PCV (3.0 to 0.7 cases per 100 000 population) (p < 0.001). For 13-valent PCV serotypes, there was a decrease in incidence between 2011 and 2014 (9.8 to 5.3 cases per 100 000 population (p < 0.001)). Serotypes unique to PPV23 and those not included in a vaccine increased from 2.3 to 5.8 and from 2.4 to 7.2 cases per 100 000 population, respectively (p < 0.001). Interpretation: In older adults, among serotypes contained in PCVs, we have shown a decrease in incidence of invasive pneumococcal disease. This is likely due to herd immunity from the childhood program. A burden of illness due to unique PPV23 serotypes and those that are not covered by a vaccine exists and has increased over time. PMID:27730119

  19. Antibody response to a seven-valent pneumococcal conjugated vaccine in patients with ataxia-telangiectasia.

    PubMed

    Sanal, Ozden; Ersoy, Fugen; Tezcan, Ilhan; Metin, Ayse; Turul, Tuba; Gariboglu, Semra; Yel, Leman

    2004-07-01

    Immunodeficiency is a characteristic feature of ataxia-telangiectasia (A-T). Humoral immunodeficiency generally consists of hypogammaglobulinemia and impaired antibody response to bacterial and viral antigens. We previously observed defective antibody response to 23-valent pneumococcal polysaccharide vaccine (PPV) in 96% of 29 patients with A-T. In this study, we investigated the antibody response to a seven-valent pneumococcal conjugate vaccine, PCV7, in 14 patients with A-T. IgG antibody levels to four pneumococcal serotypes, 6B, 14, 19F, 23F, which were included in PCV7, were measured by ELISA in pre- and postimmunization serum samples. Antibody titers against each individual Streptococcus pneumoniae serotype was considered to be positive when serotype specific pneumococcal antibody titer was higher than 10% (>10 U/mL) of the reference plasma pool level. However, when the fold increase (FI) in postimmunization antibody titer was less than two, the subject was determined to be unresponsive to the given serotype. The values were compared with the results obtained in age- and ethnic-matched children after one dose of PPV. Only two patients produced antibodies to one serotype each; one to serotype 19 with a fold increase of <2, and the other to serotype 23F with a fold increase of 5.7 based on the above criteria, although the differences between pre- and postvaccine antibody titers for serotypes 14, 19, and 23 appeared to be statistically significant. In conclusion, A-T patients failed to respond to one dose of PCV7 vaccine. Two or more doses of conjugated vaccine may be required to recruit the help of T lymphocytes in A-T patients.

  20. Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies.

    PubMed

    Choi, Eun Hwa; Zhang, Fan; Lu, Ying-Jie; Malley, Richard

    2015-12-16

    The efficacy of the serotype 3 (ST3) pneumococcal conjugate vaccine (PCV) remains unclear. While the synthesis of capsular polysaccharide (CPS) of most serotypes is wzy dependent, the strains of two serotypes, 3 and 37, synthesize CPS by the synthase-dependent pathway, resulting in a polysaccharide that is not covalently linked to peptidoglycan and can be released during growth. We hypothesized that the release of CPS during growth reduces anti-type 3 CPS antibody-mediated protection and may explain the lower efficacy of the type 3 component of PCV than that of other PCVs. The in vitro-released CPS concentrations per 10(7) CFU of ST3 and ST37 strains were significantly higher than those for the ST1, ST4, ST6B, and ST14 strains. Following intraperitoneal (i.p.) injection in mice, blood concentrations of CPS were significantly higher for the ST3 than for the ST4/5 strains. The opsonophagocytic killing assay (OPKA) titer of anti-type 3 CPS antibody was significantly reduced by type 3 CPS, culture supernatant, or serum from Streptococcus pneumoniae ST3 strain WU2-infected mice. Mice were injected with capsule-specific antibodies and challenged i.p. with or without the addition of sterile culture supernatant containing type-specific CPS. The addition of 0.2 μl of culture supernatant from WU2 inhibited passive protection, whereas 100-fold-more culture supernatant from S. pneumoniae ST4 strain TIGR4 was required for the inhibition of protection. We conclude that released type 3 CPS interferes with antibody-mediated killing and protection by anti-CPS antibodies. The relative failure of ST3 PCV may be due to CPS release, suggesting that alternative immunization approaches for ST3 may be necessary.

  1. Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies

    PubMed Central

    Choi, Eun Hwa; Zhang, Fan; Lu, Ying-Jie

    2015-01-01

    The efficacy of the serotype 3 (ST3) pneumococcal conjugate vaccine (PCV) remains unclear. While the synthesis of capsular polysaccharide (CPS) of most serotypes is wzy dependent, the strains of two serotypes, 3 and 37, synthesize CPS by the synthase-dependent pathway, resulting in a polysaccharide that is not covalently linked to peptidoglycan and can be released during growth. We hypothesized that the release of CPS during growth reduces anti-type 3 CPS antibody-mediated protection and may explain the lower efficacy of the type 3 component of PCV than that of other PCVs. The in vitro-released CPS concentrations per 107 CFU of ST3 and ST37 strains were significantly higher than those for the ST1, ST4, ST6B, and ST14 strains. Following intraperitoneal (i.p.) injection in mice, blood concentrations of CPS were significantly higher for the ST3 than for the ST4/5 strains. The opsonophagocytic killing assay (OPKA) titer of anti-type 3 CPS antibody was significantly reduced by type 3 CPS, culture supernatant, or serum from Streptococcus pneumoniae ST3 strain WU2-infected mice. Mice were injected with capsule-specific antibodies and challenged i.p. with or without the addition of sterile culture supernatant containing type-specific CPS. The addition of 0.2 μl of culture supernatant from WU2 inhibited passive protection, whereas 100-fold-more culture supernatant from S. pneumoniae ST4 strain TIGR4 was required for the inhibition of protection. We conclude that released type 3 CPS interferes with antibody-mediated killing and protection by anti-CPS antibodies. The relative failure of ST3 PCV may be due to CPS release, suggesting that alternative immunization approaches for ST3 may be necessary. PMID:26677201

  2. 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

  3. Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain.

    PubMed

    Caro-Aguilar, Ivette; Indrawati, Lani; Kaufhold, Robin M; Gaunt, Christine; Zhang, Yuhua; Nawrocki, Denise K; Giovarelli, Cecilia; Winters, Michael A; Smith, William J; Heinrichs, Jon; Skinner, Julie M

    2017-02-07

    Pneumococcal disease continues to be a medical need even with very effective vaccines on the market. Globally, there are extensive research efforts to improve serotype coverage with novel vaccines; therefore, conducting preclinical studies in different animal models becomes essential. The work presented herein focuses on evaluating a 15-valent pneumococcal conjugate vaccine (PCV15) in mice. Initially we evaluated several doses of PCV15 in Balb/c mice. The optimal vaccine dose was determined to be 0.4μg per pneumococcal polysaccharide (PS) (0.8μg of 6B) for subsequent studies. This PS dose was chosen for PCV evaluation in mice based on antibody levels determined by multiplexed electrochemiluminescent (ECL) assays, T-cell responses following in vitro stimulation with CRM197 peptides and protection from pneumococcal challenge. We then selected four mouse strains for evaluation: Balb/c, C3H/HeN, CD1 and Swiss Webster (SW), immunized with PCV15 by either intraperitoneal (IP) or intramuscular (IM) routes. We assessed IgG responses by ECL assays and functional antibody activity by multiplexed opsonophagocytic assays (MOPA). Every mouse strain evaluated responded to all 15 serotypes contained in the vaccine. Mice tended to have lower responses to serotypes 6B, 23F and 33F. The IP route of immunization resulted in higher antibody titers for most serotypes in Balb/c, C3H and SW. CD1 mice tended to respond similarly for most serotypes, regardless of route of immunization. Similar trends were observed with the four mouse strains when evaluating functional antibody activity. Given the differences in antibody responses based on mouse strain and route of immunization, it is critical to evaluate pneumococcal vaccines in multiple animal models to determine the optimal formulation before moving to clinical trials.

  4. Development and application of HPLC-RI and HPLC-MS/MS based methods for quantification of residual deoxycholate levels in pneumococcal polysaccharides.

    PubMed

    Gairola, Sunil; Gautam, Manish; Patil, Dada; Manoj Kumar, Krishna; Shinde, Pravin; Jana, S K; Dhere, Rajeev; Jadhav, Suresh

    2016-11-01

    The analysis of residual sodium deoxycholate (DOC); a detergent of biological origin used in manufacturing of polysaccharide vaccines is challenging due to complex sample matrices and the lack of suitable methods. Here we report, rapid and sensitive high-performance liquid chromatography-refractive index (HPLC-RI) and tandem mass spectrometry (HPLC-MS/MS) methods for estimation of residual DOC in pneumococcal polysaccharides. For HPLC-RI method, separation was achieved using Luna C18 column and mobile phase compositions of acetonitrile: methanol: 20 mM sodium acetate (60:05:35% v/v). For HPLC-MS/MS method, separation was achieved using a Hypersil BDS C18 column with gradient elution of methanol and water (0.1% formic acid). MS/MS method showed linearity (r(2) = 0.997) over the range of 10-320 ng/mL with limits of detection (LOD) and lower limit of quantitation (LOQ) of 3 and 10 ng/mL respectively. Precision (% RSD) and accuracy (% recovery) for both methods were in the range of 0.74-8.29% and 82.33-117.86% respectively. Sample matrices interferences were addressed following novel sample clean-up method based on liquid-liquid extraction. Both methods enabled traceable quantitation of DOC in intermediate and purified pneumococcal polysaccharides of serotypes: 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F.

  5. Application of a target enrichment-based next-generation sequencing protocol for identification and sequence-based prediction of pneumococcal serotypes

    PubMed Central

    2014-01-01

    Background The use of whole-genome sequencing in microbiology at a diagnostic level, although feasible, is still limited by the expenses associated and by the complex bioinformatics pipelines in data analyses. We describe the use of target enrichment-based next-generation sequencing for pneumococcal identification and serotyping as applied to the polysaccharide 23 valent vaccine serotypes as an affordable alternative to whole genome sequencing. Results Correct identification of Streptococcus pneumoniae and prediction of common vaccine serotypes: 12 to serotype level and the rest to serogroup levels were achieved for all serotypes with >500 reads mapped against serotypes sequences. A proportion-based criterion also enabled the identification of two serotypes present in the same sample, thus indicating the possibility of using this method in detecting co-colonizing serotypes. The results obtained were comparable to or an improvement on the currently existing molecular serotyping methods for S. pneumoniae in relation to the polysaccharide vaccine serotypes. Conclusion We propose that this method has the potential to become an affordable and adaptable alternative to whole-genome sequencing for pneumococcal identification and serotyping. PMID:24612771

  6. Safety and immunogenicity of CRM197-conjugated pneumococcal-meningococcal C combination vaccine (9vPnC-MnCC) whether given in two or three primary doses.

    PubMed

    Sigurdardottir, Sigurveig Th; Davidsdottir, Katrin; Arason, Vilhjalmur A; Jonsdottir, Olof; Laudat, France; Gruber, William C; Jonsdottir, Ingileif

    2008-08-05

    This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal-meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC-MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC-MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC-MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F (p<0.001), that also showed lower rate of responders>0.35 (6B, 23F) and >0.5 microg/mL (6B). Antibody GMCs remained lower following 9vPnC-MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC-IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC-MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.

  7. [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.

  8. SYNTHESIS OF TYPE III PNEUMOCOCCAL POLYSACCHARIDE BY SUSPENSIONS OF RESTING CELLS

    PubMed Central

    Bernheimer, Alan W.

    1953-01-01

    The capsular polysaccharide (SIII) of type III pneumococci was removed enzymatically, and the cells thus deprived of preformed SIII were washed and examined for capacity to synthesize SIII anew. The washed, decapsulated cocci lost their capacity to be agglutinated in type-specific antiserum but again became agglutinable and formed readily measurable amounts of SIII, after suspension in a solution containing only glucose and salts. Maximal SIII synthesis required the presence of glucose, magnesium, potassium and phosphate ions, and oxygen. Other fermentable sugars could be substituted for glucose but then the yield of SIII was reduced. Synthesis of SIII occurred anaerobically but was increased four- to fivefold by oxygenation of the suspension. The effects of pH and of enzyme poisons on the capacity of the cocci to form SIII are described. PMID:13052821

  9. Synthetic peptides representing T-cell epitopes act as carriers in pneumococcal polysaccharide conjugate vaccines.

    PubMed Central

    de Velasco, E A; Merkus, D; Anderton, S; Verheul, A F; Lizzio, E F; Van der Zee, R; Van Eden, W; Hoffman, T; Verhoef, J; Snippe, H

    1995-01-01

    Improvement of antibody responses to polysaccharides through their linkage to proteins is thought to be mediated by protein-specific T helper (Th) cells. To investigate whether the carrier protein of a conjugate could be substituted by a Th epitope, Streptococcus pneumoniae type 17F polysaccharide (PS) was bromoacetylated and coupled to different peptides via their carboxy-terminal cysteines. Two peptides, one from the mycobacterial 65-kDa heat shock protein (hsp65) and the other from influenza virus hemagglutinin, are well-known Th epitopes. Two other peptides were selected from the pneumolysin sequence by Th epitope prediction methods; one of them was synthesized with cysteine either at the carboxy or the amino terminus. Three conjugates consistently elicited in mice anti-PS immunoglobulin M (IgM) and IgG responses that were not observed upon immunization with derivatized PS without peptide. The same conjugates induced no anti-PS antibody responses in athymic (nu/nu) mice, whereas clear responses were elicited in euthymic (nu/+) controls, demonstrating the thymus-dependent character of these conjugates. Only the three conjugates inducing anti-PS responses were capable of eliciting antipeptide antibodies. One of the immunogenic conjugates was studied in more detail. It induced significant protection and an anti-PS IgG response comprising all subclasses. On the basis of these results and proliferation studies with peptide and conjugate-primed cells, it is concluded that linkage of Th epitopes to PS in the right orientation enhances its immunogenicity in a thymus-dependent manner. Future possibilities for using peptides as carriers for inducing antibody responses to poorly immunogenic saccharide antigens are discussed. PMID:7532630

  10. Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up

    PubMed Central

    2012-01-01

    Background Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) against acute myocardial infarction and ischaemic stroke in older adults. Methods Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals). Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors). Results Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years) were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046). We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347). Conclusions Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events. PMID:22436146

  11. [Pneumococcal disease and its prevention. The heptavalent pneumococcal conjugate vaccine].

    PubMed

    de Arístegui Fernández, J; Corretger Rauet, J M; García Martín, F; Hernández-Sampelayo, T; Moraga Llop, F A; Rodrigo Gonzalo De Liria, C; Ruiz Contreras, J

    2002-01-01

    Pneumococcal disease is a major cause of morbidity, hospitalization and mortality. Two age groups show a greater incidence and severity of the disease: children under the age of 5 years (mainly during the first 2 years of life) and adults aged more than 65 years. The heptavalent pneumococcal conjugate vaccine, which was commercialized in Spain in June 2001, is efficacious in children aged less than 2 years and, unlike the non-conjugate 23-valent vaccine, it induces immunological memory. In Spain the heptavalent vaccine covers 80 % of serotypes causing pneumococcal invasive disease and acute otitis media in children aged 2-59 months. The heptavalent vaccine has been shown to be immunogenic, efficacious and safe. It has proven efficacy in the prevention of invasive disease caused by the seven vaccine serotypes. In addition, it significantly decreases pneumonia and also prevent acute otitis media. The vaccine is preferably indicated in children aged less than 2 years; children aged 2-5 years may also benefit from the vaccine but those in risk groups should be prioritized. Greater knowledge of the epidemiology of pneumococcal disease and the efficiency of this vaccine in Spain will determine whether it should be included in the immunization schedule.

  12. A trial of 7-valent Pneumococcal Conjugate Vaccine in HIV-infected Adults

    PubMed Central

    French, Neil; Gordon, Stephen B; Mwalukomo, Thandie; White, Sarah A; Mwafulirwa, Gershom; Longwe, Herbert; Mwaiponya, Martin; Zijlstra, Eduard E; Molyneux, Malcolm E; Gilks, Charles F

    2010-01-01

    Background: Streptococcus pneumoniae is a leading and serious co-infection of HIV-infected adults, particularly in Africa. Prevention of disease by vaccination with the current 23-valent polysaccharide vaccine is sub-optimal. Protein conjugate vaccines offer a further option for protection but no data exist on their clinical efficacy in any adult population. Methods: We conducted a double-blind randomized placebo-controlled clinical efficacy trial of the seven-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adults who had recovered from documented invasive pneumococcal disease (IPD). Vaccine was given as a two dose schedule four weeks apart. The primary end-point was a further episode of IPD caused by a vaccine-serotype or serotype-6A (VST/6A) pneumococcus. Results: Between February 2003 and October 2007, 496 individuals (44% male, 88% HIV seropositive) were followed for 798 person years of observation. There were 67 IPD events in 52 individuals, all in the HIV infected sub-group. There were 24 VST/6A events (19 VST, five 6A) in 24 participants, 5 in vaccine and 19 in the placebo recipients, a vaccine efficacy of 74% (95% CI 30% - 90%). There were 73 deaths in the vaccine arm and 63 in the placebo arm, Hazard Ratio 1.18 (95% confidence intervals 0.84 -1.66). Compared to placebo, serious adverse events were significantly lower (3 vs 17, p = 0.002) and minor adverse events significantly higher (41 vs 13, p = 0.003 ) in vaccine recipients. Conclusions: The seven-valent pneumococcal conjugate vaccine protects HIV infected adults from recurrent IPD of vaccine serotype or serotype 6A. PMID:20200385

  13. 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.

  14. 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

  15. Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System.

    PubMed

    Marcus, Julia L; Baxter, Roger; Leyden, Wendy A; Muthulingam, Dharushana; Yee, Arnold; Horberg, Michael A; Klein, Daniel B; Towner, William J; Chao, Chun R; Quesenberry, Charles P; Silverberg, Michael J

    2016-10-01

    It is unclear whether HIV-infected individuals remain at higher risk of invasive pneumococcal disease (IPD) compared with HIV-uninfected individuals. We conducted a cohort study of HIV-infected and demographically matched HIV-uninfected adults within Kaiser Permanente Northern California during the period 1996-2011. We used Poisson models to obtain rate ratios (RRs) for incident IPD associated with HIV infection and other risk factors. Among 13,079 HIV-infected and 137,643 HIV-uninfected adults, the IPD rate per 100,000 person-years was 160 (n = 109 events) for HIV-infected and 8 (n = 75 events) for HIV-uninfected subjects, with an adjusted RR of 13.0 [95% confidence interval (CI): 9.1-18.7]. For HIV-infected individuals, IPD incidence per 100,000 person-years decreased by 71% during study follow-up, from 305 in 1996-1999 to 88 in 2010-2011 (p < 0.001), with an adjusted RR of 6.6 (95% CI: 2.7-16.1) compared with HIV-uninfected subjects in 2010-2011. Risk factors for IPD among HIV-infected individuals included black compared with white race/ethnicity, smoking, cancer, and higher HIV RNA levels. The 23-valent pneumococcal polysaccharide vaccination was not associated with a reduced risk of IPD in HIV-infected or HIV-uninfected individuals. Among HIV-infected IPD cases, the most common serotype was 19A (33%), and 59% of serotypes were covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Despite a dramatic decline in IPD incidence for HIV-infected adults since 1996, IPD rates were nearly sevenfold higher compared with HIV-uninfected adults in recent years, even after adjustment for risk factors. Timely antiretroviral therapy initiation, risk reduction strategies, and recent guidelines recommending PCV13 use may further reduce IPD incidence among HIV patients.

  16. [Pneumococcal surface protein A and new approaches for pneumococcal vaccine development].

    PubMed

    Vorob'ev, D S; Semenova, I B

    2011-01-01

    The problem of pneumococcal infections is pressing for the whole world. Existing vaccines based only on pneumococci polysaccharide antigens or polysaccharide antigens and diphtherial anatoxin are not capable of protecting from all serotypes of the microorganism. Reasonability of creation of pneumococcal vaccine based on surface proteins of Streptococcus pneumoniae is discussed in the literature. One of such key pneumococcal proteins is pneumococcal surface protein A (PSPA), because it is detected in all the S. pneumoniae strains, has cross activity and switches B-cell immune response to T-cell. Currently the development of conjugated vaccine based on surface proteins and capsule polysaccharides of pneumococcus seems promising.

  17. Non-Invasive Pneumococcal Pneumonia in Portugal—Serotype Distribution and Antimicrobial Resistance

    PubMed Central

    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

  18. Optimization and application of a multiplex bead-based assay to quantify serotype-specific IgG against Streptococcus pneumoniae polysaccharides: response to the booster vaccine after immunization with the pneumococcal 7-valent conjugate vaccine.

    PubMed

    Elberse, Karin E M; Tcherniaeva, Irina; Berbers, Guy A M; Schouls, Leo M

    2010-04-01

    We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre- and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R(2) values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R(2) was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 microg/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.

  19. Evaluation of the incidence of herpes zoster after concomitant administration of zoster vaccine and polysaccharide pneumococcal vaccine.

    PubMed

    Tseng, Hung Fu; Smith, Ning; Sy, Lina S; Jacobsen, Steven J

    2011-05-09

    In 2009, a revision to the zoster vaccine package insert was approved stating that the zoster vaccine and the pneumococcal vaccine should not be given concurrently because concomitant use resulted in reduced immunogenicity of the zoster vaccine. We conducted an observational study to evaluate if concomitant vaccination reduces the protective effect of the zoster vaccine. The study was conducted in Kaiser Permanente Southern California. Incidence of herpes zoster (HZ) after vaccination with a zoster vaccine in the population receiving both vaccines on the same day was compared to that in the population receiving a pneumococcal vaccine within one year to 30 days prior to zoster vaccine. Vaccinations and incident HZ cases were identified by electronic health records. The hazard ratio for incident HZ associated with concomitant vs. nonconcomitant vaccination was estimated using the Cox proportional hazard model. There were 56 incident HZ cases in the concomitant vaccination cohort and 58 in the nonconcomitant vaccination cohort, yielding a HZ incidence of 4.54 (95% confidence interval [CI], 3.43-5.89) and 4.51 (95% CI, 3.42-5.83) per 1000 person-years, respectively. The hazard ratio comparing the incidence rate of HZ in the two cohorts was 1.19 (95% CI, 0.81-1.74) in the adjusted analysis. In this study, we found no evidence of an increased risk of HZ in the population receiving zoster vaccine and pneumococcal vaccine concomitantly. The revision of the product information needs to be carefully assessed to avoid introducing barriers to patients and providers who are interested in these two important vaccines.

  20. Measurement of antibodies to pneumococcal, meningococcal and haemophilus polysaccharides, and tetanus and diphtheria toxoids using a 19-plexed assay.

    PubMed

    Whitelegg, Alison M E; Birtwistle, Jane; Richter, Alex; Campbell, John P; Turner, James E; Ahmed, Tarana M; Giles, Lynda J; Fellows, Mark; Plant, Tim; Ferraro, Alastair J; Cobbold, Mark; Drayson, Mark T; MacLennan, Calman A

    2012-03-30

    The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens.

  1. Antibody and Plasmablast Response to 13-Valent Pneumococcal Conjugate Vaccine in Chronic Lymphocytic Leukemia Patients – Preliminary Report

    PubMed Central

    Pasiarski, Marcin; Rolinski, Jacek; Grywalska, Ewelina; Stelmach-Goldys, Agnieszka; Korona-Glowniak, Izabela; Gozdz, Stanislaw; Hus, Iwona; Malm, Anna

    2014-01-01

    Background Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60–80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects. Methods Both groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization. Results Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P = 0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed. Conclusions PCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable

  2. Rationale and design of the CAPAMIS study: Effectiveness of pneumococcal vaccination against community-acquired pneumonia, acute myocardial infarction and stroke

    PubMed Central

    2010-01-01

    Background The 23-valent polysaccharide pneumococcal vaccine (PPV-23) is recommended for elderly and high-risk people, although its effectiveness is controversial. Some studies have reported an increasing risk of acute vascular events among patients with pneumonia, and a recent case-control study has reported a reduction in the risk of myocardial infarction among patients vaccinated with PPV-23. Given that animal experiments have shown that pneumococcal vaccination reduces the extent of atherosclerotic lesions, it has been hypothesized that PPV-23 could protect against acute vascular events by an indirect effect preventing pneumonia or by a direct effect on oxidized low-density lipoproteins. The main objective of this study is to evaluate the clinical effectiveness of PPV-23 in reducing the risk of pneumonia and acute vascular events (related or nonrelated with prior pneumonia) in the general population over 60 years. Methods/Design Cohort study including 27,000 individuals 60 years or older assigned to nine Primary Care Centers in the region of Tarragona, Spain. According to the reception of PPV-23 before the start of the study, the study population will be divided into vaccinated and nonvaccinated groups, which will be followed during a consecutive 30-month period. Primary Care and Hospitals discharge databases will initially be used to identify study events (community-acquired pneumonia, hospitalisation for acute myocardial infarction and stroke), but all cases will be further validated by checking clinical records. Multivariable Cox regression analyses estimating hazard ratios (adjusted for age, sex and comorbidities) will be used to estimate vaccine effectiveness. Discussion The results of the study will contribute to clarify the controversial effect of the PPV-23 in preventing community-acquired pneumonia and they will be critical in determining the posible role of pneumococcal vaccination in cardiovascular prevention. PMID:20085658

  3. Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells.

    PubMed

    Peset Llopis, M J; Harms, G; Hardonk, M J; Timens, W

    1996-04-01

    A functionally intact spleen with a marginal zone, containing B cells with high density of surface C3d-receptors (CD21), is essential for the ability to induce a primary immune response to thymus-independent type 2 (TI-2) antigens. Main representatives of natural TI-2 antigens are capsular pneumococcal polysaccharides (PPSs). In this study the localization of different types of PPS antigen is determined in human spleen tissue. Our findings indicate that a main type of TI-2 antigen, PPS, localizes preferentially in the marginal zone. PPSs show co-localization with C3, presumably C3d, at the surface of strongly CD21+ B cells equipped for rapid activation. This enables a rapid primary humoral response. The other main PPS localization at follicular dendritic cells in germinal centers, relevant for isotype switching of anti-PPS antibodies, does not seem to be dependent on the presence of specific immunoglobulin. This may explain the finding of specific IgG in an early stage after antigenic challenge. It seems likely that complement C3 fragments (likely C3d), bound to PPSs, enable PPS localization at B-cell and follicular dendritic cell surfaces by binding to CD21, the C3d receptor.

  4. Aging promotes B-1b cell responses to native, but not protein-conjugated, pneumococcal polysaccharides: implications for vaccine protection in older adults.

    PubMed

    Haas, Karen M; Blevins, Maria W; High, Kevin P; Pang, Bing; Swords, W Edward; Yammani, Rama D

    2014-01-01

    The efficacy of different vaccines in protecting elderly individuals against Streptococcus pneumoniae infections is not clear. In the current study, aged mice (22-25 months old) exhibited significantly increased susceptibility to respiratory infection with serotype 3 S. pneumoniae relative to younger adult mice, regardless of whether mice were naive or immunized with native pneumococcal polysaccharide (PPS; Pneumovax23) or protein-PPS conjugate (Prevnar-13) vaccines. Nonetheless, Pneumovax-immunized aged mice developed limited bacteremia following respiratory challenge and exhibited significantly increased survival following systemic challenge relative to Prevnar-immune aged mice and young mice that had received either vaccine. This was explained by >10-fold increases in PPS-specific immunoglobulin G (IgG) levels in Pneumovax-immunized aged mice relative to other groups. Remarkably, PPS3-specific B-cell expansion, IgG switching, plasmablast differentiation, and spleen and bone marrow antibody-secreting cell frequencies were 10-fold higher in aged mice following Pneumovax immunization relative to young mice, due to significantly increased B-1b cell participation. In summary, this study highlights (1) the need to devise strategies to enhance respiratory immunity in aged populations, (2) the diverse responses young and aged populations generate to Pneumovax vs Prevnar vaccines, and (3) the potential value of exploiting B-1b cell responses in aged individuals for increased vaccine efficacy.

  5. 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

  6. Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae causing invasive pneumococcal disease from 2009-2012 with an emphasis on serotype 19A in bacteraemic pneumonia and empyema and β-lactam resistance.

    PubMed

    Lee, Meng-Rui; Chen, Chung-Ming; Chuang, Tzu-Yi; Huang, Yu-Tsung; Hsueh, Po-Ren

    2013-11-01

    Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae isolates that cause invasive pneumococcal disease (IPD) were studied and the role of serotype 19A in the development of bacteraemic pneumonia and empyema was investigated. Subjects comprised 98 patients (56 adults and 42 children) who were treated for IPD at a university-affiliated tertiary referral centre in Taiwan during 2009-2012. Serotypes of the isolates were identified using the latex agglutination method. In vitro susceptibilities of the isolates to 13 antimicrobial agents were determined using the broth microdilution method and were interpreted as recommended by the Clinical and Laboratory Standards Institute. During the study period, bacteraemic pneumonia was the most common type of infection (43/98; 43.9%), followed by primary bacteraemia (30/98; 30.6%). Serotype 19A was the most common serotype (23/98; 23.5%) in all patients. Fourteen (70.0%) of 20 children (47.6% of all children) with serotype 19A infection had pneumonia with empyema, whilst eight patients had concomitant bacteraemia. 7-valent pneumococcal conjugated vaccine (PCV-7), PCV-10, PCV-13 and 23-valent pneumococcal polysaccharide vaccine (PPV-23) had coverage rates of 37.8%, 38.8%, 79.6% and 77.6%, respectively. A substantial increase in the proportion of serotype 15A (6.1%) and 6A (8.2%) was found. In addition, there was a significant reduction in rates of susceptibility of serotype 19A isolates to penicillin, cefotaxime and ceftriaxone but not to azithromycin or any quinolone tested compared with those of non-19A isolates. The prevalence of serotypes 19A, 15A and 6A in patients with IPD increased markedly during the period, especially in children with bacteraemic pneumonia and empyema.

  7. Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

    PubMed

    Lai, Zengzu; Schreiber, John R

    2009-05-21

    Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

  8. Randomized Controlled Study of the Safety and Immunogenicity of Pneumococcal Vaccine Formulations Containing PhtD and Detoxified Pneumolysin with Alum or Adjuvant System AS02V in Elderly Adults

    PubMed Central

    Nilsson, Anna C.; Caubet, Magalie; Pascal, Thierry G.; Van Belle, Pascale; Poolman, Jan T.; Vandepapelière, Pierre G.; Verlant, Vincent; Vink, Peter E.

    2014-01-01

    Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02V than with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.) PMID:24599529

  9. Randomized controlled study of the safety and immunogenicity of pneumococcal vaccine formulations containing PhtD and detoxified pneumolysin with alum or adjuvant system AS02V in elderly adults.

    PubMed

    Pauksens, Karlis; Nilsson, Anna C; Caubet, Magalie; Pascal, Thierry G; Van Belle, Pascale; Poolman, Jan T; Vandepapelière, Pierre G; Verlant, Vincent; Vink, Peter E

    2014-05-01

    Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02V than with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.).

  10. Pneumococcal Conjugated Vaccine Reduces the High Mortality for Community-Acquired Pneumonia in the Elderly: an Italian Regional Experience

    PubMed Central

    Gallo, Tolinda; Furlan, Patrizia; Romor, Pierantonio; Bertoncello, Chiara; Buja, Alessandra; Baldovin, Tatjana

    2016-01-01

    Background Community-acquired pneumonia (CAP) is an important cause of illness and death worldwide, particularly among the elderly. Previous studies on the factors associated with mortality in patients hospitalized for CAP revealed a direct association between the type of microorganism involved, the characteristics of the patient and mortality. Vaccination status against pneumococcal disease was not considered. We conducted a retrospective analysis on the mortality rates after a first hospitalization for CAP in north-east Italy with a view to examining especially the role of anti-pneumococcal vaccination as a factor associated with pneumonia-related mortality at one year. Method Between 2012–2013, patients aged 65+ hospitalized with a primary diagnosis of CAP, identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes 481–486, were enrolled in the study only once. Patients were divided into three groups by pneumococcal vaccination status: 1) 13-valent pneumococcal conjugate vaccine (PCV13) prior to their hospitalization; 2) 23-valent pneumococcal polysaccharide vaccine (PPV23) within 5 years before hospitalization and 3) unvaccinated or PPV23 more than 5 years prior to admission. Gender, age, length of hospital stay and influenza vaccination were considered. Comorbidities were ascertained by means of a properly coded diagnosis. Every patient was followed up for 1 year and the outcome investigated was mortality for any cause and for pneumonia. Results A total of 4,030 patient were included in the study; mean age at the time of admission to hospital was 84.3±7.7; 50.9% were female. 74.2% of subjects had at least one comorbidity; 73.7% has been vaccinated against influenza. Regard to pneumococcal vaccine, 80.4% of patients were not vaccinated, 14.5% vaccinated with PPV23 and 5.1% with PCV13. The 1-year survival rates after hospitalization for pneumonia were 83.6%, 85.9% and 89.3% in the unvaccinated, PPV23 and PCV13

  11. Pneumococcal Disease

    MedlinePlus

    ... Newsroom Blogs Image Library News Conferences Press Releases Radio Public Service Announcements Real Stories, Real People Share ... National Foundation for Infectious Diseases (NFID) Pneumococcal Disease Radio Public Service Announcement National Foundation for Infectious Diseases ( ...

  12. Meningitis - pneumococcal

    MedlinePlus

    ... causes meningitis. Causes Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type ... Saunders; 2015:chap 89. Wood JB, Peters TR. Streptococcus pneumoniae (pneumococcus). In: Kliegman RM, Stanton BF, St. Geme ...

  13. Comparison of dual influenza and pneumococcal polysaccharide vaccination with influenza vaccination alone for preventing pneumonia and reducing mortality among the elderly: A meta-analysis

    PubMed Central

    Zhang, Yan-Yang; Tang, Xue-Feng; Du, Chang-Hui; Wang, Bin-Bing; Bi, Zhen-Wang; Dong, Bi-Rong

    2016-01-01

    ABSTRACT The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718–0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707–0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates. PMID:27629584

  14. Pneumococcal vaccination--current situation and perspectives.

    PubMed

    Madar, R; Strakova, J; Baska, T; Kavcova, E; Straka, S

    2005-01-01

    The authors carried out a survey in outpatient and hospitalised patients with risk factors for invasive pneumococcal disease in a tertiary-care medical faculty affiliated hospital. Data were collected by individual interviews and verified against the medical records of all addressed patients. The authors also attempted to discover the attitude of general practitioners (GPs) from 2 Slovak districts towards the pneumococcal vaccine by means of an anonymous questionnaire. Out of the total of 154 addressed patients, 128 (83.1%) had at least one risk factor for acquiring invasive pneumococcal disease. However, only 8 (6.3%) of them had ever been administered pneumococcal vaccine. Out of 34 hospitalised patients with at least one risk factor 82.4 % had not received any pneumococcal vaccination in the past. When subdivided according to age and risk factors (chronic respiratory, cardiovascular, uropoetic, metabolic, immunne system disorders, asplenia), vaccination coverage in all groups was very low, ranging between --9.3%. In an anonymous questionnaire 74 (94.9%) out of 77 surveyed GPs referred to a lack of information on the polysaccharide pneumococcal vaccine and 22 (28.2%) expressed their general distrust towards vaccination of any kind. The main role in increasing the disturbingly low pneumococcal vaccination coverage lies in the hands of medical professionals, especially GPs who should inform their patients about the possibility of a free vaccine and who should make an effort to explain to their patients the benefit of pneumococcal vaccination. (Tab. 4, Reft 9.)

  15. Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

    PubMed Central

    2016-01-01

    The pneumococcal conjugate vaccine (PCV) was developed to overcome the limitations of the pneumococcal polysaccharide vaccine, which produces poor immunogenicity in infants younger than 2 years. As many countries have included PCVs in national immunization programs for children, the incidence of invasive pneumococcal disease caused by vaccine type Streptococcus pneumoniae has declined markedly, not only among the vaccinated pediatric population, but also among unvaccinated adults. In this review, we present a concise overview of the indirect effects of mass pediatric PCV immunization on unvaccinated adults. PMID:28032483

  16. 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.

  17. Comparison of the immunogenicity and safety of polysaccharide and protein-conjugated pneumococcal vaccines among the elderly aged 80 years or older in Japan: an open-labeled randomized study.

    PubMed

    Namkoong, Ho; Funatsu, Yohei; Oishi, Kazunori; Akeda, Yukihiro; Hiraoka, Rika; Takeshita, Kei; Asami, Takahiro; Yagi, Kazuma; Kimizuka, Yoshifumi; Ishii, Makoto; Tasaka, Sadatomo; Suzuki, Yukio; Iwata, Satoshi; Betsuyaku, Tomoko; Hasegawa, Naoki

    2015-01-03

    An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.

  18. 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

  19. 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 to ...

  20. Pneumococcal Disease Fast Facts

    MedlinePlus

    ... Home About Pneumococcal Types of Infection Risk Factors & Transmission Symptoms & Complications Diagnosis & Treatment Prevention Photos Fast Facts Pneumococcal Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For ...

  1. 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.

  2. Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gadzinowski, Janusz; Albrecht, Piotr; Hasiec, Barbara; Konior, Ryszard; Dziduch, Jerzy; Witor, Anita; Mellelieu, Tracey; Tansey, Susan P; Jones, Thomas; Sarkozy, Denise; Emini, Emilio A; Gruber, William C; Scott, Daniel A

    2011-04-05

    13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.

  3. [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.

  4. Pneumococcal Vaccination Guidance for Post-Acute and Long-Term Care Settings: Recommendations From AMDA's Infection Advisory Committee.

    PubMed

    Nace, David A; Archbald-Pannone, Laurie R; Ashraf, Muhammad S; Drinka, Paul J; Frentzel, Elizabeth; Gaur, Swati; Mahajan, Dheeraj; Mehr, David R; Mercer, William C; Sloane, Philip D; Jump, Robin L P

    2017-02-01

    Efforts at preventing pneumococcal disease are a national health priority, particularly in older adults and especially in post-acute and long-term care settings The Advisory Committee on Immunization Practices recommends that all adults ≥65 years of age, as well as adults 18-64 years of age with specific risk factors, receive both the recently introduced polysaccharide-protein conjugate vaccine against 13 pneumococcal serotypes as well as the polysaccharide vaccine against 23 pneumococcal serotypes. Nursing facility licensure regulations require facilities to assess the pneumococcal vaccination status of each resident, provide education regarding pneumococcal vaccination, and administer the appropriate pneumococcal vaccine when indicated. Sorting out the indications and timing for 13 pneumococcal serotypes and 23 pneumococcal serotypes administration is complex and presents a significant challenge to healthcare providers. Here, we discuss the importance of pneumococcal vaccination for older adults, detail AMDA-The Society for Post-Acute and Long-Term Care Medicine (The Society)'s recommendations for pneumococcal vaccination practice and procedures, and offer guidance to postacute and long-term care providers supporting the development and effective implementation of pneumococcal vaccine policies.

  5. 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

  6. Immunologic studies in pneumococcal disease.

    PubMed

    Dee, T H; Schiffman, G; Sottile, M I; Rytel, M W

    1977-06-01

    Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.

  7. 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

  8. Maternal-foetal interaction, antibody formation, and metabolic response in mice immunized with pneumococcal polysacharides.

    PubMed Central

    Lee, C J

    1980-01-01

    The maternal transfer of pneumococcal polysaccharides to foetus, as well as the antibody formation and metabolic response were studied in mice exposed to pneumococcal polysaccharides during pregnancy. Type 19 and type 57 pneumococcal polysaccharides display cross-placental transfer to foetus. These polysaccharides also transfer through mother's milk to neonates. Maternal immunization of type 19 polysaccharide during pregnancy induced higher antibody formation in the offspring than the group from non-immunized mothers. Young mice, which received a second dose of polysaccharide at 2 weeks of age, showed a higher antibody response than those which did not receive polysacharide. Treatment of mothers with anti-lymphocyte serum, following by administration of polysaccharide, significantly increased the neonatal immune response to the polysaccharide. Treatment of the mother with a high dose of type 19 or type 57 polysaccharide did not cause significant changes in neonatal growth and organ weights. The offspring from mothers treated with high doses of these polysaccharides did not exhibit abnormalities in chemical contents of their tissues. PMID:7429553

  9. [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

  10. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... to 2-Year-Old 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, ...

  11. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... Your 1- to 2-Year-Old Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your ... but also help stop the infections from spreading. Immunization Schedule PCV13 immunizations are given to all infants ...

  12. [Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance].

    PubMed

    Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T

    2008-02-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

  13. Pneumococcal Disease: Diagnosis and Treatment

    MedlinePlus

    ... of antibiotics may also slow or reverse drug-resistant pneumococcal infections. Related Pages Global Pneumococcal Vaccination World Health Organization National Foundation for Infectious Diseases Sepsis File Formats Help: How do I view ...

  14. Prevention of pneumococcal disease through vaccination.

    PubMed

    Gentile, Angela; Bazán, Virginia

    2011-09-14

    The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide-more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only

  15. Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.

    PubMed

    Patel, Shiven S; Fergeson, Jennifer E; Glaum, Mark C; Lockey, Richard F

    2016-01-01

    Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.

  16. Tailoring the strategies to specific shortages: pneumococcal conjugate vaccine.

    PubMed

    Peter, Georges

    2006-03-01

    Less than 1 year after recommendations for the routine vaccination of infants with the newly licensed 7-valent polysaccharide-protein conjugate pneumococcal vaccine were issued in February 2000, shortages of the 7-valent polysaccharide-protein conjugate pneumococcal vaccine supply began to occur. A national shortage developed in 2001, involving both the public and private sectors, and it resulted in temporary recommendations to conserve vaccine supply for infants and young children at the highest risk for invasive disease. Multiple factors contributed to this vaccine shortage, including demand that exceeded the expectations of the manufacturer and the need for compliance with the Good Manufacturing Practice of the US Food and Drug Administration. Of the possible strategies that might have averted this shortage, establishment of a vaccine stockpile is the most likely solution. However, establishing a stockpile for a newly licensed vaccine, such as 7-valent polysaccharide-protein conjugate pneumococcal vaccine, presents unique challenges. Improved communication with physicians and parents regarding changes in vaccine schedules also will promote better adherence to recommended changes and conservation of limited vaccine supplies during a shortage.

  17. A Novel ICOS-Independent, but CD28- and SAP-Dependent, Pathway of T Cell-Dependent, Polysaccharide-Specific Humoral Immunity in Response to Intact Streptococcus pneumoniae versus Pneumococcal Conjugate Vaccine

    DTIC Science & Technology

    2008-01-01

    PPS14) and the phosphorylcholine determinant (PC) of the cell wall C-polysaccharide (C-PS, teichoic acid). The protein- and PS-specific IgG responses...hydroxy-3-nitrophenyl)acetyl; PC, phosphorylcholine determi- nant of teichoic or lipoteichoic acid; Pn, intact Streptococcus pneumoniae; PPS14, capsular

  18. 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.

  19. Pneumococcal Disease: Types of Infection

    MedlinePlus

    ... Programs Related Pages Global Pneumococcal Vaccination World Health Organization National Foundation for Infectious Diseases Sepsis Types of Infection Recommend on Facebook Tweet Share Compartir ...

  20. Prevention of Community-Acquired Pneumonia with Available Pneumococcal Vaccines

    PubMed Central

    Principi, Nicola; Esposito, Susanna

    2016-01-01

    Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The main aim of this paper is to evaluate the published evidence concerning the impact of pneumococcal vaccines on the prevention of CAP in children and adults. Available data indicate that pneumococcal conjugate vaccines (PCVs) are effective in children, reducing all-cause CAP cases and bacteremic and nonbacteremic CAP cases. Moreover, at least for PCV7 and PCV13, vaccination of children is effective in reducing the incidence of CAP among adults. Recently use of PCV13 in adults alone or in combination with the pneumococcal polysaccharide vaccine has been suggested and further studies can better define its effectiveness in this group of subjects. The only relevant problem for PCV13 is the risk of a second replacement phenomenon, which might significantly reduce its real efficacy in clinical practice. Protein-based pneumococcal vaccines might be a possible solution to this problem. PMID:28029140

  1. Pneumococcal Antibody Titers

    PubMed Central

    Abghari, Pamella F.; Poowuttikul, Pavadee; Secord, Elizabeth

    2017-01-01

    Purpose: Immunoglobulin replacement is the mainstay treatment in patients with humoral immunodeficiencies, yet a handful of patients continue to develop sinopulmonary infections while on therapy. The objective of our study was to compare immunoglobulin G (IgG) pneumococcal antibody levels in patients with humoral immune deficiencies who have been on intravenous immunoglobulin (IVIG) replacement for at least 1 year to those on subcutaneous immunoglobulin (SCIG) therapy for at least 1 year. Methods: A retrospective chart review was completed on 28 patients. These patients’ ages ranged between 1 and 61 years. Pneumococcal serotype titers obtained at least 1 year after initiating therapy were compared between patients on IVIG (19 patients) and SCIG (9 patients). Results: A comparison between the groups demonstrated that SCIG achieved a higher percentage of serotype titers protective for noninvasive disease (≥1.3) and 100% protection for invasive disease (≥0.2). Our data also demonstrated a similar lack of protection (less than 50% ≥1.3) in 9N, 12F, and 23F on IVIG and 4, 9N, 12F, and 23F on SCIG. Conclusions: Our data demonstrated that serotypes 1, 3, 4, 9N, 12F, and 23F exhibited the lowest random IgG means while on IVIG, which was comparable to other published studies that looked at the mean IgG levels. In addition, our retrospective chart review demonstrated a greater number of therapeutic pneumococcal titers with SCIG in comparison to IVIG. PMID:28321436

  2. [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.

  3. Comparison of secular trends in pneumococcal serotypes causing invasive disease in Denver, Colorado (1971-2004) and serotype coverage by marketed pneumococcal vaccines.

    PubMed

    Akduman, D; Ehret, J M; Judson, F N

    2006-11-01

    Invasive pneumococcal isolates from three hospitals in Denver, CO, USA were serotyped between 1971 and 2004. Serotype 14 was most common (13.2%), and other prevalent serotypes (3, 4, 6, 9 and 19) together accounted for 44.1% of the isolates. All prevalent serotypes and 91.3% of the total isolates were covered by pneumococcal polysaccharide vaccine, while 79.1% of prevalent serotypes and 56.7% of total isolates were covered by pneumococcal conjugate vaccine. Serotypes 6, 9 and 14 were more common in the final decade than in the first decade studied (37.3% vs. 20.2%), whereas serotypes 3 and 23 were more common in the first decade (18.5% vs. 11.0%).

  4. What do we know about the cost-effectiveness of pneumococcal conjugate vaccination in older adults?

    PubMed

    Newall, A T

    2016-10-02

    The cost-effectiveness of 13-type pneumococcal conjugate vaccine (PCV13) use in older adults, and the relative merits when compared to the 23-type polysaccharide pneumococcal vaccine (PPV23), has been a topic of much debate. Although a number of economics evaluations have been conducted many of these were completed before the availability of critical data on PCV13 efficacy in older adults. Recent studies using this data have found conflicting results. This may in part reflect differences in the level of herd protection from infant pneumococcal vaccination programs in different countries. The costs and benefits of pneumococcal vaccination in adults are likely to rest on several critical parameters: the magnitude pneumococcal disease in older adults and the serotypes responsible for it, the efficacy of each vaccine against invasive and non-invasive pneumonia, the duration of vaccine protection, and differences in vaccine price. The ongoing changes in pneumococcal disease patterns highlight the need for economic evaluations to use recent serotype-specific disease estimates from the setting under consideration. In countries that do recommend PCV13 use in adults, post-implementation economic evaluation (using data from after a program is implemented) may be useful to help inform potential future changes to vaccine recommendations as well as the maximum price that should be paid for the vaccines in future negotiations.

  5. Fred Neufeld and pneumococcal serotypes: foundations for the discovery of the transforming principle.

    PubMed

    Eichmann, Klaus; Krause, Richard M

    2013-07-01

    During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today's knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld's contributions in this development, which have remained largely unknown.

  6. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  7. Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine

    PubMed Central

    Yildirim, Inci; Shea, Kimberly M.

    2015-01-01

    SYNOPSIS Universal immunization of infants and toddlers with PCVs over the past 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in IPD, all cause pneumonia, empyema, mastoiditis, acute otitis media and complicated otitis media have been reported from multiple countries where universal immunization has been implemented. The introduction of the vaccine has also led to expanded understanding of pneumococcal disease; observations have confirmed that most pneumococci are transmitted from children to adults, not all pneumococcal serotypes are equal in terms of common clinical syndromes, likelihood of antibiotic resistance, or likelihood of progression to disease once colonization occurs. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared to 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

  8. Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Sehatzadeh, S

    2012-01-01

    nasopharynx of healthy children and adults. Pneumococcus can be transmitted from person to person during close contact. The bacteria can cause illnesses such as otitis media and sinusitis, and may become more aggressive and affect other areas of the body such as the lungs, brain, joints, and blood stream. More severe infections caused by pneumococcus are pneumonia, bacterial sepsis, meningitis, peritonitis, arthritis, osteomyelitis, and in rare cases, endocarditis and pericarditis. People with impaired immune systems are susceptible to pneumococcal infection. Young children, elderly people, patients with underlying medical conditions including chronic lung or heart disease, human immunodeficiency virus (HIV) infection, sickle cell disease, and people who have undergone a splenectomy are at a higher risk for acquiring pneumococcal pneumonia. Technology Influenza and Pneumococcal Vaccines Trivalent Influenza Vaccines in Canada In Canada, 5 trivalent influenza vaccines are currently authorized for use by injection. Four of these are formulated for intramuscular use and the fifth product (Intanza®) is formulated for intradermal use. The 4 vaccines for intramuscular use are: Fluviral (GlaxoSmithKline), split virus, inactivated vaccine, for use in adults and children ≥ 6 months; Vaxigrip (Sanofi Pasteur), split virus inactivated vaccine, for use in adults and children ≥ 6 months; Agriflu (Novartis), surface antigen inactivated vaccine, for use in adults and children ≥ 6 months; and Influvac (Abbott), surface antigen inactivated vaccine, for use in persons ≥ 18 years of age. FluMist is a live attenuated virus in the form of an intranasal spray for persons aged 2 to 59 years. Immunization with current available influenza vaccines is not recommended for infants less than 6 months of age. Pneumococcal Vaccine Pneumococcal polysaccharide vaccines were developed more than 50 years ago and have progressed from 2-valent vaccines to the current 23-valent vaccines to prevent

  9. Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

    PubMed Central

    Albrich, Werner C; Madhi, Shabir A; Adrian, Peter V; van Niekerk, Nadia; Telles, Jean-Noel; Ebrahim, N; Messaoudi, Melina; Paranhos-Baccalà, Glaucia; Giersdorf, Sven; Vernet, Guy; Mueller, Beat; Klugman, Keith P

    2014-01-01

    Objective A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). Conclusions In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID:25113557

  10. 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.

  11. Pneumococcal Conjugate Vaccine (PCV13)

    MedlinePlus

    ... the United States.Treatment of pneumococcal infections with penicillin and other drugs is not as effective as ... should not get PCV13.Anyone with a severe allergy to any component of PCV13 should not get ...

  12. Pneumococcal Infections: MedlinePlus Health Topic

    MedlinePlus

    ... Disease Control and Prevention) - PDF Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumococcal Infections updates ... ray Meningitis - pneumococcal Sputum gram stain Related Health Topics Meningitis Pneumonia Sepsis Sinusitis Streptococcal Infections National Institutes ...

  13. Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients.

    PubMed

    Meerveld-Eggink, A; de Weerdt, O; van Velzen-Blad, H; Biesma, D H; Rijkers, G T

    2011-01-17

    We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ≥ 1.0 μg/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ≥ 1.0 μg/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ≥ 1.0 μg/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ≥ 1.0 μg/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ≥ 1.0 μg/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity.

  14. Clonal distribution of pneumococcal serotype 19F isolates from Ghana.

    PubMed

    Sparding, Nadja; Dayie, Nicholas T K D; Mills, Richael O; Newman, Mercy J; Dalsgaard, Anders; Frimodt-Møller, Niels; Slotved, Hans-Christian

    2015-04-01

    Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from Ghana were investigated; isolates from healthy children in Tamale and isolates from both healthy and children attending the outpatient department at a hospital in Accra. The isolates were previously identified and characterized by Gram staining, serotyping and susceptibility to penicillin. In this study, isolates of the common serotype 19F were further investigated by Multi-Locus Sequence Typing (MLST). Overall, 14 different Sequence Types (STs) were identified by MLST, of which nine were novel based on the international MLST database. Two clones within serotype 19F seem to circulate in Ghana, a known ST (ST 4194) and a novel ST (ST 9090). ST 9090 was only found in healthy children in Accra, whereas ST 4194 was found equally in all children studied. In the MLST database, other isolates of ST 4194 were also associated with serotype 19F, and these isolates came from other West African countries. The majority of isolates were penicillin intermediate resistant. In conclusion, two clones within serotype 19F were found to be dominating in pneumococcal carriage in Accra and Tamale in Ghana. Furthermore, it seems as though the clonal distribution of serotype 19F may be different from what is currently known in Ghana in that many new clones were identified. This supports the importance of continued monitoring of pneumococcal carriage in Ghana and elsewhere when vaccines, e.g., PCV-13, have been introduced to monitor the possible future spread of antimicrobial resistant clones.

  15. 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

  16. Advances in pneumococcal antibiotic resistance.

    PubMed

    Song, Jae-Hoon

    2013-10-01

    Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been evolving with the widespread use of antibiotics and the introduction of pneumococcal conjugate vaccines (PCV). Particularly, among various types of antimicrobial resistance, macrolide resistance has most remarkably increased in many parts of the world, which has been reported to be >70% among clinical isolates from Asian countries. Penicillin resistance has dramatically decreased among nonmeningeal isolates due to the changes in resistance breakpoints, although resistance to other β-lactams such as cefuroxime has increased. Multidrug resistance became a serious concern in the treatment of invasive pneumococcal diseases, especially in Asian countries. After PCV7 vaccination, serotype 19A has emerged as an important cause of invasive pneumococcal diseases which was also associated with increasing prevalence of multidrug resistance in pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and 19A, may contribute to reduce the clonal spread of drug-resistant 19A pneumococci.

  17. 13-valent pneumococcal conjugate vaccine.

    PubMed

    2011-01-01

    The 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) is the standard vaccine for the prevention of invasive pneumococcal infections in infants and children under 5 years of age. A 13-valent pneumococcal conjugate vaccine (with the addition of valences 1, 3, 5, 6A, 7F and 19A) has now been authorised to replace the 7-valent vaccine within the European Union. This new vaccine, adapted to recent epidemiological data on invasive pneumococcal infections, is supposed to cover at least 80% of pneumococcal infections in Europe. The protective potency of the 13-valent vaccine has not yet been tested in clinical trials. Clinical evaluation is based on two immunogenicity studies, in which the immunogenic potency of the 13-valent vaccine was similar to that of the 7-valent vaccine for their shared serotypes, but lower for serotypes 3, 6B and 9V. For these last two serotypes and for the new serotypes, the usual target antibody titre was reached after a booster injection. This was not the case for valence 3. * The vaccine used in immunogenicity studies did not contain polysorbate 80 (an excipient), and a non-inferiority study of the marketed vaccine containing polysorbate 80 was therefore conducted in 500 children. Non-inferiority was established for all 13 valences after the booster injection, but not for valences 6B and 23F after primary vaccination. According to the results of 10 studies, simultaneous administration of the 13-valent pneumococcal conjugate vaccine does not affect the immunogenicity of other vaccines generally administered before the age of 5 years. Other immunogenicity studies support the use of a variety of vaccine schedules for infants and children under 5 years of age who have not yet been vaccinated or who have started vaccination with the 7-valent vaccine. Increasing the number of valences in the vaccine from 7 to 13 led to no marked increase in local adverse effects (hypersensitivity, indurations, erythema) or systemic reactions

  18. Immunodeficiency Among Children with Recurrent Invasive Pneumococcal Disease

    PubMed Central

    Schejbel, Lone; Lundstedt, A.C.; Jensen, Lise; Laursen, Inga A.; Ryder, Lars P.; Heegaard, Niels H.H.; Konradsen, Helle; Christensen, Jens Jørgen; Heilmann, Carsten; Marquart, Hanne V.

    2015-01-01

    Background: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. Methods: Cases of rIPD in children 0–15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer--cell counts and concentration of immunoglobulins. B-cell function was evaluated by measuring antibody response to polysaccharide-based pneumococcal vaccination and the extent of fraction of somatic hypermutation. Toll-Like receptor (TLR) signaling function and mutations in key TLR-signaling molecules were examined. Results: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response was found in 6 children of whom 3 were C2 deficient. One patient had a severe TLR signaling dysfunction. No mutations in IRAK4, IKBKG or MYD88 were found. Conclusion: Of an unselected cohort of children with rIPD at least 11% were C2 deficient. Data suggest that screening for complement deficiencies and deficient antibody response to pneumococcal vaccines in patients with more than 1 episode of IPD is warranted. PMID:25831419

  19. 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

  20. Preclinical evaluation of a chemically detoxified pneumolysin as pneumococcal vaccine antigen

    PubMed Central

    Hermand, Philippe; Vandercammen, Annick; Mertens, Emmanuel; Di Paolo, Emmanuel; Verlant, Vincent; Denoël, Philippe; Godfroid, Fabrice

    2017-01-01

    ABSTRACT The use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sesec-typsecquence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment. Detoxi-fication was confirmed by dPly challenge in mice and histological analysis of the injection site in rats. Immunization with dPly elicited Ply-specific functional antibodies that were able to inhibit Ply activity in a hemolysis assay. In addition, immunization with dPly protected mice against lethal intranasal challenge with Ply, and intranasal immunization inhibited nasopharyngeal colonization after intranasal challenge with homologous or heterologous pneumococcal strain. Our findings supported dPly as a valid candidate antigen for further pneumococcal vaccine development. PMID:27768518

  1. Promises and pitfalls of live attenuated pneumococcal vaccines.

    PubMed

    Rosch, Jason W

    2014-01-01

    The pneumococcus is a remarkably adaptable pathogen whose disease manifestations range from mucosal surface infections such as acute otitis media and pneumonia to invasive infections such as sepsis and meningitis. Currently approved vaccines target the polysaccharide capsule, of which there are over 90 distinct serotypes, leading to rapid serotype replacement in vaccinated populations. Substantial progress has been made in the development of a universal pneumococcal vaccine, with efforts focused on broadly conserved and protective protein antigens. An area attracting considerable attention is the potential application of live attenuated vaccines to confer serotype-independent protection against mucosal and systemic infection. On the basis of recent work to understand the mucosal and systemic responses to nasal administration of pneumococci and to develop novel attenuation strategies, the prospect of a practical and protective live vaccine remains promising.

  2. Characterization of pneumococcal purpura-producing principle.

    PubMed

    Chetty, C; Kreger, A

    1980-07-01

    Purpura was grossly observable in albino mice 6 to 8 h after the intraperitoneal injection of sterile, deoxyribonuclease-treated, cell-free extracts prepared by sodium deoxycholate-induced lysis, sonic disruption, Parr bomb treatment, autolysis without sodium deoxycholate, or alternate freezing and thawing of washed suspensions of Streptococcus pneumoniae type I. Cell-free extracts obtained from sonically disrupted, heat-killed cells (100 degrees C for 20 min) did not contain purpurogenic activity. The reaction was maximal at approximately 24 h postinjection, started to fade slowly after 24 to 48 h, and usually was not grossly observable by 4 to 6 days postinjection. The purpura-producing principle (PPP) in the cell-free extract was purified by sequential ammonium sulfate precipitation, protamine sulfate precipitation, Sepharose 6B gel filtration, wheat germ lectin-Sepharose 6MB affinity chromatography, ribonuclease and trypsin treatment, and a second Sepharose 6B gel filtration step. The final preparation (i) contained glucosamine (5.6%), muramic acid (8.0%), neutral carbohydrate (12.8%), phosphate (8.0%), orcinol-reactive material (6.0%), and Lowry-reactive material (1.6%), and (ii) was free of detectable amounts of deoxyribonucleic acid, capsular polysaccharide, neuraminidase, cytolysin, and hyaluronidase. The isoelectric point and molecular size of the PPP were approximately pI 3.0 and several million daltons, respectively, and the activity remained in the supernatant fluid after centrifugation for 1 day at 105,000 x g. PPP activity was destroyed by incubation with egg white lysozyme and sodium metaperiodate but was resistant to trypsin, pronase, alpha-amylase, deoxyribonuclease, ribonuclease, alkaline phosphatase, pancreatic lipase, 7% trichloroacetic acid, 6 M urea, autoclaving (121 degrees C) for 30 min, and mild acid and alkali exposure. Our observations indicate that the PPP requires intact beta-1,4-glucosidic linkages for activity and support the working

  3. Differential Regulation of IgG Anti-Capsular Polysaccharide and Antiprotein Responses to Intact Streptococcus pneumoniae in the Presence of Cognate CD4+ T Cell Help

    DTIC Science & Technology

    2004-01-01

    polysaccharide (PPS14), the phosphorylcholine determinant of the cell wall C-polysaccharide, and the cell wall protein, pneumococcal surface protein A...a more rapid delivery of CD4 T cell help. In contrast, the IgG anti- phosphorylcholine response, although also dependent on CD4 T cells, is TCR...and/or IgG isotypes specific for the phosphorylcholine (PC) determinant of the cell wall C-polysaccharide (teichoic acid) and for the cell wall

  4. 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

  5. Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough.

    PubMed

    Hausdorff, William P; Hoet, Bernard; Adegbola, Richard A

    2015-03-01

    Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide. A heptavalent polysaccharide-protein conjugate vaccine (PCV) has proven highly effective in preventing pneumococcal disease in industrialized countries. Two higher-valent pneumococcal conjugate vaccines are now widely available, even in the poorest countries. These differ from each other in the number of serotypes and carrier proteins used for their conjugation. Some have assumed that the only meaningful clinical difference between PCV formulations is a function of the number of serotypes each contains. A careful review of recent clinical data with these and several unlicensed PCV formulations points to important similarities but also that some key properties of each vaccine likely differ from one another.

  6. 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

    PubMed

    Muema, D M; Nduati, E W; Uyoga, M; Bashraheil, M; Scott, J A G; Hammitt, L L; Urban, B C

    2015-08-01

    Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

  7. Pulmonary pathophysiology of pneumococcal pneumonia.

    PubMed

    Light, R B

    1999-09-01

    Respiratory failure is one of the most important causes of death in patients with acute pneumococcal pneumonia. There are two forms that may or may not coexist: ventilatory failure and hypoxemic respiratory failure. Ventilatory failure is principally caused by mechanical changes in the lungs resulting from pneumonia. Inflammatory exudate fills alveoli at slightly less than their normal functional residual capacity (FRC), causing a volume loss at FRC roughly proportional to the extent of the pulmonary infiltrate. Because this consolidated air space does not inflate easily at higher transpulmonary pressures, at higher lung volumes the volume loss is proportionally greater. This loss of volume reduces total lung compliance and increases the work of breathing. There is also evidence that the dynamic compliance of the remaining ventilated lung is reduced in pneumococcal pneumonia, possibly by reduction in surfactant activity, further increasing the work of breathing. Arterial hypoxemia early in acute pneumococcal pneumonia is principally caused by persistence of pulmonary artery blood flow to consolidated lung resulting in an intrapulmonary shunt, but also, to a varying degree, it is caused by intrapulmonary oxygen consumption by the lung during the acute phase and by ventilation-perfusion mismatch later. The persistence of pulmonary blood flow to consolidated lung appears to be caused by a relative failure of the hypoxic pulmonary vasoconstriction (HPV) mechanism during acute pneumonia, which is at least caused by endogenous vasodilator prostaglandins associated with the inflammatory process but also by other as yet undefined mechanisms. During convalescence, arterial oxygenation improves as blood flow to consolidated lung falls. The magnitude of the intrapulmonary shunt may be influenced by a number of factors that modify the distribution of pulmonary blood flow. Factors that tend to increase flow to consolidated lung and worsen shunt include endogenous vasodilator

  8. Towards New Broader Spectrum Pneumococcal Vaccines: The Future of Pneumococcal Disease Prevention

    PubMed Central

    Lee, Lucia H.; Gu, Xin-Xing; Nahm, Moon H.

    2014-01-01

    Seven-valent pneumococcal conjugate vaccine (PCV7) introduction and routine pediatric use has substantially reduced the burden of Streptococcus pneumoniae disease worldwide. However, a significant amount of disease burden, due to serotypes not contained in PCV7, still exists globally. A newly recognized serotype, 6C, was until recently, identified and reported as serotype 6A. This review summarizes the serotype epidemiology of pneumococcal disease pre- and post-introduction of PCV7, available post-marketing surveillance data following the introduction of higher valency pneumococcal vaccines (PCV10, PCV13) and future prospects for the development of new pneumococcal vaccines. PMID:26344470

  9. Fungal polysaccharides.

    PubMed

    San-Blas, G; Suzuki, S; Hearn, V; Pinel, C; Kobayashi, H; Mendez, C; Niño, G; Nishikawa, A; San-Blas, F; Shibata, N

    1994-01-01

    Fungal polysaccharides are cell wall components which may act as antigens or as structural substrates. As antigens, the role of mannans in Saccharomyces cerevisiae and Candida albicans, and of glycoproteins in Aspergillus fumigatus are discussed. Analyses on beta-glucan synthetase in Paracoccidioides brasiliensis and the inhibitory effect of Hansenula mrakii killer toxin on beta-glucan biosynthesis are also considered.

  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. Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens.

    PubMed Central

    Briles, D E; Forman, C; Horowitz, J C; Volanakis, J E; Benjamin, W H; McDaniel, L S; Eldridge, J; Brooks, J

    1989-01-01

    Antibodies to pneumococcal capsular polysaccharides are well known for their ability to protect against pneumococcal infection. Recent studies indicate that antibodies to cell wall antigens, including pneumococcal surface protein A and the phosphocholine (PC) determinant of teichoic acids as well as human C-reactive protein (which also binds to PC), can protect mice against pneumococcal infection. In the present study we compared the protective effects of these agents as measured by mouse protection, the blood bactericidal assay, and clearance of pneumococci from the blood and peritoneal cavity. Our findings extend previous results indicating that human C-reactive protein and antibodies to noncapsular antigens are generally less protective than anticapsular antibodies. The new results obtained indicate the following: (i) mouse protection studies with intraperitoneal and intravenous infections provide very similar results; (ii) monoclonal immunoglobulin G2a (IgG2a) antibodies to PC, like IgG1, IgG2b, and IgG3 antibodies to PC, are highly protective against pneumococcal infection in mice; (iii) human antibody to PC is able to protect against pneumococcal infection in mice; (iv) antibodies to PspA are effective at mediating blood and peritoneal clearance of pneumococci; (v) complement is required for the in vivo protective effects of both IgG and IgM antibodies to PC; (vi) IgG1, IgG2b, and IgG3 anti-PC antibodies all mediate complement-dependent lysis of PC-conjugated erythrocytes; and (vii) antibodies and human C-reactive proteins that are reactive with capsular antigens but not cell wall antigens are able to mediate significant antibacterial activity in the blood bactericidal assay. PMID:2707854

  12. Directed vaccination against pneumococcal disease

    PubMed Central

    Li, Yi; Hill, Andrew; Beitelshees, Marie; Shao, Shuai; Knight, Paul R.; Hakansson, Anders P.; Pfeifer, Blaine A.; Jones, Charles H.

    2016-01-01

    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

  13. 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.

  14. A novel flow cytometry-based assay for the quantification of antibody-dependent pneumococcal agglutination

    PubMed Central

    van der Gaast—de Jongh, Christa E.; Diavatopoulos, Dimitri A.; de Jonge, Marien I.

    2017-01-01

    The respiratory pathogen Streptococcus pneumoniae is a major cause of diseases such as otitis media, pneumonia, sepsis and meningitis. The first step towards infection is colonization of the nasopharynx. Recently, it was shown that agglutinating antibodies play an important role in the prevention of mucosal colonization with S. pneumoniae. Here, we present a novel method to quantify antibody-dependent pneumococcal agglutination in a high-throughput manner using flow cytometry. We found that the concentration of agglutinating antibodies against pneumococcal capsule are directly correlated with changes in the size and complexity of bacterial aggregates, as measured by flow cytometry and confirmed by light microscopy. Using the increase in size, we determined the agglutination index. The cutoff value was set by measuring a series of non-agglutinating antibodies. With this method, we show that not only anti-polysaccharide capsule antibodies are able to induce agglutination but that also anti-PspA protein antibodies have agglutinating capabilities. In conclusion, we have described and validated a novel method to quantify pneumococcal agglutination, which can be used to screen sera from murine or human vaccination studies, in a high-throughput manner. PMID:28288168

  15. IL-17A and complement contribute to killing of pneumococci following immunization with a pneumococcal whole cell vaccine.

    PubMed

    Campos, Ivana B; Herd, Muriel; Moffitt, Kristin L; Lu, Ying-Jie; Darrieux, Michelle; Malley, Richard; Leite, Luciana C C; Gonçalves, Viviane M

    2017-03-01

    The pneumococcal whole cell vaccine (PWCV) has been investigated as an alternative to polysaccharide-based vaccines currently in use. It is a non-encapsulated killed vaccine preparation that induces non-capsular antibodies protecting mice against invasive pneumococcal disease (IPD) and reducing nasopharyngeal (NP) carriage via IL-17A activation of mouse phagocytes. Here, we show that PWCV induces antibody and IL-17A production to protect mice against challenge in a fatal aspiration-sepsis model after only one dose. We observed protection even with a boiled preparation, attesting to the stability and robustness of the vaccine. PWCV antibodies were shown to bind to different encapsulated strains, but complement deposition on the pneumococcal surface was observed only on serotype 3 strains; using flow cytometer methodology, variations in PWCV quality, as in the boiled vaccine, were detected. Moreover, anti-PWCV induces phagocytosis of different pneumococcal serotypes by murine peritoneal cells in the presence of complement or IL-17A. These findings suggest that complement and IL-17A may participate in the process of phagocytosis induced by PWCV antibodies. IL-17A can stimulate phagocytic cells to kill pneumococcus and this is enhanced in the presence of PWCV antibodies bound to the bacterial cell surface. Our results provide further support for the PWCV as a broad-range vaccine against all existing serotypes, potentially providing protection for humans against NP colonization and IPD. Additionally, we suggest complement deposition assay as a tool to detect subtle differences between PWCV lots.

  16. A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae.

    PubMed

    Denoël, Philippe; Philipp, Mario T; Doyle, Lara; Martin, Dale; Carletti, Georges; Poolman, Jan T

    2011-07-26

    Infections caused by Streptococcus pneumoniae are a major cause of mortality throughout the world. Protein-based pneumococcal vaccines are envisaged to replace or complement the current polysaccharide-based vaccines. In this context, detoxified pneumolysin (dPly) and pneumococcal histidine triad protein D (PhtD) are two potential candidates for incorporation into pneumococcal vaccines. In this study, the protective efficacy of a PhtD-dPly vaccine was evaluated in a rhesus macaque (Macaca mulatta) model of pneumonia. The animals were immunized twice with 10 μg of PhtD and 10 μg of dPly formulated in the Adjuvant System AS02 or with AS02 alone, before they were challenged with a 19F pneumococcal strain. The survival was significantly higher in the protein-vaccinated group and seemed to be linked to the capacity to greatly reduce bacterial load within the first week post-challenge. Vaccination elicited high concentrations of anti-PhtD and anti-Ply antibodies and a link was found between survival and antibody levels. In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

    van den Bosch, W J H M

    2002-05-04

    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.

  4. Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes

    PubMed Central

    van Tonder, Andries J.; Bray, James E.; Quirk, Sigríður J.; Haraldsson, Gunnsteinn; Jolley, Keith A.; Maiden, Martin C. J.; Hoffmann, Steen; Bentley, Stephen D.; Haraldsson, Ásgeir; Erlendsdóttir, Helga; Kristinsson, Karl G.; Brueggemann, Angela B.

    2017-01-01

    The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule (‘serotype’), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within the cps loci of individual serotypes is not well understood. Investigating serotype-specific sequence variation is crucial to the design of sequence-based serotyping methodology, understanding pneumococcal conjugate vaccine (PCV) effectiveness and the design of future PCVs. The availability of large genome datasets makes it possible to assess population-level variation among pneumococcal serotypes and in this study 5405 pneumococcal genomes were used to investigate cps locus diversity among 49 different serotypes. Pneumococci had been recovered between 1916 and 2014 from people of all ages living in 51 countries. Serotypes were deduced bioinformatically, cps locus sequences were extracted and variation was assessed within the cps locus, in the context of pneumococcal genetic lineages. Overall, cps locus sequence diversity varied markedly: low to moderate diversity was revealed among serogroups/types 1, 3, 7, 9, 11 and 22; whereas serogroups/types 6, 19, 23, 14, 15, 18, 33 and 35 displayed high diversity. Putative novel and/or hybrid cps loci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated that cps locus sequence diversity varied widely between serogroups/types. Investigation of the biochemical structure of the polysaccharide capsule of major variants, particularly PCV-related serotypes and those that appear to be novel or hybrids, is warranted. PMID:28133541

  5. 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

  6. 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

  7. Rabbit antibodies to the cell wall polysaccharide of Streptococcus pneumoniae fail to protect mice from lethal challenge with encapsulated pneumococci.

    PubMed Central

    Szu, S C; Schneerson, R; Robbins, J B

    1986-01-01

    A conjugate, composed of the cell wall polysaccharide (C polysaccharide) of Streptococcus pneumoniae and bovine serum albumin (BSA), was prepared with the bifunctional agent N-succinimidyl-3-(2-pyridyldithio)-propionate. Analysis with monoclonal antibodies provided evidence that the phosphocholine (PC) moiety of the C polysaccharide was retained during the conjugation procedure. The C polysaccharide-BSA conjugate elicited antibodies to C polysaccharide in rabbits; no PC-specific antibodies were detected in globulins prepared from these hyperimmune sera obtained early and late after a second immunization. Rabbit hyperimmune sera were taken after multiple intravenous injections of the pneumococcus strain SRC-2, which has a capsulelike structure composed of the C polysaccharide. Globulin prepared from these antisera had both C polysaccharide- and PC-specific antibodies. Antibodies to C polysaccharide elicited by the C polysaccharide-BSA conjugate failed to protect mice against intraperitoneal challenge with a strain of type 3 or type 6A pneumococci. The anti-SRC-2 globulin conferred protection against both of these pneumococcal strains. Absorption of the SRC-2 globulin with C polysaccharide, however, failed to change its protective activity. These data provide evidence that antibodies to the C polysaccharide do not confer immunity against infection of mice with encapsulated pneumococci inoculated by the intraperitoneal route. Images PMID:3095243

  8. 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

  9. Pneumococcal Infections - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Pneumococcal Infections - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Traditional (繁體中文) Farsi (فارسی) Russian (Русский) Spanish (español) Vietnamese (Tiếng Việt) Chinese - Traditional ( ...

  10. Pneumococcal Disease: Risk Factors and Transmission

    MedlinePlus

    ... With conditions that weaken the immune system (HIV/AIDS, cancer, or damaged/absent spleen) With cochlear implants or cerebrospinal fluid (CSF) leaks (escape of the fluid that surrounds the brain and spinal cord) Who smoke cigarettes Transmission Pneumococcal bacteria spread from person-to-person by ...

  11. 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 ...

  12. Burden of Pneumococcal Disease in Northern Togo before the Introduction of Pneumococcal Conjugate Vaccine

    PubMed Central

    Moïsi, Jennifer C.; Makawa, Makawa-Sy; Tall, Haoua; Agbenoko, Kodjo; Njanpop-Lafourcade, Berthe-Marie; Tamekloe, Stanislas; Amidou, Moussa; Mueller, Judith E.; Gessner, Bradford D.

    2017-01-01

    Background S. pneumoniae is a leading cause of meningitis morbidity and mortality in the African meningitis belt, but little is known of its contribution to the burden of pneumonia in the region. We aimed to estimate the incidence of pneumococcal disease in children and adults in northern Togo, before the introduction of pneumococcal conjugate vaccine (PCV). Methods and findings From May 1st 2010 to April 30th 2013, we systematically enrolled all hospitalized patients meeting a case definition of suspected meningitis or clinical pneumonia, residing in Tone or Cinkasse districts, northern Togo and providing informed consent. We collected clinical data and tested biological specimens according to standardized procedures, including bacteriology and PCR testing of cerebro-spinal fluid for meningitis patients and blood cultures and whole blood lytA PCR for pneumonia patients. Chest X-rays (CXR) were interpreted using the WHO methodology. We included 404 patients with meningitis (104 <5 years of age) and 1550 with pneumonia (251 <5 years) over the study period. Of these, 78 (19%) had pneumococcal meningitis (13 <5 years), 574 (37%) had radiologically-confirmed pneumonia (83 <5 years) and 73 (5%) had culture-confirmed pneumococcal pneumonia (2 <5 years). PCV13 serotypes caused 79% (54/68) of laboratory-confirmed pneumococcal meningitis and 83% (29/35) of culture-confirmed pneumococcal pneumonia. Serotype 1 predominated in meningitis (n = 33) but not in pneumonia patients (n = 1). The incidence of pneumococcal disease was 7.5 per 100,000 among children <5 years of age and 14.8 in persons 5 years of age and above in the study area. When considering CXR-confirmed and blood PCR-positive pneumonia cases as likely pneumococcal, incidence estimates increased to 43.7 and 66.0 per 100,000 in each of these age groups, respectively. Incidence was at least 3-fold higher when we restricted the analysis to the urban area immediately around the study hospitals. Conclusions Our findings

  13. Pneumococcal conjugated vaccine: PHiD-CV.

    PubMed

    Dinleyici, Ener Cagri; Yargic, Zeynel Abidin

    2009-11-01

    At the beginning of a new century, we have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline's pediatric pneumococcal candidate vaccine, which is indicated for active immunization against invasive pneumococcal disease (IPD) and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The approved 10-valent pneumococcal vaccine (PHiD-CV) contains all serotypes in 7-valent pneumococcal conjugate vaccine (PCV-7) plus serotypes 1, 5 and 7F. Protein D from nontypeable Haemophilus influenzae is the carrier protein for eight serotypes, while tetanus and diphtheria toxins are in the carrier proteins for the remaining two serotypes. It has also been proved that PHiD-CV is immunogenic, safe and well-tolerated in children. This vaccine can be coadministered with routinely used pediatric vaccines. Noninferiority criteria of PHiD-CV compared with PCV-7 were established in shared serotypes, except for serotypes 6B and 23F, and PHiD-CV is immunogenic for additional serotypes as assessed by the percentage of subjects with antibody concentrations. PHiD-CV is also immunogenic for ten serotypes as assessed by post-primary and post-booster dose opsonophagocytic activity responses. Vaccine efficacy against IPD and other conditions should be monitored for shared serotypes and also additional serotypes during the postmarketing period. Optimal scheduling, safety and immunogenicity data in children with different risk factors for IPD, or whether it will provide herd immunity, are the questions waiting for answers in the postmarketing period. Further studies are needed to assess the potential advantages of protein D as a carrier and the potential efficacy of this new vaccine against H. influenzae. The potential public health efficacy of PHiD-CV in low-income countries

  14. Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

    PubMed Central

    2012-01-01

    Summary: Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development. PMID:22763632

  15. 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. ...

  16. Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.

    PubMed

    Gaillat, J

    2013-06-01

    13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.

  17. 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

    2016-01-01

    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.

  18. 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

  19. 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

  20. 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.

  1. PneumococcaL meningitis in french children before and after the introduction of pneumococcal conjugate vaccine.

    PubMed

    Levy, Corinne; Varon, Emmanuelle; Bingen, Edouard; Lécuyer, Aurélie; Boucherat, Michel; Cohen, Robert

    2011-02-01

    In France, despite a high rate of pneumococcal conjugate vaccine coverage, the number of cases of pneumococcal meningitis in children did not decline significantly between 2001–2002 (n = 264) and 2007–2008 (n = 244). A decline was observed among children < 2 years old (185 [70.1%] to 134 [54.9%] cases; P = 0.0004), but was counterbalanced by an increase among children ≥ 2 years old (79 [29.9%] to 110 [45.1%] cases). Mean age increased significantly, from 2.3 (median 0.8) to 3.8 (median 1.5) years. After pneumococcal conjugate vaccine 7 implementation, a wide diversity of serotypes implicated in pneumococcalmeningitis was observed; serotypes 19A and 7F were the most frequent.

  2. Comparative evaluation of a newly developed 13-valent pneumococcal conjugate vaccine in a mouse model.

    PubMed

    Park, Chulmin; Kwon, Eun-Young; Choi, Su-Mi; Cho, Sung-Yeon; Byun, Ji-Hyun; Park, Jung Yeon; Lee, Dong-Gun; Kang, Jin Han; Shin, Jinhwan; Kim, Hun

    2016-12-14

    Animal models facilitate evaluation of vaccine efficacy at relatively low cost. This study was a comparative evaluation of the immunogenicity and protective efficacy of a new 13-valent pneumococcal conjugate vaccine (PCV13) with a control vaccine in a mouse model. After vaccination, anti-capsular antibody levels were evaluated by pneumococcal polysaccharide (PnP) enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA). Also, mice were challenged intraperitoneally with 100-fold of the 50% lethal dose of Streptococcus pneumoniae. The anti-capsular IgG levels against serotypes 1, 4, 7F, 14, 18C, 19A, and 19F were high (quartile 2 >1,600), while those against the other serotypes were low (Q2 ≤ 800). Also, the OPA titres were similar to those determined by PnP ELISA. Comparative analysis between new PCV13 and control vaccination group in a mouse model exhibited significant differences in serological immunity of a few serotypes and the range of anti-capsular IgG in the population. Challenge of wild-type or neutropenic mice with serotypes 3, 5, 6A, 6B, and 9V showed protective immunity despite of induced relatively low levels of anti-capsular antibodies. With comparison analysis, a mouse model should be adequate for evaluating serological efficacy and difference in the population level as preclinical trial.

  3. Pneumococcal prophages are diverse, but not without structure or history

    PubMed Central

    Brueggemann, Angela B.; Harrold, Caroline L.; Rezaei Javan, Reza; van Tonder, Andries J.; McDonnell, Angus J.; Edwards, Ben A.

    2017-01-01

    Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA. 286 full-length/putatively full-length pneumococcal prophages were identified, of which 163 have not previously been reported. Full-length prophages clustered into four major groups and every group dated from the 1930–40 s onward. There was limited evidence for genes shared between prophage clusters. Prophages typically integrated in one of five different sites within the pneumococcal genome. 72% of prophages possessed the virulence genes pblA and/or pblB. Individual prophages and the host pneumococcal genetic lineage were strongly associated and some prophages persisted for many decades. RNA sequencing provided clear evidence of prophage gene expression. Overall, pneumococcal prophages were highly prevalent, demonstrated a structured population, possessed genes associated with virulence, and were expressed under experimental conditions. Pneumococcal prophages are likely to play a more important role in pneumococcal biology and evolution than previously recognised. PMID:28218261

  4. Pneumococcal prophages are diverse, but not without structure or history.

    PubMed

    Brueggemann, Angela B; Harrold, Caroline L; Rezaei Javan, Reza; van Tonder, Andries J; McDonnell, Angus J; Edwards, Ben A

    2017-02-20

    Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA. 286 full-length/putatively full-length pneumococcal prophages were identified, of which 163 have not previously been reported. Full-length prophages clustered into four major groups and every group dated from the 1930-40 s onward. There was limited evidence for genes shared between prophage clusters. Prophages typically integrated in one of five different sites within the pneumococcal genome. 72% of prophages possessed the virulence genes pblA and/or pblB. Individual prophages and the host pneumococcal genetic lineage were strongly associated and some prophages persisted for many decades. RNA sequencing provided clear evidence of prophage gene expression. Overall, pneumococcal prophages were highly prevalent, demonstrated a structured population, possessed genes associated with virulence, and were expressed under experimental conditions. Pneumococcal prophages are likely to play a more important role in pneumococcal biology and evolution than previously recognised.

  5. 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

  6. 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.

  7. Report of Two Cases of Aseptic Meningitis with Persistence of Pneumococcal Cell Wall Components in Cerebrospinal Fluid after Pneumococcal Meningitis▿

    PubMed Central

    Angoulvant, François; Lachenaud, Julie; Mariani-Kurkdjian, Patricia; Aubertin, Guillaume; Houdouin, Véronique; Lorrot, Mathie; de Los Angeles, Laure; Bingen, Edouard; Bourrillon, Antoine; Faye, Albert

    2006-01-01

    We describe two cases of aseptic meningitis occurring some time after pneumococcal meningitis. Both cases may have resulted from an inflammatory response to persistent pneumococcal cell membrane components, as the cerebrospinal fluid samples were positive by the Binax NOW Streptococcus pneumoniae antigen test. Potential mechanisms and diagnostic impact are discussed. PMID:17005744

  8. Pneumococcal septicemia despite pneumococcal vaccine and prescription of penicillin prophylaxis in children with sickle cell anemia.

    PubMed

    Buchanan, G R; Smith, S J

    1986-05-01

    Although polyvalent pneumococcal vaccine and prophylactic penicillin are used to prevent overwhelming Streptococcus pneumoniae septicemia in infants and young children with sickle cell anemia, infection rates remain high. We have reviewed our seven-year experience with a regimen of twice daily oral penicillin V potassium prophylaxis in 88 affected children. The median age at the start of prophylaxis was 10 months, and the median duration of prophylaxis was 29 months (range, three months to seven years). The total period of observation of patients who were prescribed penicillin was 248 person-years. Most patients also received one or two doses of polyvalent pneumococcal vaccine. Despite penicillin prophylaxis and pneumococcal vaccine, eight episodes of S pneumoniae septicemia have occurred and three have been fatal. Four episodes were in children older than 3 years. Suboptimal compliance with the prescribed oral penicillin regimen was usually apparent. With one possible exception, the infections occurred when penicillin had not been taken during the previous 24 hours. The S pneumoniae septicemia rate in this patient population, 3.2 per 100 person-years, is somewhat less than that described in previous reports of children not receiving penicillin but is still unacceptably high. Vigorous advocacy of a penicillin prophylaxis regimen does not eliminate the risk of pneumococcal septicema in this patient population.

  9. 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.

  10. Reversal of age-associated decline in immune response to Pnu-imune vaccine by supplementation with the steroid hormone dehydroepiandrosterone.

    PubMed Central

    Garg, M; Bondada, S

    1993-01-01

    Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine. PMID:8478117

  11. 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

  12. A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge

    PubMed Central

    Ochs, Martina M.; Williams, Kimberley; Sheung, Anthony; Lheritier, Philippe; Visan, Lucian; Rouleau, Nicolas; Proust, Emilie; de Montfort, Aymeric; Tang, Mei; Mari, Karine; Hopfer, Robert; Gallichan, Scott; Brookes, Roger H.

    2016-01-01

    ABSTRACT Vaccines based on conserved pneumococcal proteins are being investigated because serotype coverage by pneumococcal polysaccharide and polysaccharide conjugate vaccines is incomplete and may eventually decrease due to serotype replacement. Here, we examined the functionality of human antibodies induced by a candidate bivalent choline-binding protein A- pneumococcal histidine triad protein D (PcpA-PhtD) vaccine. Pre- and post-immune sera from subjects who had been vaccinated with the PcpA-PhtD candidate vaccine were tested in an established passive protection model in which mice were challenged by intravenous injection with Streptococcus pneumoniae serotype 3 strain A66.1. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial surface binding by serum antibodies was determined by a flow cytometry-based assay. Sera from 20 subjects were selected based on low activity of pre-immune samples in the passive protection model. Bacterial surface binding correlated more strongly with anti-PcpA (0.87; p < 0.0001) than with anti-PhtD (0.71; p < 0.0001). The odds ratio for predicting survival in the passive protection assay was higher for the anti-PcpA concentration (470 [95% confidence interval (CI), 46.8 to >999.9]) than for the anti-PhtD concentration (3.4 [95% CI, 1.9 to 5.6]) or bacterial surface binding (9.4 [95% CI, 3.6 to 24.3]). Pooled post-immune serum also protected mice against a challenge with S. pneumoniae serotype 3 strain WU2. Both anti-PcpA and anti-PhtD antibodies induced by the bivalent candidate vaccine mediate protection against S. pneumoniae. The results also showed that the ELISA titer might be useful as a surrogate for estimating the functional activity of antibodies induced by pneumococcal protein vaccines. PMID:27392182

  13. A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge.

    PubMed

    Ochs, Martina M; Williams, Kimberley; Sheung, Anthony; Lheritier, Philippe; Visan, Lucian; Rouleau, Nicolas; Proust, Emilie; de Montfort, Aymeric; Tang, Mei; Mari, Karine; Hopfer, Robert; Gallichan, Scott; Brookes, Roger H

    2016-11-01

    Vaccines based on conserved pneumococcal proteins are being investigated because serotype coverage by pneumococcal polysaccharide and polysaccharide conjugate vaccines is incomplete and may eventually decrease due to serotype replacement. Here, we examined the functionality of human antibodies induced by a candidate bivalent choline-binding protein A- pneumococcal histidine triad protein D (PcpA-PhtD) vaccine. Pre- and post-immune sera from subjects who had been vaccinated with the PcpA-PhtD candidate vaccine were tested in an established passive protection model in which mice were challenged by intravenous injection with Streptococcus pneumoniae serotype 3 strain A66.1. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial surface binding by serum antibodies was determined by a flow cytometry-based assay. Sera from 20 subjects were selected based on low activity of pre-immune samples in the passive protection model. Bacterial surface binding correlated more strongly with anti-PcpA (0.87; p < 0.0001) than with anti-PhtD (0.71; p < 0.0001). The odds ratio for predicting survival in the passive protection assay was higher for the anti-PcpA concentration (470 [95% confidence interval (CI), 46.8 to >999.9]) than for the anti-PhtD concentration (3.4 [95% CI, 1.9 to 5.6]) or bacterial surface binding (9.4 [95% CI, 3.6 to 24.3]). Pooled post-immune serum also protected mice against a challenge with S. pneumoniae serotype 3 strain WU2. Both anti-PcpA and anti-PhtD antibodies induced by the bivalent candidate vaccine mediate protection against S. pneumoniae. The results also showed that the ELISA titer might be useful as a surrogate for estimating the functional activity of antibodies induced by pneumococcal protein vaccines.

  14. Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?

    PubMed Central

    Kalyango, Joan; Alfvén, Tobias; Darenberg, Jessica; Kadobera, Daniel; Bwanga, Freddie; Peterson, Stefan; Henriques-Normark, Birgitta; Källander, Karin

    2016-01-01

    Background Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage. Objectives To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda Methods Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped. Results Overall, the carriage rate of S. pneumoniae was 56% (957/1723). Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04). The most common pneumococcal serotypes were in descending order 19F (16%), 23F (9%), 6A (8%), 29 (7%) and 6B (7%). One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13. Conclusion About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs. PMID:27829063

  15. Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guerin vaccines expressing pneumococcal surface protein A

    PubMed Central

    1994-01-01

    Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective antibody responses in mice in the absence of capsular polysaccharide. Whereas PspA is polymorphic, considerable cross-reactivity and cross- protection have been demonstrated among PspA proteins of pneumococci exhibiting different capsular and PspA serotypes. A gene segment encoding the nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guerin (rBCG) vectors, allowing for expression of PspA as a cytoplasmic or secreted protein, or a chimeric exported membrane-associated lipoprotein. All rBCG-PspA strains elicited comparable anti-PspA ELISA titers, ranging from 10(4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice. However, protective responses were observed only in animals immunized with the rBCG-PspA vaccines expressing PspA as a secreted protein or chimeric exported lipoprotein. In addition, anti- PspA immune sera elicited by the rBCG vaccines passively protected X- linked immunodeficient mice from lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular serotypes. These studies confirm previous PspA immunization studies showing cross-protection against heterologous serotypes of S. pneumoniae and demonstrate a potential for rBCG-based PspA vaccines to elicit protective humoral responses against pneumococcal disease in humans. PMID:7964500

  16. Pneumococcal DNA is not detectable in the blood of healthy carrier children by real-time PCR targeting the lytA gene.

    PubMed

    Azzari, Chiara; Cortimiglia, Martina; Moriondo, Maria; Canessa, Clementina; Lippi, Francesca; Ghiori, Federica; Becciolini, Laura; de Martino, Maurizio; Resti, Massimo

    2011-06-01

    The diagnosis of invasive pneumococcal disease (IPD) is currently based on culture methods, which lack sensitivity, especially after antibiotic therapy. Molecular methods have improved sensitivity and do not require viable bacteria; however, their use is complicated by reports of low specificity with some assays. The present study investigated the specificity of a real-time PCR targeting lytA for the detection of IPD. A group of 147 healthy children, aged 6 months to 16 years (mean 6.4 years, median 4.9 years, interquartile range 6.4 years), who were in hospital for routine examinations, were tested for pneumococcal carrier status and for the presence of detectable pneumococcal DNA in their blood by real-time PCR targeting the pneumococcal lytA gene. In addition, 35 culture-positive biological samples were analysed. Urine was examined for the presence of pneumococcal DNA and C-polysaccharide antigen. Carriage was detected in 77 of the 147 subjects (52.4 %); however, regardless of carrier status, none of the subjects had a positive result from blood. Analysis of the culture-positive biological samples yielded positive results in 100 % (15/15) of cerebrospinal fluid samples and 95 % (19/20) of blood samples. All urine samples from healthy carriers were negative for DNA, whilst antigenuria was detected in 44/77 carriers (57.1 %). In conclusion, real-time PCR is both sensitive and specific and can be a useful tool in the routine diagnosis of IPD. Its sensitivity, which surpasses that of other methods for this purpose, does not come at the cost of reduced specificity.

  17. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.

    PubMed

    Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2014-09-29

    In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.

  18. 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.

  19. Increased incidence of adult pneumococcal pneumonia during school holiday periods

    PubMed Central

    Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; McKeever, Tricia M.; Slack, Mary; Lim, Wei Shen

    2017-01-01

    Child contact is a recognised risk factor for adult pneumococcal disease. Peaks in invasive pneumococcal disease incidence observed during winter holidays may be related to changes in social dynamics. This analysis was conducted to examine adult pneumococcal community-acquired pneumonia (CAP) incidence during school holiday periods. Between September 2008 and 2013, consecutive adults admitted to hospitals covering the Greater Nottingham area with a diagnosis of CAP were studied. Pneumococcal pneumonia was detected using culture and antigen detection methods. Of 2221 adults studied, 575 (25.9%) were admitted during school holidays and 643 (29.0%) had pneumococcal CAP. CAP of pneumococcal aetiology was significantly more likely in adults admitted during school holidays compared to term time (35.3% versus 26.7%; adjusted OR 1.38, 95% CI 1.11–1.72, p=0.004). Over the 5-year period, the age-adjusted incidence of hospitalised pneumococcal CAP was higher during school holidays compared to term time (incident rate ratio 1.35, 95% CI 1.14–1.60, p<0.001); there was no difference in rates of all-cause CAP or non-pneumococcal CAP. Reported child contact was higher in individuals with pneumococcal CAP admitted during school holidays compared to term time (42.0% versus 33.7%, OR 1.43, 95% CI 1.00–2.03, p=0.046). Further study of transmission dynamics in relation to these findings and to identify appropriate intervention strategies is warranted. PMID:28326311

  20. 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.

  1. Decline in pneumococcal meningitis after the introduction of the heptavalent‐pneumococcal conjugate vaccine in northern France

    PubMed Central

    Dubos, F; Marechal, I; Husson, M O; Courouble, C; Aurel, M; Martinot, A

    2007-01-01

    Background The impact of the heptavalent‐pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in Europe has not yet been assessed. Objective To determine whether heptavalent‐pneumococcal conjugate vaccine implementation in northern France has resulted in a decrease in the incidence of pneumococcal meningitis in children. Design Multicentre retrospective cohort study from 2000 through 2005. Settings All paediatric departments of the 18 hospitals in northern France. Patients Patients <18 years of age, admitted for laboratory‐confirmed pneumococcal meningitis during the study period, were included. Interventions Data were collected from medical files and the microbiological laboratories of each hospital and compared with the regional hospital discharge codes, using a capture–recapture method. Main outcome measures The study assessed and compared global and age‐related incidence rates of pneumococcal meningitis in 2001 (pre‐vaccine era) and 2005. Results 77 cases were found through the capture–recapture method. The incidence rate of pneumococcal meningitis varied from 1.65/100 000 children <18 years in 2001 to 0.80/100 000 children in 2005 (53% reduction, 95% CI 31 to 74; p = 0.08). This has so far been significant only for children <2 years of age (8.9/100 000 in 2001 to 1.8/100 000 in 2005; 82% reduction, 95% CI 52 to 95; p = 0.03). Conclusion A decline in pneumococcal meningitis has been observed in infants since heptavalent‐pneumococcal conjugate vaccination began in our area. PMID:17626145

  2. Pneumococcal Conjugate Vaccine (PCV13): What You Need to Know

    MedlinePlus

    ... the United States. Treatment of pneumococcal infections with penicillin and other drugs is not as effective as ... should not get PCV13. Anyone with a severe allergy to any component of PCV13 should not get ...

  3. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    PubMed Central

    Joye, Sebastien; Gao, Anja; Kayemba-Kay’s, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-01

    Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death. PMID:24765491

  4. Invasive pneumococcal infection despite 7-valent conjugated vaccine.

    PubMed

    Joye, Sebastien; Gao, Anja; Kayemba-Kay's, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-25

    Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.

  5. 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

  6. Seasonal variation in penicillin susceptibility and invasive pneumococcal disease.

    PubMed

    Iroh Tam, Pui-Ying; Madoff, Lawrence C; O'Connell, Michael; Pelton, Stephen I

    2015-04-01

    We evaluated prospectively laboratory surveillance data from Massachusetts to investigate whether seasonal variation in invasive pneumococcal disease is associated with the proportion of penicillin-susceptible isolates. The proportion of penicillin-susceptible isolates associated with invasive pneumococcal disease varied by season, with proportions highest in the winter and lowest in the summer, and rates of invasive disease were highest in the autumn and winter seasons and lowest in the summer.

  7. Seasonal Variation in Penicillin Susceptibility and Invasive Pneumococcal Disease

    PubMed Central

    Tam, Pui-Ying Iroh; Madoff, Lawrence C.; O'Connell, Michael; Pelton, Stephen I.

    2014-01-01

    We evaluated prospectively laboratory surveillance data from Massachusetts to investigate whether seasonal variation in invasive pneumococcal disease is associated with the proportion of penicillin susceptible isolates. The proportion of penicillin susceptible isolates associated with invasive pneumococcal disease varied by season, with proportions highest in the winter and lowest in the summer, and rates of invasive disease were highest in the autumn and winter seasons and lowest in the summer. PMID:25379834

  8. Pneumococcal vaccination in adults: recommendations, trends, and prospects.

    PubMed

    Targonski, Paul V; Poland, Gregory A

    2007-06-01

    The US Centers for Disease Control and Prevention recommends vaccination against Streptococcus pneumoniae for all people age 65 and older and also for younger people at high risk. However, experts continue to debate the efficacy of the vaccine; most observational studies found it beneficial, while clinical trials were inconclusive as a group. Although pneumococcal vaccination may or may not protect against pneumonia or death from any cause, it does significantly decrease the risk of invasive pneumococcal disease and is worthwhile for this reason.

  9. Climate induces seasonality in pneumococcal transmission.

    PubMed

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

    2015-06-12

    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.

  10. Potential cost-effectiveness and benefit-cost ratios of adult pneumococcal vaccination in Germany

    PubMed Central

    2012-01-01

    Background Invasive (IPD, defined as detection of pneumococci in sterile body fluids like meningitis or bacteremic pneumonia) and non-invasive Streptococcus pneumoniae infections (i.e. non-bacteremic pneumonia, otitis media) in adults are associated with substantial morbidity, mortality and costs. In Germany, Pneumococcal polysaccharide vaccination (PPV23) is recommended for all persons >60 years and for defined risk groups (age 5–59). The aim of this model was to estimate the potential cost-effectiveness and benefit-cost ratios of the adult vaccination program (18 years and older), considering the launch of the pneumococcal conjugate vaccine for adults (PCV13). Methods A cross-sectional steady state Markov model was developed to estimate the outcomes of PCV13, PPV23 vaccination schemes and ‘no vaccination’. Conservative assumptions were made if no data were available for PCV13 and PPV23 respectively. The effectiveness of individual pneumococcal vaccination in adults was adjusted for expected indirect effects due to the vaccination in infants. Data on incidences, effectiveness and costs were derived from scientific literature and publicly available databases. All resources used are indicated. Benefit-cost ratios and cost-effectiveness were evaluated from the perspective of the German Statutory Health Insurance as well as from social perspective. Results Under the assumption that PCV13 has a comparable effectiveness to PCV7, a vaccination program with PCV13 revealed the potential to avoid a greater number of yearly cases and deaths in IPD and pneumonia in Germany compared to PPV23. For PCV13, the costs were shown to be overcompensated by monetary savings resulting from reduction in the use of health care services. These results would render the switch from PPV23 to PCV13 as a dominant strategy compared to PPV23 and ‘no vaccination’. Given the correctness of the underlying assumptions every Euro spent on the PCV13 vaccination scheme yields savings of 2

  11. Uronic polysaccharide degrading enzymes.

    PubMed

    Garron, Marie-Line; Cygler, Miroslaw

    2014-10-01

    In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide.

  12. Macrophage migration inhibitory factor promotes clearance of pneumococcal colonization.

    PubMed

    Das, Rituparna; LaRose, Meredith I; Hergott, Christopher B; Leng, Lin; Bucala, Richard; Weiser, Jeffrey N

    2014-07-15

    Human genetic polymorphisms associated with decreased expression of macrophage migration inhibitory factor (MIF) have been linked to the risk of community-acquired pneumonia. Because Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and nasal carriage is a precursor to invasive disease, we explored the role of MIF in the clearance of pneumococcal colonization in a mouse model. MIF-deficient mice (Mif(-/-)) showed prolonged colonization with both avirulent (23F) and virulent (6A) pneumococcal serotypes compared with wild-type animals. Pneumococcal carriage led to both local upregulation of MIF expression and systemic increase of the cytokine. Delayed clearance in the Mif(-/-) mice was correlated with reduced numbers of macrophages in upper respiratory tract lavages as well as impaired upregulation of MCP-1/CCL2. We found that primary human monocyte-derived macrophages as well as THP-1 macrophages produced MIF upon pneumococcal infection in a pneumolysin-dependent manner. Pneumolysin-induced MIF production required its pore-forming activity and phosphorylation of p38-MAPK in macrophages, with sustained p38-MAPK phosphorylation abrogated in the setting of MIF deficiency. Challenge with pneumolysin-deficient bacteria demonstrated reduced MIF upregulation, decreased numbers of macrophages in the nasopharynx, and less effective clearance. Mif(-/-) mice also showed reduced Ab response to pneumococcal colonization and impaired ability to clear secondary carriage. Finally, local administration of MIF was able to restore bacterial clearance and macrophage accumulation in Mif(-/-) mice. Our work suggests that MIF is important for innate and adaptive immunity to pneumococcal colonization and could be a contributing factor in genetic differences in pneumococcal disease susceptibility.

  13. 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

  14. 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.

  15. Nasopharyngeal Pneumococcal Density and Evolution of Acute Respiratory Illnesses in Young Children, Peru, 2009–2011

    PubMed Central

    Fan, Roger R.; Howard, Leigh M.; Griffin, Marie R.; Edwards, Kathryn M.; Zhu, Yuwei; Williams, John V.; Vidal, Jorge E.; Klugman, Keith P.; Gil, Ana I.; Lanata, Claudio F.

    2016-01-01

    We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities. PMID:27767919

  16. Rates of Pneumococcal Disease in Adults With Chronic Medical Conditions

    PubMed Central

    Shea, Kimberly M.; Edelsberg, John; Weycker, Derek; Farkouh, Raymond A.; Strutton, David R.; Pelton, Stephen I.

    2014-01-01

    Background.  Although it is widely accepted that adults with immunocompromising conditions are at greatly increased risk of pneumococcal infection, the extent of risk among immunocompetent adults with chronic medical conditions is less certain, particularly in the current era of universal vaccination of children with pneumococcal conjugate vaccines. Methods.  We conducted a retrospective cohort study using data from 3 healthcare claims repositories (2006–2010) to compare rates of pneumococcal disease in immunocompetent adults with chronic medical conditions (“at-risk”) and immunocompromised adults (“high-risk”), with rates in adults without these conditions (“healthy”). Risk profiles and episodes of pneumococcal disease—all-cause pneumonia, pneumococcal pneumonia, and invasive pneumococcal disease (IPD)—were ascertained from diagnosis, procedure, and drug codes. Results.  Rates of all-cause pneumonia among at-risk persons aged 18–49 years, 50–64 years, and ≥65 years were 3.2 (95% confidence interval [CI], 3.1–3.2), 3.1 (95% CI, 3.1–3.1), and 3.0 (95% CI, 3.0–3.0) times the rates in age-matched healthy counterparts, respectively. We identified rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and neuromuscular or seizure disorders as additional at-risk conditions for pneumococcal disease. Among persons with at-risk conditions, the rate of all-cause pneumonia substantially increased with the accumulation of concurrent at-risk conditions (risk stacking): among persons 18–49 years, rate ratios increased from 2.5 (95% CI, 2.5–2.5) in those with 1 at-risk condition to 6.2 (95% CI, 6.1–6.3) in those with 2 conditions, and to 15.6 (95% CI, 15.3–16.0) in those with ≥3 conditions. Findings for pneumococcal pneumonia and IPD were similar. Conclusions.  Despite widespread use of pneumococcal conjugate vaccines, rates of pneumonia and IPD remain disproportionately high in adults with at-risk conditions

  17. Invasive pneumococcal infection in South and West England.

    PubMed Central

    Smith, M. D.; Stuart, J.; Andrews, N. J.; Telfer Brunton, W. A.; Cartwright, K. A.

    1998-01-01

    Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines. PMID:9593479

  18. Characterization of multivalent pneumococcal conjugate vaccines.

    PubMed

    Katkocin, D M

    2000-01-01

    A new heptavalent pneumococcal conjugate vaccine, designed to protect against disease due to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was formulated with aluminium phosphate adjuvant and analysed before testing in infants. Analyses were complicated by the presence of the adjuvant, and by the low level of each antigen; for example, all serotypes were formulated at 2 microg of saccharide /dose (except 6B which was formulated at 4 microg). Type specific analyses were performed on the formulated vaccine, and included determination of immunogenicity and antigenicity; the former was measured by ELISA following immunization of rabbits, the latter was measured by rate nephelometry. Non serotype specific information was also collected, and included total and adsorbed saccharide (by Anthrone assay), and total and adsorbed protein (by Lowry assay). These preclinical data supported the use of the vaccine in infants in a large randomized double-blinded clinical trial in a multiethnic population. The results of this trial show that the vaccine is safe and efficacious. Collectively, the data will be used to support licensure of the heptavalent vaccine, and documents successful scale-up of the formulation process to manufacturing level.

  19. [Pneumococcal vaccines in children: an update].

    PubMed

    Potin, Marcela

    2014-08-01

    Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

  20. Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

    PubMed

    Werno, Anja M; Murdoch, David R

    2008-03-15

    The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

  1. Effect of Adjuvants on Response to Pneumococcal Polysaccharide Injected Intraperitoneally. Platelet-Derived Immunoregulatory Activity.

    DTIC Science & Technology

    1984-07-01

    forming cell (PFC) response in the spleen is observed [ Katz et al., J. Natl. Cancer Inst. 72:125, 1984]. This suppression has been interpFeteas due to the...University Dr. Phyllis R. Struass Department of Biology Dr. Hillel B. Levine Northeastern University Naval Biosciences Laboratory 360 Huntington Avenue

  2. 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

  3. Pneumococcal Meningitis Vaccine Breakthroughs and Failures After Routine 7-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Children in France.

    PubMed

    Godot, Cécile; Levy, Corinne; Varon, Emmanuelle; Picard, Capucine; Madhi, Fouad; Cohen, Robert

    2015-10-01

    We collected cases of pneumococcal meningitis vaccine breakthrough (VBT) and vaccine failure (VF) from 2003 to 2013 after the implementation of pneumococcal conjugate vaccines (PCVs) in France. VBT accounted for 3.2% of the cases (PCV7 era: 24 of 943, PCV13 era: 15 of 290) and VF 0.6% (PCV7 era: 6 of 943, PCV13 era: 2 of 290). VBT and VF are rare and occur in most cases in children younger than 2 years. The serotype 19F was the most frequent cause even after the introduction of PCV13.

  4. Rapid diagnosis of invasive pneumococcal disease in pediatric population.

    PubMed

    Picazo, Juan Jose; Contreras, Jesús Ruiz; Ríos, Esther; Culebras, Esther; Rodríguez-Avial, Iciar; Méndez, Cristina; Betriu, Carmen

    2013-05-01

    The aim of this study was to evaluate the Binax NOW immunochromatographic pneumococcal antigen test for the identification of Streptococcus pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease. The results were compared with those obtained by PCR. Binax NOW was applied to these samples as recommended by the manufacturer for urine and cerebrospinal samples. Detection of pneumococcal DNA was performed by real-time PCR assay targeting the autolysin gene (lytA). Of the 199 samples analyzed, 131 were positive by both Binax NOW and lytA PCR, and 36 samples were negative by both techniques. Using the real-time PCR as a comparative method to the Binax for the detection of S. pneumoniae, the sensitivity and specificity of Binax NOW was 88% and 72.5%, respectively. Of the 145 positive samples analyzed by Binax NOW, 119 showed intense coloring of the sample line and 26 showed weak intensity. Conventional culture is the most common method in clinical settings, but Binax NOW is an easier and faster test for identifying S. pneumoniae in pleural and cerebrospinal fluids from children with suspected invasive pneumococcal disease.

  5. Pneumococcal pneumonia: differences according to blood culture results

    PubMed Central

    2014-01-01

    Background Bacteremia by Streptococcus pneumoniae has been traditionally associated with poor outcomes in patients with pneumonia; however, data on its impact on outcomes are limited and are sometimes contradictory. Methods We performed a prospective study in two hospitals in northern Spain in which cases diagnosed with pneumococcal pneumonia were selected from a cohort of hospitalized patients with pneumonia between January 2001 and July 2009. We compared patients with pneumococcal bacteremic pneumonia with those with pneumococcal non-bacteremic pneumonia. Results We compared 492 patients with negative blood culture and 399 with positive culture results. Host related factors were very similar in both groups. Severity of illness on admission measured by CURB-65 score was similar in both groups. Adjusted analysis showed a greater likelihood of septic shock during in-hospital course among patients with pneumococcal bacteremia (OR, 2.1; 95% CI, 1.2–3.5; P = 0.006). Likewise, patients with positive blood culture had greater in-hospital mortality (OR 2.1; 95% CI, 1.1 - -3.9; P = 0.02), 15-day mortality (OR 3.6; 95% CI, 1.7 - 7.4; P = 0.0006), and 30-day mortality (OR, 2.7; 95% CI, 1.5 - 5; P = 0.002). Conclusions Although host related factors and severity on admission were very similar in the two groups, bacteremic patients had worse in-hospital course and outcomes. Bacteraemia in pneumococcal pneumonia is of prognostic significance. PMID:25096919

  6. 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

  7. CAPSULAR POLYSACCHARIDE OF AZOTOBACTER AGILIS.

    PubMed

    COHEN, G H; JOHNSTONE, D B

    1964-12-01

    Cohen, Gary H. (University of Vermont, Burlington), and Donald B. Johnstone. Capsular polysaccharide of Azotobacter agilis. J. Bacteriol. 88:1695-1699. 1964.-Capsular polysaccharide from Azotobacter agilis strain 132 was recovered from washed cells by alkaline digestion. The polysaccharide was purified by centrifugation, repeated alcohol precipitation, Sevag deproteinization, and treatment with ribonuclease and charcoal-cellulose. Methods of isolation and purification appeared to provide a polymer showing no evidence of heterogeneity when examined by chemical and physical methods. Colorimetric, paper chromatographic, and enzymatic analyses on both intact and acid-hydrolyzed polysaccharide indicated that the polymer contained galactose and rhamnose at a molar ratio of approximately 1.0:0.7. A sialic acid-like component was also present in the polysaccharide. The study shows significant differences in the chemical composition of the extra-cellular polysaccharide of A. agilis and that of A. vinelandii. This adds further biochemical evidence for the right of these species to independent status.

  8. 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

  9. The Differential Impact of Coadministered Vaccines, Geographic Region, Vaccine Product and Other Covariates on Pneumococcal Conjugate Vaccine Immunogenicity

    PubMed Central

    2014-01-01

    Background: Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels. Methods: We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ≥ 2 primary doses of PCV before 6 months of age in non–high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method. Results: Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC. Conclusions: PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be

  10. The polysaccharide capsule of Streptococcus pneumonia partially impedes MyD88-mediated immunity during pneumonia in mice.

    PubMed

    de Vos, Alex F; Dessing, Mark C; Lammers, Adriana J J; de Porto, Alexander P N A; Florquin, Sandrine; de Boer, Onno J; de Beer, Regina; Terpstra, Sanne; Bootsma, Hester J; Hermans, Peter W; van 't Veer, Cornelis; van der Poll, Tom

    2015-01-01

    Toll-like receptors (TLR) and the downstream adaptor protein MyD88 are considered crucial for protective immunity during bacterial infections. Streptococcus (S.) pneumoniae is a human respiratory pathogen and a large majority of clinical pneumococcal isolates expresses an external polysaccharide capsule. We here sought to determine the role of pneumococcal capsule in MyD88-mediated antibacterial defense during S. pneumonia pneumonia. Wild type (WT) and Myd88(-/-) mice were inoculated intranasally with serotype 2 S. pneumoniae D39 or with an isogenic capsule locus deletion mutant (D39∆cps), and analysed for bacterial outgrowth and inflammatory responses in the lung. As compared to WT mice, Myd88(-/-) mice infected with D39 demonstrated a modestly impaired bacterial clearance accompanied by decreased inflammatory responses in the lung. Strikingly, while WT mice rapidly cleared D39∆cps, Myd88(-/-) mice showed 105-fold higher bacterial burdens in their lungs and dissemination to blood 24 hours after infection. These data suggest that the pneumococcal capsule impairs recognition of TLR ligands expressed by S. pneumoniae and thereby partially impedes MyD88-mediated antibacterial defense.

  11. Economic perspectives on the advance market commitment for pneumococcal vaccines.

    PubMed

    Snyder, Christopher M; Begor, Wills; Berndt, Ernst R

    2011-08-01

    Pharmaceutical companies have long been reluctant to invest in producing new vaccines for the developing world because they have little prospect of earning an attractive return. One way to stimulate such investment is the use of an advance market commitment, an innovative financing program that guarantees manufacturers a long-term market. Under this arrangement, international donors pay a premium for initial doses sold to developing countries. In exchange, companies agree to continue supplying the vaccine over the longer term at more sustainable prices. This article provides a preliminary economic analysis of a pilot advance market commitment program for pneumococcal vaccines, explaining the principles behind the program's design and assessing its early performance. Spurred by the advance market commitment--and other contemporaneous initiatives that also increased resources to vaccine suppliers--new, second-generation pneumococcal vaccines have experienced a much more rapid rollout in developing countries than older first-generation vaccines.

  12. Periodic lateralized epileptiform discharges as manifestation of pneumococcal meningoencephalitis

    PubMed Central

    2011-01-01

    Periodic Lateralized Epileptiform Discharges (PLEDs) are usually seen in the context of destructive structural lesions of the cortex, more frequently in acute ischemic stroke and less common in tumours and meningoencephalitis, specially herpes simplex virus. Its origin and prognosis are uncertain but it is known that PLEDs are linked to epilectic seizures, including status epilepticus. We report on a 75-year old woman with pneumococcal meningoencephalitis who presented altered level of consciousness, acute focal deficits, convulsive seizures and PLEDs in left hemisphere. The finding of PLEDs on the electroencephalogram is related to focal lesions of heterogeneous origin, which up to date, have not been documented in pneumococcal infections of the central nervous system. Our case highlights the importance of identifying and addressing any modifiable etiologic factors of PLEDs. PMID:21703002

  13. 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...

  14. Pneumococcal Colonization in the Familial Context and Implications for Anti-Pneumococcal Immunization in Adults: Results from the BINOCOLO Project in Sicily

    PubMed Central

    Tramuto, Fabio; Amodio, Emanuele; Calamusa, Giuseppe; Restivo, Vincenzo; Costantino, Claudio; Vitale, Francesco

    2017-01-01

    The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing of pneumococcal serotypes covered by the vaccine. Oropharyngeal samples of 146 subjects belonging to 36 different family groups were molecularly tested for pneumococcal detection and serotyping. The overall prevalence of pneumococcal carriage was 65.8% (n = 96/146), whereas it was higher among schoolchildren (77.8%, n = 28/36); subjects of seven years of age had the highest odds of being colonized (odds ratio, OR = 5.176; p = 0.145). Pneumococcal serotypes included in the 13-valent conjugate vaccine formulation were largely detected in the study population and multiple serotypes colonization was considerable. Factors relating to a close proximity among people at the family level were statistically associated with pneumococcal carriage (OR = 2.121; p = 0.049), as well as active smoking habit with a clear dose-response effect (ORs = 1.017–3.326). About half of family clusters evidenced similar patterns of carried pneumococcal serotypes and the odds of sustaining a high level of intrafamilial sharing increased with household size (ORs = 1.083–5.000). This study highlighted the potential role played by the family environment in sustaining both the circulation and horizontal transmission of pneumococcus. PMID:28067813

  15. Changes in the features of invasive pneumococcal disease after introduction of the seven-valent pneumococcal conjugate vaccine in a regional core hospital of Kochi, Japan.

    PubMed

    Miyahara, Hiroyuki; Maruyama, Hidehiko; Kanazawa, Akane; Iwasaki, Yuka; Shigemitsu, Yusuke; Watanabe, Hirokazu; Tokorodani, Chiho; Miyazawa, Mari; Nakata, Yusei; Nishiuchi, Ritsuo; Kikkawa, Kiyoshi

    2015-01-01

    Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2007, invasive pneumococcal disease has declined, but the incidence of Streptococcus pneumoniae serotype 19A has risen worldwide. The present study examined changes in the features of invasive pneumococcal disease since the introduction of the PCV7 in Kochi, Japan. Pediatric cases of invasive pneumococcal disease were investigated before and after vaccine introduction (January 2008 to December 2013). Cases of invasive pneumococcal disease tended to decrease after PCV7 introduction. In addition, before introduction of the vaccine, most serotypes causing invasive pneumococcal disease were those included in the vaccine. However, after the introduction, we found cases infected by serotypes not covered by vaccine. Penicillin-resistant S. pneumoniae was the predominant serotype causing invasive pneumococcal disease before introduction of the PCV7, and the susceptibility of this serotype to antibiotics improved after vaccine introduction. Serotype isolates identified after vaccine introduction were also relatively susceptible to antibiotic therapy, but decreased susceptibility is expected.

  16. Towards the 13-valent pneumococcal conjugate universal vaccination

    PubMed Central

    Martinelli, Domenico; Pedalino, Biagio; Cappelli, Maria Giovanna; Caputi, Giovanni; Sallustio, Anna; Fortunato, Francesca; Tafuri, Silvio; Cozza, Vanessa; Germinario, Cinzia; Chironna, Maria; Prato, Rosa; surveillance of pediatric IPD, Apulian Group for the

    2014-01-01

    Pneumococcal disease epidemiology has changed after introduction of pneumococcal conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated at 78% (95% CI: −18–96%) for 2-priming doses. In Italy, PCV7 was introduced in 2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated PCV program effectiveness and its impact on S. pneumoniae diseases. PCV Effectiveness: We used the screening method. We calculated the Proportion of Population Vaccinated from immunization registries and detected cases through a laboratory-confirmed surveillance among hospitalized children ≤60 months. A confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences among children were assessed with the Chi-square or the Fisher exact test (P value < 0.05). PCV Impact: We constructed time series using outcome-specific Poisson regression models: hospitalization rate in pre-PCV era and hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13 shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0–84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated) by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21–0.90). The PCV program show promising results in terms of both PCV13 effectiveness and its impact in reducing IPD in children <5 years. PMID:24096297

  17. The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America.

    PubMed

    Giglio, Norberto; Micone, Paula; Gentile, Angela

    2011-09-14

    Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.

  18. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    PubMed Central

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  19. 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

  20. Polysaccharides of the red algae.

    PubMed

    Usov, Anatolii I

    2011-01-01

    Red algae (Rhodophyta) are known as the source of unique sulfated galactans, such as agar, agarose, and carrageenans. The wide practical uses of these polysaccharides are based on their ability to form strong gels in aqueous solutions. Gelling polysaccharides usually have molecules built up of repeating disaccharide units with a regular distribution of sulfate groups, but most of the red algal species contain more complex galactans devoid of gelling ability because of various deviations from the regular structure. Moreover, several red algae may contain sulfated mannans or neutral xylans instead of sulfated galactans as the main structural polysaccharides. This chapter is devoted to a description of the structural diversity of polysaccharides found in the red algae, with special emphasis on the methods of structural analysis of sulfated galactans. In addition to the structural information, some data on the possible use of red algal polysaccharides as biologically active polymers or as taxonomic markers are briefly discussed.

  1. 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

  2. Why were polysaccharides necessary?

    PubMed

    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.

  3. 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.

  4. 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.

  5. Polysaccharides from Extremophilic Microorganisms

    NASA Astrophysics Data System (ADS)

    Nicolaus, B.; Moriello, V. Schiano; Lama, L.; Poli, A.; Gambacorta, A.

    2004-02-01

    Several marine thermophilic strains were analyzed for exopolysaccharide production. The screening process revealed that a significant number of thermophilic microorganisms were able to produce biopolymers, and some of them also revealed interesting chemical compositions. We have identified four new polysaccharides from thermophilic marine bacteria, with complex primary structures and with different repetitive units: a galacto-mannane type from strain number 4004 and mannane type for the other strains. The thermophilic Bacillus thermantarcticus produces two exocellular polysaccharides (EPS 1, EPS 2) that give the colonies a typical mucous character. The exopolysaccharide fraction was produced with all substrates assayed, although a higher yield 400 mg liter-1 was obtained with mannose as carbon and energy source. NMR spectra confirmed that EPS 1 was a heteropolysaccharide of which the repeating unit was constituted by four different α-D-mannoses and three different β-D-glucoses. It seems to be close to some xantan polymers. EPS 2 was a mannan. Four different α-D-mannoses were found as the repeating unit. Production and chemical studies of biopolymers produced by halophilic archaea, Haloarcula species were also reported.

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

    PubMed Central

    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.; Leggio, Leila Lo; Walton, Paul H.

    2016-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which 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 the first 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

  7. Pneumococcal carriage in children attending a hospital outpatient clinic in the era of pneumococcal conjugate vaccines in Barcelona.

    PubMed

    Hernandez-Bou, Susanna; Garcia-Garcia, Juan Jose; Gene, Amadeu; Esteva, Cristina; del Amo, Eva; Muñoz-Almagro, Carmen

    2012-11-01

    Between April 2004 and March 2006 an oropharyngeal swab was obtained from 502 asymptomatic children, aged 6 months to 6 years, at a tertiary children's hospital outpatient department to assess the pneumococcal colonisation rate, risk factors, serotype distribution and antimicrobial susceptibility. Only 126 (25.3%) children had received ≥ 1 dose of PCV7. The pneumococcal carriage rate was 23.5%. Carrier rates were significantly higher in children aged ≥ 24 months and children attending daycare center. Thirty six (31.0%) of the isolates were contained in PCV7, 39 (33.6%) in PCV10 and 62 (53.4%) in PCV13. Forty-four strains (37.9%) were resistant to penicillin. Vaccine serotype (VT) strains were more likely to be penicillin-nonsusceptible S. pneumoniae than non-PCV7 serotype (NVT) strains (66.7% vs. 21.6%; P < 0.001). In our pediatric population, NVT were predominant among pneumococcal carriers whereas antibiotic resistance was significantly associated with VT. PCV13 can substantially increase the serotype coverage of S.pneumoniae in healthy carriers.

  8. Impact on CDC Guideline Compliance After Incorporating Pharmacy in a Pneumococcal Vaccination Screening Process.

    PubMed

    Pickren, Elizabeth; Crane, Brad

    2016-12-01

    Background: Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccinations were updated in 2014. Given the complexity of the guidelines and the fact that hospitals are no longer required to keep records for pneumococcal vaccinations, many hospitals are determining whether to continue this service. Objective: The primary objective of this study was to determine the impact on compliance with the revised pneumococcal vaccination guidelines from the CDC after involving pharmacy in the screening and selection processes. Secondary objectives were to determine the impact of the new process on inappropriate vaccination duplications, the time spent by pharmacy on assessments, and financial outcomes. Methods: This institutional review board (IRB)-approved, retrospective, cohort study examined all patients who received a pneumococcal vaccination from January to February 2016 after implementing a new process whereby pharmacy performed pneumococcal vaccination screening and selection (intervention group). These patients were compared to patients who received a pneumococcal vaccination from January to February 2015 (control group). Results: Of 274 patients who received a pneumococcal vaccine, 273 were included in the study. Compliance to CDC guidelines increased from 42% to 97%. Noncompliant duplications decreased from 16% to 2%. In the intervention group, labor cost for assessments and expenditure for vaccines increased. For Medicare patients, the increased reimbursement balanced the increased expenditure in the intervention group. Conclusions: Involving pharmacy in the pneumococcal vaccine screening and selection process improves compliance to CDC guidelines, but further clinical and financial analysis is needed to determine financial sustainability of the new process.

  9. The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease.

    PubMed

    Bliss, Sandra J; O'Brien, Katherine L; Janoff, Edward N; Cotton, Mark F; Musoke, Philippa; Coovadia, Hoosen; Levine, Orin S

    2008-01-01

    Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and efficacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have significantly increased risk of pneumococcal disease compared with uninfected children; the serotypes included in currently licensed or near-licensure conjugate vaccines include most serotypes that cause invasive pneumococcal disease (IPD) in HIV-infected children and adults; PCVs provide substantial protection against IPD and clinical pneumonia when given to HIV-infected infants; and HIV-infected adults gain an indirect benefit when children in the community are vaccinated. PCV should be considered as an important intervention for improving the lives of HIV-infected children.

  10. Seasonal Drivers of Pneumococcal Disease Incidence: Impact of Bacterial Carriage and Viral Activity

    PubMed Central

    Weinberger, Daniel M.; Grant, Lindsay R.; Steiner, Claudia A.; Weatherholtz, Robert; Santosham, Mathuram; Viboud, Cécile; O'Brien, Katherine L.

    2014-01-01

    Background. Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses. Methods. We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors. Results. The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%–26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, −4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%–51.4%) but not with bacteremic pneumonia. Conclusions.The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal

  11. Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

    PubMed Central

    Andam, Cheryl P.; Harris, Simon R.; Cornick, Jennifer E.; Yang, Marie; Bricio-Moreno, Laura; Kamng’ona, Arox W.; French, Neil; Heyderman, Robert S.; Kadioglu, Aras; Everett, Dean B.; Bentley, Stephen D.

    2016-01-01

    ABSTRACT Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. PMID:27677790

  12. 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.

  13. 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.

  14. Dendritic Cells Pulsed with Intact Streptococcus pneumoniae Elicit both Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses In Vivo through Distinct Mechanisms

    DTIC Science & Technology

    2002-01-07

    polysaccharide type 14; CT LA, cytotoxic T lymphocyte antigen; MFI, mean fluores- cence intensity; PC, phosphorylcholine ; PsaA, pneumococcal surface ad- hesion...chromatography (25). Phosphorylcholine (PC)- KLH, a gift of Andrew Lees (Biosynexus, Inc.), was synthesized as described previously (6). The resulting...responses to foreign and self-antigens by the CD19/ CD21 complex. Annu. Rev. Immunol. 18:393–422. 48. Harnett, W., and M.M. Harnett. 1999. Phosphorylcholine : friend or foe of the immune system? Immunol. Today. 20: 125–129.

  15. Herd immunity and pneumococcal conjugate vaccine: a quantitative model.

    PubMed

    Haber, Michael; Barskey, Albert; Baughman, Wendy; Barker, Lawrence; Whitney, Cynthia G; Shaw, Kate M; Orenstein, Walter; Stephens, David S

    2007-07-20

    Invasive pneumococcal disease in older children and adults declined markedly after introduction in 2000 of the pneumococcal conjugate vaccine for young children. An empirical quantitative model was developed to estimate the herd (indirect) effects on the incidence of invasive disease among persons >or=5 years of age induced by vaccination of young children with 1, 2, or >or=3 doses of the pneumococcal conjugate vaccine, Prevnar (PCV7), containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. From 1994 to 2003, cases of invasive pneumococcal disease were prospectively identified in Georgia Health District-3 (eight metropolitan Atlanta counties) by Active Bacterial Core surveillance (ABCs). From 2000 to 2003, vaccine coverage levels of PCV7 for children aged 19-35 months in Fulton and DeKalb counties (of Atlanta) were estimated from the National Immunization Survey (NIS). Based on incidence data and the estimated average number of doses received by 15 months of age, a Poisson regression model was fit, describing the trend in invasive pneumococcal disease in groups not targeted for vaccination (i.e., adults and older children) before and after the introduction of PCV7. Highly significant declines in all the serotypes contained in PCV7 in all unvaccinated populations (5-19, 20-39, 40-64, and >64 years) from 2000 to 2003 were found under the model. No significant change in incidence was seen from 1994 to 1999, indicating rates were stable prior to vaccine introduction. Among unvaccinated persons 5+ years of age, the modeled incidence of disease caused by PCV7 serotypes as a group dropped 38.4%, 62.0%, and 76.6% for 1, 2, and 3 doses, respectively, received on average by the population of children by the time they are 15 months of age. Incidence of serotypes 14 and 23F had consistent significant declines in all unvaccinated age groups. In contrast, the herd immunity effects on vaccine-related serotype 6A incidence were inconsistent. Increasing trends of non

  16. Antiretroviral Therapy as Prevention of … Pneumococcal Infections?

    PubMed Central

    Leporrier, Jérémie; Delbos, Valérie; Unal, Guillemette; Honoré, Patricia; Etienne, Manuel; Bouchaud, Olivier; Caron, François

    2016-01-01

    Background. Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. Methods. The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000–2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. Results. Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or “classic” risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). Conclusions. Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an “at-risk patient” targeted pneumococcal vaccination strategy. PMID:28018929

  17. Evaluation of vancomycin for therapy of adult pneumococcal meningitis.

    PubMed Central

    Viladrich, P F; Gudiol, F; Liñares, J; Pallarés, R; Sabaté, I; Rufí, G; Ariza, J

    1991-01-01

    The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy. PMID:1810180

  18. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

    PubMed Central

    Coimbra, Roney S; Voisin, Veronique; de Saizieu, Antoine B; Lindberg, Raija LP; Wittwer, Matthias; Leppert, David; Leib, Stephen L

    2006-01-01

    Background Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy. PMID

  19. Characteristics and prognosis of pneumococcal endocarditis: a case-control study.

    PubMed

    Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M

    2016-06-01

    Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p <0.01), smoking (60.7% versus 21.4%; p <0.01), the absence of previously known valve disease (82.1% versus 60.7%; p 0.047), heart failure (64.3% versus 23.2%; p <0.01) and shock (53.6% versus 23.2%; p <0.01) were more common in pneumococcal than in non-pneumococcal endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases.

  20. Preparation of polysaccharides from wax gourd.

    PubMed

    Huang, Gangliang; Tan, Jiantao; Tan, Xianchun; Peng, Daquan

    2011-08-01

    Preparation of polysaccharides from the wax gourd was studied. The crude polysaccharides were extracted by ethanol precipitation, and deproteinized by the hydrochloric acid method. The deproteinized polysaccharides were separated by column chromatography to obtain the pure polysaccharides. The pure polysaccharides have a β-D-pyranosidic bond, and their molecular weight distribution is about 22,500. It was indicated that the final product had much more purity by IR spectrum analysis, UV absorption spectrum analysis, and phenol-sulfuric acid method, respectively. It was proved that wax gourd polysaccharides were composed of rhamnose, xylose, arabinose, mannose, glucose, and galactose by thin layer chromatography.

  1. 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.

  2. Systematic Evaluation of Serotypes Causing Invasive Pneumococcal Disease among Children Under Five: The Pneumococcal Global Serotype Project

    PubMed Central

    Johnson, Hope L.; Deloria-Knoll, Maria; Levine, Orin S.; Stoszek, Sonia K.; Freimanis Hance, Laura; Reithinger, Richard; Muenz, Larry R.; O'Brien, Katherine L.

    2010-01-01

    Background Approximately 800,000 children die each year due to pneumococcal disease and >90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children <5 years of age. Methods and Findings We systematically reviewed studies with IPD serotype data among children <5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with ≥12 months of surveillance, and reporting ≥20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for ≥70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for >300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide. Conclusions A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%–88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines. Please see later in the article for the Editors' Summary PMID:20957191

  3. Changes in the composition of the pneumococcal population and in IPD incidence in The Netherlands after the implementation of the 7-valent pneumococcal conjugate vaccine.

    PubMed

    Elberse, Karin E M; van der Heide, Han G J; Witteveen, Sandra; van de Pol, Ingrid; Schot, Corrie S; van der Ende, Arie; Berbers, Guy A M; Schouls, Leo M

    2012-12-14

    The implementation of nationwide pneumococcal vaccination may lead to alterations in the pneumococcal population due to selective pressure induced by the vaccine. To monitor such changes, pneumococcal isolates causing invasive pneumococcal disease (IPD) before (2004-2005, n=1154) and after (2008-2009, n=1190) the implementation of the 7-valent pneumococcal vaccine (PCV7) in 2006 in the national immunization program (NIP) of The Netherlands were characterized by molecular typing using multiple-locus variable number tandem repeat analysis (MLVA) and capsular sequence typing (CST). The IPD incidence after the implementation of PCV7 in children <5 years of age declined, mainly due to an impressive reduction of cases caused by vaccine serotypes. In the age group of patients ≥5 years of age, the overall IPD incidence remained constant, but the IPD incidence due to vaccine serotypes declined in this age cohort as well, indicating herd immunity. IPD incidence of non-vaccine serotypes 1 and 22F isolates increased significantly and a shift in genetic background of the isolates belonging to these serotypes was observed. In general the composition of the pneumococcal population remained similar after the introduction of PCV7. Both before and after introduction of the vaccine several possible capsular switch events were noticed. We found 4 isolates from the pre-vaccination period in which the serotype 19F capsular locus had been horizontally transferred to a different genetic background. Remarkably, none of the 5 post-vaccination isolates in which we observed possible capsule switch belonged to the 19F serotype, possibly due to vaccine induced pressure. In the post-vaccine implementation period we found no evidence for capsular switch of a vaccine serotype to a non-vaccine serotype, indicating that capsular switch is not the main driving force for replacement. This study provides insights into the effects of nationwide vaccination on the pneumococcal population causing IPD.

  4. The relationship between pneumococcal serotypes and antibiotic resistance.

    PubMed

    Song, Jae-Hoon; Dagan, Ron; Klugman, Keith P; Fritzell, Bernard

    2012-04-05

    Streptococcus pneumoniae (SP) causes significant burden of disease, including invasive pneumococcal disease and noninvasive diseases such as pneumonia and acute otitis media. SP has at least 93 different capsular serotypes, with the various serotypes having different propensities for producing disease or developing antibiotic resistance. An increase in the prevalence of antibiotic-resistant SP serotypes has been observed globally. The objective of this paper was to examine the relationship between antibiotic resistance and SP serotypes, with a primary focus on studies published in the past 10 years. Changing trends in antibiotic resistance and serotype distribution during this time, including those before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), were analyzed. Factors that influence the prevalence of antibiotic-resistant serotypes include antibiotic selection pressure, the use of PCV7, and the emergence and spread of antibiotic-resistant clones. The emergence of multidrug resistant serotype 19A is of particular concern. Antibiotic-resistant SP is a global problem that must be addressed through multiple strategies, including national vaccination programs, antibiotic control programs, and ongoing surveillance.

  5. Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

    PubMed Central

    Shen, Pamela; Morissette, Mathieu C.; Vanderstocken, Gilles; Gao, Yang; Hassan, Muhammad; Roos, Abraham; Thayaparan, Danya; Merlano, Maria; Dorrington, Michael G.; Nikota, Jake K.; Bauer, Carla M. T.; Kwiecien, Jacek M.; Labiris, Renee; Bowdish, Dawn M. E.; Stevenson, Christopher S.

    2016-01-01

    Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden. PMID:26930709

  6. 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.

  7. Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis

    PubMed Central

    Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment. PMID:24699535

  8. Rethinking risk for pneumococcal disease in adults: the role of risk stacking.

    PubMed

    Pelton, Stephen I; Shea, Kimberly M; Weycker, Derek; Farkouh, Raymond A; Strutton, David R; Edelsberg, John

    2015-01-01

    Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions.

  9. Pneumococcal disease in the Arabian Gulf: recognizing the challenge and moving toward a solution.

    PubMed

    Feldman, Charles; Abdulkarim, Emad; Alattar, Fatma; Al Lawati, Faryal; Al Khatib, Hisham; Al Maslamani, Muna; Al Obaidani, Idris; Al Salah, Mosaab; Farghaly, Mohamed; Husain, Entesar H; Mokadas, Eiman

    2013-12-01

    Pneumococcal disease has substantial incidence, morbidity and mortality in older adults. Decreased birth rates and longer lifespans indicate that the global population is aging, although rates of aging differ between countries [1]. In 2010, the proportion of the population aged >60 years in the general Arab Region was 7%, and this proportion is expected to rise to 19% by 2050 for the region as a whole [2]; the United Nations estimates for the individual countries of the Arabian Gulf by 2050 are 25.7%, 24.9%, 20.7%, 26.7% and 10.5% in the Kuwait, Bahrain, Qatar, United Arab Emirates (UAE) and Oman, respectively, which are comparable to the 26.9% predicted for the USA and lower than that predicted in European countries, in which the 2050 estimates are 32.7%, 34.0% and 38.1% for France, the UK and Germany, respectively [1]. Globally and in the Gulf Region, pneumococcal disease is an increasingly important public health burden in the elderly. The burden of pneumococcal disease can be reduced by effective vaccination programs, but the recommendations on pneumococcal vaccination in adults vary widely. The major barriers to vaccine implementation among healthcare professionals are an incomplete awareness of pneumococcal disease and the vaccination options in adults. The Gulf Advocate Group calls for healthcare providers in the countries of the Arabian Gulf (Kuwait, Bahrain, Qatar, United Arab Emirates and Oman) to support awareness and education programs about adult pneumococcal disease, particularly in high-risk groups such as those >65 years of age, those with type 2 diabetes mellitus, hematological malignancy, organ and bone marrow transplantation or chronic kidney or lung diseases and pilgrims undertaking the Hajj to improve pneumococcal disease surveillance and optimize and disseminate recommendations for adult vaccination. The Gulf Advocate Group recommends following the U.S. Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccination [3,4].

  10. Late onset invasive pneumococcal disease in a liver transplanted patient: beyond the Austrian syndrome.

    PubMed

    Belvisi, V; Del Borgo, C; Morelli, F; Marocco, R; Tieghi, T; Fabietti, P; Vetica, A; Lichtner, M; Mastroianni, C M

    2013-06-01

    Invasive disease caused by Streptococcus pneumoniae is a major cause of morbidity and mortality in high-risk individuals with severe comorbidities, including asplenia, chronic alcoholism, and altered immune status. The risk of invasive pneumococcal disease has been significantly higher in transplant patients compared with the general population. Here, we report an unusual case of a disseminated pneumococcal infection with meningitis, endocarditis, spondylodiscitis, and muscle abscess in an asplenic patient on chronic immunosuppressive therapy for liver transplantation performed 17 years before.

  11. Risk of hospitalization due to pneumococcal disease in adults in Spain. The CORIENNE study

    PubMed Central

    Gil-Prieto, Ruth; Pascual-Garcia, Raquel; Walter, Stefan; Álvaro-Meca, Alejandro; Gil-De-Miguel, Ángel

    2016-01-01

    ABSTRACT Pneumococcal disease causes a high burden of disease in adults, leading to high rates of hospitalization, especially in the elderly. All hospital discharges for pneumococcal disease and pneumococcal pneumonia among adults over 18 y of age reported in first diagnostic position in 2011 (January 1, 2011 through December 31, 2011) were obtained. A total of 10,861 hospital discharges due to pneumococcal disease were reported in adults in Spain in 2011 with an annual incidence of hospitalization of 0.285 (CI 95%: 0.280–0.291) per 1,000 population over 18 y old. Case-fatality rate was 8%. Estimated cost of these hospitalisations in 2011 was more than 57 million €. Pneumococcal pneumonia accounted for the 92% of the hospital discharges All the chronic condition studied: asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, Diabetes Mellitus and immunosuppression, increased the risk of hospitalization in patients with pneumococcal pneumonia, especially in those aged 18–64 y old. Case-fatality rate among adult patients hospitalized with at least one underlying condition was significantly higher than among patients without comorbidities. Our results identified asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, chronic liver disease, Diabetes Mellitus and immunosuppression as risk groups for hospitalization. Older adults, immunocompromised patients and immunocompetent patients with underlying conditions could benefit from vaccination. PMID:26901683

  12. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

    PubMed

    Woehrl, Bianca; Brouwer, Matthijs C; Murr, Carmen; Heckenberg, Sebastiaan G B; Baas, Frank; Pfister, Hans W; Zwinderman, Aeilko H; Morgan, B Paul; Barnum, Scott R; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-10-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

  13. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

    PubMed Central

    Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

    2011-01-01

    Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

  14. Pneumococcal pneumonia prevention among adults: is the herd effect of pneumococcal conjugate vaccination in children as good a way as the active immunization of the elderly?

    PubMed

    Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico

    2016-01-01

    The indirect protection of adults as a result of pneumococcal conjugate vaccination of infants has been discussed from different epidemiological points of view. In some countries, including Italy, even after pediatric vaccination, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly. Although the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) produced encouraging results, it has not showed the efficacy of the 13-valent conjugate vaccine in preventing pneumococcal community-acquired pneumonia regardless of the number of episodes and serotype. Addressing these points by monitoring the direct impact of adult vaccination in real life distinguished from the effects of herd immunity will assist public health decision-making on the most effective adult pneumococcal vaccination strategies.

  15. Polysaccharide-Modified Synthetic Polymeric Biomaterials

    PubMed Central

    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

  16. Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D–Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media—A Double-Blind Randomized Clinical Trial in Finland

    PubMed Central

    Vesikari, Timo; Forsten, Aino; Seppä, Ilkka; Kaijalainen, Tarja; Puumalainen, Taneli; Soininen, Anu; Traskine, Magali; Lommel, Patricia; Schoonbroodt, Sonia; Hezareh, Marjan; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2016-01-01

    After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV) to children aged 2–18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media. Background This trial (ClinicalTrials.gov identifier NCT00839254), nested within a cluster-randomized double-blind invasive pneumococcal disease effectiveness study in Finland (ClinicalTrials.gov identifier NCT00861380), assessed the effectiveness of the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV or PCV10) against bacterial nasopharyngeal carriage and acute otitis media (AOM). Methods Infants (aged 6 weeks to 6 months) received the PHiD-CV or a control vaccine (hepatitis B) (schedule 3+1 or 2+1). Nasopharyngeal swabs were collected at 4 time points post-vaccination from all of the infants and at pre-vaccination from a subset. Parent-reported physician-diagnosed AOM was assessed from first vaccination until last contact (mean follow-up, 18 months). Vaccine effectiveness (VE) was derived as (1 – relative risk)*100, accounting for cluster design in AOM analysis. Significant VE was assessed descriptively (positive lower limit of the non-adjusted 95% confidence interval [CI]). Results The vaccinated cohort included 5093 infants for carriage assessment and 4117 infants for AOM assessment. Both schedules decreased vaccine-serotype carriage, with a trend toward a lesser effect from the 2+1 schedule ( VE across timpoints 19%–56% [3+1] and 1%–38% [2+1]). Trends toward reduced pneumococcal carriage (predominantly vaccine serotypes 6B, 14, 19F, and 23F), decreased carriage of vaccine-related serotype 19A, and small increases at later time points (ages 14–15 months) in non

  17. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.

    PubMed

    Skinner, Julie M; Indrawati, Lani; Cannon, Jayme; Blue, Jeffrey; Winters, Michael; Macnair, John; Pujar, Narahari; Manger, Walter; Zhang, Yuhua; Antonello, Joseph; Shiver, John; Caulfield, Michael; Heinrichs, Jon H

    2011-11-08

    The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.

  18. A Synthetic Virus-Like Particle Streptococcal Vaccine Candidate Using B-Cell Epitopes from the Proline-Rich Region of Pneumococcal Surface Protein A.

    PubMed

    Tamborrini, Marco; Geib, Nina; Marrero-Nodarse, Aniebrys; Jud, Maja; Hauser, Julia; Aho, Celestine; Lamelas, Araceli; Zuniga, Armando; Pluschke, Gerd; Ghasparian, Arin; Robinson, John A

    2015-10-16

    Alternatives to the well-established capsular polysaccharide-based vaccines against Streptococcus pneumoniae that circumvent limitations arising from limited serotype coverage and the emergence of resistance due to capsule switching (serotype replacement) are being widely pursued. Much attention is now focused on the development of recombinant subunit vaccines based on highly conserved pneumococcal surface proteins and virulence factors. A further step might involve focusing the host humoral immune response onto protective protein epitopes using as immunogens structurally optimized epitope mimetics. One approach to deliver such epitope mimetics to the immune system is through the use of synthetic virus-like particles (SVLPs). SVLPs are made from synthetic coiled-coil lipopeptides that are designed to spontaneously self-assemble into 20-30 nm diameter nanoparticles in aqueous buffer. Multivalent display of epitope mimetics on the surface of SVLPs generates highly immunogenic nanoparticles that elicit strong epitope-specific humoral immune responses without the need for external adjuvants. Here, we set out to demonstrate that this approach can yield vaccine candidates able to elicit a protective immune response, using epitopes derived from the proline-rich region of pneumococcal surface protein A (PspA). These streptococcal SVLP-based vaccine candidates are shown to elicit strong humoral immune responses in mice. Following active immunization and challenge with lethal doses of streptococcus, SVLP-based immunogens are able to elicit significant protection in mice. Furthermore, a mimetic-specific monoclonal antibody is shown to mediate partial protection upon passive immunization. The results show that SVLPs combined with synthetic epitope mimetics may have potential for the development of an effective vaccine against Streptococcus pneumoniae.

  19. A Synthetic Virus-Like Particle Streptococcal Vaccine Candidate Using B-Cell Epitopes from the Proline-Rich Region of Pneumococcal Surface Protein A

    PubMed Central

    Tamborrini, Marco; Geib, Nina; Marrero-Nodarse, Aniebrys; Jud, Maja; Hauser, Julia; Aho, Celestine; Lamelas, Araceli; Zuniga, Armando; Pluschke, Gerd; Ghasparian, Arin; Robinson, John A.

    2015-01-01

    Alternatives to the well-established capsular polysaccharide-based vaccines against Streptococcus pneumoniae that circumvent limitations arising from limited serotype coverage and the emergence of resistance due to capsule switching (serotype replacement) are being widely pursued. Much attention is now focused on the development of recombinant subunit vaccines based on highly conserved pneumococcal surface proteins and virulence factors. A further step might involve focusing the host humoral immune response onto protective protein epitopes using as immunogens structurally optimized epitope mimetics. One approach to deliver such epitope mimetics to the immune system is through the use of synthetic virus-like particles (SVLPs). SVLPs are made from synthetic coiled-coil lipopeptides that are designed to spontaneously self-assemble into 20–30 nm diameter nanoparticles in aqueous buffer. Multivalent display of epitope mimetics on the surface of SVLPs generates highly immunogenic nanoparticles that elicit strong epitope-specific humoral immune responses without the need for external adjuvants. Here, we set out to demonstrate that this approach can yield vaccine candidates able to elicit a protective immune response, using epitopes derived from the proline-rich region of pneumococcal surface protein A (PspA). These streptococcal SVLP-based vaccine candidates are shown to elicit strong humoral immune responses in mice. Following active immunization and challenge with lethal doses of streptococcus, SVLP-based immunogens are able to elicit significant protection in mice. Furthermore, a mimetic-specific monoclonal antibody is shown to mediate partial protection upon passive immunization. The results show that SVLPs combined with synthetic epitope mimetics may have potential for the development of an effective vaccine against Streptococcus pneumoniae. PMID:26501327

  20. Retrospective study of prognostic factors in pediatric invasive pneumococcal disease

    PubMed Central

    Peng, Chun-Chih; Chang, Hung-Yang; Huang, Daniel Tsung-Ning; Chang, Lung; Lei, Wei-Te

    2017-01-01

    Streptococcus pneumoniae remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of S. pneumoniae from a normally sterile site (e.g., blood, cerebrospinal fluid, synovial fluid, pericardial fluid, pleural fluid, or peritoneal fluid). The aim of this study is to survey the clinical manifestations and laboratory results of IPD and identify the prognostic factors of mortality. From January 2001 to December 2006, a retrospective review of chart was performed in a teaching hospital in Taipei. The hospitalized pediatric patients with the diagnosis of pneumonia, arthritis, infectious endocarditis, meningitis or sepsis were recruited. Among them, 50 patients were pneumococcal infections proved by positive culture results or antigen tests. Clinical manifestations, laboratory data and hospitalization courses were analyzed. The median age was 3.5-year-old and there were 30 male patients (60%). Eight patients (16%) had underlying disease such as leukemia or congenital heart disease. Hemolytic uremic syndrome (HUS) was observed in ten patients and extracorporeal membrane oxygenation (ECMO) was performed in three patients. Leukocytosis, elevated C-reactive protein and AST level were noted in most of the patients. The overall mortality rate was 10%. We found that leukopenia, thrombocytopenia and high CRP level were significant predictors for mortality. In conclusion, S. pneumoniae remains an important health threat worldwide and IPD is life-threatening with high mortality rate. We found leukopenia, thrombocytopenia, and high CRP levels to be associated with mortality in pediatric IPD, and these factors are worthy of special attention at admission. Although we failed to identify a statistically significant prognostic factor in multivariate analysis due to relatively small sample size, we suggest an aggressive antibiotic treatment in patients with these factors at admission

  1. Invasive Pneumococcal Disease After Implementation of 13-Valent Conjugate Vaccine

    PubMed Central

    Madoff, Lawrence C.; Coombes, Brandon; Pelton, Stephen I.

    2014-01-01

    OBJECTIVE: To examine whether there is a different clinical profile and severity of invasive pneumococcal disease (IPD) in children caused by nonvaccine types in the era of 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Observational study of childhood IPD in Massachusetts based on state public health surveillance data comparing pre-PCV13 (2007–2009) and post-PCV13 (2010–2012) eras. RESULTS: There were 168 pre-PCV13 cases of IPD and 85 post-PCV13 cases of IPD in Massachusetts children ≤5 years of age. PCV13 serotypes declined by 18% in the first 2 years after PCV13 use (P = .011). In the post-PCV13 phase, a higher proportion of children were hospitalized (57.6% vs 50.6%), and a higher proportion of children had comorbidity (23.5% vs 19.6%). Neither difference was statistically significant, nor were comparisons of IPD caused by vaccine and nonvaccine types. Children with comorbidities had higher rates of IPD caused by a nonvaccine type (27.6% vs 17.2%; P = .085), were more likely to be hospitalized (80.4% vs 50%; P < .0001), and were more likely to have a longer hospital stay (median of 3 days vs 0.5 days; P = .0001). CONCLUSIONS: Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. Routine vaccination with PCV13 may not be enough to reduce the risk in patients with comorbidity. PMID:25002663

  2. Polysaccharides templates for assembly of nanosilver.

    PubMed

    Emam, Hossam E; Ahmed, Hanan B

    2016-01-01

    Polysaccharides are particularly attractive in biomedical applications due to its biodegradability and biocompatibility. In addition to its ecofriendly effects and easy processing into different hydrogel shapes, made polysaccharides used on a large scale as suitable media for preparation of silver nanoparticles (AgNPs). In spite of, most of polysaccharides are water insoluble, but it has shown to be quite efficient capping agents and/or nanoreactor matrices for production of AgNPs. Several methods have been developed to get the benefit of multi-functionality for polysaccharides' macromolecules in preparation of AgNPs. Therefore, recently, preparation of nanosilver using different polysaccharides have been the focus of an exponentially increasing number of works devoted to develop nanocomposites by blending AgNPs with different polysaccharides matrices. The current review represents a wide survey for the published studies which interested in using of polysaccharides in nanosilver preparations.

  3. Sex differences in invasive pneumococcal disease and the impact of pneumococcal conjugate vaccination in the Netherlands, 2004 to 2015

    PubMed Central

    Wagenvoort, Gertjan H J; Sanders, Elisabeth A M; Vlaminckx, Bart J; de Melker, Hester E; van der Ende, Arie; Knol, Mirjam J

    2017-01-01

    Implementation of pneumococcal conjugate vaccines in the Netherlands (PCV7 in 2006 and PCV10 in 2011) for infants caused a shift in serotypes in invasive pneumococcal disease (IPD). We explored sex differences in serotype-specific IPD incidence before and after vaccine introduction. Incidences in the pre-PCV7 (June 2004–May 2006), post-PCV7 (June 2008–May 2011) and post-PCV10 period (June 2013–May 2015), stratified by age, were compared. Incidence was higher in men for all age groups (overall in men: 16.7, 15.5 and 14.4/100,000 and women: 15.4, 13.6 and 13.9/100,000 pre-PCV7, post-PCV7 and post-PCV10, respectively), except for 20–39 year-olds after PCV7 and 40–64 year-olds after PCV10 introduction. After PCV7 and PCV10 introduction, the overall IPD incidence decreased in men aged 20–39 years (from 5.3 pre-PCV7 to 4.7 and 2.6/100,000 post-PCV7 and post-PCV10, respectively), whereas it showed a temporary increase in women (from 3.9/100,000 pre-PCV7 to 5.0/100,000 post-PCV7 and back to 4.0/100,000 post-PCV10) due to replacement disease. PCV10 herd effects were observed throughout, but in women older than 40 years, a significant increase in non-PCV10 serotype offset a decrease in overall IPD incidence. Ongoing surveillance of IPD incidence by sex is important to evaluate the long-term effects of PCV implementation. PMID:28300529

  4. [Streptococcus pneumoniae Vaccination in Children and Adolescents at High Risk of Invasive Pneumococcal Disease].

    PubMed

    Tendais-Almeida, Marta; Ferreira-Magalhães, Manuel; Alves, Inês; Tavares, Margarida; Azevedo, Inês

    2015-01-01

    Introdução: Em Portugal, a vacinação anti-pneumocócica é gratuita e recomendada pela Direção-Geral da Saúde na população pediátrica de alto risco para doença invasiva pneumocócica. O objetivo deste estudo foi analisar o cumprimento vacinal numa população pediátrica seguida em consulta hospitalar. Material e Métodos: Estudo observacional transversal, em crianças com diagnóstico de alto risco de doença invasiva pneumocócica e consulta num hospital nível três, entre julho e dezembro de 2014. Os dados foram obtidos através do processo clínico, Boletim Individual de Saúde e Plataforma de Dados da Saúde®. Resultados: Dos 122 participantes, 95,9% realizaram, pelo menos, uma dose de vacina mas, destes, só 64,8% efetuaram o esquema completo. O cumprimento do esquema vacinal foi melhor nos de idade inferior a cinco anos (p < 0,01). A proporção de crianças com esquema completo foi de: 100% nas hemoglobinopatias, 100% nas infeções por vírus da imunodeficiência humana, 66,7% nos prematuros com idade gestacional ⤠28 semanas, 62,5% nos esplenectomizados e 54,7% na síndrome de Down. As crianças têm mais esquemas completos quando são seguidas em consulta de Infeciologia (100%) e de Pneumologia pediátricas (88,2%). O grupocom idade superior a cinco anos está mais vacinado com a vacina polissacarida 23-valente do que o dos 2-5 anos (74,5% vs 40,5%; p < 0,01).Discussão: A maioria da nossa população de alto risco para doença invasiva pneumocócica efetuou vacinação anti-pneumocócica, mas apenas dois terços completaram o esquema recomendado, sendo a maior falha na administração da vacina polissacarida 23-valente. Conclusões: Embora estes resultados sejam melhores do que em países europeus com recomendações semelhantes, é necessário explorar as causas das falhas observadas para otimizar a vacinação.

  5. Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

    PubMed Central

    Grigg, Jonathan; Miyashita, Lisa

    2017-01-01

    Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR–dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor. We also sought to evaluate the suitability of nasal epithelial PAFR expression in welders as a biomarker of susceptibility to infection. Finally, we investigated the generalisability of the effect of welding fumes on pneumococcal infection and growth using a variety of different welding fume samples. Nasal epithelial PAFR expression in welders and controls was analysed by flow cytometry. WF were collected using standard methodology. The effect of WF on respiratory cell reactive oxygen species production, HIF-1α expression, and pneumococcal infection was determined using flow cytometry, HIF-1α knockdown and overexpression, and pneumococcal infection assays. We found that nasal PAFR expression is significantly increased in welders compared with controls and that WF significantly increased reactive oxygen species production, HIF-1α and PAFR expression, and pneumococcal infection of respiratory cells. In unstimulated cells, HIF-1α knockdown decreased PAFR expression and HIF-1α overexpression increased PAFR expression. However, in knockdown cells pneumococcal infection was paradoxically increased and in overexpressing cells infection was unaffected. Nasal epithelial PAFR expression may be used as a biomarker of susceptibility to pneumococcal infection in order to target individuals, particularly those at high risk such as welders

  6. Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha.

    PubMed

    Grigg, Jonathan; Miyashita, Lisa; Suri, Reetika

    2017-01-01

    Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor. We also sought to evaluate the suitability of nasal epithelial PAFR expression in welders as a biomarker of susceptibility to infection. Finally, we investigated the generalisability of the effect of welding fumes on pneumococcal infection and growth using a variety of different welding fume samples. Nasal epithelial PAFR expression in welders and controls was analysed by flow cytometry. WF were collected using standard methodology. The effect of WF on respiratory cell reactive oxygen species production, HIF-1α expression, and pneumococcal infection was determined using flow cytometry, HIF-1α knockdown and overexpression, and pneumococcal infection assays. We found that nasal PAFR expression is significantly increased in welders compared with controls and that WF significantly increased reactive oxygen species production, HIF-1α and PAFR expression, and pneumococcal infection of respiratory cells. In unstimulated cells, HIF-1α knockdown decreased PAFR expression and HIF-1α overexpression increased PAFR expression. However, in knockdown cells pneumococcal infection was paradoxically increased and in overexpressing cells infection was unaffected. Nasal epithelial PAFR expression may be used as a biomarker of susceptibility to pneumococcal infection in order to target individuals, particularly those at high risk such as welders

  7. Deacetylation of sialic acid by esterases potentiates pneumococcal neuraminidase activity for mucin utilization, colonization and virulence

    PubMed Central

    Kahya, Hasan F.; Andrew, Peter W.

    2017-01-01

    Pneumococcal neuraminidase is a key enzyme for sequential deglycosylation of host glycans, and plays an important role in host survival, colonization, and pathogenesis of infections caused by Streptococcus pneumoniae. One of the factors that can affect the activity of neuraminidase is the amount and position of acetylation present in its substrate sialic acid. We hypothesised that pneumococcal esterases potentiate neuraminidase activity by removing acetylation from sialic acid, and that will have a major effect on pneumococcal survival on mucin, colonization, and virulence. These hypotheses were tested using isogenic mutants and recombinant esterases in microbiological, biochemical and in vivo assays. We found that pneumococcal esterase activity is encoded by at least four genes, SPD_0534 (EstA) was found to be responsible for the main esterase activity, and the pneumococcal esterases are specific for short acyl chains. Assay of esterase activity by using natural substrates showed that both the Axe and EstA esterases could use acetylated xylan and Bovine Sub-maxillary Mucin (BSM), a highly acetylated substrate, but only EstA was active against tributyrin (triglyceride). Incubation of BSM with either Axe or EstA led to the acetate release in a time and concentration dependent manner, and pre-treatment of BSM with either enzyme increased sialic acid release on subsequent exposure to neuraminidase A. qRT-PCR results showed that the expression level of estA and axe increased when exposed to BSM and in respiratory tissues. Mutation of estA alone or in combination with nanA (codes for neuraminidase A), or the replacement of its putative serine active site to alanine, reduced the pneumococcal ability to utilise BSM as a sole carbon source, sialic acid release, colonization, and virulence in a mouse model of pneumococcal pneumonia. PMID:28257499

  8. Critical Role of IL-22/IL22-RA1 Signaling in Pneumococcal Pneumonia.

    PubMed

    Trevejo-Nunez, Giraldina; Elsegeiny, Waleed; Conboy, Parker; Chen, Kong; Kolls, Jay K

    2016-09-01

    IL-22-IL-22R signaling plays a crucial role in regulating host defenses against extracellular pathogens, particularly in the intestine, through the induction of antimicrobial peptides and chemotactic genes. However, the role of IL-22-IL-22R is understudied in Streptococcus pneumoniae lung infection, a prevalent pathogen of pneumonia. This paper presents the findings of IL-22 signaling during a murine model of pneumococcal pneumonia and improvement of bacterial burden upon IL-22 administration. IL-22 was rapidly induced in the lung during pneumococcal infection in wild-type mice, and Il22(-/-) mice had higher pneumococcal burdens compared with controls. Additionally, mice with hepatic-specific deletion of Il22ra1 also had higher bacterial burdens in lungs compared with littermate controls after intrapulmonary pneumococcal infection, suggesting that IL-22 signaling in the liver is important to control pneumococcal pneumonia. Thus, we hypothesized that enhancement of IL-22 signaling would control pneumococcal burden in lung tissues in an experimental pneumonia model. Administration of rIL-22 systemically to infected wild-type mice decreased bacterial burden in lung and liver at 24 h postinfection. Our in vitro studies also showed that mice treated with IL-22 had increased C3 expression in the liver compared with the isotype control group. Furthermore, serum from mice treated with IL-22 had improved opsonic capacity by increasing C3 binding on S. pneumoniae Taken together, endogenous IL-22 and hepatic IL-22R signaling play critical roles in controlling pneumococcal lung burden, and systemic IL-22 decreases bacterial burden in the lungs and peripheral organs by potentiating C3 opsonization on bacterial surfaces, through the increase of hepatic C3 expression.

  9. Pneumococcal Carriage in Sub-Saharan Africa—A Systematic Review

    PubMed Central

    Usuf, Effua; Bottomley, Christian; Adegbola, Richard A.; Hall, Andrew

    2014-01-01

    Background Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. Methods A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. Results Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6–70.8) in children less than 5 years, 42.6% (95% CI: 29.9–55.4) in children 5–15 years and 28.0% (95% CI: 19.0–37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9–24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. Conclusion Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination. PMID:24465464

  10. Study of Invasive Pneumococcal Infection in Adults with Reference to Penicillin Resistance

    PubMed Central

    Muley, Vrishali Avinash; Ghadage, Dnyaneshwari Purushottam; Yadav, Gauri Eknath; Bhore, Arvind Vamanrao

    2017-01-01

    Background: Invasive pneumococcal infections often prove rapidly fatal, even where good medical treatment is readily available. In developed countries, up to 20% of people who contract pneumococcal meningitis die; however, in developing world, mortality is closer to 50%, even among hospitalized patients. The World Health Organization estimated 600,000–800,000 adult deaths each year from pneumococcal pneumonia, meningitis, and sepsis. Aims: This study aims to estimate isolation rate of invasive pneumococcal infection in adults, to determine the antimicrobial susceptibility profile of Streptococcus pneumoniae isolates and to study the associated risk factors. Materials and Methods: A total of 120 patients with suspected invasive infection such as meningitis, septicemia, and pleural effusion, were included in the study. Various clinical specimens such as pus, cerebrospinal fluid, and other sterile body fluids were processed for isolation and identification of S. pneumoniae. Kirby–Bauer disc diffusion method was performed to determine the antimicrobial susceptibility profile. Minimum inhibitory concentration test was performed to determine the penicillin resistance. Results: Of 120 patients, 40 (33.33%) cases were proven by culture to have an invasive pneumococcal infection. The most common clinical condition observed was meningitis followed by pneumonia with pleural effusion and sepsis. Pneumococcal isolates exhibited 40% resistance to cotrimoxazole and 12.73% to chloramphenicol. Two meningeal isolates exhibited penicillin resistance. Comorbidities observed in 21 (52.5%) cases were mainly Diabetes mellitus, smoking, and alcoholism. Conclusions: Invasive pneumococcal infection has poor prognosis and penicillin-resistant strains have become increasingly common. This study emphasizes the importance of judicious use of antibiotics, especially to refrain their use in mild self-limiting upper respiratory infections. PMID:28042214

  11. Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults

    PubMed Central

    Aslam, Aamir; Chapel, Helen; Ogg, Graham

    2011-01-01

    Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex-vivo StkP446–60-tetramer binding in HLA-DRB1*1501 adults. These StkP446–60-tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP446–60-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We found that ex-vivo pneumococcal-specific T cells were detectable in healthy adults and that they were enriched with cell surface markers associated with recent antigen exposure and later stages of antigen-driven differentiation. It is likely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynx and it is possible that they may be preventing subsequent colonisation and disease. PMID:22039412

  12. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics.

    PubMed

    Stephens, David S

    2011-01-01

    Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vaccine serotypes; the decrease in carriage is correlated with disease reduction in unvaccinated individuals, and the impact of herd immunity lasts for years. Based on these data, models for using herd immunity in vaccine-based prevention strategies are underway for control of meningitis in sub-Saharan Africa. Although the immunologic basis of herd immunity and impact on microbial biology need more study, protecting the unvaccinated by altering pathogen transmission dynamics is a powerful effect of PPCVs and increasingly important in vaccine introduction, implementation, and evaluation strategies.

  13. Structurally altered capsular polysaccharides produced by mutant bacteria

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

    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.

  14. Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7

    PubMed Central

    Hanke, Christiane R.; Grijalva, Carlos G.; Chochua, Sopio; Pletz, Mathias W.; Hornberg, Claudia; Edwards, Kathryn M.; Griffin, Marie R.; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Klugman, Keith P.; Vidal, Jorge E.

    2016-01-01

    Background Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine-types but little data exists from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, two years after PCV7 was introduced. Methods Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were quellung-serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by qPCR. Results The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (p=0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (p=0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increased density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were non-susceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%). Conclusions Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density. PMID:26974749

  15. Marine Polysaccharides in Pharmaceutical Applications: An Overview

    PubMed Central

    Laurienzo, Paola

    2010-01-01

    The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

  16. Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

    PubMed

    Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2014-02-01

    Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

  17. Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia

    PubMed Central

    Rai, Aswathy N.; Thornton, Justin A.; Stokes, John; Sunesara, Imran; Swiatlo, Edwin; Nanduri, Bindu

    2016-01-01

    Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro. PMID:27247105

  18. South Asia symposium on pneumococcal disease and the promise of vaccines – Meeting report

    PubMed Central

    Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram

    2016-01-01

    Despite the licensure of the pneumococcal conjugate vaccine (PCV) in the US and other Western countries for over 14 years, as of September 2014 only 4 South Asian countries were using PCV in their universal immunization program. To generate momentum toward addressing this issue a “South Asia symposium on pneumococcal disease and the promise of vaccines” was organized just prior to the 9th international symposium on pneumococci and pneumococcal diseases held in India recently. Leading scientists, program managers, and decision makers including ministry officials from the region participated in the meeting. The participants discussed available data on pneumococcal disease burden in South Asia, surveillance methods, efficacy and safety of pneumococcal conjugate vaccines (PCV), the status of PCV introduction, programmatic challenges in introducing PCV and available data on the impact of PCV in South Asia and globally. There was a strong consensus that available data on disease burden and the global experience with PCV justified the introduction PCV in all Asian countries in order to accelerate the gains in child survival in the region. PMID:27026150

  19. Nasopharyngeal antibodies to pneumococcal pneumolysin in children with acute otitis media.

    PubMed Central

    Virolainen, A; Jero, J; Käyhty, H; Karma, P; Eskola, J; Leinonen, M

    1995-01-01

    Pneumolysin, an intracellular protein toxin of all clinically relevant pneumococcal serotypes, is released in vivo during the autolysis of pneumococci and is believed to pave the way for intact pneumococci to invade and cause disease. Therefore, antibodies to pneumolysin should prevent its destructive function. We measured antibodies to pneumococcal pneumolysin in acute- and convalescent-phase nasopharyngeal aspirate samples of 120 children (median age, 2.5 years) with acute otitis media by enzyme immunoassay. Nasopharyngeal immunoglobulin M (IgM) and IgG class antibodies to pneumolysin were rarely detectable, whereas IgA class antibody was detected often, occurred independently of serum IgA antibody in serum, and correlated with the presence of the secretory component in pneumococcal antibody, indicating local production of IgA antibodies. Nasopharyngeal IgA antibody to pneumolysin was detected in 93% of the children already in the acute phase of otitis. Twenty percent of the children developed at least a threefold rise in the pneumolysin-specific IgA antibody concentration by the convalescent phase of otitis, with the youngest at 6 months of age, regardless of the pneumococcal findings in the nasopharynx or middle ear fluid. We suggest that nasopharyngeal IgA antibody to pneumolysin can be produced early in life by pneumococcal colonization. PMID:8574834

  20. The host immune dynamics of pneumococcal colonization: Implications for novel vaccine development

    PubMed Central

    Khan, M Nadeem; Pichichero, Michael E

    2015-01-01

    The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines. PMID:25668673

  1. T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

    PubMed Central

    Neill, Daniel R.; Fernandes, Vitor E.; Wisby, Laura; Haynes, Andrew R.; Ferreira, Daniela M.; Laher, Ameera; Strickland, Natalie; Gordon, Stephen B.; Denny, Paul; Kadioglu, Aras; Andrew, Peter W.

    2012-01-01

    Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design. PMID:22563306

  2. Molecular Characterization of Pneumococcal Isolates from Pets and Laboratory Animals

    PubMed Central

    van der Linden, Mark; Al-Lahham, Adnan; Nicklas, Werner; Reinert, Ralf René

    2009-01-01

    Background Between 1986 and 2008 Streptococcus pneumoniae was isolated from 41 pets/zoo animals (guinea pigs (n = 17), cats (n = 12), horses (n = 4), dogs (n = 3), dolphins (n = 2), rat (n = 2), gorilla (n = 1)) treated in medical veterinary laboratories and zoos, and 44 laboratory animals (mastomys (multimammate mice; n = 32), mice (n = 6), rats (n = 4), guinea pigs (n = 2)) during routine health monitoring in an animal facility. S. pneumoniae was isolated from nose, lung and respiratory tract, eye, ear and other sites. Methodology/Principal Findings Carriage of the same isolate of S. pneumoniae over a period of up to 22 weeks was shown for four mastomys. Forty-one animals showed disease symptoms. Pneumococcal isolates were characterized by optochin sensitivity, bile solubility, DNA hybridization, pneumolysin PCR, serotyping and multilocus sequence typing. Eighteen of the 32 mastomys isolates (56%) were optochin resistant, all other isolates were optochin susceptible. All mastomys isolates were serotype 14, all guinea pig isolates serotype 19F, all horse isolates serotype 3. Rats had serotypes 14 or 19A, mice 33A or 33F. Dolphins had serotype 23F, the gorilla serotype 14. Cats and dogs had many different serotypes. Four isolates were resistant to macrolides, three isolates also to clindamycin and tetracyclin. Mastomys isolates were sequence type (ST) 15 (serotype 14), an ST/serotype combination commonly found in human isolates. Cats, dogs, pet rats, gorilla and dolphins showed various human ST/serotype combinations. Lab rats and lab mice showed single locus variants (SLV) of human STs, in human ST/serotype combinations. All guinea pig isolates showed the same completely new combination of known alleles. The horse isolates showed an unknown allele combination and three new alleles. Conclusions/Significance The isolates found in mastomys, mice, rats, cats, dogs, gorilla and dolphins are most likely identical to human

  3. Polysaccharide-based nanocomposites and their applications

    PubMed Central

    Zheng, Yingying; Monty, Jonathan; Linhardt, Robert J.

    2014-01-01

    Polysaccharide nanocomposites have become increasingly important materials over the past decade. Polysaccharides offer a green alternative to synthetic polymers in the preparation of soft nanomaterials. They have also been used in composites with hard nanomaterials, such as metal nanoparticles and carbon-based nanomaterials. This mini review describes methods for polysaccharide nanocomposite preparation and reviews the various types and diverse applications for these novel materials. PMID:25498200

  4. Advances on Bioactive Polysaccharides from Medicinal Plants.

    PubMed

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  5. Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

    PubMed Central

    Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O’Brien, Katherine L.; Moore, Matthew R.

    2013-01-01

    Background Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. Methods and Findings Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥2 years before and ≥1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ≥65 year-olds [RR 0·74, 95% CI 0·58–0·95]). Conclusions Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude

  6. Pseudoseptic arthritis of the shoulder following pneumococcal vaccination.

    PubMed

    Floyd, Mark W; Boyce, Brandon M; Castellan, Robert M; McDonough, E Barry

    2012-01-16

    Pseudoseptic arthritis is primarily described in rheumatoid arthritis and other systemic inflammatory conditions. To our knowledge, only 1 case report of pseudoseptic arthritis associated with intra-articular injection of a pneumococcal polyvalent vaccine (PPV) has been published. Here, a second case is presented in which a patient presented with swelling, pain, and erythema of the affected shoulder. A 59-year-old woman presented to the emergency department with a 3-day history of severe pain and decreased mobility of her left shoulder after receiving a PPV vaccination. Her clinical and laboratory workup was suspicious for septic arthritis; however, magnetic resonance imaging of the affected shoulder with and without contrast showed only a partial thickness tear of the rotator cuff, fluid in the subacromial/subdeltoid bursa, and subcutaneous edema without evidence of an abscess. Based on the clinical and laboratory data, she underwent arthroscopic debridement. There was inflammatory tissue throughout the shoulder but no obvious purulent material. She did well postoperatively with a supervised range of motion rehabilitation protocol. Her cultures remained negative. At 12 weeks, she was discharged from follow-up. We suspect that the vaccination was inadvertently injected into the glenohumeral joint directly through the rotator cuff given the lack of a full-thickness tear and the patient's thin body habitus, which could explain her aseptic inflammatory arthritis.

  7. Genotypes of Invasive Pneumococcal Isolates Recently Recovered from Italian Patients

    PubMed Central

    Dicuonzo, Giordano; Gherardi, Giovanni; Gertz, Robert E.; D'Ambrosio, Fabio; Goglio, Antonio; Lorino, Giulia; Recchia, Simona; Pantosti, Annalisa; Beall, Bernard

    2002-01-01

    We examined 73 recent invasive pneumococcal isolates within selected areas of Italy for genotypic variability. Thirty-three genomic macrorestriction types were found, three of which represented multiple serotypes. Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types. Of the nine macrorestriction types found among the 22 penicillin-nonsusceptible Streptococus pneumoniae (PNSP) isolates, seven comprised isolates with allelic profiles showing five to seven allelic matches to profiles in the multilocus sequence typing database (www.mlst.net); however, three of the seven profiles represented serotypes not previously associated with these clonal clusters. Two PNSP macrorestriction types represented new clones with unique allelic profiles. Allelic profiles obtained from isolates of 3 of the 25 macrorestriction types found among the 51 penicillin-susceptible S. pneumoniae (PSSP) isolates were closely related to previously described profiles. One PSSP isolate was a novel type 24F isolate related to the multiresistant clone France9V-3. This work reports new PNSP strains and new serotype-clone associations. PMID:12354862

  8. Role of purinergic signaling in experimental pneumococcal meningitis

    PubMed Central

    Zierhut, Marco; Dyckhoff, Susanne; Masouris, Ilias; Klein, Matthias; Hammerschmidt, Sven; Pfister, Hans-Walter; Ayata, Korcan; Idzko, Marco; Koedel, Uwe

    2017-01-01

    Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR. ATP levels were determined in murine CSF and cell culture experiments. Treatment with the P2R antagonists suramin or brilliant blue G did not have any impact on disease course. This lack of effect might be attributed to meningitis-associated down-regulation of brain P2R expression and/or a drop of cerebrospinal fluid (CSF) ATP, as demonstrated by RT-PCR and ATP analyses. Supplemental cell culture experiments suggest that the reduction in CSF ATP is, at least partly, due to ATP hydrolysis by ectonucleotidases of neutrophils and macrophages. In conclusion, this study suggests that ATP-P2R signaling is only of minor or even no significance in PM. This may be explained by down-regulation of P2R expression and decreased CSF ATP levels. PMID:28300164

  9. Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia.

    PubMed

    Yamamoto, Kazuko; Ahyi, Ayele-Nati N; Pepper-Cunningham, Zachary A; Ferrari, Joseph D; Wilson, Andrew A; Jones, Matthew R; Quinton, Lee J; Mizgerd, Joseph P

    2014-02-01

    Epithelial cells line the respiratory tract and interface with the external world. Epithelial cells contribute to pulmonary inflammation, but specific epithelial roles have proven difficult to define. To discover unique epithelial activities that influence immunity during infection, we generated mice with nuclear factor-κB RelA mutated throughout all epithelial cells of the lung and coupled this approach with epithelial cell isolation from infected and uninfected lungs for cell-specific analyses of gene induction. The RelA mutant mice appeared normal basally, but in response to pneumococcus in the lungs they were unable to rapidly recruit neutrophils to the air spaces. Epithelial cells expressed multiple neutrophil-stimulating cytokines during pneumonia, all of which depended on RelA. Cytokine expression by nonepithelial cells was unaltered by the epithelial mutation of RelA. Epithelial cells were the predominant sources of CXCL5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas nonepithelial cells were major sources for other neutrophil-activating cytokines. Epithelial RelA mutation decreased whole lung levels of CXCL5 and GM-CSF during pneumococcal pneumonia, whereas lung levels of other neutrophil-recruiting factors were unaffected. Defective neutrophil recruitment in epithelial mutant mice could be rescued by administration of CXCL5 or GM-CSF. These results reveal a specialized immune function for the pulmonary epithelium, the induction of CXCL5 and GM-CSF, to accelerate neutrophil recruitment in the infected lung.

  10. Role of purinergic signaling in experimental pneumococcal meningitis.

    PubMed

    Zierhut, Marco; Dyckhoff, Susanne; Masouris, Ilias; Klein, Matthias; Hammerschmidt, Sven; Pfister, Hans-Walter; Ayata, Korcan; Idzko, Marco; Koedel, Uwe

    2017-03-16

    Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR. ATP levels were determined in murine CSF and cell culture experiments. Treatment with the P2R antagonists suramin or brilliant blue G did not have any impact on disease course. This lack of effect might be attributed to meningitis-associated down-regulation of brain P2R expression and/or a drop of cerebrospinal fluid (CSF) ATP, as demonstrated by RT-PCR and ATP analyses. Supplemental cell culture experiments suggest that the reduction in CSF ATP is, at least partly, due to ATP hydrolysis by ectonucleotidases of neutrophils and macrophages. In conclusion, this study suggests that ATP-P2R signaling is only of minor or even no significance in PM. This may be explained by down-regulation of P2R expression and decreased CSF ATP levels.

  11. Serotype distribution and antimicrobial resistance of invasive and noninvasive pneumococcal isolates in Tunisia.

    PubMed

    Marzouk, Manel; Ferjani, Asma; Bouafia, Nabiha; Harb, Hanen; Ben Salem, Youssef; Boukadida, Jalel

    2015-02-01

    Pneumococcal conjugate vaccines have not yet been introduced into the national program for childhood vaccination in Tunisia. The aim of this 7-year study was to obtain local data about serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. A total of 203 isolates of culture confirmed that S. pneumoniae was evaluated. Invasive (n=108) and noninvasive (n=95) pneumococcal isolates were obtained from patients aged from 1 month to 85 years old. Considering all age groups, vaccine coverage was 40%, 62%, and 68% for PCV7, PCV10, and PCV13 serotypes, respectively. Overall, 31% of these isolates were penicillin G nonsusceptible. The most prevalent serotypes identified were those found in currently available pneumococcal conjugate vaccines, emphasizing the importance of implementing the vaccine in the routine immunization schedule at the national level.

  12. Pneumococcal vaccination in developing countries: where does science end and commerce begin?

    PubMed

    Mathew, Joseph L

    2009-07-09

    Recently Pneumococcal vaccines have generated considerable interest in developing countries as an intervention for protecting children from pneumonia and thereby reducing childhood mortality. Many convincing scientific arguments have been put forward, although they are often based either on extension of information from developed countries, or estimation plus extrapolation of limited local data. In addition, there is also significant commercial pressure to prescribe/recommend Pneumococcal vaccine(s). Against such a background, it is important for developing countries to critically appraise the issues involved in order to make a rational choice. This brief paper explores these issues, showing that the current Pneumococcal vaccines have limited effectiveness in developing countries and the hype surrounding them is more commercial than scientific.

  13. Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil.

    PubMed

    Cardoso, Nayara Torres; Santos, Bárbara Araújo; Barbosa, André Victor; Superti, Silvana Vargas; Teixeira, Lúcia Martins; Neves, Felipe Piedade Gonçalves

    2017-03-01

    We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.

  14. Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes.

    PubMed

    Chang, Bin; Nariai, Akiyoshi; Sekizuka, Tsuyoshi; Akeda, Yukihiro; Kuroda, Makoto; Oishi, Kazunori; Ohnishi, Makoto

    2015-10-01

    Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain.

  15. Rethinking Risk for Pneumococcal Disease in Adults: The Role of Risk Stacking

    PubMed Central

    Pelton, Stephen I.; Shea, Kimberly M.; Weycker, Derek; Farkouh, Raymond A.; Strutton, David R.; Edelsberg, John

    2015-01-01

    Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions. PMID:26034770

  16. Bioactive polysaccharides and gut microbiome (abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many polysaccharides have shown the ability to reduce plasma cholesterol or postprandial glycemia. Viscosity in the small intestine seems to be required to slow glucose uptake. Cereal mixed linkage beta-glucans, psyllium, glucomannans, and other polysaccharides also seem to require higher molecula...

  17. Polysaccharide Based Hydrogels for Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Leone, Gemma; Barbucci, Rolando

    Polysaccharide based hydrogels for their physico-chemical and biological properties can be used as scaffolds for soft tissue regneration and as vehicles for drug controlled release. For both these applications, Hyaluronan shows optimal characteristics even though its quick enzymatic degradability makes this natural polysaccharide unsuitable for applications which require prolonged presence in the human organism.

  18. Solution NMR spectroscopy of food polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many polysaccharides are allowed for direct food use, where they serve a number of useful functions. In addition to possibly being a source of calories, a food polysaccharide may be a dietary fiber, bulking agent, crystallization inhibitor, thickener, encapsulant, gelling agent, foam and emulsion s...

  19. Polysaccharides in colon-specific drug delivery.

    PubMed

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  20. Unexplored possibilities of all-polysaccharide composites.

    PubMed

    Simkovic, Ivan

    2013-06-20

    Composites made solely from polysaccharides are mostly ecological because they can degrade without leaving behind ecologically harmful residues, in contrast to composites which contain synthetic polymers. Herein, the following groups of all-polysaccharide composites (APCs) are discussed: an all-cellulose group that includes cotton composites, cellulose combined with other polysaccharides, as well as those based on chitin/chitosan, heparin, hyaluronan, xylan, glucomannan, pectin, xyloglucan, arabinan, starch, carrageenan, alginate, galactan as one of the components in combination with other polysaccharides. They can be used in medical, paper, food, packing, textile, electronic, mechanical engineering and other applications. The composites were tested for absorptivity, biodegradability, crystallinity, rheology, and mechanical, optical, separation, gelling, pasting, film-forming, adhesive, antimicrobial properties, as well as water vapor permeability, water repellency, dye uptake, and fire-retardancy. Except for food applications, composites based on more than two types of polysaccharides have rarely been used and many possible combinations remain unexplored.

  1. Dynamics and Determinants of Pneumococcal Antibodies Specific against 13 Vaccine Serotypes in the Pre-Vaccination Era

    PubMed Central

    Prins-van Ginkel, Annemarijn C.; Berbers, Guy A. M.; Grundeken, Lucienne H.; Tcherniaeva, Irina; Wittenberns, Jelle I.; Elberse, Karin; Mollema, Liesbeth; de Melker, Hester E.; Knol, Mirjam J.

    2016-01-01

    Introduction Introduction of pneumococcal conjugate vaccines (PCVs) for infants decreased overall invasive pneumococcal disease (IPD), while non-vaccine serotype IPD increased. To fully understand this serotype replacement, knowledge about serotype dynamics in the pre-vaccine era is needed. In addition to IPD surveillance and carriage studies, the serotype replacement can be investigated by serosurveillance studies. The current study compared the results of two Dutch serosurveillance studies conducted in 1995–1996 (PIENTER1) and 2006–2007 (PIENTER2). Methods Participants in these studies donated a blood sample and completed a questionnaire. Pneumococcal antibodies of serotypes included in PCV13 were measured with a fluorescent-bead based multiplex immunoassay. Geometric mean antibody concentrations (GMCs) and determinants of pneumococcal antibody levels were investigated. Results GMCs were higher in PIENTER2 for serotypes 1, 6A, 6B, 9V, 18C, 19F and 23F and lower for 3 and 5. Age, day care attendance, household size, vaccination coverage, and urbanisation rate were associated with pneumococcal antibodies in children. Education level, ethnicity, age, low vaccination coverage sample, urbanisation rate, and asthma/COPD were associated with pneumococcal antibodies in elderly. The determinants significantly associated with pneumococcal IgG were slightly different for the elderly in PIENTER1 compared to the elderly in PIENTER2. Conclusion Although most of the serotype antibody levels remained stable, some of the serotype-specific antibody levels varied during the pre-vaccine era, indicating that exposure of certain serotypes changes without interference of PCVs. PMID:26796783

  2. Roles of Pneumococcal DivIB in Cell Division▿

    PubMed Central

    Le Gouëllec, Audrey; Roux, Laure; Fadda, Daniela; Massidda, Orietta; Vernet, Thierry; Zapun, André

    2008-01-01

    DivIB, also known as FtsQ in gram-negative organisms, is a division protein that is conserved in most eubacteria. DivIB is localized at the division site and forms a complex with two other division proteins, FtsL and DivIC/FtsB. The precise function of these three bitopic membrane proteins, which are central to the division process, remains unknown. We report here the characterization of a divIB deletion mutant of Streptococcus pneumoniae, which is a coccus that divides with parallel planes. Unlike its homologue FtsQ in Escherichia coli, pneumococcal DivIB is not required for growth in rich medium, but the ΔdivIB mutant forms chains of diplococci and a small fraction of enlarged cells with defective septa. However, the deletion mutant does not grow in a chemically defined medium. In the absence of DivIB and protein synthesis, the partner FtsL is rapidly degraded, whereas other division proteins are not affected, pointing to a role of DivIB in stabilizing FtsL. This is further supported by the finding that an additional copy of ftsL restores growth of the ΔdivIB mutant in defined medium. Functional mapping of the three distinct α, β, and γ domains of the extracellular region of DivIB revealed that a complete β domain is required to fully rescue the deletion mutant. DivIB with a truncated β domain reverts only the chaining phenotype, indicating that DivIB has distinct roles early and late in the division process. Most importantly, the deletion of divIB increases the susceptibility to β-lactams, more evidently in a resistant strain, suggesting a function in cell wall synthesis. PMID:18441058

  3. Lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia

    PubMed Central

    Rosendahl, Alva; Bergmann, Simone; Hammerschmidt, Sven; Goldmann, Oliver; Medina, Eva

    2013-01-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs) in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DCs-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DCs-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9) in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection. PMID:23802100

  4. Memory B Cells and Pneumococcal Antibody After Splenectomy1

    PubMed Central

    Wasserstrom, Heather; Bussel, James; Lim, Lony C.-L.; Cunningham-Rundles, Charlotte

    2010-01-01

    Splenectomized patients are susceptible to bloodstream infections with encapsulated bacteria, potentially due to loss of blood filtering but also defective production of anticarbohydrate Ab. Recent studies propose that a lack of Ab is related to reduced numbers of IgM+ CD27+ memory B cells found after splenectomy. To test this, we analyzed CD27+ memory B cell subsets, IgG, and IgM pneumococcal Ab responses in 26 vaccinated splenectomized subjects in comparison to memory B cell subsets and Ab responses in healthy controls. As shown previously, the splenectomized autoimmune subjects had fewer total, isotype switched, and IgM+ CD27+ memory B cells as compared with controls, but there was no difference in memory B cells subsets between controls and splenectomized subjects with spherocytosis. There was no difference between the geometric mean IgG Ab response between normal controls and splenectomized subjects (p = 0.51; p = 0.81). Control subjects produced more IgM Ab than splenectomized autoimmune subjects (p = 0.01) but the same levels as subjects with spherocytosis (p = 0.15.) There was no correlation between memory B cell subsets and IgG or IgM Ab responses for controls or splenectomized subjects. These data suggest that splenectomy alone may not be the sole reason for loss of memory B cells and reduced IgM antipneumococcal Ab. Because subjects with autoimmunity had splenectomy at a significantly older age than participants with spherocytosis, these data suggest that an age-related loss of extra splenic sites necessary for the maintenance or function of memory B cells may lead to impaired immunity in these subjects. PMID:18714044

  5. Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis

    PubMed Central

    2013-01-01

    Background Bacterial meningitis caused by Streptococcus pneumoniae leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status. The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content. Methods and results Eleven day old Wistar rats were infected with 1x106 cfu/ml of S. pneumoniae and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated. Conclusions Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis. PMID:23977941

  6. Influenza and pneumococcal vaccine coverage among a random sample of hospitalised persons aged 65 years or more, Victoria.

    PubMed

    Andrews, Ross M; Skull, Susan A; Byrnes, Graham B; Campbell, Donald A; Turner, Joy L; McIntyre, Peter B; Kelly, Heath A

    2005-01-01

    This study was undertaken to assess the uptake of influenza and pneumococcal vaccination based on provider records of the hospitalised elderly, a group at high risk of influenza and pneumococcal disease. The study used a random sample of 3,204 admissions at two Victorian teaching hospitals for patients, aged 65 years or more who were discharged between 1 April 2000 and 31 March 2002. Information on whether the patient had received an influenza vaccination within the year prior to admission or pneumococcal vaccination within the previous five years was ascertained from the patient's nominated medical practitioner/vaccine provider. Vaccination records were obtained from providers for 82 per cent (2,804/2,934) of eligible subjects. Influenza vaccine coverage was 70.9 per cent (95% CI 68.9-72.9), pneumococcal coverage was 52.6 per cent (95% CI 50.4-54.8) and 46.6 per cent (95% CI 44.4-48.8) had received both vaccines. Coverage for each vaccine increased seven per cent over the two study years. For pneumococcal vaccination, there was a marked increase in 1998 coinciding with the introduction of Victoria's publicly funded program. Influenza and pneumococcal vaccine coverage in eligible hospitalised adults was similar to, but did not exceed, estimates in the general elderly population. Pneumococcal vaccination coverage reflected the availability of vaccine through Victoria's publicly funded program. A nationally funded pneumococcal vaccination program for the elderly, as announced recently, should improve coverage. However, these data highlight the need for greater awareness of pneumococcal vaccine among practitioners and for systematic recording of vaccination status, as many of these subjects will soon become eligible for revaccination.

  7. Multi-Serotype Pneumococcal Nasopharyngeal Carriage Prevalence in Vaccine Naïve Nepalese Children, Assessed Using Molecular Serotyping

    PubMed Central

    Kandasamy, Rama; Gurung, Meeru; Thapa, Anushil; Ndimah, Susan; Adhikari, Neelam; Murdoch, David R.; Kelly, Dominic F.; Waldron, Denise E.; Gould, Katherine A.; Thorson, Stephen; Shrestha, Shrijana; Hinds, Jason; Pollard, Andrew J.

    2015-01-01

    Invasive pneumococcal disease is one of the major causes of death in young children in resource poor countries. Nasopharyngeal carriage studies provide insight into the local prevalence of circulating pneumococcal serotypes. There are very few data on the concurrent carriage of multiple pneumococcal serotypes. This study aimed to identify the prevalence and serotype distribution of pneumococci carried in the nasopharynx of young healthy Nepalese children prior to the introduction of a pneumococcal conjugate vaccine using a microarray-based molecular serotyping method capable of detecting multi-serotype carriage. We conducted a cross-sectional study of healthy children aged 6 weeks to 24 months from the Kathmandu Valley, Nepal between May and October 2012. Nasopharyngeal swabs were frozen and subsequently plated on selective culture media. DNA extracts of plate sweeps of pneumococcal colonies from these cultures were analysed using a molecular serotyping microarray capable of detecting relative abundance of multiple pneumococcal serotypes. 600 children were enrolled into the study: 199 aged 6 weeks to <6 months, 202 aged 6 months to < 12 months, and 199 aged 12 month to 24 months. Typeable pneumococci were identified in 297/600 (49·5%) of samples with more than one serotype being found in 67/297 (20·2%) of these samples. The serotypes covered by the thirteen-valent pneumococcal conjugate vaccine were identified in 44·4% of samples containing typeable pneumococci. Application of a molecular serotyping approach to identification of multiple pneumococcal carriage demonstrates a substantial prevalence of co-colonisation. Continued surveillance utilising this approach following the introduction of routine use of pneumococcal conjugate vaccinates in infants will provide a more accurate understanding of vaccine efficacy against carriage and a better understanding of the dynamics of subsequent serotype and genotype replacement. PMID:25643355

  8. A Cross-Sectional Observational Study of Pneumococcal Carriage in Children, Their Parents, and Older Adults Following the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine

    PubMed Central

    Hamaluba, Mainga; Kandasamy, Rama; Ndimah, Susan; Morton, Richard; Caccamo, Marisa; Robinson, Hannah; Kelly, Sarah; Field, Aimee; Norman, Lily; Plested, Emma; Thompson, Ben A.V.; Zafar, Azhar; Kerridge, Simon A.; Lazarus, Rajeka; John, Tessa; Holmes, Jane; Fenlon, Shannon N.; Gould, Katherine A.; Waight, Pauline; Hinds, Jason; Crook, Derrick; Snape, Matthew D.; Pollard, Andrew J.

    2015-01-01

    Abstract Using nasopharyngeal carriage as a marker of vaccine impact, pneumococcal colonization and its relation to invasive disease were examined in children, their parents, and older adults in the United Kingdom following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and prior to 13-valent pneumococcal conjugate vaccine (PCV13). A cross-sectional observational study was conducted, collecting nasopharyngeal swabs from children aged 25 to 55 months who had previously received 3 doses of PCV7, their parents, and adults aged ≥65 years. Pneumococcal serotyping was conducted according to World Health Organization guidelines with nontypeable isolates further analyzed by molecular serotyping. A national invasive disease surveillance program was conducted throughout the corresponding period. Pneumococcus was isolated from 47% of children, 9% of parents, and 2.2% of older adults. For these groups, the percentage of serotypes covered by PCV7 were 1.5%, 0.0%, and 15.4%, with a further 20.1%, 44.4%, and 7.7% coverage added by those in PCV13. In each group, the percentage of disease due to serotypes covered by PCV7 were 1.0%, 7.4% and 5.1% with a further 65.3%, 42.1%, and 61.4% attributed to those in PCV13. The prevalence of carriage is the highest in children, with direct vaccine impact exemplified by low carriage and disease prevalence of PCV7 serotypes in vaccinated children, whereas the indirect effects of herd protection are implied by similar observations in unvaccinated parents and older adults. PMID:25569650

  9. Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption ▿

    PubMed Central

    Schuerman, L.; Wysocki, J.; Tejedor, J. C.; Knuf, M.; Kim, K.-H.; Poolman, J.

    2011-01-01

    We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines. PMID:21994351

  10. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human Papillomavirus Vaccines AGENCY: Centers for Disease Control and...: Under the National Childhood Vaccine Injury Act (NCVIA) (42 U.S.C. 300aa-26), the CDC must...

  11. Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking

    PubMed Central

    Siegel, Steven J.; Tamashiro, Edwin; Weiser, Jeffrey N.

    2015-01-01

    Infections are a common cause of infant mortality worldwide, especially due to Streptococcus pneumoniae. Colonization is the prerequisite to invasive pneumococcal disease, and is particularly frequent and prolonged in children, though the mechanisms underlying this susceptibility are unknown. We find that infant mice exhibit prolonged pneumococcal carriage, and are delayed in recruiting macrophages, the effector cells of clearance, into the nasopharyngeal lumen. This lack of macrophage recruitment is paralleled by a failure to upregulate chemokine (C-C) motif ligand 2 (Ccl2 or Mcp-1), a macrophage chemoattractant that is required in adult mice to promote clearance. Baseline expression of Ccl2 and the related chemokine Ccl7 is higher in the infant compared to the adult upper respiratory tract, and this effect requires the infant microbiota. These results demonstrate that signals governing macrophage recruitment are altered at baseline in infant mice, which prevents the development of appropriate innate cell infiltration in response to pneumococcal colonization, delaying clearance of pneumococcal carriage. PMID:26107875

  12. Single-Step Multiplex PCR Assay for Determining 92 Pneumococcal Serotypes

    PubMed Central

    Ercibengoa, María; Santacatterina, Erica; Alonso, Marta; Pérez-Trallero, Emilio

    2016-01-01

    For pneumococcal disease surveillance, simple and cost-effective methods capable of determining all serotypes are needed. Combining a single-tube multiplex PCR with fluorescently labeled primers followed by amplicon analysis using automated fluorescent capillary electrophoresis, each serotype of 92 reference isolates and 297 recently collected clinical isolates was successfully determined. PMID:27280423

  13. Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.

    PubMed

    Tavares, Luciana P; Garcia, Cristiana C; Vago, Juliana P; Queiroz-Junior, Celso M; Galvão, Izabela; David, Bruna A; Rachid, Milene A; Silva, Patrícia M R; Russo, Remo C; Teixeira, Mauro M; Sousa, Lirlândia P

    2016-07-01

    Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases.

  14. Ofloxacin-like antibiotics inhibit pneumococcal cell wall-degrading virulence factors.

    PubMed

    Fernández-Tornero, Carlos; García, Ernesto; de Pascual-Teresa, Beatriz; López, Rubens; Giménez-Gallego, Guillermo; Romero, Antonio

    2005-05-20

    The search for new drugs against Streptococcus pneumoniae (pneumococcus) is driven by the 1.5 million deaths it causes annually. Choline-binding proteins attach to the pneumococcal cell wall through domains that recognize choline moieties, and their involvement in pneumococcal virulence makes them potential targets for drug development. We have defined chemical criteria involved in the docking of small molecules from a three-dimensional structural library to the major pneumococcal autolysin (LytA) choline binding domain. These criteria were used to identify compounds that could interfere with the attachment of this protein to the cell wall, and several quinolones that fit this framework were found to inhibit the cell wall-degrading activity of LytA. Furthermore, these compounds produced similar effects on other enzymes with different catalytic activities but that contained a similar choline binding domain; that is, autolysin (LytC) and the phage lytic enzyme (Cpl-1). Finally, we resolved the crystal structure of the complex between the choline binding domain of LytA and ofloxacin at a resolution of 2.6 Angstroms. These data constitute an important launch pad from which effective drugs to combat pneumococcal infections can be developed.

  15. Enzymatic method for improving the injectability of polysaccharides

    DOEpatents

    Griffith, William L.; Compere, Alicia L.; Holleman, James W.

    1982-01-01

    A method for enhancing the ability of polysaccharides in aqueous solution to flow through a porous medium comprises contacting the polysaccharides with an endoenzyme capable of hydrolyzing at least one of the linkages of the sugar units of the polysaccharides and maintaining the polysaccharides in contact with the enzyme under hydrolysis conditions for a time sufficient to decrease the tendency of the polysaccharides to plug the porous medium yet insufficient to decrease the viscosity of the aqueous polysaccharides by more than 25%. The partially hydrolyzed polysaccharides are useful as thickening agents for flooding water used to recover oil from oil-containing subterranean formations.

  16. Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

    PubMed

    Hirst, Ceri; Owusu-Ofori, Shirley

    2014-11-06

    Background This is an update of a Cochrane Review first published in 2002, and previously updated in 2012. People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three.Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.Objectives To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 26 June 2014.Selection criteria All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.Data collection and analysis Both authors independently extracted data and assessed trial quality.Main results Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age

  17. Vacuum Ultraviolet Action Spectroscopy of Polysaccharides

    NASA Astrophysics Data System (ADS)

    Enjalbert, Quentin; Brunet, Claire; Vernier, Arnaud; Allouche, Abdul-Rahman; Antoine, Rodolphe; Dugourd, Philippe; Lemoine, Jérôme; Giuliani, Alexandre; Nahon, Laurent

    2013-08-01

    We studied the optical properties of gas-phase polysaccharides (maltose, maltotetraose, and maltohexaose) ions by action spectroscopy using the coupling between a quadrupole ion trap and a vacuum ultraviolet (VUV) beamline at the SOLEIL synchrotron radiation facility (France) in the 7 to 18 eV range. The spectra provide unique benchmarks for evaluation of theoretical data on electronic transitions of model carbohydrates in the VUV range. The effects of the nature of the charge held by polysaccharide ions on the relaxation processes were also explored. Finally the effect of isomerization of polysaccharides (with melezitose and raffinose) on their photofragmentation with VUV photons is presented.

  18. Pneumococcal Meningitis in Children: Epidemiology, Serotypes, and Outcomes From 1997–2010 in Utah

    PubMed Central

    Ampofo, Krow; Byington, Carrie L.; Filloux, Francis; Hersh, Adam L.; Blaschke, Anne J.; Cowan, Priscilla; Korgenski, Kent; Mason, Edward O.; Pavia, Andrew T.

    2013-01-01

    BACKGROUND: After licensure of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States in 2000, the incidence of pediatric pneumococcal meningitis decreased significantly. However, cases continue to occur. It is unknown whether meningitis due to PCV7 and non-PCV7 serotypes causes similar morbidity and mortality. METHODS: We performed a retrospective cohort study of laboratory-confirmed pneumococcal meningitis among Utah children from 1997 to 2010. We reviewed medical records and obtained clinical data during the acute illness and follow-up data on neurologic sequelae. RESULTS: Sixty-eight cases of meningitis were identified. PCV7 serotypes caused 64% of cases before and 25% of cases after licensure of PCV7 (P < .01). The age range was similar before and after PCV7 licensure (P = .5). The overall case fatality rate was 13% and was similar among cases caused by PCV7 and non-PCV7 serotypes (P = .7). Children with PCV7 serotypes were more likely to require mechanical ventilation (68% vs 34%; P < .01). Of all survivors, 63% had neurologic sequelae, and the proportion was similar after infection with PCV7 or non-PCV7 serotypes (P = .1). More than one-half (54%) of all children who developed pneumococcal meningitis in the PCV7 period were eligible for PCV7 and had not been immunized. CONCLUSIONS: Pneumococcal meningitis continues to be associated with high mortality and morbidity; death and neurologic sequelae are common with both PCV7 and non-PCV7 serotype meningitis. The substantial burden of this disease and continued cases among unimmunized children reinforce the need for more effective immunization strategies and continued surveillance in the era of PCV13. PMID:23979090

  19. Influenza and Pneumococcal Vaccination in Hematological Malignancies: a Systematic Review of Efficacy, Effectiveness, and Safety

    PubMed Central

    La Torre, Giuseppe; Mannocci, Alice; Colamesta, Vittoria; D’Egidio, Valeria; Sestili, Cristina; Spadea, Antonietta

    2016-01-01

    Background The risk of getting influenza and pneumococcal disease is higher in cancer patients, and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To assess flu and pneumococcal vaccinations efficacy, effectiveness, and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in the scientific literature about the flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 22 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI=6–62%) for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI=23.2 – 63.3 %) and 39.6 % (95% CI=26%–54.1%) for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI=19.7–51.2%) for H1N1, 23% (95% CI=16.6–31.5%) for H3N2, 29% (95% CI=21.3–37%) for B. Conclusion Despite the low rate of response, flu, and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines. PMID:27648207

  20. Is household antibiotic use a risk factor for antibiotic-resistant pneumococcal infection?

    PubMed Central

    Kwan-Gett, T. S.; Davis, R. L.; Shay, D. K.; Black, S.; Shinefield, H.; Koepsell, T.

    2002-01-01

    We used microbiology and pharmacy data from health-maintenance organizations to determine whether antibiotic use by a household member increases the risk of penicillin-non-susceptible pneumococcal disease. Though it has been well established that an individual's antibiotic use increases one's risk of antibiotic-resistant infection, it is unclear whether the risk is increased if a member of one's household is exposed to antibiotics. We therefore conducted a case-control study of patients enrolled in health maintenance organizations in Western Washington and Northern California. Cases were defined as individuals with penicillin-non-susceptible pneumococcal infection; controls were individuals with penicillin-susceptible pneumococcal infection. Socioeconomic variables were obtained by linking addresses with 1997 census block group data. One-hundred and thirty-four cases were compared with 798 controls. Individual antibiotic use prior to diagnosis increased the odds of penicillin non-susceptibility, with the strongest effect seen for beta-lactam use within 2 months (OR 1.8, 95% CI 1.2, 2.8). When household antibiotic use by persons other than the patient were considered, at 4 months prior to diagnosis there was a trend towards an association between penicillin non-susceptibility and beta-lactam antibiotic use, and a possible association in a small subgroup of patients with eye and ear isolates. However, no significant overall pattern of association was seen. We conclude that though antibiotic use of any kind within 2 months prior to diagnosis is associated with an increased risk of penicillin-non-susceptible pneumococcal disease, there is no significant overall pattern of association between household antibiotic use and penicillin-non-susceptible pneumococcal infection. PMID:12558332

  1. Laboratory-based diagnosis of pneumococcal pneumonia: state of the art and unmet needs.

    PubMed

    Vernet, G; Saha, S; Satzke, C; Burgess, D H; Alderson, M; Maisonneuve, J-F; Beall, B W; Steinhoff, M C; Klugman, K P

    2011-05-01

    In view of the increasing use of pneumococcal vaccines, especially in the developing world, there is a need for appropriate diagnostics to understand the aetiology of pneumonia, to define the burden of pneumococcal disease, and to monitor vaccine efficacy and effectiveness. This article summarizes a meeting on the diagnosis, detection and serotyping of pneumococcal disease organized by PATH and Fondation Mérieux (18-20 October 2009, Fondation Mérieux Conference Centre, Les Pensières, France). Workers and experts met to discuss the gaps in the microbiology-based diagnosis of Streptococcus pneumoniae disease, with special emphasis on pneumonia. The meeting was designed to evaluate the state of the art of pneumococcal diagnostics and serotyping methodologies, identify research and development needs, and propose new guidelines to public health authorities to support the introduction of vaccines. Regarding detection, the main recommendations were to encourage chest X-rays and antigen detection in urine. Large-scale studies are needed to evaluate the diagnostic utility of test algorithms that associate chest X-rays, antigen detection in urine, S. pneumoniae quantitative PCR in nasopharyngeal aspirates and sputum, and C-reactive protein or procalcitonin measurement in blood. Efforts should be focused on proteomics to identify pneumococcus-specific antigens in urine or host markers in blood expressed during pneumonia. It was recommended to develop S. pneumoniae typing capacities, to understand the epidemiology of pneumococcal disease, and to evaluate vaccine effectiveness. Simple and effective approaches are encouraged, and new technologies based on beads, microarrays or deep sequencing should be developed to determine, in a single test capsular serotype, resistance profile and genotype.

  2. Improving pneumococcal vaccination rates of medical inpatients in urban Nepal using quality improvement measures

    PubMed Central

    Bock, Allison; Chintamaneni, Kathan; Rein, Lisa; Frazer, Tifany; Kayastha, Gyan; MacKinney, Theodore

    2016-01-01

    Streptococcus pneumoniae infection is associated with high morbidity and mortality in low income countries. In Nepal, there is a high lung disease burden and incidence of pneumonia due to multiple factors including indoor air pollution, dust exposure, recurrent infections, and cigarette smoking. Despite the ready availability of effective pneumococcal vaccines (PNV), vaccine coverage rates remain suboptimal globally. Quality Improvement (QI) principles could be applied to improve compliance, but it is a virtually new technology in Nepal. This QI study for Patan Hospital sought to introduce the concept of QI there, to measure the baseline pneumococcal vaccination rate of qualifying adult patients discharged from the medical wards and to assess reasons for non-vaccination. QI interventions were instituted to improve this rate, measuring the effectiveness of QI methods to produce the desired outcomes using the Model for Improvement, Plan-Do-Study-Change (PDSA) methodology. In the three week baseline assessment, 2 out of 81 (2%) eligible patients recalled ever receiving a prior pneumococcal vaccine; 68 (84%) unvaccinated patients responded that they were not asked or were unaware of the PNV. After the QI interventions, the pneumococcal vaccination rate significantly increased to 42% (23/56, p<0.001). Post-intervention, the leading reason for non-vaccination was cost (20%, 11/56). Only 5 (9%) unvaccinated patients were not asked or were unaware of the PNV, a significant change in that process outcome from baseline (p<0.001). Quality improvement measures were effective in increasing pneumococcal vaccination rates, despite the limited familiarity with QI methods at this major teaching hospital. QI techniques may be useful in this and other efforts to improve quality in resource-limited settings, without great cost. PMID:27933153

  3. Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis.

    PubMed

    Savva, Athina; Brouwer, Matthijs C; Roger, Thierry; Valls Serón, Mercedes; Le Roy, Didier; Ferwerda, Bart; van der Ende, Arie; Bochud, Pierre-Yves; van de Beek, Diederik; Calandra, Thierry

    2016-03-29

    Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.

  4. Pneumococcal Acquisition Among Infants Exposed to HIV in Rural Malawi: A Longitudinal Household Study

    PubMed Central

    Heinsbroek, Ellen; Tafatatha, Terence; Chisambo, Christina; Phiri, Amos; Mwiba, Oddie; Ngwira, Bagrey; Crampin, Amelia C.; Read, Jonathan M.; French, Neil

    2016-01-01

    The prevalence of Streptococcus pneumoniae (pneumococcus) carriage is higher in adults who are infected with human immunodeficiency virus (HIV) than in adults who are not. We hypothesized that infants exposed to HIV become carriers of nasopharyngeal pneumococcus earlier and more frequently than infants who are not exposed to HIV. We compared infant pneumococcal acquisition by maternal HIV status and household exposure in Karonga District, Malawi, in 2009–2011, before the introduction of pneumococcal conjugate vaccine. Nasopharyngeal swabs were collected every 4–6 weeks in the first year of life from infants with known HIV-exposure status, their mothers, and other household members. We studied infant pneumococcal acquisition by maternal HIV status, serotype-specific household exposure, and other risk factors, including seasonality. We recruited 54 infants who were exposed to HIV and 131 infants who were not. There was no significant difference in pneumococcal acquisition by maternal HIV status (adjusted rate ratio (aRR) = 1.00, 95% confidence interval (CI): 0.87, 1.15). Carriage by the mother was associated with greater acquisition of the same serotype (aRR = 3.09, 95% CI: 1.47, 6.50), but the adjusted population attributable fraction was negligible (1.9%, 95% CI: 0.0, 4.3). Serotype-specific exposure to children under 5 years of age was associated with higher acquisition (aRR = 4.30, 95% CI: 2.80, 6.60; adjusted population attributable fraction = 8.8%, 95% CI: 4.0, 13.4). We found no evidence to suggest that maternal HIV infection would affect the impact of pneumococcal vaccination on colonization in this population. PMID:26628514

  5. Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

    PubMed Central

    Savva, Athina; Brouwer, Matthijs C.; Valls Serón, Mercedes; Le Roy, Didier; Ferwerda, Bart; van der Ende, Arie; Bochud, Pierre-Yves; van de Beek, Diederik; Calandra, Thierry

    2016-01-01

    Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (−794 CATT5–8; rs5844572) and a single-nucleotide polymorphism (−173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and −173 C high-expression MIF alleles were associated with unfavorable outcome (P = 0.005 and 0.003) and death (P = 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P = 0.02] and carriage of the CATT7 allele (OR 5.12, P = 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P = 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy. PMID:26976591

  6. Development of a whole cell pneumococcal vaccine: BPL inactivation, cGMP production, and stability.

    PubMed

    Gonçalves, Viviane M; Dias, Waldely O; Campos, Ivana B; Liberman, Celia; Sbrogio-Almeida, Maria E; Silva, Eliane P; Cardoso, Celso P; Alderson, Mark; Robertson, George; Maisonneuve, Jean-François; Tate, Andrea; Anderson, Porter; Malley, Richard; Fratelli, Fernando; Leite, Luciana C C

    2014-02-19

    Pneumococcal infections impose a large burden of disease on the human population, mainly in developing countries, and the current pneumococcal vaccines offer serotype-specific protection, but do not cover all pathogenic strains, leaving populations vulnerable to disease caused by non-vaccine serotypes. The pneumococcal whole cell vaccine is a low-cost strategy based on non-capsular antigens common to all strains, inducing serotype-independent immunity. Therefore, we developed the process for the cGMP production of this cellular vaccine. Initially, three engineering runs and two cGMP runs were performed in 60-L bioreactors, demonstrating the consistency of the production process, as evaluated by the growth curves, glucose consumption and metabolite formation (lactate and acetate). Cell recovery by tangential filtration was 92 ± 13 %. We optimized the conditions for beta-propiolactone (BPL) inactivation of the bacterial suspensions, establishing a maximum cell density of OD600 between 27 and 30, with a BPL concentration of 1:4000 (v/v) at 150 rpm and 4 °C for 30 h. BPL was hydrolyzed by heating for 2h at 37 °C. The criteria and methods for quality control were defined using the engineering runs and the cGMP Lots passed all specifications. cGMP vaccine Lots displayed high potency, inducing between 80 and 90% survival in immunized mice when challenged with virulent pneumococci. Sera from mice immunized with the cGMP Lots recognized several pneumococcal proteins in the extract of encapsulated strains by Western blot. The cGMP whole cell antigen bulk and whole cell vaccine product lots were shown to be stable for up to 12 and 18 months, respectively, based upon survival assays following i.p. challenge. Our results show the consistency and stability of the cGMP whole cell pneumococcal vaccine lots and demonstrate the feasibility of production in a developing country setting.

  7. Design and optimization of a chromatographic purification process for Streptococcus pneumoniae serotype 23F capsular polysaccharide by a Design of Experiments approach.

    PubMed

    Ji, Yu; Tian, Yang; Ahnfelt, Mattias; Sui, Lili

    2014-06-27

    Multivalent pneumococcal vaccines were used worldwide to protect human beings from pneumococcal diseases. In order to eliminate the toxic organic solutions used in the traditional vaccine purification process, an alternative chromatographic process for Streptococcus pneumoniae serotype 23F capsular polysaccharide (CPS) was proposed in this study. The strategy of Design of Experiments (DoE) was introduced into the process development to solve the complicated design procedure. An initial process analysis was given to review the whole flowchart, identify the critical factors of chromatography through FMEA and chose the flowthrough mode due to the property of the feed. A resin screening study was then followed to select candidate resins. DoE was utilized to generate a resolution IV fractional factorial design to further compare candidates and narrow down the design space. After Capto Adhere was selected, the Box-Behnken DoE was executed to model the process and characterize all effects of factors on the responses. Finally, Monte Carlo simulation was used to optimize the process, test the chosen optimal conditions and define the control limit. The results of three scale-up runs at set points verified the DoE and simulation predictions. The final results were well in accordance with the EU pharmacopeia requirements: Protein/CPS (w/w) 1.08%; DNA/CPS (w/w) 0.61%; the phosphorus content 3.1%; the nitrogen 0.315% and the Methyl-pentose percentage 47.9%. Other tests of final pure CPS also met the pharmacopeia specifications. This alternative chromatographic purification process for pneumococcal vaccine without toxic organic solvents was successfully developed by the DoE approach and proved scalability, robustness and suitability for large scale manufacturing.

  8. Serogroup quantitation of multivalent polysaccharide and polysaccharide-conjugate meningococcal vaccines from China.

    PubMed

    Cook, Matthew C; Gibeault, Sabrina; Filippenko, Vasilisa; Ye, Qiang; Wang, Junzhi; Kunkel, Jeremy P

    2013-07-01

    The active components of most meningococcal vaccines are four antigenic serogroup capsular polysaccharides (A, C, Y, W135). The vaccines, monovalent or multivalent mixtures of either free polysaccharides or polysaccharides conjugated to antigenic carrier proteins, may be in liquid or lyophilised formulations, with or without excipients. Acid hydrolysis and chromatographic methods for serogroup quantitation, which were previously optimised and qualified using polysaccharide-based standards and a narrow range of real vaccines, are here challenged with multiple lots of a broad assortment of additional multivalent polysaccharide-based meningococcal vaccine products. Centrifugal filtration successfully removed all interfering lactose excipient without loss of polysaccharides to allow for the determination of Y and W135 serogroups. Replicate operations by three different analysts indicated high method reproducibility. Results indicated some lot-to-lot and product-to-product variations. However, all vaccines were within general specifications for each serogroup polysaccharide, with the exception of all lots of one polysaccharide vaccine - which by these methods were found to be deficient in the serogroup A component only. These robust techniques are very useful for the evaluation of antigen content and consistency of manufacture. The deformulation, hydrolysis and chromatographic methods may be adaptable for the evaluation of other types of polysaccharide-based vaccines.

  9. Development of an opsonin inhibition assay for evaluation of complex polysaccharide protective epitopes.

    PubMed

    McNeely, Tessie; Luo, Shengyuan; Manger, Walt; Herber, Wayne; Schofield, Tim; Tan, Charles; Newman, Kathy; Sadoff, Jerald; Donnelly, John; Cross, Alan

    2006-03-10

    The induction of opsonic antibodies directed against capsular polysaccharides (Ps) is an important mechanism by which immunization protects against the development of invasive pneumococcal (Pn) infection. In preparing Pn vaccines, it is necessary to compare different manufacturing lots of capsular Ps, or to compare oligosaccharides used for conjugate vaccines with native capsular Ps, in order to insure that important epitopes of the Ps are maintained. We have developed an opsonic-antibody inhibition assay (OIA) to compare the functional epitopes of different capsular Ps preparations in vitro. Components of the OIA are primary neutrophils, rabbit complement (C'), and type-specific antibody (Ab). After conditions for optimal opsonic killing were determined for each Pn serotype, anti-Pn Ab was pre-incubated with different dilutions of purified capsular Ps, then added to the OIA mix. Plotting the % bacteria killed versus Ps concentration (log transformed) yielded a linear curve that was used to quantify the concentration of capsular Ps which inhibited the bacteria killing by 50% (IC50). The IC50 was determined for 8 Pn Ps types. These ranged between 6 ng/ml for type 6B and 1268 ng/ml for type 23F. Importantly OIA curves were statistically identical for two different manufacturing lots of capsular Ps for the 8 Pn Ps types. We conclude that differences among capsular Ps used for Pn vaccines could be detected with an OIA assay and these differences may predict the ability of Ps preparations to induce functionally active antibody when formulated into vaccines.

  10. Polysaccharide-based Nanoparticles for Gene Delivery.

    PubMed

    Huh, Myung Sook; Lee, Eun Jung; Koo, Heebeom; Yhee, Ji Young; Oh, Keun Sang; Son, Sohee; Lee, Sojin; Kim, Sun Hwa; Kwon, Ick Chan; Kim, Kwangmeyung

    2017-04-01

    Nanoparticles based on nanotechnology and biotechnology have emerged as efficient carriers for various biopharmaceutical agents including proteins and genes. In particular, polysaccharides have attracted interest of many researchers in the drug delivery field due to their advantages such as biocompatibility, biodegradability, low toxicity, and ease of modification. A number of polysaccharides including chitosan, hyaluronic acid, and dextran, and their derivatives have been widely used as polymeric backbones for the formation of nanoparticles, which can be provided as valuable gene delivery carriers. In this review, we introduce the chemical and physical natures of different polysaccharides particularly used in biomedical applications, and then discuss recent progress in the development of polysaccharide-based nanoparticles for gene delivery.

  11. Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization.

    PubMed

    Keller, Lance E; Luo, Xiao; Thornton, Justin A; Seo, Keun-Seok; Moon, Bo Youn; Robinson, D Ashley; McDaniel, Larry S

    2015-11-01

    Current vaccinations are effective against encapsulated strains of Streptococcus pneumoniae, but they do not protect against nonencapsulated Streptococcus pneumoniae (NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects. Mammalian cytokine expression was determined in an in vivo mouse model and in an in vitro cell culture system. Systemic and mucosal mouse immunization studies were performed to determine the immunogenic potential of PspK. Murine serum and saliva were collected to quantitate specific antibody isotype responses and the ability of antibody and various proteins to inhibit epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp was able to colonize the mouse nasopharynx as effectively as encapsulated pneumococci. Systemic and mucosal immunization provided protection from colonization by PspK-positive (PspK(+)) NESp. Anti-PspK antibodies were recovered from immunized mice and significantly reduced the ability of NESp to adhere to human epithelial cells. A protein-based pneumococcal vaccine is needed to provide broad protection against encapsulated and nonencapsulated pneumococci in an era of increasing antibiotic resistance and vaccine escape mutants. We demonstrate that PspK may serve as an NESp target for next-generation pneumococcal vaccines. Immunization with PspK protected against pneumococcal colonization, which is requisite for pneumococcal disease.

  12. Monoclonal antibodies against plant cell wall polysaccharides

    SciTech Connect

    Hahn, M.G.; Bucheli, E.; Darvill, A.; Albersheim, P. )

    1989-04-01

    Monoclonal antibodies (McAbs) are useful tools to probe the structure of plant cell wall polysaccharides and to localize these polysaccharides in plant cells and tissues. Murine McAbs were generated against the pectic polysaccharide, rhamnogalacturonan I (RG-I), isolated from suspension-cultured sycamore cells. The McAbs that were obtained were grouped into three classes based upon their reactivities with a variety of plant polysaccharides and membrane glycoproteins. Eleven McAbs (Class I) recognize epitope(s) that appear to be immunodominant and are found in RG-I from sycamore and maize, citrus pectin, polygalacturonic acid, and membrane glycoproteins from suspension-cultured cells of sycamore, maize, tobacco, parsley, and soybean. A second group of five McAbs (Class II) recognize epitope(s) present in sycamore RG-I, but do not bind to any of the other polysaccharides or glycoproteins recognized by Class I. Lastly, one McAb (Class III) reacts with sycamore RG-I, sycamore and tamarind xyloglucan, and sycamore and rice glucuronoarabinoxylan, but does not bind to maize RG-I, polygalacturonic acid or the plant membrane glycoproteins recognized by Class I. McAbs in Classes II and III are likely to be useful in studies of the structure, biosynthesis and localization of plant cell wall polysaccharides.

  13. A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada.

    PubMed

    McNeil, Shelly A; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004-2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.

  14. PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

    PubMed Central

    Croney, Christina M.; Coats, Mamie T.; Nahm, Moon H.; Briles, David E.

    2012-01-01

    Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD. PMID:22539473

  15. A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada

    PubMed Central

    McNeil, Shelly A.; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high. PMID:27445530

  16. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia

    PubMed Central

    Moorthy, Anandi Narayana; Rai, Prashant; Jiao, Huipeng; Wang, Shi; Tan, Kong Bing; Qin, Liang; Watanabe, Hiroshi; Zhang, Yongliang; Teluguakula, Narasaraju; Chow, Vincent Tak Kwong

    2016-01-01

    Neutrophil extracellular traps (NETs) are released by activated neutrophils to ensnare and kill microorganisms. NETs have been implicated in tissue injury since they carry cytotoxic components of the activated neutrophils. We have previously demonstrated the generation of NETs in infected murine lungs during both primary pneumococcal pneumonia and secondary pneumococcal pneumonia after primary influenza. In this study, we assessed the correlation of pneumococcal capsule size with pulmonary NETs formation and disease severity. We compared NETs formation in the lungs of mice infected with three pneumococcal strains of varying virulence namely serotypes 3, 4 and 19F, as well as a capsule-deficient mutant of serotype 4. In primary pneumonia, NETs generation was strongly associated with the pneumococcal capsule thickness, and was proportional to the disease severity. Interestingly, during secondary pneumonia after primary influenza infection, intense pulmonary NETs generation together with elevated myeloperoxidase activity and cytokine dysregulation determined the disease severity. These findings highlight the crucial role played by the size of pneumococcal capsule in determining the extent of innate immune responses such as NETs formation that may contribute to the severity of pneumonia. PMID:27034012

  17. In vivo anti-radiation activities of the Ulva pertusa polysaccharides and polysaccharide-iron(III) complex.

    PubMed

    Shi, Jinming; Cheng, Cuilin; Zhao, Haitian; Jing, Jing; Gong, Ning; Lu, Weihong

    2013-09-01

    Polysaccharides with different molecular weights were extracted from Ulva pertusa and fractionated by ultrafiltration. Iron(III) complex of the low molecular-weight U. pertusa polysaccharides were synthesized. Atomic absorption spectrum showed that the iron content of iron(III)-polysaccharide complex was 27.4%. The comparison between U. pertusa polysaccharides and their iron(III) complex showed that iron chelating altered the structural characteristics of the polysaccharides. The bioactivity analysis showed that polysaccharide with low molecular weight was more effective than polysaccharide with high molecular weight in protecting mice from radiation induced damages on bone marrow cells and immune system. Results also proved that the anti-radiation and anti-oxidative activity of iron(III) complex of low molecular-weight polysaccharides were not less than that of low molecular-weight polysaccharides.

  18. Nasopharyngeal pneumococcal carriage of children attending day care centers in Korea: comparison between children immunized with 7-valent pneumococcal conjugate vaccine and non-immunized.

    PubMed

    Kim, Kyung-Hyo; Hong, Jung Yun; Lee, Hyunju; Kwak, Ga Young; Nam, Chan Hee; Lee, Soo Young; Oh, Eunsang; Yu, Jigui; Nahm, Moon H; Kang, Jin Han

    2011-02-01

    To confirm the effect of 7-valent pneumococcal conjugate vaccine (PCV7), pneumococcal nasopharyngeal (NP) carriage was compared between vaccinated (3 + 1 doses PCV7) and non-vaccinated children. Vaccinated subjects were recruited from highly vaccinated regions (≥ 60%), Seoul and Incheon whereas control subjects were recruited from Jeju Island where vaccination rates are low (< 15%). NP swabs were obtained from 400 children aged 18-59 months. Serotype and antibiotic susceptibility was analyzed. Pneumococcal carriage rate was 18.0% (36/200) and 31.5% (63/200) for the vaccinated and control group, respectively. Among those vaccinated, 41.7% (15/36) of the serotypes were vaccine-related type (VRT: 6A, 6C, 19A) with the most common serotype 6C. The next common type was non-typable/non-capsule 30.6% (11/36) followed by non-vaccine type 16.7% (6/36) and vaccine type (VT) serotypes were found in only 11.1% (4/36). In contrast, 52.4% (33/63) of the isolates in the control group were VT. Resistance rates for penicillin and erythromycin were lower in the vaccine group (vaccine vs control; penicillin 45.2% vs 71.4%, erythromycin 74.2% vs 90.5%, P < 0.05). Multi-drug resistance was also lower in vaccinated subjects (vaccine vs control; 45.2% vs 69.8%, P < 0.05). PCV7 reduces carriage in VT which leads to replacement of pneumococci by antibiotic susceptible VRT or non-vaccine type strains.

  19. Mycoplasma polysaccharide protects against complement

    PubMed Central

    Bolland, Jeffrey R.; Simmons, Warren L.; Daubenspeck, James M.

    2012-01-01

    Although they lack a cell wall, mycoplasmas do possess a glycocalyx. The interactions between the glycocalyx, mycoplasmal surface proteins and host complement were explored using the murine pathogen Mycoplasma pulmonis as a model. It was previously shown that the length of the tandem repeat region of the surface lipoprotein Vsa is associated with susceptibility to complement-mediated killing. Cells producing a long Vsa containing about 40 repeats are resistant to complement, whereas strains that produce a short Vsa of five or fewer repeats are susceptible. We show here that the length of the Vsa protein modulates the affinity of the M. pulmonis EPS-I polysaccharide for the mycoplasma cell surface, with more EPS-I being associated with mycoplasmas producing a short Vsa protein. An examination of mutants that lack EPS-I revealed that planktonic mycoplasmas were highly susceptible to complement killing even when the Vsa protein was long, demonstrating that both EPS-I and Vsa length contribute to resistance. In contrast, the mycoplasmas were resistant to complement even in the absence of EPS-I when the cells were encased in a biofilm. PMID:22504437

  20. Viscoelastic properties of levan polysaccharides

    NASA Astrophysics Data System (ADS)

    Noll, Kenneth; Rende, Deniz; Ozisik, Rahmi; Toksoy-Oner, Ebru

    2014-03-01

    Levan is a naturally occurring polysaccharide that is composed of β-D-fructofuranose units with β(2-6) linkages between fructose rings. It is synthesized by the action of a secreted levansucrase (EC 2.4.1.10) that converts sucrose into the levan externally (exopolysaccharide). Levan is a homopolysaccharide that is non-toxic, water soluble,, and has anti-tumor activity and low immunological response. Therefore, levan presents great potential to be used as a novel functional biopolymer in foods, feeds, cosmetics, pharmaceutical and chemical industries. Despite these favorable properties, levan has a moderately low mechanical properties and poor film forming capability. In the current study, the agglomeration behavior of levan in water and in saline solutions was investigated at 298 and 310 K by dynamic light scattering and transmission electron microscopy (TEM). The viscoelastic properties of neat and oxidized levan films were studied via nanoindentation experiments in the quasi-static and dynamic modes The material is partially based upon work supported by NSF under Grant Nos. 1200270 and 1003574, and TUBITAK 111M232.

  1. EXTRACELLULAR POLYSACCHARIDES OF AZOTOBACTER VINELANDII1

    PubMed Central

    Cohen, Gary H.; Johnstone, Donald B.

    1964-01-01

    Cohen, Gary H. (University of Vermont, Burlington), and Donald B. Johnstone. Extracellular polysaccharides of Azotobacter vinelandii. J. Bacteriol. 88:329–338. 1964.—Extracellular polysaccharides synthetized by Azotobacter vinelandii strains 155, 102, and 3A were shown to be carboxylic acid heteropolysaccharides of apparent high molecular weight. Cells were grown in a nitrogen-free, mineral broth medium with 2% sucrose. Extracellular slime was recovered by centrifugation and purified by repeated alcohol precipitation and Sevag deproteinization. Capsular polysaccharide was recovered from washed cells by mild alkaline digestion. Methods of isolation and purification appeared to provide polysaccharide showing no evidence of heterogeneity when examined by chemical and physical methods. Infrared analysis of purified slime from the three strains suggested fundamental structural similarities. Colorimetric, paper chromatographic, and enzymatic analyses on both intact and acid-hydrolyzed slime polysaccharide indicated that the polymers contained in common galacturonic acid, [α] d-glucose, and rhamnose at a ratio of approximately 43:2:1, as well as a hexuronic acid lactone, probably mannurono-lactone. However, as shown by chemical and infrared analysis, minor differences did exist; namely, slime from strain 155 and 102 contained o-acetyl groups, whereas slime from strain 3A contained none. A sialic acid-like component (1.5% of dry weight of the polysaccharide, calculated as N-acetyl neuraminic acid), was found only in the slime of strain 155. Capsular polysaccharide composition closely resembled that for slime. It is of interest that the major slime components were identical whether the energy source provided for the cells was sucrose, glucose, fructose, or ethanol. PMID:14203348

  2. [Ischemic changes and blood coagulation abnormalities as complications of pneumococcal meningitis].

    PubMed

    Sugiyama, Takashi; Uchiyama, Tsuyoshi; Takashima, Hirotsugu; Yamamoto, Daisuke; Sato, Keishiro; Shimizu, Takako; Otsuki, Yoshiro; Ohashi, Toshihiko

    2015-01-01

    One explanation for cerebral infarctions that occur as a complication of pneumococcal meningitis is blood coagulation abnormalities. We investigated the clinical features, laboratory test results, magnetic resonance imaging (MRI) findings, and pathological features of 10 patients with pneumococcal meningitis between 2006 and 2013 to examine the abnormal findings that may be associated with prognosis. Five patients (50%) that had Glasgow Outcome Scale scores between 1 and 4 were classified as the poor outcome group. In this group, the MRI revealed a high signal intensity on the diffusion-weighted image (DWI), and there was an abnormal signal along the cerebral cortex and Virchow-Robin spaces, which were characterized pathologically by ischemic changes. The plasma thrombin-antithrombin complex (TAT) levels showed greater differences between the poor and good prognosis groups than platlet and D-dimer levels; this suggested that high plasma TAT levels indicate a poor prognosis.

  3. Empyema and bacteremic pneumococcal pneumonia in children under five years of age*, **

    PubMed Central

    Cardoso, Maria Regina Alves; Nascimento-Carvalho, Cristiana Maria Costa; Ferrero, Fernando; Berezin, Eitan Naaman; Ruvinsky, Raul; Sant'Anna, Clemax Couto; Brandileone, Maria Cristina de Cunto; March, Maria de Fátima Bazhuni Pombo; Maggi, Ruben; Feris-Iglesias, Jesus; Benguigui, Yehuda; Camargos, Paulo Augusto Moreira

    2014-01-01

    We compared bacteremic pneumococcal pneumonia (BPP) and pneumococcal empyema (PE), in terms of clinical, radiological, and laboratory findings, in under-fives. A cross-sectional nested cohort study, involving under-fives (102 with PE and 128 with BPP), was conducted at 12 centers in Argentina, Brazil, and the Dominican Republic. Among those with PE, mean age was higher; disease duration was longer; and tachypnea, dyspnea, and high leukocyte counts were more common. Among those with BPP, fever and lethargy were more common. It seems that children with PE can be distinguished from those with BPP on the basis of clinical and laboratory findings. Because both conditions are associated with high rates of morbidity and mortality, prompt diagnosis is crucial. PMID:24626272

  4. Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B.

    PubMed

    Kuipers, Kirsten; Diavatopoulos, Dimitri A; van Opzeeland, Fred; Simonetti, Elles; van den Kieboom, Corné H; Kerstholt, Mariska; Borczyk, Malgorzata; van IngenSchenau, D; Brandsma, Eelke T; Netea, Mihai G; de Jonge, Marien I

    2016-11-15

    For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.

  5. Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor.

    PubMed

    Grewal, Prabhjit K; Aziz, Peter V; Uchiyama, Satoshi; Rubio, Gabriel R; Lardone, Ricardo D; Le, Dzung; Varki, Nissi M; Nizet, Victor; Marth, Jamey D

    2013-12-10

    The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis. This protection is attributable in large part to the rapid induction of a moderate thrombocytopenia by the AMR. We further show that neuraminidase activity in the blood can be manipulated to induce the clearance of AMR ligands including platelets, thereby preactivating a protective response in pneumococcal sepsis that moderates the severity of disseminated intravascular coagulation and enables host survival.

  6. Antibody response to 7-valent conjugated pneumococcal vaccine in patients with chronic lymphocytic leukaemia.

    PubMed

    Sinisalo, Marjatta; Vilpo, Juhani; Itälä, Maija; Väkeväinen, Merja; Taurio, Jyrki; Aittoniemi, Janne

    2007-12-21

    Chronic lymphocytic leukaemia (CLL) is a common adulthood mature B-cell neoplasm. Infections are the most important cause of mortality in this condition, and Streptococcus pneumoniae has been considered the most important single pathogen. We investigated the immunogenicity of 7-valent pneumococcal conjugate vaccine in patients with CLL. The study material comprised 52 patients with CLL and 25 age- and sex-matched controls. The subjects were vaccinated with Prevenar pneumococcal conjugate vaccine. Serum samples were taken for antibody determinations before and four weeks after vaccination. Antibody response rates to vaccine antigens were lower in patients with CLL compared to controls. However, if the vaccine had been administered at an early stage of the disease, i.e. before commencement of chemotherapy and the development of hypogammaglobulinaemia, a significant vaccination response to at least six antigens was obtained in almost 40% of the CLL patients. Our results indicate that early administration of conjugate vaccine may be beneficial in CLL.

  7. Invasive pneumococcal disease complicated by cerebral vasculitis, transient diabetes insipidus and spondylodiscitis.

    PubMed

    Ribeiro, Sofia; Domingues, Vital; Faria, Raquel M; Mendonça, Teresa

    2013-08-19

    Invasive pneumococcal disease (IPD) is a potential life-threatening situation that requires immediate recognition and treatment. Cerebrovascular complications are uncommon and have been reported less frequently in adults than in children. We report a case of 59-year-old man with IPD complicated by cerebral vasculitis, transient central diabetes insipidus and spondylodiscitis. Each of these complications is rare and needs specific approach. Their association is even rarer and to the best of our knowledge this is the first case reported.

  8. Recurrent Invasive Pneumococcal Disease in Children: Underlying Clinical Conditions, and Immunological and Microbiological Characteristics

    PubMed Central

    Alsina, Laia; Basteiro, Maria G.; de Paz, Hector D.; Iñigo, Melania; de Sevilla, Mariona F.; Triviño, Miriam; Juan, Manel; Muñoz-Almagro, Carmen

    2015-01-01

    Purpose Clinical, immunological and microbiological characteristics of recurrent invasive pneumococcal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions. Methods All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection. Results 593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 children). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with reinfection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapy treatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder. Conclusions recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection. PMID:25738983

  9. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia.

    PubMed

    Aspa, Javier; Rajas, Olga; de Castro, Felipe Rodríguez

    2008-02-01

    Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development

  10. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice

    PubMed Central

    Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

    2016-01-01

    Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future. PMID:27196107

  11. Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

    PubMed

    Pope, Caroline; Oliver, Elizabeth H; Ma, Jiangtao; Langton Hewer, Claire; Mitchell, Tim J; Finn, Adam

    2015-03-30

    Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.

  12. Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

    PubMed

    Barichello, Tatiana; Ceretta, Renan A; Generoso, Jaqueline S; Moreira, Ana Paula; Simões, Lutiana R; Comim, Clarissa M; Quevedo, João; Vilela, Márcia Carvalho; Zuardi, Antonio Waldo; Crippa, José A; Teixeira, Antônio Lucio

    2012-12-15

    Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10μl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

  13. Pneumococcal sepsis, peritonitis, and cellulitis at the first episode of nephrotic syndrome.

    PubMed

    Naseri, Mitra

    2013-09-01

    Bacterial infections are common in patients with nephrotic syndrome, including peritonitis, sepsis, meningitis, urinary tract infection, and cellulitis. An 8-year-old boy presented with colicky abdominal pain, vomiting, swollen and painful erythematous lesions around the umbilicus and in anterior surface of left thigh (cellulitis), mild generalized edema, and ascites. The microorganism isolated from peritoneal fluid and blood cultures was Pneumococcus. Association of pneumococcal sepsis, peritonitis, and cellulitis has been rarely reported in nephrotic syndrome.

  14. Galectin-3 Reduces the Severity of Pneumococcal Pneumonia by Augmenting Neutrophil Function

    PubMed Central

    Farnworth, Sarah L.; Henderson, Neil C.; MacKinnon, Alison C.; Atkinson, Kirsten M.; Wilkinson, Tom; Dhaliwal, Kevin; Hayashi, Katsutoshi; Simpson, A. John; Rossi, Adriano G.; Haslett, Christopher; Sethi, Tariq

    2008-01-01

    The Gram-positive Streptococcus pneumoniae is the leading cause of community-acquired pneumonia worldwide, resulting in high mortality. Our in vivo studies show that galectin-3−/− mice develop more severe pneumonia after infection with S. pneumoniae, as demonstrated by increased bacteremia and lung damage compared to wild-type mice and that galectin-3 reduces the severity of pneumococcal pneumonia in part by augmenting neutrophil function. Specifically, we show that 1) galectin-3 directly acts as a neutrophil-activating agent and potentiates the effect of fMLP, 2) exogenous galectin-3 augments neutrophil phagocytosis of bacteria and delays neutrophil apoptosis, 3) phagocytosis of apoptotic neutrophils by galectin-3−/− macrophages is less efficient compared to wild type, and 4) galectin-3 demonstrates bacteriostatic properties against S. pneumoniae in vitro. Furthermore, ad-back of recombinant galectin-3 in vivo protects galectin-3-deficient mice from developing severe pneumonia. Together, these results demonstrate that galectin-3 is a key molecule in the host defense against pneumococcal infection. Therapeutic strategies designed to augment galectin-3 activity may both enhance inflammatory cell function (by directly affecting neutrophil responsiveness and prolonging neutrophil longevity) and have direct bacteriostatic activity, improving clinical outcomes after severe pneumococcal infection. PMID:18202191

  15. Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens.

    PubMed

    Apiwattanakul, Nopporn; Thomas, Paul G; Kuhn, Raymond E; Herbert, De'Broski R; McCullers, Jonathan A

    2014-10-01

    Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common.

  16. A Pneumococcal Protein Array as a Platform to Discover Serodiagnostic Antigens Against Infection*

    PubMed Central

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

    2015-01-01

    Pneumonia is one of the most common and severe diseases associated with Streptococcus pneumoniae infections in children and adults. Etiological diagnosis of pneumococcal pneumonia in children is generally challenging because of limitations of diagnostic tests and interference with nasopharyngeal colonizing strains. Serological assays have recently gained interest to overcome some problems found with current diagnostic tests in pediatric pneumococcal pneumonia. To provide insight into this field, we have developed a protein array to screen the antibody response to many antigens simultaneously. Proteins were selected by experimental identification from a collection of 24 highly prevalent pediatric clinical isolates in Spain, using a proteomics approach consisting of “shaving” the cell surface with proteases and further LC/MS/MS analysis. Ninety-five proteins were recombinantly produced and printed on an array. We probed it with a collection of sera from children with pneumococcal pneumonia. From the set of the most seroprevalent antigens, we obtained a clear discriminant response for a group of three proteins (PblB, PulA, and PrtA) in children under 4 years old. We validated the results by ELISA and an immunostrip assay showed the translation to easy-to-use, affordable tests. Thus, the protein array here developed presents a tool for broad use in serodiagnostics. PMID:26183717

  17. Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA.

    PubMed

    Nelson, George E; Gershman, Kenneth A; Swerdlow, David L; Beall, Bernard W; Moore, Matthew R

    2012-02-01

    Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3× the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, ≈17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics.

  18. Adult immunization with 13-valent pneumococcal vaccine in Campania region, South Italy: an economic evaluation.

    PubMed

    Liguori, Giorgio; Parlato, Antonino; Zamparelli, Alessandro Sanduzzi; Belfiore, Patrizia; Gallé, Francesca; Di Onofrio, Valeria; Riganti, Carla; Zamparelli, Bruno

    2014-01-01

    Pneumococcal pneumonia has a high clinical burden in terms of morbidity, mortality and hospitalization rate, with heavy implications for worldwide health systems. In particular, higher incidence and mortality rates of community-acquired pneumonia (CAP) cases, with related costs, are registered among elderly. This study aimed to an economic evaluation about the immunization with PCV13 in the adult population in Campania region, South Italy. For this purpose we performed, considering a period of 5 y, a budget impact analysis (BIA) and a cost-effectiveness analysis which considered 2 scenarios of immunization compared with lack of immunization for 2 targeted cohorts: first, the high risk subjects aged 50-79 y, and second the high risk individuals aged 50-64 y, together with all those aged 65 y. Regarding the first group, the decrease of pneumonia could give savings equal to €29,005,660, while the immunization of the second cohort could allow savings equal to €10,006,017. The economic evaluation of pneumococcal vaccine for adult groups represents an essential instrument to support health policies. This study showed that both hypothesized immunization strategies could produce savings. Obtained results support the use of pneumococcal conjugate vaccine for adults. This strategy could represent a sustainable and savings-producer health policy.

  19. Increased utilization of influenza and pneumococcal vaccines in an elderly hospitalized population.

    PubMed

    Bloom, H G; Bloom, J S; Krasnoff, L; Frank, A D

    1988-10-01

    This study compared three interventions designed to increase acceptance of influenza and pneumococcal vaccines among elderly hospitalized patients. All individuals 65 and older able to give informed consent (73 patients) who were admitted to one medical floor of an acute care hospital were randomized to one of three groups. All groups received informational pamphlets explaining influenza and pneumococcal disease, their respective vaccines, and indications for their use. The first group received pamphlets only, the second received nursing follow-up, and the third received trained volunteer follow-up. Patients on another medical floor served as controls. The results showed a significant improvement in vaccine acceptance in all three study groups compared to controls for both influenza (78% vs 0%) and pneumococcal (75% vs 0%) vaccines. The differences among the three groups were not significant. No significant differences were found among patients accepting or refusing vaccination with regard to diagnosis, age, length of stay, sex, or having a private physician. We conclude that a simple educational program followed by offering vaccination before hospital discharge can be easily implemented, and dramatically increase immunization rates in this high risk group.

  20. The pneumococcal alpha-glycerophosphate oxidase enhances nasopharyngeal colonization through binding to host glycoconjugates.

    PubMed

    Mahdi, Layla K; Higgins, Melanie A; Day, Christopher J; Tiralongo, Joe; Hartley-Tassell, Lauren E; Jennings, Michael P; Gordon, David L; Paton, Adrienne W; Paton, James C; Ogunniyi, Abiodun D

    2017-03-03

    Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.

  1. Biochemical properties of polysaccharides from black pepper.

    PubMed

    Chun, Hyug; Shin, Dong Hoon; Hong, Bum Shik; Cho, Won Dai; Cho, Hong Yon; Yang, Han Chul

    2002-09-01

    The purified polysaccharides from Piper nigrum were prepared as follows: a hot water extract of pepper seeds was fractionated by ultrafiltration with a 5-kDa-membrane cartridge. A fraction with 5 kDa or bigger molecules was successively purified by open column chromatography on DEAE-Toyopearl 650C and Bio-gel P-60 with each active fraction, resulting in PN-Ib and PN-IIa, purified anti-complementary polysaccharides. None of the anti-complementary activity of any polysaccharide was changed by pronase digestion or polymyxin B treatment, but they were decreased by periodate oxidation. Analysis of component sugar and molecular mass determination of the anti-complementary polysaccharides indicated that PN-Ib with an average molecular mass of 21 kDa contained 88.5% glucose and other negligible minor monosaccharides, while PN-IIa showed a different monosaccharide composition, which contained a significant proportion of galactose, arabinose, galacturonic acid and rhamnose. The molar ratio of galactose and arabinose of PN-IIa (48 kDa) was 1.93:1. PN-1 did not react with beta-glucosyl Yariv reagent, however, PN-IIa did react, which indicated that PN-IIa might be an arabinogalactan. Based upon these results, the usefulness of purified anti-complementary polysaccharides from Piper nigrum is suggested as a supplement for immune enhancement.

  2. Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

    DOEpatents

    Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

    2011-02-08

    Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

  3. Immobilized phosphorylase for synthesis of polysaccharides from glucose

    NASA Technical Reports Server (NTRS)

    Marshall, D. L.

    1972-01-01

    Continuous processes for enzymatic production of carbohydrates from glucose are discussed. Key reactant in process is identified as phosphorylase which catalyzes reversible formation or degradation of polysaccharide. Chemical compounds and reactions to synthesize polysaccharides are analyzed.

  4. Ice nucleation activity of polysaccharides

    NASA Astrophysics Data System (ADS)

    Bichler, Magdalena; Felgitsch, Laura; Haeusler, Thomas; Seidl-Seiboth, Verena; Grothe, Hinrich

    2015-04-01

    Heterogeneous ice nucleation is an important process in the atmosphere. It shows direct impact on our climate by triggering ice cloud formation and therefore it has much influence on the radiation balance of our planet (Lohmann et al. 2002; Mishchenko et al. 1996). The process itself is not completely understood so far and many questions remain open. Different substances have been found to exhibit ice nucleation activity (INA). Due to their vast differences in chemistry and morphology it is difficult to predict what substance will make good ice nuclei and which will not. Hence simple model substances must be found and be tested regarding INA. Our work aims at gaining to a deeper understanding of heterogeneous ice nucleation. We intend to find some reference standards with defined chemistry, which may explain the mechanisms of heterogeneous ice nucleation. A particular focus lies on biological carbohydrates in regards to their INA. Biological carbohydrates are widely distributed in all kingdoms of life. Mostly they are specific for certain organisms and have well defined purposes, e.g. structural polysaccharides like chitin (in fungi and insects) and pectin (in plants), which has also water-binding properties. Since they are widely distributed throughout our biosphere and mostly safe to use for nutrition purposes, they are well studied and easily accessible, rendering them ideal candidates as proxies. In our experiments we examined various carbohydrates, like the already mentioned chitin and pectin, as well as their chemical modifications. Lohmann U.; A Glaciation Indirect Aerosol Effect Caused by Soot Aerosols; J. Geoph. Res.; Vol. 24 No.4; pp 11-1 - 11-4; 2002 Mishchenko M.I., Rossow W.B., Macke A., Lacis A. A.; Sensitivity of Cirrus Cloud Albedo, Bidirectional Reflectance and Optical Thickness Retrieval Accuracy to Ice Particle Shape, J. Geoph. Res.; Vol. 101, No D12; pp. 16,973 - 16,985; 1996

  5. Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

    PubMed

    Yamamoto, Natsuo; Kerfoot, Steven M; Hutchinson, Andrew T; Dela Cruz, Charles S; Nakazawa, Naomi; Szczepanik, Marian; Majewska-Szczepanik, Monika; Nazimek, Katarzyna; Ohana, Noboru; Bryniarski, Krzysztof; Mori, Tsutomu; Muramatsu, Masamichi; Kanemitsu, Keiji; Askenase, Philip W

    2016-01-01

    We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset.

  6. [Statement of the Advisory Immunization Committee of the Chilean Society of Infectious Diseases on the emergence of serotype 19A pneumococcal infection and the use of pneumococcal conjugated vaccine in Chilean children].

    PubMed

    Potin, Marcela; Fica, Alberto; Wilhem, Jan; Cerda, Jaime; Contreras, Lily; Escobar, Carola; Moreno, Gabriela; Muñoz, Alma; Véliz, Liliana

    2016-06-01

    Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.

  7. Depolymerization of sulfated polysaccharides under hydrothermal conditions.

    PubMed

    Morimoto, Minoru; Takatori, Masaki; Hayashi, Tetsuya; Mori, Daiki; Takashima, Osamu; Yoshida, Shinichi; Sato, Kimihiko; Kawamoto, Hitoshi; Tamura, Jun-ichi; Izawa, Hironori; Ifuku, Shinsuke; Saimoto, Hiroyuki

    2014-01-30

    Fucoidan and chondroitin sulfate, which are well known sulfated polysaccharides, were depolymerized under hydrothermal conditions (120-180°C, 5-60min) as a method for the preparation of sulfated polysaccharides with controlled molecular weights. Fucoidan was easily depolymerized, and the change of the molecular weight values depended on the reaction temperature and time. The degree of sulfation and IR spectra of the depolymerized fucoidan did not change compared with those of untreated fucoidan at reaction temperatures below 140°C. However, fucoidan was partially degraded during depolymerization above 160°C. Nearly the same depolymerization was observed for chondroitin sulfate. These results indicate that hydrothermal treatment is applicable for the depolymerization of sulfated polysaccharides, and that low molecular weight products without desulfation and deformation of the initial glycan structures can be obtained under mild hydrothermal conditions.

  8. Learning from microbial strategies for polysaccharide degradation.

    PubMed

    Hemsworth, Glyn R; Déjean, Guillaume; Davies, Gideon J; Brumer, Harry

    2016-02-01

    Complex carbohydrates are ubiquitous in all kingdoms of life. As major components of the plant cell wall they constitute both a rich renewable carbon source for biotechnological transformation into fuels, chemicals and materials, and also form an important energy source as part of a healthy human diet. In both contexts, there has been significant, sustained interest in understanding how microbes transform these substrates. Classical perspectives of microbial polysaccharide degradation are currently being augmented by recent advances in the discovery of lytic polysaccharide monooxygenases (LPMOs) and polysaccharide utilization loci (PULs). Fundamental discoveries in carbohydrate enzymology are both advancing biological understanding, as well as informing applications in industrial biomass conversion and modulation of the human gut microbiota to mediate health benefits.

  9. Influence of polysaccharides on wine protein aggregation.

    PubMed

    Jaeckels, Nadine; Meier, Miriam; Dietrich, Helmut; Will, Frank; Decker, Heinz; Fronk, Petra

    2016-06-01

    Polysaccharides are the major high-molecular weight components of wines. In contrast, proteins occur only in small amounts in wine, but contribute to haze formation. The detailed mechanism of aggregation of these proteins, especially in combination with other wine components, remains unclear. This study demonstrates the different aggregation behavior between a buffer and a model wine system by dynamic light scattering. Arabinogalactan-protein, for example, shows an increased aggregation in the model wine system, while in the buffer system a reducing effect is observed. Thus, we could show the importance to examine the behavior of wine additives under conditions close to reality, instead of simpler buffer systems. Additional experiments on melting points of wine proteins reveal that only some isoforms of thaumatin-like proteins and chitinases are involved in haze formation. We can confirm interactions between polysaccharides and proteins, but none of these polysaccharides is able to prevent haze in wine.

  10. Cellular immunity to Bacteroides fragilis capsular polysaccharide

    PubMed Central

    1982-01-01

    The polysaccharide capsule of Bacteroides fragilis has been shown to be important in the virulence of the organism. The capsular polysaccharide (CP) of B. fragilis has been extensively purified. Using a murine model of intraabdominal abscess formation, we have been able to demonstrate cellular immunity to the capsular polysaccharide of B. fragilis. Immunization of C57BL/10J mice with the CP over 5 wk prevents abscess formation when the mice are challenged with B. fragilis intraperitoneally. This immunity can be transferred to naive mice with spleen cells from immune animals. The immune cells bear Thy-1.2 and Ly- 2.2 antigens. The immune response has been shown to be antigen specific, but not H-2 restricted. The possibility that these immune cells are suppressor T cells is discussed. The experimental system presented provides a model for the examination of the cellular interactions responsible for abscess formation and the cellular response to bacterial pathogens. PMID:6174672

  11. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older--United States, 2015.

    PubMed

    Kim, David K; Bridges, Carolyn B; Harriman, Kathleen H

    2015-02-06

    In October 2014, the Advisory Committee on Immunization Practices (ACIP) approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2015. This schedule provides a summary of ACIP recommendations for the use of vaccines routinely recommended for adults aged 19 years or older in two figures, footnotes for each vaccine, and a table that describes primary contraindications and precautions for commonly used vaccines for adults. Changes in the 2015 adult immunization schedule from the 2014 schedule included the August 2014 recommendation for routine administration of the 13-valent pneumococcal conjugate vaccine (PCV13) in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all adults aged 65 years or older, the August 2014 revision on contraindications and precautions for the live attenuated influenza vaccine (LAIV), and the October 2014 approval by the Food and Drug Administration to expand the approved age for use of recombinant influenza vaccine (RIV). These revisions were also reviewed and approved by the American College of Physicians, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and American College of Nurse-Midwives.

  12. Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru

    PubMed Central

    2013-01-01

    Background The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. Methods A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. Results Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (−US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. Conclusions The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely

  13. [Component analysis on polysaccharides in exocarp of Ginkgo biloba].

    PubMed

    Song, G; Xu, A; Chen, H; Wang, X

    1997-09-01

    This paper reports the content and component analysis on polysaccharides in exocarp of Ginkgo biloba. The results show that the content of total saccharides is 89.7%; content of polysaccharides is 84.6%; content of reductic saccharides is 5.1%; the polysaccharides are composed of glucose, fructose, galactose and rhamnose.

  14. Risk factors for levofloxacin-nonsusceptible Streptococcus pneumoniae in community-acquired pneumococcal pneumonia: a nested case-control study.

    PubMed

    Kang, C-I; Song, J-H; Kim, S H; Chung, D R; Peck, K R; So, T M; Hsueh, P-R

    2014-01-01

    This study was performed to evaluate the clinical features of community-onset levofloxacin-nonsusceptible pneumococcal pneumonia and to identify risk factors for levofloxacin resistance. Using the database of a surveillance study of community-acquired pneumococcal infections in Asian countries, we conducted a nested case-control study to identify risk factors for levofloxacin-nonsusceptible S. pneumoniae in community-acquired pneumonia in adults. Of 981 patients with pneumococcal pneumonia, 46 (4.7 %) had levofloxacin-nonsusceptible S. pneumoniae, of whom 39 evaluable cases were included in the analysis. All cases were from Korea, Taiwan, and Hong Kong. Among patients with levofloxacin-susceptible S. pneumoniae, 490 controls were selected based on patient country. Of the 39 cases of levofloxacin-nonsusceptible pneumococcal pneumonia, 23 (59.0 %) were classified as healthcare-associated, while 164 (33.5 %) of the 490 controls of levofloxacin-susceptible S. pneumoniae (P = 0.001) were classified as healthcare-associated. Multivariate analysis showed that previous treatment with fluoroquinolones, cerebrovascular disease, and healthcare-associated infection were significantly associated with levofloxacin-nonsusceptible pneumococcal pneumonia (all P < 0.05). Levofloxacin-nonsusceptible pneumococci pose an important new public health threat in our region, and more information on the emergence and spread of these resistant strains will be necessary to prevent spread throughout the population.

  15. Polysaccharide-based strategies for heart tissue engineering.

    PubMed

    Silva, Amanda K A; Juenet, Maya; Meddahi-Pellé, Anne; Letourneur, Didier

    2015-02-13

    Polysaccharides are abundant biomolecules in nature presenting important roles in a wide variety of living systems processes. Considering the structural and biological functions of polysaccharides, their properties have raised interest for tissue engineering. Herein, we described the latest advances in cardiac tissue engineering mediated by polysaccharides. We reviewed the data already obtained in vitro and in vivo in this field with several types of polysaccharides. Cardiac injection, intramyocardial in situ polymerization strategies, and scaffold-based approaches involving polysaccharides for heart tissue engineering are thus discussed.

  16. Antibiotic resistance and serotype distribution of invasive pneumococcal diseases before and after introduction of pneumococcal conjugate vaccine in the Kingdom of Saudi Arabia (KSA).

    PubMed

    Shibl, Atef M; Memish, Ziad A; Al-Kattan, Khaled M

    2012-12-31

    Streptococcus pneumoniae is one of the most common bacterial causes of morbidity and mortality worldwide, causing life threatening infections such as meningitis, pneumonia and febrile bacteremia, particular among young children. The severity and frequency of S. pneumoniae infection and emergence of drug-resistant isolates have highlighted the need for prevention of invasive pneumococcal disease (IPD) as the best method for controlling disease; to better achieve this, more information is needed about serotype distribution and patterns of antibiotic resistance in children in the Kingdom of Saudi Arabia (KSA). Cases of pneumococcal infections in children aged <5 years, recorded in hospitals throughout KSA from 2005 to 2010 were reviewed for serotyping and for antibiotic susceptibility. This covers the time period just before limited introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2006, to its introduction into the national immunization program in 2008, until right after a switch to PCV13 in 2010. Case definition required isolation of S. pneumoniae from blood, cerebrospinal fluid, or any sterile biological fluid. Isolates from 311 eligible cases were collected from different regions across KSA, 250 from blood and 61 from cerebrospinal fluid. The most frequently isolated IPD serotypes were 23F, 19F, 6B, 5 and 1. Over the course of the study, there was significant rise of serotype 19A (covered by PCV13 but not PCV7), which accounted for 20% of isolates of IPD in Western and 5% in Central regions in the last 2 years in KSA. There was a notable decrease in serotype 18C over this period, one of the PCV7 serotypes. Serotype coverage for PCV7, PCV10, PCV13 in children <5 years was 53%, 80%, and 91%, respectively across the Kingdom from 2005 to 2010. A total of 66% of IPD isolates were penicillin-resistant, and 62% were erythromycin-resistant. Continued surveillance is critical to measure the emerging of new serotypes and antibiotic resistance strain, and the

  17. Extraction and characterization of sugar beet polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugar Beet Pulp (SBP), contains 65 to 80% (dry weight) of potentially valuable polysaccharides. We separated SBP into three fractions. The first fraction, extracted under acid conditions, was labeled pectin, the second was comprised of two sub fractions solubilized under alkaline conditions and wa...

  18. Fucoidans — sulfated polysaccharides of brown algae

    NASA Astrophysics Data System (ADS)

    Usov, Anatolii I.; Bilan, M. I.

    2009-08-01

    The methods of isolation of fucoidans and determination of their chemical structures are reviewed. The fucoidans represent sulfated polysaccharides of brown algae, the composition of which varies from simple fucan sulfates to complex heteropolysaccharides. The currently known structures of such biopolymers are presented. A variety of the biological activities of fucoidans is briefly summarised.

  19. Aldehyde-containing urea-absorbing polysaccharides

    NASA Technical Reports Server (NTRS)

    Mueller, W. A.; Hsu, G. C.; Marsh, H. E., Jr. (Inventor)

    1977-01-01

    A novel aldehyde containing polymer (ACP) is prepared by reaction of a polysaccharide with periodate to introduce aldehyde groups onto the C2 - C3 carbon atoms. By introduction of ether and ester groups onto the pendant primary hydroxyl solubility characteristics are modified. The ACP is utilized to absorb nitrogen bases such as urea in vitro or in vivo.

  20. Bacillus subtilis biofilm induction by plant polysaccharides

    PubMed Central

    Beauregard, Pascale B.; Chai, Yunrong; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

    2013-01-01

    Bacillus subtilis is a plant-beneficial Gram-positive bacterium widely used as a biofertilizer. However, relatively little is known regarding the molecular processes underlying this bacterium's ability to colonize roots. In contrast, much is known about how this bacterium forms matrix-enclosed multicellular communities (biofilms) in vitro. Here, we show that, when B. subtilis colonizes Arabidopsis thaliana roots it forms biofilms that depend on the same matrix genes required in vitro. B. subtilis biofilm formation was triggered by certain plant polysaccharides. These polysaccharides served as a signal for biofilm formation transduced via the kinases controlling the phosphorylation state of the master regulator Spo0A. In addition, plant polysaccharides are used as a source of sugars for the synthesis of the matrix exopolysaccharide. The bacterium's response to plant polysaccharides was observed across several different strains of the species, some of which are known to have beneficial effects on plants. These observations provide evidence that biofilm genes are crucial for Arabidopsis root colonization by B. subtilis and provide insights into how matrix synthesis may be triggered by this plant. PMID:23569226

  1. Anticorrosive Microbial Polysaccharides: Structure-Function Relationships

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water-soluble microbial polysaccharides are often implicated in biofilm formation and are believed to mediate cell-cell aggregation and adhesion to surfaces. Generally, biofilm formation is considered harmful or undesirable, as it leads to increased drag, plugging of pores, dimished heat transfer, ...

  2. Plant-Polysaccharide-Degrading Enzymes from Basidiomycetes

    PubMed Central

    Rytioja, Johanna; Hildén, Kristiina; Yuzon, Jennifer; Hatakka, Annele; de Vries, Ronald P.

    2014-01-01

    SUMMARY Basidiomycete fungi subsist on various types of plant material in diverse environments, from living and dead trees and forest litter to crops and grasses and to decaying plant matter in soils. Due to the variation in their natural carbon sources, basidiomycetes have highly varied plant-polysaccharide-degrading capabilities. This topic is not as well studied for basidiomycetes as for ascomycete fungi, which are the main sources of knowledge on fungal plant polysaccharide degradation. Research on plant-biomass-decaying fungi has focused on isolating enzymes for current and future applications, such as for the production of fuels, the food industry, and waste treatment. More recently, genomic studies of basidiomycete fungi have provided a profound view of the plant-biomass-degrading potential of wood-rotting, litter-decomposing, plant-pathogenic, and ectomycorrhizal (ECM) basidiomycetes. This review summarizes the current knowledge on plant polysaccharide depolymerization by basidiomycete species from diverse habitats. In addition, these data are compared to those for the most broadly studied ascomycete genus, Aspergillus, to provide insight into specific features of basidiomycetes with respect to plant polysaccharide degradation. PMID:25428937

  3. The role of television advertising in increasing pneumococcal vaccination coverage among the elderly, North Coast, New South Wales, 2006.

    PubMed

    Wallace, Cate; Corben, Paul; Turahui, John; Gilmour, Robin

    2008-10-01

    North Coast Area Health Service (NCAHS) conducted a seven week television advertising campaign to raise community awareness of the availability of free adult pneumococcal vaccination and to increase coverage among North Coast residents in high risk groups. Effectiveness of the campaign was evaluated by examining vaccine ordering patterns of North Coast vaccination providers from 2005/2006 as a proxy for vaccination coverage. In the months during and immediately following (June-September 2006) the advertising campaign, a significantly higher proportion of vaccines were despatched to North Coast immunisation service providers. The advertising campaign was an effective strategy to promote vaccination among NCAHS residents not immunised in the first year of the National Pneumococcal Program for Older Australians. This higher immunisation coverage is expected to contribute to the statewide trend of significant reductions in invasive pneumococcal disease (IPD) notifications.

  4. Immunogenicity and safety of CRM₁₉₇ conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants.

    PubMed

    Mallet, Eric; Brachet, Elisabeth; Fernsten, Philip; Laudat, France; Razmpour, Ahmad; Gruber, William C

    2011-08-05

    Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ≥0.35μg/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated.

  5. Sulfated polysaccharides and immune response: promoter or inhibitor?

    PubMed

    Chen, D; Wu, X Z; Wen, Z Y

    2008-06-01

    Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.

  6. Structure-function relationships of immunostimulatory polysaccharides: A review.

    PubMed

    Ferreira, Sónia S; Passos, Cláudia P; Madureira, Pedro; Vilanova, Manuel; Coimbra, Manuel A

    2015-11-05

    Immunostimulatory polysaccharides are compounds capable of interacting with the immune system and enhance specific mechanisms of the host response. Glucans, mannans, pectic polysaccharides, arabinogalactans, fucoidans, galactans, hyaluronans, fructans, and xylans are polysaccharides with reported immunostimulatory activity. The structural features that have been related with such activity are the monosaccharide and glycosidic-linkage composition, conformation, molecular weight, functional groups, and branching characteristics. However, the establishment of structure-function relationships is possible only if purified and characterized polysaccharides are used and selective structural modifications performed. Aiming at contributing to the definition of the structure-function relationships necessary to design immunostimulatory polysaccharides with potential for preventive or therapeutical purposes or to be recognized as health-improving ingredients in functional foods, this review introduces basic immunological concepts required to understand the mechanisms that rule the potential claimed immunostimulatory activity of polysaccharides and critically presents a literature survey on the structural features of the polysaccharides and reported immunostimulatory activity.

  7. Polysaccharide-producing bacteria isolated from paper machine slime deposits.

    PubMed

    Rättö, M; Suihko, M-L; Siika-aho, M

    2005-03-01

    Development of novel enzymatic methods for slime deposit control in paper mills requires knowledge of polysaccharide-producing organisms and the polysaccharide structures present in deposits. In this work, 27 polysaccharide-producing bacteria were isolated from slime samples collected from different parts of a paper machine. Most of the isolates produced polysaccharides in liquid culture and nine of them were selected for production of polysaccharides for characterisation. The selected isolates belonged to seven different genera: Bacillus, Brevundimonas, Cytophaga, Enterobacter, Klebsiella, Paenibacillus and Starkeya. Using ribotyping, partial 16S rDNA sequencing, physiological tests and fatty acid analysis, four of the nine isolates: Bacillus cereus, Brevundimonas vesicularis, K. pneumoniae and P. stellifer were identified to the species level. Production of polysaccharides by the selected isolates varied between 0.07 and 1.20 g L(-1), the highest amount being produced by B. vesicularis. The polysaccharides were heteropolysaccharides with varying proportions of galactose, glucose mannose, rhamnose fucose and uronic acids.

  8. Laboratory surveillance of invasive pneumococcal disease in Australia, 2003 predicting the future impact of the universal childhood conjugate vaccine program.

    PubMed

    Watson, Michael; Roche, Paul; Bayley, Kathy; Bell, Jan M; Collignon, Peter; Gilbert, Gwendolyn L; Hogg, Geoff; Keil, Anthony D; Krause, Vicki; Murphy, Denise; Smith, Helen V; Brown, Mitchell; Stylianopoulos, Joanne; Turnidge, John

    2004-01-01

    A comprehensive invasive pneumococcal disease (IPD) laboratory surveillance program was carried out in Australia in 2003. This program provided data on the prevalence of pneumococcal serotypes and antimicrobial resistance. There were 1,995 isolates tested with 34 per cent (683) from children aged less than five years and 27 per cent (535) from the elderly aged more than 65 years. One thousand eight hundred and sixty were isolates from blood, 79 from CSF and 56 from other sterile sites. In young children, 84 per cent of isolates were a serotype and 92 per cent a serogroup in the 7-valent pneumococcal conjugate vaccine (7vPCV). Of penicillin resistant isolates in children less than five years of age 85 per cent and 98 per cent were a serotype and serogroup in the 7vPCV respectively. When the universal 7vPCV vaccine program in young children is introduced in 2005, a proportion of cases of IPD should also be prevented in young adults (estimated reduction of 54 cases annually) and elderly Australians (an estimated reduction of 110 cases annually) as a result of improved herd immunity. Pneumococcal serotypes with higher rates of penicillin resistance (19F, 14 and 6B) were more prevalent in the elderly than in young children. In contrast, erythromycin resistance was more common in children less than five years of age (24%) compared to the elderly (15%). The predominant serotype with erythromycin resistance in Australia was serotype 14 and thus there is likely to be a major reduction in erythromycin resistance as a result of 7vPCV vaccination. Continued surveillance of pneumococcal serotype distribution and antibiotic susceptibility will be essential in order to identify serotype replacement by non-vaccine serotypes and to monitor the overall impact of current and future vaccine programs on invasive pneumococcal disease in Australia, not only in young children but also in other age groups.

  9. Insight Into Resistance Phenotypes of Emergent Non 13-valent Pneumococcal Conjugate Vaccine Type Pneumococci Isolated From Invasive Disease After 13-valent Pneumococcal Conjugate Vaccine Implementation in France

    PubMed Central

    Janoir, Claire; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2016-01-01

    Background. In 2010, the pneumococcal 13-valent conjugate vaccine (PCV13), containing 6 additional serotypes including the multidrug-resistant 19A, replaced the PCV7 in France. This study aimed at analyzing trends in antibiotic resistance in invasive pneumococcal disease (IPD) isolates in France after PCV13 introduction. Methods. A total of 5243 pneumococci isolated from IPD in 2008–2009 (late PCV7 era) and 2011–2012 (PCV13 era) were studied according to their serotype and antibiotic resistance profile. Multilocus sequence typing analysis was performed on strains of the predominant serotypes (12F and 24F) isolated from young children. Results. Overall, the prevalence of antibiotic resistance decreased in France (−21.5% for penicillin from 2008–2009 to 2011–2012), mainly driven by the decline of the 19A serotype. Among non-PCV13 serotypes that concomitantly emerged, serotypes 12F, 24F, 15A, and 35B were consistently associated with resistance to 1 or more antibiotics. In children under 2 years, serotypes 15A, 35B, and 24F accounted together for 37.8% and 31.9% of penicillin-nonsusceptible and erythromycin-resistant isolates, respectively. Chloramphenicol and cotrimoxazole resistance were mainly associated with serotypes 12F and 24F, respectively. Genetic analysis showed that although emergence of serotype 12F pneumococci resulted from the expansion of various pre-existing lineages, increase in serotype 24F was related to the clonal expansion of the ST162 penicillin-susceptible cotrimoxazole-resistant lineage. Conclusions. We showed that decline of PCV13-related IPD was associated with a decline in antibiotic resistance in France, but that it likely favored the spread of several resistant nonvaccine serotypes. However, antibiotic resistance does not seem to be the only element that may drive this phenomenon. PMID:26955644

  10. Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis.

    PubMed

    Vivas, M; Force, E; Tubau, F; El Haj, C; Ariza, J; Cabellos, C

    2015-07-01

    This study aimed to determine the effect of dexamethasone in combination with low-dose or high-dose daptomycin for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. Efficacy (ΔCFU/mL) and cerebrospinal fluid (CSF) levels of daptomycin at 15mg/kg and 25mg/kg were studied in a rabbit model of pneumococcal meningitis, comparing them with the same doses in combination with dexamethasone at 0.125mg/kg every 12h over a 26-h period against two different Streptococcus pneumoniae strains, HUB 2349 and ATCC 51916 with daptomycin minimum inhibitory concentrations (MICs) of 0.09mg/L and 0.19mg/L, respectively. Daptomycin levels in CSF were lower when dexamethasone was given concurrently. Against strain HUB 2349, therapeutic failure occurred with daptomycin 15mg/kg+dexamethasone; daptomycin 25mg/kg+dexamethasone was better at reducing bacterial counts than the lower dose throughout treatment. Against the highly cephalosporin-resistant ATCC 51916 strain, daptomycin 15mg/kg+dexamethasone achieved a lower bacterial decrease than daptomycin 15mg/kg alone, and therapeutic failure at 24h occurred in the daptomycin 15mg/kg+dexamethasone group. Addition of dexamethasone to a 25mg/kg daptomycin dose did not affect the efficacy of daptomycin: it remained bactericidal throughout treatment. In conclusion, against the studied strains, low-dose (15mg/kg/day) daptomycin is affected by concomitant use of dexamethasone: CSF levels are reduced and its bacterial efficacy is affected. At a higher daptomycin dose (25mg/kg/day), however, the use of dexamethasone does not alter efficacy; the combination appears to be a good choice for the treatment of pneumococcal meningitis.

  11. Diversity of pneumococcal surface protein A (PspA) among prevalent clones in Spain

    PubMed Central

    2009-01-01

    Background PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66) and nasopharyngeal healthy carriage in children (n = 46). Results PspA family 2 was predominant among invasive (63.6%) and carriage (54.3%) pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST) related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain6B-ST90, Spain14-ST18, Colombia5-ST289, Sweden1-ST306, Denmark14-ST230 and Sweden1-ST304 clones. Clade 3 was associated with Spain23F-ST81, Spain9V-ST156, Tennessee14-ST67, Netherlands3-ST180 and Netherlands7F-ST191 clones. Clade 4 was related to Sweden15A-ST63, Netherlands18C-ST113 and Greece21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates. Conclusion PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children. PMID:19419534

  12. Insights into molecular plasticity of choline binding proteins (pneumococcal surface proteins) by SAXS.

    PubMed

    Buey, Rubén M; Monterroso, Begoña; Menéndez, Margarita; Diakun, Greg; Chacón, Pablo; Hermoso, Juan Antonio; Díaz, J Fernando

    2007-01-12

    Phosphocholine moieties decorating the pneumococcal surface are used as a docking station for a family of modular proteins, the so-called choline binding proteins or CBPs. Choline recognition is essential for CBPs function and may also be a determinant for their quaternary structure. There is little knowledge about modular arrangement or oligomeric structures in this family. Therefore, we have used the small angle X-ray scattering (SAXS) technique combined with analytical ultracentrifugation in order to model the three-dimensional envelope of two highly different CBPs: the phage encoded Cpl-1 lysozyme and the pneumococcal phosphorylcholine esterase Pce. Both enzymes have an N-terminal catalytic module and a C-terminal choline-binding module (CBM) that attaches them to the bacterial surface and comprises six and ten sequence repeats in Cpl-1 and Pce, respectively. SAXS experiments have shown an inherent conformational plasticity in Cpl-1 that accounts for the different relative position of these regions in the solution and crystal structures. Dimerization of Cpl-1 upon choline binding has been also visualised for the first time, and monomer-monomer interactions take place through the first CBR where a non-canonical choline binding site has now been identified. This mode of association seems to be independent of the absence or presence of the Cpl-1 catalytic module and reveals that the arrangement of the monomers differs from that previously found in the isolated CBM dimer of pneumococcal LytA amidase. In contrast, Pce displays the same modular disposition in the solution and crystal structures, and remains almost invariant upon choline binding. The present results suggest that protein dimerization and duplication of CBRs may be alternative but not equivalent ways of improving cell wall recognition by CBPs, since they provide different interaction geometries for choline residues present in (lipo)teichoic acids.

  13. TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity.

    PubMed

    Puchta, Alicja; Naidoo, Avee; Verschoor, Chris P; Loukov, Dessi; Thevaranjan, Netusha; Mandur, Talveer S; Nguyen, Phuong-Son; Jordana, Manel; Loeb, Mark; Xing, Zhou; Kobzik, Lester; Larché, Maggie J; Bowdish, Dawn M E

    2016-01-01

    Monocyte phenotype and output changes with age, but why this occurs and how it impacts anti-bacterial immunity are not clear. We found that, in both humans and mice, circulating monocyte phenotype and function was altered with age due to increasing levels of TNF in the circulation that occur as part of the aging process. Ly6C+ monocytes from old (18-22 mo) mice and CD14+CD16+ intermediate/inflammatory monocytes from older adults also contributed to this "age-associated inflammation" as they produced more of the inflammatory cytokines IL6 and TNF in the steady state and when stimulated with bacterial products. Using an aged mouse model of pneumococcal colonization we found that chronic exposure to TNF with age altered the maturity of circulating monocytes, as measured by F4/80 expression, and this decrease in monocyte maturation was directly linked to susceptibility to infection. Ly6C+ monocytes from old mice had higher levels of CCR2 expression, which promoted premature egress from the bone marrow when challenged with Streptococcus pneumoniae. Although Ly6C+ monocyte recruitment and TNF levels in the blood and nasopharnyx were higher in old mice during S. pneumoniae colonization, bacterial clearance was impaired. Counterintuitively, elevated TNF and excessive monocyte recruitment in old mice contributed to impaired anti-pneumococcal immunity since bacterial clearance was improved upon pharmacological reduction of TNF or Ly6C+ monocytes, which were the major producers of TNF. Thus, with age TNF impairs inflammatory monocyte development, function and promotes premature egress, which contribute to systemic inflammation and is ultimately detrimental to anti-pneumococcal immunity.

  14. Risk factors for serotype 19A carriage after introduction of 7-valent pneumococcal vaccination

    PubMed Central

    2011-01-01

    Background After the implementation of 7-valent pneumococcal conjugate vaccine (PCV7), in several countries, serotype 19A is now the serotype most frequently involved in pneumococcal diseases and carriage. To determine factors potentially related to 19A nasopharyngeal (NP) carriage we analyzed data from an ongoing prospective French national surveillance study of pneumococcal NP carriage in young children. Methods NP swabs were obtained from children aged 6 to 24 months, either during routine check-ups with normal findings, or when they presented with acute otitis media (AOM). The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Factors influencing pneumococcal carriage and carriage of penicillin non-susceptible (PNSP), 19A and PNS-19A were investigated by multivariate logistic regression. Results From 2006 to 2009, 66 practitioners enrolled 3507 children (mean age 13.6 months), of whom, 98.3% of children had been vaccinated with PCV7 and 33.4% of children attended daycare centres (DCC). Serotype 19A was found in 10.4% of the overall population, 20.5% of S. pneumoniae carriers (n = 1780) and 40.8% of PNSP carriers (n = 799). Among 19A strains, 10.7% were penicillin-susceptible, 80% intermediate and 9.3% fully resistant. Logistic regression analysis showed that the main factors associated with PNSP carriage were AOM (OR = 3.09, 95% CI [2.39;3.98]), DCC (OR = 1.70, 95% CI [1.42;2.03]), and recent antibiotic use (OR = 1.24, 95% CI [1.05;1.47]. The main factors predictive of 19A carriage were recent antibiotic use (OR = 1.81, 95% CI [1.42;2.30]), AOM (OR = 1.67, 95% CI [1.11;2.49]), DCC (OR = 1.56, 95% CI [1.21;2.2] and young age, <12 months (OR = 1.51, 95% CI [1.16;1.97]). Conclusion In a population of children aged from 6 to 24 months with a high rate of PCV7 vaccination coverage, we found that antibiotic exposure, DCC attendance and AOM were linked to 19A carriage. PMID:21501471

  15. Surveillance of the impact of pneumococcal conjugate vaccines in developing countries.

    PubMed

    Rodgers, Gail L; Klugman, Keith P

    2016-01-01

    Infection due to Streptococcus pneumoniae is a leading cause of morbidity and mortality in young children, especially in developing countries. With the support of Gavi, the Vaccine Alliance, the majority of these countries have introduced pneumococcal conjugate vaccines (PCV) into their national immunization programs and early data demonstrate a high degree of effectiveness, translating to enormous public health benefit through both direct and indirect (herd) effects. Future vaccination strategy may be focused on maintaining herd effects rather than individual protection. Evaluation of vaccine-type carriage, particularly in pneumonia cases, may be an easy, feasible way of measuring continued vaccine impact.

  16. A Computerized Pneumococcal Vaccination Reminder System in the Adult Emergency Department

    PubMed Central

    Dexheimer, Judith W; Talbot, Thomas R.; Ye, Fei; Shyr, Yu; Jones, Ian; Gregg, William M; Aronsky, Dominik

    2011-01-01

    Background Pneumococcal vaccination is an effective strategy to prevent invasive pneumococcal disease in the elderly. Emergency Department (ED) visits present an underutilized opportunity to increase vaccination rates; however, designing a sustainable vaccination program in an ED is challenging. We examined whether an information technology supported approach would provide a feasible and sustainable method to increase vaccination rates in an adult ED. Methods During a 1-year period we prospectively evaluated a team-oriented, workflow-embedded reminder system that integrated four different information systems. The computerized triage application screened all patients 65 years and older for pneumococcal vaccine eligibility with information from the electronic patient record. For eligible patients the computerized provider order entry system reminded clinicians to place a vaccination order, which was passed to the order tracking application. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the ED. Multivariate logistic regression analysis was used to estimate the odds ratios and their 95% confidence intervals, representing the overall relative risks of ED workload related variables associated with vaccination rate. Results Among 3,371 patients 65 years old and older screened at triage 1,309 (38.8%) were up-to-date with pneumococcal vaccination and 2,062 (61.2%) were eligible for vaccination. Of the eligible patients, 621 (30.1%) consented to receive the vaccination during their ED visit. Physicians received prompts for 428 (68.9%) patients. When prompted, physicians declined to order the vaccine in 192 (30.9%) patients, while 222 (10.8%) of eligible patients actually received the vaccine. The computerized reminder system increased vaccination rate from a baseline of 38.8% to 45.4%. Vaccination during the ED visit was associated younger age (OR: 0.972, CI: 0

  17. Polysaccharide structure of tetrasporic red seaweed Tichocarpus crinitus.

    PubMed

    Byankina Barabanova, A O; Sokolova, E V; Anastyuk, S D; Isakov, V V; Glazunov, V P; Volod'ko, A V; Yakovleva, I M; Solov'eva, T F; Yermak, I M

    2013-10-15

    Sulfated polysaccharide isolated from tetrasporic plants of Tichocarpus crinitus was investigated. The polysaccharide was isolated by two methods: with water extraction at 80 °C (HT) and with a mild alkaline extraction (AE). The extracted polysaccharides were presented by non-gelling ones only, while galactose and 3,6-AG were the main monosaccharides, at the same time amount of 3,6-AG in AE polysaccharides was the similar to that of HT. According to methods of spectroscopy and mass spectrometry, the polysaccharide from tetrasporic T. crinitus contains main blocks of 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl while 6-sulfated 4-linked galactopyranosyl resudies are randomly distributed along the polysaccharide chain. The alkaline treatment of HT polysaccharide results in obtaining polysaccharide with regular structure that composed of alternating 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl residues. Native polysaccharide (HT) possessed both high anticoagulant and antiplatelet activity measured by fibrin clotting and platelet aggregation induced by collagen. This activity could be connected with peculiar chemical structure of HT polysaccharide which has high sulfation degree and contains also 3,6-anhydrogalactose in the polymer chain.

  18. α-Amylase-assisted extraction of polysaccharides from Panax ginseng.

    PubMed

    Sun, Lin; Wu, Di; Ning, Xin; Yang, Guang; Lin, Ziheng; Tian, Meihong; Zhou, Yifa

    2015-04-01

    In this paper, α-amylase-assisted extraction was used to isolate the polysaccharide that remained in hot water-extracted ginseng. The yield of the polysaccharide was 9.0%, almost equal to that of the hot water-extracted polysaccharide. Using anion exchange and gel permeation chromatography, the polysaccharide was fractionated into a neutral polysaccharide fraction and six pectic fractions. The neutral fraction accounted for 76% of the polysaccharide and contained both amylopectin and amylose. The pectic polysaccharide fractions were identified to be arabinogalactan, type-I rhamnogalacturonan and homogalacturonan-type pectin by high-performance liquid chromatography, Fourier transform-infrared and nuclear magnetic resonance analysis. Structural and lymphocyte proliferation activity results showed that these polysaccharides were different from those extracted by hot water, indicating that ginseng contains complex polysaccharides with diverse structures, which results in its diverse pharmacological activities. The α-amylase-assisted extraction is a novel method for preparing ginseng polysaccharides and could be applied toward the further study and exploration of ginseng. These findings provide technical and theoretical support for ginseng pharmacology.

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

    PubMed Central

    Ramdani-Bouguessa, N.; Ziane, H.; Bekhoucha, S.; Guechi, Z.; Azzam, A.; Touati, D.; Naim, M.; Azrou, S.; Hamidi, M.; Mertani, A.; Laraba, A.; Annane, T.; Kermani, S.; Tazir, M.

    2015-01-01

    Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria. PMID:26106481

  20. Effects of selenizing angelica polysaccharide and selenizing garlic polysaccharide on immune function of murine peritoneal macrophage.

    PubMed

    Gao, Zhenzhen; Liu, Kuanhui; Tian, Weijun; Wang, Hongchao; Liu, Zhenguang; Li, Youying; Li, Entao; Liu, Cui; Li, Xiuping; Hou, Ranran; Yue, Chanjuan; Wang, Deyun; Hu, Yuanliang

    2015-07-01

    The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 μg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator.

  1. Crystallization and preliminary X-ray diffraction studies of the carbohydrate-recognition domain of SIGN-R1, a receptor for microbial polysaccharides and sialylated antibody on splenic marginal zone macrophages

    PubMed Central

    Silva-Martin, Noella; Schauer, Joseph D.; Park, Chae Gyu; Hermoso, Juan A.

    2009-01-01

    SIGN-R1, or CD209b, is a mouse C-type lectin receptor that is expressed at high levels on macrophages in lymphoid tissues, especially within the marginal zone of the spleen. SIGN-R1 can bind and mediate the uptake of various microbial polysaccharides, including dextrans, lipopolysaccharides and pneumococcal capsular polysaccharides. It has been shown that SIGN-R1 mediates the clearance of encapsulated pneumococcus, complement fixation via binding C1q independent of antibody and innate resistance to pneumococcal infection. Recently, SIGN-R1 has also been demonstrated to bind sialylated antibody and mediate its activity to suppress autoimmunity. The carbohydrate-recognition domain (CRD) of SIGN-R1 has been cloned and overexpressed in a soluble secretory form in mammalian Chinese hamster ovary (CHO) cells. The CRD protein of SIGN-R1 was purified from CHO cell-culture supernatant and concentrated for crystallization using the hanging-drop vapour-diffusion method at 291 K. Crystals grew from a mixture of 2 M ammonium sulfate in 0.1 M bis-tris pH 5.5. Single crystals, which belonged to the monoclinic space group C2 with unit-cell parameters a = 146.72, b = 92.77, c = 77.06 Å, β = 121.66°, allowed the collection of a full X-ray data set to a maximum resolution of 1.87 Å. PMID:20054124

  2. Immunogenic properties of Klebsiella pneumoniae type 2 capsular polysaccharide.

    PubMed Central

    Robert, A; Jouin, H; Fournier, J M

    1986-01-01

    The immunoprotective activity of Klebsiella pneumoniae K2 cell surface preparations and purified capsular polysaccharide was tested in mice. The 50% protective dose (PD50), expressed as capsular polysaccharide content, was 2 ng for cell surface preparations and 50 ng for purified capsular polysaccharide. Both preparations lost their immunoprotective activity after alkali treatment. Immune sera were raised in rabbits immunized with cell surface preparations. The precipitating and hemagglutinating capacity of these antisera was tested against either purified capsular polysaccharide or alkali-treated capsular polysaccharide. No difference was observed between the reactivity of the antisera against each antigen. The protective activity of these sera was tested on mice in passive transfer experiments, before and after absorption with either purified capsular polysaccharide or alkali-treated capsular polysaccharide. The sera lost their protective activity after absorption with purified capsular polysaccharide and after absorption with alkali-treated capsular polysaccharide. These experiments show that the difference in immunoprotective activity of cell surface preparations, purified capsular polysaccharide, and alkali-treated capsular polysaccharide is not due to a difference in their antigenic determinants. Cell surface preparations and purified capsular polysaccharide were fractionated by gel filtration on Sepharose 4B and by ultracentrifugation on cesium chloride density gradients. Three forms of capsular polysaccharide have been characterized. (i) A form of capsular polysaccharide with a very high protective activity (PD50 = 2 ng) that copurified with protein and lipopolysaccharide and was characterized by a low coefficient of distribution (Kd = 0.20) and a low density (1.5 to 1.6 g/cm3). (ii) A form of capsular polysaccharide with an intermediate protective activity (PD50 = 50 ng), contamined by less than 3% protein and 1% lipopolysaccharide, with a Kd of 0.35, and

  3. POLYPEPTIDE AND POLYSACCHARIDE PROCESSING IN HYPERTHERMOPHILIC MICROORGANISMS

    SciTech Connect

    KELLY, ROBERT M.

    2008-12-22

    This project focused on the microbial physiology and biochemistry of heterotrophic hyperthermophiles with respect to mechanisms by which these organisms process polypeptides and polysaccharides under normal and stressed conditions. Emphasis is on two model organisms, for which completed genome sequences are available: Pyrococcus furiosus (growth Topt of 98°C), an archaeon, and Thermotoga maritima (growth Topt of 80°C), a bacterium. Both organisms are obligately anaerobic heterotrophs that reduce sulfur facultatively. Whole genome cDNA spotted microarrays were used to follow transcriptional response to a variety of environmental conditions in order to identify genes encoding proteins involved in the acquisition, synthesis, processing and utilization of polypeptides and polysaccharides. This project provided new insights into the physiological aspects of hyperthermophiles as these relate to microbial biochemistry and biological function in high temperature habitats. The capacity of these microorganisms to produce biohydrogen from renewable feedstocks makes them important for future efforts to develop biofuels.

  4. Microbial extracellular polysaccharides and plagioclase dissolution

    SciTech Connect

    Welch, S.A.; Barker, W.W.; Banfield, J.F.

    1999-05-01

    Bytownite feldspar was dissolved in batch reactors in solutions of starch (glucose polymer), gum xanthan (glucose, mannose, glucuronic acid), pectin (poly-galacturonic acid), and four alginates (mannuronic and guluronic acid) with a range of molecular weights (low, medium, high and uncharacterized) to evaluate the effect of extracellular microbial polymers on mineral dissolution rates. Solutions were analyzed for dissolved Si and Al as an indicator of feldspar dissolution. At neutral pH, feldspar dissolution was inhibited by five of the acid polysaccharides, gum xanthan, pectin, alginate low, alginate medium, alginate high, compared to an organic-free control. An uncharacterized alginate substantially enhanced both Si and Al release from the feldspar. Starch, a neutral polysaccharide, had no apparent effect. Under mildly acidic conditions, initial pH {approx} 4, all of the polymers enhanced feldspar dissolution compared to the inorganic controls. Si release from feldspar in starch solution exceeded the control by a factor of three. Pectin and gum xanthan increased feldspar dissolution by a factor of 10, and the alginates enhanced feldspar dissolution by a factor of 50 to 100. Si and Al concentrations increased with time, even though solutions were supersaturated with respect to several possible secondary phases. Under acidic conditions, initial pH {approx} 3, below the pK{sub a} of the carboxylic acid groups, dissolution rates increased, but the relative increase due to the polysaccharides is lower, approximately a factor of two to ten. Microbial extracellular polymers play a complex role in mineral weathering. Polymers appear to inhibit dissolution under some conditions, possibly by irreversibly binding to the mineral surfaces. The extracellular polysaccharides can also enhance dissolution by providing protons and complexing with ions in solution.

  5. Polysaccharide Nanosystems for Future Progress in Cardiovascular Pathologies

    PubMed Central

    Silva, Amanda Karine Andriola; Letourneur, Didier; Chauvierre, Cédric

    2014-01-01

    Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nanosystems. Polysaccharide-based nanosystems may be designed for interacting in several biological processes. In particular, the atherothrombotic pathology is highly concerned by polysaccharide-mediated recognition. Atherothrombotic diseases, regardless of the anatomical localization, remain the main causes of morbidity and mortality in the industrialized world. This review intends to provide an overview on polysaccharide-based nanosystems as drug delivery systems and targeted contrast agents for molecular imaging with an emphasis on the treatment and imaging of cardiovascular pathologies. PMID:24723980

  6. Marked increase in biofilm-derived rough pneumococcal variants and rifampin-resistant strains not due to hex gene mutations.

    PubMed

    McEllistrem, M Catherine; Scott, Jennifer R; Zuniga-Castillo, Jacobo; Khan, Saleem A

    2009-06-01

    Otitis, pneumonia, and meningitis are tissue-based pneumococcal infections that can be associated with biofilms. The emergence of phenotypic rough variants, also known as acapsular small-colony variants, is essential for pneumococcal biofilm formation. These rough variants can increase nearly 100-fold in biofilms over time and can arise through single nucleotide polymorphisms (SNPs), deletions, or tandem duplications in the first gene of the capsular operon, cps3D. We detected a 100-fold increase in rifampin-resistant (Rif(r)) mutants in biofilms compared to planktonic cultures using a nonvaccine serotype 3 strain, which is causing an increasing number of cases of otitis in the 7-valent pneumococcal conjugate vaccine era. Since both rough variants and Rif(r) strains can arise through SNPs, they could emerge due to alteration of the mismatch repair (MMR) system. The Hex system, a pneumococcal MMR system, repairs mismatches during replication and transformation. In this study, no mutations were detected in the hexAB gene sequences among several rough variants with unique mutations in the cps3D gene. Within a hexA null mutant grown in broth, we detected only a 17.5-fold increase in rough variants compared to the wild-type parental strain. Taken together, these data suggest that mutations in the hex genes and modulation of hexA activity are unlikely to account for the generation of biofilm-derived rough variants.

  7. [Epidemiological analysis of the incidence of invasive and non-invasive pneumococcal infections in different population groups].

    PubMed

    Martynova, A V; Turkutiukov, V B

    2007-01-01

    Despite modern achievements in diagnostics and treatment, invasive and non-invasive pneumococcal infections remain a topical public health problem. To a large extent, it is connected with the absence or inconsistence of evidence-based information on this kind of infection. In this paper, retrospective analysis of the incidence of pneumococcal infections was performed on the basis of medical records available today in every health institution; the peculiarities of their nosologic structure were revealed. Among invasive forms, pneumococcal pneumonias prevailed (50.06%); apparent hypodiagnostics of pneumococcal meningitis was noted (only 4.02%). Among non-invasive forms, acute otitis with various complications prevailed (47.5%), acute sinusitis was registered in 37.5% of cases, and other ENT diseases (sphenoiditis, frontitis, ethmoiditis, etc.) were registered in 15% of cases. The study found that the main risk factors in these patients had been different ENT diseases which the patients had suffered from during the previous three months before the actual illness. Thus, the necessity for the development and perfection of techniques of microbiological diagnostics and the development of epidemiological control methods on their basis are obvious.

  8. Budget impact analysis of a pneumococcal vaccination programme in the 65-year-old Spanish cohort using a dynamic model

    PubMed Central

    2013-01-01

    Background This study aimed to assess the costs and clinical benefits of the 13-valent pneumococcal conjugate vaccine (PCV13) administered annually to the 65-year-old cohort in Spain versus the alternative of not vaccinating patients and treating them only when infected. Methods Cases of pneumococcal disease avoided were calculated through a dynamic model based on the work of Anderson and May (1999). Sixty-six percent of the 65-year-old cohort was assumed to have been vaccinated with one PCV13 dose (304,492 subjects). Base-case estimated vaccine effectiveness and serotype coverage were 58% and 60%, respectively. Disease-related costs were calculated based on published data. Results Over the 5-year period, a total of 125,906 cases of pneumococcal disease would be avoided. Net savings of €102 million would be obtained. The cost-saving distribution was not homogeneous, starting in the 2nd year and increasing through the 5th. To demonstrate model robustness, an additional scenario analysis was performed using extreme values of model parameters (vaccination programme coverage, vaccine effectiveness, discount rate and disease costs). Under those scenarios, net savings were always achieved. Conclusions Based on the assumptions of the model, the 65-year-cohort pneumococcal vaccination campaign appears to be a cost-saving intervention in the Spanish population under different scenarios. PMID:23578307

  9. Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine candidate confer serotype independent protection against Streptococcus pneumoniae in mice.

    PubMed

    Wu, Kaifeng; Yao, Run; Wang, Hong; Pang, Dan; Liu, Yusi; Xu, Hongmei; Zhang, Shuai; Zhang, Xuemei; Yin, Yibing

    2014-07-16

    Despite the availability of effective vaccines, Streptococcus pneumoniae is still one of the major infectious diseases causing substantial morbidity and mortality in children under 5 years old. In this study, we demonstrate the protective efficacy of S. pneumoniae SPY1, a novel live attenuated vaccine strain against pneumococcal infection in murine models. This strain was characterized by defects in three important pneumococcal virulence factors including capsule, teichoic acids and pneumolysin. The lactate dehydrogenase assays and in vivo animal experiments demonstrated a significantly attenuated virulence and a reduced nasopharyngeal colonization for the SPY1 strain. We also show that mucosal and systemic immunization with the live SPY1 strain induced protective immune responses against pneumococci. Mucosal immunization with SPY1 offered better protection against colonization challenge with strains TIGR4 and serotype 19F than systemic SPY1 immunization. In invasive infection models, mucosal vaccination with the SPY1 strain conferred complete protection against D39 and clinical serotype 6B and 3 strains. Notably, intranasal vaccination with the SPY1 strain conferred superior protection against pneumococcal invasive disease compared with the commercial available vaccines. SPY1 strain was shown to elicit high levels of serotype-independent antibodies and a mixed cellular immune response. Besides, the SPY1 serum was able to passively protect mice against invasive challenge with D39 strain, indicating the protective effect of the antibody-mediated responses. Together, the SPY1 strain may be a promising live vaccine strain to protect pneumococcal infection.

  10. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    PubMed Central

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections. PMID:27766231

  11. Capsular switching as a strategy to increase pneumococcal virulence in experimental otitis media model.

    PubMed

    Sabharwal, Vishakha; Stevenson, Abbie; Figueira, Marisol; Orthopoulos, George; Trzciński, Krzysztof; Pelton, Stephen I

    2014-04-01

    We hypothesized that capsular switch event, in which pneumococcus acquires a new capsule operon by horizontal gene transfer, may result in emergence of strains with increased virulence in acute otitis media. Using serotype 6A strain from a patient with invasive pneumococcal disease and clonally distant serotype 6C strain isolated from asymptomatic carrier we created 6A:6C (6A background with 6C capsule) capsular transformants and applied whole genome macro-restriction analysis to assess conservation of the 6A chassis. Next, we assessed complement (C3) and antibodies deposition on surface of pneumococcal cells and tested capsule recipient, capsule donor and two 6A:6C transformants for virulence in chinchilla experimental otitis media model. Both 6A:6C(1 or 2) transformants bound less C3 compared to 6C capsule-donor strain but more compared to serotype 6A capsule-recipient strain. Pneumococci were present in significantly higher proportion of ears among animals challenged with either of two 6A:6C(1 or 2) transformants compared to chinchillas infected with 6C capsule-donor strain [p < 0.001] whereas a significantly decreased proportion of ears were infected with 6A:6C(1 or 2) transformants as compared to 6A capsule-recipient strain. Our observations though limited to two serotypes demonstrate that capsular switch events can result in Streptococcus pneumoniae strains of enhanced virulence for respiratory tract infection.

  12. Vitamin D Promotes Pneumococcal Killing and Modulates Inflammatory Responses in Primary Human Neutrophils.

    PubMed

    Subramanian, Karthik; Bergman, Peter; Henriques-Normark, Birgitta

    2017-02-28

    Streptococcus pneumoniae is a major human pathogen and a leading cause of pneumonia, septicemia, and meningitis worldwide. Despite clinical studies linking vitamin D deficiency and pneumonia, molecular mechanisms behind these observations remain unclear. In particular, the effects of vitamin D on neutrophil responses remain unknown. Using pneumococcal strains, primary neutrophils isolated from human blood, and sera from patients with frequent respiratory tract infections (RTIs), we investigated the effects of vitamin D on neutrophil bactericidal and inflammatory responses, including pattern recognition receptors, antimicrobial peptides, and cytokine regulation. We found that vitamin D upregulated pattern recognition receptors, TLR2, and NOD2, and induced the antimicrobial human neutrophil peptides (HNP1-3) and LL-37, resulting in increased killing of pneumococci in a vitamin D receptor-dependent manner. Antibodies targeting HNP1-3 inhibited bacterial killing. Vitamin D supplementation of serum from patients with bacterial RTIs enhanced neutrophil killing. Moreover, vitamin D lowered inflammatory cytokine production by infected neutrophils via IL-4 production and the induction of suppressor of cytokine signaling (SOCS) proteins SOCS-1 and SOCS-3, leading to the suppression of NF-κB signaling. Thus, vitamin D enhances neutrophil killing of S. pneumoniae while dampening excessive inflammatory responses and apoptosis, suggesting that vitamin D could be used alongside antibiotics when treating pneumococcal infections.

  13. Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003-2013.

    PubMed

    von Mollendorf, Claire; Cohen, Cheryl; Tempia, Stefano; Meiring, Susan; de Gouveia, Linda; Quan, Vanessa; Lengana, Sarona; Karstaedt, Alan; Dawood, Halima; Seetharam, Sharona; Lekalakala, Ruth; Madhi, Shabir A; Klugman, Keith P; von Gottberg, Anne

    2016-02-01

    In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.

  14. In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

    PubMed Central

    Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

    2016-01-01

    The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

  15. Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China

    PubMed Central

    Chen, Jing Jing; Yuan, Lin; Huang, Zhen; Shi, Nian Min; Zhao, Yu Liang; Xia, Sheng Li; Li, Guo Hua; Li, Rong Cheng; Li, Yan Ping; Yang, Shu Yuan; Xia, Jie Lai

    2016-01-01

    Introduction The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7). Methods and analysis 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12–15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed. Ethics and dissemination Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance. Trial registration number NCT02736240. PMID:27798013

  16. Rheological studies of polysaccharides for skin scaffolds.

    PubMed

    Almeida, Nalinda; Mueller, Anja; Hirschi, Stanley; Rakesh, Leela

    2014-05-01

    Polysaccharide hydrogels are good candidates for skin scaffolds because of their inherent biocompatibility and water transport properties. In the current study, hydrogels were made from a mixture of four polysaccharides: xanthan gum, konjac gum, iota-carrageenan, and kappa-carrageenan. Gel formation, strength, and structure of these polysaccharides were studied using rheological and thermal techniques. All gel samples studied were strong gels at all times because of the gradual water loss. However, after 12 h of storage, elastic (G') and loss (G'') moduli of hydrogel mixture containing all the ingredients is of one to two orders of magnitude greater than that of mixtures not containing either xanthan gum or iota-carrageenan, which confirmed the varied levels of gel strength. This is mainly due to the rate of water loss in each of these mixtures, resulting in gels of varying structures and dynamic moduli over a period of time. Iota-carrageenan and xanthan gum differ in their effect on gel strength and stability in combination with konjac gum and kappa-carrageenan.

  17. The diversity of Klebsiella pneumoniae surface polysaccharides

    PubMed Central

    Heinz, Eva; Wyres, Kelly L.; Ellington, Matthew J.; Kowarik, Michael; Holt, Kathryn E.; Thomson, Nicholas R.

    2016-01-01

    Klebsiella pneumoniae is considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present in K. pneumoniae. We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500 K. pneumoniae whole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulent K. pneumoniae, were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes. PMID:28348868

  18. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  19. Iron oxyhydroxide mineralization on microbial extracellular polysaccharides

    SciTech Connect

    Chan, Clara S.; Fakra, Sirine C.; Edwards, David C.; Emerson, David; Banfield, Jillian F.

    2010-06-22

    Iron biominerals can form in neutral pH microaerophilic environments where microbes both catalyze iron oxidation and create polymers that localize mineral precipitation. In order to classify the microbial polymers that influence FeOOH mineralogy, we studied the organic and mineral components of biominerals using scanning transmission X-ray microscopy (STXM), micro X-ray fluorescence ({mu}XRF) microscopy, and high-resolution transmission electron microscopy (HRTEM). We focused on iron microbial mat samples from a creek and abandoned mine; these samples are dominated by iron oxyhydroxide-coated structures with sheath, stalk, and filament morphologies. In addition, we characterized the mineralized products of an iron-oxidizing, stalk-forming bacterial culture isolated from the mine. In both natural and cultured samples, microbial polymers were found to be acidic polysaccharides with carboxyl functional groups, strongly spatially correlated with iron oxyhydroxide distribution patterns. Organic fibrils collect FeOOH and control its recrystallization, in some cases resulting in oriented crystals with high aspect ratios. The impact of polymers is particularly pronounced as the materials age. Synthesis experiments designed to mimic the biomineralization processes show that the polysaccharide carboxyl groups bind dissolved iron strongly but release it as mineralization proceeds. Our results suggest that carboxyl groups of acidic polysaccharides are produced by different microorganisms to create a wide range of iron oxyhydroxide biomineral structures. The intimate and potentially long-term association controls the crystal growth, phase, and reactivity of iron oxyhydroxide nanoparticles in natural systems.

  20. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

    Cardoso, Matias J; Costa, Rui R; Mano, João F

    2016-02-05

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  1. Nanofiltration of polysaccharides from Agaricus subrufescens.

    PubMed

    Camelini, C M; Rezzadori, K; Benedetti, S; Proner, M C; Fogaça, L; Azambuja, A A; Giachini, A J; Rossi, M J; Petrus, J C C

    2013-12-01

    A simplified submerged airlift cultivation was established for the production of biomass from Agaricus subrufescens. In this work, soluble polysaccharides extracted from fungal mycelium, fruiting bodies, and the residual culture media were concentrated by nanofiltration. Total and high molar mass polysaccharides and soluble solids were determined in the concentrate for the three extracts. Additionally, the permeate flow, the influences of temperature and pressure, and the resistance to the permeate flow during filtration were also evaluated. Ayield of 5.5 g/L of biomass with 35%glucose conversion was obtained when 0.5 g/L of initial inoculum was employed. Average specific speed of growth was 0.4/day, with biomass productivity of about 0.76 g/(L day). Nanofiltration has yielded polysaccharide increases of 85, 82, and 92% in the extracts from fruiting bodies, mycelium, and liquid media, respectively. A reduction in the permeate flow was observed during filtration, and it was compensated by higher pressures and temperatures. The higher resistance to the permeate flux was caused by polarization due to concentration (polarized gel layer), reaching values of 88% for the culture media. Maximal resistance caused by the membrane reached values of 40% for the extract from the fruiting bodies. On the other hand, resistance caused by fouling was responsible for less than 3.5%. In conclusion, nanofiltration is efficient to concentrate these functional compounds extracted from A. subrufescens and can, therefore, be applied in different biotechnological areas.

  2. Evaluation of Phosphorylated Psyllium Seed Polysaccharide as a Release Retardant

    PubMed Central

    Rao, Monica R. P.; Warrier, Deepa U.; Rao, Shivani H.

    2015-01-01

    The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model. PMID:26798177

  3. [Improvement on microwave technology of extracting polysaccharide from yacon leaves].

    PubMed

    Li, Jing-wei; Liu, Jian; Yang, Yong; Zheng, Ming-min; Rong, Ting-zhao

    2007-11-01

    According to the extraction ratio of polysaccharide in yacon leaves, the comparison between microwave extraction and traditional hot water extraction was conducted, and the two-factor and three-level experiment on the microwave extraction of polysaccharide from yacon leaves was investigated. The result showed that the extraction ratio of polysaccharide by using microwave extraction was better than that by using traditional hot water extraction. Moreover, according to the result of variance analysis and multiple comparison, the optimum conditions for extraction of polysaccharide by using microwave technology from yacon leaves were as follows: 280W microwave power for 2 times and 15 minutes at every time.

  4. Antibacterial and antiviral study of dialdehyde polysaccharides

    NASA Astrophysics Data System (ADS)

    Song, Le

    Concerns for microbial contamination and infection to the general population, especially the spread of drug-resistant microorganisms, have greatly increased. Polymeric biocides have been found to be a feasible strategy to inactivate drug-resistant bacteria. However, current polymeric biocide systems involve multi-step chemical reactions and they are not cost-effective. Desirable antimicrobial systems need to be designed to be environmentally friendly, broad-spectrum effective against microorganisms, flexible for various delivery methods and economically affordable. We demonstrated that dialdehyde polysaccharides (including dialdehyde starch and dialdehdye cellulose) were broad-spectrum polymeric biocides against gram-positive/negative bacteria, bacteriophages and human virus. These polymers can be easily converted from starch and cellulose through one-step periodate oxidation. Destructions of microorganism by dialdehyde polysaccharides have been achieved in aqueous suspension or by solid surface contact. The dialdehdye functions of dialdehdye polysaccharides were found to be the dominant action against microorganism. The reactivity of the dialdehyde functionality was found to be pH-dependent as well as related to the dispersion of dialdehyde polysaccharides. Degradation of dialdehyde starch during cooking was confirmed. Degradation of dialdehyde starch was more liable in alkaline condition. Carboxylic acid and conjugated aldehyde functionalities were the two main degradation products, confirmed from the spectroscopic studies. The pH effect on the polysaccharide structure and the corresponding antimicrobial activity was very complicated. No decisive conclusions could be obtained from this study. Liner inactivation kinetics was found for dialdehyde starch aqueous suspension against bacteria. This linear inactivation kinetics was derived from the pseudo-first chemical reaction between the dialdehyde starch and the bacteria. The established inactivation kinetics was

  5. Dendritic Cell-Derived Exosomes Express a Streptococcus pneumoniae Capsular Polysaccharide Type 14 Cross-Reactive Antigen That Induces Protective Immunoglobulin Responses against Pneumococcal Infection in Mice

    DTIC Science & Technology

    2007-01-01

    exosome biogenesis (9). Thus, dendritic cell (DC)-derived exo- somes are enriched in major histocompatibility complex (MHC), T-cell costimulatory and...biotinylated by activation with cyanogen bromide and coupling to biotin-LC- Hydrazide (Pierce, Rockford, IL) essentially as described by Lucas et al. (25...in the enzyme-linked immunosorbent assays (ELISAs). Detection and quantitation of tetraspan-containing microvesicles. The pres- ence of complexed

  6. Immunomodulatory dietary polysaccharides: a systematic review of the literature

    PubMed Central

    2010-01-01

    Background A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides. Methods Studies were identified by conducting PubMed and Google Scholar electronic searches and through reviews of polysaccharide article bibliographies. Only articles published in English were included in this review. Two researchers reviewed data on study design, control, sample size, results, and nature of outcome measures. Subsequent searches were conducted to gather information about polysaccharide safety, structure and composition, and disposition. Results We found 62 publications reporting statistically significant effects of orally ingested glucans, pectins, heteroglycans, glucomannans, fucoidans, galactomannans, arabinogalactans and mixed polysaccharide products in rodents. Fifteen controlled human studies reported that oral glucans, arabinogalactans, heteroglycans, and fucoidans exerted significant effects. Although some studies investigated anti-inflammatory effects, most studies investigated the ability of oral polysaccharides to stimulate the immune system. These studies, as well as safety and toxicity studies, suggest that these polysaccharide products appear to be largely well-tolerated. Conclusions Taken as a whole, the oral polysaccharide literature is highly heterogenous and is not sufficient to support broad product structure/function generalizations. Numerous dietary polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in numerous animal tissues, including the blood, GI tract and spleen. Glucan extracts from the Trametes versicolor mushroom improved survival and

  7. Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

    PubMed

    Francis, J P; Richmond, P C; Strickland, D; Prescott, S L; Pomat, W S; Michael, A; Nadal-Sims, M A; Edwards-Devitt, C J; Holt, P G; Lehmann, D; van den Biggelaar, A H J

    2017-03-01

    In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

  8. Immunogenicity and safety of PNEUMOVAX II manufactured by a new process in older adults.

    PubMed

    Mair, Stuart; Fiquet, Anne; Meghlaoui, Gilles; Thomas, Stephane; Ledesma, Emilio

    2009-09-01

    In response to increased demand for the 23-valent pneumococcal vaccine PNEUMOVAX II, a new manufacturing process has been implemented that improves the consistency and increases the scale of production. This double-blind, randomized, clinical study compared the immunogenicity and safety profiles of the new-process PNEUMOVAX II (n = 111) formulated with all 23 new process polysaccharides to the former-process PNEUMOVAX II (n = 109) formulation in adults aged > or =50 years. The primary aim of the study was to compare the post-vaccination geometric mean of antibody titres (GMT) to pneumococcal serotypes 3 and 8 in recipients of new- and former-process PNEUMOVAX II. The post-vaccination GMTs for serotypes 3 and 8 elicited by the new-process PNEUMOVAX II [1.40 (95% confidence interval, 1.21-1.63) and 10.78 (95% CI, 9.10-12.77), respectively] were non-inferior to those elicited by the former-process PNEUMOVAX II [1.24 (95% CI, 1.07-1.43) and 9.72 (95% CI, 8.22-11.50), respectively]. Both PNEUMOVAX II formulations were well tolerated; there were no vaccine-related serious adverse events. A total of 74 (66.7%) subjects in the new-process group and 66 (60.6%) in the former-process group had at least one injection-site reaction or vaccine-related systemic event within 14 days following vaccination. There was a trend for higher incidence of two solicited injection-site reactions (erythmea and induration) and three solicited systemic events (asthenia, chills and body aches) with the new- versus former-process PNEUMOVAX II, but these were mainly of mild intensity and short duration. The new-process PNEUMOVAX(R II thus showed similar immunogenicity to the former-process vaccine for pneumococcal serotypes 3 and 8 and both vaccines were well tolerated in older subjects.

  9. Programmed protection of foreign DNA from restriction allows pathogenicity island exchange during pneumococcal transformation.

    PubMed

    Johnston, Calum; Martin, Bernard; Granadel, Chantal; Polard, Patrice; Claverys, Jean-Pierre

    2013-02-01

    In bacteria, transformation and restriction-modification (R-M) systems play potentially antagonistic roles. While the former, proposed as a form of sexuality, relies on internalized foreign DNA to create genetic diversity, the latter degrade foreign DNA to protect from bacteriophage attack. The human pathogen Streptococcus pneumoniae is transformable and possesses either of two R-M systems, DpnI and DpnII, which respectively restrict methylated or unmethylated double-stranded (ds) DNA. S. pneumoniae DpnII strains possess DpnM, which methylates dsDNA to protect it from DpnII restriction, and a second methylase, DpnA, which is induced during competence for genetic transformation and is unusual in that it methylates single-stranded (ss) DNA. DpnA was tentatively ascribed the role of protecting internalized plasmids from DpnII restriction, but this seems unlikely in light of recent results establishing that pneumococcal transformation was not evolved to favor plasmid exchange. Here we validate an alternative hypothesis, showing that DpnA plays a crucial role in the protection of internalized foreign DNA, enabling exchange of pathogenicity islands and more generally of variable regions between pneumococcal isolates. We show that transformation of a 21.7 kb heterologous region is reduced by more than 4 logs in dpnA mutant cells and provide evidence that the specific induction of dpnA during competence is critical for full protection. We suggest that the integration of a restrictase/ssDNA-methylase couplet into the competence regulon maintains protection from bacteriophage attack whilst simultaneously enabling exchange of pathogenicicy islands. This protective role of DpnA is likely to be of particular importance for pneumococcal virulence by allowing free variation of capsule serotype in DpnII strains via integration of DpnI capsule loci, contributing to the documented escape of pneumococci from capsule-based vaccines. Generally, this finding is the first evidence for a

  10. Solomonseal Polysaccharide and Sulfated Codonopsis pilosula Polysaccharide Synergistically Resist Newcastle Disease Virus

    PubMed Central

    Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Zhang, Cunshuai; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    Five combinations of three ratios (PS9-sPS1, PS7-sPS3 and PS6-sPS4) were prepared with polysaccharide (PS) and sulfated polysaccharide (sPS). The antiviral activities of these compounds were subsequently compared in vitro using the MTT assay, observation of the virus structure and immunofluorescence. The results demonstrated that SP9-sCP1, CP7-sCA3, EP7-sAP3, CA9-sEP1 and EP7-sCA3 presented higher activities, and SP9-sCP1 displayed the highest virus inhibition rate and clearly killed the virus and inhibited viral antigen expression. In an in vivo test, 28-day-old chickens were challenged with Newcastle disease virus (NDV) and were administered the five drug combinations. On day 14 after the challenge, the morbidity, mortality and cure rate in each group were calculated. The results indicated that SP9-sCP1 presented the lowest morbidity and mortality and the highest cure rate. These results indicate that Solomonseal polysaccharide and sulfated Codonopsis pilosula polysaccharide synergistically resist NDV. Moreover, SP9-sCP1 had the highest efficacy and may be used as a new antiviral drug. PMID:25692886

  11. Macrophage immunomodulatory activity of polysaccharides isolated from Opuntia polyacantha

    PubMed Central

    Schepetkin, Igor A.; Xie, Gang; Kirpotina, Liliya N.; Klein, Robyn A.; Jutila, Mark A.; Quinn, Mark T.

    2008-01-01

    Opuntia polyacantha (prickly pear cactus) has been used extensively for its nutritional properties; however, less is known regarding medicinal properties of Opuntia tissues. In the present study, we extracted polysaccharides from O. polyacantha and used size-exclusion chromatography to fractionate the crude polysaccharides into four polysaccharide fractions (designated as Opuntia polysaccharides C-I to C-IV). The average Mr of fractions C-I through C-IV was estimated to be 733, 550, 310, and 168 kDa, respectively, and sugar composition analysis revealed that Opuntia polysaccharides consisted primarily of galactose, galacturonic acid, xylose, arabinose, and rhamnose. Analysis of the effects of Opuntia polysaccharides on human and murine macrophages demonstrated that all four fractions had potent immunomodulatory activity, inducing production of reactive oxygen species, nitric oxide, tumor necrosis factor α, and interleukin 6. Furthermore, modulation of macrophage function by Opuntia polysaccharides was mediated, at least in part, through activation of nuclear factor κB. Together, our results provide a molecular basis to explain a portion of the beneficial therapeutic properties of extracts from O. polyacantha and support the concept of using Opuntia polysaccharides as an immunotherapeutic adjuvant. PMID:18597716

  12. Bacterial Extracellular Polysaccharides in Biofilm Formation and Function

    PubMed Central

    Limoli, Dominique H.; Jones, Christopher J.; Wozniak, Daniel J.

    2015-01-01

    Microbes produce a biofilm matrix consisting of proteins, extracellular DNA, and polysaccharides that is integral in the formation of bacterial communities. Historical studies of polysaccharides revealed that their overproduction often alters the colony morphology and can be diagnostic in identifying certain species. The polysaccharide component of the matrix can provide many diverse benefits to the cells in the biofilm, including adhesion, protection, and structure. Aggregative polysaccharides act as molecular glue, allowing the bacterial cells to adhere to each other as well as surfaces. Adhesion facilitates the colonization of both biotic and abiotic surfaces by allowing the bacteria to resist physical stresses imposed by fluid movement that could separate the cells from a nutrient source. Polysaccharides can also provide protection from a wide range of stresses, such as desiccation, immune effectors, and predators such as phagocytic cells and amoebae. Finally, polysaccharides can provide structure to biofilms, allowing stratification of the bacterial community and establishing gradients of nutrients and waste products. This can be advantageous for the bacteria by establishing a heterogeneous population that is prepared to endure stresses created by the rapidly changing environments that many bacteria encounter. The diverse range of polysaccharide structures, properties, and roles highlight the importance of this matrix constituent to the successful adaptation of bacteria to nearly every niche. Here, we present an overview of the current knowledge regarding the diversity and benefits that polysaccharide production provides to bacterial communities within biofilms. PMID:26185074

  13. Macrophage immunomodulatory activity of polysaccharides isolated from Opuntia polyacantha.

    PubMed

    Schepetkin, Igor A; Xie, Gang; Kirpotina, Liliya N; Klein, Robyn A; Jutila, Mark A; Quinn, Mark T

    2008-10-01

    Opuntia polyacantha (prickly pear cactus) has been used extensively for its nutritional properties; however, less is known regarding medicinal properties of Opuntia tissues. In the present study, we extracted polysaccharides from O. polyacantha and used size-exclusion chromatography to fractionate the crude polysaccharides into four polysaccharide fractions (designated as Opuntia polysaccharides C-I to C-IV). The average M(r) of fractions C-I through C-IV was estimated to be 733, 550, 310, and 168 kDa, respectively, and sugar composition analysis revealed that Opuntia polysaccharides consisted primarily of galactose, galacturonic acid, xylose, arabinose, and rhamnose. Analysis of the effects of Opuntia polysaccharides on human and murine macrophages demonstrated that all four fractions had potent immunomodulatory activity, inducing production of reactive oxygen species, nitric oxide, tumor necrosis factor alpha, and interleukin 6. Furthermore, modulation of macrophage function by Opuntia polysaccharides was mediated, at least in part, through activation of nuclear factor kappaB. Together, our results provide a molecular basis to explain a portion of the beneficial therapeutic properties of extracts from O. polyacantha and support the concept of using Opuntia polysaccharides as an immunotherapeutic adjuvant.

  14. In vitro antioxidant activity of polysaccharide from Gardenia jasminoides ellis

    USGS Publications Warehouse

    Fan, Y.; Ge, Z.; Luo, A.

    2011-01-01

    A water-soluble polysaccharide, GP, was isolated from Gardenia jasminoides Ellis through hot water extraction followed by ethanol precipitation. The in vitro free radicals scavenging tests exhibited that GP has significant scavenging abilities especially for ABTS, DPPH, and hydroxyl radicals, which suggests that the polysaccharide GP is a novel antioxidant. ?? 2011 Academic Journals.

  15. Structural modification of polysaccharides: A biochemical-genetic approach

    NASA Technical Reports Server (NTRS)

    Kern, Roger G.; Petersen, Gene R.

    1991-01-01

    Polysaccharides have a wide range of industrial and biomedical applications. An industry trend is underway towards the increased use of bacteria to produce polysaccharides. Long term goals of this work are the adaptation and enhancement of saccharide properties for electronic and optic applications. In this report we illustrate the application of enzyme-bearing bacteriophage on strains of the enteric bacterium Klebsiella pneumoniae, which produces a polysaccharide with the relatively rare rheological property of drag-reduction. This has resulted in the production of new polysaccharides with enhanced rheological properties. Our laboratory is developing techniques for processing and structurally modifying bacterial polysaccharides and oligosaccharides which comprise their basic polymeric repeat units. Our research has focused on bacteriophage which produce specific polysaccharide degrading enzymes. This has lead to the development of enzymes generated by bacteriophage as tools for polysaccharide modification and purification. These enzymes were used to efficiently convert the native material to uniform-sized high molecular weight polymers, or alternatively into high-purity oligosaccharides. Enzyme-bearing bacteriophage also serve as genetic selection tools for bacteria that produce new families of polysaccharides with modified structures.

  16. Methods of saccharification of polysaccharides in plants

    DOEpatents

    Howard, John; Fake, Gina

    2014-04-29

    Saccharification of polysaccharides of plants is provided, where release of fermentable sugars from cellulose is obtained by adding plant tissue composition. Production of glucose is obtained without the need to add additional .beta.-glucosidase. Adding plant tissue composition to a process using a cellulose degrading composition to degrade cellulose results in an increase in the production of fermentable sugars compared to a process in which plant tissue composition is not added. Using plant tissue composition in a process using a cellulose degrading enzyme composition to degrade cellulose results in decrease in the amount of cellulose degrading enzyme composition or exogenously applied cellulase required to produce fermentable sugars.

  17. (Lipo)polysaccharide interactions of antimicrobial peptides.

    PubMed

    Schmidtchen, Artur; Malmsten, Martin

    2015-07-01

    Due to rapidly increasing resistance development against conventional antibiotics, as well as problems associated with diseases either triggered or deteriorated by infection, antimicrobial and anti-inflammatory peptides have attracted considerable interest during the last few years. While there is an emerging understanding of the direct antimicrobial function of such peptides through bacterial membrane destabilization, the mechanisms of their anti-inflammatory function are less clear. We here summarize some recent results obtained from our own research on anti-inflammatory peptides, with focus on peptide-(lipo)polysaccharide interactions.

  18. Gut microbiota, host health, and polysaccharides.

    PubMed

    Xu, Xiaofei; Xu, Pingping; Ma, Chungwah; Tang, Jian; Zhang, Xuewu

    2013-01-01

    The intestinal microbiota is a complicated ecosystem that influences many aspects of host physiology (i.e. diet, disease development, drug metabolism, and regulation of the immune system). It also exhibits spatial patterning and temporal dynamics. In this review, the effects of internal and external (environmental) factors on intestinal microbiota are discussed. We describe the roles of the gut microbiota in maintaining intestinal and immune system homeostasis and the relationship between gut microbiota and diseases. In particular, the contributions of polysaccharides, as the most abundant diet components in intestinal microbiota and host health are presented. Finally, perspectives for research avenues relating to gut microbiota are also discussed.

  19. Use of insertional inactivation to facilitate studies of biological properties of pneumococcal surface protein A (PspA)

    PubMed Central

    1987-01-01

    PspA is a cell surface protein of Streptococcus pneumoniae that is present on a number of clinical isolates as well as the nonencapsulated laboratory strain Rx1. In a previous report we have shown that mAbs directed against PspA can protect mice from at least some of the pneumococcal strains bearing this protein. In our present report we have produced insertional inactivation mutants that lack PspA and have used these mutants to demonstrate that PspA can play a role in pneumococcal virulence and that anti-PspA immunity can lead to protection against pneumococcal infection. PspA- mutants were obtained using derivatives of plasmid pVA891 carrying chromosomal fragments from Rx1. From one of the mutants, we cloned a 550 bp fragment of the pneumococcal gene into pVA891 and transferred this chimeric plasmid, designated pKSD300, into Escherichia coli. After transformation of pKSD300 into Rx1, PspA production is not detected. In colony hybridization experiments, the 550 bp fragment hybridizes specifically to pneumococcal isolates in a pattern consistent with the hypothesis that the fragment is a portion of the pspA structural gene that is different from the portions coding for the antigenic determinants detected by mAbs Xi64 or Xi126. When X-linked immunodeficient (xid) CBA/N mice were immunized with wild-type Rx1, they were resistant to challenge with type 3 strain WU2. However, when these mice were immunized with a PspA- mutant of Rx1, they failed to survive the subsequent challenge, indicating that immunity to PspA can contribute to the resistance to pneumococcal infection. Using pKSD300 we insertionally inactivated pspA in D39, a virulent strain of S. pneumoniae. When injected intravenously there was a 10-fold greater reduction of the mutant pneumococci in the blood, as compared to the wild-type D39. PMID:3546575

  20. Acute Primary Pneumococcal Purulent Pericarditis With Cardiac Tamponade: A Case Report and Literature Review.

    PubMed

    Patel, Hiren; Patel, Charmi; Soni, Mrugesh; Patel, Amit; Banda, Venkat

    2015-10-01

    Bacterial pericarditis is a rapidly progressive and highly fatal infection, and is often diagnosed postmortem in half of the cases. Even with drainage and antibiotics, the mortality rate is high. Gram-positive cocci, specifically Streptococcus penumoniae, have been the most common cause of bacterial pericarditis with a preceding primary site of infection. Following the introduction of antibiotics in the 1940s and more recently the pneumococcal conjugate vaccine, the incidence has drastically decreased.We describe an extremely rare case of primary streptococcus pneumoniae purulent pericarditis that presented with cardiac tamponade. The patient was successfully treated with broad-spectrum antibiotics and urgent pericardiocentesis.Due to the high mortality rate with purulent pericarditis, a high index of suspicion is needed when acute pericarditis is suspected for early diagnosis to instate appropriate therapy with antibiotics and drainage.

  1. Perimenopausal pneumococcal tubo-ovarian abscess--a case report and review.

    PubMed Central

    Seshadri, Srividya; Kirwan, John; Neal, Tim

    2004-01-01

    BACKGROUND: Genital tract infections in females secondary to Streptococcus pneumoniae (pneumococcus) are unusual. Tubo-ovarian abscess resulting from such an infection is a rare occurrence and diagnosis is not always easy. This report demonstrates the problems of recognizing this condition and summarizes the pathomechanism, investigations leading to a diagnosis and the subsequent management. CASE: A rare case of a tubo-ovarian abscess caused by pneumococcus, occurring in a previously healthy 48-year-old woman, is presented. The tubo-ovarian abscess may have developed insidiously and probably had an acute exacerbation prior to presentation. CONCLUSION: This case is unusual in that there were no identifiable initiating events for the source of the pneumococcal infection. Early recognition of a tubo-ovarian abscess is important in order to prevent the associated morbidity and mortality. This condition has the propensity to mimic a neoplasm. PMID:15460193

  2. Blood-group-A-like substance in a preparation of pneumococcal vaccine.

    PubMed

    Siber, G R; Ambrosino, D M; Gorgone, B C

    1982-05-01

    A platel