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Sample records for heptavalent conjugate pneumococcal

  1. Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

    Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S

    2008-01-01

    Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine...... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children Hospital, Denmark 1996-2007, were retrospectively reviewed. Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children

  2. Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age

    Cesati Laura

    2007-02-01

    Full Text Available Abstract Background Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7 has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children. Methods A total of 1,571 healthy infants (910 males aged 75–105 days (median 82 days were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib and PCV-7 (n = 819 or the hexavalent vaccine alone (n = 752 at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12. Results Among the 1,555 subjects (98.9% who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group. Conclusion Our findings show the effectiveness of the simplified

  3. Current face of acute otitis media: microbiology and prevalence resulting from widespread use of heptavalent pneumococcal conjugate vaccine.

    Brunton, Stephen

    2006-01-01

    Many causes can be proposed for a change in the microbiologic makeup of a specific disease state. However, when viewed through the scope of recent events, only one is likely to be the true cause of a change in the microbiology of acute otitis media (AOM): the release and widespread use of heptavalent pneumococcal conjugate vaccine (PCV-7). The aim of this report was to review the microbiology and prevalence of AOM before and after the release and widespread use of PCV-7. For this brief review, we used a MEDLINE search to identify English-language literature related to the microbiology of AOM before and after the release of PCV-7 in 2000 in the United States (key terms: acute otitis media, AOM, Haemophilus influenzae, H influenzae, Streptococcus pneumoniae, and S pneumoniae; years: 1980-2005). Studies using tympanocentesis to identify the pathogen in recurrent or persistent AOM were examined; US studies reporting AOM microbiology before and after the release of PCV-7 in the same population were considered for the post-PCV-7 analysis. Following the release of PCV-7, a decrease in the overall rates of AOM was noted. This decrease brings into question the resultant effect on the microbiology of AOM. Our literature search revealed 2 studies that examined the microbiology of AOM before and after the release of PCV-7 in the United States. These 2 studies, conducted in dispersed geographic regions (rural Kentucky and Rochester, New York), illustrated a change in the predominant causative pathogen in AOM, from S pneumoniae to H influenzae in the population of children 7 to 24 months of age with recurrent AOM. Given the time period of the change, these shifts could be related to the release and widespread use of PCV-7. Since the 1990s, the predominant causative pathogen in recurrent AOM changed from S pneumoniae to H influenzae, possibly as a result of the release and widespread use of PCV 7. Although PCV-7 use was slowed from August 2001 to May 2003 and again from February

  4. Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

    Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S

    2008-01-01

    Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children vaccine (PCV7) into the Danish routine...... children vaccination....... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children children

  5. Effect of seven-valent pneumococcal conjugate vaccine on staphylococcus aureus colonisation in a randomised controlled trial

    van Gils, E.J.M.; Hak, E.; Veenhoven, R.H.; Rodenburg, G.D.; Bogaert, D.; Bruin, J.P.; van Alphen, L.

    2011-01-01

    Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the

  6. Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids Evaluación de la vacuna neumocócica 7-valente en la respuesta humoral de niños con SIDA Evaluation of humoral response to heptavalent pneumococcal conjugate vaccine in HIV-infected children

    Isabel de Camargo Costa

    2008-10-01

    Paulo (Sureste de Brasil, en 2002-2003. La dosis de anticuerpos IgG contra los polisacáridos de la cápsula neumocócica fue realizada por medio de ensayo inmuno enzimático (ELISA. Los anticuerpos fueron dosificados inmediatamente antes y un mes después de la aplicación de la segunda dosis de la vacuna. Se utilizaron dos criterios para evaluar la respuesta a la vacuna: títulos de anticuerpos ? 1,3 ?g/mL en la serología post-inmunización y aumento ?4 veces en los títulos de la serología post-inmunización con relación a la pre-inmunización. RESULTADOS: Para el primer criterio (?1,3 ?g/mL, 26 (65% niños obtuvieron respuesta serológica con la vacuna, 12 (30% de ellas presentaron títulos de IgG post-inmunización en niveles de por lo menos 1,3 ?g/mL para todos los serotipos. Para el segundo criterio (incremento >4 veces en los títulos para cuatro serotipos o mas, se obtuvo respuesta serológica en 15 (37,5% niños. CONCLUSIONES: La respuesta frente a la vacuna fue considerada satisfactoria, con aumento estadísticamente significativo de los títulos geométricos promedios post-vacunales con relación a los pre-vacunales para todos los serotipos estudiados.OBJECTIVE: Invasive pneumococcal disease is a major cause of death in HIV-infected children. The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children. METHODS: Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo, Brazil, between 2002 and 2003. Enzyme immunoassay (ELISA was used to measure IgG antibody titers against pneumococcus capsule. Antibodies were measured immediately before and 1 month after the second dose of the vaccine. Two response criteria were used: IgG titers >1.3 µg/mL in the post-immunization serology and an increase of at least 4-fold in post- compared to pre

  7. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko

    2008-01-01

    OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with

  8. Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina.

    Giglio, Norberto D; Cane, Alejandro D; Micone, Paula; Gentile, Angela

    2010-03-08

    Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial. To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina. A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination. Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination. From the society's perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00. The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae. The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity. Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV

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

    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...

  10. Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

    van Werkhoven, Cornelis H; Hollingsworth, Rosalind C; Huijts, Susanne M; Bolkenbaas, Marieke; Webber, Chris; Patterson, Scott; Sanders, Elisabeth A M; Bonten, Marc J M

    2016-01-01

    BACKGROUND: Herd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older

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

    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 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 (potitis 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.

  12. Nasopharyngeal Pneumococcal Colonization among Children after Pneumococcal Conjugate Vaccine Introduction

    Manoochehr Karami

    2017-08-01

    Full Text Available World Health Organization has recommended all countries to introduction of Pneumococcal Conjugate Vaccine (PCV in routine immunization schedule, especially those countries with higher rate of mortality in children. However, Islamic Republic of Iran and more than 50 other countries including Algeria, Antigua and Barbuda, Belarus, Belize, Bhutan, Bosnia and Herzegovina, Brunei Darussalam, Cabo Verde, Chad, China, Comoros, Cook Islands, Croatia, Cuba, Czech Republic, Democratic People's Republic of Korea, Dominica, Egypt, Equatorial Guinea, Estonia, Gabon, Grenada, Guinea, Haiti, India, Jamaica, Jordan, Malaysia, Maldives, Malta, Montenegro, Nauru, Poland, Romania, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Serbia, Seychelles, Slovenia, Somalia, South Sudan, Sri Lanka, Syrian Arab Republic, Tajikistan, Thailand, The former Yugoslav Republic of Macedonia, Timor-Leste, Tonga, Tunisia, Turkmenistan, Tuvalu, Ukraine, Vanuatu, and Viet Namhave not introduced PCV till April 2016.

  13. Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality

    Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M

    2014-01-01

    BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or ...

  14. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were...

  15. Pneumococcal vaccines: the impact of conjugate vaccine

    Mäkelä, P. Helena; Siber, George R; Klugman, Keith P

    2008-01-01

    ... of Streptococcus pneumoniae with Complement Proteins 83 Margaret K. Hostetter III. Clinical Disease and Epidemiology 8 Epidemiology, Diagnosis, and Treatment of Serious Pneumococcal Infections in Chi...

  16. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    Sebastien Joye

    2013-03-01

    Full Text Available 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.

  17. CLINICAL AND IMMUNOLOGICAL EFFECT OF PNEUMOCOCCAL CONJUGATED VACCINES IN IMMUNOCOMPROMISED PATIENTS

    A.A. Tarasova

    2010-01-01

    Full Text Available Invasive pneumococcal infection is the most frequent cause of death in patients with immunodeficiences. The antibiotics used previously for prevention purposes are not efficient enough due to the developing antibiotic resistance. Polysaccharide pneumococcal vaccines create short-lived immunity. The overview summarizes the experience of applying conjugated pneumococcal vaccines in patients with primary immunodeficiences, HIV infection, oncological and rheumatic diseases. Key words: pneumococcal infection, pneumococcal conjugated vaccines, children, immunosuppression. (Pediatric Pharmacology. – 2010; 7(5:18-23

  18. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

    Echániz-Avilés Irma Gabriela

    2001-01-01

    Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html

  19. Optimal serotype compositions for Pneumococcal conjugate vaccination under serotype replacement.

    Nurhonen, Markku; Auranen, Kari

    2014-02-01

    Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including

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

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Influence of the Co-Administration of Heptavalent Conjugate Vaccine PCV7-TT on the Immunological Response Elicited by VA-MENGOC-BC® and Heberpenta®-L in Rabbits.

    Espinosa-Viñals, Carlos; García-Rivera, Dagmar; Rodríguez Noda, Laura; Amador Gómez, Aylín; Nicot, Milagros; Valle, Orialys; Núñez, Juan F; Martin, Yanet; Santana, Darielys; Valdés, Yury; Vérez Bencomo, Vicente

    2017-05-01

    Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.

  2. INTERNATIONAL EXPERIENCE OF ADMINISTRATION OF PNEUMOCOCCAL CONJUGATED VACCINES: PROBLEMS, PROGRESS, PERSPECTIVES

    M.V. Fedoseenko

    2009-01-01

    Full Text Available This article presents the review of results of International conference on pneumococcal conjugated vaccines. Main results of international experience in the field of control of pneumococcal infection spreading are analyzed. Authors present modern data of clinical and economic effectiveness and safety of pneumococcal conjugated vaccine RCV-7, and describe experience of administration of vaccines of next generation – PCV-10 and PCV-13.Key words: children, pneumococcal infections, prophylaxis, vaccines.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(1:130-134

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

    Ann Lindstrand

    Full Text Available 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.To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda.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.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.About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs.

  4. Pneumococcal meningitis: epidemiological profile pre‐ and post‐introduction of the pneumococcal 10‐valent conjugate vaccine

    Tatiane E. Hirose

    2015-03-01

    Conclusion: Even after a short time of use, the 10‐valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine.

  5. Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination.

    Che, Datian; Zhou, Hua; He, Jinchun; Wu, Bin

    2014-02-07

    The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.

  6. Pneumococcal meningitis: epidemiological profile pre- and post-introduction of the pneumococcal 10-valent conjugate vaccine

    Tatiane E. Hirose

    2015-03-01

    Full Text Available Objectives: To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. Method: Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN, from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009 were compared to 134 cases from the post-vaccine period (2010-2011. Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA. Results: There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population, while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%. Conclusion: Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine. Resumo: Objetivos: Avaliar os possíveis efeitos da introdução da vacina pneumocócica conjugada 10 valente no calendário vacinal no Paraná sobre os casos de meningite pneumocócica; avaliar a distribuição dos

  7. Economic evaluation of pneumococcal conjugate vaccination in The Gambia.

    Kim, Sun-Young; Lee, Gene; Goldie, Sue J

    2010-09-03

    Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia

  8. Economic evaluation of pneumococcal conjugate vaccination in The Gambia

    Kim Sun-Young

    2010-09-01

    Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce

  9. Cost-effectiveness of pneumococcal conjugate vaccination in Croatia.

    Vučina, V Višekruna; Filipović, S Kurečić; Kožnjak, N; Stamenić, V; Clark, A D; Mounaud, B; Blau, J; Hoestlandt, C; Kaić, B

    2015-05-07

    Pneumococcus is a known cause of meningitis, pneumonia, sepsis, and acute otitis media in children and adults globally. Two new vaccines for children have the potential to prevent illness, disability, and death, but these vaccines are expensive. The Croatian Ministry of Health has considered introducing the vaccine in the past, but requires economic evidence to ensure that the limited funds available for health care will be used in the most effective way. Croatia appointed a multidisciplinary team of experts to evaluate the cost-effectiveness of introducing pneumococcal conjugate vaccination (PCV) into the national routine child immunization program. Both 10-valent and 13-valent PCV (PCV10 and PCV13) were compared to a scenario assuming no vaccination. The TRIVAC decision-support model was used to estimate cost-effectiveness over the period 2014-2033. We used national evidence on demographics, pneumococcal disease incidence and mortality, the age distribution of disease in children, health service utilization, vaccine coverage, vaccine timeliness, and serotype coverage. Vaccine effectiveness was based on evidence from the scientific literature. Detailed health care costs were not available from the Croatian Institute for Health Insurance at the time of the analysis so assumptions and World Health Organization (WHO) estimates for Croatia were used. We assumed a three-dose primary vaccination schedule, and an initial price of US$ 30 per dose for PCV10 and US$ 35 per dose for PCV13. We ran univariate sensitivity analyses and multivariate scenario analyses. Either vaccine is estimated to prevent approximately 100 hospital admissions and one death each year in children younger than five in Croatia. Compared to no vaccine, the discounted cost-effectiveness of either vaccine is estimated to be around US$ 69,000-77,000 per disability-adjusted life-years (DALYs) averted over the period 2014-2033 (from the government or societal perspective). Only two alternative scenarios

  10. Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands

    van Deursen, A. M.M.; Schurink-van't Klooster, Tessa M; Man, W. H.; van de Kassteele, J.; van Gageldonk-Lafeber, Arianne B; Bruijning-Verhagen, P. C.J.L.; de Melker, Hester E.; Sanders, E. A.M.; Knol, Mirjam J.

    2017-01-01

    Background The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the

  11. EXPERIENCE OF USE OF PNEUMOCOCCAL CONJUGATED 7-VALENT VACCINE IN SOME REGIONS OF RUSSIA

    A.A. Ruleva

    2010-01-01

    Full Text Available An experience of immunization with pneumococcal conjugated 7-valent vaccine Prevenar in 234 children under 5 years old with different state of health was analyzed. There were no any severe reactions, postvaccinal complications or local reactions to the vaccine injection. Mild and moderate postvaccinal reactions were detected in 3,4% (n = 8 of children. The vaccine can be used in children under 5 years old.Key words: children, vaccination, pneumococcal conjugated 7-valent vaccine, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:119-123

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

    Francesca Fortunato

    2015-01-01

    Full Text Available 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.

  13. From individual to herd protection with pneumococcal vaccines: the contribution of the Cuban pneumococcal conjugate vaccine implementation strategy

    Nivaldo Linares-Pérez

    2017-07-01

    Full Text Available A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.

  14. Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis

    Tinevimbo Shiri, DrPhD

    2017-01-01

    Full Text Available Summary: Background: The full extent to which childhood pneumococcal conjugate vaccines (PCV can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease. Methods: In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016, updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010. Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup. Findings: Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8–10·3 for grouped serotypes contained in the seven-valent PCV (PCV7, and 9·5 years (6·1–16·6 for the grouped six additional serotypes contained in the 13-valent PCV (PCV13 but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23 decreased at similar rates per year in adults aged 19–64 years (relative risk [RR] 0·85, 95% CrI 0·75–0·95 and 65 years and older (0·87, 0·84–0·90. However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13. Interpretation: Population childhood PCV programmes will lead, on average, to substantial protection across the whole population

  15. Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil

    Indianara Maria Grando

    2015-02-01

    Full Text Available The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009 and post-vaccination (2011-2012 periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

  16. Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy.

    Pelton, Stephen I; Dagan, Ron; Gaines, Beverly M; Klugman, Keith P; Laufer, Dagna; O'Brien, Katherine; Schmitt, Heinz J

    2003-04-02

    Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.

  17. Pneumococcal conjugate vaccine – a health priority | Zar | South ...

    Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccineserotype- specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in ...

  18. Estimating the Clinical and Economic Impact of Maintaining use of 13-valent Pneumococcal Conjugate Vaccine (PCV13) in Mexico

    Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond

    2017-01-01

    Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential heal...

  19. PHARMACOECONOMIC ASSESSMENT OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN IMMUNIZATION OF CHILDREN IN RUSSIAN FEDERATION

    ​A. V. Rudakova

    2014-01-01

    Full Text Available Aim: cost-effectiveness assessment and budget impact analysis for 13-valent pneumococcal conjugate vaccine (PCV13 in infant immunization program in Russian Federation. Materials and methods: 10 year modeling with social perspective (direct medical and indirect costs and life expectancy with discounting by 3,5% per year and population effect based on results of clinical studies, global PCV13 use and Russian epidemiological data has been established. Budget impact has been analyzed without discounting. Direct effect was assessed by influence on pneumococcal meningitis, bacteremia, pneumonia and acute otitis media (AOM incidence, population effect — by pneumococcal meningitis and hospitalized all-cause pneumonia incidence. Results: Possible PCV13 effectiveness was estimated as 76,6% for invasive pneumococcal diseases (IPD and 23,7% for hospitalized cases of AOM. Vaccination (per 100 000 vaccinated infants can prevent 13,8 lethal cases in vaccinated population and 171,1 — in unvaccinated population. Cost-effectiveness ratio for PCV13 is estimated as 32,400 rubles / LYG and 32,400 rubles / QALY. Cost of 1 lethal case prevention is 140 100 rubles, additional cost for 10 years is 111,5 rubles per child. Conclusions: PCV13 mass vaccination of infants in Russian Federation is highly cost-effective and will significantly cut expenses due to pneumococcal diseases treatment. 

  20. Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model

    Bakır Mustafa

    2012-11-01

    Full Text Available Abstract Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7. We compare the cost effectiveness of a 13-valent PCV (PCV-13 and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.

  1. A randomized study to evaluate the immunogenicity and safety of a heptavalent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, haemophilus influenzae b, and meningococcal serogroup C combination vaccine administered to infants at 2, 4 and 12 months of age.

    Thollot, Franck; Scheifele, David; Pankow-Culot, Heidemarie; Cheuvart, Brigitte; Leyssen, Maarten; Ulianov, Liliana; Miller, Jacqueline M

    2014-12-01

    The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines. In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated. Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups. The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.

  2. Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines by GC-MSD.

    Kim, John S; Laskowich, Erin R; Arumugham, Rasappa G; Kaiser, Raymond E; MacMichael, Gregory J

    2005-12-15

    A simple and sensitive gas chromatographic method was designed for quantitative analysis of Streptococcus pneumoniae capsular polysaccharides, activated polysaccharides, and polysaccharide conjugates. Pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharide or conjugate were subjected to methanolysis in 3N hydrochloric acid in methanol followed by re-N-acetylation and trimethylsilylation. Derivatized samples were chromatographed and detected using gas chromatography with mass selective detector. Gas chromatographic results were compared with colorimetric values with agreement of 92 to 123% over the range of all samples tested. Monosaccharides released during methanolysis included hexoses, uronic acids, 6-deoxy-hexoses, amino sugars, and alditols. Quantitative recovery of monosaccharides was achieved for all serotypes by the use of a single methanolysis, derivatization, and chromatography procedure. Response factors generated from authentic monosaccharide standards were used for quantitation of pneumococcal polysaccharides and conjugates with confirmation of peak assignments by retention time and mass spectral analysis. This method allows saccharide quantitation in multivalent pneumococcal vaccine intermediates and final drug products with low-level detection (10 pg) and peak purity.

  3. EXPERIENCE OF APPLICATION AND SAFETY ASSESSMENT OF THE 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN UNDER-5 CHILDREN

    M. V. Fedoseenko

    2014-01-01

    Full Text Available Compulsory use of the 7-valent pneumococcal conjugate vaccine in the framework of national pediatric immunization schedules of the developed countries resulted in significant decrease in the prevalence of the pneumococcal infections induced by the vaccinal serotypes. However, a growth in prevalence of the pneumonia and acute otitis media caused by non-vaccinal strains has also been observed. This required introduction of a new 13-valent pneumococcal conjugate vaccine with a wider range of pneumococcal population coverage. The experience of application accumulated in various countries (2010 onwards and results of the authors’ observations indicate high safety of the 13-valent pneumococcal conjugate vaccine for both healthy under-5 children and patients with various medical issues. The article presents results of the 13-valent pneumococcal conjugate vaccination tolerance assessment. The study involved 110 children from 2 months to 5 years of age. In most cases immunization concurred with other pediatric vaccines. The incidence of local reactions in vaccinated children did not exceed 33%, of generalized reactions – 11%. The authors observed a comparable incidence of side reactions in both virtually healthy children and children with various medical issues.

  4. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

    Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard

    2015-01-01

    BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...

  5. Cost-effectiveness analysis of a universal vaccination programme with the 7-valent pneumococcal conjugate vaccine (PCV-7) in Sweden

    Bergman, Annika; Hjelmgren, Jonas; Ortqvist, Ake

    2008-01-01

    The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs...... of pneumococcal septicaemia among adults. The incremental cost per QALY and LY gained was estimated to Euro 29,200 and Euro 51,400, respectively. When herd immunity was accounted for, the cost per QALYand LY gained was estimated to Euro 5500 and Euro 6600, respectively. Thus, the health benefits of a national...... and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show...

  6. The cost-effectiveness of a 13-valent pneumococcal conjugate vaccination for infants in England.

    van Hoek, Albert Jan; Choi, Yoon Hong; Trotter, Caroline; Miller, Elizabeth; Jit, Mark

    2012-11-26

    In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time. To investigate the cost effectiveness of the introduction of PCV-13. Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether. Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30 years, vaccine price of £49.60 a dose+£7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%. To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. [Bacteremic pneumococcal pneumonia].

    Pineda Solas, V; Pérez Benito, A; Domingo Puiggros, M; Larramona Carrera, H; Segura Porta, F; Fontanals Aymerich, D

    2002-11-01

    Streptococcus pneumonia is the most common bacterial cause of community-acquired pneumonia in children. The reference standard for etiological diagnosis is isolation of S. pneumoniae from blood Since the advent of conjugate vaccines, disease caused by this organism can now be prevented. Many studies have been performed of the global incidence of invasive pneumococcal infections and of pneumococcal meningitis but few studies investigated bacteremic pneumococcal pneumonia and its complications in children. To determine the incidence, patient characteristics, clinical signs, laboratory data, percentage and days of hospitalization, response to antibiotic treatment, antibiotic resistance, complications and causal serogroups of bacteremic pneumococcal pneumonia in our environment in order to estimate requirements for systematic vaccination programs. From January 1990 to May 2001, data on all pediatric cases of invasive pneumococcal infections diagnosed in our hospital were collected. Several characteristics of patients with bacteremic pneumococcal pneumonia were analyzed. Bacteremic pneumococcal pneumonia was diagnosed in patients with positive blood or pleural fluid cultures for S. pneumoniae and radiographically evident pulmonary infiltrate. The incidence of both types of pneumonia were determined according to population census data. All S. pneumonia strains were sent to the Pneumococci Reference Laboratory of the Instituto Carlos III in Madrid for serotyping. We estimated the serotype coverage of the pneumococcal 7-valent conjugate vaccine according to the serotypes included in this vaccine and their distribution. Forty cases of bacteremic pneumococcal pneumonia were diagnosed, yielding an incidence of 17,10 and 5 cases per 10(5) children aged less than 2, 4 and 15 years old respectively. The mean age was 50 months and 43% were aged less than 4 years. Peaks occurred in January, March, April and May. A total of 77.5% of the patients were admitted to hospital and the

  8. VACCINATION OF PREMATURE INFANTS AND CHILDREN WITH CONGENITAL HEART DISEASE IN IRKUTSK USING CONJUGATED PNEUMOCOCCAL VACCINES

    S. V. Il'ina

    2013-01-01

    Full Text Available Study aim: analyzing the results of pneumococcal infection vaccination conducted to reduce infantile morbidity and mortality in 2011-2012 at the expenses of the Irkutsk municipal budget. Patients and methods. Vaccination using the 7- and 13-valent pneumococcal conjugated vaccine was conducted for more than 700 risk group children: premature infants, children with congenital heart diseases or bronchopulmonary dysplasia from 2 months to 2 years of age. 193 vaccinated children had been observed for 1.5 years. 30% of premature infants and 46% of children with congenital heart diseases were vaccinated using the PCV7/PCV13 vaccine at the age of 2-6 months, 52 and 40% - at the age of 7-11 months, accordingly. The PCV7/PCV13 vaccine was administered together with other vaccines of the national preventive vaccination calendar in 65% of cases. Results. Rate of general post-vaccinal reactions (body temperature increase from 37.6 to 38.0oC – 4%; no local reactions were registered. No other unfavorable phenomena were noted in the post-vaccinal period. No cases of pneumonia, meningitis, acute otitis media and bronchoobstructive syndrome were registered within the observation period. Conclusions: pneumococcal infection vaccination of premature infants with congenital heart diseases and bronchopulmonary dysplasia conducted in Irkutsk proved high efficacy and safety of the used vaccine – PCV7/PCV13. 

  9. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.

    Daniel R Feikin

    Full Text Available 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. These findings may not

  10. Invasive pneumococcal disease : Clinical outcomes and patient characteristics 2-6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period, the Netherlands

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

    2016-01-01

    Background Implementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical

  11. Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

    Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark

    2012-01-01

    Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, −15%; range, +14% to −24%) and continued to decline afterward (mean, −19%; range, +7% to −48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134

  12. Adverse reactions to simultaneous influenza and pneumococcal conjugate vaccinations in children : randomized double-blind controlled trial

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Smulders, Sara; Hoes, Arno W; Hak, Eelko

    In a randomized double-blind controlled trial, the safety was assessed of simultaneous administration of influenza and pneumococcal conjugate vaccines in children with previous physician-diagnosed respiratory tract infections. In total, 579 children aged 18-72 months were assigned to receive

  13. The effect of immunization with pneumococcal conjugated vaccines on Streptococcus pneumoniae resistance patterns in acute otitis media

    Tal Marom

    2017-10-01

    Full Text Available Following the introduction of 7- and 13-pneumococcal conjugate vaccines (PCVs in Israel, we demonstrated that within Streptococcus pneumoniae (Sp positive middle ear cultures, obtained from young children with severe acute otitis media (AOM episodes, there were more penicillin-susceptible and less multi-drug resistant Sp isolates in PCV immunized children.

  14. Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil

    Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra

    2017-01-01

    Background: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used t...

  15. Progress towards meningitis prevention in the conjugate vaccines era

    Cristina Aparecida Borges Laval

    Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

  16. Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

    Stubbs Liz

    2009-08-01

    Full Text Available Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months living in 29 communities in 2003 and 818 children (mean age 35 months in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL strains (15% overall was detected in serotypes (descending order 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL strains (5% overall, was detected in serotypes (descending order 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80% in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined

  17. Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

    Fletcher, Mark A.; Fritzell, Bernard

    2012-01-01

    Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

  18. [Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era].

    Pumarola, Felix; Salamanca de la Cueva, Ignacio; Sistiaga-Hernando, Alessandra; García-Corbeira, Pilar; Moraga-Llop, Fernando A; Cardelús, Sara; McCoig, Cynthia; Gómez Martínez, Justo Ramón; Rosell Ferrer, Rosa; Iniesta Turpin, Jesús; Devadiga, Raghavendra

    2016-11-01

    Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years. Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425). Middle-ear-fluid samples were collected by tympanocentesis or spontaneous otorrhea and cultured for bacterial identification. Culture-negative samples were further analyzed using polymerase chain reaction (PCR). Of 125 confirmed AOM episodes in 124 children, 117 were analyzed (median age: 17 months (range: 3-35); eight AOM episodes were excluded from analyses. Overall, 69% (81/117) episodes were combined culture- and PCR-positive for ≥1 bacterial pathogen; 44% (52/117) and 39% (46/117) were positive for Haemophilus influenzae (Hi) and Streptococcus pneumoniae (Spn), respectively. 77 of 117 episodes were cultured for ≥1 bacteria, of which 63 were culture-positive; most commonly Spn (24/77; 31%) and Hi (32/77; 42%). PCR on culture-negative episodes identified 48% Hi- and 55% Spn-positive episodes. The most common Spn serotype was 19F (4/24; 17%) followed by 19A (3/24; 13%); all Hi-positive episodes were non-typeable (NTHi). 81/117 AOM episodes (69%) occurred in children who had received ≥1 pneumococcal vaccine dose. NTHi and Spn were the main etiological agents for AOM in Spain. Impact of pneumococcal vaccination on AOM requires further evaluation in Spain, after higher vaccination coverage rate is reached. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Economic impact of pneumococcal conjugate vaccination in Brazil, Chile, and Uruguay.

    Constenla, Dagna O

    2008-08-01

    To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7) in Brazil, Chile, and Uruguay. A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. At the rate of diphtheria-tetanus-pertussis (DTP) vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884,841 disability-adjusted life years (DALYs) yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil) to US$ 2019 (Chile). At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125,050,497 versus US$ 153,965,333), making it cost effective and cost-saving. The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccinatfon at the current price is affordable to these countries.

  20. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico

    Maricruz Gutiérrez Brito

    2013-06-01

    Full Text Available OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13 after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.

  1. Pediatric invasive pneumococcal disease caused by vaccine serotypes following the introduction of conjugate vaccination in Denmark

    Harboe, Zitta B; Valentiner-Branth, Palle; Ingels, Helene

    2013-01-01

    A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction...... of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one...... of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F...

  2. Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules.

    Leach, Amanda Jane; Wigger, Christine; Andrews, Ross; Chatfield, Mark; Smith-Vaughan, Heidi; Morris, Peter Stanley

    2014-08-11

    In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p = 0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD -12% [95% CI -19 to -5] p = 0.0004], and TMP in 17% versus 14% (RD -3% [95% CI -8 to 2] p = 0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio = 0.6 [95% CI 0.4 to 0.8] p = 0.001). Additional children in the household were a risk factor for OM (OR = 2.4 [95% CI 2 to 4] p = 0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than

  3. Impact of the introduction of the pneumococcal conjugate vaccine in the Brazilian routine childhood national immunization program.

    Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard

    2016-05-27

    Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

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

    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.

  5. Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

    Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa

    2018-05-01

    Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

  6. Post-introduction economic evaluation of pneumococcal conjugate vaccination in Ecuador, Honduras, and Paraguay

    Dagna O. Constenla

    Full Text Available OBJECTIVE:A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV programs in Ecuador, Honduras, and Paraguay from the societal perspective. METHODS: Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. RESULTS: Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY averted for the 10-valent PCV (PCV10 and the 13-valet PCV (PCV13 ranged from US$ 796 (Honduras to US$ 1 340 (Ecuador and from US$ 691 (Honduras to US$ 1 166 (Ecuador respectively. At a reduced price (US$ 7 per dose, the cost per DALY averted ranged from US$ 327 (Honduras to US$ 528 (Ecuador and from US$ 281 (Honduras to US$ 456 (Ecuador for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. CONCLUSIONS: The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.

  7. Post-introduction economic evaluation of pneumococcal conjugate vaccination in Ecuador, Honduras, and Paraguay.

    Constenla, Dagna O

    2015-11-01

    A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV) programs in Ecuador, Honduras, and Paraguay from the societal perspective. Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY) averted for the 10-valent PCV (PCV10) and the 13-valet PCV (PCV13) ranged from US$ 796 (Honduras) to US$ 1 340 (Ecuador) and from US$ 691 (Honduras) to US$ 1 166 (Ecuador) respectively. At a reduced price (US$ 7 per dose), the cost per DALY averted ranged from US$ 327 (Honduras) to US$ 528 (Ecuador) and from US$ 281 (Honduras) to US$ 456 (Ecuador) for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.

  8. Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia.

    Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark

    2017-02-15

    The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia. The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price. The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025. Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains

  9. Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada

    Earnshaw Stephanie R

    2012-04-01

    Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public

  10. Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan.

    Cho, Ying-Chun; Chiu, Nan-Chang; Lu, Chun-Yi; Huang, Daniel Tsung-Ning; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Chi, Hsin

    2017-12-01

    After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.

  11. 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

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

    2004-01-01

    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

  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

    May, J.C. E-mail: may@cber.fda.gov; Rey, L. E-mail: louis.rey@bluewin.ch; Lee, C.-J.; Arciniega, Juan

    2004-10-01

    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. No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.

    Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K

    2016-06-01

    A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

    Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

    2017-09-01

    Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody

  15. Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

    Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf

    2017-04-01

    In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

  16. Beyond new vaccine introduction: the uptake of pneumococcal conjugate vaccine in the African Region.

    Olayinka, Folake; Ewald, Leah; Steinglass, Robert

    2017-01-01

    The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.

  17. Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

    Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H

    2016-09-07

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged Peru. Copyright © 2016. Published by Elsevier Ltd.

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

    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 (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

  19. Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation.

    dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B

    2013-12-09

    The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination

  20. Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly

    Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica

    2014-01-01

    Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted

  1. Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools.

    Chaiyakunapruk, Nathorn; Somkrua, Ratchadaporn; Hutubessy, Raymond; Henao, Ana Maria; Hombach, Joachim; Melegaro, Alessia; Edmunds, John W; Beutels, Philippe

    2011-05-12

    Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example

  2. Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

    Grant A Mackenzie

    2012-01-01

    Full Text Available Routine use of pneumococcal conjugate vaccines (PCVs in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

  3. Cost-effectiveness of pneumococcal conjugate vaccination in the prevention of child mortality: an international economic analysis.

    Sinha, Anushua; Levine, Orin; Knoll, Maria D; Muhib, Farzana; Lieu, Tracy A

    2007-02-03

    Routine vaccination of infants against Streptococcus pneumoniae (pneumococcus) needs substantial investment by governments and charitable organisations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate these data into an economic analysis of pneumococcal vaccination of infants in countries eligible for financial support from the Global Alliance for Vaccines & Immunization (GAVI). We constructed a decision analysis model to compare pneumococcal vaccination of infants aged 6, 10, and 14 weeks with no vaccination in the 72 countries that were eligible as of 2005. We used published and unpublished data to estimate child mortality, effectiveness of pneumococcal conjugate vaccine, and immunisation rates. Pneumococcal vaccination at the rate of diptheria-tetanus-pertussis vaccine coverage was projected to prevent 262,000 deaths per year (7%) in children aged 3-29 months in the 72 developing countries studied, thus averting 8.34 million disability-adjusted life years (DALYs) yearly. If every child could be reached, up to 407,000 deaths per year would be prevented. At a vaccine cost of International 5 dollars per dose, vaccination would have a net cost of 838 million dollars, a cost of 100 dollars per DALY averted. Vaccination at this price was projected to be highly cost-effective in 68 of 72 countries when each country's per head gross domestic product per DALY averted was used as a benchmark. At a vaccine cost of between 1 dollar and 5 dollars per dose, purchase and accelerated uptake of pneumococcal vaccine in the world's poorest countries is projected to substantially reduce childhood mortality and to be highly cost-effective.

  4. Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.

    Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R

    2016-11-21

    Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse

  5. Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine.

    Silvio D Brugger

    2010-07-01

    Full Text Available Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7.Nasopharyngeal swabs (n 1120 were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP analysis. Serotypes were identified by agglutination, multiplex PCR and microarray.Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38. Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status.Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.

  6. Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ▿

    Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

    2010-01-01

    The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all thr...

  7. A nationwide study on the impact of pneumococcal conjugate vaccination on antibiotic use and ventilation tube insertion in Denmark 2000-2014

    Howitz, Michael Frantz; Harboe, Zitta Barrella; Ingels, Helene

    2017-01-01

    Introduction of Pneumococcal Conjugated Vaccines (PCV) in national immunization programs have been successful in reducing the number of invasive and lower respiratory pneumococcal infections. The impact of the vaccines on upper respiratory infections caused by pneumococci is less clear although...... these account for most pneumococcal infections. In this study, we used likely proxies for respiratory infections in children, such as antibiotic use and ventilation tube insertions (VTI), to estimate the impact of the vaccine on a national level. The study was designed as a population-based retrospective...... reversed to near year 2000 levels after the introduction of PCV. This indicates that implementation of pneumococcal vaccines in the Childhood Vaccination Programme has likely reduced the incidence of upper respiratory diseases due to pneumococci in Denmark....

  8. Impact of protein D-containing pneumococcal conjugate vaccines on non-typeable Haemophilus influenzae acute otitis media and carriage.

    Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas

    2017-07-01

    Protein D-containing vaccines may decrease acute otitis media (AOM) burden and nasopharyngeal carriage of non-typeable Haemophilus influenzae (NTHi). Protein D-containing pneumococcal conjugate vaccine PHiD-CV (Synflorix, GSK Vaccines) elicits robust immune responses against protein D. However, the phase III Clinical Otitis Media and PneumoniA Study (COMPAS), assessing PHiD-CV efficacy against various pneumococcal diseases, was not powered to demonstrate efficacy against NTHi; only trends of protective efficacy against NTHi AOM in children were shown. Areas covered: This review aims to consider all evidence available to date from pre-clinical and clinical phase III studies together with further evidence emerging from post-marketing studies since PHiD-CV has been introduced into routine clinical practice worldwide, to better describe the clinical utility of protein D in preventing AOM due to NTHi and its impact on NTHi nasopharyngeal carriage. Expert commentary: Protein D is an effective carrier protein in conjugate vaccines and evidence gathered from pre-clinical, clinical and observational studies suggest that it also elicits immune response that can help to reduce the burden of AOM due to NTHi. There remains a need to develop improved vaccines for prevention of NTHi disease, which could be achieved by combining protein D with other antigens.

  9. The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

    Azarian, Taj; Grant, Lindsay R; Arnold, Brian J; Hammitt, Laura L; Reid, Raymond; Santosham, Mathuram; Weatherholtz, Robert; Goklish, Novalene; Thompson, Claudette M; Bentley, Stephen D; O'Brien, Katherine L; Hanage, William P; Lipsitch, Marc

    2018-04-01

    In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998-2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998-2000) than the preceding period (2006-2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal

  10. The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome

    Hammitt, Laura L.; Santosham, Mathuram; Goklish, Novalene; Thompson, Claudette M.; Bentley, Stephen D.; O’Brien, Katherine L.

    2018-01-01

    In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998–2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998–2000) than the preceding period (2006–2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein

  11. The effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion at 7 and 24 months of age.

    Straetemans, M.; Palmu, A.; Auranen, K.; Zielhuis, G.A.; Kilpi, T.

    2003-01-01

    OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. METHODS: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled

  12. Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

    Bosch, Astrid A T M; van Houten, Marlies A.; Bruin, Jacob P.; Wijmenga-Monsuur, Alienke J.; Trzciński, Krzysztof; Bogaert, Debby; Rots, Nynke Y.; Sanders, Elisabeth A M

    2016-01-01

    After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents.

  13. Differential B-cell memory around the 11-month booster in children vaccinated with a 10- or 13-valent pneumococcal conjugate vaccine

    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

  14. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    2010-08-11

    ... very sick. It causes blood infections, pneumonia, and meningitis, mostly in young children. (Meningitis... have many causes, and PCV13 only works against the types of pneumococcal bacteria targeted by the... the parent or legal representative in the case of a child) receiving vaccines covered under the...

  15. Pneumococcal conjugate vaccination at birth in a high-risk setting: no evidence for neonatal T-cell tolerance.

    van den Biggelaar, Anita H J; Pomat, William; Bosco, Anthony; Phuanukoonnon, Suparat; Devitt, Catherine J; Nadal-Sims, Marie A; Siba, Peter M; Richmond, Peter C; Lehmann, Deborah; Holt, Patrick G

    2011-07-26

    Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Retrospective economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Australia: Uncertain herd impact on pneumonia critical.

    Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G

    2016-01-12

    Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV

  17. The effect of pneumococcal conjugate vaccines on incidence and microbiology associated with complicated acute otitis media.

    Laursen, B B; Danstrup, C S; Hoffmann, S; Nørskov-Lauritsen, N; Christensen, A L B; Ovesen, T

    2017-10-01

    The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM). A retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared. A total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified. The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21% in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12% in the PCV13-era. The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12% to 38% and 44%, respectively. In the M + AM group, SP decreased to 10% in the PCV13-era compared with 44% in the pre-vaccine era and 41% in the PCV7-era. An increase in GAS from 15% in the pre-vaccine era and PCV7-era to 30% in the PCV13-era was observed. The "no growth" percentage increased from 13% in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era. Introduction of PCV7 and PCV13 has been associated with an overall

  18. Influence of pneumococcal conjugate vaccines on acute otitis media in Japan.

    Sasaki, Atsushi; Kunimoto, Masaru; Takeno, Sachio; Sumiya, Takahiro; Ishino, Takashi; Sugino, Hirotoshi; Hirakawa, Katsuhiro

    2017-11-01

    This study investigated: (i) changes in the incidence of acute otitis media (AOM) following introduction of public funding for free inoculation with 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) and (ii) changes in the rate of myringotomies for AOM (MyfA) in children 1year following the publication of the first edition of the clinical practice guidelines for the diagnosis and management of AOM in children in Japan. PCV7 was launched on the Japanese market in 2010 and gained public funding in 2011. PCV7 was replaced with PCV13 in November 2013. Using the Japan Medical Data Center Claims Database, an 11-year study conducted between January 2005 and December 2015 investigated the decline in the incidence of visits to medical institutions (VtMI) due to all-cause AOM in children <15years. The rate of MyfA from January 2007 to December 2015was also investigated and changes before and after introduction of public funding for PCV7 (pfPCV7) and PCV13 (pfPCV13) for children were examined. Statistical data for the age group between 10 years and <15years served as the control. An analysis was conducted to examine changes for each age group, from infants that had received PCVs to children <5years. Statistical analysis was performed using the chi-square test and Ryan's multiple comparison tests. Ryan's multiple comparison tests were applied at a 5% level of significance. Due to significant changes in the guidelines on the indications for myringotomy introduced in 2013, statistical analysis of the rate of MyfA was limited to the pre- and post-PCV7 period. After introduction of pfPCV7 and pfPCV13, no significant suppression of the incidence of VtMI was observed in any age group. There was a gradual decline in the rate of MyfA after 2011. Compared to the control group, significant differences in all age groups from infants to children <5years were observed (p<0.009, chi-square test). Within 2 years after the introduction of PCV7, a significant

  19. Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil

    Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra

    2017-01-01

    Background Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used...... to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries. Methods We evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle......-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine...

  20. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  1. Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial.

    William S Pomat

    Full Text Available Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7 given in a 0-1-2-month (neonatal schedule with that of the routine 1-2-3-month (infant schedule.We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV at age 9 months. Serotype-specific serum IgG for PCV7 (VT serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs and proportions with concentration ≥ 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001 and 9V (p<0.05 and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001 at age 2 months in the neonatal (one month post-dose2 PCV7 than in the infant group (one month post-dose1 PCV7. PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.ClinicalTrials.gov NCT00219401.

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

    Albert Jan van Hoek

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

  3. Estimating the Clinical and Economic Impact of Maintaining use of 13-valent Pneumococcal Conjugate Vaccine (PCV13) in Mexico

    Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond

    2017-01-01

    Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential health and economic implications of switching from PCV13 to PCV10 in Mexico. Methods A decision-analytic model was developed to estimate public health and economic impact of maintaining PCV13 compared with switching to PCV10 in Mexico. Disease incidence at time of potential switch for invasive pneumococcal disease (IPD), pneumonia (PNE) and acute otitis media (AOM) was obtained from Dirección General de Epidemiología and the published literature. Historical data was used to estimate IPD trends under different infant vaccine pressures and the model forecasted disease across the population. For each vaccination program, health outcomes and associated health-care costs were estimated. Costs, utility weights, and risk of disease-specific complications were derived from published sources. Results In the base case, continued use of PCV13 would result in significantly fewer cases of pneumococcal disease than switching to PCV10 in Mexico (See Table 1). Despite a higher vaccine cost, PCV13 was cost-saving compared with PCV10 in the base case and across a number of scenarios evaluated. Table 1: Total cases and costs associated with maintaining use of PCV13 vs. switching to PCV10 in Mexico over a 10 year period PCV13 PCV10 Difference IPD 16,808 17,248 −440 AOM 7,023,448 7,245,446 −221,998 PNE 1,743,115 1,831,936 −88,821 Deaths 19,457 19,867 −410 Total QALYs 864,069,669 864,068,101 1,568 Total Cost $258,353,508,707 $264,927,566,637 −$6,574,057,930 ICER PCV13 Dominant Costs are

  4. Population snapshot of Streptococcus pneumoniae causing invasive disease in South Africa prior to introduction of pneumococcal conjugate vaccines.

    Kedibone M Ndlangisa

    Full Text Available We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD prior to routine use of pneumococcal conjugate vaccines (PCV in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60% from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ≥5 years was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC 217, 98% of all serotype 1] and 14 [CC230, 43%], some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]. In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively. Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12 and 64% (9/14 of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction.

  5. Choosing between 7-, 10- and 13-valent pneumococcal conjugate vaccines in childhood: a review of economic evaluations (2006-2014).

    Wu, David Bin-Chia; Chaiyakunapruk, Nathorn; Chong, Huey-Yi; Beutels, Philippe

    2015-03-30

    Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch. This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006. We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies. Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study. A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer. Copyright © 2015 Elsevier

  6. Using an Inpatient Quality Improvement Curriculum for Internal Medicine Residents to Improve Pneumococcal Conjugate Vaccine Administration Rates.

    Jolin, Jonathan; van Aalst, Robertus; Volpp, Bryan; Taylor, Thomas; Cohen, Emily

    2018-06-01

    Pneumococcal infections are an important source of morbidity and mortality in older adults and persons with compromised immune systems. New recommendations from the Advisory Committee on Immunization Practices (ACIP) became available September 2014, which included recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13). A study was conducted to increase the PCV13 vaccination rates of hospitalized patients at the White River Junction Veterans Affairs Medical Center (White River Junction, Vermont) through the use of a resident-driven quality improvement (QI) project. From December 2014 through April 2016, 16 internal medicine inpatient residents addressed inpatient PCV13 vaccination rates by participating in the facility's QI curriculum. Eight Plan-Do-Study-Act cycles were used, including discharge template editing, electronic reminders, and the discovery of a vaccination administration documentation error in the record through data validation. The measure was the monthly percentage of patients who received PCV13 vaccination (vaccination completion rate) of those discharged from the hospital medicine service who were due for PCV13 vaccination. The percentage of veterans discharged with an up-to-date PCV13 vaccination on discharge increased from approximately 30% to 87% and was sustained. Despite being driven by many different residents, this project demonstrates that continuous improvement can be achieved through a structured and iterative process while providing active learning of core QI concepts to residents. It also displays a method in which new guidelines can be incorporated into practice in an effective manner. Finally, this project is an example of how resident-driven data validation can lead to further improvement. Published by Elsevier Inc.

  7. Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.

    Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel

    2017-09-12

    Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd

  8. Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

    Diez-Domingo, Javier; Gurtman, Alejandra; Bernaola, Enrique; Gimenez-Sanchez, Francisco; Martinon-Torres, Federico; Pineda-Solas, Valentin; Delgado, Alfonso; Infante-Marquez, Pilar; Liang, John Z; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2013-11-04

    Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing

  9. Nasopharyngeal carriage of Streptococcus pneumoniae among HIV-infected and -uninfected children <5 years of age before introduction of pneumococcal conjugate vaccine in Mozambique.

    Jennifer R Verani

    Full Text Available Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south, Nampula (urban-north, and Manhiça (rural-south. We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727, with similar prevalences among HIV-infected (81.5%, 339/416 and HIV-uninfected (79.1%, 246/311 children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123, Nampula (83.7%, 82/98, Manhiça (84.6%, 165/195. Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%, 23F (13.1%, 6A (9.2%, 6B (6.2% and 19A (5.2% were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268 of children were colonized with a PCV10 serotype and 49.7% (n = 361 with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in

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

    Starla Hayward

    2016-04-01

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

  11. [Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

    Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

    2009-06-01

    To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

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

    Francesca Lombardi

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

  13. Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

    Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S

    2017-01-01

    Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal

  14. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States.

    Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard

    2007-11-01

    The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.

  15. Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study.

    Stefan Flasche

    2011-04-01

    Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

  16. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered to older infants and children naïve to pneumococcal vaccination.

    Wysocki, Jacek; Brzostek, Jerzy; Szymański, Henryk; Tetiurka, Bogusław; Toporowska-Kowalska, Ewa; Wasowska-Królikowska, Krystyna; Sarkozy, Denise A; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2015-03-30

    Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children vaccine (PCV13) has been developed and approved in many countries worldwide. Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to vaccine doses only; and Group 3 (aged 24 to vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination. Copyright © 2015. Published by Elsevier Ltd.

  17. Meningitis - pneumococcal

    Pneumococcal meningitis; Pneumococcus - meningitis ... Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the ...

  18. Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) in patients with untreated Smoldering Multiple Myeloma (SMM): A pilot study.

    Bahuaud, Mathilde; Bodilis, Hélène; Malphettes, Marion; Maugard Landre, Anaïs; Matondo, Caroline; Bouscary, Didier; Batteux, Frédéric; Launay, Odile; Fermand, Jean-Paul

    2017-11-01

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month. At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination. Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.

  19. Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13 in patients with untreated Smoldering Multiple Myeloma (SMM: A pilot study

    Mathilde Bahuaud

    2017-11-01

    Full Text Available Smoldering multiple myeloma (SMM is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM, a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM pre and post routine-vaccination with PCV13.Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA. The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month.At 1 month post vaccination, 12 patients (60% were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total of the 12 responders had persistent immunity, and only 2 (10% of total at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination.Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection. Keywords: Immunology, Vaccines, Infectious disease

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

    Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23) For children Administer PCV13 ...

  1. Pneumonia Prevention during a Humanitarian Emergency: Cost-effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine and Pneumococcal Conjugate Vaccine in Somalia.

    Gargano, Lisa M; Hajjeh, Rana; Cookson, Susan T

    2015-08-01

    Pneumonia is a leading cause of death among children less than five years old during humanitarian emergencies. Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae are the leading causes of bacterial pneumonia. Vaccines for both of these pathogens are available to prevent pneumonia. Problem This study describes an economic analysis from a publicly funded health care system perspective performed on a birth cohort in Somalia, a country that has experienced a protracted humanitarian emergency. An impact and cost-effectiveness analysis was performed comparing: no vaccine, Hib vaccine only, pneumococcal conjugate vaccine 10 (PCV10) only, and both together administered through supplemental immunization activities (SIAs). The main summary measure was the incremental cost per disability-adjusted life-years (DALYs) averted. One-way sensitivity analysis was conducted for uncertainty in parameter values. Each SIA would avert a substantial number of cases and deaths. Compared with no vaccine, the DALYs averted by two SIAs for two doses of Hib vaccine was US $202.93 (lower and upper limits: $121.80-$623.52), two doses of PCV10 was US $161.51 ($107.24-$227.21), and two doses of both vaccines was US $152.42 ($101.20-$214.42). Variables that influenced the cost-effectiveness for each strategy most substantially were vaccine effectiveness, case fatality rates (CFRs), and disease burden. The World Health Organization (WHO) defines a cost-effective intervention as costing one to three times the per capita gross domestic product (GDP; in 2011, for Somalia=US $112). Based on the presented model, Hib vaccine alone, PCV10 alone, or Hib vaccine and PCV10 given together in SIAs are cost-effective interventions in Somalia. The WHO/Strategic Advisory Group of Experts decision-making factors for vaccine deployment appear to have all been met: the disease burden is large, the vaccine-related risk is low, prevention in this setting is more feasible than treatment, the vaccine

  2. Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

    Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

    2016-01-01

    Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and

  3. General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines.

    Leach, Amanda J; Wigger, Christine; Beissbarth, Jemima; Woltring, Donna; Andrews, Ross; Chatfield, Mark D; Smith-Vaughan, Heidi; Morris, Peter S

    2016-07-01

    This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. The general health, particularly ear health, of little children

  4. Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.

    Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert

    2017-07-01

    : Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015. We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA). A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P  vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination. Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the

  5. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines Al encuentro del reto: prevención de la enfermedad neumocócica con vacunas conjugadas

    Irma Gabriela Echániz-Avilés

    2001-08-01

    Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.htmlStreptococcus pneumoniae es uno de los principales agentes causantes de enfermedades invasoras y no invasoras en la población pediátrica y sigue representando uno de los principales problemas de salud pública a nivel mundial. La incidencia creciente de cepas resistentes a diversos antimicrobianos ha complicado el tratamiento y manejo de varias de las manifestaciones de la enfermedad neumocócica. Con éstas consideraciones, la mejor estrategia de manejo es la prevención de éstas enfermedades a través de la vacunación. A pesar de que se han estudiado diversas vacunas neumocócicas conjugadas en niños, solo una

  6. Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine

    Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise

    2009-01-01

    BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy....... RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77...

  7. Serotype distribution in non-bacteremic pneumococcal pneumonia

    Benfield, Thomas Lars Vibe; Skovgaard, Marlene; Schønheyder, Henrik Carl

    2013-01-01

    There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP).......There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP)....

  8. Changes in the incidence of pneumonia, bacterial meningitis, and infant mortality 5 years following introduction of the 13-valent pneumococcal conjugate vaccine in a "3+0" schedule.

    Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick

    2017-01-01

    Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time. The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.

  9. ASSESSMENT OF TOLERABILITY OF PNEUMOCOCCAL CONJUGATE VACCINE AND THE INFLUENCE OF THE VACCINATION ON THE INCIDENCE OF RESPIRATORY INFECTIONS IN CHILDREN DURING THE FIRST FIVE YEARS OF LIFE IN THE SAKHA REPUBLIC (YAKUTIA

    N.V. Savvina

    2011-01-01

    Full Text Available One of the most frequent etiology agent of upper respiratory tract infection is pneumococcus. Most susceptible to this infection are children under 5 years old. It is known that the only effective prevention of pneumococcal infections is a specific immunoprophylaxis. Authors represent their own experience of vaccination for the child population at risk. The analysis of the effectiveness of 7-valent conjugate pneumococcal vaccine in 596 children under 5 years old is demonstrated. The immunization is revealed low reactogeni city of vaccine and evident clinical effect. Thus, this vaccine may be recommended for inclusion in a regional immunization schedule in Republic of Sakha (Yakutia.Key words: children, pneumococcal infection, vaccine prophylaxis.

  10. Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV in young Latin American children: A double-blind randomized controlled trial.

    Miguel W Tregnaghi

    2014-06-01

    Full Text Available 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.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, 67.1% (95% CI: 17.0%, 86.9% against vaccine serotype clinically

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

    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

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

    Alienke J Wijmenga-Monsuur

    Full Text Available 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.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.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.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 important for PCV evaluation. How

  13. Safety of 13-valent pneumococcal conjugate vaccine in infants and children: meta-analysis of 13 clinical trials in 9 countries.

    Thompson, Allison; Gurtman, Alejandra; Patterson, Scott; Juergens, Christine; Laudat, France; Emini, Emilio A; Gruber, William C; Scott, Daniel A

    2013-10-25

    Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13. To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers. A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination. Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed. PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience. Copyright © 2013

  14. [Emergence of invasive pneumococcal disease caused by non-vaccine serotypes in the era of the 7-valent conjugate vaccine].

    González Martínez, F; Navarro Gómez, M L; Saavedra Lozano, J; Santos Sebastián, M M; Rodríguez Fernández, R; González Sanchéz, M; Cercenado Mansilla, E; Hernández-Sampelayo Matos, T

    2014-03-01

    There has been an increased incidence in invasive pneumococcal disease (IPD) produced by non-vaccine serotype (NVS) of Streptococcus pneumoniae after the introduction of PCV7. Our objective was to describe the epidemiological, clinical and microbiological characteristics of IPD caused by NVS in a tertiary hospital in Madrid. Retrospective (1998-2004) and prospective (2005-2009) study evaluating IPD caused by NVS in children. The study was divided into three periods: P1 (1998-2001) when PCV7 was not commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. We analyzed 155 cases of IPD. One hundred and fifty of these isolates were serotyped (100 were NVS). There was an increase in the prevalence of IPD from P1 (31%) to P2 (54%) and P3 (91%). The most relevant emerging serotypes were 19A, 7F, 1, 5, 3 and 15C. The most significant clinical syndromes produced by some specific serotypes were as follows: lower respiratory tract infection (LRTI) by serotypes 1, 3, 5 and 15C; LRTI, primary bacteremia and meningitis by serotype 19A; and primary bacteremia by serotype 7F (66%). The large majority (83.8%) of NVS were sensitive to penicillin. There has been an increased prevalence of IPD caused by NVS since the introduction of PCV7. These changes should prompt the introduction of new pneumococcal vaccines, which include most of the NVS, in the childhood immunization calendar to prevent IPD in children. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  15. FACTS AND OPINIONS ON USEFULNESS OF PNEUMOCOCCAL VACCINE

    M.P. Kostinov

    2009-01-01

    Full Text Available The article describes the problem of pneumococcal infections (pneumonias, meningitis, otitis in children and adults. The modern opportunities of vaccinoprophylaxis and its usefulness in public health service are shown. The perspectives and questions on safety and effectiveness of pneumococcal conjugated 7-valent vaccine as the basic method of pneumococcal infections prophylaxis in infants and children from risk groups (with bronchial asthma, sickle-cell anemia, etc. are presented in details.Key words: children, pneumococcal infection, vaccination, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(4:79-83

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

    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 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 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 pneumonia, including hypoxemia and death, have markedly decreased. PMID:28052071

  17. Difference between Japanese Secondary and Tertiary Medical Facilities Regarding Changes in the Hospitalization of Children for Pneumonia after the Introduction of the Pneumococcal Conjugate Vaccine.

    Haro, Kaoru; Ogawa, Masato; Hoshina, Takayuki; Kojiro, Masumi; Kusuhara, Koichi

    2017-05-24

    This study aimed to compare hospitalization of children for pneumonia between secondary and tertiary medical facilities, which hospitalize many children without and with underlying diseases, respectively, after the introduction of the pneumococcal conjugate vaccine (PCV). Our retrospective study included children admitted to the Department of Pediatrics at Kitakyushu General Hospital, a secondary medical facility, and the Hospital of the University of Occupational and Environment Health, Japan, a tertiary medical facility, from 2009 to 2013 for pneumonia. We compared the change in the rate of hospitalization for pneumonia after the introduction of the 7-valent PCV between the secondary and tertiary medical facilities. Hospitalization of patients with pneumonia declined by 28.8% in our secondary medical facility. In particular, hospitalization for pneumonia other than confirmed mycoplasmal or viral pneumonia was significantly reduced by 49.2%. In contrast, hospitalization of patients with pneumonia did not decline in our tertiary medical facility. After the introduction of PCV, hospitalization of children for pneumonia was not reduced at the tertiary medical facility. Various other pathogens besides pneumococcus may be associated with the development of pneumonia in children with underlying diseases.

  18. 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.

    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.

  19. Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.

    Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

    2011-03-01

    The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

  20. Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

    Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S

    2018-05-02

    Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.

  1. PNEUMOCOCCAL INFECTION IN CHILDREN: OPPORTUNITIES OF PROPHYLAXIS

    S.M. Kharit

    2009-01-01

    Full Text Available The article is dedicated to the actual problem of modern health care — pneumococcal infections and opportunities of its prophylaxis. Authors describe risk groups of development of invasive pneumococcal infections. A characteristics of available at the present times in Russia and all over the world vaccines, including pneumococcal 7-valent vaccine (PCV7 Prevenar, intended to the prophylaxis of pneumococcal infections in children under the age 2 months — 5 years old. An experience of PCV7 use in the world in analyzed. The article gives an estimation of perspectives of inclusion of PCV7 to the national immunizations schedule.Key words: children, pneumococcal infections, prophylaxis, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:62-69

  2. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya

    Burton, Deron C.; Bigogo, Godfrey M.; Audi, Allan O.; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R.; Ochieng, Peter M.; Mogeni, Ondari D.; Otieno, George A.; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K.; Chen, Robert; Farrington, Paddy; Montgomery, Joel M.; Breiman, Robert F.; Scott, J. Anthony G.; Laserson, Kayla F.

    2015-01-01

    There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274

  3. A qualitative study on knowledge, perceptions, and attitudes of mothers and health care providers toward pneumococcal conjugate vaccine in Bandung, West Java, Indonesia.

    Harjaningrum, Agnes Tri; Kartasasmita, Cissy; Orne-Gliemann, Joanna; Jutand, Marthe-Aline; Goujon, Nicolas; Koeck, Jean-Louis

    2013-03-01

    Due to the high burden of pneumonia in Indonesia, the inclusion of pneumococcal conjugate vaccine (PCV) into Indonesia's National Immunization Program (NIP) is recommended by World Health Organization. Prior to the introduction of new vaccines, it is imperative to assess the perceptions of the public and medical community about the disease and the vaccine. The purpose of this qualitative study was to explore the knowledge, perceptions, and attitudes of mothers and health care providers (HCPs) toward PCV in Bandung, West Java, Indonesia. Fifty-five respondents (26 mothers and 29 HCPs) were interviewed at public and private health care facilities in Bandung using semi-structured interviews in May-June 2011. Data were analyzed manually according to pre-defined themes. Although most mothers had low knowledge about PCV, did not perceive themselves as susceptible to the disease, perceived that cost was the main barrier to PCV access, and obtained little information on PCV, they considered pneumonia as a severe disease and a priority health problem, perceived benefits of the vaccine, and were likely to adopt it. Similarly, knowledge about PCV among most HCPs was limited. Despite perceiving cost as the main barrier, most HCPs perceived benefits of the vaccine, susceptibility and severity of the disease, regarded pneumonia as a priority health problem, and were likely to suggest the new vaccination. Despite the poor knowledge of mothers and HCPs about PCV, they are aware of the high burden of pneumonia and the need for a vaccine in the NIP. Perceived severity and benefits among mothers, and, additionally, perceived susceptibility among HCPs were manifested in the willingness to accept PCV. The findings would contribute to better understanding the factors, which could support decision-making about vaccine introduction, and be utilized for developing suitable messages for mothers and HCPs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

    Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart

    2014-12-01

    Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.

  5. Pneumococcal Disease

    ... pneumococcal disease kills one in every four to five people over the age of 65 who gets it. ... A second PPSV23 vaccine is recommended for these persons five years after the first PPSV23. CDC recommends only ...

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

    Manuel Alexander Haasis

    Full Text Available 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.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.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.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.

  7. How Are New Vaccines Prioritized in Low-Income Countries? A Case Study of Human Papilloma Virus Vaccine and Pneumococcal Conjugate Vaccine in Uganda.

    Wallace, Lauren; Kapirir, Lydia

    2017-04-08

    To date, research on priority-setting for new vaccines has not adequately explored the influence of the global, national and sub-national levels of decision-making or contextual issues such as political pressure and stakeholder influence and power. Using Kapiriri and Martin's conceptual framework, this paper evaluates priority setting for new vaccines in Uganda at national and sub-national levels, and considers how global priorities can influence country priorities. This study focuses on 2 specific vaccines, the human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV). This was a qualitative study that involved reviewing relevant Ugandan policy documents and media reports, as well as 54 key informant interviews at the global level and national and sub-national levels in Uganda. Kapiriri and Martin's conceptual framework was used to evaluate the prioritization process. Priority setting for PCV and HPV was conducted by the Ministry of Health (MoH), which is considered to be a legitimate institution. While respondents described the priority setting process for PCV process as transparent, participatory, and guided by explicit relevant criteria and evidence, the prioritization of HPV was thought to have been less transparent and less participatory. Respondents reported that neither process was based on an explicit priority setting framework nor did it involve adequate representation from the districts (program implementers) or publicity. The priority setting process for both PCV and HPV was negatively affected by the larger political and economic context, which contributed to weak institutional capacity as well as power imbalances between development assistance partners and the MoH. Priority setting in Uganda would be improved by strengthening institutional capacity and leadership and ensuring a transparent and participatory processes in which key stakeholders such as program implementers (the districts) and beneficiaries (the public) are

  8. A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.

    Lim, Fong Seng; Koh, Mia Tuang; Tan, Kah Kee; Chan, Poh Chong; Chong, Chia Yin; Shung Yehudi, Yeo Wee; Teoh, Yee Leong; Shafi, Fakrudeen; Hezareh, Marjan; Swinnen, Kristien; Borys, Dorota

    2014-10-02

    The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in

  9. Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

    Szenborn, L; Osipova, I V; Czajka, H; Kharit, S M; Jackowska, T; François, N; Habib, M A; Borys, D

    2017-09-25

    Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. PHiD-CV was immunogenic and well tolerated in 2

  10. The epidemiology of pneumococcal carriage and infections in Malaysia.

    Le, Cheng-Foh; Jefferies, Johanna M; Yusof, Mohd Yasim Mohd; Sekaran, Shamala Devi; Clarke, Stuart C

    2012-06-01

    In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.

  11. Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.

    van den Bergh, Menno R; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H; Sanders, Elisabeth A M

    2016-07-01

    Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.

  12. Estimating the cost-effectiveness of pneumococcal conjugate vaccination in Brazil Cálculo de la relación costo-efectividad de la vacuna conjugada antineumocócica en Brasil

    Glaucia Vespa

    2009-12-01

    Full Text Available OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35 per dose, vaccination would cost annually R$ 4 289 (US$ 2,211 per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.OBJETIVO: Comparar los costos y los beneficios de la aplicación de la vacuna conjugada antineumocócica en comparación con la no vacunación, desde las perspectivas del sistema de salud y la sociedad. MÉTODOS: A partir de fuentes reconocidas, se estimaron la incidencia y la mortalidad por enfermedad neumocócica invasora, neumonía y otitis media aguda (OMA para una cohorte hipotética de niños desde su nacimiento hasta los 5 años. RESULTADOS: Se estimó que un programa de vacunación universal con una vacuna conjugada antineumocócica sería capaz de evitar anualmente 1 047 casos de la enfermedad invasora, 58 226 casos de neumonía y 209 862 casos de OMA. Si se considera el efecto de la inmunidad de grupo, el programa evitaría 1,3 millones de casos

  13. Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study.

    Sirima, Sodiomon B; Tiono, Alfred; Gansané, Zakaria; Siribié, Mohamadou; Zongo, Angèle; Ouédraogo, Alphonse; François, Nancy; Strezova, Ana; Dobbelaere, Kurt; Borys, Dorota

    2017-05-01

    Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in children with sickle cell disease (SCD), who are at increased risk for infections. In this phase III, open-label, single-center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age (vaccines; children 7-11 months of age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD-CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity. Responses to other antigens were measured by enzyme-linked immunosorbent assay. Adverse events were recorded. One month postprimary vaccination, for each vaccine serotype ≥98% of infants in the vaccination in children vaccination. Safety and reactogenicity profiles were similar in children with or without SCD. PHiD-CV was immunogenic with an acceptable safety profile in children with and without SCD starting vaccination at 8 weeks to 23 months of age.

  14. Association of infant pneumococcal vaccination with pneumococcal pneumonia among mothers : A nested case-control study using the GPRD

    Hak, Eelko; Shea, Kimberly M.; Jick, Susan S.

    2013-01-01

    Since implementation of infant immunization with 7-valent pneumococcal conjugate vaccine (PCV7), increased rates of pneumococcal pneumonia have been reported among adults. Using a cohort of mother-infant pairs identified from the General Practice Research Database in the UK we found that from 2006

  15. Cepas invasivas de pneumococo isoladas de crianças e adolescentes em Salvador Invasive pneumococcal strains isolated from children and adolescents in Salvador

    Cristiana M. Nascimento-Carvalho

    2003-06-01

    Full Text Available OBJETIVOS: descrever resistência antimicrobiana e sorotipos de cepas de pneumococo. MÉTODOS: durante 57 meses, foi conduzida uma vigilância de cepas invasivas de pneumococo de pacientes com idade OBJECTIVE: describe the antimicrobial resistance and serotype distribution of pneumococcal strains. METHODS: in a 57-month period, a laboratory-based surveillance of invasive pneumococcal strains from patients aged < 20 years was conducted. Pneumococcus was identified by means of tests for solubility in bile and optochin. Pneumococcal resistance to penicillin was screened by 1µg oxacillin disc and minimal inhibitory concentration was determined for the strains not susceptible to penicillin. Disc diffusion and broth microdilution methods were used for surveillance of resistance to other antimicrobials. Pneumococci were serotyped by means of the Neufeld-Quellung reactions. RESULTS: of 70 patients, 57.1% were males. The mean age was 1.92 yrs (mean 3.19 + 3.66 yrs, range 1 month to 19.5 yrs; 52.9% and 81.4% were < 2 yrs and < 5 yrs, respectively. The strains were isolated from blood (91.4%, CSF (2.9%, pleural (2.9%, peritoneal (1.4% and abscess (1.4% fluids from patients with pneumonia (77.1%, fever without localizing signs (10.0%, meningitis (4.3%, others (8.6%. Resistance was detected to penicillin (20.0%, trimethoprim-sulfamethoxazole (65.7%, tetracycline (21.4%, ofloxacin (6.3%, erythromycin (5.7%, clindamycin (2.9%. All tested strains were susceptible to chloramphenicol and vancomycin. Among penicillin-resistant strains, high resistance was detected in one, the same that showed intermediate resistance to cefotaxime. The most frequent serotypes were: 14 (22.9%, 5 and 6A (10.0% each, 6B and 19F (8.6% each, 9V, 18C and 23F (5.7% each. Resistance to penicillin was detected in serotypes 14 (71.4%, 6B and 19F (14.3% each. CONCLUSIONS: of 70 strains, 67.2% were classified as serotypes included in the heptavalent conjugate pneumococcal vaccine as well as

  16. 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.

    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.

  17. Safety, tolerability, and immunogenicity of 7-valent pneumococcal conjugate vaccine in older infants and young children in China who are naive to pneumococcal vaccination: Results of a phase 4 open-label trial.

    Li, Rongcheng; Huang, Lirong; Mo, Shunping; Li, Junchun; Zhou, Xin; Chen, Zhangjing; Liang, John; Young, Mariano; Giardina, Peter C; Scott, Daniel A

    2015-07-09

    This postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China. Healthy children 121 days to vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study. Prevaccination serotype-specific GMCs were generally low in subjects children 24 to 90% of subjects had IgG≥0.35 μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG≥0.35 μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n=4), and there was 1 study withdrawal; none of these were considered treatment related. In China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. [Invasive pneumococcal disease in the Community of Valencia. Six years of surveillance (2007-2012)].

    Ciancotti Oliver, Lucía Rosa; Huertas Zarco, Isabel; Pérez Pérez, Elvira; Carmona Martí, Esther; Carbó Malonda, Rosa; Gil Bru, Ana; González Moran, Francisco

    2015-03-01

    The introduction of conjugated anti-pneumonia vaccines has led to a change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of this study is to describe the trends in IPD in the Community of Valencia during the period 2007-2012. A retrospective, descriptive and longitudinal study was conducted on IPD in the Community of Valencia during the period 2007-2012, The information sources used were the Epidemiological Surveillance Analysis (Análisis de la Vigilancia Epidemiológica (AVE)) and the Valencian Microbiology Network (Red Microbiológica Valenciana (RedMIVA)) of the Valencia Health Department. The incidence of IPD decreased between 2007 and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5 cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26% to 12% (p=.23) was observed in the proportion of cases due to the serotypes contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A, 7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year-olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes significantly increased from 42.3% to 56.7% in the general population (p=.002), and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). The results of this study show a reduction in the incidence of IPD, with a decrease in the proportion of cases produced by vaccine serotypes, and an increase in the proportion of those not vaccinated. Epidemiological Surveillance is necessary to monitor the trends in the disease. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Treatment and prevention of invasive pneumococcal disease.

    Domínguez-Alegría, A R; Pintado, V; Barbolla, I

    2018-02-12

    Invasive pneumococcal disease is a severe infection that mainly affects patients with associated comorbidity. The paediatric conjugate vaccination has resulted in a change in the adult vaccination strategy. The antibiotic resistance of pneumococcus is not currently a severe problem. Nevertheless, the World Health Organisation has included pneumococcus among the bacteria whose treatment requires the introduction of new drugs, such as ceftaroline and ceftobiprole. Although the scientific evidence is still limited, the combination of beta-lactams and macrolides is recommended as empiric therapy for bacteraemic pneumococcal pneumonia. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  20. 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.

    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

  1. 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

    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

    2017-01-01

    ABSTRACT 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 children younger than 24 months, and reduced vaccine-serotype NPC. PMID:28368738

  2. Epidemiology and population structure of serotypes 1, 5 and 7f carried by children in Portugal from 1996-2010 before introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines.

    Sónia T Almeida

    Full Text Available Among the over 90 serotypes of Streptococcus pneumoniae described, serotypes 1, 5, and 7F account for a significant proportion of invasive disease worldwide and are now covered by the most recent 10- and 13-valent pneumococcal conjugate vaccines (PCVs. The epidemiology of these serotypes in carriage remains poorly studied because they are rarely detected. We aimed to gain insights into the epidemiology and population structure of serotypes 1, 5 and 7F carried by children in Portugal before PCV10 and PCV13 became widely used. Isolates obtained in cross-sectional studies carried out over a 15-year period (1996-2010 were retrospectively pooled and characterized. Of 5,123 pneumococci obtained, 70 were associated with serotypes 1 (n = 21, 5 (n = 7, and 7F (n = 42. The highest prevalence detected was 3.3% for serotype 1 in 2006, 1% for serotype 5 in 2009, and 3.3% for serotype 7F in 2006; Serotype 1 was associated with PMEN international clones Sweden(1-28(ST306 and Sweden(1-40(ST304; serotype 5 was associated with Colombia(5-19(ST289; and serotype 7F was associated with Netherlands(7F-39(ST191. All these isolates were fully susceptible. Most carriers of serotypes 1 (86%, 5 (86%, and 7F (91% were older than two years but a significant association with older age was only observed for serotype 7F (p = 0.006. Evidence for cross-transmission was obtained. In conclusion, we were able to detect and characterize the rarely carried serotypes 1, 5, and 7F among healthy children in Portugal. These data will constitute an important baseline for upcoming surveillance studies aimed to establish the impact of novel PCVs targeting these serotypes in carriage.

  3. PROPHYLAXIS OF PNEUMOCOCCAL INFECTION IN CHILDREN HAS POSITIVE EFFECT ON ALL POPULATION

    M.V. Fedoseenko

    2008-01-01

    Full Text Available Modern data of effectiveness prophylaxis of pneumococcal infection in children younger 1 year old with vaccine is presented in this article. Including of 7 - valency pneumococcal conjugated vaccine (PCV-7 in immunization program of some countries resulted in decrease of morbidity as in vaccinated group, as in all population. It was marked that vaccination with PCV-7 plays important pathogenetic role in termination of hidden forms of disease and prevention of spreading of pneumococcal infection, including the most severe types, hardly treated with antibiotics.Key words: children, pneumococcal infection, vaccination.

  4. Economic impact of pneumococcal conjugate vaccination in Brazil, Chile, and Uruguay Impacto económico de la vacuna antineumocócica conjugada en Brasil, Chile y Uruguay

    Dagna O. Constenla

    2008-08-01

    Full Text Available OBJECTIVES: To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7 in Brazil, Chile, and Uruguay. METHODS: A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. RESULTS: At the rate of diphtheria-tetanus-pertussis (DTP vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884 841 disability-adjusted life years (DALYs yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil to US$ 2 019 (Chile. At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125 050 497 versus US$ 153 965 333, making it cost effective and cost-saving. CONCLUSIONS: The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccination at the current price is affordable to these countries.OBJETIVOS: Evaluar el impacto económico de la aplicación de la vacuna antineumocócica conjugada heptavalente (PCV7 en Brasil, Chile y Uruguay. MÉTODOS: Se elaboró un modelo analítico de decisiones para comparar la vacunación antineumocócica de los niños de 0-5 años de edad con la no vacunación, en Brasil, Chile y Uruguay. Los costos y los desenlaces para la salud se analizaron desde el punto de vista de la sociedad. Al análisis económico se incorporaron los costos y los datos demográficos, epidemiológicos y de la vacuna. RESULTADOS

  5. Cost-effectiveness of infant pneumococcal vaccination in the Netherlands

    Vemer, P.; Postma, M.J.

    2013-01-01

    Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic

  6. Pneumococcal disease: Closing the gap

    Ashfaq Hasan

    2015-01-01

    Full Text Available oday, India is home to 99 million elderly people. By 2050, the number of elderly in this country will have gone up to 300 million1. With an increase in life expectancy from 32 years at the time of independence to 67.14 years in 20121, 10% of the population finds itself labeled as ‘senior citizen’. Inevitably, age brings with it comorbidities, immune senescence and pneumococcal disease. Pneumonia, in deference to its considerable morbidity and mortality, was exalted by Sir William Osler to its dubious pedestal of “Captain of all these Men of Death”. Unsurprisingly, immune debility and in several regions of the planet increasing antibiotic resistance, have ensured that pneumococcal pneumonia continues to take a large toll of senior citizens. Death rates have hardly budged over the last three decades. In India, pneumonia accounts for 25-30% deaths in the elderly3, a fatality rate almost unrivalled by most other terminal diseases. Among 15 high-burden countries, India has the dubious distinction of ranking third from last in the Global Action Plan for Pneumonia and Diarrhea (GAPPD4. During the World Immunization Week 2015 (April 24th to 30th, the ‘Close the Immunization Gap’ campaign gains crucial importance. Immunization, long vaunted as one of the most successful and cost-effective health interventions there is, prevent 2 to 3 million deaths every year, and saves enor-mous hospitalization costs and prevents loss of productivity. The recently published CAPiTA study (Community Acquired Pneumonia Immunization Trial in Adults, evaluated the efficacy of a novel 13-valent conju-gate vaccine for Pneumococcal pneumonia a vac-cine proven for its efficacy in children for the first time in older adults over 85,000 of them. Childhood vaccination with ‘PCV-13’, of course, was instrumental in reducing nasopharyngeal carriage of Strep pneumonia and decreasing the prevalence of Pneumococcal disease in the community at large. Altogether, the idea

  7. Pathophysiology of pneumococcal meningitis

    Geldhoff, M.

    2016-01-01

    Bacterial meningitis is a serious infectious disease, involving the membranes surrounding the brain and spinal cord, and the subarachnoid space. In the Netherlands most common causative agents are Streptococcus pneumoniae (72%) and Neisseria meningitidis (11%). The incidence of pneumococcal

  8. Pneumococcal Vaccines (PCV, PPSV)

    ... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... cochlear implants. Why Are the PCV and PPSV Vaccines Recommended? Children younger than 2 years old, adults ...

  9. The immunological mechanisms that control pneumococcal carriage.

    Simon P Jochems

    2017-12-01

    Full Text Available Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.

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

    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. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

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

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

    2015-01-01

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

  12. Recommendations for pneumococcal immunization outside routine childhood immunization programs in Western Europe.

    Castiglia, Paolo

    2014-10-01

    The global burden of pneumococcal diseases is high, with young children and adults≥50 years of age at highest risk of infection. Two types of vaccine are available for the prevention of pneumococcal diseases caused by specific Streptococcus pneumoniae serotypes: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV7, PCV10, and PCV13). Despite pneumococcal immunization programs in adults and children, the burden in adults has remained high. Most European countries have national or local/regional vaccination recommendations. The objective of this review was to provide an overview of the government recommendations for pneumococcal vaccination outside routine childhood vaccination programs for 16 Western European countries as of August 2014. We found that recommendations for pneumococcal immunization across Europe are complex and vary greatly among countries in terms of age groups and risk groups recommended for vaccination, as well as which vaccine should be administered. Clarifying or simplifying these recommendations and improving their dissemination could help to increase pneumococcal vaccine uptake and decrease the high burden of pneumococcal diseases in adults, both through a direct effect of the vaccine and via a herd effect in unvaccinated individuals.

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

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

    2015-01-01

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

  14. Effectiveness of pneumococcal conjugate vaccine and rotavirus ...

    Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive ...

  15. Pneumococcal conjugate vaccines for preventing otitis media

    Jansen, Angelique G S C; Hak, Eelko; Veenhoven, Reinier H; Damoiseaux, Roger A M J; Schilder, Anne G M; Sanders, Elisabeth A M

    2009-01-01

    BACKGROUND: Acute otitis media (AOM) is a very common early infancy and childhood disease. The marginal benefits of antibiotics on AOM, the increasing problem of bacterial resistance to antibiotics, and the huge estimated direct and indirect annual costs associated with otitis media (OM) have

  16. Pneumococcal conjugate vaccines for preventing otitis media

    Fortanier, Alexandre C.; Venekamp, Roderick P.; Boonacker, Chantal W. B.; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger A. M. J.

    2014-01-01

    BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual

  17. Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.

    Hamaluba, Mainga; Kandasamy, Rama; Upreti, Shyam R; Subedi, Giri R; Shrestha, Shrijana; Bhattarai, Shiva; Gurung, Meeru; Pradhan, Rahul; Voysey, Merryn; Gurung, Santosh; Pradhan, Shachi; Thapa, Anushil K; Maharjan, Rakesh; Kiran, Usha; Kerridge, Simon A; Hinds, Jason; van der Klis, Fiona; Snape, Matthew D; Murdoch, David R; Kelly, Sarah; Kelly, Dominic F; Adhikari, Neelam; Thorson, Stephen; Pollard, Andrew J

    2015-04-01

    Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40-60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2-4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 μg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 μg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 μg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study

  18. [Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].

    Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena

    2015-01-01

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice

    Pavliakova, Danka; Moncrief, J. Scott; Lyerly, David M.; Schiffman, Gerald; Bryla, Dolores A.; Robbins, John B.; Schneerson, Rachel

    2000-01-01

    Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile. PMID:10722615

  20. Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas

    Vanesa Reijtman

    2013-03-01

    Full Text Available A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM 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.Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA y con infecciones invasivas (INV en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar

  1. Contribution to the coordination chemistry of penta, hexa and heptavalent ions of 5f elements

    Musikas, Claude.

    1978-01-01

    This report has two main parts in which are discussed results dealing with: - aquo and hydroxo complexes of penta, hexa and heptavalent ions of 5f elements - pseuso halides complexes of these ions (SCN - , N 3 - , CN - ). It has been shown, by spectrophotometric and electrochemical measurements that U (V) possesses an aquo ion more acid than the known UO 2 + ion. This form is observed as insoluble hydroxid near pH 3.0 or as soluble polynuclear hydroxo complexes at lower pH. Hydroxo anionic complexes of U (VI) have been observed and one can precise the mecanism of hydrolysis of UO 2 ++ ions beyond he hydroxid UO 2 (OH) 2 . At pH 9 to 12, polynuclear species with low negative charge have been observed. At pH 13, others OH - ions enter in the coordination sphere of UO 2 ++ and mononuclear species are obtained. Reduction of polynuclear species leads to mixed hydroxo complexes of 'blue type'. Studies of hydrolysis of NpO 2 + allow to propose an hydrolysis mechanism similar to UO 2 ++ one. With electrochemical methods that in acidic media Np (VII) is present as NpO 3 + ions. Solubility product of NpO 3 OH has been measured. The second part is devoted to pseudohalides complexes of UO 2 ++ , UO 2 + and NpO 2 + ions [fr

  2. Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013.

    Sadia Shakoor

    Full Text Available While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81 of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults. Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52 or CSF specimens (n = 59. Serogroup 18 was the most common serogroup causing meningitis in children <5 years, accounting for 21% of cases (n = 13. The 10-valent pneumococcal conjugate vaccine (PCV 10 or PCV10- related serotypes were found in 61% (n = 47 of childhood (age 0-15 years meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48. Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease.

  3. Impact of pneumococcal vaccines use on invasive pneumococcal disease in Nunavik (Quebec from 1997 to 2010

    Jean-Baptiste Le Meur

    2014-01-01

    Full Text Available Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23. At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD in relation to PPSV23 and PCV7 use. Study design and methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997–2010. Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997–2001 vs. 10/100,000 in 2004–2010 (p<0.01. Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11. Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.

  4. Pneumococcal Disease: Diagnosis and Treatment

    ... the cause. In the case of pneumococcal disease, antibiotics can help prevent severe illness. Diagnosis If doctors suspect invasive ... In addition to the vaccine, appropriate use of antibiotics may also slow or reverse drug-resistant pneumococcal infections. Related Links ... Formats Help: How do I view different file formats (PDF, ...

  5. Pneumococcal vaccination in adults: rationale, state of the art and perspectives.

    Icardi, G; Sticchi, L; Bagnasco, A; Iudici, R; Durando, P

    2012-06-01

    Streptococcus pneumoniae (SP) is a leading cause of morbidity and mortality worldwide. Despite the availability, since the early 1980s, of a 23-valent pneumococcal polysaccharide vaccine (PP V23), its recommendation and increased use in the last decades, and the indirect benefits against invasive pneumococcal diseases following the pediatric immunization strategies with the 7-valent pneumococcal conjugate vaccine (PCV7), pneumoccal diseases, particularly Community Acquired Pneumonia (CAP), still remain a substantial burden among older adults in Western countries. The recent availability on the market of a second generation of pneumococcal conjugate vaccines, with an enlarged spectrum of protection against some serotypes not included in the PCV7 (i.e., the 13-valent pneumococcal conjugate vaccine--PCV13), opens new interesting perspectives for improving the control of this significant health-care issue among the entire population. The most interesting and up-dated epidemiological data regarding the impact of SP in adults and the elderly in Western countries, together with the available evidence concerning the efficacy and effectiveness of the PPV23 in the same population, are reported and discussed below.

  6. Recurrent invasive pneumococcal disease in children

    Ingels, Helene; Lambertsen, Lotte; Harboe, Zitta B

    2014-01-01

    %, and 78% of the cases would have been covered by the 7-, 10-, and 13-valent pneumococcal conjugate vaccines, respectively. Conclusions: Of children with an IPD episode, 2.4% experienced rIPD, and an underlying disease was documented in 66% of these children. Investigation of underlying conditions...... laboratory-confirmed cases of IPD in children aged 0-15 y were identified from the Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Denmark for the period 1980-2013. rIPD was defined as isolation of Streptococcus pneumoniae from any normally sterile site ≥ 30 days after an initial...... positive culture. Clinical data were obtained for all children with rIPD. Results: Of all children with IPD, 2.4% (59/2418) experienced at least 1 episode of rIPD, and an underlying condition was documented in 39 (66%). Immune deficiency due to transplantation (n = 9) was the most common disease; however...

  7. Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice

    Vliegenthart, J.F.G.; Jansen, W.T.M.; Hogenboom, S.; Thijssen, M.J.L.; Kamerling, J.P.; Verhoef, J.; Snippe, H.; Verheul, A.F.M.

    2001-01-01

    The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were

  8. Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis Rentabilidad médica de la vacunación antineumocócica en América Latina y el Caribe: un análisis regional

    Anushua Sinha

    2008-11-01

    Full Text Available OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.OBJETIVO: En América Latina y el Caribe, la vacunación sistemática de niños contra Streptococcus pneumoniae podría requerir inversiones considerables de los gobiernos y organizaciones donantes. Al evaluar estas inversiones se requiere

  9. Costo-efectividad de la vacunación universal antineumocócica en Uruguay Cost-effectiveness of universal pneumococcal vaccination in Uruguay

    Gustavo Giachetto Larraz

    2010-08-01

    Full Text Available OBJETIVO: Evaluar la relación costo-efectividad del programa de vacunación universal con la vacuna antineumocócica conjugada heptavalente (VCN7 en niños menores de 5 años en Uruguay. MÉTODOS: Se desarrolló un modelo Markov simulando una cohorte de 48 000 niños nacidos en 2007 y su evolución hasta los 76 años de edad. El caso base usó un esquema de tres dosis con una duración estimada de protección de cinco años. La presunción de eficacia y efectividad de la vacuna se realizó acorde con estudios realizados en Estados Unidos con ajuste a la prevalencia-incidencia de serotipos en Uruguay. Los resultados se expresaron como costo incremental por año de vida ganado (AVG y por año de vida [ganado] ajustado por calidad (AVAC. RESULTADOS: Para el caso base, el costo incremental fue de US$ 7 334,6 por AVG y US$ 4 655,8 por AVAC, previniéndose 8 muertes y 4 882 casos de otitis, 56 bacteriemias-sepsis, 429 neumonías y 7 meningitis. El modelo muestra sensibilidad a variaciones en eficacia, costo de la vacuna y tasa de mortalidad por neumonía. CONCLUSIONES: El programa de vacunación universal con VCN7 en Uruguay es altamente costo-efectivo y, en consecuencia, recomendable para otros países con carga de enfermedad neumocócica y cobertura de serotipos similares a Uruguay.OBJECTIVE: Evaluate the cost-effectiveness ratio of the program for universal vaccination with heptavalent pneumococcal conjugate vaccine (PCV7 in children under 5 years of age in Uruguay. METHODS: A Markov model was developed that simulated a cohort of 48 000 children born in 2007 and their progress to age 76. The baseline case used a regimen of three doses with estimated protection for five years. The presumption of vaccine efficacy and effectiveness was based on studies conducted in the United States with adjustment for serotype prevalence-incidence in Uruguay. The results were expressed as the incremental cost per life year gained (LYG and quality-adjusted life year

  10. Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales.

    Yoon Hong Choi

    Full Text Available England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7 with its 13-valent equivalent (PCV13, partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether.A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13.Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether.Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.

  11. Pneumococcal Infections: MedlinePlus Health Topic

    ... Prevention, Immunization Action Coalition) - 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 ...

  12. Sampling methods for the study of pneumococcal carriage: a systematic review.

    Gladstone, R A; Jefferies, J M; Faust, S N; Clarke, S C

    2012-11-06

    Streptococcus pneumoniae is an important pathogen worldwide. Accurate sampling of S. pneumoniae carriage is central to surveillance studies before and following conjugate vaccination programmes to combat pneumococcal disease. Any bias introduced during sampling will affect downstream recovery and typing. Many variables exist for the method of collection and initial processing, which can make inter-laboratory or international comparisons of data complex. In February 2003, a World Health Organisation working group published a standard method for the detection of pneumococcal carriage for vaccine trials to reduce or eliminate variability. We sought to describe the variables associated with the sampling of S. pneumoniae from collection to storage in the context of the methods recommended by the WHO and those used in pneumococcal carriage studies since its publication. A search of published literature in the online PubMed database was performed on the 1st June 2012, to identify published studies that collected pneumococcal carriage isolates, conducted after the publication of the WHO standard method. After undertaking a systematic analysis of the literature, we show that a number of differences in pneumococcal sampling protocol continue to exist between studies since the WHO publication. The majority of studies sample from the nasopharynx, but the choice of swab and swab transport media is more variable between studies. At present there is insufficient experimental data that supports the optimal sensitivity of any standard method. This may have contributed to incomplete adoption of the primary stages of the WHO detection protocol, alongside pragmatic or logistical issues associated with study design. Consequently studies may not provide a true estimate of pneumococcal carriage. Optimal sampling of carriage could lead to improvements in downstream analysis and the evaluation of pneumococcal vaccine impact and extrapolation to pneumococcal disease control therefore

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

    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. Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

    de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

    2015-06-11

    Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

  15. An evaluation of emerging vaccines for childhood pneumococcal pneumonia

    Zhang Jian Shayne F

    2011-04-01

    Full Text Available Abstract Background Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA vaccine offering protection for all serotypes. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism (over 80% that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9

  16. Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children.

    Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas

    2014-06-01

    Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study

    Harboe, Zitta B; Thomsen, Reimar W; Riis, Anders

    2009-01-01

    BACKGROUND: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD). METHODS AND FINDINGS: In a nationwide population-based...

  18. Enfermedad neumocócica invasiva en la población infantil de la Comunidad Valenciana Invasive pneumococcal disease in children in the community of Valencia, Spain

    M. Goicoechea-Sáez

    2003-12-01

    .Objective: Pneumococcal disease is an important cause of morbidity and mortality in children. The recent authorization of the heptavalent conjugate vaccine has increased interest in this disease. The objective of this study was to identify the epidemiological and clinical characteristics of this disease, as well as its outcome in the pediatric population of the Autonomous Community of Valencia. Method: Data were obtained from the medical records of children aged less than 15 years who were positive for pneumococcus isolation on admission to hospital between 1996 and 2000. All the public hospitals of the Autonomous Community of Valencia were included. Changes in incidence were evaluated by comparing rates and outcomes (sequelae and lethality through frequency and age distribution. Results: One hundred twenty-seven cases were registered, giving a mean annual rate of 3.89/105 inhabitants aged less than 15 years. The rate was 20.14 in children aged less than 2 years. A total of 29.1% of the children had previous health problems. The main clinical manifestations included sepsis/bacteremia (38%, pneumonia (31% and meningitis (24%. At discharge sequelae were present in 10 children, 75% of whom were aged less than 2 years. Eight children died (6.3% lethality. Conclusions: In the period and region studied, pneumococcal infection was present mainly in children aged less than 2 years and in those with previous health problems. In the last few years, mortality has increased. Thus, inclusion of pneumococcal disease in the epidemiological surveillance system would be appropriate to achieve more precise estimations of its epidemiological patterns and to determine whether the conjugate vaccine represents a solution to the problems currently associated with this bacteria.

  19. Vaccination for the control of childhood bacterial pneumonia - Haemophilus influenzae type b and pneumococcal vaccines

    Diana C Otczyk

    2013-01-01

    Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia.  The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children.  However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement.  The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes.  Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries.  The next generation of pneumococcal vaccines have advanced to clinical trials.

  20. Population-based surveillance for invasive pneumococcal disease in homeless adults in Toronto.

    Agron Plevneshi

    Full Text Available 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

  1. Economic aspects of pneumococcal pneumonia: a review of the literature.

    De Graeve, Diana; Beutels, Philippe

    2004-01-01

    In this review, the economic aspects of pneumococcal pneumonia are analysed, including the costs, cost effectiveness and cost benefit of treatment and prevention. We identified eight cost-of-illness studies, 15 analyses comparing the costs of different treatment options and 15 economic evaluations of prevention that met our search criteria. The studies were conducted largely in Europe and the US. Most pertained to community-acquired pneumonia (CAP) in general, without specific analysis of pneumococcus-related illness. Many of the studies were considered to be of poor quality for the following reasons: comparison without randomisation or control variables, disregard of health outcomes, small sample size, restriction of costs to drug costs and vague or disputable sources of cost information. In the US, hospitalisation costs resulting from CAP can be estimated to be between US 7,000 dollars and US 8,000 dollars per admission or US 4 million dollars per 100,000 population. Hospitalisation costs are significant (representing about 90% of total costs), but are much lower in Europe than in the US (one-third to one-ninth of the US estimates in the UK and Spain, respectively). In general, economic studies of treatment for pneumococcal pneumonia are in line with clinical evidence. A drug with proven clinical effectiveness would also appear to be supported from an economic stand point. Furthermore, economic data support an early switch from an intravenous to an oral antibacterial, the use of quinolones for inpatients with CAP, and also the use of guidelines built on clinical evidence. Of all the possible preventive strategies for pneumococcal pneumonia, only vaccination has been subjected to economic evaluation. Pneumococcal polysaccharide vaccine seems relatively cost effective (and potentially cost saving) for those between 65 and 75 years of age, for military recruits and for HIV positive patients with a sufficiently high CD4 cell count. Evaluations of the pneumococcal

  2. Mortality reductions for older adults differ by race/ethnicity and gender since the introduction of adult and pediatric pneumococcal vaccines.

    Soneji, Samir; Metlay, Joshua

    2011-01-01

    We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups. We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates. Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline. PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.

  3. Characterization of some pneumococcal bacteriophages

    Porter, R.D.; Guild, W.R.

    1976-01-01

    The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 x 10 10 to 4 x 10 10 PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages ω3 and ω8 each have linear double-stranded DNA of 33 x 10 6 daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol percent, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, ω3 and ω8 have D 37 values of 33 and 55 J/m 2 , respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between ω3 and ω8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages

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

    Kirkham, Lea-Ann S; Wiertsema, Selma P; Corscadden, Karli J; Mateus, Tulia; Mullaney, Gemma L; Zhang, Guicheng; Richmond, Peter C; Thornton, Ruth B

    2017-03-01

    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 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. Copyright © 2017 Kirkham et al.

  5. Prevalence of nasopharyngeal antibiotic-Resistant pneumococcal ...

    Conclusion: Pneumococcal resistance was significant in this group of children with easy access to paediatric services and antibiotic use. The implication of such high resistance for the treatment of pneumococcal diseases is that high-dose amoxicillin is the preferred empirical oral therapy for treatment of otitis media.

  6. [Nasopharyngeal carriage of pneumococcal serotypes in healthy pre-school aged children after 7-valent pneumococcal vaccine].

    García-Vera, César; Ruiz Andrés, María Ángeles; Arana Navarro, Teresa; Moneo Hernández, Isabel; Castillo Laita, José Antonio; Macipe Costa, Rosa; Revillo Pinilla, María José

    2011-06-11

    To determine the characteristics influencing pneumococcal serotype colonization in healthy pre-school aged children, the distribution of serotypes and their antimicrobial susceptibility, after the introduction of pneumococcal 7-valent conjugate vaccine (VNC-7 v). SUJETOS AND METHODS: Nasopharyngeal samples were collected from children under 6 years of age attending well-child examinations in the province of Zaragoza (Spain). Logistic regression was used to study different variables related to the status of the carriers. Of the 371 children studied 30.7% were found to be carriers. With a vaccine coverage rate of 66%, factors related with presence of pneumococcal carriage were found to be the number of siblings (OR 1.44; CI 95% 1.05-1.97 for each sibling), attending a school or child day care centre (OR 3.99; CI 95% 2.00-7.96) and suffering from a minor upper respiratory tract infection (URTI) (OR 1.72; CI 95% 1.02-2.90). Only 8.7% corresponded to VNC-7 v serotypes. The most common non VNC-7 v serotypes isolated were 19A, 6A, 15B, 11, and 15A. Significantly greater resistance was detected among VNC-7 v serotypes. Children in the setting of this study carried pneumococci more commonly when they have siblings, attend school or day care, or suffer from minor URTI. In the VNC-7 v vaccine era, VNC-7 v serotypes have become rare occurrences (8.7%) and emerging serotypes present better susceptibility to antibiotics. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  7. Combination of pneumococcal surface protein A (PspA with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice.

    Maria Leonor S Oliveira

    Full Text Available Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP that is currently part of the DTP (diphtheria-tetanus-pertussis vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low protected mice against challenge with two

  8. New pneumococcal conjugate vaccine introductions in four sub ...

    African countries: a cross-country analysis of health systems' impacts ... Health and Development, London School of Hygiene and Tropical Medicine, .... from the post introduction evaluation methodology20. .... cine in Kenya, Ethiopia and Cameroon before and after ..... and Health Systems: Summary of Main Themes and.

  9. Epidemiological burden of invasive pneumococcal disease in children and adolescents with predisposing risk factors.

    Falleiros-Arlant, Luiza Helena; Berezin, Eitan Naaman; Avila-Aguero, Maria Luisa; Pirez, Maria Catalina; Gentile, Angela; Richardson, Vesta; Brea, Jose; Mariño, Cristina

    2015-09-01

    Some medical conditions constitute important risk factors for the development of invasive pneumococcal diseases in children and adolescents aged from 5 to 19 years. Conjugate vaccines have potential efficacy in this scenario, but are not available in many Latin American public healthcare systems for this age group. This study aimed to estimate the preventable fraction of invasive pneumococcal diseases among individuals aged from 5 to 19 years with associated risk factors for its development. Data regarding the Latin America population, risk factors prevalence and conjugate vaccines efficacy were obtained from the literature. Total population at risk ranged from 17.3 to 64.6 million of individuals and asthma was the most impacting risk factor. According to SIREVA, PCV13 provided a 62.9% serotypes coverage in individuals from 5 to 29 years in 2012, potentially increasing the covered population from [8,338,457-31,057,620] with PCV10 to [10,906,356-40,622,078] with PCV13. To date, according to available efficacy data, the hypothetically immunized population ranged from 11.4 to 42.4 million, representing 7.0% to 26.0% of the total population in this age group. Vaccination in risk groups should be encouraged, as it potentially contributes to the reduction in the number of cases of invasive pneumococcal disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals...

  11. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  12. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  13. Streptococcus pneumoniae serotype-2 childhood meningitis in Bangladesh: a newly recognized pneumococcal infection threat.

    Samir K Saha

    Full Text Available BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26% of cases. Ninety eight percent (45/46 of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3. The serotype-2 strains had three closely related pulsed field gel electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2

  14. Cost-effectiveness analysis of pneumococcal vaccination for infants in China.

    Maurer, Kristin A; Chen, Huey-Fen; Wagner, Abram L; Hegde, Sonia T; Patel, Tejasi; Boulton, Matthew L; Hutton, David W

    2016-12-07

    Although China has a high burden of pneumococcal disease among young children, the government does not administer publicly-funded pneumococcal conjugate vaccines (PCV) through its Expanded Program on Immunization (EPI). We evaluated the cost-effectiveness of publicly-funded PCV-7, PCV-10, and PCV-13 vaccination programs for infants in China. Using a Markov model, we simulated a cohort of 16 million Chinese infants to estimate the impact of PCV-7, PCV-10, and PCV-13 vaccination programs from a societal perspective. We extrapolated health states to estimate the effects of the programs over the course of a lifetime of 75years. Parameters in the model were derived from a review of the literature. We found that PCV-7, PCV-10, and PCV-13 vaccination programs would be cost-effective compared to no vaccination. However, PCV-13 had the lowest incremental cost-effectiveness ratio ($11,464/QALY vs $16,664/QALY for PCV-10 and $18,224/QALY for PCV-7) due to a reduction in overall costs. Our sensitivity analysis revealed that the incremental cost-effectiveness ratios were most sensitive to the utility of acute otitis media, the cost of PCV-13, and the incidence of pneumonia and acute otitis media. The Chinese government should take steps to reduce the burden of pneumococcal diseases among young children through the inclusion of a pneumococcal conjugate vaccine in its EPI. Although all vaccinations would be cost-effective, PCV-13 would save more costs to the healthcare system and would be the preferred strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition

    Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

    2014-01-01

    BACKGROUND: Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult

  16. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its...

  17. Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia.

    Aljunid, Syed; Abuduxike, Gulifeiya; Ahmed, Zafar; Sulong, Saperi; Nur, Amrizal Muhd; Goh, Adrian

    2011-09-21

    Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).

  18. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

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

    2011-01-01

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

  19. Hyposplenism as a cause of pneumococcal meningoencephalitis in an adult patient with coeliac disease

    Paolo Caraceni

    2013-03-01

    Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.

  20. The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.

    Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

    2014-01-01

    Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge. Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers. Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.

  1. Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7 in the context of the annual influenza epidemic and a severe influenza pandemic

    Strutton David R

    2010-01-01

    Full Text Available Abstract Background Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1 outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7 on pneumococcal disease incidence and mortality during a typical influenza season (13/100 and a severe influenza pandemic (30/100. Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd protection of non-vaccinated persons. Results The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd protection in the unvaccinated. Conclusions PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.

  2. Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic.

    Rubin, Jaime L; McGarry, Lisa J; Klugman, Keith P; Strutton, David R; Gilmore, Kristen E; Weinstein, Milton C

    2010-01-21

    Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.

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

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

    2014-01-01

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

  4. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial.

    Anna Roca

    2011-10-01

    Full Text Available Introduction of pneumococcal conjugate vaccines (PCVs of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.A cluster-randomized (by village trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006. Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults to receive one dose of PCV-7 (11 vaccinated villages or meningococcal serogroup C conjugate vaccine (10 control villages. Cross-sectional surveys (CSSs to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS, and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively. A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively. The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age and adults (≥15 y of age at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively. Differences in the prevalence of

  5. Evaluation of anti-pneumococcal capsular antibodies as adjunctive therapy in experimental pneumococcal meningitis

    Brandt, Christian; Frimodt-Moller, N; Lundgren, Jens Dilling

    2006-01-01

    OBJECTIVE: Bacteraemia concomitant with meningitis has been shown to greatly affect outcome. Consequently, the efficacy of serotype-specific anti-pneumococcal antiserum (APAS) was investigated in a rat model of pneumococcal meningitis. METHODS: Rats were infected with Streptococcus pneumoniae...... serotype 3. All rats received ceftriaxone starting 26 h post-infection. APAS was administered either at the time of infection or 26 h post-infection and effects were compared with rats treated with antibiotics only. RESULTS AND CONCLUSION: A significant clinical benefit was found when APAS was given...... at the time of infection whereas no effect was found when administered 26 h after infection. This work indicates that the clinical value of using APAS in pneumococcal meningitis may be limited...

  6. The epidemiology of invasive pneumococcal disease in the Canadian North from 1999 to 2010

    Melissa Helferty

    2013-08-01

    Full Text Available Introduction . The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009 and 13-valent (PCV-13 vaccines (2010. A 23-valent polysaccharide (PPV-23 vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010. Methods . A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada. Results . From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year. Incidence was greatest among infants aged <2 years and among those aged 65 years and older, with an average annual incidence of 133 and 67 cases per 100,000 population, respectively. After a peak in incidence in 2008, rates among infants have declined. Incidence rates varied from 2 to 16 times greater, depending on the year, among Aboriginals compared to non-Aboriginals. Hospitalization was reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical manifestations varied, with some patients reporting >1 manifestation. Pneumonia was the most common (70%, followed by bacteremia/septicaemia (30% and meningitis (8%. Approximately, 42% of cases aged <2 years in 2009 and 2010 had serotypes covered by the PCV-13. In addition, the majority (89% of serotypes isolated in cases

  7. Severe febrile systemic reaction to pneumococcal vaccine.

    Hasan, Syed; Yousef, Mahmoud; Shridharani, Sachin

    2005-02-01

    Polyvalent pneumococcal polysaccharide vaccine (Pneumovax, PPV) has been shown to substantially reduce the risk of Streptococcus pneumoniae infections in susceptible individuals. Side effects, such as mild local erythema, induration, pain and fever, have been reported with various frequencies. Rarely, systemic symptoms, including high fever, headache, nausea and photophobia, have been reported in the literature. This case report describes a 38-year-old male who developed severe and prolonged local and systemic symptoms necessitating hospitalization following a dose of pneumovax.

  8. Thrombotic Thrombocytopenic Purpura Associated with Pneumococcal Sepsis

    Jeffrey R Schriber

    1993-01-01

    Full Text Available The first documented case of thrombotic thrombocytopenic purpura (TTP associated with pneumococcal septicemia is reported. This association has been previously demonstrated with hemolytic uremic syndrome. The patient presented with recurrent seizures, oliguric renal failure, fever, thrombocytopenia and microangiopathic hemolytic anemia; coagulation studies were normal. Blood and sputum cultures were positive for Streptococcus pneumoniae. The patient responded to therapy with plasmapheresis and antiplatelet agents as well as antibiotics. Coincident infection should be searched for in all cases of TTP.

  9. Antibiotic Resistance in Childhood with Pneumococcal Infection

    Ali Gunes

    2013-10-01

    Full Text Available Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with meningitis, sepsis and urinary tract infections who admitted Dicle University Medicine School Children Clinic and Diyarbakir Pediatric Hospital Between December 2004-April 2007. Reproducing clinical specimens with alpha-hemolysis, optochin-sensitive, bile soluble and gram-positive diplococci morphology was defined as S. pneumoniae. The antimicrobial susceptibilities of strains were measured by the E-test method. MIC values of penicillin against pneumococci was accepted as <0.06 mg / ml value of the sensitive, 0.12-1μg/ml mid-level resistance, ≥ 2 mg / ml value of the high-level resistance. Results: It was found 16% mid-level penicillin resistance and 3.2% high-level penicillin resistance by E-test method. 80.7% of Strains were percent of the penicillin-sensitive. Seftiriakson resistance was found as 3.2%. there was not Vancomycin resistance. Discussion: We think penicillin therapy is enough effective for pneumococcal infections except serious conditions such as meningitis and sepsis. Also we think it should be supported by multicenter studies.

  10. The Saudi Thoracic Society pneumococcal vaccination guidelines-2016

    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 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

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

    Engelen-Lee, J.Y.; Brouwer, M.C.; Aronica, E.; van de Beek, D.

    2016-01-01

    Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and

  12. Pneumococcal meningitis: Clinical-pathological correlations (meningene-path)

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

    2016-01-01

    Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and

  13. Therapy for pneumococcal infection at the millennium: doubts and certainties.

    Ball, P

    1999-07-26

    Rapidly burgeoning worldwide multiple drug-resistant pneumococcal serotypes pose an urgent demand for new management approaches. Perhaps modern intensive care methods may have alternatives to offer. Indeed, standard assessments such as the admission APACHE II score may overestimate individual risk of death in severe CAP, and mortality can be reduced. However, among those at highest risk for mortality in the early phase of invasive disease, the conclusions reached 2-3 decades ago, that it is questionable whether a more effective drug than penicillin can be developed, and that a reduction in the number of deaths consequent to this infection can be accomplished only by widespread immunoprophylactic measures, remain inescapable. Clearly, as discussed elsewhere in this supplement, the continuing validity of these 20-year-old conclusions and the global prevalence of DRSP demand the development and marketing of new conjugate vaccines, although more widespread use of the existing 23-valent polysaccharide vaccine among high-risk populations is essential in the interim. With respect to resistance selection pressures, antibiotic prescription control may provide the answer. However, patient expectations of antibiotic therapy for trivial respiratory infection is high and, in the United Kingdom, 75% of previously healthy adults will receive it; those who do not will usually consult another physician in an effort to secure such therapy. Thus, without the intervention of government or managed care organizations, self-regulation in prescribing is unlikely. The evidence for beta-lactam treatment failure in meningitis has led to alternative approaches, with vancomycin as the primary agent. Penicillins may remain effective for otitis media, but oral cephalosporins are suspect. Data on pediatric pneumococcal pneumonia continue to suggest use of beta-lactams, at least for disease caused by strains with intermediate penicillin sensitivity. Pallares et al concluded that penicillins and

  14. PCR deduction of invasive and colonizing pneumococcal serotypes from Venezuela: a critical appraisal.

    Bello Gonzalez, Teresita; Rivera-Olivero, Ismar Alejandra; Sisco, María Carolina; Spadola, Enza; Hermans, Peter W; de Waard, Jacobus H

    2014-04-15

    Serotype surveillance of Streptococcus pneumoniae is indispensable for evaluating the potential impact of pneumococcal conjugate vaccines. Serotyping by the standard Quellung reaction is technically demanding, time consuming, and expensive. A simple and economical strategy is multiplex PCR-based serotyping. We evaluated the cost effectiveness of a modified serial multiplex PCR (mPCR), resolving 24 serotypes in four PCR reactions and optimally targeting the most prevalent invasive and colonizing pneumococcal serotypes found in Venezuela. A total of 223 pneumococcal isolates, 140 invasive and 83 carriage isolates, previously serotyped by the Quellung reaction and representing the 18 most common serotypes/groups identified in Venezuela, were serotyped with the adapted mPCR. The mPCR serotyped 76% of all the strains in the first two PCR reactions and 91% after four reactions, correctly identifying 17 serotypes/groups. An isolate could be serotyped with mPCR in less than 2 minutes versus 15 minutes for the Quellung reaction, considerably lowering labor costs. A restrictive weakness of mPCR was found for the detection of 19F strains. Most Venezuelan 19F strains were not typeable using the mPCR, and two 19F cps serotype variants were identified. The mPCR assay is an accurate, rapid, and economical method for the identification of the vast majority of the serotypes from Venezuela and can be used in place of the standard Quellung reaction. An exception is the identification of serotype 19F. In this setting, most 19F strains were not detectable with mPCR, demonstrating a need of serology-based quality control for PCR-based serotyping.

  15. Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious respiratory diseases and hospitalization rates in children

    Wanderci Marys Oliveira Abrão

    2015-02-01

    Full Text Available INTRODUCTION: In 2010, to reduce the occurrence of serious pneumococcal disease, the Ministry of Health in Brazil incorporated the 10-valent pneumococcal vaccine in the immunization schedule of children younger than two years of age. The objective of this study was to evaluate the impact of vaccination on the incidence of infectious respiratory diseases in infants before and after the introduction of the 10-valent pneumococcal vaccine. METHODS: This cross-sectional study involved primary care and hospital networks from a city in Minas Gerais State, Brazil, between 2009 and 2012. RESULTS: A 40% reduction in the prevalence of community-acquired pneumonia (CAP was observed after introducing the pneumococcal conjugate vaccine. Male children were 28% more likely to develop the disease. The prevalence ratio ([PR] = 1.96, 95% CI: 1.52 to 2.53, p < 0.05 suggested that not being vaccinated was associated with the occurrence of pneumonia. The prevalence of CAP was 70% lower (PR 0.30, 95% CI: 0.24 to 0.37, p<0.05 in children vaccinated as recommended compared to children with delayed vaccination, suggesting that the updated vaccine schedule improves protection. CONCLUSIONS: Immunization with the 10-valent pneumococcal vaccine appeared to reduce the number of pneumonia cases in children during the study period. Prospective studies are needed to confirm the efficacy of the vaccine against the occurrence of pneumococcal pneumonia.

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

    Ruth Link-Gelles

    2016-12-01

    Full Text Available 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, geocoding, 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. Keywords: Socioeconomic status, PCV13, Pneumococcus, Pneumococcal vaccine, Vaccine effectiveness, Matched case-control

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

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

    2016-01-01

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

  18. Estimating health service utilization for treatment of pneumococcal disease: the case of Brazil.

    Sartori, A M C; Novaes, C G; de Soárez, P C; Toscano, C M; Novaes, H M D

    2013-07-02

    Health service utilization (HSU) is an essential component of economic evaluations of health initiatives. Defining HSU for cases of pneumococcal disease (PD) is particularly complex considering the varying clinical manifestations and diverse severity. We describe the process of developing estimates of HSU for PD as part of an economic evaluation of the introduction of pneumococcal conjugate vaccine in Brazil. Nationwide inpatient and outpatient HSU by children under-5 years with meningitis (PM), sepsis (PS), non-meningitis non-sepsis invasive PD (NMNS), pneumonia, and acute otitis media (AOM) was estimated. We assumed that all cases of invasive PD (PM, PS, and NMNS) required hospitalization. The study perspective was the health system, including both the public and private sectors. Data sources were obtained from national health information systems, including the Hospital Information System (SIH/SUS) and the Notifiable Diseases Information System (SINAN); surveys; and community-based and health care facility-based studies. We estimated hospitalization rates of 7.69 per 100,000 children under-5 years for PM (21.4 for children Brazil. Estimating HSU for noninvasive disease was challenging, particularly in the case of outpatient care, for which secondary data are scarce. Information for the private sector is lacking in Brazil, but estimates were possible with data from the public sector and national population surveys. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Pediatric Invasive Pneumococcal Disease in Guatemala City: Importance of Serotype 2.

    Gaensbauer, James T; Asturias, Edwin J; Soto, Monica; Holt, Elizabeth; Olson, Daniel; Halsey, Neal A

    2016-05-01

    To inform estimations of the potential impact of recently introduced pneumococcal conjugate vaccine (PCV), we report results of 11 years of pre-PCV surveillance for invasive pneumococcal disease (IPD) among children in Guatemala City. Cases of IPD in children younger than 5 years were identified by active surveillance at 3 referral hospitals in Guatemala City from October 1996 through 2007. Clinical and demographic data were obtained, and isolates of Streptococcus pneumoniae from normally sterile sites were serotyped using latex agglutination and confirmed by Quellung reaction. Four hundred fifty-two cases of IPD were identified with a case fatality rate of 21%. Meningitis was the most common cause of death (77% of all deaths) and occurred more often in infancy (median age 5 months) than other clinical syndromes. Of the 137 isolates serotyped, type 1 (26 cases, 17%), type 2 (25 cases, 16%) and type 5 (18 cases, 12%) were the most common. Serotype 2 was associated with a higher case fatality rate (28%), higher rate of meningitis (68%) and occurred in younger infants (median age, 3.5 months) than other common serotypes. Recently introduced PCV13 includes 73% of observed serotypes in the study. Infants with IPD presented at a young age. Serotype 2, rarely reported as a significant cause of IPD and not included in available PCVs, was a common cause of disease in this population. PCV13 introduction in Guatemala, begun in 2013, may not have as great an impact in disease reduction as has been observed in other countries.

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

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

    2017-01-01

    Child contact is a recognised risk factor for adult pneumococcal disease. Peaks in invasive pneumococcal disease incidence observed during winter holidays may be related to changes in social dynamics. This analysis was conducted to examine adult pneumococcal community-acquired pneumonia (CAP) incidence during school holiday periods. Between September 2008 and 2013, consecutive adults admitted to hospitals covering the Greater Nottingham area with a diagnosis of CAP were studied. Pneumococcal pneumonia was detected using culture and antigen detection methods. Of 2221 adults studied, 575 (25.9%) were admitted during school holidays and 643 (29.0%) had pneumococcal CAP. CAP of pneumococcal aetiology was significantly more likely in adults admitted during school holidays compared to term time (35.3% versus 26.7%; adjusted OR 1.38, 95% CI 1.11–1.72, p=0.004). Over the 5-year period, the age-adjusted incidence of hospitalised pneumococcal CAP was higher during school holidays compared to term time (incident rate ratio 1.35, 95% CI 1.14–1.60, pholidays compared to term time (42.0% versus 33.7%, OR 1.43, 95% CI 1.00–2.03, p=0.046). Further study of transmission dynamics in relation to these findings and to identify appropriate intervention strategies is warranted. PMID:28326311

  1. INCIDENCE OF PNEUMOCOCCAL INFECTION IN THE WESTERN EUROPEAN COUNTRIES. INTERNATIONAL EXPERIENCE IN USING SEVEN-VALENT PNEUMOCOCCAL CONJUGATED VACCINE

    article editorial

    2008-01-01

    Full Text Available 20 февраля 2008 г. в рамках XII Конгресса педиатров России состоялся симпозиум «Пневмококковая инфекция: опасная и непредсказуемая. Можно ли предотвратить беду?», на котором был представлен доклад доктора Дэвида Макинтоша. Д. Макинтош занимает должность почетного педиатра в детской больнице «Грейт Ормонд Стрит» в Лондоне (Великобритания. Сегодня мы предлагаем Вашему вниманию доклад доктора, в котором он использовал собственные материалы и данные профессора Ральфа Рене Райнера (Германия.(Педиатрическая фармакология 2008;5(2:51-53

  2. Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease.

    Sousa, Adrian; Pérez-Rodríguez, Maria Teresa; Nodar, Andrés; Martínez-Lamas, Lucía; Vasallo, Francisco Jose; Álvarez-Fernández, Maximiliano; Crespo, Manuel

    2017-06-22

    Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). We present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. A total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0

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

    Sparding, Nadja; Dayie, Nicholas Tete Kwaku Dzifa; Mills, Richael O.

    2015-01-01

    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 Gh...... 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....

  4. A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

    Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

    2015-12-16

    Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information

  5. Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis

    Andersen, Christian Østergaard; Leib, S.L.; Rowland, Ian J

    2010-01-01

    ABSTRACT: BACKGROUND: Bacteremia and systemic complications both play important roles in brain pathophysiological alterations and the outcome of pneumococcal meningitis. Their individual contributions to the development of brain damage, however, still remain to be defined. METHODS: Using an adult...... rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n=11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype......-specific pneumococcal antibodies (n=14), and III. uninfected controls (n=6). RESULTS: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P=0.0003). Also, meningitis with an attenuation of bacteremia...

  6. NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5 - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during...

  7. NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  8. Influence of bacterial interactions on pneumococcal colonization of the nasopharynx.

    Shak, Joshua R; Vidal, Jorge E; Klugman, Keith P

    2013-03-01

    Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. NNDSS - Table II. Invasive pneumococcal disease, all ages

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, all ages - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  10. Delayed cerebral thrombosis complicating pneumococcal meningitis: an autopsy study

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

    2018-01-01

    Background: Delayed cerebral thrombosis (DCT) is a devastating cerebrovascular complication in patients with excellent initial recovery of pneumococcal meningitis. The aetiology is unknown, but direct bacterial invasion, activation of coagulation or post-infectious immunoglobulin deposition has been

  11. NNDSS - Table II. Invasive pneumococcal disease, age <5

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, age <5 - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  12. Promoting pneumococcal immunizations among rural Medicare beneficiaries using multiple strategies.

    Johnson, Elizabeth A; Harwell, Todd S; Donahue, Peg M; Weisner, M'liss A; McInerney, Michael J; Holzman, Greg S; Helgerson, Steven D

    2003-01-01

    Vaccine-preventable diseases among adults are major contributing causes of morbidity and mortality in the United States. However, adult immunizations continue to be underutilized in both urban and rural areas. To evaluate the effectiveness of a community-wide education campaign and mailed reminders promoting pneumococcal immunizations to rural Medicare beneficiaries. We implemented a community-wide education campaign, and mailed reminders were sent to Medicare beneficiaries in 1 media market in Montana to increase pneumococcal immunizations. In a second distinct media market, mailed reminders only were sent to beneficiaries. The proportion of respondents aged 65 years and older aware of pneumococcal immunizations increased significantly from baseline to follow-up among respondents both in the education-plus-reminder (63% to 78%, P = 0.04) and the reminder-only (64% to 74%, P = 0.05) markets. Overall from 1998 to 1999, there was a 3.7-percentage-point increase in pneumococcal immunization claims for Medicare beneficiaries in the education-plus-reminder market and a 1.5-percentage-point increase in the reminder-only market. Medicare beneficiaries sent reminders in the education-plus-reminder market compared to those in the reminder-only market were more likely to have a claim for pneumococcal immunization in 1999 (odds ratio 1.18, 95% confidence interval 1.08 to 1.28). The results suggest that these quality improvement strategies (community education plus reminders and reminders alone) modestly increased pneumococcal immunization awareness and pneumococcal immunization among rural adults. Mailed reminder exposure was associated with an increased prevalence of pneumococcal immunizations between 1998 and 1999 and was augmented somewhat by the education campaign.

  13. Spermidine Biosynthesis and Transport Modulate Pneumococcal Autolysis

    Potter, Adam J.

    2014-01-01

    Polyamines are small cationic molecules that have far-reaching roles in biology. In the case of pathogenic bacteria, these functions include those central to their pathogenesis. Streptococcus pneumoniae is a major bacterial pathogen, causing a diverse range of diseases that account for significant morbidity and mortality worldwide. In this work, we characterize the polyamine biosynthetic pathway of S. pneumoniae, demonstrating that this organism produces spermidine from arginine. The synthesis of spermidine was found to be nonessential for growth in a polyamine-free chemically defined medium. However, mutant strains lacking the ability to synthesize or transport spermidine displayed a significant delay in the onset of autolysis. We provide evidence for a model in which spermidine modulates the activity of the major autolysin LytA in the pneumococcal cell wall compartment via interactions with negatively charged molecules, such as teichoic acids. PMID:25092031

  14. Pediatric invasive pneumococcal disease in Senegal.

    Ba, I D; Ba, A; Faye, P M; Thiongane, A; Attiyé Kane, M; Sonko, A; Diop, A; Deme Ly, I; Diouf, F N; Ndiaye, O; Leye, M M M; Cissé, M F; Ba, M

    2015-01-01

    We aimed to describe the clinical, epidemiological, and outcome characteristics of IPD case patients hospitalized at the Albert-Royer National Children's Hospital (French acronym CHNEAR) to evaluate the disease burden of IPDs in a pediatric hospital of Dakar (Senegal). All children aged 0-15 years hospitalized at the CHNEAR between January 1st, 2008 and December 31st, 2013 for a documented IPD were included in the study. Medical history, risk factors, clinical, bacteriological, and outcome data was collected. Data was then analyzed using the SPSS software, version 16 (Pearson's Chi(2) test: a P-valueSenegal. Infants<2 years of age are particularly affected. The very high case fatality (17%) was significantly associated with meningeal infection sites hence the need for better access to pneumococcal vaccines. Copyright © 2015. Published by Elsevier SAS.

  15. Characterization of a pneumococcal meningitis mouse model

    Mook-Kanamori Barry

    2012-03-01

    Full Text Available Abstract Background S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation. Methods Adult mice (C57BL/6 were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 104, 105, 106 and 107 CFU and survival studies were performed. Cerebrospinal fluid (CSF, brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6 and 30 hours (n = 6. Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex® in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies. Results Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs. Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively. Conclusion We have developed and validated a murine model of pneumococcal meningitis.

  16. Burden of vaccine-preventable pneumococcal disease in hospitalized adults: A Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study.

    LeBlanc, Jason J; ElSherif, May; Ye, Lingyun; MacKinnon-Cameron, Donna; Li, Li; Ambrose, Ardith; Hatchette, Todd F; Lang, Amanda L; Gillis, Hayley; Martin, Irene; Andrew, Melissa K; Boivin, Guy; Bowie, William; Green, Karen; Johnstone, Jennie; Loeb, Mark; McCarthy, Anne; McGeer, Allison; Moraca, Sanela; Semret, Makeda; Stiver, Grant; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; McNeil, Shelly A

    2017-06-22

    Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized

  17. A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

    Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

    2008-08-18

    CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

  18. Pediatric Acute Otitis Media in the Era of Pneumococcal Vaccination.

    Tawfik, Kareem O; Ishman, Stacey L; Altaye, Mekibib; Meinzen-Derr, Jareen; Choo, Daniel I

    2017-05-01

    Objectives (1) Describe longitudinal trends in annual prevalence of hospital admission for pediatric acute otitis media (AOM) and complications of AOM (CAOM) since introduction of pneumococcal vaccination in 2000 and (2) describe the longitudinal trend of prevalence of hospital admission for pneumococcal meningitis in children with AOM-related diagnoses in the postvaccination era. Study Design Retrospective analysis of Kids' Inpatient Database from 2000 to 2012. Setting Community, nonrehabilitation hospitals. Subjects and Methods To determine annual prevalence of admission for AOM/CAOM, nationally weighted frequencies of children aged otitis media, acute mastoiditis, suppurative labyrinthitis, and/or acute petrositis were collected. The frequency of coexisting pneumococcal meningitis diagnoses among these patients was also collected. Trend analysis of prevalences of admission for AOM/CAOM and for pneumococcal meningitis occurring in the setting of AOM/CAOM from 2000 to 2012 was performed. Results Between 2000 and 2012, annual prevalence of admission for AOM/CAOM decreased from 3.956 to 2.618 per 100,000 persons ( P < .0001) (relative risk reduction 34%). Declines in admission prevalence were most pronounced in children <1 year of age (from 22.647 to 8.715 per 100,000 persons between 2000 and 2012, P < .0001) and 1 to 2 years of age (from 13.652 to 5.554 per 100,000 persons between 2000 and 2012, P < .0001). For all ages, the admission prevalence for pneumococcal meningitis and concomitant AOM/CAOM decreased (from 1.760 to 0.717 per 1,000,000 persons, P < .0001) over the study period. Conclusions The prevalence of hospital admission for pediatric AOM/CAOM has declined since the advent of pneumococcal vaccination. Admission rates for pneumococcal meningitis with AOM/CAOM have similarly declined.

  19. RAPID DETECTION OF PNEUMOCOCCAL ANTIGEN IN PLEURAL FLUID OF PATIENTS WITH COMMUNITY ACQUIRED PNEUMONIA

    BOERSMA, WG; LOWENBERG, A; HOLLOWAY, Y; KUTTSCHRUTTER, H; SNIJDER, JAM; KOETER, GH

    Background Detection of pneumococcal antigen may help to increase the rate of diagnosis of pneumococcal pneumonia. This study was designed to determine the value of rapid detection of pneumococcal antigen in pleural fluid from patients with community acquired pneumonia. Methods Thoracentesis was

  20. Long-term mortality after IPD and bacteremic versus non-bacteremic pneumococcal pneumonia

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

    2017-01-01

    Short-term mortality after invasive pneumococcal disease (IPD) and pneumococcal pneumonia is high but data on long-term mortality (including the comparison between bacteremic and non-invasive/non-bacteremic pneumococcal pneumonia) within the first years after diagnosis are scarce. Adult patients

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

    Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn

    2016-01-01

    This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded...

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

    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. PMID:26451658

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

    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.

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

    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

  5. Using the 4 Pillars Practice Transformation Program to Increase Pneumococcal Immunizations for Older Adults: A Cluster-Randomized Trial.

    Zimmerman, Richard K; Brown, Anthony E; Pavlik, Valory N; Moehling, Krissy K; Raviotta, Jonathan M; Lin, Chyongchiou J; Zhang, Song; Hawk, Mary; Kyle, Shakala; Patel, Suchita; Ahmed, Faruque; Nowalk, Mary Patricia

    2017-01-01

    To test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars Practice Transformation Program, to increase adult pneumococcal vaccination. Randomized controlled cluster trial (RCCT) in Year 1 (June 1, 2013 to May 31, 2014) and pre-post study in Year 2 (June 1, 2014 to January 31, 2015) with data analyzed in 2016. Baseline year was June 1, 2012, to May 31, 2013. Demographic and vaccination data were derived from deidentified electronic medical record extractions. Primary care practices (n = 25) stratified according to metropolitan area (Houston, Pittsburgh), location (rural, urban, suburban), and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n = 13) or Year 2 (n = 12). Individuals aged 65 and older at baseline (N = 18,107; mean age 74.2; 60.7% female, 16.5% non-white, 15.7% Hispanic). The 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) vaccination rates and percentage point (PP) changes in vaccination rates. In the Year 1 RCCT, PPSV vaccination rates increased significantly in all intervention and control groups, with average increases ranging from 6.5 to 8.7 PP (P < .001). The intervention was not related to greater likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh but not in Houston. In a RCCT, PPSV vaccination rates increased in the intervention and control groups in Year 1. In a pre-post study, private primary care practices actively participating in the 4 Pillars Practice Transformation Program improved PPSV and PCV uptake significantly more than practices that were in the maintenance phase of the study. © 2016, Copyright the Authors Journal compilation © 2016, The American

  6. Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis

    Brandt, Christian T; Holm, David; Liptrot, Matthew

    2008-01-01

    BACKGROUND: Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain. METHODS: Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study...... rats: (1) rats with attenuated bacteremia resulting from intravenous injection of serotype-specific pneumococcal antibody, (2) rats with early-onset bacteremia resulting from concomitant intravenous infection, or (3) a meningitis control group. The blood-brain barrier (BBB) breakdown, ventricle size......, brain water distribution, and brain pathologic findings were analyzed using magnetic resonance morphological and functional imaging. Laboratory data and clinical disease scores were obtained. RESULTS: Attenuation of the bacteremic component of pneumococcal meningitis improved clinical disease symptoms...

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

    Quesne Gilles

    2003-11-01

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

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

    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.

  9. Pneumococcal Serotypes Colonise the Nasopharynx in Children at Different Densities.

    Fernanda Rodrigues

    Full Text Available Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve and relative abundance (microarray and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher and 3, 38 and non-typeables (lower (p<0.05 with a similar hierarchy when only a single serotype carriage was assessed. There was no evidence of any overall density differences between children with single or multiple serotypes detected but serotypes with mid-range densities were more prevalent. The hierarchy of distinct pneumococcal serotype carriage densities described here for the first time, may help explain the dynamics of transmission between children.

  10. 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.

    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. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  11. Effect of early measles vaccine on pneumococcal colonization

    Hansen, Nadja Skadkær; Byberg, Stine; Hervig Jacobsen, Lars

    2017-01-01

    BACKGROUND: Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection....... OBJECTIVE: We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. METHOD: The study was conducted in 2013-2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block...

  12. Using Dynamic Transmission Modeling to Determine Vaccination Coverage Rate Based on 5-Year Economic Burden of Infectious Disease: An Example of Pneumococcal Vaccine.

    Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen

    2015-05-01

    Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  13. Characterization of pneumococcal purpura-producing principle.

    Chetty, C; Kreger, A

    1980-07-01

    hypothesis that activity is associated with pneumococcal peptidoglycan solubilized by the bacterium's autolysin.

  14. Host and microbe characteristics of pneumococcal colonization in elderly

    Krone, C.L.

    2013-01-01

    The focus of this thesis was to investigate various aspects of pneumococcal – host –commensal interactions in the respiratory tract of the elderly. Furthermore, we aimed to address the paucity of information regarding the underlying mechanisms of disease in this high risk group. Since Streptococcus

  15. Patient outcome in adults with pneumococcal meningitis or ...

    Among these, 158 of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n=64), 20% for pneumococcaemic pneumonia (n=92) and 26% for patients with pneumococcaemia without localising signs (n=43). Lowered conscious level (OR 5.8, p<0.001), hypotension(OR ...

  16. Pneumococcal Pneumonia and Pandemic H1N1

    2012-06-06

    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  17. Identification, variation and transcription of pneumococcal repeat sequences

    2011-01-01

    Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

  18. PNEUMOCOCCAL INFECTION: MODERN VIEW ON THE ISSUE AND PREVENTION

    V.К. Tatochenko

    2007-01-01

    Full Text Available Pneumococci are spread everywhere and they are very often a component of the microflora of the upper respiratory tracts. The level of the pneumococcus carriage is correlated with age. Among children the highest frequency is observed at the age of 4,5 years (up to 90% of cases, among adults it is 5–10%. According to international and Russian data, pneumococcal infection causes up to 76% of all the aetiologically deciphered cases of community cacquired pneumonia among adults and up to 94% (aggravated cases among children. The most frequent clinical forms of pneumococcal infection among children are acute otitis media (over 30%, pneumonia and meningitis (about 5–20% of all purulent bacterial meningitis, among adults — meningitis and sepsis. In 1998, in Russia was registered the first and still the only vaccine for the prevention of pneumococcal infection — Pneumo 23 (Sanofi Pasteur. The vaccine consists of 23 antic gens of the most dangerous pneumococcus serotypes and is used for the prevention of all the forms of pneumococcal infection. The composition of Pneumo 23 corresponds to 85% of pneumococcus serotypes circulating across Europe and to 90% serotypes resistant to penicillin. According to Russian data Pneumo 23 consists of about 80% of pneumococcus serotypes isolated in healthy carriers and ill with acute respiratory diseases and of 92% of serotypes in those suffering from acute bronchitis and pneumonia. The results of the clinical studies allow us to recommend the use of the given vaccine in a complex therapy of children, suffering from latent TB infection, often recurrent episodes of bronchopulmonary pathologies, ENT diseases, bronchial asthma and other chronic diseases.Key words: therapy, pediatrics, pneumonia, bronchial asthma, chronic obstructive lungs disease, prevention, treatment, pneumococcal infection.

  19. Pharmacists as providers: targeting pneumococcal vaccinations to high risk populations.

    Taitel, Michael; Cohen, Ed; Duncan, Ian; Pegus, Cheryl

    2011-10-19

    Older adults and persons with chronic conditions are at increased risk for pneumococcal disease. Severe pneumococcal disease represents a substantial humanistic and economic burden to society. Although pneumococcal vaccination (PPSV) can decrease risk for serious consequences, vaccination rates are suboptimal. As more people seek annual influenza vaccinations at community pharmacies, pharmacists have the ability to identify at-risk patients and provide PPSV. The objective of this study was to evaluate the impact of pharmacists educating at-risk patients on the importance of receiving a pneumococcal vaccination. Using de-identified claims from a large, national pharmacy chain, all patients who had received an influenza vaccination between August 1, 2010 and November 14, 2010 and who were eligible for PPSV were identified for the analysis. Based on the Advisory Committee on Immunization Practices recommendations, at-risk patients were identified as over 65 years of age or as aged 2-64 with a comorbid conditions. A benchmark medical and pharmacy claims database of commercial and Medicare health plan members was used to derive a PPSV vaccination rate typical of traditional care delivery to compare to pharmacy-based vaccination. Period incidence of PPSV was calculated and compared. Among the 1.3 million at-risk patients who were vaccinated by a pharmacist during the study period, 65,598 (4.88%) also received a pneumococcal vaccine. This vaccination rate was significantly higher than the benchmark rate of 2.90% (34,917/1,204,104; pvaccination rate (6.60%; 26,430/400,454) of any age group. Pharmacists were successful at identifying at-risk patients and providing additional immunization services. Concurrent immunization of PPSV with influenza vaccination by pharmacists has potential to improve PPSV coverage. These results support the expanding role of community pharmacists in the provision of wellness and prevention services. Copyright © 2011 Elsevier Ltd. All rights

  20. An audit of influenza and pneumococcal vaccination in rheumatology outpatients.

    Sowden, Evin; Mitchell, William S

    2007-07-04

    Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p risk factors was confirmed as significant in determining vaccination status by logistic regression for both influenza (OR 10.89, p < 0.001) and streptococcus pneumoniae (OR 4.55, p = 0.002). The diagnosis of rheumatoid arthritis was also found to be a significant factor for pneumococcal vaccination (OR 5.1, p = 0.002). There was a negative trend suggesting that patients on major immunosuppressants are less likely to be immunised against pneumococcal antigen (OR 0.35, p = 0.067). Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.

  1. Pneumococcal conjugate vaccines; impact on nasopharyngeal bacterial carriage and optimizing vaccination strategies

    Spijkerman, J.

    2013-01-01

    The aim of this thesis was to first assess nasopharyngeal bacterial carriage to evaluate population effects after introduction of PCV7 in the NIP in 2006 and to assess the potential impact of PCV10 as introduced in 2011 on carriage of NTHi in a randomized trial (Part One) and second, to assess

  2. Genetic diversity of pneumococcal surface protein A in invasive pneumococcal isolates from Korean children, 1991-2016.

    Yun, Ki Wook; Choi, Eun Hwa; Lee, Hoan Jong

    2017-01-01

    Pneumococcal surface protein A (PspA) is an important virulence factor of pneumococci and has been investigated as a primary component of a capsular serotype-independent pneumococcal vaccine. Thus, we sought to determine the genetic diversity of PspA to explore its potential as a vaccine candidate. Among the 190 invasive pneumococcal isolates collected from Korean children between 1991 and 2016, two (1.1%) isolates were found to have no pspA by multiple polymerase chain reactions. The full length pspA genes from 185 pneumococcal isolates were sequenced. The length of pspA varied, ranging from 1,719 to 2,301 base pairs with 55.7-100% nucleotide identity. Based on the sequences of the clade-defining regions, 68.7% and 49.7% were in PspA family 2 and clade 3/family 2, respectively. PspA clade types were correlated with genotypes using multilocus sequence typing and divided into several subclades based on diversity analysis of the N-terminal α-helical regions, which showed nucleotide sequence identities of 45.7-100% and amino acid sequence identities of 23.1-100%. Putative antigenicity plots were also diverse among individual clades and subclades. The differences in antigenicity patterns were concentrated within the N-terminal 120 amino acids. In conclusion, the N-terminal α-helical domain, which is known to be the major immunogenic portion of PspA, is genetically variable and should be further evaluated for antigenic differences and cross-reactivity between various PspA types from pneumococcal isolates.

  3. The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.

    Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

    2016-07-25

    Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Optical phase conjugation

    Fisher, Robert A

    1983-01-01

    This book appears at a time of intense activity in optical phase conjugation. We chose not to await the maturation of the field, but instead to provide this material in time to be useful in its development. We have tried very hard to elucidate and interrelate the various nonlinear phenomena which can be used for optical phase conjugation.

  5. Pneumococcal meningitis post-cochlear implantation: preventative measures.

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

    2010-11-01

    Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis. Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention. Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route. The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis. Copyright © 2010 American Academy of Otolaryngology–Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

  6. An audit of influenza and pneumococcal vaccination in rheumatology outpatients

    Mitchell William S

    2007-07-01

    Full Text Available Abstract Background Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. Method We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Results Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p Conclusion Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.

  7. Advance market commitment for pneumococcal vaccines: putting theory into practice.

    Cernuschi, Tania; Furrer, Eliane; Schwalbe, Nina; Jones, Andrew; Berndt, Ernst R; McAdams, Susan

    2011-12-01

    Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013.This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty - and the AMC's apparent early success - in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields.

  8. Pneumococcal lipoproteins involved in bacterial fitness, virulence, and immune evasion.

    Kohler, Sylvia; Voß, Franziska; Gómez Mejia, Alejandro; Brown, Jeremy S; Hammerschmidt, Sven

    2016-11-01

    Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a serious pathogen causing a variety of diseases. The dynamic interaction between pneumococci and resident host cells during colonization of the upper respiratory tract and at the site of infection is critical for bacterial survival and the development of disease. Pneumococcal lipoproteins are peripherally anchored membrane proteins and have pivotal roles in bacterial fitness including envelope stability, cell division, nutrient acquisition, signal transduction, transport (as substrate-binding proteins of ABC transporter systems), resistance to oxidative stress and antibiotics, and protein folding. In addition, lipoproteins are directly involved in virulence-associated processes such as adhesion, colonization, and persistence through immune evasion. Conversely, lipoproteins are also targets for the host response both as ligands for toll-like receptors and as targets for acquired antibodies. This review summarizes the multifaceted roles of selected pneumococcal lipoproteins and how this knowledge can be exploited to combat pneumococcal infections. © 2016 Federation of European Biochemical Societies.

  9. Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older

    Salsench Elisabet

    2010-03-01

    Full Text Available Abstract Background The 23-valent polysaccharide pneumococcal vaccine (PPV is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD among people over 60 years. Methods Population-based case-control study that included 88 case patients over 60 years-old with a laboratory-confirmed IPD (bacteraemic pneumonia, meningitis or sepsis and 176 outpatient control subjects who were matched by primary care centre, age, sex and risk stratum. Adjusted odds ratios (ORs for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was estimated as (1 - OR ×100. Results Pneumococcal vaccination rate was significantly lower in cases than in control subjects (38.6% vs 59.1%; p = 0.002. The adjusted vaccine effectiveness was 72% (OR: 0.28; 95% CI: 0.15-0.54 against all IPD and 77% (OR: 0.23; 95% CI: 0.08-0.60 against vaccine-type IPD. Vaccination was significantly effective against all IPD in both age groups: 60-79 years-old (OR 0.32; 95% CI: 0.14-0.74 and people 80 years or older (OR: 0.29; 95% CI: 0.09-0.91. Vaccination appears significantly effective as for high-risk immunocompetent subjects (OR: 0.29; 95% CI: 0.11-0.79 as well as for immunocompromised subjects (OR: 0.12; 95% CI: 0.03-0.53. Conclusion These findings confirm the effectiveness of the 23-valent PPV against IPD, and they also support the benefit of vaccination in preventing invasive infections among high-risk and older people.

  10. Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease.

    Weimer, Kristin E D; Armbruster, Chelsie E; Juneau, Richard A; Hong, Wenzhou; Pang, Bing; Swords, W Edward

    2010-10-01

    Otitis media is an extremely common pediatric infection and is mostly caused by bacteria that are carried within the nasopharyngeal microbiota. It is clear that most otitis media cases involve simultaneous infection with multiple agents. Chinchillas were infected with nontypeable Haemophilus influenzae, Streptococcus pneumoniae, or a combination of both organisms, and the course of disease was compared. In vitro experiments were also performed to address how coinfection impacts biofilm formation. The incidence of systemic disease was reduced in coinfected animals, compared with those infected with pneumococcus alone. Pneumococci were present within surface-attached biofilms in coinfected animals, and a greater proportion of translucent colony type was observed in the coinfected animals. Because this colony type has been associated with pneumococcal biofilms, the impact of coinfection on pneumococcal biofilm formation was investigated. The results clearly show enhanced biofilm formation in vitro by pneumococci in the presence of H. influenzae. Based on these data, we conclude that coinfection with H. influenzae facilitates pneumococcal biofilm formation and persistence on the middle ear mucosal surface. This enhanced biofilm persistence correlates with delayed emergence of opaque colony variants within the bacterial population and a resulting decrease in systemic infection.

  11. Evaluating the costs of pneumococcal disease in selected Latin American countries.

    Constenla, Dagna

    2007-10-01

    To estimate the costs of pneumococcal disease in Brazil, Chile and Uruguay, to describe how these costs vary between different patient groups, and to discuss factors that affect these cost variations. The cost of pneumococcal disease was estimated from the health care perspective. For each country, baseline cost estimates were primarily developed using health resources information from patient-level data and facility-specific cost data. A regression model was constructed separately for four types of pneumococcal diseases. The skewness-kurtosis test and the Cook-Weisberg test were performed to test the normality of the residuals and the heteroscedasticity, respectively. The treatment of pneumococcal meningitis generated up to US$ 5 435 per child. The treatment costs of pneumococcal pneumonia were lower, ranging from US$ 372 per child to US$ 3 483 per child. Treatment of acute otitis media cost between US$ 20 per child and US$ 217 per child. The main source of treatment costs variations was level of service provided and country in which costs were incurred. However, the tendency of costs to change with these variables was not statistically significant at the 5% level for most pneumococcal disease models. Pneumococcal disease resulted in significant economic burden to selected health care systems in Latin America. The patterns of treatment cost of pneumococcal disease showed a great deal of variation.

  12. Antibody Responses to Pneumococcal Polysaccharide Vaccine in Taiwanese Patients with Chronic Obstructive Pulmonary Disease

    Chih-Cheng Lai

    2007-01-01

    Conclusion: Taiwanese elderly adults with COPD, even in advanced age, can mount a significant antibody response to pneumococcal polysaccharide vaccine. This study may support the existing recommendation that pneumococcal vaccine be offered to persons ≥ 65 years old with COPD. [J Formos Med Assoc 2007;106(3: 196-203

  13. [Pneumococcal carriage in mothers and children of the Panare Amerindians from the State of Bolivar, Venezuela].

    Bello Gonzalez, T.; Rivera-Olivero, I.A.; Pocaterra, L.; Spadola, E.; Araque, M.; Hermans, P.W.M.; Waard, J.H. de

    2010-01-01

    In North America, the indigenous groups have been identified as a population with increased risk of pneumococcal colonization and pneumococcal invasive disease. However, little information is available from South American natives. In the present study we evaluated the nasopharyngeal carriage and

  14. Recurrent severe invasive pneumococcal disease in an adult with previously unknown hyposplenia

    Ballegaard, Vibe C; Schejbel, Lone; Hoffmann, Steen

    2015-01-01

    was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of severe......BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode...... of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and apparently...

  15. Using the 4 Pillars™ Immunization Toolkit to Increase Pneumococcal Immunizations for Older Adults: A Cluster Randomized Trial

    Zimmerman, Richard K.; Brown, Anthony E.; Pavlik, Valory N.; Moehling, Krissy K.; Raviotta, Jonathan M.; Lin, Chyongchiou J.; Zhang, Song; Hawk, Mary; Kyle, Shakala; Patel, Suchita; Ahmed, Faruque; Nowalk, Mary Patricia

    2016-01-01

    BACKGROUND Quality improvement in primary care has focused on improving adult immunization. OBJECTIVES Test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars™ Immunization Toolkit, to increase adult pneumococcal vaccination. DESIGN Randomized controlled cluster trial (RCCT) in Year 1 (6/1/2013–5/31/2014) and a pre-post study in Year 2 (6/1/2014–1/31/2015) with data analyzed in 2016. Baseline year was 6/1/2012–5/31/2013. Demographic and vaccination data were derived from de-identified EMR extractions. SETTING 25 primary care practices stratified by city (Houston, Pittsburgh), location (rural, urban, suburban) and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n=13) or Year 2 (n=12). PARTICIPANTS A cohort of 18,107 patients ≥65 years at baseline with a mean age of 74.2 years; 60.7% were women, 16.5% were non-white and 15.7% were Hispanic. INTERVENTION The Toolkit, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) rates and percentage point (PP) changes. RESULTS In the RCCT, all intervention and control groups had significantly higher PPSV vaccination rates with average increases ranging from 6.5–8.7 PP (P<0.01). The intervention was not related to higher likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh, but not in Houston. CONCLUSION In a randomized controlled cluster trial, both intervention and control groups increased PPSV among adults ≥65 years. In a pre-post study, private primary care practices using the 4 Pillars™ Immunization Toolkit significantly improved PPSV and PCV uptake compared with practices that were in the maintenance phase of the study. PMID:27755655

  16. Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination

    Mackenzie Grant

    2009-02-01

    Full Text Available Abstract Background Aboriginal children in remote Australia have high rates of complicated middle ear disease associated with Streptococcus pneumoniae and other pathogens. We assessed the effectiveness of pneumococcal vaccination for prevention of otitis media in this setting. Methods We compared two birth cohorts, one enrolled before (1996–2001, and the second enrolled after introduction of 7-valent pneumococcal conjugate and booster 23-valent polysaccharide vaccine (2001–2004. Source populations were the same for both cohorts. Detailed examinations including tympanometry, video-recorded pneumatic otoscopy and collection of discharge from tympanic membrane perforations, were performed as soon as possible after birth and then at regular intervals until 24 months of life. Analyses (survival, point prevalence and incidence were adjusted for confounding factors and repeated measures with sensitivity analyses of differential follow-up. Results Ninety-seven vaccinees and 51 comparison participants were enrolled. By age 6 months, 96% (81/84 of vaccinees and 100% (41/41 of comparison subjects experienced otitis media with effusion (OME, and by 12 months 89% and 88% experienced acute otitis media (AOM, 34% and 35% experienced tympanic membrane perforation (TMP and 14% and 23% experienced chronic suppurative otitis media (CSOM. Age at the first episode of OME, AOM, TMP and CSOM was not significantly different between the two groups. Adjusted incidence of AOM (incidence rate ratio: 0.88 [95% confidence interval (CI: 0.69–1.13] and TMP (incidence rate ratio: 0.63 [0.36–1.11] was not significantly reduced in vaccinees. Vaccinees experienced less recurrent TMP, 9% (8/95 versus 22% (11/51, (odds ratio: 0.33 [0.11–1.00]. Conclusion Results of this study should be interpreted with caution due to potential bias and confounding. It appears that introduction of pneumococcal vaccination among Aboriginal infants was not associated with significant changes

  17. Verifying influenza and pneumococcal immunization status of children in 2009-2010 from primary care practice records and from the North Carolina Immunization Registry.

    Poehling, Katherine A; Vannoy, Lauren; Peters, Timothy R

    2013-01-01

    The North Carolina Immunization Registry (NCIR) has been available since 2004. We sought to measure its utilization among practices that provide primary care for children who are enrolled in a prospective influenza surveillance study. This study included children aged 0.5-17 years who presented with fever or acute respiratory symptoms to an emergency department or inpatient setting in Winston-Salem, North Carolina, from September 1, 2009, through May 19, 2010. Study team members verified influenza and pneumococcal immunization status by requesting records from each child's primary care practice and by independently reviewing the NCIR. We assessed agreement of nonregistry immunization medical records with NCIR data using the kappa statistic. Fifty-six practices confirmed the immunization status of 292 study-enrolled children. For most children (238/292, 82%), practices verified the child's immunizations by providing a copy of the NCIR record. For 54 children whose practices verified their immunizations by providing practice records alone, agreement with the NCIR by the kappa statistic was 0.6-0.7 for seasonal and monovalent H1N1 influenza vaccines and 0.8-0.9 for pneumococcal conjugate and polysaccharide vaccines. A total of 221 (98%) of 226 enrolled children younger than 6 years of age had 2 or more immunizations documented in the NCIR. NCIR usage may vary in other regions of North Carolina. More than 95% of children younger than 6 years of age had 2 or more immunizations documented in the NCIR; thus, the Centers for Disease Control and Prevention 2010 goal for immunization information systems was met in this population. We found substantial agreement between practice records and the NCIR for influenza and pneumococcal immunizations in children.

  18. Qualidade conjugal: mapeando conceitos

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  19. Conjugate Gaze Palsies

    ... version Home Brain, Spinal Cord, and Nerve Disorders Cranial Nerve Disorders Conjugate Gaze Palsies Horizontal gaze palsy Vertical ... Version. DOCTORS: Click here for the Professional Version Cranial Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia ...

  20. Conjugated Polymer Solar Cells

    Paraschuk, Dmitry Y

    2006-01-01

    This report results from a contract tasking Moscow State University as follows: Conjugated polymers are promising materials for many photonics applications, in particular, for photovoltaic and solar cell devices...

  1. Polymers for Protein Conjugation

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

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

    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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Wittwer Matthias

    2006-06-01

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

  4. Molecular epidemiology of pneumococcal isolates from children in China

    Li-Hua Kang

    2016-04-01

    Full Text Available Objectives: To investigate the molecular epidemiology of pneumococcal isolates in Chongqing, China. Methods: In this cross-sectional study, 51 invasive Streptococcus pneumoniae (S. pneumoniae strains were from children with invasive pneumococcal disease (IPD and 32 carriage strains from healthy children from January 2010 to December 2013 at the Children’s Hospital of Chongqing Medical University, Chongqing, China. Multilocus sequence typing was used to identify the sequence types (STs. Capsular serotypes were determined by multiplex polymerase chain reaction. Drug susceptibility and resistance was determined by minimum inhibitory concentrations. Results: In this study, 11 serotypes were identified among the 83 S. pneumoniae clinical isolates tested. Prevalent serotypes were 19A (20.4%, 6A/B (20.4%, 19F (15.7%, 14 (14.5%, and 23F (10.8%. Serotype 19F was the most frequent carriage strain, and serotype 19A was the most frequent invasive strain. The ST983 was the most prevalent ST for carriage strains, and ST320 was the most prevalent ST for invasive strains. For gene analysis, psaA (99.5% and piaA (98.6% were present and much conserved in all pneumococci tested. The cps2A and pcsB genes were more frequent in invasive isolates than carriage strains. Antimicrobial resistance rates of invasive pneumococcal isolates to erythromycin, penicillin, meropenem, cefotaxime, and clindamycin were higher than the carriage isolates from children. Conclusion: Our epidemiological evidence shows that 19A, 6A/B, 19F, 14, and 23F remain the most prevalent serotypes, which can be targeted by PCV13. Genotypes and drug resistance varied between carriage and invasive strains. The PsaA and PiaA may be good protein vaccine candidates.

  5. Pneumococcal pneumonia: clinical features, diagnosis and management in HIV-infected and HIV noninfected patients.

    Madeddu, Giordano; Fois, Alessandro Giuseppe; Pirina, Pietro; Mura, Maria Stella

    2009-05-01

    In this review, we focus on the clinical features, diagnosis and management of pneumococcal pneumonia in HIV-infected and noninfected patients, with particular attention to the most recent advances in this area. Classical clinical features are found in young adults, whereas atypical forms occur in immunocompromised patients including HIV-infected individuals. Bacteremic pneumococcal pneumonia is more frequently observed in HIV-infected and also in low-risk patients, according to the Pneumonia Severity Index (PSI). Pneumococcal pneumonia diagnostic process includes physical examination, radiologic findings and microbiologic diagnosis. However, etiologic diagnosis using traditional culture methods is difficult to obtain. In this setting, urinary antigen test, which recognizes Streptococcus pneumoniae cell wall C-polysaccharide, increases the probability of etiologic diagnosis. A correct management approach is crucial in reducing pneumococcal pneumonia mortality. The use of the PSI helps clinicians in deciding between inpatient and outpatient management in immunocompetent individuals, according to Infectious Diseases Society of America (IDSA)-American Thoracic Society (ATS) guidelines. Recent findings support PSI utility also in HIV-infected patients. Recently, efficacy of pneumococcal vaccine in reducing pneumococcal disease incidence has been evidenced in both HIV-infected and noninfected individuals. Rapid diagnosis and correct management together with implementation of preventive measures are crucial in order to reduce pneumococcal pneumonia related incidence and mortality in HIV-infected and noninfected patients.

  6. Celiac Disease and Increased Risk of Pneumococcal Infection: A Systematic Review and Meta-Analysis.

    Simons, Malorie; Scott-Sheldon, Lori A J; Risech-Neyman, Yesenia; Moss, Steven F; Ludvigsson, Jonas F; Green, Peter H R

    2018-01-01

    Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease. Relevant studies were identified using electronic bibliographic searches of PubMed, OVID, Medline, and EMBASE (1980 to February 2017) and reviewing abstracts from major conferences in gastroenterology. Using number of events in celiac patients and referent patients, we calculated a summary relative risk of pneumococcal infections. All analyses were conducted in Comprehensive Meta-Analysis software using random-effects assumptions. Of a total of 156 articles, 3, representing 3 large databases (the Swedish National Inpatient Register; the Oxford Record Linkage Study; and the English National Hospital Episode Statistics) were included. Each compared patients with celiac disease and confirmed pneumococcal infection to a specific reference group: inpatients and/or the general population. Overall, the odds of pneumococcal infection were higher among hospitalized celiac patients compared with controls (odds ratio 1.66; 95% confidence interval 1.43-1.92). There was no evidence of heterogeneity (Q[1] = 1.17, P = .56, I 2  = 0%). Celiac disease is associated with an increased risk of pneumococcal infection. Preventive pneumococcal vaccination should be considered for those with celiac disease, with special attention to those aged 15-64 years who have not received the scheduled pneumococcal vaccination series as a child. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.

    Morpeth, Susan C; Deloria Knoll, Maria; Scott, J Anthony G; Park, Daniel E; Watson, Nora L; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; O'Brien, Katherine L; Thea, Donald M; Adrian, Peter V; Ahmed, Dilruba; Antonio, Martin; Bunthi, Charatdao; DeLuca, Andrea N; Driscoll, Amanda J; Githua, Louis Peter; Higdon, Melissa M; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Kwenda, Geoffrey; Makprasert, Sirirat; Mazumder, Razib; Moore, David P; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Sow, Samba O; Tamboura, Boubou; Whistler, Toni; Zeger, Scott L; Murdoch, David R

    2017-06-15

    We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  8. Systemic steroid reduces long-term hearing loss in experimental pneumococcal meningitis

    Worsøe, Lise Lotte; Brandt, C.T.; Lund, S.P.

    2010-01-01

    Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have...... generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis.......Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have...

  9. Seasonal changes in climatic parameters and their relationship with the incidence of pneumococcal bacteraemia in Denmark

    Tvedebrink, Torben; Lundbye-Christensen, Søren; Thomsen, R.W.

    2008-01-01

    The seasonal variation in the incidence of invasive pneumococcal disease is well recognized, but little is known about its relationship with actual changes in climatic parameters. In this 8-year longitudinal population-based study in Denmark, a harmonic sinusoidal regression model was used...... to examine whether preceding changes in climatic parameters corresponded with subsequent variations in the incidence of pneumococcal bacteraemia, independently of seasonal variation. The study shows that changes in temperature can be used to closely predict peaks in the incidence of pneumococcal bacteraemia...

  10. Some pathogenetic aspects of experimental pneumococcal meningitis in acute period

    V. V. Pilipenko

    2011-01-01

    Full Text Available Morphological displays of cerebral microcirculation derangements in a brain cortex with their semiquantitative estimation have been studied in experimental mice model of the first 24-72 hours period of pneumococcal meningitis.Also displays oxidative stress and activity antioxidative protectional system by means of definition of markers of these processes – malondialdehide, reduced glutathione and glucose-6-phosphate-dehydrogenase activity have been investigated. The received results testify to morphological signs of the expressed derangements of cerebral microcirculation in a brain cortex already by first 24 hour of an experimental meningitis. The maximum expressiveness oxidative stress and activity antioxidative protectional system of reduced glutathione with the max activity of glucose-6-phosphatedehydrogenase in a mice brain cortex was noted at first 48hour durations of experimental disease. Signs of irreversible changes of mice cortex neurons are not revealed at 24–72-hour duration of experimental pneumococcal meningitis.

  11. Peptide-Carrier Conjugation

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  12. Photoluminescence in conjugated polymers

    Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.

    2002-01-01

    Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light

  13. DNA-cell conjugates

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2018-05-15

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  14. DNA-cell conjugates

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  15. Immune response capacity after human splenic autotransplantation - Restoration of response to individual pneumococcal vaccine subtypes

    Leemans, R; Manson, W; Snijder, JAM; Smit, JW; Klasen, HJ; The, TH; Timens, W

    Objective To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. Summary Background Data After splenectomy, patients

  16. PNEUMOCOCCAL INFECTION AND ASSOCIATED DISEASES — A SERIOUS PROBLEM OF MODERN HEALTH CARE

    A.A. Baranov

    2008-01-01

    Full Text Available Pneumococcal infection is one of the most widespread reasons for the development of infections of the respiratory passages (otitis, sinusitis in children. At the same time, it may act as an etiological factor of severe urgent conditions, such as pneumococcal meningitis and pneumococcal pneumonia, especially in children under 2 years old. A reliable method for preventing this infection is specific immunological prophylaxis. The article covers in detail the issue of vaccination in Russia and in other countries. The necessity of vaccination of all infants is demonstrated, as well as the necessity of participation in resolving this issue not only of pediatricians but governmental institutions as well in order to enhance safety and efficiency of vaccination and include this vaccine into the national calendar.Key words: pneumococcal infection, forms, complications, vaccination, national vaccination calendar, risk groups, children.

  17. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults

    Shak, J.R.; Cremers, A.J.H.; Gritzfeld, J.F.; Jonge, M.I. de; Hermans, P.W.M.; Vidal, J.E.; Klugman, K.P.; Gordon, S.B.

    2014-01-01

    Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and

  18. Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

    Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  19. Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

    Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

    2014-02-12

    Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

  20. The uptake of influenza and pneumococcal vaccination among immunocompromised patients attending rheumatology outpatient clinics.

    Haroon, Muhammad

    2011-07-01

    PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.

  1. Systemic steroid reduces long-term hearing loss in experimental pneumococcal meningitis

    Worsøe, Lise Lotte; Brandt, C.T.; Lund, S.P.

    2010-01-01

    Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have...... generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis....

  2. Health related quality of life in patients with community-acquired pneumococcal pneumonia in France

    Andrade, Luiz Flavio; Saba, Grèce; Ricard, Jean-Damien; Messika, Jonathan; Gaillat, Jacques; Bonnin, Pierre; Chidiac, Christian; Illes, Hajnal-Gabriela; Laurichesse, Henri; Detournay, Bruno; Petitpretz, Patrick; de Pouvourville, Gérard

    2018-01-01

    Background Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. Methods A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae ...

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

    Luciano Cesar Pontes Azevedo

    Full Text Available 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.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.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. Furthermore, this study provides a baseline

  4. Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis

    2013-01-01

    Background Inflammasomes are multi-protein intracellular signaling complexes that have recently been hypothesized to play a role in the regulation of the inflammation response. We studied associations between inflammasome-associated cytokines IL-1β and IL-18 in cerebrospinal fluid (CSF) of patients with bacterial meningitis and clinical outcome, and pneumococcal serotype. In a murine model of pneumococcal meningitis we examined the pathophysiological roles of two inflammasome proteins, NLRP3 (Nod-like receptor protein-3) and adaptor protein ASC (apoptosis-associated speck-like protein). Methods In a nationwide prospective cohort study, CSF cytokine levels were measured and related to clinical outcome and pneumococcal serotype. In a murine model of pneumococcal meningitis using Streptococcus pneumoniae serotype 3, we examined bacterial titers, cytokine profiles and brain histology at 6 and 30 hours after inoculation in wild-type (WT), Asc and Nlrp3 deficient mice. Results In patients with bacterial meningitis, CSF levels of inflammasome associated cytokines IL-1β and IL-18 were related to complications, and unfavorable disease outcome. CSF levels of IL-1β were associated with pneumococcal serotype (pmeningitis, which may dependent on the pneumococcal serotype. PMID:23902681

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

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

    2011-01-01

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

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

    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.

  7. Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.

    Maria A Said

    Full Text Available Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD, and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP using systematic study methods and the availability of a urine antigen assay.We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT with blood and/or sputum culture in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%. The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%. The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6% of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia

  8. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

    Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

    2016-01-01

    Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

  9. Drug treatment of pneumococcal pneumonia in the elderly.

    Neralla, Sridhar; Meyer, Keith C

    2004-01-01

    Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance. Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy. Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple

  10. Immunodeficiency among children with recurrent invasive pneumococcal disease

    Ingels, Helene; Schejbel, Lone; Lundstedt, A C

    2015-01-01

    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......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...

  11. Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity.

    Christenson, Brith; Pauksen, Karlis; Sylvan, Staffan P E

    2008-04-28

    The present prospective study was conducted from 2003-2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area.The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS) even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. In 2003, the total study population was 41,059, of which 12,907 (31%) received influenza vaccine of these, 4,447 (11%) were administered the pneumococcal vaccine. In 2004, 14,799 (34%) individuals received the influenza vaccine and 8,843 (21%) the pneumococcal vaccine and in 2005 16,926 (39%) individuals were given the influenza vaccine and 12,340 (28%) the pneumococcal vaccine.Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine). Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age). For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75-84-year old age group and in all age-groups during the influenza season 2005. The present study confirmed the

  12. Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity

    Sylvan Staffan PE

    2008-04-01

    Full Text Available Abstract Background The present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area. The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. Results In 2003, the total study population was 41,059, of which 12,907 (31% received influenza vaccine of these, 4,447 (11% were administered the pneumococcal vaccine. In 2004, 14,799 (34% individuals received the influenza vaccine and 8,843 (21% the pneumococcal vaccine and in 2005 16,926 (39% individuals were given the influenza vaccine and 12,340 (28% the pneumococcal vaccine. Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine. Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age. For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza

  13. Antibody Response is More Likely to Pneumococcal Proteins Than to Polysaccharide After HIV-associated Invasive Pneumococcal Disease

    Kantsø, Bjørn; Green, Nicola; Goldblatt, David

    2015-01-01

    to at least 1 protein compared to 51% of non-IPD controls. HIV IPD cases responded to more proteins than non-IPD controls (8.6 ± 8.4 vs 4.2 ± 7.6 proteins; P = .01), and had a significantly higher probability of yielding an antibody response to the proteins PiaA, PsaA, and PcpA. Twenty-two percent of HIV......-infected individuals with IPD had a serotype-specific antibody response. Younger age at the time of IPD was the only predictor of a serotype-specific pneumococcal antibody response, whereas we did not identify predictors of a protein-specific antibody response. CONCLUSIONS: Antibody responses occurred more frequently...

  14. Immunization With a Pneumococcal Polysaccharide Vaccine in Children With Juvenile Idiopathic Arthritis Without Systemic Manifestations: a Prospective Study

    Ekaterina I. Alexeeva

    2017-01-01

    Full Text Available Background. Patients with juvenile idiopathic arthritis (JIA have an increased risk of being infected. Approximately half of all serious infections in children with JIA are associated with airway involvement.Objective. Our aim was to study the efficacy and safety of the pneumococcal 13-valent conjugate vaccine (PCV in children with JIA.Methods. In a prospective cohort study, 5 groups were formed:  children with JIA in the remission phase on methotrexate therapy  (group 1 or etanercept (group 2, with JIA in the active phase prior  to the appointment of methotrexate (group 3 or etanercept (group  4, control group (conditionally healthy children. 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment  of methotrexate or etanercept in patients in the active phase. The  main study outcome was the proportion of patients with a protective  ( 40 mg/L level of specific anti-pneumococcal antibodies (anti-SPP IgG to Streptococcus pneumoniae 4 weeks after vaccination. In  addition, we assessed the incidence of infectious events before and  after vaccination as well as changes in the content of a high-sensitivity C-reactive protein, S100 protein, and post-vaccination period.Results. The study included 125 children. Four weeks after  vaccination, the protective level of anti-SPP IgG was established in  21 (84% patients in the 1st, 23 (92% in the 2nd, 22 (88% in the  3rd, 24 (96% in the 4th and 5th groups (p =1.0. Increase in the  concentration of S100 protein and high-sensitivity C-reactive protein  after vaccination was not noted. JIA exacerbation episodes were not  recorded in any patient. After immunization, the total number of infectious events decreased in all observed groups (p 0.001. Serious adverse events were not registered during the study.Conclusion. Vaccination with the 13-valent PCV in children with JIA  is highly effective

  15. Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis

    Klein, Matthias; Brouwer, Matthijs C.; Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter; van de Beek, Diederik; Koedel, Uwe

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels

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

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

    2014-02-01

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

  17. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

    2014-01-01

    Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  18. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Joshua R Shak

    Full Text Available Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63% of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14 was seen compared to that in the presence of H. influenzae (12/16. Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008 compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  19. Influenza and pneumococcal vaccine uptake among nursing home residents in Nottingham, England: a postal questionnaire survey

    Vivancos Roberto

    2008-05-01

    Full Text Available Abstract Background Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes. Methods A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls. Results 30% (16/53 of respondents reported having a policy addressing influenza vaccination and 15% (8/53 had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47. The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06. This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46 Conclusion The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.

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

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

    2016-06-01

    Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Dynamics of Severe and Non-Severe Invasive Pneumococcal Disease in Young Children in Israel Following PCV7/PCV13 Introduction.

    Glikman, Daniel; Dagan, Ron; Barkai, Galia; Averbuch, Diana; Guri, Alex; Givon-Lavi, Noga; Ben-Shimol, Shalom

    2018-05-10

    The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on non-severe IPD (mostly occult bacteremia) has not yet been fully elucidated.We assessed severe and non-severe IPD (SIPD and NSIPD, respectively) rate dynamics in children <5 years in Israel before and after PCV7/PCV13 implementation. A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015, were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not-hospitalized or hospitalized in a non-intensive care unit <5 days, without mortality). Three sub-periods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated. Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified.In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined non-significantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR=0.4; 0.32-0.51) and 64% (IRR=0.36; 0.32-0.42), respectively. Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the two groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

  2. The impact of residency and urbanicity on Haemophilus influenzae Type b and pneumococcal immunization in Shanghai Children: a Retrospective Cohort Study.

    Abram L Wagner

    Full Text Available BACKGROUND: Haemophilus influenzae type b (Hib vaccine and pneumococcal conjugate vaccine (PCV are relatively expensive, newly introduced vaccines in China. This study evaluates the impact of residency and urbanicity on Hib vaccine and PCV coverage for children aged 2 to 7 years living in Shanghai, China, in August 2012. METHODS: In this exploratory cohort study, a sample of children aged 2 to 7 years, all of whom were eligible to have received the complete series of Hib vaccine and PCV, was obtained from the Shanghai Immunization Program Information System. Three measures of vaccination coverage for Hib vaccine and PCV were examined: dose 1 coverage, series completion, and timeliness of dose 1 vaccination. Multivariable binomial regression was used to estimate the difference in vaccination coverage between locals and the floating population. RESULTS: Dose 1 coverage was 50.9% for Hib vaccine and 11.4% for PCV for the 28,141 abstracted pediatric records. For both vaccines, dose 1 coverage was higher in locals than in the floating population. The disparity in coverage between locals and the floating population was greater in suburban areas than urban areas. Of all children who received dose 1, 79.7% completed the Hib vaccine series, and 91.3% completed the PCV series. Timely dose 1 coverage was 8.2% for Hib vaccine and 0.5% for PCV. CONCLUSION: Low vaccination coverage and extremely low levels of timely dose 1 vaccination indicate that current vaccination efforts are inadequate to reduce the burden of Hib and pneumococcal disease among Chinese children, especially infants. Government funding of the Hib vaccine and PCV through the Expanded Program on Immunization would increase uptake and could also ensure that improvement in the timeliness of administration and series completion is targeted for all demographic groups.

  3. The changing epidemiology of invasive pneumococcal disease in aboriginal and non-aboriginal western Australians from 1997 through 2007 and emergence of nonvaccine serotypes.

    Lehmann, Deborah; Willis, Judith; Moore, Hannah C; Giele, Carolien; Murphy, Denise; Keil, Anthony D; Harrison, Catherine; Bayley, Kathy; Watson, Michael; Richmond, Peter

    2010-06-01

    BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007; the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those Aboriginal children. IPD rates decreased by >30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV campaign is needed. An immunization register covering all age groups should be established.

  4. Incidencia de enfermedad neumocócica invasiva en Cantabria (1995-2001 e implicaciones para el calendario vacunal Incidence of invasive pneumococcal disease in Cantabria, Spain, (1995-2001 and implications for the childhood inmunization schedule

    A. González

    2003-12-01

    Full Text Available Objetivo: Describir la incidencia de enfermedad neumocócica invasiva en Cantabria en los años 1995-2001. Método: Consulta de los registros del conjunto mínimo básico de datos (CMBD de los hospitales públicos de Cantabria, así como altas de los hospitales privados, registro de enfermedades de declaración obligatoria (EDO, y diagnósticos microbiológicos e historias clínicas de los niños ingresados en el Servicio de Pediatría del Hospital Cantabria (el hospital de referencia de tercer nivel. Resultados: Se obtuvo una incidencia de meningitis de 5,55, 5,03 y 0,76/100.000 en los niños Objective: To describe the incidence of invasive pneumococcal disease in Cantabria (Spain between 1995 and 2001. Method: We reviewed the records of the Minimum Data Set (MDS of public hospitals in Cantabria, discharges from private hospitals and the registry of diseases of mandatory reporting, as well as the microbiologic diagnoses and medical records of children discharged from the Pediatric Service of the Cantabria Hospital (the tertiary care hospital in our autonomous community. Results: We obtained a meningitis incidence of 5.55, 5.03 and 0.76/100,000 in children < 2 years, ≥ 2 and < 5 years, and ≥ 5 years respectively, and an incidence of invasive disease of 11.11, 11.32 and 1.49/100,000 in the same age groups. Conclusions: The incidence of meningitis and invasive pneumococcal disease in Cantabria is low. We discuss factors that should be taken into account when introducing the pneumococcal conjugate vaccine in the childhood immunization schedule of Cantabria.

  5. Using Inverse Problem Methods with Surveillance Data in Pneumococcal Vaccination

    Sutton, Karyn L.; Banks, H. T.; Castillo-Chavez, Carlos

    2010-01-01

    The design and evaluation of epidemiological control strategies is central to public health policy. While inverse problem methods are routinely used in many applications, this remains an area in which their use is relatively rare, although their potential impact is great. We describe methods particularly relevant to epidemiological modeling at the population level. These methods are then applied to the study of pneumococcal vaccination strategies as a relevant example which poses many challenges common to other infectious diseases. We demonstrate that relevant yet typically unknown parameters may be estimated, and show that a calibrated model may used to assess implemented vaccine policies through the estimation of parameters if vaccine history is recorded along with infection and colonization information. Finally, we show how one might determine an appropriate level of refinement or aggregation in the age-structured model given age-stratified observations. These results illustrate ways in which the collection and analysis of surveillance data can be improved using inverse problem methods. PMID:20209093

  6. [Do organizational barriers to pneumococcal and influenza vaccine access exist?].

    Rousseau, Louise; Guay, Maryse; Archambault, Denis; El m'ala, Zahra; Abdelaziz, Nadia

    2007-01-01

    Despite the implementation of a Quebec immunization program against influenza and pneumococcal disease (PQIIP), vaccine coverage has remained low. There have been many studies on personal barriers to vaccination, but few have explored other kinds of barriers. To explore the presence of barriers in relation to the organization of the health care system and to propose recommendations for increasing vaccine coverage. Within a mixed protocol, a phone survey of 996 people in the target population and a case study implicating the follow-up of the PQIIP with all the site and actor categories via 43 semistructured interviews and 4 focus groups were realized. Survey data underwent a descriptive statistical analysis. Qualitative analysis followed the Miles and Huberman approach. The results indicate the presence of barriers with regard to information accessibility. These include access to: the physicians' recommendation, knowledge of the efficacy or the security of vaccines, and admissibility of clients to the PQIIP. Organizational barriers were also found to limit access to vaccination, especially in terms of restricted choices of time and location. Coordination and incentives mechanisms are not optimal. Removal of organizational barriers depends more on strategic rather than structural factors. Addressing organizational barriers should be an important component of strategies aimed at improving vaccine coverage. Public health authorities should focus on strategic management of the information and inter-organizational environment.

  7. Conversion of Deletions during Recombination in Pneumococcal Transformation

    Lefevre, J. C.; Mostachfi, P.; Gasc, A. M.; Guillot, E.; Pasta, F.; Sicard, M.

    1989-01-01

    Genetic analysis of 16 deletions obtained in the amiA locus of pneumococcus is described. When present on donor DNA, all deletions increased drastically the frequency of wild-type recombinants in two-point crosses. This effect was maximal for deletions longer than 200 bases. It was reduced for heterologies shorter than 76 bases and did not exist for very short deletions. In three-point crosses in which the deletion was localized between two point mutations, we demonstrated that this excess of wild-type recombinants was the result of a genetic conversion. This conversion extended over several scores of bases outside the deletion. Conversion takes place during the heteroduplex stage of recombination. Therefore, in pneumococcal transformation, long heterologies participated in this heteroduplex configuration. As this conversion did not require an active DNA polymerase A gene it is proposed that the mechanism of conversion is not a DNA repair synthesis but involves breakage and ligation between DNA molecules. Conversion of deletions did not require the Hex system of correction of mismatched bases. It differs also from localized conversion. It appears that it is a process that evolved to correct errors of replication which lead to long heterologies and which are not eliminated by other systems. PMID:2599365

  8. Selective and genetic constraints on pneumococcal serotype switching.

    Nicholas J Croucher

    2015-03-01

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

  9. Pneumococcal Induced T-activation with Resultant Thrombotic Microangiopathy

    J.W. Oliver

    2010-01-01

    Full Text Available Thrombotic microangiopathies are disorders resulting from platelet thromboses forming in the microvasculature with resultant schistocyte forms. Hemolytic uremic syndrome (HUS is a microangiopathic hemolytic anemia often complicated by acute renal failure in children. HUS is typically caused by bacterial infection, most commonly enterohemorrhagic Escherichia coli. Neuraminidase-producing organisms, such as Streptococcus pneumoniae have also been reported as potential etiologies. The pathogenesis in these cases involves cleavage of sialic acid residues from the surfaces of erythrocytes, platelets, and glomerular capillary endothelial cells, exposing the Thomsen-Friedenreich antigen, a process known as T-activation. We describe a 2-year-old girl who presented with pneumococcal pneumonia and sepsis ultimately resulting in a thrombotic microangiopathy with acute renal failure, most consistent with HUS. The patient's direct antiglobulin test was positive. Polyagglutination was observed with human adult serum, but not with umbilical cord serum. Her red blood cells (RBCs were reactive against peanut and soybean lectins, but not Salvia sclarea or Salvia horminum lectins. These findings are consistent with T-activation. Clinicians should be cognizant of the possibility of T-activation with resultant HUS in patients infected with neuraminidase-producing bacteria. Such patients may be difficult to identify using monoclonal typing antisera, as these typically do not have anti-T antibodies. Whether such patients are at risk for transfusion-associated hemolysis is debatable.

  10. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

    Scott Pangonis MD

    2016-02-01

    Full Text Available Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date.

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

    Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J

    2016-08-01

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

  12. Organometallic B12-DNA conjugate

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

  13. Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study.

    Dominguez, Angela; Salleras, Lluis; Fedson, David S; Izquierdo, Conchita; Ruiz, Laura; Ciruela, Pilar; Fenoll, Asuncion; Casal, Julio

    2005-05-01

    Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study. We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination. Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period. Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.

  14. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    Frederiksen, B.; Specht, L.; Henrichsen, J.

    1989-01-01

    Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antib......Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase...

  15. Conjugation in Escherichia coli

    Boyer, Herbert

    1966-01-01

    Boyer, Herbert (Yale University, New Haven, Conn.). Conjugation in Escherichia coli. J. Bacteriol. 91:1767–1772. 1966.—The sex factor of Escherichia coli K-12 was introduced into an E. coli B/r strain by circumventing the host-controlled modification and restriction incompatibilities known to exist between these closely related strains. The sexual properties of the constructed F+ B strain and its Hfr derivatives were examined. These studies showed that the E. coli strain B/r F+ and Hfr derivatives are similar to the E. coli strain K-12 F+ and Hfr derivatives. However, the site of sex factor integration was found to be dependent on the host genome. PMID:5327905

  16. Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine

    Nagel, J.; Saxne, T.; Geborek, P.

    2017-01-01

    in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus...

  17. Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage by respiratory pathogens among Greenlandic children

    Navne, Johan Emdal; Koch, Anders; Slotved, Hans-Christian

    2017-01-01

    . Overall carriage rate of S. pneumoniae remained unchanged from 2011 to 2013 (51% and 56%, p=0.13), but significant serotype shifts were observed among both vaccinated and unvaccinated children with marked reductions in carriage of vaccine-type pneumococci, counterbalanced by increasing carriage of non...

  18. Electrochromic in conjugated polymers

    Picado Valenzuela, Alfredo

    2007-01-01

    This revision considered object the description of one of the materials with the greatest potential in the field of electrochromic (mainly in the visible region): the conjugated polymers (CP), area of enormous potential both now and in a short time ahead. The CP are insulating materials and organic semiconductors in a state not doped. They can be doped positively or negatively being observed a significant increase in the conductivity and being generated a color change in these materials. The understanding of how optical properties vary based on the chemical structure of the polymer or its mixtures and more precisely of the alternatives that can be entered into the conjugated system or π system to obtain a material that besides to be flexible, environmentally stable, presents the colored states. The revision was centred chiefly in the polypyrrole (Ppy), the polythiophene (PTh) and their derivatives such as poly (3.4-ethylenedioxythiophene) (PEDOT). The advantage of using monomers with variable structure, to adjust the composition of the copolymer, or to blend with the PC, allows to obtain a variety of colored states that can be modulated through the visible spectrum and even with applications to wavelengths outside of this region. Because the PC presented at least two different colored states can be varied continuously as a function of the voltage applied. In some cases, they may submit multicoloured statements, which offers a range of possibilities for their application in flexible electronic devices type screens and windows. Applications include smart windows, camouflage clothing and data screens. This type of material is emerging as one of the substitutes of the traditional inorganic semiconductor, with the advantage of its low cost, high flexibility and the possibility to generate multiple colors through the handling of the monomers in the structure and control of energy of his band gap. (author) [es

  19. Phylogenetic analysis of emergent Streptococcus pneumoniae serotype 22F causing invasive pneumococcal disease using whole genome sequencing.

    Walter H B Demczuk

    Full Text Available Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13 in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD has declined from 55% (n = 1492 in 2010 to 31% (n = 764 in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183 to 11% (n = 283. Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117 were identified among a serotype 22F/ST433 clonal complex (CC, including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.

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

    Alfonso Olaya-Abril

    Full Text Available 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. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  2. Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

    Helmi, Nawal; Andrew, Peter W; Pandya, Hitesh C

    2015-05-15

    Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Block-conjugate-gradient method

    McCarthy, J.F.

    1989-01-01

    It is shown that by using the block-conjugate-gradient method several, say s, columns of the inverse Kogut-Susskind fermion matrix can be found simultaneously, in less time than it would take to run the standard conjugate-gradient algorithm s times. The method improves in efficiency relative to the standard conjugate-gradient algorithm as the fermion mass is decreased and as the value of the coupling is pushed to its limit before the finite-size effects become important. Thus it is potentially useful for measuring propagators in large lattice-gauge-theory calculations of the particle spectrum

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

    2001-12-01

    Medical Center. San pathogen is an even greater threat to some subpopulations in Diego, CA; Wyeth Lederle Vaccines: LT David Cute, MC USN, Erica...Butler JC. Tenover FC, Elliott JA, Facklam RR. Emergence of 43. Musher DM, Luchi MJ, Watson DA, Hamilton R, Baughn RE: Pneumococcal drug-resistant

  5. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis

    Zwijnenburg, Petra J. G.; van der Poll, Tom; Florquin, Sandrine; Akira, Shizuo; Takeda, Kiyoshi; Roord, John J.; van Furth, A. Marceline

    2003-01-01

    To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

  6. Threshold shift: effects of cochlear implantation on the risk of pneumococcal meningitis.

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

    2007-04-01

    The study goals were to examine whether cochlear implantation increases the risk of meningitis in the absence of other risk factors and to understand the pathogenesis of pneumococcal meningitis post cochlear implantation. Four weeks following surgery, 54 rats (18 of which received a cochleostomy alone, 18 of which received a cochleostomy and acute cochlear implantation using standard surgical techniques, and 18 of which received a cochlear implant) were infected with Streptococcus pneumoniae via three different routes of bacterial inoculation (middle ear, inner ear, and intraperitoneal) to represent all potential routes of bacterial infection from the upper respiratory tract to the meninges. The presence of a cochlear implant reduced the threshold of bacteria required to cause pneumococcal meningitis from all routes of infection in healthy animals. The presence of a cochlear implant increases the risk of pneumococcal meningitis regardless of the route of bacterial infection. Early detection and treatment of pneumococcal infection such as otitis media may be required, as cochlear implantation may lead to a reduction of infectious threshold for meningitis.

  7. Predicting pneumococcal community-acquired pneumonia in the emergency department: evaluation of clinical parameters.

    Huijts, S M; Boersma, W G; Grobbee, D E; Gruber, W C; Jansen, K U; Kluytmans, J A J W; Kuipers, B A F; Palmen, F; Pride, M W; Webber, C; Bonten, M J M

    2014-12-01

    The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  8. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    Frederiksen, B; Specht, L; Henrichsen, J

    1989-01-01

    response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....

  9. A life-style physical activity intervention and the antibody response to pneumococcal vaccination in women

    Long, J.E.; Ring, C.; Bosch, J.A.; Eves, F.; Drayson, M.T.; Calver, R.; Say, V.; Allen, D.; Burns, V.E.

    2013-01-01

    Objective: To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women. Methods: Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n

  10. ADULT RESPIRATORY-DISTRESS SYNDROME (ARDS) DUE TO BACTEREMIC PNEUMOCOCCAL PNEUMONIA

    MANNES, GPM; BOERSMA, WG; BAUR, CHJM; POSTMUS, PE

    We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus

  11. Did the dutch pneumococcal vaccination campaign decrease the need for antibiotics in children?

    Gefenaite, Giedre; Bijlsma, Maarten J.; Bos, Jens; Hak, Eelko

    2013-01-01

    Background: Streptococcus pneumoniae is responsible for a significant amount of respiratory infections and acute otitis media (AOM) and use of antibiotics in children. In June 2006 a four-dose 7-valent pneumococcal vaccination campaign (PVC) was introduced in the Netherlands; 94% of children born

  12. Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

    Vassal-Stermann, Emilie; Lacroix, Monique; Gout, Evelyne

    2014-01-01

    Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal c...

  13. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.

    Zwijnenburg, P.J.G.; Poll, van der T.; Florquin, S; Akira, S; Takeda, K; Roord, J.J.; Furth, van A.M.

    2003-01-01

    To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

  14. Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model.

    Trzciński, Krzysztof; Li, Yuan; Weinberger, Daniel M; Thompson, Claudette M; Cordy, Derrick; Bessolo, Andrew; Malley, Richard; Lipsitch, Marc

    2015-09-15

    Competitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself. Streptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by

  15. Entanglements in Conjugated Polymers

    Xie, Renxuan; Lee, Youngmin; Aplan, Melissa; Caggiano, Nick; Gomez, Enrique; Colby, Ralph

    Conjugated polymers, such as poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly-((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(thiophen-5-yl)-2,1,3-benzothiadiazole]-2',2''-diyl) (PFTBT), are widely used as hole and electron transport materials in a variety of electronic devices. However, fundamental knowledge regarding chain entanglements and nematic-to-isotropic transition is still lacking and are crucial to maximize charge transport properties. A systematic melt rheology study on P3HT with various molecular weights and regio regularities was performed. We find that the entanglement molecular weight Me is 5.0 kg/mol for regiorandom P3HT, but the apparent Me for regioregular P3HT is significantly higher. The difference is postulated to arise from the presence of a nematic phase only in regioregular P3HT. Analogously, PFTBT shows a clear rheological signature of the nematic-to-isotropic transition as a reversible sharp transition at 278 C. Shearing of this nematic phase leads to anisotropic crystalline order in PFTBT. We postulate that aligning the microstructure will impact charge transport and thereby advance the field of conducting polymers. National Science Foundation.

  16. Protein carriers of conjugate vaccines

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  17. INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

    Giuseppe La Torre

    2016-09-01

    Full Text Available 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 asses 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 scientific literature about 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 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% 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 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.

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

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

    2016-01-01

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

  19. A life-style physical activity intervention and the antibody response to pneumococcal vaccination in women.

    Long, Joanna E; Ring, Chris; Bosch, Jos A; Eves, Francis; Drayson, Mark T; Calver, Rebecca; Say, Vanessa; Allen, Daniel; Burns, Victoria E

    2013-10-01

    To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women. Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n = 44) or control (advisory leaflet; n = 45) intervention. Pneumococcal vaccination was administered at 12 weeks, and antibody titers (11 of the 23 contained in the pneumococcal vaccine) were determined before vaccination and 4 weeks and 6 months later. Physical activity, aerobic fitness, body composition, and psychological factors were measured before and after the intervention. The intervention group displayed a greater increase in walking behavior (from mean [standard deviation] = 82.16 [90.90] to 251.87 [202.13]) compared with the control condition (111.67 [94.64] to 165.16 [117.22]; time by group interaction: F(1,68) = 11.25, p = .001, η(2) = 0.14). Quality of life also improved in the intervention group (from 19.37 [3.22] to 16.70 [4.29]) compared with the control condition (19.97 [4.22] to 19.48 [5.37]; time by group interaction: F(1,66) = 4.44, p = .039, η(2) = 0.06). However, no significant effects of the intervention on antibody response were found (time by group η(2) for each of the 11 pneumococcal strains ranged from 0.001 to 0.018; p values all >.264). Participation in a life-style physical activity intervention increased subjective and objective physical activity levels and quality of life but did not affect antibody response to pneumococcal vaccination.

  20. CXCR1/2 Antagonism Is Protective during Influenza and Post-Influenza Pneumococcal Infection

    Luciana P. Tavares

    2017-12-01

    Full Text Available RationaleInfluenza A infections are a leading cause of morbidity and mortality worldwide especially when associated with secondary pneumococcal infections. Inflammation is important to control pathogen proliferation but may also cause tissue injury and death. CXCR1/2 are chemokine receptors relevant for the recruitment of neutrophils. We investigated the role of CXCR1/2 during influenza, pneumococcal, and post-influenza pneumococcal infections.MethodsMice were infected with influenza A virus (IAV or Streptococcus pneumoniae and then treated daily with the CXCR1/2 antagonist DF2162. To study secondary pneumococcal infection, mice were infected with a sublethal inoculum of IAV then infected with S. pneumoniae 14 days later. DF2162 was given in a therapeutic schedule from days 3 to 6 after influenza infection. Lethality, weight loss, inflammation, virus/bacteria counts, and lung injury were assessed.ResultsCXCL1 and CXCL2 were produced at high levels during IAV infection. DF2162 treatment decreased morbidity and this was associated with decreased infiltration of neutrophils in the lungs and reduced pulmonary damage and viral titers. During S. pneumoniae infection, DF2162 treatment decreased neutrophil recruitment, pulmonary damage, and lethality rates, without affecting bacteria burden. Therapeutic treatment with DF2162 during sublethal IAV infection reduced the morbidity associated with virus infection and also decreased the magnitude of inflammation, lung damage, and number of bacteria in the blood of mice subsequently infected with S. pneumoniae.ConclusionModulation of the inflammatory response by blocking CXCR1/2 improves disease outcome during respiratory influenza and pneumococcal infections, without compromising the ability of the murine host to deal with infection. Altogether, inhibition of CXCR1/2 may be a valid therapeutic strategy for treating lung infections caused by these pathogens, especially controlling secondary bacterial

  1. NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations

    Chapman, Stephen J; Khor, Chiea C; Vannberg, Fredrik O; Rautanen, Anna; Segal, Shelley; Moore, Catrin E; Davies, Robert J O; Day, Nicholas P; Peshu, Norbert; Crook, Derrick W; Berkley, James A; Williams, Thomas N; Scott, J Anthony; Hill, Adrian V S

    2011-01-01

    The proinflammatory transcription factor nuclear factor-kappaB (NF-κB) plays a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-κB inhibitor IκB-α associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IκB-ζ gene NFKBIZ in the development of invasive pneumococcal disease has not previously been reported. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium block and all four polymorphisms within the equivalent, shorter Kenyan linkage disequilibrium block displayed either significant association with invasive pneumococcal disease or a trend towards association. For each polymorphism, heterozygosity was associated with protection from invasive pneumococcal disease when compared to the combined homozygous states (e.g. for rs600718, Mantel-Haenszel 2×2 χ2=7.576, P=0.006, OR=0.67, 95% CI for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2×2 χ2=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to invasive pneumococcal disease in humans. The study of multiple populations may aid fine-mapping of associations within extensive regions of strong linkage disequilibrium (‘transethnic mapping’). PMID:19798075

  2. 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.

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

    2016-11-30

    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. 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. Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. 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). 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. 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 to the NHS. These savings could be used to implement other life-saving interventions

  3. Conjugated Fatty Acid Synthesis

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  4. Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

    Aprianto, Rieza; Slager, Jelle; Holsappel, Siger; Veening, Jan-Willem

    2016-01-01

    BACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we

  5. Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover

    Beurskens, Charlotte J. P.; Aslami, Hamid; Kuipers, Maria T.; Horn, Janneke; Vroom, Margreeth B.; van Kuilenburg, André B. P.; Roelofs, Joris J. T. H.; Schultz, Marcus J.; Juffermans, Nicole P.

    2012-01-01

    Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Subjects were

  6. Childhood pneumococcal disease burden in Argentina Carga por enfermedad neumocócica en niños de Argentina

    Federico Ariel Augustovski

    2009-05-01

    Full Text Available OBJECTIVES: To understand the disease burden of pneumococcal disease (PD, a major cause of childhood morbidity and mortality in Argentina, and to draw a baseline against which the need for and effectiveness of vaccination with pneumococcal conjugate vaccines might be measured. METHODS: A Markov model was constructed to estimate incidence and mortality rates of PD-meningitis (MEN, bacteremia/septicemia (BACT, pneumonia (PNEU, acute otitis media (AOM-among a hypothetical, birth cohort of 750 000 Argentine infants born in 2006-2015. A systematic review of the literature was performed to select and incorporate input parameters. Life years and costs in 2006 US$ were expressed as both undiscounted and discounted. RESULTS: The number of PD episodes estimated to occur over a 10-year period in the hypothetical birth cohort were: MEN, 225; BACT, 2 841; PNEU, 2 628; and AOM, 2 066 719. Chronic sequelae of MEN could be expected to cause neurological damage in 43 children and severe hearing issues in 28. Results indicate that there would be 78 PD-related deaths in the cohort (29% due to MEN; 54%, BACT; and 17%, PNEU. The undiscounted life-expectancy for individuals in the birth cohort was estimated to be 72.4 years (29.0 years discounted. Mean, undiscounted, lifetime costs attributed to PD for each child of the cohort totaled US$ 167 (US$ 151 discounted, imposing a total, cohort cost-burden of more than US$ 126 million (US$ 113 million discounted. CONCLUSIONS: The study shows that PD imposes a significant health and economic burden on the Argentine population. This information is essential for assessing the potential health and economic impact of introducing pneumococcal conjugate vaccine into the national immunization schedule.OBJETIVOS: Analizar la carga que provoca la enfermedad neumocócica (EN, una importante causa de morbimortalidad infantil en Argentina y establecer una línea de base a partir de la cual se pueda medir la necesidad y la eficacia del

  7. Research study of conjugate materials; Conjugate material no chosa kenkyu

    NONE

    1998-03-01

    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  8. Dominance of multidrug-resistant Denmark(14)-32 (ST230) clone among Streptococcus pneumoniae serotype 19A isolates causing pneumococcal disease in Bulgaria from 1992 to 2013.

    Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio

    2015-02-01

    A pneumococcal conjugate vaccine (PCV10) was introduced in Bulgarian national immunization program since April 2010. Clonal composition based on pulsed-field gel electrophoresis and multilocus sequence typing genotyping of 52 serotype 19A Streptococcus pneumoniae isolates was analyzed. These were invasive and respiratory isolates collected between 1992 and 2013 from both children (78.8% clone. The most frequent sequence type (ST) was ST230 (48.1%) and together with four other closely related STs (15.4%), belonging to ST1611, ST276, ST7466, and ST2013, which were single- and double-locus variants; they were included in the main CC230. The disappearance of highly drug-resistant ST663 clone and emergence of new clones as CC320 and CC199 was also observed among the rest 19A isolates. A comparison of clonal composition between invasive and noninvasive isolates did not show a great genetic diversity among both kinds of isolates. Continuous surveillance of serotype 19A population following the introduction of PCV10 is essential to evaluate the impact of the vaccine on the epidemiology of this serotype.

  9. Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in elderly residents of a long-term care facility

    M. Teresa Valenzuela B.

    Full Text Available S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrolment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.

  10. Conjugated polymer nanoparticles, methods of using, and methods of making

    Habuchi, Satoshi

    2017-03-16

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  11. Conjugated polymer nanoparticles, methods of using, and methods of making

    Habuchi, Satoshi; Piwonski, Hubert Marek; Michinobu, Tsuyoshi

    2017-01-01

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  12. Conjugated polymer zwitterions and solar cells comprising conjugated polymer zwitterions

    Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao

    2018-06-05

    A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.

  13. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates.

    Farooqui, Habib; Jit, Mark; Heymann, David L; Zodpey, Sanjay

    2015-01-01

    The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3-3.9 million) episodes of severe pneumonia and 0.35 million (0.31-0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49-0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92-119 thousand) pneumococcal deaths occurred in India. The top contributors to India's pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results

  14. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates.

    Habib Farooqui

    Full Text Available The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3-3.9 million episodes of severe pneumonia and 0.35 million (0.31-0.40 million all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths Madhya Pradesh (6.6% children, 9% cases, 12% deaths, and Rajasthan (6.6% children, 8% cases, 11% deaths. Further, we estimated that 0.56 million (0.49-0.64 million severe episodes of pneumococcal pneumonia and 105 thousand (92-119 thousand pneumococcal deaths occurred in India. The top contributors to India's pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our

  15. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

    Farooqui, Habib; Jit, Mark; Heymann, David L.; Zodpey, Sanjay

    2015-01-01

    The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our

  16. Factors associated with influenza and pneumococcal vaccine uptake among rheumatoid arthritis patients in Denmark invited to participate in a pneumococcal vaccine trial (Immunovax_RA)

    Nguyen, MTT; Lindegaard, H.; Hendricks, O.

    2017-01-01

    the survey during scheduled follow-up visits. The questionnaire included questions concerning previous influenza and pneumococcal vaccine uptake, attitudes about vaccination, and socio-demographic factors. Factors associated with recalled vaccine uptake were assessed by multivariate logistic regression....... Results: A total of 192 RA patients completed the survey, 134 (70%) of whom were women and 90 (47%) were aged ≥ 65 years. Sixty-seven patients (35%) received conventional disease-modifying anti-rheumatic drugs (cDMARDs) and 125 (65%) combination therapy with biological disease-modifying anti...

  17. Serotipos de neumococo en niños portadores antes de la vacunación antineumocócica en el Perú Pneumococcal serotypes in carrier children prior to the introduction of anti-pneumococcal vaccines in Peru

    Erik H. Mercado

    2012-03-01

    Full Text Available Objetivos. Determinar la frecuencia y distribución de serotipos de S. pneumoniae en portadores nasofaríngeos sanos menores de dos años previa al uso universal de la vacuna conjugada antineumocócica en el Perú. Materiales y métodos. Entre los años 2007 y 2009 se tomaron muestras de hisopado nasofaríngeo a 2123 niños sanos entre 2 y 24 meses de edad en los consultorios de crecimiento y desarrollo o vacunación de hospitales y centros de salud de siete ciudades del Perú: costa (Lima, Piura; sierra (Cusco, Abancay, Arequipa y Huancayo y selva (Iquitos. Las cepas de neumococo fueron aisladas e identificadas en el laboratorio central del proyecto en Lima y serotipificadas por reacción de Quellung en el Laboratorio de Referencia de Neumococo del Centro de Control y Prevención de Enfermedades. Resultados. Se encontró 27,0% (573/2123 de portadores nasofaríngeos sanos de neumococo. En las 526 cepas analizadas se encontraron 42 serotipos; los más frecuentes fueron: 19F (18,1%, 6B (14,3%; 23F (8,9% y 14 (6,5%. Conclusiones. La distribución de serotipos vacunales en las cepas analizadas fue de 50,0% para los serotipos presentes en la vacuna conjugada heptavalente; 50,2% para los serotipos presentes en la vacuna decavalente y 57,2% para la vacuna 13-valente.Objectives. To determine the carriage rate and serotype distribution of Streptococcus pneumoniae in the nasopharynx of healthy children younger than 2 years prior to the universal use of the pneumococcal conjugate vaccines in Peru. Materials and methods. Between 2007 and 2009 we collected nasopharyngeal swab samples from 2,123 healthy children aged 2 to 24 months in the vaccination and healthy children consultation offices of pediatric hospitals and health centers in 7 cities in Peru: on the coast (Lima, Piura, highlands (Cusco, Abancay, Arequipa and Huancayo and amazon basin (Iquitos. The pneumococcal strains were isolated and identified at the central laboratory of the project in Lima

  18. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L

    2014-01-01

    BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course...... and the volume and size of brain ventricles were positively correlated (Spearman Rank, p volume and the extent of apoptosis (p > 0.05). CONCLUSIONS: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly...... of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live...

  19. Empyema and bacteremic pneumococcal pneumonia in children under five years of age

    Maria Regina Alves Cardoso

    2014-01-01

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

  20. Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

    Lundbo, Lene F; Harboe, Zitta Barrella; Clausen, Louise N

    2016-01-01

    NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). METHODS: Cases with IPD and IMD and controls were identified......BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes.......86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. CONCLUSIONS: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis....

  1. Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

    Ishimaru, Naoto; Ohnishi, Hisashi; Nishiuma, Teruaki; Doukuni, Ryota; Umezawa, Kanoko; Oozone, Sachiko; Kuramoto, Emi; Yoshimura, Sho; Kinami, Saori

    2013-01-01

    Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

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

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

    2016-01-01

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

  3. Redefining risk categories for pneumococcal disease in adults: critical analysis of the evidence

    Daniel Curcio

    2015-08-01

    Conclusions: The ORs for CAP and IPD of patients with two or more comorbidities, with or without smoking, were found to be similar to the ORs for CAP and IPD described in the literature for patients currently classified as high risk. The potential impact of multiple, stacking comorbidities is underestimated and there is a need for the risk categories for pneumococcal disease to be redefined.

  4. Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

    Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

    2013-01-01

    Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

  5. Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

    Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

    2013-08-20

    Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

  6. EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

  7. Pneumococcal peritonitis in peritoneal dialysis - three case reports and literature review

    Pereira, Tiago Assis; Vizinho, Ricardo; Branco, Patricia; Gaspar, Augusta; Barata, José Diogo

    2015-01-01

    Peritonitis and catheter-related infections are a frequent complication in peritoneal dialysis, usually driven by commensal microorganisms. They carry a significant morbidity and mortality burden and have known consequences on viability of peritoneal dialysis and patient survival. This article describes three clinical cases, in which three different peritoneal dialysis patients presented pneumococcal peritonitis, two of which were related with obvious previous or concomitant respiratory sympt...

  8. Audit and Feedback: A Quality Improvement Study to Increase Pneumococcal Vaccination Rates.

    Clark, Rebecca Culver; Carter, Kimberly Ferren; Jackson, Julie; Hodges, Deborah

    The purpose of this quality improvement study was to explore the impact of audit and feedback on the pneumococcal immunization rate for at-risk adults in ambulatory settings. Study findings support the hypothesis that timely, individualized audit and feedback can have a positive impact on immunization rate; generalized feedback that did not provide actionable information did not have the same impact. The difference between the interventions was significant, χ (1, N = 1993) = 124.7, P <.001.

  9. Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation.

    Wren, John T; Blevins, Lance K; Pang, Bing; King, Lauren B; Perez, Antonia C; Murrah, Kyle A; Reimche, Jennifer L; Alexander-Miller, Martha A; Swords, W Edward

    2014-11-01

    Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

    Auranen, Kari; Syrjänen, Ritva; Leino, Tuija; Kilpi, Terhi

    2016-01-01

    For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.

  11. Frequency of resistance to penicillin and erythromycin of pneumococcal strains that caused ottis media

    Jovanović Luka

    2017-01-01

    Full Text Available Introduction: Streptococcus pneumoniae is an important human pathogen and the most common cause of acute otitis media (AOM, especially in children. It is also a common cause of community acquired pneumonia, sepsis and bacterial meningitis. Drug of choice in the treatment of these disease are beta lactam antibiotics, and the first alternative are macrolides. The increasing prevalence of resistance to penicillin and macrolides, among pneumococci, has considerably complicated the treatment. Aim: The aim of this study was to determine susceptibility of pneumococcal isolates from pediatric AOM in Serbia to antibiotics. Material and methods: Antimicrobial susceptibility testing of 61 pneumococcal AOM was performed, collected from December 2014 to December 2015, using disk diffusion method and E test. Macrolide resistance profile was determined by double disk diffusion test. Results: In our study, 40 strains (65.6% showed reduced sensitivity to penicillin and erythromycin. There were 9 (14.8% high resistant isolates to penicillin, while 31 (50.8% showed reduced susceptibility. The most frequent resistance phenotype was cMLS. Co-resistance to penicillin and macrolides was found in 14.8% strains. Conclusion: Our results showed high resistance rate of S. pneumoniae, which causes AOM among children, to penicillin and macrolides. Further active surveillance of pneumococcal susceptibility to antibiotics is necessary, and use of these medications in empirical therapy should be limited.

  12. Influenza and pneumococcal vaccination and varicella status in inflammatory arthritis patients.

    McCarthy, E M

    2011-11-15

    Patients with inflammatory arthritis are at increased risk of vaccine preventable infections. This risk is increased by immunomodulatory therapies. Vaccination for influenza and pneumococcal disease reduces the risk. Severe cases of varicella infection have occurred in patients on biologic therapies. We sought to identify vaccination rates for commonly acquired infections and to ascertain varicella immune status in patients with inflammatory arthritis. 100 patients with inflammatory arthritis were administered a standardised questionnaire. Data collected included age, diagnosis, vaccination history, history of varicella, treatment and the presence of other indications for vaccination. 58 patients (58%) had not received the influenza vaccine in the past year. Only 19 patients (19%) had ever received pneumococcal vaccine. Anti TNF use did not predict vaccination (p = .46). An increasing number of co morbid conditions predicted both pneumococcal (p < 0.003) and influenza vaccine (p < 0.03) administration. Nineteen patients (19%) gave no history of varicella infection, none having had varicella titres checked pre treatment. Immunisation rates in patients with inflammatory arthritis on immunosuppressive therapies are low. Immunisation schedules should be available for each patient during rheumatology and general practice consultations.

  13. Influenza and pneumococcal vaccination rates among Vietnamese, Asian, and non-Hispanic white Americans.

    Daniels, Nicholas A; Gildengorin, Ginny; Nguyen, Tung T; Liao, Youlian; Luong, Thien-Nhien; McPhee, Stephen J

    2010-06-01

    Vaccination data for Asian Americans are comparable to those for whites, possibly because they are reported in aggregate rather than for subgroups. We compared influenza and pneumococcal vaccination rates among eligible Asian Americans and white Americans, and for Vietnamese Americans as a subgroup, and assessed factors associated with these vaccinations. Cross-sectional study of data collected from three ethnic groups over 4 years by telephone survey. Data were weighted for selection probability and population estimates and analyzed by multivariate logistic regression. Vietnamese Americans had a higher rate of influenza vaccination (61%) than Asian Americans (45%) and white Americans (52%), and lower rate of pneumococcal vaccination (41%) than Asian Americans (56%), both lower than white Americans (67%). When analyzed as a subgroup, Vietnamese Americans had a higher influenza vaccination rate, but a lower pneumococcal vaccination rate, compared to Asian Americans and white Americans, which may indicate that health behaviors and outcomes can differ widely among Asian subgroups. Analyses of preventive care measures in Asian Americans should focus on subgroups to ensure accuracy and quality of assessments.

  14. Conjugal Pairing in Escherichia Coli

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  15. Persistence Mechanisms of Conjugative Plasmids

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting the suc...

  16. Orderings for conjugate gradient preconditionings

    Ortega, James M.

    1991-01-01

    The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.

  17. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

    2016-08-01

    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

    REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

  19. Purification of SUMO conjugating enzymes and kinetic analysis of substrate conjugation

    Yunus, Ali A.; Lima, Christopher D.

    2009-01-01

    SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417

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

    Williams, B Adam; 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

    2016-06-01

    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. © The Author 2016. Published by

  1. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis.

    Winthrop, Kevin L; Silverfield, Joel; Racewicz, Arthur; Neal, Jeffrey; Lee, Eun Bong; Hrycaj, Pawel; Gomez-Reino, Juan; Soma, Koshika; Mebus, Charles; Wilkinson, Bethanie; Hodge, Jennifer; Fan, Haiyun; Wang, Tao; Bingham, Clifton O

    2016-04-01

    To evaluate tofacitinib's effect upon pneumococcal and influenza vaccine immunogenicity. We conducted two studies in patients with rheumatoid arthritis using the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and the 2011-2012 trivalent influenza vaccine. In study A, tofacitinib-naive patients were randomised to tofacitinib 10 mg twice daily or placebo, stratified by background methotrexate and vaccinated 4 weeks later. In study B, patients already receiving tofacitinib 10 mg twice daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation. In both studies, titres were measured 35 days after vaccination. Primary endpoints were the proportion of patients achieving a satisfactory response to pneumococcus (twofold or more titre increase against six or more of 12 pneumococcal serotypes) and influenza (fourfold or more titre increase against two or more of three influenza antigens). In study A (N=200), fewer tofacitinib patients (45.1%) developed satisfactory pneumococcal responses versus placebo (68.4%), and pneumococcal titres were lower with tofacitinib (particularly with methotrexate). Similar proportions of tofacitinib-treated and placebo-treated patients developed satisfactory influenza responses (56.9% and 62.2%, respectively), although fewer tofacitinib patients (76.5%) developed protective influenza titres (≥1:40 in two or more of three antigens) versus placebo (91.8%). In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively). Among patients starting tofacitinib, diminished responsiveness to PPSV-23, but not influenza, was observed, particularly in those taking concomitant methotrexate. Among existing tofacitinib users, temporary drug discontinuation had limited

  2. [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].

    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

  3. Cost-Effectiveness of a Program to Eliminate Disparities in Pneumococcal Vaccination Rates in Elderly Minority Populations: An Exploratory Analysis

    Michaelidis, Constantinos I.; Zimmerman, Richard K.; Nowalk, Mary Patricia; Smith, Kenneth J.

    2013-01-01

    Objective Invasive pneumococcal disease is a major cause of preventable morbidity and mortality in the United States, particularly among the elderly (>65 years). There are large racial disparities in pneumococcal vaccination rates in this population. Here, we estimate the cost-effectiveness of a hypothetical national vaccination intervention program designed to eliminate racial disparities in pneumococcal vaccination in the elderly. Methods In an exploratory analysis, a Markov decision-analysis model was developed, taking a societal perspective and assuming a 1-year cycle length, 10-year vaccination program duration, and lifetime time horizon. In the base-case analysis, it was conservatively assumed that vaccination program promotion costs were $10 per targeted minority elder per year, regardless of prior vaccination status and resulted in the elderly African American and Hispanic pneumococcal vaccination rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the program. Results The incremental cost-effectiveness of the vaccination program relative to no program was $45,161 per quality-adjusted life-year gained in the base-case analysis. In probabilistic sensitivity analyses, the likelihood of the vaccination program being cost-effective at willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%, respectively. Conclusions In a conservative analysis biased against the vaccination program, a national vaccination intervention program to ameliorate racial disparities in pneumococcal vaccination would be cost-effective. PMID:23538183

  4. 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.

    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

  5. 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.

    Robert Cilveti

    Full Text Available 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

  6. Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.

    Smith, Jennifer G; Metzger, Nicole L

    2011-11-01

    Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the

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

    Elisa Ramos-Sevillano

    2016-03-01

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

  8. Use of Pneumococcal Disease Epidemiology to Set Policy and Prevent Disease during 20 Years of the Emerging Infections Program.

    Moore, Matthew R; Whitney, Cynthia G

    2015-09-01

    Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years.

  9. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.

    Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

    2016-04-01

    Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Epithelial Cell–Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia

    Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A.; Zabinski, Mary C.; Yuen, Constance K.; Lung, Wing Yi; Gower, Adam C.; Belkina, Anna C.; Ramirez, Maria I.; Deng, Jane C.; Quinton, Lee J.; Jones, Matthew R.

    2016-01-01

    Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6GbrightCD11bbright neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia. PMID:27064756

  11. Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia.

    Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A; Zabinski, Mary C; Yuen, Constance K; Lung, Wing Yi; Gower, Adam C; Belkina, Anna C; Ramirez, Maria I; Deng, Jane C; Quinton, Lee J; Jones, Matthew R; Mizgerd, Joseph P

    2016-09-01

    Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6G(bright)CD11b(bright) neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia.

  12. Sensitivity, Specificity, and Positivity Predictors of the Pneumococcal Urinary Antigen Test in Community-Acquired Pneumonia.

    Molinos, Luis; Zalacain, Rafael; Menéndez, Rosario; Reyes, Soledad; Capelastegui, Alberto; Cillóniz, Catia; Rajas, Olga; Borderías, Luis; Martín-Villasclaras, Juan J; Bello, Salvador; Alfageme, Inmaculada; Rodríguez de Castro, Felipe; Rello, Jordi; Ruiz-Manzano, Juan; Gabarrús, Albert; Musher, Daniel M; Torres, Antoni

    2015-10-01

    Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia. We assessed the sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia. We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia. The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressureantibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%. The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test.

  13. IMMUNIZATION OF CHILDREN AGAINST PNEUMOCOCCAL DISEASE: PRACTICAL ASPECTS FROM THE STANDPOINT OF AN OTOLARYNGOLOGIST

    S. G. Gubanova

    2014-01-01

    Full Text Available The article describes the results of studying the effectiveness of vaccination of children with allergic disorders and frequently ill children against pneumococcal diseases. The effectiveness and good tolerability of the vaccine was detected. A follow-up study of the vaccinated children was performed. The positive effect of vaccination on the incidence of acute respiratory diseases, acute adenoiditis and acute otitis media in all groups of children was shown. The positive effect of vaccination on the degree of hyperplasia of adenoid tissue in the nasopharynx of frequently ill children was proved.

  14. Structure Property Relationships in Organic Conjugated Systems

    O'Neill, Luke

    2008-01-01

    A series of pi(п) conjugated oligomers containing 1 to 6 monomer units were studied by absorption and photoluminescence spectroscopies. The results are discussed and examined with regard to the variation of the optical properties with the increase of effective conjugation length. It was found that there was a linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length. The relationships are in good agreement with the si...

  15. Predictors of Uptake and Timeliness of Newly Introduced Pneumococcal and Rotavirus Vaccines, and of Measles Vaccine in Rural Malawi: A Population Cohort Study.

    Hazzie Mvula

    Full Text Available Malawi introduced pneumococcal conjugate vaccine (PCV13 and monovalent rotavirus vaccine (RV1 in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV. We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting.Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression.Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36, 19 days (IQR 8-36 for RV1 dose 1 and 20 days (IQR 3-46 for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule.Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.

  16. Conjugated Polymers for Energy Production

    Livi, Francesco

    This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates...... polymerization method for industrial production of polymers. Several DArP protocols have been employed for the synthesis of PPDTBT leading to polymers with high structural regularity and photovoltaic performances comparable with the same materials synthesized via Stille cross-coupling polymerization...

  17. Novel ?-cyclodextrin?eosin conjugates

    Benkovics, G?bor; Afonso, Damien; Darcsi, Andr?s; B?ni, Szabolcs; Conoci, Sabrina; Fenyvesi, ?va; Szente, Lajos; Malanga, Milo; Sortino, Salvatore

    2017-01-01

    Eosin B (EoB) and eosin Y (EoY), two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy an...

  18. Test of charge conjugation invariance

    Nefkens, B.M.K.; Prakhov, S.; Gaardestig, A.; Clajus, M.; Marusic, A.; McDonald, S.; Phaisangittisakul, N.; Price, J.W.; Starostin, A.; Tippens, W.B.; Allgower, C.E.; Spinka, H.; Bekrenev, V.; Koulbardis, A.; Kozlenko, N.; Kruglov, S.; Lopatin, I.; Briscoe, W.J.; Shafi, A.; Comfort, J.R.

    2005-01-01

    We report on the first determination of upper limits on the branching ratio (BR) of η decay to π 0 π 0 γ and to π 0 π 0 π 0 γ. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(η→π 0 π 0 γ) -4 at the 90% confidence level, in support of C invariance of isoscalar electromagnetic interactions of the light quarks. We have also measured BR(η→π 0 π 0 π 0 γ) -5 at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions

  19. Unusual Manifestation of Severe Conjugated Hyperbilirubinemia in an Infant with Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome

    Jung-Pin Chen

    2007-01-01

    Full Text Available Streptococcus pneumoniae is an uncommon etiologic organism in children with hemolytic uremic syndrome (HUS. Historically, severe S. pneumoniae-associated HUS usually has a poor clinical outcome. The clinical manifestations of marked jaundice and hepatic dysfunction in this form of HUS are extremely rare. We report a 10-month-old female infant with S. pneumoniae-associated HUS who had the unusual manifestation of severely elevated conjugated bilirubin and hepatic transaminases. Screening for viral hepatitis was negative, and evidence of biliary obstruction and hepatotoxic drug exposure was also absent. The patient was treated with antihypertensive agents for 2.5 months and required peritoneal dialysis for a period of 26 days. Hepatic function returned to normal on the 8th day of hospitalization. Renal function was mildly impaired at 1-year follow-up. Our report suggests that severe conjugated hyperbilirubinemia is a rare manifestation of S. pneumoniae-associated HUS in children. It is important for pediatricians that pneumococcal infection with severe hematologic and renal disorders should be investigated for evidence of S. pneumoniae-associated HUS. [J Formos Med Assoc 2007;106(2 Suppl:S17-S22

  20. Conjugated polymers developed from alkynes

    Yajing Liu; Jacky W.Y.Lam; Ben Zhong Tang

    2015-01-01

    The numerous merits of conjugated polymers(CPs) have encouraged scientists to develop a variety of synthetic routes to CPs with diverse structures and functionalities. Among the large scope of substrates,alkyne plays an important role in constructing polymers with conjugated backbones. In addition to some well-developed reactions including Glaser–Hay and Sonogashira coupling, azide/thiol-yne click reaction and cyclotrimerization, some novel alkyne-based reactions have also been explored such as oxidative polycoupling, decarbonylative polycoupling and multicomponent tandem polymerizations. his review focuses on the recent progress on the synthetic methodology of CPs in the last ive years using monomers with two or more triple bonds and some of their high-technological applications. Selected examples of materials properties of these CPs are given in this review, such as luorescence response to chemical or physical stimuli, magnetism, white light emission, cell imaging and bioprobing. Finally, a short perspective is raised in regard to the outlook of the preparation methodologies, functionalities as well as potential applications of CPs in the future.

  1. Subgap Absorption in Conjugated Polymers

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  2. Subgap absorption in conjugated polymers

    Sinclair, M.; Seager, C.H. (Sandia National Labs., Albuquerque, NM (USA)); McBranch, D.; Heeger, A.J. (California Univ., Santa Barbara, CA (USA)); Baker, G.L. (Bell Communications Research, Inc., Red Bank, NJ (USA))

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of < 10{sup {minus}5}, Photothermal Deflection Spectroscopy (PDS) is ideal for determining the absorption coefficients of thin films of transparent'' materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination. 11 refs., 4 figs.

  3. First Report of a Case of Pneumococcal Meningitis Which Did Not Respond to the Ceftriaxone Therapy despite the Isolated Organism Being Sensitive to This Antibiotic In Vitro

    Maryam Mojtabavi

    2011-01-01

    Full Text Available A 60-year-old man presented with pneumococcal meningitis which did not respond to the ceftriaxone therapy, in spite of in-vitro susceptibility (minimal inhibitory concentration of 0.016 μg/dLit of the isolated organism to this antibacterial agent, although ceftriaxone is still the drug of choice for such pneumococcal meningitis. Review of published articles revealed no report of clinical resistance in organisms which were susceptible to the same antimicrobial agent in vitro. This alarming emergence of isolates with in vivo resistance should be considered and even could lead to a shift in the empirical antibiotic therapy for pneumococcal infections.

  4. Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

    Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2014-04-14

    Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

  5. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

    Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti

    2008-01-01

    Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022

  6. A Case of Invasive Pneumococcal Infection with Septic Shock and Rare Complications

    John R. Woytanowski

    2017-01-01

    Full Text Available Invasive pneumococcus is a serious illness with potentially devastating outcomes. A 64-year-old female with a medical history of psoriatic arthritis and diabetes was transferred from an outside hospital for ventilator dependent respiratory failure and altered mental status. She initially presented with worsening back pain and was found to have leukocytosis with bandemia and acute renal failure but she was in septic shock upon arrival to our tertiary care center. Her blood cultures grew Streptococcus pneumoniae and MRI of the brain revealed pus within the posterior lateral ventricles and multiple infarcts. MRI of the spine revealed a psoas abscess. Transesophageal echocardiogram revealed mitral valve vegetation and her right eye developed endogenous endophthalmitis. She was treated with intravenous and intravitreal antibiotics and underwent drainage of the abscess with no improvement in mental status. Repeat imaging revealed multiple new thalamic, basal ganglia, and parietal lobe infarcts likely from septic emboli. After a protracted ICU stay, the patient’s family opted for comfort care. The incidence of invasive pneumococcal infections has declined rapidly since the advent of antibiotics and vaccines. With the growing incidence of antibiotic resistance as well as the emergence of new immunomodulating drugs for various pathologies, there is a concern that invasive infections will reemerge. Ventriculitis and endogenous endophthalmitis are very rare complications of pneumococcal bacteremia.

  7. c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

    Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

    2009-01-01

    Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

  8. Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4.

    Nagai, Kosuke; Domon, Hisanori; Maekawa, Tomoki; Oda, Masataka; Hiyoshi, Takumi; Tamura, Hikaru; Yonezawa, Daisuke; Arai, Yoshiaki; Yokoji, Mai; Tabeta, Koichi; Habuka, Rie; Saitoh, Akihiko; Yamaguchi, Masaya; Kawabata, Shigetada; Terao, Yutaka

    2018-03-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia. Our previous study suggested that S. pneumoniae autolysis-dependently releases intracellular pneumolysin, which subsequently leads to lung injury. In this study, we hypothesized that pneumococcal autolysis induces the leakage of additional intracellular molecules that could increase the pathogenicity of S. pneumoniae. Liquid chromatography tandem-mass spectrometry analysis identified that chaperone protein DnaK, elongation factor Tu (EF-Tu), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were released with pneumococcal DNA by autolysis. We demonstrated that recombinant (r) DnaK, rEF-Tu, and rGAPDH induced significantly higher levels of interleukin-6 and tumor necrosis factor production in peritoneal macrophages and THP-1-derived macrophage-like cells via toll-like receptor 4. Furthermore, the DNA-binding activity of these proteins was confirmed by surface plasmon resonance assay. We demonstrated that pneumococcal DnaK, EF-Tu, and GAPDH induced the production of proinflammatory cytokines in macrophages, and might cause host tissue damage and affect the development of pneumococcal diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein.

    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M; Di Guilmi, Anne Marie; Frachet, Philippe

    2012-12-14

    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (K(D) = 0.34-2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response.

  10. Human and Pneumococcal Cell Surface Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Proteins Are Both Ligands of Human C1q Protein*

    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M.; Di Guilmi, Anne Marie; Frachet, Philippe

    2012-01-01

    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (KD = 0.34–2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response. PMID:23086952

  11. Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

    Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M

    2015-01-01

    Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA

  12. Identification of protective pneumococcal T(H17 antigens from the soluble fraction of a killed whole cell vaccine.

    Kristin L Moffitt

    Full Text Available Mucosal or parenteral immunization with a killed unencapsulated pneumococcal whole cell antigen (WCA with an adjuvant protects mice from colonization by a T(H17 CD4+ cell-mediated mechanism. Using preparative SDS gels, we separated the soluble proteins that compose the WCA in order to identify fractions that were immunogenic and protective. We screened these fractions for their ability to stimulate IL-17A secretion from splenocytes obtained from mice immunized with WCA and adjuvant. We identified 12 proteins within the stimulatory fractions by mass spectrometry; these proteins were then cloned, recombinantly expressed and purified using an Escherichia coli expression system. The ability of these proteins to induce IL-17A secretion was then evaluated by stimulation of mouse splenocytes. Of the four most stimulatory proteins, three were protective in a mouse pneumococcal serotype 6B colonization model. This work thus describes a method for identifying immunogenic proteins from the soluble fraction of pneumococcus and shows that several of the proteins identified protect mice from colonization when used as mucosal vaccines. We propose that, by providing protection against pneumococcal colonization, one or more of these proteins may serve as components of a multivalent pneumococcal vaccine.

  13. Pneumococcal infections in humans are associated with increased apoptosis and trafficking of type 1 cytokine-producing T cells

    Kemp, Kåre; Bruunsgaard, Helle; Skinhøj, Peter

    2002-01-01

    , little is known regarding the T-cell response during in vivo infections in humans. The purpose of this study was to test the hypothesis that activated T cells producing type 1 cytokines were engaged in the host response to pneumococcal infections. The phenotype and function of T cells were studied in 22...

  14. Pneumococcal and influenza vaccination status of hospitalized adults with community acquired pneumonia and the effects of vaccination on clinical presentation.

    Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Sayıner, Abdullah; Cilli, Aykut; Kılınc, Oguz; Sakar Coskun, Aysın; Hazar, Armağan; Kokturk, Nurdan; Filiz, Ayten; Polatli, Mehmet

    2017-09-02

    Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP. Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available. In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission. This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect the clinical outcomes.

  15. CodY Regulates Thiol Peroxidase Expression as Part of the Pneumococcal Defense Mechanism against H2O2 Stress

    Hajaj, Barak; Yesilkaya, Hasan; Shafeeq, Sulman; Zhi, Xiangyun; Benisty, Rachel; Tchalah, Shiran; Kuipers, Oscar P; Porat, Nurith

    2017-01-01

    Streptococcus pneumoniae is a facultative anaerobic pathogen. Although it maintains fermentative metabolism, during aerobic growth pneumococci produce high levels of H2O2, which can have adverse effects on cell viability and DNA, and influence pneumococcal interaction with its host. The pneumococcus

  16. No intention to comply with influenza and pneumococcal vaccination : behavioural determinants among smokers and non-smokers

    Looijmans-van den Akker, I; van den Heuvel, P.M.; Verheij, Th J M; van Delden, J J M; van Essen, G A; Hak, E

    OBJECTIVE: Smoking increases the risk for influenza and pneumococcal disease, but vaccination uptake is lower among smokers than non-smokers. We therefore aimed to determine reasons for not complying with vaccination among smokers and non-smokers. METHOD: In 2005 a self-administered questionnaire

  17. Pneumococcal Replicative State in Relation to its Adherence Capacity to A549-cell Line: A Preliminary in vitro Analysis

    Mohd Desa, M. N.

    2011-01-01

    Full Text Available This study was to compare the replication capacity of pneumococcal isolates (serotypes 1, 7F, 19F and 23F with their adherence pattern to monolayer cells (A549. For standardization purposes, all isolates showed a normal growth curve in both bacteriological (THB + 0.5% yeast extract with and without 2% FBS and cell culture media (RPMI + 2% FBS. In the former media, a shorter lag phase was observed for isolate serotypes 1 and 7F in presence of serum while in the later; growth yield was lower for all isolates with stationary phase approaching OD600 of 0.01 as compared to 1.0 in bacteriological media. In the replicative analysis at different growth phases of the isolates in cell culture media, growth capacity at 3 h post-incubation was frequently twice as that at 1 h, and that at early-log phase was frequently higher than that at mid-log phase at both post-incubation times. Adherence was frequently the least at early-log phase although the isolates were in the most active state of replication to increase the number of pneumococcal cells to adhere. At mid- and late-log phases, pneumococcal adherence was frequently higher although the replication was reduced. This study marks the potential correlation between pneumococcal growth fitness and adherence capacity whereby the later may not be superior during the early growth phase.

  18. Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

    Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard

    2014-01-01

    BACKGROUND: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2......, on susceptibility and disease severity of IPD in previously healthy children aged

  19. Evaluation of a disturbance of cerebrospinal fluid circulation after pneumococcal meningitis, using a new cysternography method (Indium 111)

    Sulman, C.; Goudemand, M.; Caron, J.C.

    1974-01-01

    An isotope cisternography using 111 In was performed in a 61 year old woman with pneumococcal meningits. A disturbance of cerebrospinal fluid circulation was exhibited. 111 In was found to be of interest for isotope cisternography. The principal clinical indications of this investigation were summarized [fr

  20. Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in the United Kingdom.

    Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

    2009-02-01

    This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.

  1. Preconditioning the modified conjugate gradient method ...

    In this paper, the convergence analysis of the conventional conjugate Gradient method was reviewed. And the convergence analysis of the modified conjugate Gradient method was analysed with our extension on preconditioning the algorithm. Convergence of the algorithm is a function of the condition number of M-1A.

  2. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  3. Tetrafullerene conjugates for all-organic photovoltaics

    Fernández, G.; Sánchez, L.; Veldman, D.; Wienk, M.M.; Atienza, C.M.; Guldi, D.M.; Janssen, R.A.J.; Martin, N.

    2008-01-01

    The synthesis of two new tetrafullerene nanoconjugates in which four C60 units are covalently connected through different -conjugated oligomers (oligo(p-phenylene ethynylene) and oligo(p-phenylene vinylene)) is described. The photovoltaic (PV) response of these C60-based conjugates was evaluated by

  4. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  5. The Conjugate Acid-Base Chart.

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  6. Bio-Conjugates for Nanoscale Applications

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  7. Class, Kinship Density, and Conjugal Role Segregation.

    Hill, Malcolm D.

    1988-01-01

    Studied conjugal role segregation in 150 married women from intact families in working-class community. Found that, although involvement in dense kinship networks was associated with conjugal role segregation, respondents' attitudes toward marital roles and phase of family cycle when young children were present were more powerful predictors of…

  8. Misonidazole-glutathione conjugates in CHO cells

    Varghese, A.J.; Whitmore, G.F.

    1984-01-01

    Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

  9. Approximate error conjugation gradient minimization methods

    Kallman, Jeffrey S

    2013-05-21

    In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

  10. Modelling conjugation with stochastic differential equations

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

    2010-01-01

    Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared......Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...... using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared...

  11. Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae before conjugate vaccine introduction: a prediction model based on a meta-analysis.

    Olivier Le Polain de Waroux

    Full Text Available INTRODUCTION: Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children. METHODS: We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT serotypes in older age groups as a function of that in <5 y olds. RESULTS: Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y and both that in school aged children (5-17 y olds and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5-17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5-17 y olds and adults as a function of that in children <5 years of age. CONCLUSION: Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.

  12. Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae before conjugate vaccine introduction: a prediction model based on a meta-analysis.

    Le Polain de Waroux, Olivier; Flasche, Stefan; Prieto-Merino, David; Edmunds, W John

    2014-01-01

    Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children. We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5-17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5-17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5-17 y olds and adults as a function of that in children <5 years of age. Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.

  13. [Contribution of urinary pneumococcal antigen detection combined with the research of legionella antigen for diagnosis of pneumonia in hospitalized patients].

    Honoré, S; Trillard, M; Ould-Hocine, Z; Lesprit, P; Deforges, L; Legrand, P

    2004-10-01

    Bacteriological confirmation of pneumonia (PNM) in hospitalized patients is often erratic or belated. Because of importance of prognosis, early adaptation of treatment requires an empirical antimicrobial therapy (generally aminopenicillin and macrolide combination). The starting therapeutic strategy should profit by a fast and reliable test asserting a pneumococcal etiology. The Binax Now S. pneumoniae (BNP) test allows an urinary pneumococcal antigen (UPA) detection using an immunochromatographic membrane assay within 15 minutes. We first evaluated the BNP test for 28 patients with pneumococcal PNM proved by culture, and 118 negative control patients without PNM. The BNP test was then evaluated by testing urine from 158 hospitalized patients with a clinical picture of PNM (community-acquired: 90, nosocomial: 68) for whom a research of urinary Legionella antigen (Binax Now) was prescribed and was positive for only two cases. 57 patients (36.1%) were hospitalized in ICU. The sensitivity was 71.4% (85.7% for the 21 bacteriemic PNM), and the specificity was 98.3%; that is consistent with previous published data. Among the 158 patients with PNM, UPA was detected in 17 cases (10.8%): 15 within the community-acquired PNM (16.7%) and 2 (2.9%) within the nosocomial cases. The pneumococcal etiology was confirmed by bacteriological samples in 7/17 patients (6 by blood cultures). The 10 others showed clinical and radiological features in agreement with a pneumococcal PNM. Among the 141 patients with negative AUP, S. pneumoniae was isolated from 6 of them (2 in blood cultures). The Binax Now S. pneumoniae test allowed a fast and reliable etiological diagnosis in 10.8% of hospitalized PNM (16.7% of the community-acquired cases) having a research of urinary Legionella antigen (conceiving with severity factors). So it could conduce to an improved adjustment of the starting antimicrobial therapy of hospitalized adult patients with PNM.

  14. Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients

    Kronborg, Gitte; Weis, Nina; Madsen, Hans O

    2002-01-01

    for pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae....... The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role......Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor...

  15. A Mechanism of Unidirectional Transformation, Leading to Antibiotic Resistance, Occurs within Nasopharyngeal Pneumococcal Biofilm Consortia.

    Lattar, Santiago M; Wu, Xueqing; Brophy, Jennifer; Sakai, Fuminori; Klugman, Keith P; Vidal, Jorge E

    2018-05-15

    Streptococcus pneumoniae acquires genes for resistance to antibiotics such as streptomycin (Str) or trimethoprim (Tmp) by recombination via transformation of DNA released by other pneumococci and closely related species. Using naturally transformable pneumococci, including strain D39 serotype 2 (S2) and TIGR4 (S4), we studied whether pneumococcal nasopharyngeal transformation was symmetrical, asymmetrical, or unidirectional. Incubation of S2 Tet and S4 Str in a bioreactor simulating the human nasopharynx led to the generation of Spn Tet/Str recombinants. Double-resistant pneumococci emerged soon after 4 h postinoculation at a recombination frequency (rF) of 2.5 × 10 -4 while peaking after 8 h at a rF of 1.1 × 10 -3 Acquisition of antibiotic resistance genes by transformation was confirmed by treatment with DNase I. A high-throughput serotyping method demonstrated that all double-resistant pneumococci belonged to one serotype lineage (S2 Tet/Str ) and therefore that unidirectional transformation had occurred. Neither heterolysis nor availability of DNA for transformation was a factor for unidirectional transformation given that the density of each strain and extracellular DNA (eDNA) released from both strains were similar. Unidirectional transformation occurred regardless of the antibiotic-resistant gene carried by donors or acquired by recipients and regardless of whether competence-stimulating peptide-receptor cross talk was allowed. Moreover, unidirectional transformation occurred when two donor strains (e.g., S4 Str and S19F Tmp ) were incubated together, leading to S19F Str/Tmp but at a rF 3 orders of magnitude lower (4.9 × 10 -6 ). We finally demonstrated that the mechanism leading to unidirectional transformation was due to inhibition of transformation of the donor by the recipient. IMPORTANCE Pneumococcal transformation in the human nasopharynx may lead to the acquisition of antibiotic resistance genes or genes encoding new capsular variants

  16. The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

    Gyhrs, A; Pedersen, B K; Bygbjerg, I

    1991-01-01

    (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

  17. Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

    Francis, J P; Richmond, P C; Strickland, D; Prescott, S L; Pomat, W S; Michael, A; Nadal-Sims, M A; Edwards-Devitt, C J; Holt, P G; Lehmann, D; van den Biggelaar, A H J

    2017-03-01

    In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. © 2016 British Society for Immunology.

  18. Cross-sectional study on attitudes among general practitioners towards pneumococcal vaccination for middle-aged and elderly population in Hong Kong.

    Lancelot W H Mui

    Full Text Available OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64 and elderly population (over 65 in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%. Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1, and attending 6 pneumonia cases or more per year (ORm 2.28 were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41, consultation not related to vaccination (ORm 0.45 and limited time (ORm 0.38 were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.

  19. [Pharmaco-economic aspects of vaccination against invasive pneumococcal infections in persons over 65 years of age; review of the literature on cost effectiveness analysis].

    Postma, M J; Heijnen, M L A; Beutels, Ph; Jager, J C

    2002-05-04

    To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly. Review of the literature. Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions. We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses. The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.

  20. Novel Aflatoxin Derivatives and Protein Conjugates

    Reinhard Niessner

    2007-03-01

    Full Text Available Aflatoxins, a group of structurally related mycotoxins, are well known for their toxic and carcinogenic effects in humans and animals. Aflatoxin derivatives and protein conjugates are needed for diverse analytical applications. This work describes a reliable and fast synthesis of novel aflatoxin derivatives, purification by preparative HPLC and characterisation by ESI-MS and one- and two-dimensional NMR. Novel aflatoxin bovine serum albumin conjugates were prepared and characterised by UV absorption and MALDI-MS. These aflatoxin protein conjugates are potentially interesting as immunogens for the generation of aflatoxin selective antibodies with novel specificities.

  1. Bacterial Invasion of the Inner Ear in Association With Pneumococcal Meningitis

    Møller, Martin Nue; Brandt, Christian; Østergaard, Christian

    2014-01-01

    OBJECTIVE: To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. STUDY DESIGN: A well-established adult rat model of Streptococcus pneumoniae meningitis was used. METHODS: Thirty rats were inoculated intrathecally with S. pneumoniae...... scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial...... spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. CONCLUSION: From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral...

  2. Analysis of invasive pneumonia-causing strains of Streptococcus pneumoniae: serotypes and antimicrobial susceptibility.

    Yoshioka, Cristina R M; Martinez, Marina B; Brandileone, Maria C C; Ragazzi, Selma B; Guerra, Maria L L S; Santos, Silvia R; Shieh, Huei H; Gilio, Alfredo E

    2011-01-01

    To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de São Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. The study included 107 children. The most common serotypes were 14 (36.5%), 1 (16%), 5 (14.6%), 6B (6.3%) and 3 (4.2%). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9%, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC ≤ 2 µg/mL) in 100 cases (93.5%) and displayed intermediate resistance (MIC = 4 µg/mL) in 7 cases (6.5%). No strains were penicillin-resistant (MIC ≥ 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

  3. Prevalence and trend in the use of hospital-based standing orders programs for influenza and pneumococcal vaccination.

    Pentakota, Sri Ram; Halperin, William

    2007-08-01

    In 2002, federal regulations authorized the use of standing orders programs (SOPs) for promoting influenza and pneumococcal vaccination. In 2003, the New Jersey Hospital Association conducted a demonstration project illustrating the efficacy of SOPs, and the state health department informed healthcare facilities of their benefits. We describe the prevalence of reported use of SOPs in New Jersey hospitals in 2003 and 2005 and identify hospital characteristics associated with the use of SOPs. A survey was mailed to the directors of infection control at 117 New Jersey hospitals during the period from January to May 2005 (response rate, 90.6%). Data on hospital characteristics were obtained from hospital directories and online resources. The prevalence of use of SOPs for influenza vaccination was 50% (95% confidence interval [CI], 40.1%-59.9%) in 2003, and it increased to 78.3% (95% CI, 69.2%-85.7%) in 2005. The prevalence of SOP use for pneumococcal vaccination was similar. In 2005, the reported rate of use of SOPs for inpatients (influenza vaccination, 76.4%; pneumococcal vaccination, 75.5%) was significantly higher than that for outpatients (influenza vaccination, 9.4%; pneumococcal vaccination, 8.5%). Prevalence ratios for SOP use comparing acute care and non-acute care hospitals were 1.71 (95% CI, 1.2-2.5) for influenza vaccination SOPs and 1.8 for (95% CI, 1.2-2.7) pneumococcal vaccination SOPs. Acute care hospitals with a ratio of admissions to total beds greater than 36.7 reported greater use of SOPs for pneumococcal vaccination, compared with those that had a ratio of less than 36.7. The increase in the prevalence of reported use of SOPs among New Jersey hospitals in 2005, compared with 2003, was contemporaneous with SOP-related actions taken by the federal government, the state government, and the New Jersey Hospital Association. Opportunities persist for increased use of SOPs among non-acute care hospitals and for outpatients.

  4. Kinetics of antibodies against pneumococcal proteins and their relationship to nasopharyngeal carriage in the first two months of life.

    Awa L Mendy

    Full Text Available The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants.One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples.The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9 higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004, but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009, 6 (p = 0.002 and 8 (p<0.0001. At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001, compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI: 0.49 (0.26-0.92, p = 0.03], but not PspA and rPly, were associated with protection against carriage in the infants.Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S

  5. Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal Pneumonia.

    Ajayi, Oluwadamilare O; Norton, Nancy B; Gress, Todd W; Stanek, Ronald J; Mufson, Maurice A

    2017-05-01

    Streptococcus pneumoniae infection is the most common cause of community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD) carries a high case fatality rate. We investigated the lifespan of adults who recovered from IPD during a 32-year follow-up. We determined whether adults discharged after an episode of IPD from hospitals affiliated with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate analysis, life expectancy using life tables for West Virginia, years of potential life lost and serotype occurrence. The study group comprised 155 adults who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%) patients lived longer than their life expectancy. Of the 13 comorbid diseases analyzed, cancer and neurologic diseases and the number of comorbid diseases suffered by each patient were the significant variables associated with survival. The mean years of potential life lost was 9.936 years. Only serotype 12 of 31 serotypes recovered occurred more often in patients who survived for 11 or more years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). The fact that most adult patients who recovered from IPD died before their documented life expectancy argues for the pernicious severity of IPD and the importance of immunization of adults with pneumococcal vaccines. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  6. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

    Tatiana Barichello

    2011-01-01

    Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

  7. Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

    Shigeo Hanada

    Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

  8. Using the overlay assay to qualitatively measure bacterial production of and sensitivity to pneumococcal bacteriocins.

    Maricic, Natalie; Dawid, Suzanne

    2014-09-30

    Streptococcus pneumoniae colonizes the highly diverse polymicrobial community of the nasopharynx where it must compete with resident organisms. We have shown that bacterially produced antimicrobial peptides (bacteriocins) dictate the outcome of these competitive interactions. All fully-sequenced pneumococcal strains harbor a bacteriocin-like peptide (blp) locus. The blp locus encodes for a range of diverse bacteriocins and all of the highly conserved components needed for their regulation, processing, and secretion. The diversity of the bacteriocins found in the bacteriocin immunity region (BIR) of the locus is a major contributor of pneumococcal competition. Along with the bacteriocins, immunity genes are found in the BIR and are needed to protect the producer cell from the effects of its own bacteriocin. The overlay assay is a quick method for examining a large number of strains for competitive interactions mediated by bacteriocins. The overlay assay also allows for the characterization of bacteriocin-specific immunity, and detection of secreted quorum sensing peptides. The assay is performed by pre-inoculating an agar plate with a strain to be tested for bacteriocin production followed by application of a soft agar overlay containing a strain to be tested for bacteriocin sensitivity. A zone of clearance surrounding the stab indicates that the overlay strain is sensitive to the bacteriocins produced by the pre-inoculated strain. If no zone of clearance is observed, either the overlay strain is immune to the bacteriocins being produced or the pre-inoculated strain does not produce bacteriocins. To determine if the blp locus is functional in a given strain, the overlay assay can be adapted to evaluate for peptide pheromone secretion by the pre-inoculated strain. In this case, a series of four lacZ-reporter strains with different pheromone specificity are used in the overlay.

  9. Cognitive deficits following exposure to pneumococcal meningitis: an event-related potential study

    Kihara Michael

    2012-03-01

    Full Text Available Abstract Background Pneumococcal meningitis (PM is a severe and life-threatening disease that is associated with cognitive impairment including learning difficulties, cognitive slowness, short-term memory deficits and poor academic performance. There are limited data on cognitive outcomes following exposure to PM from Africa mainly due to lack of culturally appropriate tools. We report cognitive processes of exposed children as measured by auditory and visual event-related potentials. Methods Sixty-five children (32 male, mean 8.4 years, SD 3.0 years aged between 4-15 years with a history of PM and an age-matched control group of 93 children (46 male; mean 8.4 years, SD 2.7 years were recruited from a well-demarcated study area in Kilifi. In the present study, both baseline to peak and peak-to-peak amplitude differences are reported. Results Children with a history of pneumococcal meningitis had significantly longer auditory P1 and P3a latencies and smaller P1 amplitudes compared to unexposed children. In the visual paradigm, children with PM seemingly lacked a novelty P3a component around 350 ms where control children had a maximum, and showed a lack of stimulus differentiation at Nc. Further, children with exposure to PM had smaller peak to peak amplitude (N2-P1 compared to unexposed children. Conclusion The results suggest that children with a history of PM process novelty differently than do unexposed children, with slower latencies and reduced or absent components. This pattern suggests poorer auditory attention and/or cognitive slowness and poorer visual attention orienting, possibly due to disruption in the functions of the lateral prefrontal and superior temporal cortices. ERPs may be useful for assessment of the development of perceptual-cognitive functions in post brain-injury in African children by providing an alternate way of assessing cognitive development in patient groups for whom more typical standardized neuropsychological

  10. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

    Hadley, S.W.; Wilbur, D.S.

    1990-01-01

    The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-[125I/131I]iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-[125I/131I]iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-[131I]iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was ∼ a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate

  11. Conjugate descent formulation of backpropagation error in ...

    nique of backpropagation was popularized in a paper by Rumelhart, et al. ... the training of a multilayer neural network using a gradient descent approach applied to a .... superior convergence of the conjugate descent method over a standard ...

  12. Soluble polymer conjugates for drug delivery.

    Minko, Tamara

    2005-01-01

    The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

  13. Structure Property Relationships in Organic Conjugated Systems

    O'Neill, Luke; Lynch, Patrick; McNamara, Mary

    2005-01-01

    A series of π conjugated oligomers were studied by absorption and photoluminescence spectroscopy. A linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transition energies, it was observed that the Sto...

  14. Diffeomorphisms Holder conjugate to Anosov diffeomorphisms

    Gogolev, Andrey

    2008-01-01

    We show by means of a counterexample that a $C^{1+Lip}$ diffeomorphism Holder conjugate to an Anosov diffeomorphism is not necessarily Anosov. The counterexample can bear higher smoothness up to $C^3$. Also we include a result from the 2006 Ph.D. thesis of T. Fisher: a $C^{1+Lip}$ diffeomorphism Holder conjugate to an Anosov diffeomorphism is Anosov itself provided that Holder exponents of the conjugacy and its inverse are sufficiently large.

  15. Rapid modification of retroviruses using lipid conjugates

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  16. Safety of Combination of a Tetravalent Meningococcal Conjugate Vaccine Against Serogroups A, C, Y, W-135 With Other Vaccine Preparations: a Prospective Study of a Series of Cases Among Healthy Children and Children With Various Health Abnormalities

    Leyla S. Namazova-Baranova

    2017-01-01

    Full Text Available Meningococcal infection is an acute disease caused by Neisseria meningitidis, which proceeds with a diverse clinical aspect from nasopharyngitis to meningococcal meningitis and meningococcemia. Since 2014, a tetravalent meningococcal conjugate vaccine has been registered in Russia. This vaccine creates protection against serogroups A, C, W-135, Y and can be used from the age of nine months to 55 years. The actual issue is a vaccine tolerability, including when combined with other vaccine preparations.Objective: Our aim was to evaluate the safety of a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y and W-135 when it is combined with other vaccine preparations.Methods. A prospective full-design study assessed the tolerability of immunization with a meningococcal conjugate vaccine, both in case of monovaccination and in combination with a pneumococcal 13-valent conjugate vaccine, measles-mumps-rubella, viral hepatitis A, influenza, and chicken pox vaccines.Results. 97 children aged from 9 months to 18 years were vaccinated, 20 of them were healthy and 77 had medical issues (with allergic pathology, ENT diseases, cardiovascular and nervous system diseases, lung diseases as well as orphan diseases. Among vaccinated children, general reactions were observed in 3/97 (3.1% children, local reactions — in 5 (5.2%. The post-vaccination period passed asymptomatically and uneventfully in the prevailing majority of children vaccinated with a tetravalent meningococcal conjugate vaccine (in 91, 93.8%.Conclusion. The immunization with a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y, W-135 is well tolerated, both in case of monovaccination and in combination with other vaccine preparations, in healthy children of different age groups and in patients with different health status.

  17. The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies

    Spencer, Brady L.; Shenoy, Anukul T.; Orihuela, Carlos J.; Nahm, Moon H.

    2017-01-01

    As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acety...

  18. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection

    Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S

    2012-01-01

    The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation...... to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse...... of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci....

  19. Pneumococcal Pneumonia

    ... Cause Disease , May 30, 2018 NIH Begins Testing Ebola Treatment in Early-Stage Trial , May 23, 2018 ... visit the MedlinePlus flu site . Credit: NIAID Colorized structur