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Sample records for 7-valent pneumococcal vaccine

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. Potential carrier priming effect in Australian infants after 7-valent pneumococcal conjugate vaccine introduction

    PubMed Central

    Tashani, Mohamed; Jayasinghe, Sanjay; Harboe, Zitta B; Rashid, Harunor; Booy, Robert

    2016-01-01

    AIM To investigate evidence of clinical protection in infants after one dose of 7-valent pneumococcal conjugate vaccine (7vPCV) owing to carrier priming. METHODS Using Australian National Notifiable Diseases Surveillance System data, we conducted a descriptive analysis of cases of vaccine type invasive pneumococcal disease (VT-IPD) during “catch-up” years, when 7vPCV was carrier primed by prior administration of DTPa vaccine. We compared the number of VT-IPD cases occurring 2-9 wk after a single dose of 7vPCV (carrier primed), with those < 2 wk post vaccination, when no protection from 7vPCV was expected yet. Further comparison was conducted to compare the occurrence of VT-IPD cases vs non-VT-IPD cases after a single carrier-primed dose of 7vPCV. RESULTS We found four VT-IPD cases occurring < 2 wk after one carrier primed dose of 7vPCV while only one case occurred 2-9 wk later. Upon further comparison with the non-VT-IPD cases that occurred after one carrier primed dose of 7vPCV, two cases were detected within 2 wk, whereas seven occurred within 2-9 wk later; suggesting a substantial level of protection from VT-IPD occurring from 2 wk after carrier-primed dose of 7vPCV. CONCLUSION This data suggest that infants may benefit from just one dose of 7vPCV, likely through enhanced immunity from carrier priming effect. If this is proven, an adjusted 2-dose schedule (where the first dose of PCV is not given until after DTPa) may be sufficient and more cost-effective. PMID:27610348

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France

    PubMed Central

    2012-01-01

    Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion The carriage

  15. Streptococcus pneumoniae nasopharyngeal carriage in children attending day-care centers in the central region of Portugal, in the era of 7-valent pneumococcal conjugate vaccine.

    PubMed

    Rodrigues, Fernanda; Nunes, Sónia; Sá-Leão, Raquel; Gonçalves, Guilherme; Lemos, Luís; de Lencastre, Hermínia

    2009-12-01

    The 7-valent pneumococcal conjugate vaccine became available in Portugal in 2001. Although not included in the national immunization program, vaccination coverage is high (over 60%). We studied for the first time the rates of nasopharyngeal (NP) carriage of pneumococci, antibiotic resistance patterns and serotypes among children attending day-care centers (DCCs) in Coimbra, a city in the Central Region of Portugal. Between January and February 2007, a cross-sectional study was conducted among children aged 6 months to 6 years attending eight DCCs. NP swabs were obtained from 507 children: 76.7% had received at least one dose of 7-valent pneumococcal conjugate vaccine and 64.3% were age-appropriately vaccinated. The global pneumococcal carriage rate was 61.3%. Colonization proportions varied with age and number of children attending each DCC. Serotyping revealed that 20.7% of the pneumococci were vaccine types (VTs), 70.8% were non-VTs, and 8.5% were nontypeable. Serotype 19F was the second most frequent serotype being detected in 10.5% of the samples. While global NP carriage was not associated with vaccination status, non-VTs were predominant among vaccinated children, who had significantly lower prevalence of VT. Of all isolates, 15.7% had penicillin minimum inhibitory concentrations that ranged between 0.12 and 2 microg/ml. The proportion of resistant strains was significantly higher among VT and unvaccinated children. In conclusion, the rates of vaccination and prevalence of pneumococcal NP were high. Rates of antimicrobial resistance were similar to those found in studies conducted in Oeiras and Lisbon. This study is a platform for future surveillance activities.

  16. Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

    PubMed

    Picón, Teresa; Alonso, Lucía; García Gabarrot, Gabriela; Speranza, Noelia; Casas, Mariana; Arrieta, Fernando; Camou, Teresa; Rosa, Raquel; De Oliveira, Lucia Helena; Verani, Jennifer Rabke

    2013-07-02

    The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥ 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥ 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

  17. Comparability of antibody response to a booster dose of 7-valent pneumococcal conjugate vaccine in infants primed with either 2 or 3 doses.

    PubMed

    Rodenburg, Gerwin D; van Gils, Elske J M; Veenhoven, Reinier H; Jones, Nienke; Tcherniaeva, Irina; Hak, Eelko; van Alphen, Loek; Berbers, Guy A M; Sanders, Elisabeth A M

    2010-02-03

    In this cohort study we compared IgG antibody levels between infants immunized with 7-valent CRM197-conjugated pneumococcal vaccine (PCV-7) at 2, 4 and 11 months and at 2, 3, 4 and 11 months of age, as measured by double adsorption ELISA. Pre- and post-booster levels following the 2+1- and 3+1-dose schedule were comparable for 5 out of 7 serotypes except for serotypes 6B and 19F. The proportion of children reaching post-booster antibody thresholds were comparable except for 6B (>or=1.0 microg/ml and >or=5.0 microg/ml) and 19F (>or=5.0 microg/ml). Surveillance studies are warranted for vaccine impact on 6B and 19F disease cases after reduced-dose PCV-7 schedules.

  18. Serotyping and multilocus sequence typing of Streptococcus pneumoniae isolates from the blood and posterior nares of Japanese children prior to the introduction of 7-valent pneumococcal conjugate vaccine.

    PubMed

    Oishi, Tomohiro; Wada, Akihito; Chang, Bin; Toyabe, Shinichi; Uchiyama, Makoto

    2011-01-01

    In Japan, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. To assess the effects of PCV7 on invasive pneumococcal infection in children, a population-based prospective survey has been conducted in 10 prefectures. As a part of the study, blood and nasopharyngeal isolates from children admitted to the Shibata Hospital, Niigata Prefecture, were analyzed for determining the serotypes, their susceptibilities to antimicrobial agents, and multilocus sequence types. Sixteen blood isolates were obtained from October 2007 to December 2009. Sixty-three nasopharyngeal isolates were obtained from the posterior nares of 118 children with pneumonia from April to September 2008. The coverage rates of the blood and nasopharyngeal isolates for PCV7 were 81.3% and 57.1%, respectively. Although none of these children had received PCV7, serotype 19A isolates were recovered from 12.5% (2/16) of the blood samples and 12.7% (8/63) of the nasopharyngeal samples. The sequence type of a nasopharyngeal isolate of serotype 19A was ST320, and the minimum inhibitory concentration of penicillin G was 4 μg/mL. In addition to the continuous prospective survey of pneumococcal infection, early introduction of the 13-valent conjugate vaccine, in which the 19A conjugate is included, will be necessary in Japan.

  19. 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

  20. Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

    PubMed Central

    Kashiwagi, Yasuyo; Miyata, Akiko; Kumagai, Takuji; Maehara, Kouji; Suzuki, Eitarou; Nagai, Takao; Ozaki, Takao; Nishimura, Naoko; Okada, Kenji; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-01-01

    Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines both became recommended in Japan in 2010. In this study, cytokine production was investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (DPT), Hib, and PCV7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. Higher IL-1β levels were produced when cultures were stimulated with PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced the production of IL-1β. Although Hib induced higher levels of IL-6, no significant difference was observed in IL-6 production with the concurrent stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced higher levels of TNF-α and human G-CSF. Cytokine profiles were examined in serum samples obtained from 61 vaccine recipients with febrile reactions and 18 recipients without febrile illness within 24 h of vaccination. No significant difference was observed in cytokine levels of IL-1β, IL-4, IL-6, IL-10, IL-12, IFN-γ, MIP-1, TNF-α, and prostaglandin E2 (PGE2) in sera between the two groups. However, significantly higher levels of human G-CSF were observed in recipients with febrile illness than in those without febrile reactions. Further investigations of the significance of elevated serum G-CSF levels are required in vaccine recipients with febrile illness. PMID:24589970

  1. Immunogenicity of a hexavalent vaccine co-administered with 7-valent pneumococcal conjugate vaccine. Findings from the National Immunisation Programme in The Netherlands.

    PubMed

    Whelan, Jane; Hahné, Susan; Berbers, Guy; van der Klis, Fiona; Wijnands, Yvonne; Boot, Hein

    2012-06-01

    The hexavalent vaccine Infanrix hexa was introduced into the national childhood vaccination schedule in the Netherlands in 2006. It is offered, concomitantly with pneumococcal vaccine (Prevenar), to children at increased risk of hepatitis B, administered in a 4-dose schedule at 2, 3, 4 and 11 months of age. We assessed the immunogenicity of the HBV component of Infanrix hexa co-administered with Prevenar, and compared pertussis and Hib components in Infanrix hexa with the standard Infanrix-IPV+Hib vaccine. Target thresholds for immune responses were achieved for all antigens studied. Over 99% (163/164) of children vaccinated with Infanrix hexa achieved an adequate immune response (≥ 10 mIU/ml) to the HBV component and peak anti-HBs geometric mean concentration (GMC) was 2264 mIU/ml (95%CI:1850-2771 mIU/ml). The GMC of a pertussis component, filamentous hemagglutinin (FHA), of Infanrix-hexa was significantly lower in children vaccinated with Infanrix hexa and Prevenar than in children vaccinated with Infanrix-IPV+Hib. Universal infant HBV vaccination using Infanrix hexa was introduced in The Netherlands in 2011. Despite very high rates of seroconversion for the HBV component of Infanrix hexa, its long term immunogenicity and effectiveness should be monitored after concomitant vaccination.

  2. Serotype and clonal evolution of penicillin-nonsusceptible invasive Streptococcus pneumoniae in the 7-valent pneumococcal conjugate vaccine era in Italy.

    PubMed

    Gherardi, Giovanni; D'Ambrosio, Fabio; Visaggio, Daniela; Dicuonzo, Giordano; Del Grosso, Maria; Pantosti, Annalisa

    2012-09-01

    The percentage of invasive penicillin-nonsusceptible pneumococci (PNSSP) isolated in Italy in the seven-valent pneumococcal conjugate vaccine (PCV7) era moderately increased in comparison to the pre-PCV7 era. Increase of nonvaccine serotypes was observed among PNSSP. The most frequent PNSSP clones were the same as those identified in the pre-PCV7 era, although they were present in different proportions. Clonal expansion, emergence of new clones, and acquisition of penicillin resistance by established clones contributed to the maintenance of penicillin resistance.

  3. Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program

    PubMed Central

    Abdelnour, Arturo; Arguedas, Adriano; Dagan, Ron; Soley, Carolina; Porat, Nurith; Mercedes Castrejon, Maria; Ortega-Barria, Eduardo; Colindres, Romulo; Pirçon, Jean-Yves; DeAntonio, Rodrigo; Van Dyke, Melissa K.

    2015-01-01

    Abstract Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9

  4. Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy.

    PubMed

    Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo

    2011-11-28

    A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

    PubMed

    Abdelnour, Arturo; Arguedas, Adriano; Dagan, Ron; Soley, Carolina; Porat, Nurith; Castrejon, Maria Mercedes; Ortega-Barria, Eduardo; Colindres, Romulo; Pirçon, Jean-Yves; DeAntonio, Rodrigo; Van Dyke, Melissa K

    2015-01-01

    Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9

  11. 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 ...

  12. 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

  13. 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.

  14. 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, ...

  15. 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 ...

  16. [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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

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

    Code of Federal Regulations, 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...

  3. 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...

  4. 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...

  5. 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 ...

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

    PubMed

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

    2015-12-01

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

  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. Evolving microbiology of complicated acute otitis media before and after introduction of the pneumococcal conjugate vaccine in France.

    PubMed

    Dupont, Damien; Mahjoub-Messai, Farah; François, Martine; Doit, Catherine; Mariani-Kurkdjian, Patricia; Bidet, Philippe; Bonacorsi, Stéphane; Carol, Agnès; Bingen, Edouard

    2010-09-01

    We compare the microbiology of otopathogens causing recurrent acute otitis media (AOM) or AOM treatment failure in 600 children during 2000 to 2008 before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7). Streptococcus pneumoniae predominated before PCV-7 introduction and during 2007 to 2008, whereas Haemophilus influenzae predominated during 2005 to 2006. S. pneumoniae 19A became the most frequent serotype after PCV-7 introduction.

  9. 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.)

  10. [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.

  11. 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

  12. 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

  13. Immunogenicity and safety of a combined diphtheria, tetanus, 5-component acellular pertussis, inactivated poliomyelitis, Haemophilus type b conjugate vaccine when administered concurrently with a pneumococcal conjugate vaccine: a randomized, open-label, phase 3 study.

    PubMed

    Bernstein, Henry H; Noriega, Fernando

    2011-03-03

    A phase 3 randomized, multicenter study evaluated the safety and immunogenicity of a combined diphtheria, tetanus, 5-component acellular pertussis, inactivated poliomyelitis, Haemophilus influenzae type b conjugate vaccine (DTaP(5)-IPV/Hib) administered at the same visit with 7-valent pneumococcal conjugate vaccine (PCV7, concurrent group) or at separate visits (separated by ≥ 15 days; staggered group). DTaP(5)-IPV/Hib was administered at 2, 4, 6, and 15 months of age, and PCV7 was administered concurrently or at 3, 5, 7, and 16 months of age. The study results found that DTaP(5)-IPV/Hib is safe and immunogenic when given concurrently with 7-valent pneumococcal conjugate vaccine.

  14. [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.

  15. [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.

  16. 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 ...

  17. 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

  18. 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

  19. 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

  20. 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

  1. [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.

  2. 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.

  3. Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

    PubMed

    Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela

    2017-02-01

    Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0-9 y ("target" of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y.

  4. 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 ...

  5. 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

  6. 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

  7. 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.

  8. The impact of B-cell perturbations on pneumococcal conjugate vaccine response in HIV-infected adults.

    PubMed

    Johannesson, Thomas G; Søgaard, Ole S; Tolstrup, Martin; Petersen, Mikkel S; Bernth-Jensen, Jens M; Østergaard, Lars; Erikstrup, Christian

    2012-01-01

    Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count as follows: 20 ART-naïve (no prior ART), 62 ART-responders (received ART, and CD4 count >500 cells/µl), and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl). All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist) at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ)-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.

  9. 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.

  10. 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

  11. Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015

    PubMed Central

    Picazo, Juan; Ruiz-Contreras, Jesús; Casado-Flores, Juan; Negreira, Sagrario; Baquero, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2017-01-01

    In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014–15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity. PMID:28207888

  12. 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.

  13. [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.

  14. Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies

    PubMed Central

    Wysocki, Jacek; Brzostek, Jerzy; Konior, Ryszard; Panzer, Falko G.; François, Nancy A.; Ravula, Sudheer M.; Kolhe, Devayani A.; Song, Yue; Dieussaert, Ilse; Schuerman, Lode; Borys, Dorota

    2017-01-01

    ABSTRACT To investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 – Study A) and 5 years (NCT00891176 – Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination. PMID:27736293

  15. Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies.

    PubMed

    Wysocki, Jacek; Brzostek, Jerzy; Konior, Ryszard; Panzer, Falko G; François, Nancy A; Ravula, Sudheer M; Kolhe, Devayani A; Song, Yue; Dieussaert, Ilse; Schuerman, Lode; Borys, Dorota

    2016-10-13

    To investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 - Study A) and 5 years (NCT00891176 - Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination.

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

    PubMed Central

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

    2015-01-01

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

  17. 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

  18. Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

    PubMed Central

    Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bechini, Angela

    2017-01-01

    ABSTRACT Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002–2007) and vaccination period (VP, 2009–2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0–9 y (“target” of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y. PMID:27925848

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Postlicensure surveillance for pre-specified adverse events following the 13-valent pneumococcal conjugate vaccine in children.

    PubMed

    Tseng, Hung Fu; Sy, Lina S; Liu, In-Lu Amy; Qian, Lei; Marcy, S Michael; Weintraub, Eric; Yih, Katherine; Baxter, Roger; Glanz, Jason M; Donahue, James; Naleway, Allison; Nordin, James; Jacobsen, Steven J

    2013-05-24

    Although no increased risk was detected for serious adverse events in the prelicensure trials for the 13-valent pneumococcal vaccine, Prevnar 13(®) (PCV13), continued monitoring of rare but serious adverse events is necessary. A surveillance system using cohort study design was set up to monitor safety of PCV13 immediately after it was included in the childhood immunization program in the United States. The exposed population included children of 1 month to 2 years old who received PCV13 from April, 2010 to January, 2012 from the eight managed care organizations participating in the Vaccine Safety Datalink Project in the United States. The historical unexposed population was children of the same age who received the 7-valent pneumococcal conjugate vaccine Prevnar 7(®) (PCV7) in 2007 (or 2005 depending on the outcome of interest) to 2009. The risk of pre-specified adverse events in the risk window following PCV13 was repeatedly compared to that in the historical comparison group. The number of doses included in the study was 599,229. No increased risk was found for febrile seizures, urticaria or angioneurotic edema, asthma, thrombocytopenia, or anaphylaxis. An increased risk for encephalopathy was not confirmed following the medical record review. The relative risk for Kawasaki disease in 0-28 days following vaccination was 1.94 (95% confidence interval: 0.79-4.86), comparing PCV13 to PCV7. Comparing to PCV7 vaccine, we identified no significant increased risk of pre-specified adverse events in the Vaccine Safety Datalink study cohort. The possible association between PCV13 and Kawasaki disease may deserve further investigation.

  4. [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.

  5. 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.

  6. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants' vaccination?

    PubMed

    Azzari, Chiara; Cortimiglia, Martina; Nieddu, Francesco; Moriondo, Maria; Indolfi, Giuseppe; Mattei, Romano; Zuliani, Massimo; Adriani, Beatrice; Degl'Innocenti, Roberto; Consales, Guglielmo; Aquilini, Donatella; Bini, Giancarlo; Di Natale, Massimo Edoardo; Canessa, Clementina; Ricci, Silvia; de Vitis, Elisa; Mangone, Giusi; Bechini, Angela; Bonanni, Paolo; Pasinato, Angela; Resti, Massimo

    2016-01-01

    The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.

  7. 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...

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    PubMed

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  15. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines

    PubMed Central

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela

    2016-01-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  16. Impact of 13-Valent Pneumococcal Conjugate Vaccine Used in Children on Invasive Pneumococcal Disease in Children and Adults in the United States: Analysis of Multisite, Population-based Surveillance

    PubMed Central

    Moore, Matthew R.; Link-Gelles, Ruth; Schaffner, William; Lynfield, Ruth; Lexau, Catherine; Bennett, Nancy M.; Petit, Susan; Zansky, Shelley M.; Harrison, Lee H.; Reingold, Arthur; Miller, Lisa; Scherzinger, Karen; Thomas, Ann; Farley, Monica M.; Zell, Elizabeth R.; Taylor, Thomas H.; Pondo, Tracy; Rodgers, Loren; McGee, Lesley; Beall, Bernard; Jorgensen, James H.; Whitney, Cynthia G.

    2016-01-01

    SUMMARY Background In 2000, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the U.S. and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and modest increases in non-PCV7-type IPD. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the U.S. immunization schedule. We evaluated the effect of PCV13 use in children on IPD in children and adults in the U.S. Methods We used laboratory- and population-based data on incidence of IPD from CDC’s Emerging Infections Program / Active Bacterial Core surveillance in a time-series model to estimate the impact of vaccination. Cases of IPD during July 2004–June 2013 were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13/nonPCV7). Findings Compared with incidence expected among children <5 years old if PCV7 alone had been continued, incidence of IPD overall and IPD caused by PCV13/nonPCV7 serotypes declined by 64% (95% interval estimate [IE] 59–68 %) and 93% (95%IE 91–94), respectively, by July 2012–June 2013. Among adults, incidence of IPD overall and PCV13/nonPCV7-type IPD also declined by 12–32% and 58–72%, respectively, depending on age. In all age groups, reductions were driven principally by changes in incidence of serotypes 19A and 7F. We estimate that over 30,000 cases of IPD and 3,000 deaths were averted in the first 3 years following PCV13 introduction. Interpretation PCV13 has reduced IPD among all ages when used routinely in children in the U.S. Serotypes 19A and 7F, which emerged after PCV7 introduction, have been effectively controlled. PMID:25656600

  17. 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.

  18. 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

  19. 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.

  20. 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-vaccine

  1. 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

  2. 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.

  3. 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

  4. [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.

  5. 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

  6. 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

  7. Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012-2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes.

    PubMed

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

    2016-01-01

    Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009-2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012-2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.

  8. Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012–2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes

    PubMed Central

    Horácio, Andreia N.; Silva-Costa, Catarina; Lopes, Joana P.; Ramirez, Mário; Melo-Cristino, José; Vaz, Teresa

    2016-01-01

    Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012–2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009–2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012–2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates. PMID:27790208

  9. 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.

  10. Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model

    PubMed Central

    Delgleize, Emmanuelle; Leeuwenkamp, Oscar; Theodorou, Eleni; Van de Velde, Nicolas

    2016-01-01

    Objectives In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. Design CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. Setting Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Population Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Interventions Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. Outcome measures The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). Results Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. Conclusions This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Immunogenicity

    PubMed Central

    2014-01-01

    Background: Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants. Methods: We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ≥2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ≤6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region. Results: From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 “2+1” (2 primary plus booster) and 42 “3+1” schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ≤6 months of age (3+0). Conclusions: While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  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. 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

  12. 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.

  13. Invasive pneumococci before the introduction of pneumococcal conjugate vaccine in Turkey: antimicrobial susceptibility, serotype distribution, and molecular identification of macrolide resistance.

    PubMed

    Altun, Hatice Uludag; Hascelik, Gülsen; Gür, Deniz; Eser, Özgen Köseoglu

    2015-02-01

    This study evaluates the antimicrobial susceptibilities and serotype distributions of invasive Streptococcus pneumoniae (SP) isolates identified in a Turkish hospital before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The susceptibilities of all isolates were determined by evaluating six antibiotics: penicillin (PEN), ceftriaxone (CRO), levofloxacin (LEV), erythromycin (ERY), clindamycin (CD), and vancomycin (VAN). Serotyping and amplification of macrolide resistance genes were performed. Sixteen (50%) and four (2%) isolates were resistant to PEN and LEV, respectively. No isolates demonstrated VAN resistance. Intermediate resistance to CRO was found in 4% of all invasive isolates. Twenty-three (12.6%) isolates were resistant to ERY. Four (2%) invasive SP isolates demonstrated multidrug resistance. Serogroups 3, 5, 6, 8, 9, and 23 were the most common in both age groups. The potential coverage rates of PCV7 and PCV13 were 44.1 and 66.1% in children and 39.8 and 71.5% in adults, respectively. Continuous surveillance of antimicrobial resistance is required.

  14. 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.

  15. Postvaccination Increase in Serotype 19A Pneumococcal Disease in Norway Is Driven by Expansion of Penicillin-Susceptible Strains of the ST199 Complex

    PubMed Central

    Steinbakk, Martin; Aaberge, Ingeborg S.; Caugant, Dominique A.

    2012-01-01

    Serotype replacement in invasive pneumococcal disease has been observed after widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7). Replacement is dominated by penicillin-nonsusceptible serotype 19A in several countries. Antibiotic selection pressure has been proposed to interact with immunization, leading to rapid replacement. In Norway, where prescription of antibiotics is limited, post-PCV7 replacement by serotype 19A is dominated by penicillin-susceptible clones. Hence, serotype 19A replacement occurs, although it is not driven by antibiotic selection pressure. PMID:22237889

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Concomitant administration of hepatitis A vaccine with measles/mumps/rubella/varicella and pneumococcal vaccines in healthy 12- to 23-month-old children.

    PubMed

    Yetman, Robert J; Shepard, Julie S; Duke, Anton; Stek, Jon E; Petrecz, Maria; Klopfer, Stephanie O; Kuter, Barbara J; Schödel, Florian P; Lee, Andrew W

    2013-08-01

    This open-label, multicenter, randomized, comparative study evaluated immunogenicity, safety and tolerability of concomitant (Group 1; n=330) vs. non-concomitant (Group 2; n=323) VAQTA™ (25U/0.5 mL) (hepatitis A vaccine; HAV) with ProQuad™ (measles/mumps/rubella/varicella; MMRV) and Prevnar™ (7-valent pneumococcal; PCV-7) in healthy, 12-23 mo old children. Group 1 received HAV/MMRV/PCV-7 concomitantly on Day 1 and second doses of HAV/MMRV at Week 24. Group 2 received MMRV/PCV-7 on Day 1, HAV at Weeks 6 and 30 and MMRV at Week 34. Hepatitis A seropositivity rate (SPR: ≥10 mIU/mL; 4 weeks postdose 2), varicella zoster-virus (VZV) SPR (≥5 gpELISA units/mL) and geometric mean titers (GMT) to S. pneumoniae were examined. Injection-site and systemic adverse experiences (AEs) and daily temperatures were collected. Hepatitis A SPR were 100% for Group 1 and 99.4% for Group 2 after two HAV doses; risk difference=0.7 (95%CI: -1.4,3.8, non-inferior) regardless of initial serostatus. VZV SPR was 93.3% for Group 1 and 98.3% for Group 2; risk difference=-5.1 (95%CI: -9.3, -1.4; non-inferior). S. pneumoniae GMT fold-difference (7 serotypes) ranged from 0.9 to 1.1; non-inferior. No statistically significant differences in the incidence of individual AEs were seen when HAV was administered concomitantly vs. non-concomitantly. Three (all Group 2 post-administration of MMRV/PCV-7) of 11 serious AEs were considered possibly vaccine-related: dehydration and gastroenteritis (same subject) on Day 52; febrile seizure on Day 9. No deaths were reported. Antibody responses to each vaccine given concomitantly were non-inferior to HAV given non-concomitantly with MMRV and PCV-7. Administration of HAV with PCV-7 and MMRV had an acceptable safety profile in 12- to 23-mo-old children.

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status

    PubMed Central

    Madhi, Shabir A.; Koen, Anthonet; Jose, Lisa; van Niekerk, Nadia; Adrian, Peter V.; Cutland, Clare; François, Nancy; Ruiz-Guiñazú, Javier; Yarzabal, Juan-Pablo; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2017-01-01

    Abstract Background: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children. Methods: Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9–10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster. Results: Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related. Conclusion: PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status. PMID:28079828

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Vaccination response following aerobic exercise: can a brisk walk enhance antibody response to pneumococcal and influenza vaccinations?

    PubMed

    Long, Joanna E; Ring, Christopher; Drayson, Mark; Bosch, Jos; Campbell, John P; Bhabra, Jagraj; Browne, David; Dawson, Joel; Harding, Sarah; Lau, Jamie; Burns, Victoria E

    2012-05-01

    High intensity acute exercise at the time of vaccination has been shown to enhance the subsequent antibody response. This study examines whether an acute moderate intensity aerobic intervention prior to vaccination can enhance antibody response to pneumonia and half dose influenza vaccination. Sixty young (age (SD)=22.0 (6.1) years) and 60 older (age (SD)=57.5 (6.5) years) adults attended the laboratory on two separate occasions. At the first session, baseline antibody titres were determined, before participants completed either a brisk walk around campus at >55% of their age-predicted heart rate maximum, or a resting control condition, for 45 min. After the intervention, all participants received a full-dose pneumococcal vaccination and a half-dose influenza vaccination. Four weeks later, participants returned for a follow up blood sample. Multivariate ANOVA revealed an increase in total antibody titres against the influenza vaccine (F((12,106))=25.76, p<.001, η(2)=.75) and both the IgM (F((12,106))=17.10, p<.001, η(2)=.66) and IgG (F((12,106))=25.76, p<.001, η(2)=.75) antibody titres against the pneumococcal vaccine. However, there were no significant Time×Group interactions (p's all >.15), indicating that a 45 min brisk walk prior to vaccination did not affect antibody response to either the influenza or pneumonia vaccine. The results suggest that higher intensity exercise is necessary to augment antibody response to vaccination.

  15. 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.

  16. 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.

  17. The effect of physicians' awareness on influenza and pneumococcal vaccination rates and correlates of vaccination in patients with diabetes in Turkey: an epidemiological Study "diaVAX".

    PubMed

    Satman, Ilhan; Akalin, Sema; Cakir, Bekir; Altinel, Serdar

    2013-12-01

    We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been

  18. 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

  19. 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.

  20. 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%).

  1. 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

  2. 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.

  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. 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

  5. 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.

  6. 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.

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

    MedlinePlus

    ... the CDC Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html CDC review ... at the highest risk. Before there was a vaccine, the United States saw: more than 700 cases ...

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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 ...

  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. Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation; a PneumoCarr meeting report March 27-28, 2012, Geneva.

    PubMed

    Goldblatt, David; Ramakrishnan, Meena; O'Brien, Katherine

    2013-12-17

    An international consultation was convened in March 2012 to provide feedback on the Case for Carriage, a summary statement by the Pneumococcal Carriage Consortium (PneumoCarr) proposing nasopharyngeal (NP) colonization as a supplementary or alternative endpoint in vaccine licensure. PneumoCarr members provided information to vaccine manufacturers, regulators and the WHO on the evidence for NP carriage as a precursor to pneumococcal disease, standardization of laboratory methods for the detection of multiple serotype carriage, definition and estimation of pneumococcal vaccine efficacy against carriage (VE-col), and the direct and indirect impact of vaccination on carriage. Manufacturers and regulators had the opportunity to respond to the information compiled by PneumoCarr and share their perspectives. VE-col as a licensure endpoint may be more useful for the next generation pneumococcal vaccine products, particularly those for which the immunological correlate of protection is not established, whereas it may be less needed for pneumococcal conjugate vaccines which have an established licensure pathway. The consultation supported the importance of NP carriage data as a critical element linking vaccine impact on the individual direct risk of disease to the population-level impact: indirect effects such as herd protection and serotype replacement. The indirect effects of vaccination, however, are not currently established as part of the licensure process and to include them would be a paradigm shift for regulatory agencies who currently consider this information in the post-licensure setting. More discussion and consensus-building is needed around the rationale and optimal mechanism to include carriage data in the licensure pathway for new pneumococcal vaccines. The WHO and national advisory groups on immunization policy may have an important role in considering the evidence for the indirect benefit of vaccination as informed by its impact on NP carriage.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

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

    PubMed

    Ingels, Helene Andrea Sinclair

    2015-07-01

    Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease.  Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of

  8. 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.

  9. Impact of the pneumococcal 10-valent vaccine on reducing hospitalization for community-acquired pneumonia in children

    PubMed Central

    da Silva, Sandra Rodrigues; de Mello, Luane Marques; da Silva, Anderson Soares; Nunes, Altacílio Aparecido

    2016-01-01

    Abstract Objective: To describe and analyze the occurrence of hospitalizations for community-acquired pneumonia in children before and after the pneumococcal 10-valent conjugate vaccine implementation into the National Immunization Program. Methods: This is an ecological study that includes records of children younger than one year old, vaccinated and not vaccinated with the pneumococcal 10-valent conjugate vaccine in the periods pre- and post-inclusion of the vaccine in the National Immunization Program in the area covered by the Regional Health Superintendence of Alfenas, state of Minas Gerais, Brazil. Vaccination was considered as the exposure factor and hospitalization for community-acquired pneumonia as the endpoint, using secondary annual data by municipality. The prevalence ratio and its 95% confidence interval (95%CI) were used to verify the association between variables. The Z test was used to calculate the difference between proportions. Results: Considering the 26 municipalities of the Regional Health Superintendence of Alfenas, there was a significant reduction in hospitalizations for community-acquired pneumonia in children younger than one year of age, with prevalence ratio (PR)=0.81 (95%CI: 0.74-0.89; p<0.05), indicating a 19% lower prevalence of hospitalization for community-acquired pneumonia in the post-vaccination period. Conclusions: The results suggest the effectiveness of the pneumococcal 10-valent conjugate vaccine in preventing severe cases of community-acquired pneumonia in children younger than one year of age. PMID:27108092

  10. 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.

  11. 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

  12. Automated capillary Western dot blot method for the identity of a 15-valent pneumococcal conjugate vaccine.

    PubMed

    Hamm, Melissa; Ha, Sha; Rustandi, Richard R

    2015-06-01

    Simple Western is a new technology that allows for the separation, blotting, and detection of proteins similar to a traditional Western except in a capillary format. Traditionally, identity assays for biological products are performed using either an enzyme-linked immunosorbent assay (ELISA) or a manual dot blot Western. Both techniques are usually very tedious, labor-intensive, and complicated for multivalent vaccines, and they can be difficult to transfer to other laboratories. An advantage this capillary Western technique has over the traditional manual dot blot Western method is the speed and the automation of electrophoresis separation, blotting, and detection steps performed in 96 capillaries. This article describes details of the development of an automated identity assay for a 15-valent pneumococcal conjugate vaccine, PCV15-CRM197, using capillary Western technology.

  13. Prevalence of influenza vaccination and pneumococcal vaccination in elderly and high-risk patients seen in a university general medicine clinic.

    PubMed

    Lai, Hoang; Aronow, Wilbert S; Gutwein, Andrew H

    2008-01-01

    Charts of 240 unselected patients (149 women and 91 men), mean age 74 +/- 7 years (range, 64-95 years), seen in a university general medicine clinic at Westchester Medical Center/New York Medical College between April 2004 and April 2007 were reviewed for the use of influenza vaccination and pneumococcal vaccination. Of the 240 patients, 108 (45%) had cardiovascular disease, 183 (76%) had hypertension, 70 (29%) had diabetes mellitus, 32 (13%) had chronic pulmonary disease, 30 (13%) had cancer, 26 (11%) had chronic renal disease, and 19 (8%) had no chronic illness. Of the 240 patients, 24 (10%) refused influenza vaccination and two (1%) had a hypersensitivity to eggs. Of 240 patients, 18 (8%) refused pneumococcal vaccination. Of 94 patients who did not refuse influenza vaccination or were allergic to eggs during the winter season of October 2004 through January 2005, 58 (62%) had influenza vaccination. Ninety-two of 172 patients (54%) had influenza vaccination during October 2005 through January 2006. Ninety-seven of 136 patients (71%) had influenza vaccination during October 2006 through January 2007. Of 222 patients, 111 (50%) had pneumococcal vaccination during 2004 through 2007.

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

    PubMed Central

    Sehatzadeh, S

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  15. [Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update].

    PubMed

    González-Romo, F; Picazo, J J; García Rojas, A; Labrador Horrillo, M; Barrios, V; Magro, M C; Gil Gregorio, P; de la Cámara, R; Rodríguez, A; Barberán, J; Botía Martínez, F; Linares Rufo, M; Jimeno Sanz, I; Portolés, J M; Sanz Herrero, F; Espinosa Arranz, J; García-Sánchez, V; Galindo Izquierdo, M; Mascarós, E

    2017-04-01

    Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved.

  16. 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.

  17. Cost-effectiveness analysis of infant universal routine pneumococcal vaccination in Malaysia and Hong Kong.

    PubMed

    Wu, David Bin-Chia; Roberts, Craig; Lee, Vivian Wing Yan; Hong, Li-Wen; Tan, Kah Kee; Mak, Vivienne; Lee, Kenneth Kwing Chin

    2016-01-01

    Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.

  18. 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.

  19. 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

  20. 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.

  1. [Advice of the French Superior Council on Public Health (section on transmissible diseases) relative to vaccination by heptavalent pneumococcal conjugate vaccine (Prevanar). Meeting of March 8, 2002].

    PubMed

    2002-08-01

    This article is the full-length text (including arguments and recommendations) written by the Conseil Supérieur d'Hygiène Publique de France, in its session of march 8th 2002, expressing its opinion on the immunization policy with the heptavalent pneumococcal conjugate vaccine (Prevenar).

  2. Serotypes not Included in 13-Valent Pneumococcal Vaccine as Causes of Acute Otitis Media with Spontaneous Tympanic Membrane Perforation in a Geographic Area with High Vaccination Coverage.

    PubMed

    Marchisio, Paola; Esposito, Susanna; Picca, Marina; Baggi, Elena; Terranova, Leonardo; Orenti, Annalisa; Biganzoli, Elia; Principi, Nicola

    2016-12-15

    In 177 children living in an area with high 13-valent pneumococcal conjugate vaccine (PCV13) coverage who had acute otitis media (AOM) complicated with spontaneous tympanic membrane perforation (STMP), Streptococcus pneumoniae was identified in the middle ear fluid of 48 (27.1%) subjects, with 37 (77.1%) cases caused by non-PCV13 serotypes.

  3. 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

  4. [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.

  5. Prospective safety monitoring of Haemophilus influenzae type b and heptavalent pneumococcal conjugate vaccines in Kagoshima, Japan.

    PubMed

    Nishi, Junichiro; Tokuda, Koichi; Imuta, Naoko; Minami, Taketsugu; Kawano, Yoshifumi

    2013-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine (PRP-T) and heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in December 2008 and February 2010, respectively. The concurrent administration of these vaccines is routinely performed worldwide. However, the safety of the simultaneous administration of these vaccines has not been fully evaluated in Japan, because it has rarely been performed thus far. We conducted a 2-year prospective, observational, multicenter study on PRP-T and PCV7 safety from February 2009 through January 2011 in 29 facilities located in Kagoshima Prefecture, Japan. Objective severe adverse events included anaphylactoid reaction, encephalitis/encephalopathy, neurological events, severe focal reactions, systemic eruption/urticaria, fever above 39℃ within 2 days after inoculation, and other complications requiring hospitalization. The incidences of these events for PRP-T and PCV7 administration were 0.68% (76/11,197) and 0.92% (28/3,049), respectively. No deaths or subsequent complications were reported during the course of the study. There was no significant difference in the incidence of severe adverse events between the single and co-administration groups for both vaccines: PRP-T, 0.55% (31/5,662) versus 0.81% (45/5,535; P = 0.11); PCV7, 0.88% (11/1,247) versus 0.94% (17/1,802; P = 0.86). These results suggest that the simultaneous administration of vaccines including PRP-T and/or PCV7 does not increase the incidence of severe adverse events in Japanese children.

  6. 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 ...

  7. 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 platelet transfusion from a blood group O donor, immunized 1 month before with Pneumovax, caused a hemolytic reaction in a blood group A recipient. Forty-five of 59 group O donors (76%) and all of nine group B donors immunized with Pneumovax had a fourfold or higher anti-A response. Half of the anti-A antibody in high titered donors was in the IgG fraction. Pneumovax contained approximately 30 micrograms of an A-like substance per dose; polyvalent pneumococcal vaccines prepared by two other manufactures contained very low and probably subimmunogenic concentrations. Several culture media prepared from animal tissues contained as antigen of similar physical, immunologic, and chemical properties, and were the most likely source of the contaminant. Manufacturing procedures have since been revised to eliminate A-like substances.

  8. 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

  9. 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.

  10. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    PubMed

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices.

  11. 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

  12. The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi

    PubMed Central

    Kidane, Teklay; Chirwa, Geoffrey; Tesfaye, Neghist; Prescott, Marta R; Scotney, Soleine T; Valle, Moussa; Abebe, Sintayehu; Tambuli, Adija; Malewezi, Bridget; Mohammed, Tahir; Kobayashi, Emily; Wootton, Emily; Wong, Renee; Dosani, Rahima; Subramaniam, Hamsa; Joseph, Jessica; Yavuz, Elif; Apple, Aliza; Le Tallec, Yann; Kang’ethe, Alice

    2016-01-01

    Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the ‘backlog cohort’, comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries’ plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. PMID:26856361

  13. 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

  14. 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.

  15. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

    PubMed Central

    Dowling, David J.; van Haren, Simon D.; Scheid, Annette; Bergelson, Ilana; Kim, Dhohyung; Mancuso, Christy J.; Foppen, Willemina; Fresh, Lynn; Theriot, Terese B.; Lackner, Andrew A.; Fichorova, Raina N.; Smirnov, Dmitri; Vasilakos, John P.; Beaurline, Joe M.; Tomai, Mark A.; Midkiff, Cecily C.; Alvarez, Xavier; Blanchard, James L.; Gilbert, Margaret H.; Aye, Pyone Pyone

    2017-01-01

    Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197–specific neonatal CD4+ cells, activation of newborn and infant Streptococcus pneumoniae polysaccharide–specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10–100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development. PMID:28352660

  16. 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

  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. 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

  19. The potential impact of pneumococcal conjugate vaccine in Africa: Considerations and early lessons learned from the South African experience.

    PubMed

    Madhi, Shabir A; Nunes, Marta C

    2016-01-01

    The introduction of pneumococcal conjugate vaccine (PCV) into the South African public immunization program since 2009 adopted a novel vaccination schedule of 3 doses at 6, 14 and 40 weeks of age. Over the past 5 y it has been shown that infant PCV immunization in South Africa is effective in reducing the burden of invasive pneumococcal disease (IPD) among HIV-infected and HIV-uninfected children. Furthermore, indirect protection of unvaccinated age-groups (including high risk groups such as HIV-infected adults) against IPD was demonstrated despite the absence of any substantial catch-up campaign of older children. This indirect effect against IPD is corroborated by the temporal reduction in vaccine-serotype colonization among age-groups targeted for PCV immunization as well as unvaccinated HIV-infected and HIV-uninfected adults, which was evident within 2 y of PCV introduction into the immunization program. Vaccine effectiveness has also been demonstrated in children against presumed bacterial pneumonia. The evaluation of the impact of PCV in South Africa, however, remains incomplete. The knowledge gaps remaining include the evaluation of PCV on the incidence of all-cause pneumonia hospitalization among vaccinated and unvaccinated age-groups. Furthermore, ongoing surveillance is required to determine whether there is ongoing replacement disease by non-vaccine serotypes, which could offset the early gains associated with the immunization program in the country.

  20. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

    PubMed

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.

  1. Vaccines (immunizations) - overview

    MedlinePlus

    ... diphtheria, mumps, measles, pertussis (whooping cough), meningitis, and polio. Many of these infections can cause serious or ... MMR - vaccine Pneumococcal conjugate vaccine Pneumococcal polysaccharide ... (vaccine) Rotavirus vaccine Tdap vaccine Tetanus - vaccine

  2. Cost-utility analysis of 10- and 13-valent pneumococcal conjugate vaccines: Protection at what price in the Thai context?

    PubMed Central

    Kulpeng, Wantanee; Leelahavarong, Pattara; Rattanavipapong, Waranya; Sornsrivichai, Vorasith; Baggett, Henry C.; Meeyai, Aronrag; Punpanich, Warunee; Teerawattananon, Yot

    2015-01-01

    Objective This study aims to evaluate the costs and outcomes of offering the 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) in Thailand compared to the current situation of no PCV vaccination. Methods Two vaccination schedules were considered: two-dose primary series plus a booster dose (2 + 1) and three-dose primary series plus a booster dose (3 + 1). A cost-utility analysis was conducted using a societal perspective. A Markov simulation model was used to estimate the relevant costs and health outcomes for a lifetime horizon. Costs were collected and values were calculated for the year 2010. The results were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality adjusted life year (QALY) gained, with future costs and outcomes being discounted at 3% per annum. One-way sensitivity analysis and probabilistic sensitivity analysis using a Monte Carlo simulation were performed to assess parameter uncertainty. Results Under the base case-scenario of 2 + 1 dose schedule and a five-year protection, without indirect vaccine effects, the ICER for PCV10 and PCV13 were THB 1,368,072 and THB 1,490,305 per QALY gained, respectively. With indirect vaccine effects, the ICER of PCV10 was THB 519,399, and for PCV13 was THB 527,378. The model was sensitive to discount rate, the change in duration of vaccine protection and the incidence of pneumonia for all age groups. Conclusions At current prices, PCV10 and PCV13 are not cost-effective in Thailand. Inclusion of indirect vaccine effects substantially reduced the ICERs for both vaccines, but did not result in cost effectiveness. PMID:23588084

  3. Empyema due to Streptococcus Pneumoniae Serotype 9V in a Child Immunized with 13-Valent Conjugated Pneumococcal Vaccine

    PubMed Central

    Sütçü, Murat; Aktürk, Hacer; Karagözlü, Fatih; Somer, Ayper; Gürler, Nezahat; Salman, Nuran

    2017-01-01

    Background: Clinical vaccine failure is the occurence of the specific vaccine-preventable disease in an appropriately and fully vaccinated person after enough time has elapsed for protection against the antigens of the vaccine to develop. Fully immunized cases with pneumoccal vaccine may sometimes develop a complicated pneumonia with empyema caused by a vaccine serotype. Case Report: A 2 year-old male patient was admitted with the complaints of fever. On the basis of findings and laboratory results, the patient was diagnosed as having empyema. He was successfully treated with parenteral antibiotics and chest tube drainage. The pleural fluid culture and hemoculture of the patient yielded penicillin-susceptible pneumococci and the isolate was identified as serotype 9V. The patient had been vaccinated with a 13-valent pneumococcal conjugate vaccine according to the Turkish national immunization schedule at 2, 4, 6 and 12 months of age. His medical history and basic immunological profile were inconsistent with a primary immunodeficiency. Conclusion: The failure of the PCV13 vaccine may results in a complicated pneumonia with empyema. It is important to investigate serotypes of pneumococci in these cases to determine other possible vaccine failures due to PCV13 and to study the underlying mechanisms. PMID:28251028

  4. Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects.

    PubMed

    Lloyd, Adam; Patel, Nishma; Scott, David A; Runge, Claus; Claes, Christa; Rose, Markus

    2008-02-01

    In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

  5. Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany.

    PubMed

    Imöhl, Matthias; Reinert, Ralf René; van der Linden, Mark

    2015-10-01

    Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany. Most of the isolates originated from adults ≥16 years (82.5%), while 17.5% were obtained from children <16 years. Penicillin resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0

  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. 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 ...

  8. A 4-month-old baby presenting with dermal necrotizing granulomatous giant cell reaction at the injection site of 13-valent pneumococcal conjugate vaccine: a case report

    PubMed Central

    2014-01-01

    Introduction Adjuvants (for example, aluminum salts) are frequently incorporated in licensed vaccines to enhance the host immune response. Such vaccines include the pneumococcal conjugate, combinations of diphtheria–tetanus/acellular pertussis, tetanus– diphtheria/acellular pertussis, hepatitis B, some Haemophilus influenzae type b, hepatitis A, and human papillomavirus. These preparations have been associated with complicated local adverse events, especially if administered subcutaneously or intradermally in comparison to deep intramuscular injection. We describe a severe inflammatory reaction at the site of an injection of 13-valent pneumococcal conjugate vaccine. Case presentation A 4-month-old Arab baby boy developed dermal necrotizing granulomatous giant cell reaction at the injection site (right anterior thigh) of the second dose of 13-valent pneumococcal conjugate vaccine. Ziehl–Neelsen and periodic-acid Schiff were negative. This reaction probably resulted from improper intramuscular administration because the first (at 2 months of age) and third (at 10 months of age) doses were uneventful. Conclusions Dermal necrotizing granulomatous reactions are a serious complication of the 13-valent pneumococcal conjugate vaccine. Health care providers need to administer this preparation deeply into a muscle mass. Completing the vaccine series is an acceptable option. Physicians are encouraged to report their experience with completing vaccine series following adverse events. PMID:25152179

  9. DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein.

    PubMed

    Ferreira, Daniela M; Miyaji, Eliane N; Oliveira, Maria Leonor S; Darrieux, Michelle; Arêas, Ana Paula M; Ho, Paulo L; Leite, Luciana C C

    2006-04-01

    Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

  10. Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines

    PubMed Central

    Hadjipanayis, Adamos; Efstathiou, Elisavet; Alexandrou, Maria; Panayiotou, Loukia; Zachariadou, Chrystalla; Petrou, Panayiotis; Papaevangelou, Vasiliki

    2016-01-01

    The objective of the study was to describe the incidence of pneumococcal nasopharyngeal carriage, serotype distribution and antibiotic resistance profile of pneumococcal nasopharyngeal isolates in healthy children aged 6 to 36 months following the implementation of conjugate vaccines. A nasopharyngeal swab was collected from 1105 healthy children following a stratified random sampling between September 2013 and April 2014. Demographics, vaccination status and data on possible risk factors were recorded. Isolates were serotyped and tested for antibiotic susceptibility. The nasopharyngeal carriage rate was 25.3%. Among 1105 children enrolled, 393 had received PCV13 and 685 PCV10. The prevailing isolated serotypes were: 23A (14.3%), 15A (8.9%), 6C (8.6%), 23B (7.5%), 19A (5.4%) and 15B (5%). The proportion of non-vaccine serotypes, PCV10 serotypes, PCV13 additional serotypes (3, 6A, 19A) was 76.8%, 2.1% and 10.4% respectively. Although children, who were fully or partially vaccinated with PCV13, were 63% less likely to be colonized with additional PCV13 serotypes compared to those vaccinated with PCV10, the difference is not significant (95%Cl = 0.14–1.02, p = 0.053). The highest antibiotic non-susceptible rates were found for erythromycin (28.2%) and penicillin (27.9%). The overall multidrug resistance rate was 13.2%, with serotypes 24F (4/6), 15A (14/25) and 19A (6/15) being the main contributors. Carriage rate was similar between children vaccinated with PCV10 or PCV13. The high incidence of 15A serotype which is also multidrug resistant should be underlined. Ongoing surveillance is needed to monitor the dynamics on nasopharyngeal carriage. PMID:27706247

  11. 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

  12. 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

  13. Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

    PubMed

    Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

    2016-12-01

    In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

  14. A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries

    PubMed Central

    2013-01-01

    Background A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. Methods We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. Results The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. Conclusions The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy

  15. The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review

    PubMed Central

    2013-01-01

    Background Two of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST). Methods We systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (≥2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST. Results We identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects

  16. Health Gains and Financial Protection from Pneumococcal Vaccination and Pneumonia Treatment in Ethiopia: Results from an Extended Cost-Effectiveness Analysis

    PubMed Central

    Johansson, Kjell Arne; Memirie, Solomon Tessema; Pecenka, Clint; Jamison, Dean T.; Verguet, Stéphane

    2015-01-01

    Background Pneumonia and pneumococcal disease cause a large disease burden in resource-constrained settings. We pursue an extended cost-effectiveness analysis (ECEA) of two fully publicly financed interventions in Ethiopia: pneumococcal vaccination for newborns and pneumonia treatment for under-five children in Ethiopia. Methods We apply ECEA methods and estimate the program impact on: (1) government program costs; (2) pneumonia and pneumococcal deaths averted; (3) household expenses related to pneumonia/pneumococcal disease treatment averted; (4) prevention of household medical impoverishment measured by an imputed money-metric value of financial risk protection; and (5) distributional consequences across the wealth strata of the country population. Available epidemiological and cost data from Ethiopia are applied and the two interventions are assessed separately at various incremental coverage levels. Results Scaling-up pneumococcal vaccines at around 40% coverage would cost about $11.5 million and avert about 2090 child deaths annually, while a 10% increase of pneumonia treatment to all children under 5 years of age would cost about $13.9 million and avert 2610 deaths annually. Health benefits of the two interventions publicly financed would be concentrated among the bottom income quintile, where 30–40% of all deaths averted would be expected to occur in the poorest quintile. In sum, the two interventions would eliminate a total of $2.4 million of private household expenditures annually, where the richest quintile benefits from around 30% of the total private expenditures averted. The financial risk protection benefits would be largely concentrated among the bottom income quintile. The results are most sensitive to variations in vaccine price, population size, number of deaths due to pneumonia, efficacy of interventions and out-of-pocket copayment share. Conclusions Vaccine and treatment interventions for children, as shown with the illustrative examples of

  17. 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

  18. Effect of Serotype on Focus and Mortality of Invasive Pneumococcal Disease: Coverage of Different Vaccines and Insight into Non-Vaccine Serotypes

    PubMed Central

    van Hoek, Albert Jan; Andrews, Nick; Waight, Pauline A.; George, Robert; Miller, Elizabeth

    2012-01-01

    Background Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13). Method Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients’ diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5–64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines. Results The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines’ coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals. Conclusion Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss. PMID:22815698

  19. Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: the Australian experience.

    PubMed

    Hull, Brynley P; Menzies, Robert; Macartney, Kristine; McIntyre, Peter B

    2013-04-08

    Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix(®)) and three (RotaTeq(®)) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11-17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced.

  20. Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case-control study.

    PubMed

    Guevara, Marcela; Barricarte, Aurelio; Torroba, Luis; Herranz, Mercedes; Gil-Setas, Alberto; Gil, Francisco; Bernaola, Enrique; Ezpeleta, Carmen; Castilla, Jesús

    2016-01-01

    We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001-2004), overall IPD incidence in 2011-2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14-0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09-0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02-7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01-0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.

  1. A review of economic evaluations of 13-valent pneumococcal conjugate vaccine (PCV13) in adults and the elderly

    PubMed Central

    Dirmesropian, S; Wood, JG; MacIntyre, CR; Newall, AT

    2015-01-01

    The 13-valent pneumococcal conjugated vaccine (PCV13) is already recommended for some adult groups and is being considered for wider use in many countries. In order to identify the strengths and limitations of the existing economic evaluation studies of PCV13 in adults and the elderly a literature review was conducted. The majority of the studies identified (9 out of 10) found that PCV13 was cost-effective in adults and/or the elderly. However, these results were based on assumptions that could not always be informed by robust evidence. Key uncertainties included the efficacy of PCV13 against non-invasive pneumonia and the herd immunity effect of childhood vaccination programs. Emerging trial evidence on PCV13 in adults from the Netherlands offers the ability to parameterize future economic evaluations with empirical efficacy data. However, it is important that these estimates are used thoughtfully when they are transferred to other settings. PMID:25933180

  2. The Impact of Order Set Use on Pneumococcal Vaccination at the Time of Admission and at the Time of Discharge for Adult Patients in an Acute Inpatient Setting

    ERIC Educational Resources Information Center

    Mathew, Rekha

    2012-01-01

    Background: Pneumococcal vaccination (PV) is important as Streptococcus pneumoniae accounts for one third of all hospitalizations for community-acquired pneumonia. In 2009, 1.1 million people in the U.S. were hospitalized with pneumonia and more than 50,000 people died from the disease. The Centers for Disease Control and Prevention recommend that…

  3. 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.

  4. 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

  5. Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

    PubMed

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

    2015-01-01

    This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

  6. Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China

    PubMed Central

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

    2015-01-01

    This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670

  7. 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

  8. 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.

  9. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    PubMed

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  10. Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

    PubMed

    Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús

    2014-05-07

    Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ≥ 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13.

  11. Response to Wu et al. — Cost-effectiveness analysis of infant pneumococcal vaccination in Malaysia and Hong Kong

    PubMed Central

    Varghese, Lijoy; Mungall, Bruce; Zhang, Xu-Hao; Hoet, Bernard

    2016-01-01

    ABSTRACT A recently published paper that assessed the comparative cost-effectiveness of the 2 pneumococcal conjugate vaccines (PCVs) in Malaysia and Hong Kong reported that the 13-valent PCV vaccine (PCV13) is a better choice compared to the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV or PCV10) from both a payer and societal perspective as well as under various scenarios. However, the analysis relied on a large number of assumptions that were either erroneous or did not take into account the most recent body of evidence available. A rigorous evaluation of the underlying assumptions is necessary to present a fair and balanced analysis for decision-making. PMID:27459265

  12. 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.

  13. Bacterial Meningitis in Brazil: Baseline Epidemiologic Assessment of the Decade Prior to the Introduction of Pneumococcal and Meningococcal Vaccines

    PubMed Central

    Azevedo, Luciano Cesar Pontes; Toscano, Cristiana M.; Bierrenbach, Ana Luiza

    2013-01-01

    Background Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010. Methods and Findings All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8%) were due to bacterial meningitis (excluding tuberculosis). Of these, 34,997 (31.7%) were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000–2002 to 2.14/100,000 in 2009–2010 (p<0.01). Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter. Conclusions Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil

  14. 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

  15. 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.

  16. Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese infants: a randomised, controlled trial

    PubMed Central

    2013-01-01

    Background Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants. Methods This phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age. Results Within 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or

  17. Hidden Efficiencies: Making Completion of the Pediatric Vaccine Schedule More Efficient for Physicians

    PubMed Central

    Ciarametaro, Mike; Bradshaw, Steven E.; Guiglotto, Jillian; Hahn, Beth; Meier, Genevieve

    2015-01-01

    Abstract The objective of this work is to demonstrate the potential time and labor savings that may result from increased use of combination vaccinations. The study (GSK study identifier: HO-12-4735) was a model developed to evaluate the efficiency of the pediatric vaccine schedule, using time and motion studies. The model considered vaccination time and the associated labor costs, but vaccination acquisition costs were not considered. We also did not consider any efficacy or safety differences between formulations. The model inputs were supported by a targeted literature review. The reference year for the model was 2012. The most efficient vaccination program using currently available vaccines was predicted to reduce costs through a combination of fewer injections (62%) and less time per vaccination (38%). The most versus the least efficient vaccine program was predicted to result in a 47% reduction in vaccination time and a 42% reduction in labor and supply costs. The estimated administration cost saving with the most versus the least efficient program was estimated to be nearly US $45 million. If hypothetical 6- or 7-valent vaccines are developed using the already most efficient schedule by adding additional antigens (pneumococcal conjugate vaccine and Haemophilus influenzae type b) to the most efficient 5-valent vaccine, the savings are predicted to be even greater. Combination vaccinations reduce the time burden of the childhood immunization schedule and could create the potential to improve vaccination uptake and compliance as a result of fewer required injections. PMID:25634165

  18. Streptococcus pneumoniae carriage among healthy and sick pediatric patients before the generalized implementation of the 13-valent pneumococcal vaccine in Morocco from 2010 to 2011.

    PubMed

    Jroundi, Imane; Mahraoui, Chafik; Benmessaoud, Rachid; Moraleda, Cinta; Munoz Almagro, Carmen; Seffar, Meryem; Tligui, Houssain; Kettani, Selma C; Benjelloun, Badr S; Alonso, Pedro L; Bassat, Quique

    Nasopharyngeal carriage studies provide insights into the local prevalence of circulating pneumococcal serotypes. These data are critical to vaccination monitoring, as they allow for the prediction and assessment of impact. Very little data are available on the carriage of pneumococcal serotypes in Morocco. Here, we describe the prevalence of Streptococcus pneumoniae carriage and serotype distribution among 697 pediatric patients with ages ranging from 2 to 59 months who were admitted to a Moroccan hospital with severe pneumonia, as well as 195 healthy infants and young children who were recruited at a vaccination clinic. Carriage rates were 40.5% (79/195) for healthy children and 22.8% (159/697) for sick children. The most commonly observed circulating serotypes included 6A, 6B and 19F, all of which are included in the current 13-valent anti-pneumococcal conjugate vaccine that was recently introduced in Morocco. Monitoring of circulating serotypes remains necessary after vaccine introduction to assess whether serotype replacement is occurring.

  19. 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.

  20. 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.

  1. Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.

    PubMed

    Prymula, Roman; Chlibek, Roman; Splino, Miroslav; Kaliskova, Eva; Kohl, Igor; Lommel, Patricia; Schuerman, Lode

    2008-08-18

    This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.

  2. Differential B-Cell Memory Around the 11-Month Booster in Children Vaccinated With a 10- or 13-Valent Pneumococcal Conjugate Vaccine

    PubMed Central

    van Westen, Els; Wijmenga-Monsuur, Alienke J.; van Dijken, Harry H.; van Gaans-van den Brink, Jacqueline A. M.; Kuipers, Betsy; Knol, Mirjam J.; Berbers, Guy A. M.; Sanders, Elisabeth A. M.; Rots, Nynke Y.; van Els, Cécile A. C. M.

    2015-01-01

    Background. Both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) induce immunological memory against Streptococcus pneumoniae infections caused by vaccine serotypes. In addition to comparing serum antibody levels, we investigated frequencies of serotype-specific plasma cells (PCs) and memory B-cells (Bmems) as potential predictors of long-term immunity around the booster vaccination at 11 months of age. Methods. Infants were immunized with PCV10 or PCV13 at 2, 3, 4, and 11 months of age. Blood was collected before the 11-month booster or 7–9 days afterward. Serotype-specific immunoglobulin G (IgG) levels were determined in serum samples by multiplex immunoassay. Circulating specific PCs and Bmems against shared serotypes 1, 6B, 7F, and 19F and against PCV13 serotypes 6A and 19A were measured in peripheral blood mononuclear cells by enzyme-linked immunospot assay. Results. No major differences in IgG levels and PC frequencies between groups were found for the 4 shared serotypes. Notably, PCV13 vaccination resulted in higher frequencies of Bmems than PCV10 vaccination, both before and after the booster dose, for all 4 shared serotypes except for serotype 1 postbooster. For PCV13-specific serotypes 6A and 19A, the IgG levels and frequencies of PCs and Bmems were higher in the PCV13 group, pre- and postbooster, except for PC frequencies prebooster. Conclusions. Both PCVs are immunogenic and induce measurable IgG, PC, and Bmem booster responses at 11 months. Compared to PCV10, vaccination with PCV13 was associated with overall similar IgG levels and PC frequencies but with higher Bmem frequencies before and after the 11-month booster. The clinical implications of these results need further follow-up. Clinical Trials Registration. NTR3069. PMID:25838290

  3. Levels and functionality of antibodies after pneumococcal conjugate vaccine in schedules with different timing of the booster dose.

    PubMed

    van Westen, Els; Rodenburg, Gerwin D; van Gils, Elske J M; Tcherniaeva, Irina; Berbers, Guy A M; Cowell, Lucy; Goldblatt, David; Rots, Nynke Y; van den Dobbelsteen, Germie P J M; Sanders, Elisabeth A M

    2013-12-02

    The seven-valent pneumococcal conjugate vaccine (PCV7) has been introduced in most high-income countries, although with differences in age, timing and number of primary doses before 6 months of age and presence and timing of a booster vaccination. The objective was to determine and compare the IgG antibody levels and functionality of IgG responses (avidity and opsonophagocytoses) at 1 and 2 years of age following 2 primary doses with a booster at 11 or 24 months of age. Children received PCV7 at 2 and 4 months (2-dose group), or at 2, 4 and 11 months (2+1-dose group), or no PCV7 (controls) before 1 year of age. All children received a PCV7 dose at 24 months of age. At the age of 12 months, the 2+1-dose group had higher IgG levels and functional antibody levels, compared to the 2-dose group for all serotypes, but at 25 months the difference between the 2-dose and 2+1-dose groups had disappeared for most serotypes. The kinetics of opsonophagocytic antibodies were in line with the specific IgG antibody levels for most serotypes, although differences between the 2-dose and the 2+1-dose group were more pronounced in OPA activity as compared to the IgG levels especially at the age of 24 months. Delaying the booster dose from 11 months to 24 months after 2 primary doses resulted in significantly higher OPA GMTs one month after the booster dose. This must, however, be balanced against the risk of leaving children unboosted between the age of 11 and 24 months at a time when disease risk is still high. Local decisions about the timing of a booster dose should also take into account vaccine coverage and the indirect herd effect in a well vaccinated population. Trial registration clinicaltrials.gov Identifier: NCT00189020.

  4. 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.

  5. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques

    PubMed Central

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-01-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [18F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [18F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  6. 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

  7. 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.

  8. Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine.

    PubMed

    Principi, Nicola; Iughetti, Lorenzo; Cappa, Marco; Maffeis, Claudio; Chiarelli, Franco; Bona, Gianni; Gambino, Monia; Ruggiero, Luca; Patianna, Viviana; Matteoli, Maria Cristina; Marigliano, Marco; Cipriano, Paola; Parlamento, Silvia; Esposito, Susanna

    2016-01-01

    This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6-17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14-0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35-0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13-0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90-2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07-0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

  9. Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine

    PubMed Central

    Principi, Nicola; Iughetti, Lorenzo; Cappa, Marco; Maffeis, Claudio; Chiarelli, Franco; Bona, Gianni; Gambino, Monia; Ruggiero, Luca; Patianna, Viviana; Matteoli, Maria Cristina; Marigliano, Marco; Cipriano, Paola; Parlamento, Silvia; Esposito, Susanna

    2016-01-01

    This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6–17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14–0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35–0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13–0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90–2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07–0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations. PMID:26575615

  10. Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986–2009☆

    PubMed Central

    Rudolph, Karen; Bruce, Michael; Bruden, Dana; Zulz, Tammy; Wenger, Jay; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2015-01-01

    We investigated serotype 6A/6C invasive pneumococcal disease (IPD) incidence, genetic diversity, and carriage before and after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Alaska. IPD cases (1986–2009) were identified through population-based laboratory surveillance. Isolates were initially serotyped by conventional methods, and 6C isolates were differentiated from 6A by polymerase chain reaction. Among invasive and carriage isolates initially typed as 6A, 35% and 50% were identified as 6C, respectively. IPD rates caused by serotype 6A or 6C among children <5 years did not change from the pre- to post-PCV7 period (P = 0.71 and P = 0.09, respectively). Multilocus sequence typing of IPD isolates revealed 28 sequence types. The proportion of serotype 6A carriage isolates decreased from 7.4% pre-PCV7 to 1.8% (P < 0.001) during 2008–2009; the proportion of serotype 6C carriage isolates increased from 3.0% to 8.4% (P = 0.004) among children <5 years. Continued surveillance is warranted to monitor changes in serotype distribution and prevalence. PMID:23276772

  11. Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines.

    PubMed

    Reijtman, Vanesa; Fossati, Sofía; Hernández, Claudia; Sommerfleck, Patricia; Bernáldez, Patricia; Litterio, Mirta; Berberian, Griselda; Regueira, Mabel; Lopardo, Horacio

    2013-01-01

    A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

  12. Meeting the need for advocacy, social mobilisation and communication in the introduction of three new vaccines in South Africa - successes and challenges.

    PubMed

    Baleta, Adele F; van den Heever, Johann; Burnett, Rosemary J

    2012-09-07

    Advocacy, social mobilisation and communication are key components of the successful introduction of new vaccines into childhood immunisation schedules. The development of many new vaccines and the innovation of finance mechanisms, means more efficacious vaccines are becoming available to children in developing countries. At the same time, communication technology is developing at a rapid rate, and with the dramatic decrease in vaccine-preventable diseases over the past few decades, the public have become increasingly exposed to confusing and conflicting information about the need for vaccination. The science of vaccines has become more complex, making effective, clear and consistent communication for healthcare workers and caregivers critical to the uptake of and adherence to life-saving vaccination. The introduction of two new vaccines, the 7-valent pneumococcal conjugate vaccine and the rotavirus vaccine together with the new pentavalent vaccine, which includes inactivated polio vaccine and replaced the former combination vaccine with four antigens, into the South African Expanded Programme on Immunisation over a short period of time, has been met with a number of challenges, some of which led to a lowering of confidence in the Department of Health to deliver on its promises. Had consistent advocacy, social mobilisation and communication efforts not been in place, efforts to make an impact on the burden of disease may not have been as successful. This paper focuses on the lessons learned about effective advocacy with decision makers, social mobilisation, communication with parents and caregivers, and training healthcare workers regarding the introduction of the new vaccines.

  13. 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

  14. Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

    PubMed

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003) to the PCV13 era (2010-2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

  15. Clonal Expansion of the Macrolide Resistant ST386 within Pneumococcal Serotype 6C in France

    PubMed Central

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002–2003) to the PCV13 era (2010–2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter. PMID:24603763

  16. Invasive pneumococcal diseases in children in Hokkaido, Japan from April 2000, to March 2015.

    PubMed

    Sakata, Hiroshi

    2016-01-01

    In Japan, the 7-valent pneumococcal conjugate vaccine (PCV-7) became commercially available as a voluntary vaccine in March 2010. It was included in the routine immunization schedule in April 2013 and was replaced by PCV-13 in November 2013. We evaluated 146 cases of invasive pneumococcal disease (IPD) in 142 children (2 developed the disease twice, and 1 developed it three times) treated in the northern district of Hokkaido, Japan from April 2000 to March 2015, before and after the introduction of PCV-7. The incidence rate per 100,000 people aged <5 years showed an increasing trend between April 2000 and March 2010, and reached 87.5 per 100,000 people per year between April 2009 and March 2010, which was immediately before the introduction of PCV-7. Subsequently, the incidence rate started to show a decreasing trend and reached as low as 9.5 per 100,000 people per year between April 2013 and March 2014. However, the incidence rate showed an increasing trend again between April 2014 and March 2015, reaching 33.4 per 100,000 people per year. Serotyping was performed for the 77 strains collected between April 2000 and March 2010. The most frequently isolated serotype was 6B (31.2%), followed by 23F (14.3%) and 19F (13.0%). Among them, 55 strains were covered by PCV-7 (71.4%), and 64 strains were covered by PCV-13 (83.1%). Of the 33 strains collected between April 2010 and March 2015, 14 were covered by PCV-7 (42.4%) and 16 were covered by PCV-13 (48.4%), showing a significant decrease (p < 0.01).

  17. Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children.

    PubMed

    Lagos, Rosanna E; Muñoz, Alma E; Levine, Myron M; Lepetic, Alejandro; François, Nancy; Yarzabal, Juan Pablo; Schuerman, Lode

    2011-05-01

    The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ≥0.2 µg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ≥8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ≥8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D.

  18. The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies

    PubMed Central

    Satzke, Catherine; Dunne, Eileen M.; Porter, Barbara D.; Klugman, Keith P.; Mulholland, E. Kim

    2015-01-01

    Background The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Methods and Findings Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Conclusions Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor

  19. [Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2006].

    PubMed

    2006-01-01

    Based on the evidence available, the Vaccines Advisory Committee (VAC) of the Spanish Association of Pediatrics reports and comments on the new developments in vaccines that have taken place in 2005 and recommends some modifications to the vaccination schedule for 2006. In agreement with changes in the product monographs for the meningococcal C vaccine, the VAC recommends two doses for the three commercially available preparations with a booster dose in the second year of life. The European Medicines Evaluation Agency (EMEA) has temporarily suspended the sale of the Hexavac vaccine due to doubts about its long-term protection against hepatitis B. The VAC continues to support the use of these combined vaccines. Currently only Infranrix Hexa is available in Spain. The recommendation of vaccinating adolescents with a booster dose of pertussis vaccine via the administration of an acellular preparation of low antigenic load together with the adult diphtheria and tetanus vaccine remains valid. Vaccination against chickenpox in susceptible children aged more than 12 months old continues to be recommended. There is wide coverage for the 7-valent pneumococcal conjugate vaccine in many areas of Spain. In view of the studies published, the VAC reiterates the need for universal immunization by introducing this vaccine in the official vaccination schedule. Finally, other vaccines not included in this schedule are discussed, with special mention of the advisability of influenza vaccination in children, according to the recommendations of the VAC available at the beginning of each season on the web site of the Spanish Association of Pediatrics www.aeped.es; www. vacunasaep.org.

  20. 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.

  1. 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

  2. Detection of Streptococcus pneumoniae and identification of pneumococcal serotypes by real-time polymerase chain reaction using blood samples from Italian children ≤ 5 years of age with community-acquired pneumonia.

    PubMed

    Marchese, Anna; Esposito, Susanna; Coppo, Erika; Rossi, Giovanni A; Tozzi, Alberto; Romano, Mariateresa; Da Dalt, Liviana; Schito, Gian Carlo; Principi, Nicola

    2011-09-01

    Streptococcus pneumoniae is a leading cause of severe life-threatening infections. Laboratory identification and serotyping of this pathogens is desirable to monitor vaccine impact and coverage; however, especially in pediatric patients, the yield of traditional microbiological diagnostic procedures can be very low. The aim of this study was to develop real-time polymerase chain reaction (PCR)-based assays to be performed directly on blood samples to identify the most common capsular serotypes causing pneumonia in Italian children (≤ 5 years of ages) after the introduction of the 7-valent conjugate vaccine. Our real-time PCR-based assays showed high sensitivity (at least 35 fg of pneumococcal DNA), and they were validated with 49 well-characterized pneumococcal isolates, 8 nonpneumococcal isolates, 13 simulated blood clinical samples loaded with S. pneumoniae of known serotypes, and 46 blood clinical samples. All the strains tested and the simulated blood clinical samples were correctly typed by the technique. Real-time PCR allowed serotyping in 37/46 children ≤ 5 years of age (80.4%) in whom pneumonia was diagnosed in four Italian hospitals. Non-PCV7 serotypes accounted for at least 47.8% (22/46) of cases, serotype 19A being the most common (34.7%, 16/46). Although, it is not known at present whether the incidence of 19A serotype is attributable to the use of PCV7 only, expanding pneumococcal serotype coverage has clearly the potential to prevent a larger number of pneumonias in Italian children less than ≤ 5 years of age. Molecular methods are of increasing importance in the diagnosis of pneumococcal pneumonia and in monitoring serotype distribution and replacement.

  3. 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

  4. The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines.

    PubMed

    Ishiwada, Naruhiko; Hishiki, Haruka; Nagasawa, Koo; Naito, Sachiko; Sato, Yasunori; Chang, Bin; Sasaki, Yuko; Kimura, Kouji; Ohnishi, Makoto; Shibayama, Keigo

    2014-09-22

    The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.

  5. Staphylococcus aureus and Streptococcus pneumoniae interaction and response to pneumococcal vaccination: Myth or reality?

    PubMed Central

    Reiss-Mandel, Aylana; Regev-Yochay, Gili

    2016-01-01

    S. aureus and S. pneumoniae are both common pathogens that are also carried by a large proportion of healthy individuals in the nasal and nasopharyngeal spaces. A negative association between carriage of S. aureus and S. pneumoniae has been reported in children in various epidemiologic studies from different geographical regions. Most studies found that the negative association between S. pneumoniae and S. aureus was significant only for carriage of vaccine-type S. pneumoniae strains. In this review, we summarize the various suggested mechanisms of this suggested bacterial interference, and the clinical implications reported following PCV introduction to date in various geographical regions. PMID:26905680

  6. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

    PubMed

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

  7. 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.

  8. 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

  9. 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.

  10. Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States.

    PubMed

    Marshall, Gary S; Marchant, Colin D; Blatter, Mark; Friedland, Leonard R; Aris, Emmanuel; Miller, Jacqueline M

    2011-02-01

    An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

  11. 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.

  12. Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants

    PubMed Central

    Wijmenga-Monsuur, Alienke J.; van Westen, Els; Knol, Mirjam J.; Jongerius, Riet M. C.; Zancolli, Marta; Goldblatt, David; van Gageldonk, Pieter G. M.; Tcherniaeva, Irina; Berbers, Guy A. M.; Rots, Nynke Y.

    2015-01-01

    Background & Aims Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV) are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster. Methods Dutch infants (n = 132) were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes. Results One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs) for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group. Conclusion Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA) and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are

  13. Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial

    PubMed Central

    Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guiñazú, Javier Ruiz; Ortega-Barría, Eduardo; Yarzábal, Juan P.; Schuerman, Lode

    2014-01-01

    Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM

  14. 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 ( ...

  15. 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 ...

  16. Impact of Pneumococcal Conjugate Vaccines on the Incidence of Pneumonia in Hospitalized Children after Five Years of Its Introduction in Uruguay

    PubMed Central

    Hortal, María; Estevan, Miguel; Meny, Miguel; Iraola, Inés; Laurani, Hilda

    2014-01-01

    Background Data on the burden of pneumococcal disease and the most frequent serotypes demonstrated that invasive disease and pneumonia were important manifestations affecting children under 5 years of age. Therefore, pneumococcal diseases prevention became a public health priority. Uruguay was the first Latin American country to incorporate PCV7 into its National Immunization Program. The aim of this study is to compare the incidence rates for hospitalized pneumonia in children from the pre PCV introduction period and the following five years of PCVs application in Uruguay. Methods and Findings Population-based surveillance of pneumonia hospitalization rates, in children, less than 14 years of age, had been performed prior pneumococcal vaccination, and continued following PCV7 introduction and PCV13 replacement, using the same methodology. Hospitalized children with pneumonia were enrolled from January 1, 2009 through December 31st, 2012. The study was carried out in an area with a population of 238,002 inhabitants of whom 18, 055 were under five years of age. Patients with acute lower respiratory infections for whom a chest radiograph was performed on admission were eligible. Digitalized radiographs were interpreted by a reference radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267 with consolidated and 1,430 with non consolidated pneumonia of which incidence decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001–2004 and 2009–2012 comparison showed a significant difference of 20.4% for consolidated pneumonia hospitalizations. A significant incidence decline was recorded among children 6 to 35 months of age. Conclusions An overall significant reduction in pneumonia hospitalizations was observed following the introduction of PCV7 and furthermore following the change to PCV13. PMID:24905093

  17. Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

    PubMed Central

    Toscano, Cristiana M.; Alencar, Gizelton P.; Alvarez, Andrés; Valenzuela, Maria T.; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C.; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R.; de Oliveira, Lucia H.

    2016-01-01

    Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. Methods This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. Results There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively. Conclusion PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE. PMID:27058873

  18. [Impact of PCV10 pneumococcal vaccine on mortality from pneumonia in children less than one year of age in Santa Catarina State, Brazil].

    PubMed

    Kupek, Emil; Vieira, Ilse Lisiane Viertel

    2016-03-01

    The aim of this study was to evaluate the impact of PCV10 pneumococcal vaccine on mortality from pneumonia in children less than one year of age in Santa Catarina State, Brazil, comparing the four years prior and the four years subsequent to the vaccine's introduction in 2010. This ecological study used data from the Mortality Information System and vaccination coverage of children less than one year. Data were grouped by municipalities of residence and regions. Average mortality from pneumonia in children under one year decreased from 29.69 to 23.40 per 100,000, comparing 2006-2009 and 2010-2013, or a reduction of 11%. However there were differences between regions with a drop in mortality (Grande Florianópolis, Sul, Planalto Norte, and Nordeste) and others with an increase in the annual rates (Oeste, Itajaí, and Serra). In short, the state as a whole showed 11% reduction in mortality from pneumonia in children less than one year of age, four years after implementing routine PCV10 vaccination in the National Immunization Program, but with heterogeneous effects when comparing regions of the state.

  19. Consensus Recommendation for India and Bangladesh for the Use of Pneumococcal Vaccine in Mass Gatherings with Special Reference to Hajj Pilgrims

    PubMed Central

    Mathai, Dilip; Shamsuzzaman, Abul Khair Mohammad; Feroz, Ahrar Ahmed; Virani, Amin R; Hasan, Ashfaq; Ravi Kumar, KL; Ansari, Khalid; Forhad Hossain, Khandaker ATM; Marda, Mahesh; Wahab Zubair, MA; Ali, Mohammed Mukarram; Ashraf, N; Basha, Riyaz; Mirza, Shaeq; Ahmed, Shafeeq; Akhtar, Shamim; Ashraf, Syed Mustafa; Haque, Zahirul

    2016-01-01

    Respiratory tract infections are prevalent among Hajj pilgrims with pneumonia being a leading cause of hospitalization. Streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during Hajj. There is a significant burden of pneumococcal disease in India, which can be prevented. Guidelines for preventive measures and adult immunization have been published in India, but the implementation of the guidelines is low. Data from Bangladesh are available about significant mortality due to respiratory infections; however, literature regarding guidelines for adult immunization is limited. There is a need for extensive awareness programs across India and Bangladesh. Hence, there was a general consensus about the necessity for a rapid and urgent implementation of measures to prevent respiratory infections in pilgrims traveling to Hajj. About ten countries have developed recommendations for pneumococcal vaccination in Hajj pilgrims: France, the USA, Kuwait, Qatar, Bahrain, the UAE (Dubai Health Authority), Singapore, Malaysia, Egypt, and Indonesia. At any given point whether it is Hajj or Umrah, more than a million people are present in the holy places of Mecca and Madina. Therefore, the preventive measures taken for Hajj apply for Umrah as well. This document puts forward the consensus recommendations by a group of twenty doctors following a closed-door discussion based on the scientific evidence available for India and Bangladesh regarding the prevention of respiratory tract infections in Hajj pilgrims. PMID:27942192

  20. 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.

  1. Serotypes and Antibiotic Susceptibility of Streptococcus pneumoniae Isolates from Invasive Pneumococcal Disease and Asymptomatic Carriage in a Pre-vaccination Period, in Algeria.

    PubMed

    Ziane, Hanifa; Manageiro, Vera; Ferreira, Eugénia; Moura, Inês B; Bektache, Soumia; Tazir, Mohamed; Caniça, Manuela

    2016-01-01

    In Algeria, few data is available concerning the distribution of pneumococcal serotypes and respective antibiotic resistance for the current pre-vaccination period, which is a public health concern. We identified the most frequent Streptococcus pneumoniae serogroup/types implicated in invasive pneumococcal disease (IPD; n = 80) and carriage (n = 138) in Algerian children younger than 5 years old. Serogroup/types of 78 IPD isolates were identified by capsular typing using a sequential multiplex PCR. Overall, serotypes 14, 19F, 6B, 23F, 18C, 1, 5, 7F, 19A, and 3 (55% of PCV7 serotypes, 71.3% of PCV10, and 90% of PCV13) were identified. Additionally, 7.5% of the non-vaccine serotypes 6C, 9N/L, 20, 24F, 35B, and 35F, were observed. In the case of S. pneumoniae asymptomatic children carriers, the most common serogroup/types were 6B, 14, 19F, 23F, 4, 9V/A, 1, 19A, 6A, and 3 (42.7% of PCV7 serotypes, 44.2% of PCV10, and 58% of PCV13). For 6.1% of the cases co-colonization was detected. Serotypes 14, 1, 5, and 19A were more implicated in IPD (p < 0.01), whereas serotype 6A was exclusively isolated from carriers (p < 0.01). Deaths associated with IPD were related to serotypes 19A, 14, 18C, and one non-typeable isolate. Among IPD related to vaccine serotypes, the rates of penicillin non-susceptible isolates were higher in no meningitis cases (80%) than in meningitis (66.7%), with serotypes 14, 19A, 19F, and 23F presenting the highest MIC levels (>2μg/ml). Resistance to cefotaxime was higher in isolates from meningitis (40.5%); however, resistance to erythromycin and co-trimoxazole (>40%) was more pronounced in no-meningeal forms. Overall, our results showed that PCV13 conjugate vaccine would cover up to 90% of the circulating isolates associated with IPD in Algeria, highlighting the importance of monitoring the frequency of S. pneumoniae serogroups/types during pre- and post-vaccination periods.

  2. Serotypes and Antibiotic Susceptibility of Streptococcus pneumoniae Isolates from Invasive Pneumococcal Disease and Asymptomatic Carriage in a Pre-vaccination Period, in Algeria

    PubMed Central

    Ziane, Hanifa; Manageiro, Vera; Ferreira, Eugénia; Moura, Inês B.; Bektache, Soumia; Tazir, Mohamed; Caniça, Manuela

    2016-01-01

    In Algeria, few data is available concerning the distribution of pneumococcal serotypes and respective antibiotic resistance for the current pre-vaccination period, which is a public health concern. We identified the most frequent Streptococcus pneumoniae serogroup/types implicated in invasive pneumococcal disease (IPD; n = 80) and carriage (n = 138) in Algerian children younger than 5 years old. Serogroup/types of 78 IPD isolates were identified by capsular typing using a sequential multiplex PCR. Overall, serotypes 14, 19F, 6B, 23F, 18C, 1, 5, 7F, 19A, and 3 (55% of PCV7 serotypes, 71.3% of PCV10, and 90% of PCV13) were identified. Additionally, 7.5% of the non-vaccine serotypes 6C, 9N/L, 20, 24F, 35B, and 35F, were observed. In the case of S. pneumoniae asymptomatic children carriers, the most common serogroup/types were 6B, 14, 19F, 23F, 4, 9V/A, 1, 19A, 6A, and 3 (42.7% of PCV7 serotypes, 44.2% of PCV10, and 58% of PCV13). For 6.1% of the cases co-colonization was detected. Serotypes 14, 1, 5, and 19A were more implicated in IPD (p < 0.01), whereas serotype 6A was exclusively isolated from carriers (p < 0.01). Deaths associated with IPD were related to serotypes 19A, 14, 18C, and one non-typeable isolate. Among IPD related to vaccine serotypes, the rates of penicillin non-susceptible isolates were higher in no meningitis cases (80%) than in meningitis (66.7%), with serotypes 14, 19A, 19F, and 23F presenting the highest MIC levels (>2μg/ml). Resistance to cefotaxime was higher in isolates from meningitis (40.5%); however, resistance to erythromycin and co-trimoxazole (>40%) was more pronounced in no-meningeal forms. Overall, our results showed that PCV13 conjugate vaccine would cover up to 90% of the circulating isolates associated with IPD in Algeria, highlighting the importance of monitoring the frequency of S. pneumoniae serogroups/types during pre- and post-vaccination periods. PMID:27379023

  3. 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.

  4. 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

  5. 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

  6. 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–vaccine

  7. Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

    PubMed

    Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan

    2016-08-01

    Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

  8. Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

    PubMed

    Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan

    2016-01-29

    Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

  9. 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

  10. 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.

  11. Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines

    PubMed Central

    Haasis, Manuel Alexander; Ceria, Joyce Anne; Kulpeng, Wantanee; Teerawattananon, Yot; Alejandria, Marissa

    2015-01-01

    Objectives The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies. Methods A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty. Results With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program. Conclusion The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers. PMID:26131961

  12. Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children - A randomized controlled trial.

    PubMed

    Sáez-Llorens, Xavier; Rowley, Stella; Wong, Digna; Rodríguez, Mirna; Calvo, Arlene; Troitiño, Marisol; Salas, Albino; Vega, Vielka; Castrejón, Maria Mercedes; Lommel, Patricia; Pascal, Thierry G; Hausdorff, William P; Borys, Dorota; Ruiz-Guiñazú, Javier; Ortega-Barría, Eduardo; Yarzabal, Juan Pablo; Schuerman, Lode

    2017-02-25

    We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15-18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children <24 months, which declined thereafter with age. Pre-booster VE against C-AOM was 30.7% [12.9, 44.9]; post-booster, -6.7% [-36.4, 16.6]. PHiD-CV VE was 17.7% [-6.1, 36.2] against moderate and 32.7% [-20.5, 62.4] against severe C-AOM. VE against vaccine-serotype pneumococcal NPC was 31.2% [5.3, 50.3] 3 months post-booster, and 25.6% [12.7, 36.7] across all visits. NTHi colonization rates were low and no significant reduction was observed. PHiD-CV showed efficacy against C-AOM and B-AOM in children younger than 24

  13. Decrease in Hospitalizations for Pneumonia in Children under Five Years of Age in an Indian Reservation in Panama after the Introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7)

    PubMed Central

    Nieto Guevara, Javier; Daza, Carlos

    2013-01-01

    This study quantifies the impact of Heptavalent-Pneumococcal Conjugate Vaccine (PCV7) in Panama on indigenous children younger than 5 years old, based on clinical pneumonia cases. This study demonstrates a significant 41.2% reduction in hospitalizations and 38.6% reduction in referrals for pneumonia following the introduction of PCV7. Burden of disease from pneumonia appears reduced in the ≤12-month- and 13-to-24-month-old groups. PMID:23762081

  14. Streptococcus pneumoniae Serotypes 9 and 14 Circulating in Brazil over a 23-Year Period Prior to Introduction of the 10-Valent Pneumococcal Conjugate Vaccine: Role of International Clones in the Evolution of Antimicrobial Resistance and Description of a Novel Genotype.

    PubMed

    Pinto, Tatiana C A; Kegele, Fabíola C O; Dias, Cícero A G; Barros, Rosana R; Peralta, José M; Merquior, Vânia L C; Carvalho, Maria da Gloria; Chochua, Sopio; Hawkins, Paulina; McGee, Lesley; Teixeira, Lucia M

    2016-11-01

    Antimicrobial-resistant pneumococcal strains have been detected worldwide since the 1960s. In Brazil, the first penicillin-nonsusceptible pneumococci (PNSP) were reported in the 1980s, and their emergence and dissemination have been mainly attributed to serogroup 9 and serotype 14 strains, especially those highly related to recognized international clones. In the present study, antimicrobial susceptibility testing and multilocus sequence typing were performed on 315 pneumococcal isolates belonging to serogroup 9 (n = 99) or serotype 14 (n = 216), recovered from patients or asymptomatic carriers between 1988 and 2011 in Brazil, in order to trace changes in antimicrobial resistance and genotypes prior to the full introduction of the pneumococcal conjugate vaccine in the country. Over the 23-year study period, the PNSP levels increased, and four clonal complexes (CC156, CC66, CC15, and CC5401) have played important roles in the evolution and dissemination of pneumococcal isolates belonging to serogroup 9 and serotype 14, as well as in the emergence of antimicrobial resistance, in the pre-pneumococcal-vaccination era. The earliest PNSP strains detected in this study belonged to serotype 9N/ST66 and were single locus variants of the international clone Tennessee(14)-18 ST67 (CC66). The first serotype 14 PNSP isolates were identified in 1990 and were related to the England(14)-9 ST9 (CC15) clone. Serotype 14 PNSP variants of the Spain(9V)-3 ST156 clone with elevated penicillin MICs and nonsusceptibility to other beta-lactams were detected in 1995 and showed an increasing trend over the years. The results also indicated that introduction of ST156 in our region was preceded by the emergence of trimethoprim-sulfamethoxazole resistance and by the dissemination of ST162. In addition to the presence of successful international clones, a novel regional serotype 14 genotype (CC5401) has emerged in 1996.

  15. 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

  16. Impact of ten-valent pneumococcal conjugate vaccine on pneumonia in Finnish children in a nation-wide population-based study

    PubMed Central

    Palmu, Arto A.; Rinta-Kokko, Hanna; Nohynek, Hanna; Nuorti, J. Pekka; Kilpi, Terhi M.; Jokinen, Jukka

    2017-01-01

    Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Program (NVP) in September 2010 using a 2+1 schedule (3, 5, 12 months). We estimated the direct and indirect effects of PCV10 on pneumonia among children to evaluate the public health impact of the vaccine. Methods We conducted a nation-wide population-based, observational study comparing rates of pneumonia in children before and after the NVP introduction. For the total (direct and indirect) effect, the cohort of vaccine-eligible children (born June 1, 2010 or later) was followed until the end of 2013 (age range 3–42 months). For the indirect effect, a cohort of older children (age range 7–71 months) not eligible for the PCV vaccination was followed from 2011 to 2013. Both cohorts were compared with two season- and age-matched reference cohorts before NVP introduction. Hospitals’ in- and outpatient discharge notifications with ICD-10 diagnoses compatible with pneumonia (J10.0, J11.0, J12-J18, J85.1 or J86) as set by the hospital pediatricians were collected from the national Care Register. The main outcome was hospital-treated primary pneumonia (HTPP), defined as primary diagnosis of pneumonia after in-patient hospitalization. We compared rates of pneumonia in the NVP target and reference cohorts by using Poisson regression models. Results The rate of HTPP episodes was 5.3/1000 person-years in the combined reference cohorts and 4.1/1000 person-years in the target cohort vaccine-eligible children. Compared with the reference cohort, the relative rate reduction in target cohort was 23% (95%CI 18–28) and the absolute reduction 1.3/1000 person-years. In the indirect effect evaluation, we observed continued increase in HTPP incidence until 2011 with a subsequent reduction of 18% (95%CI 10–25) during years 2012 to 2013. Number of empyema diagnoses remained low. Conclusions A substantial decrease in pneumonia rates was observed both among

  17. Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.

    PubMed

    Soothill, Germander; Darboe, Saffiatou; Bah, Gibril; Bolarinde, Lawal; Cunnington, Aubrey; Anderson, Suzanne T

    2016-12-01

    There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015.Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5-14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib.The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA.

  18. Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination

    PubMed Central

    Soothill, Germander; Darboe, Saffiatou; Bah, Gibril; Bolarinde, Lawal; Cunnington, Aubrey; Anderson, Suzanne T.

    2016-01-01

    Abstract There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015. Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5–14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib. The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA. PMID:27930540

  19. Safety, reactogenicity and immunogenicity of a booster dose of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children

    PubMed Central

    Dicko, Alassane; Santara, Gaoussou; Mahamar, Almahamoudou; Sidibe, Youssoufa; Barry, Amadou; Dicko, Yahia; Diallo, Aminata; Dolo, Amagana; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Strezova, Ana; Borys, Dorota; Schuerman, Lode

    2013-01-01

    Background: Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was previously shown to be immunogenic and well tolerated in Malian children. Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe, Asia and Latin America but are lacking for Africa. The present study evaluated further the safety, reactogenicity and immunogenicity of a fourth consecutive (booster) dose of PHiD-CV. Results: Low incidences of AEs with grade 3 intensity (2.1% of subjects) were observed. There were no reports of large swelling reactions and serious adverse events. One month post-booster vaccination, for each vaccine pneumococcal serotype, at least 97.8% of subjects had antibody concentrations ≥ 0.2 μg/ml, and at least 97.1% of subjects had opsonophagocytic activity ≥ 8. From pre- to post-booster, a 12.3-fold increase in anti-protein D geometric mean concentration was observed. Methods: This phase III, open-label study was conducted in Ouelessebougou, Mali, between November 2009 and June 2010. The study population consisted of Malian children previously primed (3 doses) with PHiD-CV in study NCT00678301 receiving a fourth consecutive (booster) dose of PHiD-CV in the second year of life. The incidences of adverse events (AEs) with grade 3 intensity (primary objective) or of any intensity (secondary objective), and the immunogenicity (secondary objective) of the PHiD-CV booster dose were assessed. Conclusion: A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. (ClinicalTrials.gov identifier: NCT00985465) PMID:23291945

  20. Changes in fluoroquinolone-resistant Streptococcus pneumoniae after 7-valent conjugate vaccination, Spain.

    PubMed

    de la Campa, Adela G; Ardanuy, Carmen; Balsalobre, Luz; Pérez-Trallero, Emilio; Marimón, Jose M; Fenoll, Asunción; Liñares, Josefina

    2009-06-01

    Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4-8 microg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC >or=16 microg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733) appeared in 2006.

  1. Changes in Fluoroquinolone-Resistant Streptococcus pneumonia after 7-Valent Conjugate Vaccination, Spain

    PubMed Central

    Ardanuy, Carmen; Balsalobre, Luz; Pérez-Trallero, Emilio; Marimón, Jose M.; Fenoll, Asunción; Liñares, Josefina

    2009-01-01

    Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4–8 μg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC ≥16 μg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733) appeared in 2006. PMID:19523289

  2. Immunogenicity of a combination vaccine containing diphtheria toxoid, tetanus toxoid, three-component acellular pertussis, hepatitis B, inactivated polio virus, and Haemophilus influenzae type b when given concomitantly with 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gimenez-Sanchez, Francisco; Kieninger, Dorothee M; Kueper, Kathrin; Martinon-Torres, Federico; Bernaola, Enrique; Diez-Domingo, Javier; Steul, Kathrin; Juergens, Christine; Gurtman, Alejandra; Giardina, Peter; Liang, John Z; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2011-08-11

    Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix(®) hexa/Infanrix(®)-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules.

  3. Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study.

    PubMed

    Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode

    2015-01-01

    Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children.

  4. Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study

    PubMed Central

    Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode

    2015-01-01

    Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children PMID:26020101

  5. 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

  6. 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.).

  7. Incidence of pediatric invasive pneumococcal disease in the Island of Majorca (2008-2010), an area with non-universal vaccination, and estimations of serotype & children population coverage by available conjugate vaccines

    PubMed Central

    2013-01-01

    Background The World Health Organization reported in 2007 that inclusion of PCV7 in national immunization programs should be seen as a priority, also encouraging countries to conduct appropriate surveillances for monitoring the impact of vaccination. These analyses should be conducted in specific geographical areas and should be aimed to evolution of invasive pneumococcal disease (IPD), by age groups, clinical presentation, and vaccine serotypes (and non-vaccine serotypes to detect possible replacement). This study aimed to monitor the evolution of IPD incidence in children <15 years requiring hospitalization in the Island of Majorca. Methods A prospective clinical surveillance of all culture and/or PCR-confirmed IPD in children <15 years was performed in all hospitals in the Island of Majorca (approximately 900,000 inhabitants) from January 2008 to December 2010. Incidence rate (IR) was calculated as cases/100000 inhabitants using children population data. Results 66 IPDs were identified: 39 (59.1%) parapneumonic pneumococcal empyema (PPE), 16 (24.2%) bacteremic pneumonia (BP), 7 (10.6%) primary bacteremia, 3 (4.5%) meningitis, and 1 (1.5%) osteomyelitis. IRs in the three-year study period were: 64.22 for children 12- < 24 months, 37.21 for those 24-59 months, 22.62 for those <12 months, and 3.98 for children >59 months. By study year, IRs were 21.25 in 2008, 19.89 in 2009 and 9.80 in 2010. The reduction found in 2010 was significant and due to significant reductions in IRs of IPDs caused by serotypes included in PCV10 and PCV13. Overall, estimated serotype coverage by conjugate vaccines was 12.1% for PCV7, 37.9% for PCV10 and 65.2% for PCV13. Of the 66 hospitalized children with IPD, 20 had received at least one dose of PCV7 (13 cases with identified serotype). None of these 13 cases was caused by PCV7 serotypes, all were caused by PCV13 serotypes and only 53.8% by PCV10 serotypes. Conclusions The results of the present study evidence the importance of

  8. Characterization of the antibody response elicited by immunization with pneumococcal surface protein A (PspA) as recombinant protein or DNA vaccine and analysis of protection against an intranasal lethal challenge with Streptococcus pneumoniae.

    PubMed

    Vadesilho, Cintia F M; Ferreira, Daniela M; Moreno, Adriana T; Chavez-Olortegui, Carlos; Machado de Avila, Ricardo A; Oliveira, Maria Leonor S; Ho, Paulo L; Miyaji, Eliane N

    2012-01-01

    Pneumococcal surface protein A (PspA) is an important candidate for a vaccine against pneumococcal infections. DNA vaccines expressing PspA were shown to protect mice against intraperitoneal and colonization challenge models in mice. We now show that a DNA vaccine expressing PspA from clade 4 (pSec-pspA4Pro) is also able to elicit protection against an intranasal lethal challenge model at levels similar to the recombinant protein PspA4Pro adjuvanted with alum. PspA4Pro + alum induced an IgG response characterized by a high IgG1/IgG2a ratio, leading to a lack of binding of anti-PspA IgG2a antibodies to intact pneumococci in vitro, which is in contrast to the response elicited by pSec-pspA4Pro. Epitopes recognized by the sera were mapped and antibodies induced by immunization with PspA4Pro + alum showed positive reaction with several synthetic peptides, mostly located in the first half of the protein. On the other hand, antibodies induced by the DNA vaccine showed reactivity with only two peptides. Though both strategies were protective against the intranasal lethal challenge model, the elicited humoral responses differ significantly, with the detection of important differences in the Fc (IgG1/IgG2a ratios) and Fab (recognized epitopes) regions of the induced antibodies.

  9. Immunogenicity, Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

    PubMed Central

    Hammitt, Laura L.; Ojal, John; Bashraheil, Mahfudh; Morpeth, Susan C.; Karani, Angela; Habib, Ahsan; Borys, Dorota; Goldblatt, David; Scott, J. Anthony G

    2014-01-01

    Background The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown. Methods 600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination. Results Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups. Conclusions Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease. Trial Registration ClinicalTrials.gov NCT01028326 PMID:24465570

  10. Systematic review of economic evaluations of vaccination programs in mainland China: Are they sufficient to inform decision making?

    PubMed

    Pan, Xiong-Fei; Griffiths, Ulla K; Pennington, Mark; Yu, Hongjie; Jit, Mark

    2015-11-17

    The purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland China. We searched for economic evaluations of vaccination in China published prior to August 3, 2015 in eight English-language and three Chinese-language databases. Each article was appraised against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We found 23 papers evaluating vaccines against hepatitis B (8 articles), Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles), Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1 article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six Chinese-language articles conformed to fewer than half of the 19 criteria items. The main criteria that studies failed to conform to included: inappropriate measurement (20 articles) and valuation (18 articles) of treatment and/or vaccination costs, no discussion about distributional implications (18 articles), missing major health outcomes (14 articles), no discussion about generalizability to other contexts (14 articles), and inadequate sensitivity analysis (13 articles). In addition, ten studies did not include major cost components of vaccination programs, and nine did not report outcomes in terms of life years even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a societal perspective for analysis. All studies concluded that the appraised vaccination programs were cost-effective except for one evaluation of universal 7-valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the five studies on PCV-7 showed poor overall quality, and the number of studies on vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion, major methodological flaws and reporting problems exist in current economic evaluations of vaccination programs in China. Local

  11. Vaccine schedule compliance among very low birth weight infants in Lima, Peru

    PubMed Central

    Ochoa, Theresa J; Zea-Vera, Alonso; Bautista, Rossana; Davila, Carmen; Salazar, José Antonio; Bazán, Carlos; López, Luis; Ecker, Lucie

    2015-01-01

    Objective There is little information about vaccine schedule compliance in very-low-birth-weight infants in developing countries. The aim of the study was to describe the compliance with the vaccine schedule among this population in Lima, Peru. Patients and Methods We conducted a prospective cohort study in four hospitals in Lima in infants with a birth-weight of less than 1500g, followed from birth up to 12 months of age every 2 weeks. The date and age at administration of each vacccine was recorded. Results 222 infants were enrolled. The median birth-weight was 1,250g (range 550-1,499g) and the median gestational age was 30.0 weeks (range 23-37 weeks). The mean age for the first pentavalent (DPT, Hib, HepB) and oral polio vaccine administration was 4.3 ± 1.4 months in infants with a birth-weight of <1000g vs. 3.1 ± 1.0 in infants with a birth-weight 1000- 1500g (p<0.001); 4.1 ± 0.9 vs. 3.3 ± 1.1 for rotavirus (p<0.05); and 5.1 ± 2.1 vs. 4.3 ± 1.8 for the 7-valent pneumococcal conjugated vaccine. Only 35% had received the three doses of oral polio and pentavalent vaccine by seven months, although by nine months 81% had received these vaccines. Conclusions Vaccination of very-low-birth-weight infants in Peru is significantly delayed, especially in infants with a birth-weight of <1000g. Urgent educational interventions targeting physicians and nurses should be implemented in order to improve vaccination rates and timing in these high risk populations. PMID:25448091

  12. Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12–15 Months

    PubMed Central

    Mufson, Maurice A.; Diaz, Clemente; Leonardi, Michael; Harrison, Christopher J.; Grogg, Stanley; Carbayo, Antonio; Carlo-Torres, Simon; JeanFreau, Robert; Quintero-Del-Rio, Ana; Bautista, Gisele; Povey, Michael; Da Costa, Christopher; Nicholson, Ouzama; Innis, Bruce L.

    2015-01-01

    Background M-M-RTMII (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (PriorixTM, GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States. Methods In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12–15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed. Results Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3–99.2% (measles), 89.7–90.7% (mumps), and 97.5–98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups. Conclusions Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. Clinical Trials Registration NCT00861744; etrack; 111870 PMID:26582873

  13. Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae

    PubMed Central

    Tostes, Rafaella O.; Rodrigues, Tasson C.; da Silva, Josefa B.; Schanoski, Alessandra S.; Oliveira, Maria Leonor S.

    2017-01-01

    A promising alternative vaccine candidate to reduce the burden of pneumococcal diseases is the protein antigen PspA (Pneumococcal surface protein A). Since concomitant colonization with two or more pneumococcal strains is very common in children, we aimed to determine if immunization with PspA would be able to control co-colonization. We evaluated nasal immunization with recombinant PspA (rPspA) in a model of co-colonization with two strains expressing different PspAs. Mice were immunized intranasally with rPspAs from clades 1 to 4 (rPspA1, rPspA2, rPspA3 or rPspA4) using whole-cell pertussis vaccine (wP) as adjuvant. Mice were then challenged with a mixture of two serotype 6B isolates St491/00 (PspA1) and St472/96 (PspA4). Immunization with rPspA1+wP and rPspA4+wP reduced colonization with both strains and the mixture of rPspA1+rPspA4+wP induced greater reduction than a single antigen. Immunization rPspA1+rPspA4+wP also reduced colonization when challenge experiments were performed with a mixture of isolates of serotypes 6B (PspA3) and 23F (PspA2). Furthermore, none of the tested formulations led to a pronounced increase in colonization of one isolate over the other, showing that the vaccine strategy would not favor replacement. Interestingly, the adjuvant wP by itself already led to some reduction in pneumococcal colonization, indicating the induction of non-specific immune responses. Anti-rPspA IgG was observed in serum, nasal wash (NW) and bronchoalveolar lavage fluid (BALF) samples, whereas animals inoculated with formulations containing the adjuvant wP (with or without rPspA) showed higher levels of IL-6 and KC in NW and increase in tissue macrophages, B cells and CD4+T cells in BALF. PMID:28103277

  14. 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.

  15. Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study.

    PubMed

    Cilveti, Robert; Olmo, Montserrat; Pérez-Jove, Josefa; Picazo, Juan-José; Arimany, Josep-Lluis; Mora, Emiliano; Pérez-Porcuna, Tomás M; Aguilar, Ignacio; Alonso, Aurora; Molina, Francesc; Del Amo, María; Mendez, Cristina

    2017-01-01

    The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would

  16. Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study

    PubMed Central

    Olmo, Montserrat; Pérez-Jove, Josefa; Picazo, Juan-José; Arimany, Josep-Lluis; Mora, Emiliano; Pérez-Porcuna, Tomás M.; Aguilar, Ignacio; Alonso, Aurora; Molina, Francesc; del Amo, María; Mendez, Cristina

    2017-01-01

    The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would

  17. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study

    PubMed Central

    McCollum, Eric D.; Nambiar, Bejoy; Deula, Rashid; Zadutsa, Beatiwel; Bondo, Austin; King, Carina; Beard, James; Liyaya, Harry; Mankhambo, Limangeni; Lazzerini, Marzia; Makwenda, Charles; Masache, Gibson; Bar-Zeev, Naor; Kazembe, Peter N.; Mwansambo, Charles; Lufesi, Norman; Costello, Anthony; Armstrong, Ben

    2017-01-01

    Background The pneumococcal conjugate vaccine’s (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia. Methods and Findings Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children <5 years at seven hospitals, 18 health centres, and with 38 community health workers in two districts, central Malawi. Eligible children had clinical pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation <90% defined hypoxemic pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children <5 years. We observed a shift towards disease without danger signs, as the proportion of cases with danger signs decreased by 65% (-46%, -77%, p<0.0001). These results were generally robust to plausible alternative model specifications. Conclusions Thirty months after PCV13

  18. 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.

  19. [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

  20. Expansion of Serotype Coverage in the Universal Pediatric Vaccination Calendar: Short-Term Effects on Age- and Serotype-Dependent Incidence of Invasive Pneumococcal Clinical Presentations in Madrid, Spain

    PubMed Central

    Ruiz-Contreras, Jesus; Casado-Flores, Juan; Negreira, Sagrario; García-de-Miguel, Maria-Jesus; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2013-01-01

    In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13

  1. Expansion of serotype coverage in the universal pediatric vaccination calendar: short-term effects on age- and serotype-dependent incidence of invasive pneumococcal clinical presentations in Madrid, Spain.

    PubMed

    Picazo, Juan; Ruiz-Contreras, Jesus; Casado-Flores, Juan; Negreira, Sagrario; García-de-Miguel, Maria-Jesus; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2013-10-01

    In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13

  2. [Pneumococcal vaccination in general practice].

    PubMed

    Vajer, Péter; Tamás, Ferenc; Urbán, Róbert; Torzsa, Péter; Kalabay, László

    2015-02-01

    Bevezetés: Az invazív pneumococcusbetegség előfordulása 50 éves kortól emelkedik. Vakcináció ajánlott, az átoltottság mégis igen alacsony. Célkitűzés: A szerzők az influenza ellen oltottak tájékoztatásának, a tájékoztatást nyújtó kilétének hatását vizsgálták az oltás felvételére. Módszer: Húsz praxisban, a 2012/2013-as influenzaoltási kampányban megjelenő 50 év feletti személyek kérdőívet töltöttek ki és tájékoztatást kaptak a pneumoccusvakcináció fontosságáról. Eredmények: 4000 személy közül 576 kért receptet, a nők 16,5%-a, a férfiak 11,6%-a (OR 1,67; CI 95% 1,37–2,04; p<0,001), átlagéletkoruk 70,95 év, illetve 69,8 év volt (OR 1,01; CI 95% 1,00–1,02; p<0,05). Családorvosi tájékoztatás esetén a védőoltást kérők aránya 33,6%, asszisztensnő általi tájékoztatás esetén 8% volt (OR 6,33; CI 95% 5,23–7,67; p<0,001), a védőoltást felvevőknél ez az arány 17,7%, illetve 4,4% volt. A családorvosok 6,3-szer több vakcinát adtak be, mint az azt megelőző évben (p<0,001). Következtetések: A családorvosok a pneumococcusvakcinációval kapcsolatban hatékonyabb tájékoztatást nyújtanak, mint az asszisztensek. Az intenzív tájékoztatás jelentősen növeli a pneumococcusvakcináció felvételi arányát. Orv. Hetil., 2015, 156(5), 186–191.

  3. Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2006-2010.

    PubMed

    Naidu, Latika; Chiu, Clayton; Habig, Andrew; Lowbridge, Christopher; Jayasinghe, Sanjay; Wang, Han; McIntyre, Peter; Menzies, Robert

    2013-12-31

    This report outlines the major positive impacts of vaccines on the health of Aboriginal and Torres Strait Islander people from 2007 to 2010, as well as highlighting areas that require further attention. Hepatitis A disease is now less common in Aboriginal and Torres Strait Islander children than in their non-Indigenous counterparts. Hepatitis A vaccination for Aboriginal and Torres Strait Islander children was introduced in 2005 in the high incidence jurisdictions of the Northern Territory, Queensland, South Australia and Western Australia. In 2002–2005, there were 20 hospitalisations for hepatitis A in Aboriginal and Torres Strait Islander children aged<5 years--over 100 times more common than in other children--compared to none in 2006/07–2009/10. With respect to invasive pneumococcal disease (IPD), there has been a reduction of 87% in notifications of IPD caused by serotypes contained in 7-valent pneumococcal conjugate vaccine (7vPCV) since the introduction of the childhood 7vPCV program among Aboriginal and Torres Strait Islander children. However, due to a lower proportion of IPD caused by 7vPCV types prior to vaccine introduction, the decline in total IPD notifications has been less marked in Aboriginal and Torres Strait Islander children than in other children. Higher valency vaccines (10vPCV and 13vPCV) which replaced 7vPCV from 2011 are likely to result in a greater impact on IPD and potentially also non-invasive disease, although disease caused by non-vaccine serotypes appears likely to be an ongoing problem. Among Aboriginal and Torres Strait Islander people aged ≥50 years, there have been recent increases in IPD, which appear related to low vaccination coverage and highlight the need for improved coverage in this high-risk target group. Since routine meningococcal C vaccination for infants and the high-school catch-up program were implemented in 2003, there has been a significant decrease in cases caused by serogroup C. However, the predominant

  4. Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

    DTIC Science & Technology

    2006-08-01

    Isotype Responses to Intact Streptococcus pneumoniae , but Not to a Soluble Pneumococcal Conjugate Vaccine1,2 Quanyi Chen, Goutam Sen, and Clifford M...intact Streptococcus pneumoniae (Pn). Because type 1 IL-1R (IL-1R1) signaling is MyD88 dependent, a role for endogenous IL-1 was determined. IL-1R1... Streptococcus pneumoniae (Pn), a Gram-positive extracellular bacterium, elicits T cell-inde- pendent (TI) IgM responses specific for the

  5. Impact and Effectiveness of 10 and 13-Valent Pneumococcal Conjugate Vaccines on Hospitalization and Mortality in Children Aged Less than 5 Years in Latin American Countries: A Systematic Review

    PubMed Central

    de Oliveira, Lucia Helena; Camacho, Luiz Antonio B.; Coutinho, Evandro S. F.; Martinez-Silveira, Martha S.; Carvalho, Ana Flavia; Ruiz-Matus, Cuauhtemoc; Toscano, Cristiana M.

    2016-01-01

    Background Several Latin American and Caribbean (LAC) countries have introduced pneumococcal conjugate vaccine (PCV-10 or PCV-13) in their routine national immunization programs. Objectives We aimed to summarize the evidence of PCV impact and effectiveness in children under 5 years old in the LAC Region. Methods We conducted a systematic review of the literature on impact or effectiveness of PCVs on deaths or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis and sepsis. We searched Medline, WoS, Lilacs, Scopus, Central and gray literature published in any language from 2009 to January 2016. We included studies addressing the outcomes of interest in children in the target age group, and with the following designs: randomized trials, cohort or case-control, interrupted time series with at least three data points before and after the intervention, and before-after studies. Screening of citations, data extraction, and risk of bias assessment were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analysis of the effectiveness measurements and sensitivity analysis were conducted. Effectiveness is reported as 1-OR or 1-RR for case control or cohort/clinical trials, and as percent change of disease incidence rates for before-after studies. Results We identified 1,085 citations, 892 from databases and 193 from other sources. Of these, 22 were further analyzed. Studies were from Brazil, Chile, Uruguay, Argentina, Peru and Nicaragua. Effectiveness ranged from 8.8–37.8% for hospitalizations due to X-ray confirmed pneumonia, 7.4–20.6% for clinical pneumonia, and 13.3–87.7% for meningitis hospitalizations, and 56–83.3% for IPD hospitalization, varying by age, outcome definition, type of vaccine and study design. Conclusions Available evidence to date indicates significant impact of both PCV-10 and PCV-13 in the outcomes studied, with no evidence of the superiority of one

  6. Population Snapshot of Streptococcus pneumoniae Serotype 19A Isolates before and after Introduction of Seven-Valent Pneumococcal Vaccination for French Children▿

    PubMed Central

    Mahjoub-Messai, Farah; Doit, Catherine; Koeck, Jean-Louis; Billard, Typhaine; Evrard, Bénédicte; Bidet, Philippe; Hubans, Christine; Raymond, Josette; Levy, Corinne; Cohen, Robert; Bingen, Edouard

    2009-01-01

    Serotype 19A Streptococcus pneumoniae strains are now more frequent in French children than before the introduction of a seven-valent conjugate vaccine (PCV7). By applying multilocus sequence typing to 144 serotype 19A isolates collected before and after beginning PCV7 vaccination, we detected clonal expansion of the preexisting penicillin-intermediate sequence type 276. PMID:19109482

  7. Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

    PubMed Central

    Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

    2014-01-01

    In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have

  8. 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

  9. 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

  10. 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].

  11. 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

  12. 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

  13. 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.

  14. Recent trends in pediatric bacterial meningitis in Japan--a country where Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines have just been introduced.

    PubMed

    Shinjoh, Masayoshi; Iwata, Satoshi; Yagihashi, Tatsuhiko; Sato, Yoshitake; Akita, Hironobu; Takahashi, Takao; Sunakawa, Keisuke

    2014-08-01

    To investigate the trends in incidence and the characteristics of bacterial meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7-valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010, respectively, which was 5-20 years after their introduction in western countries. The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was performed in 2011 and 2012. We analyzed the epidemiological and clinical data, and compared the information obtained in the previous nationwide survey database. We also investigated the risk factors for disease outcome. In the 2011-2012 surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae, Streptococcus agalactiae and Escherichia coli were the main organisms. The number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.31 in 2009 to 0.43 in 2012 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30 to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2012. The median patient age was 10-12 months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001-2012 among the four organisms. Risk factors for death and sequelae were convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children.

  15. 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

  16. 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.

  17. 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

  18. Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine (PHiD-CV) co-administered with DTPa-combined vaccines in children: An open-label, randomized, controlled, non-inferiority trial

    PubMed Central

    Falup-Pecurariu, Oana; Man, Sorin C.; Neamtu, Mihai L.; Chicin, Gratiana; Baciu, Ginel; Pitic, Carmen; Cara, Alexandra C.; Neculau, Andrea E.; Burlea, Marin; Brinza, Ileana L.; Schnell, Cristina N.; Sas, Valentina; Lupu, Valeriu V.; François, Nancy; Swinnen, Kristien; Borys, Dorota

    2017-01-01

    ABSTRACT Prophylactic paracetamol administration impacts vaccine immune response; this study (www.clinicaltrials.gov: NCT01235949) is the first to assess PHiD-CV immunogenicity following prophylactic ibuprofen administration. In this phase IV, multicenter, open-label, randomized, controlled, non-inferiority study in Romania (November 2010–December 2012), healthy infants were randomized 3:3:3:1:1:1 to prophylactically receive immediate, delayed or no ibuprofen (IIBU, DIBU, NIBU) or paracetamol (IPARA, DPARA, NPARA) after each of 3 primary doses (PHiD-CV at age 3/4/5 months co-administered with DTPa-HBV-IPV/Hib at 3/5 and DTPa-IPV/Hib at 4 months) or booster dose (PHiD-CV and DTPa-HBV-IPV/Hib; 12–15 months). Non-inferiority of immune response one month post-primary vaccination in terms of percentage of infants with anti-pneumococcal antibody concentrations ≥0.2 µg/mL (primary objective) was demonstrated if the upper limit (UL) of the 98.25% confidence interval of difference between groups (NIBU vs IIBU, NIBU vs DIBU) was <10% for ≥7/10 serotypes. Immunogenicity and reactogenicity/safety were evaluated, including confirmatory analysis of difference in fever incidences post-primary vaccination in IBU or DIBU group compared to NIBU. Of 850 infants randomized, 812 were included in the total vaccinated cohort. Non-inferiority was demonstrated for both comparisons (UL was <10% for 9/10 vaccine serotypes; exceptions: 6B [NIBU], 23F [IIBU]). However, fever incidence post-primary vaccination in the IIBU and DIBU groups did not indicate a statistically significant reduction. Prophylactic administration (immediate or delayed) of paracetamol decreased fever incidence but seemed to reduce immune response to PHiD-CV, except when given only at booster. Twenty-seven serious adverse events were reported for 15 children; all resolved and were not vaccination-related. PMID:27541270

  19. Increase in numbers of beta-lactam-resistant invasive Streptococcus pneumoniae in Brazil and the impact of conjugate vaccine coverage.

    PubMed

    Brandileone, Maria-Cristina C; Casagrande, Silvana Tadeu; Guerra, Maria-Luiza L S; Zanella, Rosemeire Cobo; Andrade, Ana-Lucia S S; Di Fabio, José-Luis

    2006-05-01

    A comprehensive investigation of invasive Streptococcus pneumoniae was carried out in Brazil as part of the programme of the national epidemiological surveillance system. The investigation provided data on the trends of resistance to antimicrobial agents. A total of 6470 isolates of S. pneumoniae collected in the country from 1993 to 2004 were tested. During this period of time, the number of penicillin-resistant strains rose from 10.2 to 27.9%. The proportions of intermediate and high-level resistant strains in 1993, which were 9.1 and 1.1%, respectively, rose to 22.0 and 5.9% in 2004. Geometric mean MICs for penicillin increased after the year 2000, to 0.19 microg ml(-1) in 2004; most of these isolates were from patients with pneumonia and from children under 5 years old, and belonged to serotype 14. There was a significant increase in the number of isolates belonging to serotypes included in the 7-valent conjugate vaccine from children under 5 years old: from 48.6% in 1993 to 69.6% in 2004, mainly related to an increase in the frequency of serotype 14 isolates. From 2000 to 2004, meningitis isolates showed higher resistance rates to cefotaxime (2.6%) compared to non-meningitis isolates (0.7%); percentages of isolates resistant to trimethoprim-sulfamethoxazole, tetracycline, erythromycin, chloramphenicol and rifampicin were 65, 14.6, 6.2, 1.3 and 0.7 %, respectively. No levoflaxin resistance was observed. Multidrug resistance was identified in 4.6% of isolates, of which 3.8% were resistant to three classes, 0.7% to four classes and 0.1% to five classes of antimicrobial agent. The study provides valuable information that may support empirical antimicrobial therapy for severe S. pneumoniae infections in Brazil, and emphasizes the need for conjugate pneumococcal vaccination.

  20. What is behind the ear drum? The microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination

    PubMed Central

    Mills, Nikki; Best, Emma J; Murdoch, David; Souter, Melanie; Neeff, Michel; Anderson, Trevor; Salkeld, Lesley; Ahmad, Zahoor; Mahadevan, Murali; Barber, Colin; Brown, Colin; Walker, Cameron; Walls, Tony

    2015-01-01

    Aim This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media. Methods Between May and November 2011, MEF and NP samples from 325 children aged <3 years were collected in three major centres in New Zealand at the time of ventilation tube insertion. An age-matched non-otitis-prone comparison group of 137 children had NP samples taken. A questionnaire was completed by both groups. Results Immunisation coverage with at least one dose of PCV7 was 97%. Haemophilus influenzae was cultured in 19.4% of MEF and was polymerase chain reaction (PCR) positive in 43.4%. S. pneumoniae and Moraxella catarrhalis were cultured in <10% of MEF samples but were PCR positive for 23.1% and 38.7%, respectively. H. influenzae was the most common organism isolated from NP samples (60%) in the grommet group, while M. catarrhalis (56%) was the most common in the non-otitis prone group. S. pneumoniae was more commonly found in the nasopharynx of children with ear disease (41% vs. 29%). 19F was the most prominent S. pneumoniae serotype in NP samples of both groups, but no serotype dominated in MEF. Ninety-five per cent of H. influenzae isolates were confirmed to be non-typeable H. influenzae. Conclusion In this cohort of children with established ear disease requiring surgical intervention, non-typeable H. influenzae is the dominant pathogen in both the nasopharynx and MEF. PMID:25175818

  1. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  2. 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

  3. 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.

  4. 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

  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

    , for the pneumococcal vaccine. Expression of HIF-1α in unexposed respiratory cells inhibits basal pneumococcal infection via PAFR-independent mechanisms. PMID:28278175

  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

    , for the pneumococcal vaccine. Expression of HIF-1α in unexposed respiratory cells inhibits basal pneumococcal infection via PAFR-independent mechanisms.

  7. 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 ...

  8. 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

  9. Self-reported vaccination in the elderly

    PubMed Central

    Reyes-Ortiz, Carlos; Borda, Miguel German; Arciniegas, Antonio

    2016-01-01

    Objectives: To determine the frequency of vaccination in older adults within the city of Bogotá and to estimate the association with sociodemographic and health factors. Methods: This is a secondary data analysis from the SABE-Bogotá Study, a cross-sectional population-based study that included a total of 2,000 persons aged 60 years. Weighted percentages for self-reported vaccination [influenza, pneumococcal, tetanus] were determined. The association between vaccination and covariates was evaluate by logistic regression models. Results: A total of 73.0% of respondents received influenza, 57.8% pneumococcal and 47.6% tetanus vaccine. Factors independently associated with vaccination included: 1- age (65-74 years had higher odds of receiving vaccinations, compared to 60-64 years); 2- socioeconomic status (SES) (higher SES had lower odds of having influenza and pneumococcal vaccines, compared to those with lower SES); 3- health insurance (those with contributive or subsidized health insurance had higher odds (between 3 and 5 times higher) of having vaccinations, compared to those with no insurance); 4- older adults with better functional status (greater Lawton scores) had increased odds for all vaccinations; 5- older adults with higher comorbidity had increased odds for influenza and pneumococcal vaccinations. Conclusion: Vaccination campaigns should be strengthened to increase vaccination coverage, especially in the group more reticent to vaccination or vulnerable to reach it such as the disabled elder. PMID:27226661

  10. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  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. 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.

  13. 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

  14. 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.

  15. 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

  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. 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

  18. 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.

  19. 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.

  20. 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

  1. Vaccinating welders against pneumonia

    PubMed Central

    Palmer, Keith T; Cosgrove, Martin P

    2013-01-01

    Background In 2011 the Department of Health in England recommended that welders should each receive a single dose of the 23-valent pneumococcal vaccine (PPV23). This review assesses the evidence behind the advice and its practical implications. Method The review was informed by a systematic search in Medline, which related pneumonia to welding and/or exposure to metal fume, and was supplemented using the personal libraries of the authors. Findings There is consistent evidence that welders die more often of pneumonia, especially lobar pneumonia, are hospitalised more often with lobar and pneumococcal pneumonia, and more often develop invasive pneumococcal disease (IPD). It is estimated that one case of IPD may be prevented over a 10-year period by vaccinating 588 welders against pneumococcal infection. Conclusions A good case exists that employers should offer PPV23 vaccination to welders and other employees exposed to metal fume. Additionally, reasonable measures must be taken to minimise exposure to welding fume and welders should be encouraged not to smoke. PMID:22764269

  2. 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

  3. 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.

  4. 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

  5. Vaccination-related shoulder dysfunction.

    PubMed

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

    We present two cases of shoulder pain and weakness following influenza and pneumococcal vaccine injections provided high into the deltoid muscle. Based on ultrasound measurements, we hypothesize that vaccine injected into the subdeltoid bursa caused a periarticular inflammatory response, subacromial bursitis, bicipital tendonitis and adhesive capsulitis. Resolution of symptoms followed corticosteroid injections to the subacromial space, bicipital tendon sheath and glenohumeral joint, followed by physical therapy. We conclude that the upper third of the deltoid muscle should not be used for vaccine injections, and the diagnosis of vaccination-related shoulder dysfunction should be considered in patients presenting with shoulder pain following a vaccination.

  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. 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. 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

  9. Immunizations: vaccinations in general.

    PubMed

    Wiley, Catherine C

    2015-06-01

    The childhood immunization schedule is complex and nuanced. Although serious adverse reactions to immunizations are uncommon, clinicians must be well-versed in these reactions as well as the contraindications and precautions to each vaccine. • Conjugate vaccine technology links polysaccharide antigens to carrier proteins, triggering T-cell-dependent immunity to polysaccharides, thereby strengthening immune memory. • On the basis of some research evidence and consensus, live vaccines are generally contraindicated in immunocompromised patients and in pregnancy. Most live vaccines can be administered to household contacts of immunocompromised patients. • On the basis of some research and consensus, modified administration of meningococcal, pneumococcal, and less commonly, other vaccines may be indicated to protect immunocompromised patients. • On the basis of disease epidemiology and consensus, international travelers should be up-to-date with all routine immunizations; depending on destination, additional vaccines or immune globulin may be required.

  10. Vaccine herd effect.

    PubMed

    Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

    2011-09-01

    Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.

  11. 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.

  12. 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

  13. 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

  14. Clonal and serotype dynamics of serogroup 6 isolates causing invasive pneumococcal disease in Portugal: 1999-2012

    PubMed Central

    Diamantino-Miranda, Jorge; Aguiar, Sandra Isabel; Carriço, João André; Melo-Cristino, José

    2017-01-01

    Although serogroup 6 was among the first to be recognized among Streptococcus pneumoniae, several new serotypes were identified since the introduction of pneumococcal conjugate vaccines (PCVs). A decrease of the 6B-2 variant among invasive pneumococcal disease (IPD), but not 6B-1, was noted post conjugate vaccine introduction, underpinned by a decrease of CC273 isolates. Serotype 6C was associated with adult IPD and increased in this age group representing two lineages (CC315 and CC395), while the same lineages expressed other serogroup 6 serotypes in children. Taken together, these findings suggest a potential cross-protection of PCVs against serotype 6C IPD among vaccinated children but not among adults. Serotype 6A became the most important serogroup 6 serotype in children but it decreased in adult IPD. No other serogroup 6 serotypes were detected, so available phenotypic or simple genotypic assays remain adequate for distinguishing serotypes within serogroup 6 isolates. PMID:28152029

  15. [Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2004].

    PubMed

    2004-05-01

    The Vaccine Assessment Committee of the Spanish Association of Pediatrics discusses vaccine developments in 2003 and recommends some modifications to the vaccination schedule. The recommendation of substituting the oral polio vaccine for the inactivated polio vaccine, suppressing the fifth dose, is maintained. The introduction of the conjugate pneumococcal vaccine and the varicella vaccine is stressed. Concerning the meningococcal C vaccine, the improvement introduced by being able to immunize with just two doses is discussed. In agreement with the information received from the European Medicines Agency, there appear to be no well-founded reasons to abandon hexavalent preparations.

  16. 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

  17. Immunization of Aged Mice with a Pneumococcal Conjugate Vaccine Combined with an Unmethylated CpG-Containing Oligodeoxynucleotide Restores Defective Immunoglobulin G Antipolysaccharide Responses and Specific CD4+-T-Cell Priming to Young Adult Levels

    DTIC Science & Technology

    2006-04-01

    various antiviral and antibacterial vaccines, in- cluding those for intact Streptococcus pneumoniae (7, 14, 38, 40). This is correlated with a reduced... Streptococcus pneumoniae polysaccharide vac- cine: age and dose responses, safety, persistence of antibody, revaccination, and simultaneous administration of...immunity and type 1 humoral immunity to Streptococcus pneumoniae are mediated by MyD88 but differ in their relative levels of dependence on Toll-like

  18. 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.

  19. Vaccinations in patients with hematological malignancies.

    PubMed

    Tsigrelis, C; Ljungman, P

    2016-03-01

    Patients with hematological malignancies are at risk for a number of infections that are potentially preventable by vaccinations such as pneumococcal infections and influenza. Treatment, especially with anti-B-cell antibodies and hematopoietic stem cell transplantation (HSCT), negatively impacts the response to vaccination for several months. It is therefore recommended that patients be vaccinated before initiating immunosuppressive therapy if possible. The risk of side-effects with inactivated vaccines is low, but care has to be taken with live vaccines, such as varicella-zoster virus vaccine, since severe and fatal complications have been reported. HSCT patients require repeated doses of most vaccines to achieve long-lasting immune responses. New therapeutic options for patients with hematological malignancies that are rapidly being introduced into clinical practice will require additional research regarding the efficacy of vaccinations. New vaccines are also in development that will require well-designed studies to ascertain efficacy and safety.

  20. Safety and immunogenicity of fully liquid DTaP₅-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP₃-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study.

    PubMed

    Berner, Reinhard; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

    2012-07-27

    This study compared the safety and immunogenicity of DTaP₅-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP₃-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP₅-IPV-Hib was noninferior to DTaP₃-HBV-IPV/Hib. DTaP₅-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP₃-HBV-IPV/Hib. Fully liquid DTaP₅-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP₅-IPV-Hib (NCT ID: NCT00355654).

  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. 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

  3. 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 ( ...

  4. 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 ...

  5. Development of Streptococcus pneumoniae Vaccines Using Live Vectors

    PubMed Central

    Wang, Shifeng; Curtiss, Roy

    2014-01-01

    Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines. PMID:25309747

  6. 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

  7. Global Routine Vaccination Coverage, 2015.

    PubMed

    Casey, Rebecca M; Dumolard, Laure; Danovaro-Holliday, M Carolina; Gacic-Dobo, Marta; Diallo, Mamadou S; Hampton, Lee M; Wallace, Aaron S

    2016-11-18

    In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). Based on 2015 WHO and United Nations Children's Fund (UNICEF) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (DTP3), the first dose of measles-containing vaccine (MCV1) and the third dose of polio vaccine (Pol3) has remained stable (84%-86%) since 2010. From 2014 to 2015, estimated global coverage with the second MCV dose (MCV2) increased from 39% to 43% by the end of the second year of life and from 58% to 61% when older age groups were included. Global coverage was higher in 2015 than 2010 for newer or underused vaccines, including rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b (Hib) vaccine, and 3 doses of hepatitis B (HepB3) vaccine. Coverage estimates varied widely by WHO Region, country, and district; in addition, for the vaccines evaluated (MCV, DTP3, Pol3, HepB3, Hib3), wide disparities were found in coverage by country income classification. Improvements in equity of access are necessary to reach and sustain higher coverage and increase protection from vaccine-preventable diseases for all persons.

  8. Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine—Burkina Faso, 2011–2013

    PubMed Central

    Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangare, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Hema-Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Sanou, Soufian; Ba, Absatou Ky; Novak, Ryan T.; Van Beneden, Chris

    2016-01-01

    Background Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. Methods Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). Results During 2011–2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (<1 year), 5.4 (1–4 years), 7.2 (5–14 years), and 3.0 (≥15 years). Overall CFR was 23% and highest among children aged <1 year (32%) and adults ≥30 years (30%). Of 1,528 cases, 1,036 (68%) were serotyped: 71% were PCV13-associated serotypes, 14% were non-PCV13-associated serotypes, and 15% were non-typeable by PCR. Serotypes 1 (45%) and 12F/12A/12B/44/46 (8%) were most common. Among children aged <1 year, serotypes 5 (15%), 6A/6B (13%) and 1 (12%) predominated. Conclusions In Burkina Faso, the highest morbidity and mortality due to pneumococcal meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden. PMID:27832151

  9. A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi.

    PubMed

    Lu, Ying-Jie; Zhang, Fan; Sayeed, Sabina; Thompson, Claudette M; Szu, Shousun; Anderson, Porter W; Malley, Richard

    2012-05-14

    Pneumococcal and Salmonella typhi infections are two major diseases for children in developing countries. For typhoid fever, licensed Vi polysaccharide vaccines are ineffective in children <2-year old. While investigational Vi conjugate vaccines have been shown effective in clinical trials, they are currently only available to restricted areas. Pneumococcal capsular polysaccharide conjugate vaccines are highly effective in children, but suffer from some limitations including cost and limited serotype coverage. We have previously shown that a fusion conjugate vaccine, consisting of pneumococcal fusion protein PsaA and pneumolysoid (PdT) conjugated to a polysaccharide, results in enhanced antibody and CD4+ Th17 cell responses as well as protection against pneumococcal colonization and disease in mice. Here we applied this approach to develop a bivalent vaccine against pneumococcus and S. typhi. Two species-conserved pneumococcal antigens (SP1572 or SP2070) were fused to the nonhemolytic pneumolysoid PdT. SP1572-PdT was then conjugated to Vi polysaccharide and SP2070-PdT was conjugated to the pneumococcal cell wall polysaccharide (CWPS; also conserved). Mice immunized with this bivalent conjugate were protected against pneumococcal colonization and sepsis challenges, and made anti-Vi antibody concentrations higher by 40-fold compared to mice that received equimolar mixtures of the antigens. An enhanced killing of Vi-bearing Salmonellae in vitro was demonstrated from plasma of mice that received the fusion conjugate but not the mixture of antigens. Our results support further evaluation of this bivalent immunogen for the prevention of pneumococcal colonization and disease, and of typhoid fever.

  10. Comparative estimation of coverage between national immunization program vaccines and non-NIP vaccines in Korea.

    PubMed

    Choe, Young June; Yang, Jae Jeong; Park, Sue K; Choi, Eun Hwa; Lee, Hoan Jong

    2013-09-01

    This study aimed to describe the differences in vaccination coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to identify factors affecting the difference. Nationwide face-to-face interview-based questionnaire survey among randomly selected 4,374 participants aged 7-83 months was conducted. Vaccination coverage analyzed according to the birth cohorts, geographic areas, and socio-demographic characteristics. We found that NIP vaccines recorded higher primary vaccination coverage compared to non-NIP vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate was rotavirus vaccine (30.7%), which was introduced recently. On multivariate analysis, having a sibling were significantly associated with lower uptake of Hib vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while, older mother's age and attendance to daycare center were significantly associated with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the data suggests potential disparity in accessing non-NIP vaccines in Korea. Expansion of NIP to include non-NIP vaccines can provide better protection against the diseases through increased coverage.

  11. Sex and Gender Impact Immune Responses to Vaccines Among the Elderly.

    PubMed

    Fink, Ashley L; Klein, Sabra L

    2015-11-01

    In response to the recommended vaccines in older-aged individuals, sex differences occur in response to those that protect against influenza, tetanus, pertussis, shingles, and pneumococcal infections. The efficacy of vaccines recommended for older-aged adults is consistently greater for females than for males. Gender differences as well as biological sex differences can influence vaccine uptake, responses, and outcome in older-aged individuals, which should influence guidelines, formulations, and dosage recommendations for vaccines in the elderly.

  12. Sex and Gender Impact Immune Responses to Vaccines Among the Elderly

    PubMed Central

    Fink, Ashley L.

    2015-01-01

    In response to the recommended vaccines in older-aged individuals, sex differences occur in response to those that protect against influenza, tetanus, pertussis, shingles, and pneumococcal infections. The efficacy of vaccines recommended for older-aged adults is consistently greater for females than for males. Gender differences as well as biological sex differences can influence vaccine uptake, responses, and outcome in older-aged individuals, which should influence guidelines, formulations, and dosage recommendations for vaccines in the elderly. PMID:26525340

  13. Status of New Vaccine Introduction - Worldwide, September 2016.

    PubMed

    Loharikar, Anagha; Dumolard, Laure; Chu, Susan; Hyde, Terri; Goodman, Tracey; Mantel, Carsten

    2016-10-21

    Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries. However, with the support of global partners, including the World Health Organization (WHO) and the United Nations Children's Fund, which assist with vaccine prequalification and procurement, as well as Gavi, the Vaccine Alliance (Gavi) (4), which provides funding and shapes vaccine markets through forecasting and assurances of demand in low-income countries in exchange for lower vaccine prices, vaccines are now introduced more rapidly. Based on data compiled in the WHO Immunization Vaccines and Biologicals Database* (5), this report describes the current status of introduction of Haemophilus influenzae type b (Hib), hepatitis B, pneumococcal conjugate, rotavirus, human papillomavirus, and rubella vaccines, and the second dose of measles vaccine. As of September 2016, a total of 191 (99%) of 194 WHO member countries had introduced Hib vaccine, 190 (98%) had introduced hepatitis B vaccine, 132 (68%) had introduced pneumococcal conjugate vaccine (PCV), and 86 (44%) had introduced rotavirus vaccine into infant vaccination schedules. Human papillomavirus vaccine (HPV) had been introduced in 67 (35%) countries, primarily targeted for routine use in adolescent girls. A second dose of measles-containing vaccine (MCV2) had been introduced in 161 (83%) countries, and rubella vaccine had been introduced in 149 (77%). These efforts support the commitment outlined in the Global Vaccine Action Plan (GVAP), 2011-2020 (2), endorsed by the World Health

  14. [Vaccination: a programme for the whole life].

    PubMed

    Lang, Pierre Olivier; Michel, Jean-Pierre

    2010-11-10

    In 2010 in Switzerland, vaccine-preventable infectious diseases still cause a significant morbi-mortality, notably among old adults. While the vaccination-based prevention in the aged population has been neglected for a long time, the two European geriatrics and gerontology societies, EUGMS, IAGG-ER has recently proposed a vaccine schedule dedicated to adults aged over 60 and promote a life-course vaccination programme. To convince of the importance of such measures in Switzerland, this article: recounts the beneficial impact of vaccines on the incidence of measles, pertussis, diphtheria, tetanus as well as influenza and pneumococcal diseases; presents the burden of these infectious diseases among the population no or insufficiently immunized; demonstrates that vaccinating in the respect of a life-course vaccine programme will reduce considerably the burden of these infectious disease.

  15. 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

  16. 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;