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Sample records for acellular pertussis vaccine

  1. Composition of acellular pertussis and combination vaccines: a general review.

    Science.gov (United States)

    Jadhav, S S; Gairola, S

    1999-06-01

    Since the development and introduction of the acellular pertussis vaccine in Japan in the early eighties, we have come a long way in using this component in combination with other vaccines. However, the basic problem in development of an effective and safe pertussis vaccine is that the antigens to induce complete protection against clinical pertussis and the precise mechanism by which pertussis vaccine confers immunity is yet unknown. Hence, the composition of future acellular pertussis vaccine remains an open issue. Recently, acellular pertussis vaccine has been licensed for the booster doses in the U.S.A. and for primary immunization of infants in Italy and Germany. A multicentric trial has been carried out to compare the serological response and adverse reactions of 13 acellular pertussis vaccines. These vaccines contained one or more of the four components, i.e. FHA, PT, 69 kDa OMP and fimbriae. All vaccines were associated with substantially fewer and less adverse reactions and were more immunogenic with respect to antibodies against the added antigens. DTP vaccines in the near future will have combinations of other components and the key antigen for combination will be acellular pertussis component which is going to replace whole cell pertussis component in DTP vaccines. In view of this, manufacturers like ourselves from the developing countries are still groping in the dark, uncertain whether we should have a single component acellular pertussis vaccine or multicomponent one. This will have a major impact on the cost of production, the final cost of the combination vaccines and the regulatory issues that we will have to tackle in view of the recent thinking on harmonization in the pharmaceutical industry. Copyright 1999 The International Association for Biologicals.

  2. Tetanus–diphtheria–acellular pertussis vaccination for adults: an update

    Science.gov (United States)

    2017-01-01

    Although tetanus and diphtheria have become rare in developed countries, pertussis is still endemic in some developed countries. These are vaccine-preventable diseases and vaccination for adults is important to prevent the outbreak of disease. Strategies for tetanus, diphtheria, and pertussis vaccines vary from country to country. Each country needs to monitor consistently epidemiology of the diseases and changes vaccination policies accordingly. Recent studies showed that tetanus–diphtheria–acellular pertussis vaccine for adults is effective and safe to prevent pertussis disease in infants. However, vaccine coverage still remains low than expected and seroprevalence of protective antibodies levels for tetanus, diphtheria, and pertussis decline with aging. The importance of tetanus–diphtheria–acellular pertussis vaccine administration should be emphasized for the protection of young adult and elderly people also, not limited to children. PMID:28168170

  3. Effectiveness of acellular pertussis vaccination during childhood (Spain).

    Science.gov (United States)

    Plans, P; Toledo, D; Sala, M R; Camps, N; Villanova, M; Rodríguez, R; Alvarez, J; Solano, R; García-Cenoz, M; Barrabeig, I; Godoy, P; Minguell, S

    2016-12-01

    Pertussis vaccination with 4-5 doses of acellular vaccines is recommended in Spain to all children at 2 months to 6 years of age. The effectiveness of the acellular pertussis vaccination was assessed in this study by comparing the incidence of secondary pertussis in vaccinated (4-5 doses) and unvaccinated or partially vaccinated (0-3 doses) household contacts 1-9 years old of confirmed cases of pertussis in Spain in 2012-13. Eighty-five percent of contacts had been vaccinated with 4-5 doses of acellular pertussis vaccines. During the 2-year study period, 64 cases of secondary pertussis were detected among 405 household contacts 1-9 years old: 47 among vaccinated and 17 among unvaccinated or partially vaccinated contacts. The effectiveness for preventing secondary pertussis, calculated as 1 minus the relative risk (RR) of secondary pertussis in vaccinated vs. unvaccinated/partially vaccinated contacts, was 50 % [95 % confidence interval (CI): 19-69 %, p Spain.

  4. Pertactin deficient Bordetella pertussis present a better fitness in mice immunized with an acellular pertussis vaccine.

    Science.gov (United States)

    Hegerle, N; Dore, G; Guiso, N

    2014-11-20

    Bordetella pertussis is the etiologic agent of whooping cough and has been the target of vaccination for over fifty years. The latest strategies include the use of acellular pertussis vaccines that induce specific immunity against few virulence factors amongst which pertactin is included in three and five component acellular pertussis vaccines. Recently, it has been reported that B. pertussis clinical isolates loose the production of this adhesin in regions reaching high vaccine coverage with vaccines targeting this virulence factor. We here demonstrate that isolates not producing pertactin are capable of sustaining longer infection as compared to pertactin producing isolates in an in vivo model of acellular pertussis immunization. Loosing pertactin production might thus provide a selective advantage to these isolates in this background, which could account for the upraise in prevalence of these pertactin deficient isolates in the population.

  5. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertus......Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids...

  6. REACTOGENICITY OF ACELLULAR PERTUSSIS VACCINE AND THE POSSIBILITY OF ITS USE IN ELDER CHILDREN

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    M.G. Galitskaya

    2008-01-01

    Full Text Available As is know, in the past few years, the incidence of pertussis has increased again. The article reveals the reasons of this phenomenon and the possible solutions for this problem. Besides, comparative analysis of the whole cell vaccine used in this country as within the framework of the national immunizations schedule and modern acellular vaccines is made. Results of multicenter research, convincingly proving the safety and efficiency of acellular pertussis vaccine, are presented.Key words: pertussis, prophylaxis, whole cell vaccine, acellular vaccine, efficiency, children.

  7. Does tetanus-diphtheria-acellular pertussis vaccination interfere with serodiagnosis of pertussis infection?

    Science.gov (United States)

    Pawloski, Lucia C; Kirkland, Kathryn B; Baughman, Andrew L; Martin, Monte D; Talbot, Elizabeth A; Messonnier, Nancy E; Tondella, Maria Lucia

    2012-06-01

    An anti-pertussis toxin (PT) IgG enzyme-linked immunosorbent assay (ELISA) was analytically validated for the diagnosis of pertussis at a cutoff of 94 ELISA units (EU)/ml. Little was known about the performance of this ELISA in the diagnosis of adults recently vaccinated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine, which contains PT. The goal of this study was to determine when the assay can be used following Tdap vaccination. A cohort of 102 asymptomatic health care personnel (HCP) vaccinated with Tdap (Adacel; Sanofi Pasteur) were aged 19 to 79 years (median, 47 years) at vaccination. For each HCP, specimens were available for evaluation at 2 to 10 time points (prevaccination to 24 months postvaccination), and geometric mean concentrations (GMC) for the cohort were calculated at each time point. Among 97 HCP who responded to vaccination, a mixed-model analysis with prediction and tolerance intervals was performed to estimate the time at which serodiagnosis can be used following vaccination. The GMCs were 8, 21, and 9 EU/ml at prevaccination and 4 and 12 months postvaccination, respectively. Eight (8%) of the 102 HCP reached antibody titers of ≥94 EU/ml during their peak response, but none had these titers by 6 months postvaccination. The calculated prediction and tolerance intervals were <94 EU/ml by 45 and 75 days postvaccination, respectively. Tdap vaccination 6 months prior to testing did not confound result interpretation. This seroassay remains a valuable diagnostic tool for adult pertussis.

  8. Risk of Brain Damage Following Pertussis Immunization with Whole-Cell cf Acellular Vaccines

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    J Gordon Millichap

    2004-06-01

    Full Text Available Serious neurological disorders reported following whole-cell (WC in comparison to acellular (AC pertussis vaccines (PV were evaluated by the Genetic Centers of America, Silver Spring, MD.

  9. Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis.

    Science.gov (United States)

    Li, Zenglan; Zhang, Yan; Wang, Qi; Li, Zhengjun; Liu, Yongdong; Zhang, Songping; Zhang, Guifeng; Ma, Guanghui; Luo, Jian; Su, Zhiguo

    2016-07-25

    Development of acellular pertussis vaccine (aPV) requires purification of several components from Bordetella pertussis. While the components pertussis toxin (PT) and filamentous hemagglutinin (FHA) have been successfully purified, the third component, pertactin, proves to be a difficult target due to its very low concentration. In order to solve its purification problem, we performed the surface potential analysis with GRASP2 program. The results demonstrated that there are two major charge patches, one negative and one positive, which are located separately on this linear protein. For this special feature, we designed a dual ion exchange chromatography strategy including an anionic exchange and a cationic exchange process for separation of pertactin from the heat extract of B. pertussis. The initial anionic exchange chromatography concentrated the product from 1.7% to 14.6%, with recovery of 80%. The second cationic exchange chromatography increased the purity to 33%, with recovery of 83%. The final purification was accomplished by hydrophobic interaction chromatography, yielding a purity of 96%. The total recovery of the three columns was 61%. Characterization of the purified antigen was performed with CD, intrinsic fluorescence, HP-SEC and western-blot, showing that the purified protein kept its natural conformation and immune-reactivity. The rationally designed process proved to be feasible, and it is suitable for large-scale preparation of the third aPV component pertactin.

  10. Should acellular pertussis vaccine be recommended to healthcare professionals?

    Directory of Open Access Journals (Sweden)

    José Cassio de Moraes

    Full Text Available The aim of this study was to describe recent changes in the epidemiology of pertussis and existing policies regarding recommended and mandatory occupational vaccinations for healthcare professionals (HCPs. The authors carried out an extensive review of references on the PubMed and SciELO databases and the official sites of the World Health Organization, Pan American Health Organization, Centers for Disease Control and Prevention, and Brazilian Ministry of Health, using the keywords pertussis, vaccines and healthcare professionals. Vaccination against pertussis is recommended for HCPs in the United States, Canada, nine European countries, Australia, Hong Kong, Singapore, Costa Rica, Argentina and Uruguay, and in some countries it is compulsory. In Brazil, only one publication discussing the risk of pertussis among HCPs was found. Considering the reemergence of pertussis and the great number of associated hospitalizations and deaths registered in 2011, it is necessary to review public policies regarding HCP pertussis vaccination, particularly among workers in frequent contact with young babies.

  11. Should acellular pertussis vaccine be recommended to healthcare professionals?

    Directory of Open Access Journals (Sweden)

    José Cassio de Moraes

    2013-07-01

    Full Text Available The aim of this study was to describe recent changes in the epidemiology of pertussis and existing policies regarding recommended and mandatory occupational vaccinations for healthcare professionals (HCPs. The authors carried out an extensive review of references on the PubMed and SciELO databases and the official sites of the World Health Organization, Pan American Health Organization, Centers for Disease Control and Prevention, and Brazilian Ministry of Health, using the keywords pertussis, vaccines and healthcare professionals. Vaccination against pertussis is recommended for HCPs in the United States, Canada, nine European countries, Australia, Hong Kong, Singapore, Costa Rica, Argentina and Uruguay, and in some countries it is compulsory. In Brazil, only one publication discussing the risk of pertussis among HCPs was found. Considering the reemergence of pertussis and the great number of associated hospitalizations and deaths registered in 2011, it is necessary to review public policies regarding HCP pertussis vaccination, particularly among workers in frequent contact with young babies.

  12. Pertussis epidemic despite high levels of vaccination coverage with acellular pertussis vaccine.

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    Sala-Farré, Maria-Rosa; Arias-Varela, César; Recasens-Recasens, Assumpta; Simó-Sanahuja, Maria; Muñoz-Almagro, Carmen; Pérez-Jové, Josefa

    2015-01-01

    We describe the pertussis epidemic, based only on confirmed whooping cough cases. We have analyzed data on the diagnosis, epidemiology and vaccine history in order to understand the factors that might explain the trends of the disease. A descriptive study of the confirmed pertussis cases reported during 2011 in the Vallès region (population 1,283,000). Laboratory criteria for confirmed pertussis cases include isolation of Bordetella pertussis from a clinical specimen or detection of B. pertussis by PCR in nasopharyngeal swabs. A total of 421 pertussis confirmed cases were reported, which was the highest incidence reported in the last decade (33 cases/100,000 people/year in 2011). The highest incidence rate was among infants less than 1 year old (448/100,000), followed by children 5-9 years old (154/100,000). Pertussis cases aged 2 months-1 year were 90% vaccinated following the current DTaP schedule for their age group in Catalonia, and cases of 5-9 years were 87% fully vaccinated with 5 doses of DTaP vaccine. There were no deaths, although 8% of cases were hospitalized. Pertussis was more severe in infants, 30% required hospitalization despite having received the vaccine doses corresponding to their age. Children of 5-9 years were most often identified as primary cases in households or school clusters. Despite high levels of vaccination coverage, pertussis circulation cannot be controlled at all. The results question the efficacy of the present immunization programmes. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Comparative effectiveness of acellular versus whole-cell pertussis vaccines in teenagers.

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    Klein, Nicola P; Bartlett, Joan; Fireman, Bruce; Rowhani-Rahbar, Ali; Baxter, Roger

    2013-06-01

    During the 1990s, the United States switched from combined diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines to combined acellular pertussis (DTaP) vaccines because of safety concerns. After a 2010-2011 pertussis outbreak, we sought to evaluate whether disease risk in 10 to 17 year olds differed between those who previously received DTwP from those who received DTaP. A case-control study among individuals born from 1994 to 1999 who received 4 pertussis-containing vaccines during the first 2 years of life at Kaiser Permanente Northern California (KPNC). We separately compared pertussis polymerase chain reaction (PCR)-positive cases with PCR-negative and KPNC-matched controls. We assessed risk of pertussis relative to vaccine type in early childhood (4 DTwPs, mixed DTwP/DTaP, or 4 DTaPs) by using conditional logistic regression stratified for calendar time and adjusted for gender, race, medical clinic, and receipt of reduced antigen content acellular pertussis (Tdap) vaccine. We compared 138 PCR-positive cases with 899 PCR-negative and 54 339 KPNC-matched controls. Teenagers who had received 4 DTwPs were much less likely to be pertussis PCR-positive than those who had received 4 DTaPs (odds ratio 5.63, 95% confidence interval 2.55-12.46) or mixed DTwP/DTaP vaccines (odds ratio 3.77, 95% confidence interval 1.57-9.07). Decreasing number of DTwP doses was significantly associated with increased pertussis risk (P vaccines in childhood were more protected during a pertussis outbreak than were those who received DTaP vaccines.

  14. Tetanus-diphtheria-acellular pertussis vaccination of adults in the USA.

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    Gidengil, Courtney A; Sandora, Thomas J; Lee, Grace M

    2008-07-01

    Pertussis is an important cause of morbidity and mortality, and its incidence has been increasing in adolescents and adults over the past two decades. Waning immunity in adolescents and adults may be partially responsible. Adults can suffer significant illness from pertussis and its complications, such as pneumonia, rib fractures and syncope. Moreover, adults serve as a source of disease for infants, who are more vulnerable to severe complications and even death. The economic burden of pertussis is substantial, in terms of both medical and nonmedical costs. Fortunately, the burden of pertussis disease can now be safely and effectively reduced by vaccinating adults with tetanus-diphtheria-acellular pertussis (Tdap) vaccine. Further research is needed to elucidate the role of vaccination in pregnant women and those over 65 years of age, and also to determine whether further booster doses of Tdap are needed.

  15. T-Cell Responses before and after the Fifth Consecutive Acellular Pertussis Vaccination in 4-Year-Old Dutch Children

    NARCIS (Netherlands)

    Schure, Rose-Minke; Hendrikx, Lotte H.; de Rond, Lia G. H.; Ozturk, Kemal; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2012-01-01

    Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-t

  16. Lack of association between mannose binding lectin and antibody responses after acellular pertussis vaccinations.

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    Kirsi Gröndahl-Yli-Hannuksela

    Full Text Available BACKGROUND: Mannose-binding lectin (MBL is one of the key molecules in innate immunity and its role in human vaccine responses is poorly known. This study aimed to investigate the possible association of MBL polymorphisms with antibody production after primary and booster vaccinations with acellular pertussis vaccines in infants and adolescents. METHODOLOGY/PRINCIPAL FINDINGS: Five hundred and sixty eight subjects were included in this study. In the adolescent cohort 355 subjects received a dose of diphtheria and tetanus toxoids and acellular pertussis (dTpa vaccine ten years previously. Follow-up was performed at 3, 5 and 10 years. Infant cohort consisted of 213 subjects, who had received three primary doses of DTaP vaccine at 3, 5, and 12 months of age according to Finnish immunization program. Blood samples were collected before the vaccinations at 2,5 months of age and after the vaccinations at 13 months and 2 years of age. Concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, and pertactin and antibodies to diphtheria and tetanus toxoids were measured by standardized enzyme-linked immunosorbant assay. Single nucleotide polymorphisms of MBL2 gene exon1 (codons 52, 54, 57 were examined. MBL serum concentration was also measured from the adolescent cohort. No association was found with MBL2 exon 1 polymorphisms and antibody responses against vaccine antigens, after primary and booster dTpa vaccination. CONCLUSIONS: This study indicates that MBL polymorphisms do not affect the production and persistence of antibodies after acellular pertussis vaccination. Our finding also suggests that MBL might not be involved in modulating antibody responses to the vaccines made of purified bacterial proteins.

  17. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Schure, Rose-Minke; Ozturk, Kemal; de Rond, Lia G. H.; de Greeff, S. C.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12 mo

  18. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    Science.gov (United States)

    Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  19. Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.

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    Talbird, Sandra E; Graham, Jonathan; Mauskopf, Josephine; Masseria, Cristina; Krishnarajah, Girishanthy

    2015-01-01

    The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U

  20. Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013.

    Science.gov (United States)

    O'Halloran, Alissa C; Lu, Peng-Jun; Williams, Walter W; Ding, Helen; Meyer, Sarah A

    2016-07-01

    The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy.

  1. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  2. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  3. Antibody responses to individual Bordetella pertussis fimbrial antigen Fim2 or Fim3 following immunization with the five-component acellular pertussis vaccine or to pertussis disease.

    Science.gov (United States)

    Alexander, Frances; Matheson, Mary; Fry, Norman K; Labram, Briony; Gorringe, Andrew R

    2012-11-01

    Bordetella pertussis expresses two serologically distinct fimbriae (Fim2 and Fim3) which are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and antibody responses to these antigens have been shown to be associated with protection. Studies to date have assessed the IgG response to this vaccine using a copurified mixture of Fim2 and Fim3, and the response to the individual antigens has not been characterized. We have purified separate Fim2 and Fim3 from strains that express either Fim2 or Fim3 and have used these antigens in an enzyme-linked immunosorbent assay (ELISA) to quantify IgG responses following immunization with 5-component acellular pertussis vaccine in 15-month-old, 4- to 6-year-old, and 11- to 18-year-old subjects. All individuals showed increases in Fim2 and Fim3 IgG concentrations following immunization, with 3-fold-greater Fim2 than Fim3 IgG concentrations seen in the younger two age groups. Fim2 IgG concentrations were 1.5-fold greater than Fim3 IgG concentrations in the 11- to 18-year-olds. We have also compared Fim2 and Fim3 IgG concentrations in individuals with prolonged cough who were diagnosed as having recent pertussis using a pertussis toxin (Ptx) IgG ELISA with individuals with prolonged cough but without elevated Ptx IgG concentrations. Individuals with evidence of recent pertussis had greater Fim3 IgG concentrations, consistent with the predominant serotype of isolates obtained in the United Kingdom. However, a surprising number of individuals had moderate Fim2 IgG concentrations despite very few isolates of that serotype obtained in the sampling period.

  4. Collaborative study on a Guinea pig serological method for the assay of acellular pertussis vaccines.

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    Winsnes, R; Sesardic, D; Daas, A; Terao, E; Behr-Gross, M-E

    2009-10-01

    An international collaborative study (coded BSP083) was performed under the aegis of the Biological Standardisation Programme supported by the Council of Europe and the European Commission, with the aim of replacing the in vivo challenge assays for potency determination of combined acellular pertussis (aP) vaccines by a refined procedure also allowing reduction of animal use. This study investigates whether the immunogenicity of aP vaccine components could be assayed in a guinea pig (gp) serology model, using the same vaccine immunising doses as for D and T components potency testing, instead of using separate animals as is currently done. The BSP83 project is a follow up of 3 former collaborative studies (coded BSP019, BSP034 and BSP035) on serological methods for the potency testing of tetanus (T) and diphtheria (D) vaccines for human use. The use of gp instead of mice serology has the advantage of providing a larger volume of good quality antiserum for the assay of several vaccine components in the same sample, hence providing the opportunity for animal sparing. The results of Phase I of the study demonstrated that gp serology may be a useful method for the immunogenicity assay of acellular pertussis vaccines. This was confirmed in Phase II of the study, using 7 different combined aP vaccines in an international collaborative study involving 17 laboratories from both public and private sectors. Clear dose-response relationships were observed for different vaccines by ELISA, for antibodies against aP antigens, i.e. pertussis toxin (PT), filamentous haemagglutinin (FHA), fimbrial agglutinogens-2/3 (Fim 2/3) and pertactin (PRN). Intra- and inter-laboratory variations of aP ELISA results were found to be within an acceptable range. For some combined vaccines, however, the range of vaccine dilutions for immunisation confirmed to be optimal for D and T potency testing may not provide optimal dose-response for all aP components. Method adjustments may thus be required

  5. Persistence of T-cell immune response induced by two acellular pertussis vaccines in children five years after primary vaccination.

    Science.gov (United States)

    Palazzo, Raffaella; Carollo, Maria; Bianco, Manuela; Fedele, Giorgio; Schiavoni, Ilaria; Pandolfi, Elisabetta; Villani, Alberto; Tozzi, Alberto E; Mascart, Françoise; Ausiello, Clara M

    2016-01-01

    The resurgence of pertussis suggests the need for greater efforts to understand the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of T memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (Glaxo-SmithKline Biologicals). We evaluated magnitude and duration of T-cell responses to pertussis toxin (PT) by measuring T-cell proliferation, cytokines (IL-2 and IFNγ) production and memory subsets in two groups of children 5 years after primary vaccination. Some of the enrolled children received only primary vaccination, while others had the pre-school boost dose. Positive T-cell responses to PT were detected in 36% of children. Percentage of responsive children, T-cell proliferation and CD4IL-2+ cells were significantly higher in the children primed with Hexavac than in those who received Infanrix vaccine. No major effects of the boost on PT-specific proliferation were observed. Overall, our data documented a persistence of T-cell memory against PT in a minor fraction of children 5 years after primary vaccination. The different responses induced by Hexavac and Infanrix vaccine could rely on differences in PT inactivation process or excipients/adjuvants formulations.

  6. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults

    DEFF Research Database (Denmark)

    Thierry-Carstensen, Birgit; Jordan, Karina; Uhlving, Hilde Hylland

    2012-01-01

    Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults.......Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults....

  7. Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine.

    Science.gov (United States)

    Weston, Wayde; Messier, Marc; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara

    2011-11-01

    The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix(®), GlaxoSmithKline Biologicals; Tdap-B: or Adacel(®), Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).

  8. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

    Science.gov (United States)

    Broder, Karen R; Cortese, Margaret M; Iskander, John K; Kretsinger, Katrina; Slade, Barbara A; Brown, Kristin H; Mijalski, Christina M; Tiwari, Tejpratap; Weston, Emily J; Cohn, Amanda C; Srivastava, Pamela U; Moran, John S; Schwartz, Benjamin; Murphy, Trudy V

    2006-03-24

    During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate

  9. Vaccination with tetanus, diphtheria, and acellular pertussis vaccine of pregnant women enrolled in Medicaid--Michigan, 2011-2013.

    Science.gov (United States)

    Housey, Michelle; Zhang, Fan; Miller, Corinne; Lyon-Callo, Sarah; McFadden, Jevon; Garcia, Erika; Potter, Rachel

    2014-09-26

    In October 2011, the Advisory Committee on Immunization Practices (ACIP) first recommended the routine administration of a tetanus, diphtheria, and acellular pertussis vaccine (Tdap) during pregnancy as a strategy to protect infants from pertussis (also known as whooping cough). This recommendation applied to women previously unvaccinated with Tdap and specified the optimal vaccination time as late second or third trimester (after 20 weeks' gestation). By vaccinating pregnant women, infants, who are at highest risk for mortality and morbidity from pertussis, gain passive immunity from maternal antibodies transferred to them in utero. Since this recommendation was made, little has been published on the percentage of women receiving Tdap during pregnancy. In Michigan, Medicaid pays for costs of pregnancy for approximately 40% of births. Infants enrolled in Medicaid are a particularly vulnerable population; in Michigan, their all-cause mortality is higher than that of privately insured infants. To assess vaccination coverage among pregnant women enrolled in a publicly funded insurance program in Michigan, Medicaid administrative claims data and statewide immunization information system data for mothers of infants born during November 2011-February 2013 were analyzed. This report describes the results of that analysis, which indicated that only 14.3% of these women received Tdap during pregnancy, with rates highest (17.6%) among non-Hispanic, non-Arab whites and lowest (6.8%) among Arab women. Vaccination was related to maternal age and gestational age at birth, but not to adequacy of prenatal care. In 2013, recognizing the importance of Tdap for every pregnancy, ACIP revised its guidelines to include a Tdap dose during every pregnancy. Ensuring that all infants receive the protection against pertussis afforded by maternal vaccination will require enhanced efforts to vaccinate pregnant women.

  10. Impact of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccinations on Reported Pertussis Cases Among Those 11 to 18 Years of Age in an Era of Waning Pertussis Immunity: A Follow-up Analysis.

    Science.gov (United States)

    Skoff, Tami H; Martin, Stacey W

    2016-05-01

    There is accumulating literature on waning acellular pertussis vaccine-induced immunity, confirming the results of studies assessing the duration of protection of pertussis vaccines. To evaluate the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine's effect over time among those 11 to 18 years old, while accounting for the transition from whole-cell to acellular pertussis vaccines for the childhood primary series. Extended, retrospective analysis of reported pertussis cases between January 1, 1990, and December 31, 2014, in the United States. The analysis included all nationally reported pertussis cases. US Tdap vaccination program and the transition from whole-cell to acellular pertussis vaccines. Rate ratios of reported pertussis incidence (defined as incidence among 11- to 18-year-old individuals divided by the combined incidence in all other age groups) modeled with segmented regression analysis and age-specific trends in reported pertussis incidence over time. Between 1990 and 2014, 356 557 pertussis cases were reported in the United States. Of those, 191 914 (53.8%) were female and 240 665 (67.5%) were white. Overall incidence increased from 1.7 in 100 000 to 4.0 in 100 000 between 1990 and 2003, while latter years were dominated by epidemic peaks. Incidence was highest among infants younger than 1 year throughout the analysis period. Pertussis rates were comparable among all other age groups until the late 2000s, when an increased burden of pertussis emerged among children 1 to 10 years old, resulting in the second highest age-specific incidence. By 2014, 11- to 18-year-old individuals once again had the second highest incidence. While slope coefficients from segmented regression analysis showed a positive impact of Tdap immediately following introduction (slope, -0.4959; P < .001), a reversal in trends was observed in 2010 when rates of disease among 11- to 18-year-old individuals increased at a faster rate than

  11. Vacina acelular contra pertússis para adolescentes Acellular pertussis vaccine for adolescents

    Directory of Open Access Journals (Sweden)

    Aroldo P. de Carvalho

    2006-07-01

    vacina é em torno de 6 a 12 anos. As avaliações sobre o impacto econômico do uso rotineiro da vacina em adolescentes evidenciam uma relação custo-benefício positiva. Os resultados do impacto epidemiológico dependem da qualidade do diagnóstico para que os dados reflitam a realidade da doença. CONCLUSÕES: Embora existam algumas questões a serem esclarecidas, a literatura disponível sinaliza a possibilidade para a solução do .ressurgimento. da coqueluche com o uso da vacina dTpa. Talvez a estratégia da utilização de uma dose de reforço na adolescência, substituindo a vacina dupla contra difteria e tétano, seja uma medida a ser prontamente indicada.BACKGROUND: The use of whole-cell pertussis vaccine has led to a significant decline in incidence of the disease among children. This change in the epidemiological profile led to an increased number of cases among teenagers and adults, as a result of loss of immunity to the disease or vaccine after approximately 10 years. An increased number of cases was also observed among non-immunized or partially immunized infants. Licensure of the DTP vaccine against diphtheria, tetanus, and acellular pertussis formulated specifically for patients over 10 years of age (Tdap suggests the possibility of controlling pertussis in the most affected age groups over the past few years. SOURCES OF DATA: Data were collected from MEDLINE. The research was limited to the period between January 1995 and January 2006. SUMMARY OF THE FINDINGS: In some countries there are two Tdap vaccines licensed for patients over 10 years of age. One of them contains five immunogenic components of Bordetella pertussis (pertussis toxin, filamentous hemagglutinin, fimbriae 2 and 3, and pertactin, and the other contains three components (pertactin, filamentous hemagglutinin, and inactivated pertussis toxin, the latter being the only one licensed in Brazil up to now. Although the composition of the two vaccines differs, studies show that they have

  12. Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix(®)): results of two randomized trials.

    Science.gov (United States)

    Weston, Wayde M; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara

    2012-02-21

    Pertussis can cause significant morbidity in elderly patients, who can also transmit this disease to infants and young children. There is little data available on the use of acellular pertussis vaccines in recipients ≥65 years of age. Two studies examined the safety and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine (Boostrix(®)) in healthy ≥65 year olds. In Study A subjects received single doses of Tdap and seasonal influenza vaccine either co-administered or given one month apart. In Study B subjects received either Tdap or tetanus-diphtheria (Td) vaccine. Antibodies were measured before and one month after vaccination. Reactogenicity and safety were actively assessed using diary cards. A total of 1104 subjects 65 years of age and older received a Tdap vaccination in the two studies. In study A, no differences in immune responses to Tdap or influenza vaccine were observed between co-administered or sequentially administered vaccines. In study B, Tdap was non-inferior to Td with respect to diphtheria and tetanus seroprotection, and anti-pertussis GMCs were non-inferior to those observed in infants following a 3-dose diphtheria, tetanus and acellular pertussis (DTaP) primary vaccination series, in whom efficacy against pertussis was demonstrated. Reports of adverse events were similar between Tdap and Td groups. Tdap was found to be immunogenic in subjects ≥65 years, with a safety profile comparable to US-licensed Td vaccine. Tdap and influenza vaccine may be co-administered without compromise of either the reactogenicity or immunogenicity profiles of the two vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden.

    Science.gov (United States)

    Storsaeter, J; Olin, P; Renemar, B; Lagergård, T; Norberg, R; Romanus, V; Tiru, M

    1988-09-01

    A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.

  14. Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What the Canadian public knows and wants to know.

    Science.gov (United States)

    Halperin, B A; MacDougall, D; MacKinnon-Cameron, D; Li, L; McNeil, S A; Langley, J M; Halperin, S A

    2015-11-27

    Tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in Canada but uptake is low. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults to identify potential barriers and facilitators to Tdap uptake. A survey was undertaken on a geographically representative sample of Canadian adults (n=4023) and 8 focus groups (62 participants) were conducted nationwide. The survey revealed that knowledge about pertussis and Tdap was low (38.3% correct answers). Only 36.0% of respondents reported being aware that all adults were recommended to receive Tdap and only 10.7% reported being immunized; 36.7% did not know whether they had received Tdap. Respondents who were aware of the immunization recommendations were twice as likely to be immunized (16.6% vs. 8.3%; pvaccination with Tdap are not reaching the general public in Canada and an alternative strategy will be required to improve Tdap vaccine uptake.

  15. Effect of schedule on reactogenicity and antibody persistence of acellular and whole-cell pertussis vaccines: value of laboratory tests as predictors of clinical performance.

    Science.gov (United States)

    Miller, E; Ashworth, L A; Redhead, K; Thornton, C; Waight, P A; Coleman, T

    1997-01-01

    The performance of four acellular pertussis vaccines containing between two and five pertussis antigens combined with diphtheria and tetanus toxoids was compared with that of British whole-cell diphtheria/tetanus/pertussis (DTP) vaccine both in laboratory assays for potency, toxicity and immunogenicity, and for reactogenicity and immunogenicity in infants. Clinical responses were evaluated in double blind randomized Phase II trials using 3/5/9 month and 2/3/4 month schedules. The acellular DTPs had much lower toxicity than whole-cell DTP in laboratory tests and were significantly less pyrogenic than whole-cell DTP under both schedules. Local reactions were not consistently lower in acellular than whole-cell vaccinees and varied with the source of the diphtheria and tetanus antigens used. Differences in endotoxin level and content of active pertussis toxin (PT) between acellular DTP vaccines were not clinically significant. The reactogenicity advantage of the acellular vaccines was substantially reduced under the 2/3/4 month schedule due to the reduced reactogenicity of the whole-cell DTP vaccine when given at a younger age. There was no relationship between antigen content measured in micrograms per dose and ELISA antibody responses to filamentous haemagglutinin (FHA) and PT in infants, nor was murine immunogenicity predictive of immunogenicity in humans. Antibody response to PT was attenuated in the whole-cell group under the 2/3/4 month schedule but was unaffected in the group receiving acellular vaccines with individually purified components; antibody response to pertactin (69 kDa antigen) was similar in recipients of the whole-cell and component acellular vaccines under the 2/3/4 month schedule. PT antibody persistence until 4-5 years of age was significantly better in recipients of the component acellular than either the whole-cell vaccine or the co-purified acellular vaccine under the 3/5/9 month schedule. However, diphtheria antitoxin levels were reduced in

  16. Whooping cough vaccines: production of virulent B. pertussis

    NARCIS (Netherlands)

    Thalen, M.

    2008-01-01

    key words: acellular, fed batch, metabolism, pertussis toxin The production of acellular pertussis in comparison with whole cell pertussis vaccines demands 5 to 25 times the amount of B. pertussis' virulence factors such as pertussis toxin (PT), to produce the same number of vaccine doses. An i

  17. Antibody responses to Bordetella pertussis Fim2 or Fim3 following immunization with a whole-cell, two-component, or five-component acellular pertussis vaccine and following pertussis disease in children in Sweden in 1997 and 2007.

    Science.gov (United States)

    Hallander, Hans; Advani, Abdolreza; Alexander, Frances; Gustafsson, Lennart; Ljungman, Margaretha; Pratt, Catherine; Hall, Ian; Gorringe, Andrew R

    2014-02-01

    Bordetella pertussis fimbriae (Fim2 and Fim3) are components of a five-component acellular pertussis vaccine (diphtheria-tetanus-acellular pertussis vaccine [DTaP5]), and antibody responses to fimbriae have been associated with protection. We analyzed the IgG responses to individual Fim2 and Fim3 in sera remaining from a Swedish placebo-controlled efficacy trial that compared a whole-cell vaccine (diphtheria-tetanus-whole-cell pertussis vaccine [DTwP]), a two-component acellular pertussis vaccine (DTaP2), and DTaP5. One month following three doses of the Fim-containing vaccines (DTwP or DTaP5), anti-Fim2 geometric mean IgG concentrations were higher than those for anti-Fim3, with a greater anti-Fim2/anti-Fim3 IgG ratio elicited by DTaP5. We also determined the responses in vaccinated children following an episode of pertussis. Those who received DTaP5 showed a large rise in anti-Fim2 IgG, reflecting the predominant Fim2 serotype at the time. In contrast, those who received DTwP showed an equal rise in anti-Fim2 and anti-Fim3 IgG concentrations, indicating that DTwP may provide a more efficient priming effect for a Fim3 response following contact with B. pertussis. Anti-Fim2 and anti-Fim3 IgG concentrations were also determined in samples from two seroprevalence studies conducted in Sweden in 1997, when no pertussis vaccine was used and Fim2 isolates predominated, and in 2007, when either DTaP2 or DTaP3 without fimbriae was used and Fim3 isolates predominated. Very similar distributions of anti-Fim2 and anti-Fim3 IgG concentrations were obtained in 1997 and 2007, except that anti-Fim3 concentrations in 1997 were lower. This observation, together with the numbers of individuals with both anti-Fim2 and anti-Fim3 IgG concentrations, strongly suggests that B. pertussis expresses both Fim2 and Fim3 during infection.

  18. Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults

    Science.gov (United States)

    Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

    2017-01-01

    ABSTRACT Background: An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). Methods: A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18–35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. Results: A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. Conclusion: In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed

  19. Improving pertussis vaccines by lipopolysaccharide engineering

    NARCIS (Netherlands)

    Geurtsen, J.J.G.

    2007-01-01

    Pertussis or whooping cough is a highly contagious respiratory tract disease that is caused by the Gram-negative bacterium Bordetella pertussis. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and 1950s, and later of acellular pertussis (aP) vaccines in the 1980s and 1990s, led to a

  20. Safety and immunogenicity of tetanus-diphtheria-acellular pertussis vaccine administered to children 10 or 11 years of age.

    Science.gov (United States)

    Marshall, Gary S; Pool, Vitali; Greenberg, David P; Johnson, David R; Sheng, Xiaohua; Decker, Michael D

    2014-11-01

    Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  1. Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What Canadian health care providers know and need to know.

    Science.gov (United States)

    MacDougall, D; Halperin, B A; MacKinnon-Cameron, D; Li, L; McNeil, S A; Langley, J M; Halperin, S A

    2015-01-01

    The tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (N =1,167). In addition, 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was awareness of and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients are at significant risk of getting pertussis, and to feel that they have sufficient information (p vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization, and suggestions were provided to better translate recommendations to front-line practitioners.

  2. Safety of a tetanus-diphtheria-acellular pertussis vaccine when used off-label in an elderly population.

    Science.gov (United States)

    Tseng, Hung Fu; Sy, Lina S; Qian, Lei; Marcy, S Michael; Jackson, Lisa A; Glanz, Jason; Nordin, Jim; Baxter, Roger; Naleway, Allison; Donahue, James; Weintraub, Eric; Jacobsen, Steven J

    2013-02-01

    Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

  3. A quantitative analysis for the ADP-ribosylation activity of pertussis toxin: an enzymatic-HPLC coupled assay applicable to formulated whole cell and acellular pertussis vaccine products.

    Science.gov (United States)

    Cyr, T; Menzies, A J; Calver, J; Whitehouse, L W

    2001-06-01

    The majority of the biological effects of pertussis toxin (PT) are the result of a toxin-catalyzed transfer of an adenosine diphosphate-ribose (ADP-ribose) moiety from NAD(+)to the alpha-subunits of a subset of signal-transducing guanine-nucleotide-binding proteins (G-proteins). This generally leads to an uncoupling of the modified G-protein from the corresponding receptor and the loss of effector regulation. This assay is based on the PT S1 subunit enzymatic transfer of ADP-ribose from NAD to the cysteine moiety of a fluorescent tagged synthetic peptide homologous to the 20 amino acid residue carboxyl-terminal sequence of the alpha-subunit of the G(i3)protein. The tagged peptide and the ADP-ribosylated product were characterized by HPLC/MS and MS/MS for structure confirmation. Quantitation of this characterized ADP-ribosylated fluorescently tagged peptide was by HPLC fluorescence using Standard Addition methodology. The assay was linear over a five hr incubation period at 20 degrees C at PT concentrations between 0.0625 and 4.0 microg/ml and the sensitivity of the assay could be increased several fold by increasing the incubation time to 24 h. Purified S1 subunit of PT exhibited 68.1+/-10.1% of the activity of the intact toxin on a molar basis, whereas the pertussis toxin B oligomer, the genetically engineered toxoid, (PT-9K/129G), and several of the other components of the Bordetella pertussis organism possessed little (<0.6%) or no detectable ribosylation activity. Commonly used pertussis vaccine reference materials, US PV Lot #11, BRP PV 66/303, and BRP PV 88/522, were assayed by this method against Bordetella pertussis Toxin Standard 90/518 and demonstrated to contain, respectively, 0.323+/-0.007, 0.682+/-0.045, and 0.757+/-0.006 microg PT/ml (Mean+/-SEM) or in terms of microg/vial: 3.63, 4.09 and 4.54, respectively. A survey of several multivalent pertussis vaccine products formulated with both whole cell as well as acellular components indicated that

  4. Reporter cell lines for detection of pertussis toxin in acellular pertussis vaccines as a functional animal-free alternative to the in vivo histamine sensitization test.

    Science.gov (United States)

    Hoonakker, Marieke E; Verhagen, Lisa M; van der Maas, Larissa; Sloots, Arjen; Hendriksen, Coenraad F M

    2017-02-22

    Detoxified pertussis toxin (pertussis toxoid) is a major antigen in acellular pertussis vaccines. Testing these vaccines on the presence of residual pertussis toxin (PTx) and reversion to toxicity is performed by the regulatory required in vivo Histamine Sensitization test (HIST). Lack of mechanistic understanding of the HIST, technical handicaps and animal welfare concerns, have promoted the development of alternative methods. As the majority of the cellular effects of PTx depend on its ability to activate intracellular pathways involving cAMP, the in vitro cAMP-PTx assay was developed. Although this assay could be used to detect PTx activity, it lacked sensitivity and robustness for use in a quality control setting. In the present study, novel reporter cell lines (CHO-CRE and A10-CRE) were generated that stably express a reporter construct responsive to changes in intracellular cAMP levels. These reporter cell lines were able to detect PTx in a concentration-dependent manner when combined with fixed amounts of forskolin. The CHO-CRE cell line enabled detection of PTx in the context of a multivalent vaccine containing aP, with a sensitivity equal to the HIST. However, the sensitivity of the A10-CRE cells was insufficient for this purpose. The experiments also suggest that the CHO-CRE reporter cell line might be suitable for assessment of cellular effects of PTd reverted to PTx. The CHO-CRE reporter cell line provides a platform that meets the criteria for specificity and sensitivity and is a promising in vitro model with potential to replace the HIST. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Relative contribution of Th1 and Th17 cells in adaptive immunity to Bordetella pertussis: towards the rational design of an improved acellular pertussis vaccine.

    Directory of Open Access Journals (Sweden)

    Pádraig J Ross

    Full Text Available Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa. One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells.

  6. Predictors of tetanus-diphtheria- acellular pertussis vaccination among adults receiving tetanus vaccine in the United States: data from the 2008 national health interview survey.

    Science.gov (United States)

    Johns, Tracy L; Roetzheim, Richard; Chen, Ren

    2013-04-01

    BACKGROUND . The incidence of pertussis in the United States has been increasing. Adult vaccination is important to reduce disease burden and prevent transmission to infants at high risk of complications. The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been available in the United States since 2005 and is indicated as a one-time replacement for the routine tetanus-diphtheria (Td) booster. However, among adults receiving tetanus vaccination, only about half receive Tdap. PURPOSE . To identify predictors of adult Tdap vaccination among individuals who receive tetanus vaccine. METHODS . National Health Interview Survey data from 2008 were analyzed in 2011. Respondents were 18 to 64 years old, received tetanus vaccination during 2005-2008, and were aware if it contained pertussis. Predictors of Tdap vaccination were identified with multivariate logistic regression using procedures for complex survey methods. RESULTS . Overall, 51.1% of respondents received Tdap. Vaccination was less likely for those 50 to 64 years old compared with those 18 to 24 years old (odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.38-0.96). Some college education was associated with higher odds of vaccination compared with lower education levels (OR = 1.55, 95% CI = 1.16-2.07). Having 2 to 3 office visits (OR = 2.01, 95% CI = 1.32-3.06) or 4 to 9 office visits (OR = 1.60, 95% CI = 1.06-2.42) in the previous year increased the odds of vaccination compared with no visits. Individuals with functional limitation due to illness had lower odds compared with no limitation (OR = 0.70, 95% CI = 0.54-0.91). CONCLUSIONS . In 2008, 51.1% of adult Td vaccinations included pertussis, suggesting continued efforts to remove barriers are needed. Interventions should target older, functionally impaired, and educationally disadvantaged populations.

  7. Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

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    Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

    2015-07-31

    Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadirvaccination would be feasible in the majority of the seronegative patients. In patients with a CD4 count>200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases.

  8. Reduced-antigen, combined diphtheria, tetanus and acellular pertussis vaccine, adsorbed (Boostrix®): a review of its properties and use as a single-dose booster immunization.

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    McCormack, Paul L

    2012-09-10

    Reduced-antigen, combined diphtheria, tetanus and three-component acellular pertussis vaccine (Tdap; Boostrix®) is indicated for booster vaccination against diphtheria, tetanus and pertussis in individuals from age four years onwards in Europe and from age 10 years onwards in the US. Compared with infant formulations used for primary vaccination, Tdap contains reduced quantities (10-50%) of all toxoids and antigens, which are adsorbed to either ≤0.39 mg/dose (US licensed formulation) or 0.5 mg/dose (rest-of-world formulation) of aluminium adjuvant. The reduced antigen content is designed to avoid the increasing reactogenicity historically seen with the fourth and fifth doses of infant vaccine. This article reviews the immunogenicity, protective efficacy and reactogenicity of Tdap booster administered to children, adolescents and adults, including those aged ≥65 years. In clinical trials, a single booster dose of Tdap induced seroprotective levels of antibodies to diphtheria and tetanus toxoids in virtually all children and adolescents, and in a high proportion of adults and elderly individuals at approximately 1 month post-vaccination irrespective of their vaccination history. In all age groups, seropositivity rates for antibodies against pertussis antigens were ≥90% (including in unvaccinated adolescents), and booster response rates were high. Tdap was safely co-administered with other common vaccines without significantly affecting the immune responses. The immunogenicity and reactogenicity profiles of booster doses of Tdap were generally similar to those of infant diphtheria-tetanus-whole-cell pertussis vaccine and infant diphtheria-tetanus-acellular pertussis vaccine in children aged 4-6 years, and infant diphtheria-tetanus vaccine in older children. In adolescents and adults, the immunogenicity and reactogenicity of Tdap were generally similar to those of reduced-antigen diphtheria-tetanus vaccine, reduced-antigen diphtheria

  9. Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

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    Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

    2013-12-01

    The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

  10. Quality of the Haemophilus influenzae type b (Hib) antibody response induced by diphtheria-tetanus-acellular pertussis/Hib combination vaccines.

    Science.gov (United States)

    Denoël, Philippe A; Goldblatt, David; de Vleeschauwer, Isabel; Jacquet, Jeanne-Marie; Pichichero, Michael E; Poolman, Jan T

    2007-10-01

    It has been repeatedly observed that mixing Haemophilus influenzae type b (Hib) conjugate vaccines with acellular pertussis-containing vaccines (diphtheria-tetanus-acellular pertussis [DTPa]) resulted in a reduced magnitude of the anti-polyriboseribitolphosphate antibody response compared to that obtained when Hib vaccines were administered separately and not mixed. Nevertheless, the quality and functionality of the immune responses have been shown to be the same. With the purpose of investigating the quality of the anti-Hib immune responses that are elicited under different vaccination regimens, we report here four primary and booster-based pediatric clinical trials in which Hib vaccine was either mixed with DTPa or diphtheria-tetanus-whole-cell pertussis (DTPw)-based vaccines or was coadministered. Our results show that avidity maturation of the antibodies was lower when primary vaccination involved DTPa mixed with Hib compared to when DTPa and Hib were coadministered. No such difference was observed between mixed and separately administered Hib when associated with DTPa-hepatitis B virus-inactivated poliovirus or DTPw-based vaccines. All different combinations and regimens elicited the same opsonophagocytic and bactericidal activity as well as the same ability to protect in a passive infant rat protection assay. The functional activity of mixed DTPa-based and Hib vaccines was similar to that of mixed DTPw-based/Hib combinations. In conclusion, in vitro and in vivo data as well as postmarketing vaccine effectiveness data attest to the ability of DTPa-based/Hib combination vaccines to effectively prevent Hib-induced disease in children.

  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

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    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.

  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

    Science.gov (United States)

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

    2004-09-01

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

  13. Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

    Science.gov (United States)

    John, T; Voysey, M; Yu, L M; McCarthy, N; Baudin, M; Richard, P; Fiquet, A; Kitchin, N; Pollard, A J

    2015-08-26

    This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.

  14. Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines.

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    Hegerle, Nicolas; Guiso, Nicole

    2014-09-01

    Bordetella pertussis causes whooping cough in humans, a highly transmissible respiratory disease life threatening for unvaccinated infants. Vaccination strategies were thus introduced worldwide with great success in developed countries reaching high vaccine coverage with efficacious vaccines. In the late 20th/early 21st century, acellular pertussis vaccines replaced whole cell pertussis vaccines but B. pertussis still circulates and evolves in humans, its only known reservoir. The latest transformation of this pathogen, and of its close relative Bordetella parapertussis, is the loss of pertactin production, a virulence factor included in different acellular pertussis vaccines. The real impact of this evolution on acellular pertussis vaccines efficacy and effectiveness should be assessed through standardized surveillance and isolation of B. pertussis and B. parapertussis worldwide.

  15. Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine and Guidance for Use as a Booster Dose.

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    Liang, Jennifer; Wallace, Greg; Mootrey, Gina

    2015-09-04

    On March 24, 2015, the Food and Drug Administration licensed an additional combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated poliovirus (IPV) vaccine (DTaP-IPV) (Quadracel, Sanofi Pasteur Inc.). Quadracel is the second DTaP-IPV vaccine to be licensed for use among children aged 4 through 6 years in the United States (1). Quadracel is approved for administration as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series in children aged 4 through 6 years who have received 4 doses of DTaP-IPV-Hib (Pentacel, Sanofi Pasteur) and/or DTaP (Daptacel, Sanofi Pasteur) vaccine (2,3). This report summarizes the indications for Quadracel vaccine and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.

  16. Pertussis specific T-cell immunity in Dutch children: Differences after whole-cell versus acellular vaccination

    NARCIS (Netherlands)

    Schure, R.M.

    2014-01-01

    Bordetella pertussis is the causative bacteria of whooping cough. Whooping cough is a highly contagious infection, which is characterized by coughing with whooping and post-tussive vomiting. In particular, infants under 6 months of age who have not been fully vaccinated, are at risk for serious comp

  17. The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development.

    Science.gov (United States)

    Preston, Andrew

    2016-05-01

    Whooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies.

  18. Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine.

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    Tomovici, A; Barreto, L; Zickler, P; Meekison, W; Noya, F; Voloshen, T; Lavigne, P

    2012-03-30

    Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Report on the international workshop on alternatives to the murine histamine sensitization test (HIST) for acellular pertussis vaccines: state of the science and the path forward.

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    Isbrucker, Richard; Arciniega, Juan; McFarland, Richard; Chapsal, Jean-Michel; Xing, Dorothy; Bache, Christina; Nelson, Sue; Costanzo, Angele; Hoonakker, Marieke; Castiaux, Amélie; Halder, Marlies; Casey, Warren; Johnson, Nelson; Jones, Brett; Doelling, Vivian; Sprankle, Cathy; Rinckel, Lori; Stokes, William

    2014-03-01

    Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.

  20. Pertussis vaccines: position paper of Indian Academy of Pediatrics (IAP).

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    Vashishtha, Vipin M; Bansal, C P; Gupta, Sailesh G

    2013-11-08

    Pertussis continues to be a major public health problem in both developing and developed countries. Data on exact burden and incidence of pertussis in the developing countries including India is sparse. However, the disease is widespread, even if not adequately measurable. Pertussis incidence has been increasing steadily in the last decade especially in industrialized countries. Outbreaks are reported from many developed countries in recent years despite widespread use of acellular pertussis vaccines with high coverage. The current status of coverage with pertussis vaccines is still sub-optimal in many states of the country. There is scarcity of data on vaccine efficacies of both whole-cell and acellular pertussis vaccines from India and other developing countries. Most of the recommendations on pertussis vaccination are based on the experience gained from the use of them in industrialized countries. Taking in to the consideration the recent evidence of faster waning of acellular pertussis vaccines in comparison to whole-cell vaccines and superior priming with whole-cell than acellular pertussis vaccines, Indian Academy of Pediatrics has now revised its recommendations pertaining to pertussis immunization in office practice. The Academy has now proposed whole-cell pertussis vaccines for the primary series of infant vaccination. Guidelines are also now issued on the preference of a particular acellular product. The Academy has also recommended use of Tdap during each pregnancy to provide protection to the very young infants. It urges the Government of India to initiate studies on the quality of available pertussis vaccines in India and to set indigenous national guidelines for the manufacturers to produce and market different pertussis vaccines in the country.

  1. Decennial administration in young adults of a reduced-antigen content diphtheria, tetanus, acellular pertussis vaccine containing two different concentrations of aluminium.

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    Vandermeulen, Corinne; Theeten, Heidi; Rathi, Niraj; Kuriyakose, Sherine; Han, Htay Htay; Sokal, Etienne; Hoppenbrouwers, Karel; Van Damme, Pierre

    2015-06-12

    Regular booster vaccination might be necessary throughout life to protect against pertussis infection. Nevertheless the duration of protection after booster vaccination remains unclear. In this study, antibody persistence up to 10 years after previous vaccination of adolescents (N=478) with combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa, Boostrix™, GlaxoSmithKline Belgium) containing 0.5mg, 0.3mg or 0.133mg of aluminium was assessed. The immunogenicity, reactogenicity and safety of a decennial booster dTpa dose were also investigated. Young adults vaccinated as adolescents in the initial booster study were invited to participate in an assessment of antibody persistence at years 8.5 and 10, and to receive a dTpa booster dose at year 10 with immunogenicity assessment one month later. Those who originally received the 0.5mg or 0.3mg formulations received the same vaccine at year 10. Those in the 0.133mg group received the 0.5mg formulation. Reactogenicity and safety endpoints were captured until 30 days after booster vaccination. Prior to the decennial booster at year 8.5 and year 10, all participants had seroprotective antibodies for diphtheria (ELISA or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti-pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All participants were seropositive for antibodies for filamentous haemagglutinin and pertactin at both time points. The decennial booster dose induced robust increases in antibody GMCs to all antigens. The post-booster anti-PT geometric mean concentration was 82.5EL.U/ml (95%CI 67.0-101.6) and 124.0 (103.5-148.5) in the 0.3mg and 0.5mg groups, respectively. The reactogenicity and safety profile of the decennial booster dose was consistent with the known safety profile of dTpa. No serious adverse events were reported. Decennial booster vaccination with either of the two licensed formulations of dTpa was highly immunogenic and well

  2. Acellular pertussis booster in adolescents induces Th1 and memory CD8+ T cell immune response.

    Directory of Open Access Journals (Sweden)

    Nikolaus Rieber

    Full Text Available In a number of countries, whole cell pertussis vaccines (wcP were replaced by acellular vaccines (aP due to an improved reactogenicity profile. Pertussis immunization leads to specific antibody production with the help of CD4(+ T cells. In earlier studies in infants and young children, wcP vaccines selectively induced a Th1 dominated immune response, whereas aP vaccines led to a Th2 biased response. To obtain data on Th1 or Th2 dominance of the immune response in adolescents receiving an aP booster immunization after a wcP or aP primary immunization, we analyzed the concentration of Th1 (IL-2, TNF-α, INF-γ and Th2 (IL-4, IL-5, IL-10 cytokines in supernatants of lymphocyte cultures specifically stimulated with pertussis antigens. We also investigated the presence of cytotoxic T cell responses against the facultative intracellular bacterium Bordetella pertussis by quantifying pertussis-specific CD8(+ T cell activation following the aP booster immunization. Here we show that the adolescent aP booster vaccination predominantly leads to a Th1 immune response based on IFNgamma secretion upon stimulation with pertussis antigen, irrespective of a prior whole cell or acellular primary vaccination. The vaccination also induces an increase in peripheral CD8(+CD69(+ activated pertussis-specific memory T cells four weeks after vaccination. The Th1 bias of this immune response could play a role for the decreased local reactogenicity of this adolescent aP booster immunization when compared to the preceding childhood acellular pertussis booster. Pertussis-specific CD8(+ memory T cells may contribute to protection against clinical pertussis.

  3. Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine.

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    Baxter, Roger; Hansen, John; Timbol, Julius; Pool, Vitali; Greenberg, David P; Johnson, David R; Decker, Michael D

    2016-11-01

    An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults.

  4. 无细胞百日咳疫苗特异性毒性检测方法现状及展望%Current status and prospect of specific methods for determination of toxicity of an acellular pertussis vaccine

    Institute of Scientific and Technical Information of China (English)

    夏德菊; 郭林达

    2014-01-01

    百日咳毒素是百日咳杆菌重要的保护性抗原,经化学方法脱毒成为百日咳类毒素后制成的无细胞百日咳疫苗(acellular pertussis vaccine,APV)具有残余毒性和毒性逆转的可能性,所以建立特异性毒性检测方法对于保证APV的安全性是十分必要的.此文就国内外APV特异性毒性检测方法的现状做一综述,并结合近几年国外研究的毒性检测新方法进行展望.%Pertussis toxin (PT) is a major protective antigen of Bordetella pertussis and its detoxified form obtained by a chemical process is an important component of an acellular pertussis vaccine (APV).In view of the possibility of residual toxicity or toxicity reversion of PT in the vaccines,specific tests are required to assure safety of the vaccines.This paper reviews specific methods for determination of toxicity of APV and prospect of new tests in the world.

  5. The Role of the Aceullular Pertussis Vaccine and the Comeback of 'Pertussis Pete'?

    Directory of Open Access Journals (Sweden)

    John M Conly

    2001-01-01

    Full Text Available Pertussis or whooping cough is an acute infectious disease of the respiratory tract caused principally by Bordetella pertussis and less commonly by Bordetella parapertussis (1. Until two decades ago, pertussis in adults was a medical curiosity (2-4, but with the purification of specific Bordetella species antigens, the development of reliable enzyme immunoassays allowing accurate serological diagnosis and better understanding of the duration of immunity from vaccination, it has been clearly demonstrated that B pertussis is a common cause of prolonged cough in adults. Indeed, its incidence has been increasing gradually over the past decade in both adults and adolescents. Given the recognition of the importance of pertussis as a cause of prolonged cough in adults and the advent of the new acellular pertussis vaccines, it is timely to review current concepts of the pathogenesis of pertussis, its epidemiology in adults and the utility of the anticipated impact of the acellular vaccine.

  6. Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

    Science.gov (United States)

    Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

    2010-04-01

    This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

  7. 无细胞百日咳疫苗纯化新工艺的建立%Development of a novel procedure for purification of acellular pertussis vaccine

    Institute of Scientific and Technical Information of China (English)

    吴腾捷; 张斌; 张青; 郑丽华; 瞿爱东

    2013-01-01

    目的 建立适合大规模生产的无细胞百日咳疫苗(Acellular pertussis vaccine,APV)纯化新工艺,使疫苗主要成分的比例稳定可控.方法 复苏百日咳菌种并传代培养,在大罐发酵培养收获前,调整菌液的pH值至弱酸性,再通过离心获得上清液,经超滤浓缩和脱盐处理,使用阳离子交换层析进行目的组分的分离纯化,纯化产物经SDS-PAGE分离并经Western blot鉴定,确定最佳纯化条件.用建立的层析纯化新工艺连续纯化3批APV,检测各项指标,验证该工艺的重复性.结果 收获前菌液pH值调至5.8~6.0,可使疫苗主要保护抗原在上清液中的含量明显提高;采用强阳离子交换层析的方法,从目的蛋白的捕获到多组分的分离提纯可一步完成,各目的蛋白组分的纯度均可达85%以上,回收率可达90%以上;建立的纯化新工艺具有良好的重复性.结论 初步建立了可线性放大、适合APV大规模生产的层析纯化新工艺,为疫苗质量标准的提高奠定了基础.%Objective To develop a novel procedure suitable for large-scale production of acellular pertussis vaccine (APV). Methods Bordetella pertussis strain was resuscitated and subcultured. The pH value of fermentation liquid of B. pertussis was adjusted to weak acidity before harvest. Supernatant was collected after centrifugation, concentrated by ultrafiltration and subjected to desalting, from which the target components were purified by cation exchange chromatog-raphy. The purified protein was identified by SDS-PAGE and Western blot, based on which the condition for purification was optimized. Three successive batches of APV were purified by the developed procedure and tested for various quality indexes to verify the reproducibility of the procedure. Results Adjusting the pH value of fermentation liquid to 5. 8~6. 0 before harvest increased the content of major protective antigen in supernatant significantly. By strong cation exchange

  8. What to do about pertussis vaccines? Linking what we know about pertussis vaccine effectiveness, immunology and disease transmission to create a better vaccine.

    Science.gov (United States)

    Bolotin, Shelly; Harvill, Eric T; Crowcroft, Natasha S

    2015-11-01

    Pertussis (whooping cough) is a respiratory disease caused by the bacterium Bordetella pertussis. Despite the implementation of immunization programs and high vaccine coverage in most jurisdictions, pertussis is still one of the most common vaccine-preventable diseases, suggesting that the current vaccines and immunization schedules have not been sufficiently effective. Several factors are thought to contribute to this. The acellular pertussis vaccine that has been used in many jurisdictions since the 1990s is less effective than the previously used whole-cell vaccine, with immunity waning over time. Both whole-cell and acellular pertussis vaccines are effective at reducing disease severity but not transmission, resulting in outbreaks in vaccinated cohorts. In this review, we discuss various limitations of the current approaches to protection from pertussis and outline various options for reducing the burden of pertussis on a population level.

  9. Immunogenicity, Safety, and Antibody Persistence at 3, 5, and 10 Years Postvaccination in Adolescents Randomized to Booster Immunization with a Combined Tetanus, Diphtheria, 5-Component Acellular Pertussis, and Inactivated Poliomyelitis Vaccine Administered with a Hepatitis B Virus Vaccine Concurrently or 1 Month Apart

    OpenAIRE

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2014-01-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This...

  10. Whooping cough, twenty years from acellular vaccines introduction.

    Science.gov (United States)

    Greco, D; Esposito, S; Tozzi, A; Pandolfi, E; Icardi, G; Giammanco, A

    2015-01-01

    Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

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

    Science.gov (United States)

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

    2016-07-01

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

  12. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults.

    Science.gov (United States)

    Thierry-Carstensen, Birgit; Jordan, Karina; Uhlving, Hilde Hylland; Dalby, Tine; Sørensen, Charlotte; Jensen, Anders Mørup; Heilmann, Carsten

    2012-08-10

    Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults. To obtain clinical documentation of the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis combination vaccine (TdaP), when given as a booster vaccination to adults. The trial was double-blind, controlled and randomised. 802 healthy adults, aged 18-55 years who had completed childhood vaccination with diphtheria, tetanus and whole cell pertussis vaccine (DTwP), were booster vaccinated with TdaP or Td. Blood samples were taken before and one month after the vaccination for serological analysis and adverse events were recorded during the one-month-follow-up period. The monocomponent acellular pertussis vaccine (aP) in the TdaP vaccine was immunogenic in adults with 92.0% of TdaP vaccinated subjects obtaining an anti-pertussis toxin (anti-PT) antibody booster response. TdaP was non-inferior to Td in eliciting seroprotective anti-tetanus and diphtheria antibody concentrations with more than 98% of subjects obtaining post-vaccination seroprotective concentrations (≥ 0.1 IU/mL). T and d booster response rates were 93.0% and 97.5%, respectively. The frequencies of solicited local adverse reactions were low and comparable between TdaP and Td vaccinees. In the TdaP group, 30.7% reported pain, 4.2% swelling and 2.0% erythema at the injection site. The most frequent solicited general symptoms were headache (20.4%), fatigue (17.0%) and myalgia (10.0%). In the Td group, 35.7% reported pain, 2.5% swelling and 3.2% erythema at the injection site, whereas headache, fatigue and myalgia were reported by 15.7%, 14.5% and 12.5%, respectively. In conclusion, TdaP Vaccine SSI was safe and immunogenic when given as a booster vaccination to adults. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Pertussis vaccine in pregnant women: safety and uptake

    Directory of Open Access Journals (Sweden)

    Munoz FM

    2016-03-01

    Full Text Available Flor M Munoz Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA Abstract: Pertussis continues to be an important cause of morbidity and mortality in children worldwide, particularly among infants too young to be vaccinated or who are unvaccinated and unprotected by naturally acquired passive antibodies from their mothers. Vaccination of women during pregnancy with an adult formulation of acellular pertussis vaccine in combination with tetanus and diphtheria toxoids (Tdap [tetanus, reduced diphtheria and acellular pertussis vaccine] is recommended in several industrialized countries to boost the levels of maternal antibodies that are transferred transplacentally and protect infants during the period of life when they are more likely to succumb to pertussis. Data from clinical and epidemiologic studies are supportive of the safety and effectiveness of maternal immunization with pertussis vaccines. Tdap is safe and well tolerated in pregnant women. Local and systemic reactogenicity is similar to that observed in nonpregnant adults, and no serious adverse events have been attributed to Tdap vaccination during pregnancy. Maternal antibodies elicited by the vaccine are efficiently transferred to the fetus through the placenta, and studies have consistently found that infants born to vaccinated mothers have significantly higher concentrations of pertussis antibodies than infants of nonvaccinated mothers. Although a correlate of protection against pertussis is unknown, higher concentrations of antibodies are likely to result in protection of young infants. A reduction in infant pertussis has been shown to occur when high vaccine coverage rates are achieved by pregnant women, as reported in the UK vaccination program. Furthermore, as more vaccine programs incorporate Tdap vaccination during pregnancy, prospective and epidemiologic data will be available to continuously assess the safety and efficacy of

  14. Bordetella pertussis fimbriae (Fim): relevance for vaccines.

    Science.gov (United States)

    Gorringe, Andrew R; Vaughan, Thomas E

    2014-10-01

    Bordetella pertussis produces two serologically distinct fimbriae, Fim2 and Fim3. Expression of these antigens is governed by the BvgA/S system and by the length of a poly(C) tract in the promoter of each gene. Fim2 and Fim3 are important antigens for whole cell pertussis vaccines as clinical trials have shown an association of anti-fimbriae antibody-mediated agglutination and protection. The current five component acellular pertussis vaccine contains co-purified Fim2/3 and provided good efficacy in clinical trials with the anti-Fim antibody response correlating with protection when pre and post exposure antibody levels were analysed. The predominant serotype of B. pertussis isolates has changed over time in most countries but it is not understood whether this is vaccine-driven or whether serotype is linked to the prevailing predominant genotype. Recent studies have shown that both Fim2 and Fim3 are expressed during infection and that Fim2 is more immunogenic than Fim3 in the acellular vaccine.

  15. Analysis of Bordetella pertussis populations in European countries with different vaccination policies.

    NARCIS (Netherlands)

    Amersfoorth, S C M van; Schouls, L M; Heide, H G J van der; Advani, A; Hallander, H O; Bondeson, K; König, C H W von; Riffelmann, M; Vahrenholz, C; Guiso, N; Caro, V; Njamkepo, E; He, Q; Mertsola, J; Mooi, F R

    2005-01-01

    Despite the widespread use of pertussis vaccines during the last decades, pertussis has remained an endemic disease with frequent epidemic outbreaks. Currently two types of vaccines are used: whole-cell vaccines (WCVs) and recently developed acellular vaccines (ACVs). The long-term aim of our studie

  16. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older - Advisory Committee on Immunization Practices (ACIP), 2012.

    Science.gov (United States)

    2012-06-29

    Since 2005, the Advisory Committee on Immunization Practices (ACIP) has recommended a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine booster dose for all adolescents aged 11 through 18 years (preferred at 11 through 12 years) and for those adults aged 19 through 64 years who have not yet received a dose. In October 2010, despite the lack of an approved Tdap vaccine for adults aged 65 years and older, ACIP recommended that unvaccinated adults aged 65 years and older be vaccinated with Tdap if in close contact with an infant, and that other adults aged 65 years and older may receive Tdap. In July 2011, the Food and Drug Administration (FDA) approved expanding the age indication for Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) to aged 65 years and older. In February 2012, ACIP recommended Tdap for all adults aged 65 years and older. This recommendation supersedes previous Tdap recommendations regarding adults aged 65 years and older.

  17. Diphtheria, Tetanus, Pertussis: Ask the Experts

    Science.gov (United States)

    ... Tetanus, Pertussis Ask the Experts: Diseases & Vaccines Diphtheria, Tetanus, Pertussis Ask the Experts Home Combination Vaccines Diphtheria ... have died. How many doses of pediatric diphtheria-tetanus-acellular pertussis (DTaP) vaccine does an infant need ...

  18. Diphtheria, pertussis (whooping cough, and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction

    Directory of Open Access Journals (Sweden)

    Mahendra K Patel

    2012-01-01

    Full Text Available A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough, and tetanus (DPT vaccine used for routine immunization. Postreaction computed tomography (CT scan of brain, magnetic resonance imaging (MRI of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries.

  19. Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years.

    Science.gov (United States)

    Carlsson, R M; Gustafsson, L; Hallander, H O; Ljungman, M; Olin, P; Gothefors, L; Nilsson, L; Netterlid, E

    2015-07-17

    Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20μg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5μg). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350).

  20. Antibody persistence after primary and booster doses of a pentavalent vaccine against diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type B vaccine among Thai children at 18-19 months of age.

    Science.gov (United States)

    Chotpitayasunondh, Tawee; Thisyakorn, Usa; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate; Ortiz, Esteban

    2012-03-01

    The World Health Organization recommends a booster dose of a pertussis-containing vaccine for children aged 1-6 years, preferably during the second year of life. This study assessed the immunogenicity and safety of a pentavalent combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and conjugated-Hib polysaccharide antigens, [(DTaP-IPV//PRP-T (Pentaxim)], as a booster at 18-19 months of age. Participants had received primary doses of the same vaccine at 2, 4 and 6 months of age. Antibody concentrations were measured immediately before and one month after the booster dose. Adverse events were evaluated from parental reports. Geometric mean concentrations (GMCs) or titers (GMTs) decreased from post-primary to pre-booster vaccination; however, at least 94.4% of children had protective levels of anti-tetanus (> or = 0.01 IU/ml), antipoliovirus (> or = 81/dil) and anti-PRP (Hib, > or = 0.15 microg/ml) antibodies prior to the booster. Anti-diphtheria antibody titers > or = 0.01 IU/ml were also observed in the majority of children pre-booster. One month after the booster, seroprotection rates were 99.4% for PRP (> or = 1.0 microg/ml), 95.0% for diphtheria (> or = 0.10 IU/ml) and 100% for tetanus (> or = 0.1 IU/ml) and poliovirus types 1, 2, 3 (> or = 81/dil). At least 93.1% of subjects had 4 fold post-booster increases in anti-pertussis antibody titers. GMCs increased from 14.0 to 307.3 EU/ml and from 13.9 to 271.9 EU/ml for anti-PT and anti-FHA, respectively. Anti-PRP GMC increased from 1.2 to 62.2 microg/ml. The booster was well tolerated. A booster dose during the second year of life was safe and induced a strong immune response, indicative of long-term protection.

  1. Pertussis vaccination and whooping cough: and now what?

    Science.gov (United States)

    Guiso, Nicole

    2014-10-01

    Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or Bordetella parapertussis that are only known to infect humans. This severe and acute respiratory disease presents epidemic cycles and became a vaccine-preventable disease in the 1940s/1950s when developed countries introduced vaccination. The first type of vaccine developed against this disease was a whole-cell pertussis (wP) vaccine containing inactivated B. pertussis bacteria. Most developed countries produced their own vaccine and given the pediatric nature of the disease at the time of licensure, infants and toddlers were the primary targets and were thus massively vaccinated. The characterization of few virulence factors produced by B. pertussis enabled the development of second-generation pertussis vaccines called the acellular pertussis (aP) vaccines. These only contain 1-5 purified, detoxified B. pertussis proteins and were first introduced in Japan around 30 years ago. Australia, Europe and North America introduced aP vaccines approximately 15 years later, which replaced wP vaccines since then.

  2. The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam

    OpenAIRE

    Maertens, Kirsten; Hoang, Thi Thu Ha; Nguyen, Trung Dac; Caboré, Raïssa Nadège; Duong, Thi Hong; Huygen, Kris; Hens, Niel; Van Damme, Pierre; Dang, Duc Anh; Leuridan, Elke

    2016-01-01

    Background.  Maternal vaccination with an acellular pertussis (aP)–containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccin...

  3. Bordetella pertussis iron regulated proteins as potential vaccine components.

    Science.gov (United States)

    Alvarez Hayes, Jimena; Erben, Esteban; Lamberti, Yanina; Principi, Guido; Maschi, Fabricio; Ayala, Miguel; Rodriguez, Maria Eugenia

    2013-08-01

    Bordetella pertussis is the etiologic agent of whooping cough, an illness whose incidence has been increasing over the last decades. Pertussis reemergence despite high vaccination coverage, together with the recent isolation of circulating strains deficient in some of the vaccine antigens, highlight the need for new vaccines. Proteins induced under physiological conditions, such as those required for nutrient acquisition during infection, might represent good targets for better preventive strategies. By mean of serological proteome analysis we identified two novel antigens of B. pertussis potentially involved in iron acquisition during host colonization. We had previously demonstrated that one of them, designated IRP1-3, is protective against pertussis infection in mice. In the present study, we show that the other antigen, named AfuA (BP1605), is a highly antigenic protein, exposed on the bacterial surface, conserved among clinical isolates and expressed during infection. Immunization of mice with the recombinant AfuA induced opsonophagocytic antibodies which could explain the protection against B. pertussis infection conferred by mice immunization with rAfuA. Importantly, we found that the addition of rAfuA and rIRP1-3 proteins to the commercial three pertussis components acellular vaccine significantly increased its protective activity. Taken together, our results point at these two antigens as potential components of a new generation of acellular vaccines.

  4. Whooping Cough and the Pertussis Vaccine

    Science.gov (United States)

    ... Gynecology Medical Conditions Nutrition & Fitness Emotional Health Whooping Cough and the Pertussis Vaccine Posted under Health Guides . ... Content Key Facts Pertussis is also called Whooping Cough. The best way to protect yourself from Pertussis ...

  5. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study

    OpenAIRE

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2015-01-01

    abstract The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese ch...

  6. Whooping Cough (Pertussis)

    Science.gov (United States)

    ... to 5 days following the start of antibiotic treatment. Prevention Whooping cough can be prevented with the pertussis vaccine , which is part of the DTaP (diphtheria, tetanus, acellular pertussis) immunization . DTaP immunizations are routinely given ...

  7. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    Science.gov (United States)

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination.

  8. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    Tetanus, Diphtheria and Pertussis (Tdap) Vaccine In every pregnancy, a woman starts out with a 3-5% ... This sheet talks about whether exposure to the tetanus, diphtheria, and pertussis (or Tdap) vaccine may increase ...

  9. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    Tetanus, Diphtheria and Pertussis (Tdap) Vaccine In every pregnancy, a woman starts out with a 3-5% ... This sheet talks about whether exposure to the tetanus, diphtheria, and pertussis (or Tdap) vaccine may increase ...

  10. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-03

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.

  11. The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam

    Science.gov (United States)

    Maertens, Kirsten; Hoang, Thi Thu Ha; Nguyen, Trung Dac; Caboré, Raïssa Nadège; Duong, Thi Hong; Huygen, Kris; Hens, Niel; Van Damme, Pierre; Dang, Duc Anh; Leuridan, Elke

    2016-01-01

    Background. Maternal vaccination with an acellular pertussis (aP)–containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccine dose in this randomized controlled clinical trial. Methods. Thirty infants of Tdap (tetanus, diphtheria, and acellular pertussis)–vaccinated pregnant women and 37 infants of women vaccinated with a tetanus-only vaccine received a fourth aP-containing vaccine dose in the second year of life. Blood was taken 1 month after the fourth infant dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT), and diphtheria toxoid (DT) were measured using commercially available enzyme-linked immunosorbent assays (ELISA). Results. One month after the booster dose, significantly lower antibody titers were measured in the Tdap group for anti-TT IgG (P antibody titers were comparable for both groups. A rise in antibody concentrations was elicited for all (except DT) antigens after boosting. Conclusions. The present results indicate that the blunting of infant pertussis responses induced by maternal immunization, measured after a primary series of aP vaccines, was resolved with the booster aP vaccine dose. These results add to the evidence for national and international decision makers on maternal immunization as a vaccination strategy for protection of young infants against infectious diseases. PMID:27838673

  12. Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

    Science.gov (United States)

    Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

    2014-06-30

    The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

  13. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    Directory of Open Access Journals (Sweden)

    Valérie Bouchez

    2015-09-01

    Full Text Available Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN, were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA or pertussis toxin (PT deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells.

  14. Immunogenicity of Sabin inactivated poliovirus vaccine induced by diphtheria-tetanus-acellular pertussis and Sabin inactivated poliovirus combined vaccine%DTaP-sIPV联合疫苗中SabinIPV 免疫原性研究

    Institute of Scientific and Technical Information of China (English)

    马艳; 孙明波; 秦敏; 胡慧琼; 姬光; 冯玲; 高娜; 顾洁; 谢炳锋; 何继红

    2011-01-01

    目的 探讨吸附无细胞百白破-Sabin株脊髓灰质炎联合疫苗(DTaP-sIPV)的制备工艺,并比较不同配比的DTaP-sIPV中Sabin株脊髓灰质炎灭活疫苗(SabinIPV)三针基础免疫大鼠的中和抗体效价,为确定联合疫苗的最佳制备工艺及抗原剂量配比提供参考.方法 用不同配比的SabinIPV,制备两批DTaP-sIPV,进行各项指标的检定及稳定性试验,并联合单独的Sabin IPV和GSK制备的DTaP-wIPV对56只Wistar大鼠进行3针免疫,每针间隔1个月,每次免疫后30 d采血并分离血清,采用微量中和试验测定血清中抗脊髓灰质炎病毒3个型别的中和抗体效价.结果 两批DTaPsIPV的各项检定指标均符合三部(2005版)要求,且稳定性良好.大鼠经3针基础免疫后,其Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎病毒中和抗体的几何平均滴度均显著上升,3针免疫后抗体阳转率已经达到100%.结论 经此制备的DTaP-sIPV安全、稳定、有效,且DTaP-sIPV中的SabinIPV在大鼠中有良好的免疫效果,经3针免疫可产生高水平的中和抗体.%Objective In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine ( DTaPsIPV) , the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. Methods Two batches of DTaP-sIPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostriixTM-polio, GSK, Belgium) as control group,the DTaP-sIPV were administrated on three-dose schedule at 0,1,2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. Results Two batches of prepared DTaP-sIPV and control sIPV were according to the requirement of Chinese Pharmacopoeia ( Volume Ⅲ , 2005 edition) and showed

  15. Population dynamics of Bordetella pertussis in Finland and Sweden, neighbouring countries with different vaccination histories.

    Science.gov (United States)

    Elomaa, Annika; Advani, Abdolreza; Donnelly, Declan; Antila, Mia; Mertsola, Jussi; He, Qiushui; Hallander, Hans

    2007-01-15

    Pertussis is an infectious disease of the respiratory tract in humans caused by Bordetella pertussis. Despite extensive vaccinations, pertussis has remained endemic and re-emerged. In Finland, a whole-cell pertussis vaccine has been used since 1952 with high coverage. In Sweden, whole-cell vaccinations were introduced in 1953 but ceased in 1979, and pertussis vaccinations with acellular vaccines were introduced in 1996. Two epidemic peaks occurred in Sweden in 1999 and 2002 and in Finland in 1999 and 2003. We compared Finnish (N=193) and Swedish (N=455) B. pertussis isolates circulating in 1998-2003 together with vaccine strains used in these neighbouring countries with different vaccination histories. The isolates were analysed by serotyping, genotyping of pertussis toxin S1 subunit and pertactin, and pulsed-field gel electrophoresis. The results suggest that the sequential epidemics were caused by clonal expansion of a certain B. pertussis strain possibly transmitted from Sweden to Finland. The roles of antigenic variation in immunity-driven evolution of B. pertussis in both countries are discussed.

  16. Estimates of Pertussis Vaccine Effectiveness in United States Air Force Pediatric Dependents

    Science.gov (United States)

    2015-06-22

    medical treatment facility; OR, odds ratio; PCR, polymerase chain reaction; Tdap, tetanus , diphtheria toxoids, and acellular pertus- sis; U.S., United...interval; ClinChem, Clinical Chemistry Database; DFA, direct fluorescent antibody; DTaP, diphtheria, tetanus toxoids, and acellular pertussis; MTF...100,000 people) [8,9]. The Advisory Committee on Immunization Practices (ACIP) recommends vaccination with diphtheria, tetanus toxoids, and http

  17. Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of a Fully Liquid Combination Diphtheria–Tetanus Toxoid–Five-Component Acellular Pertussis (DTaP5), Inactivated Poliovirus (IPV), and Haemophilus influenzae Type b (Hib) Vaccine Compared with a DTaP3-IPV/Hib Vaccine Administered at 3, 5, and 12 Months of Age

    Science.gov (United States)

    Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

    2013-01-01

    This study compared the levels of immunogenicity and safety of diphtheria–tetanus toxoid–five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP5-IPV-Hib) and DTaP3-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP5-IPV-Hib to DTaP3-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP5-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.) PMID:23966556

  18. Randomized, controlled, multicenter study of the immunogenicity and safety of a fully liquid combination diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and haemophilus influenzae type b (Hib) vaccine compared with a DTaP3-IPV/Hib vaccine administered at 3, 5, and 12 months of age.

    Science.gov (United States)

    Vesikari, Timo; Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

    2013-10-01

    This study compared the levels of immunogenicity and safety of diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP(5)), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP(5)-IPV-Hib) and DTaP(3)-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP(5)-IPV-Hib to DTaP(3)-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP(5)-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.).

  19. Genomic analysis of isolates from the United Kingdom 2012 pertussis outbreak reveals that vaccine antigen genes are unusually fast evolving.

    Science.gov (United States)

    Sealey, Katie L; Harris, Simon R; Fry, Norman K; Hurst, Laurence D; Gorringe, Andrew R; Parkhill, Julian; Preston, Andrew

    2015-07-15

    A major outbreak of whooping cough, or pertussis, occurred in 2012 in the United Kingdom (UK), with nearly 10 000 laboratory-confirmed cases and 14 infant deaths attributed to pertussis. A worldwide resurgence of pertussis has been linked to switch to the use of acellular pertussis vaccines and the evolution of Bordetella pertussis away from vaccine-mediated immunity. We have conducted genomic analyses of multiple strains from the UK outbreak. We show that the UK outbreak was polyclonal in nature, caused by multiple distinct but closely related strains. Importantly, we demonstrate that acellular vaccine antigen-encoding genes are evolving at higher rates than other surface protein-encoding genes. This was true even prior to the introduction of pertussis vaccines but has become more pronounced since the introduction of the current acellular vaccines. The fast evolution of vaccine antigen-encoding genes has serious consequences for the ability of current vaccines to continue to control pertussis. © 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.

  20. Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b vaccine; Infanrix™ hexa

    Science.gov (United States)

    Baldo, Vincenzo; Bonanni, Paolo; Castro, Marcela; Gabutti, Giovanni; Franco, Elisabetta; Marchetti, Federico; Prato, Rosa; Vitale, Francesco

    2014-01-01

    Infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11–12 mo of age was pioneered in Italy. The 3-5-11 schedule is now used in a growing number of European countries. Infanrix™ hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. We reviewed available clinical trial data describing the immunogenicity of DTPa-HBV-IPV/Hib when administered at 3, 5, and 11 mo of age, and conducted an analysis of safety using global and Italian post-marketing surveillance data. In Italy, DTPa-HBV-IPV/Hib has a demonstrated safety record extending over a decade of use, it has been associated with record levels of vaccine coverage, and with sustained disease control in vaccinated cohorts. Hexavalent vaccines will continue to contribute to high vaccine coverage in Italy and across Europe. PMID:24004825

  1. Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type B vaccine; Infanrix™ hexa: twelve years of experience in Italy.

    Science.gov (United States)

    Baldo, Vincenzo; Bonanni, Paolo; Castro, Marcela; Gabutti, Giovanni; Franco, Elisabetta; Marchetti, Federico; Prato, Rosa; Vitale, Francesco

    2014-01-01

    Infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11-12 mo of age was pioneered in Italy. The 3-5-11 schedule is now used in a growing number of European countries. Infanrix™ hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. We reviewed available clinical trial data describing the immunogenicity of DTPa-HBV-IPV/Hib when administered at 3, 5, and 11 mo of age, and conducted an analysis of safety using global and Italian post-marketing surveillance data. In Italy, DTPa-HBV-IPV/Hib has a demonstrated safety record extending over a decade of use, it has been associated with record levels of vaccine coverage, and with sustained disease control in vaccinated cohorts. Hexavalent vaccines will continue to contribute to high vaccine coverage in Italy and across Europe.

  2. Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type B vaccine; Infanrix™ hexa: twelve years of experience in Italy.

    OpenAIRE

    Baldo, V; P. Bonanni; Castro, M.; GABUTTI, G.; Franco, E.; Marchetti, F.; Prato, R.; F. Vitale

    2014-01-01

    Infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11–12 mo of age was pioneered in Italy. The 3-5-11 schedule is now used in a growing number of European countries. Infanrix™ hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. We reviewed available clinical trial data describing the immunogenicity of DTPa-HBV-IPV/Hib when administered at 3, 5, and 11 mo of age...

  3. 吸附无细胞百白破联合疫苗的免疫原性及免疫持久性%Immunogenicity and immune persistence of adsorbed diphtheria, tetanus and acellular pertussis combined vaccine

    Institute of Scientific and Technical Information of China (English)

    邹光荣; 兰红; 项美娟; 杨汝沛; 杨晓明; 侯启明; 张量智; 王丽蝉; 李军

    2013-01-01

    目的 观察武汉生物制品研究所有限责任公司(以下简称武汉公司)吸附无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)的免疫原性和免疫持久性.方法 于2007年9月在成都地区选择670名未接种过百白破联合疫苗,无百日咳、白喉、破伤风疾病史的足月出生的健康婴儿,按2∶1比例随机接种3剂观察疫苗(武汉公司生产的DTaP)和对照疫苗(某厂家生产的DTaP),进行基础免疫,每剂间隔1个月,2009年3月进行加强免疫,接种剂量均为0.5ml/(剂·人).基础免疫接种前和全程接种后30~ 50 d、加强免疫前和加强免疫后1个月、1、2、3年分别采集静脉血,分离血清,经ELISA法测定百日咳毒素抗体(pertussis toxin antibody,PT-Ab)、丝状凝集素抗体(filamentous hemagglutinin antibody,FHA-Ab)、白喉抗体(diphtheria antibody,D-Ab)、破伤风抗体(tetanus antibody,T-Ab)GMT,若免疫前抗体为阳性,则计算4倍增长率.结果 基础免疫试验组351例、对照组193例完成了全程接种,即544例受种者符合方案要求.DTaP基础免疫后,试验组与对照组的4种抗体阳转率及抗体4倍增长率差异均无统计学意义(P>0.05);试验组FHA-Ab GMT明显高于对照组,差异有统计学意义(P<0.05).加强免疫前,试验组与对照组4种抗体阳转率差异无统计学意义(P>0.05);加强免疫后1个月,试验组FHA-Ab阳转率明显高于对照组,差异有统计学意义(P<0.05);加强免疫后1、2、3年,试验组与对照组4种抗体阳转率和抗体GMT差异均无统计学意义(P>0.05);加强免疫后1年,4种抗体GMT均高于有效保护水平,加强免疫后2年,PT-Ab和FHA-Ab GMT已降至保护水平以下,加强免疫后3年,D-Ab、T-Ab GMT仍高于保护水平.结论 武汉公司生产的DTaP具有较好的免疫原性和免疫持久性.

  4. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  5. Antibody response patterns to Bordetella pertussis antigens in vaccinated (primed) and unvaccinated (unprimed) young children with pertussis.

    Science.gov (United States)

    Cherry, James D; Heininger, Ulrich; Richards, David M; Storsaeter, Jann; Gustafsson, Lennart; Ljungman, Margaretha; Hallander, Hans O

    2010-05-01

    In a previous study, it was found that the antibody response to a nonvaccine pertussis antigen in children who were vaccine failures was reduced compared with the response in nonvaccinated children who had pertussis. In two acellular pertussis vaccine efficacy trials in Sweden, we studied the convalescent-phase enzyme-linked immunosorbent assay (ELISA) geometric mean values (GMVs) in response to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM 2/3) in vaccine failures and controls with pertussis. In Germany, the antibody responses to Bordetella pertussis antigens PT, FHA, PRN, and FIM-2 were analyzed by ELISA according to time of serum collection after onset of illness in children with pertussis who were vaccine failures or who were previously unvaccinated. Antibody values were also compared by severity of clinical illness. In Sweden, infants who had received a PT toxoid vaccine and who were vaccine failures had a blunted response to the nonvaccine antigen FHA compared with the response in children who had received a PT/FHA vaccine. Similarly, infants who had pertussis and who had received a PT/FHA vaccine had a blunted response to the nonvaccine antigens PRN and FIM 2/3 compared with the response in children who were vaccine failures and who had received a PT, FHA, PRN, and FIM 2/3 vaccine. In Germany, in sera collected from 0 to 15 days after pertussis illness onset, the GMVs for all 4 antigens (PT, FHA, PRN, and FIM-2) were significantly lower in an unvaccinated group than in children who were diphtheria-tetanus-acellular pertussis (DTaP) vaccine failures. In the unvaccinated group, the GMV of the PT antibody rose rapidly over time so that it was similar to that of the DTaP vaccine recipients at the 16- to 30-day period. In contrast, the antibody responses to FHA, PRN, and FIM-2 at all time periods were lower in the diphtheria-tetanus vaccine (DT) recipients than in the DTaP vaccine failures. In both Sweden and Germany

  6. Approaches to New Generation Vaccines against Pertussis and Identification of Virulence Factors

    OpenAIRE

    Gasperini, Gianmarco

    2017-01-01

    Despite high vaccination coverage world-wide, whooping cough, a highly contagious disease caused by Bordetella pertussis, is recently increasing in occurrence suggesting that novel vaccine formulations targeted at the prevention of colonization and transmission should be investigated. In order to identify new candidates for inclusion in the acellular formulation, we used spontaneously released outer membrane vesicles (OMV) as a potential source of key adhesins. In the first part of the study,...

  7. Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin.

    Science.gov (United States)

    Williams, Margaret M; Sen, Kathryn; Weigand, Michael R; Skoff, Tami H; Cunningham, Victoria A; Halse, Tanya A; Tondella, M Lucia

    2016-02-01

    A Bordetella pertussis strain lacking 2 acellular vaccine immunogens, pertussis toxin and pertactin, was isolated from an unvaccinated infant in New York State in 2013. Comparison with a French strain that was pertussis toxin-deficient, pertactin wild-type showed that the strains carry the same 28-kb deletion in similar genomes.

  8. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women.

    Science.gov (United States)

    Huygen, Kris; Caboré, Raïssa Nadège; Maertens, Kirsten; Van Damme, Pierre; Leuridan, Elke

    2015-08-07

    Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012-2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus. Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine

  9. Serum IgA responses against pertussis proteins in infected and Dutch wP or aP vaccinated children: an additional role in pertussis diagnostics.

    Directory of Open Access Journals (Sweden)

    Lotte H Hendrikx

    Full Text Available BACKGROUND: Whooping cough is a respiratory disease caused by Bordetella pertussis, which induces mucosal IgA antibodies that appear to be relevant in protection. Serum IgA responses are measured after pertussis infection and might provide an additional role in pertussis diagnostics. However, the possible interfering role for pertussis vaccinations in the induction of serum IgA antibodies is largely unknown. METHODS/PRINCIPAL FINDINGS: We compared serum IgA responses in healthy vaccinated children between 1 and 10 years of age with those in children who despite vaccinations recently were infected with Bordetella pertussis. All children have been vaccinated at 2, 3, 4 and 11 months of age with either the Dutch whole-cell pertussis (wP vaccine or an acellular pertussis (aP vaccine and additionally received an aP booster vaccination at 4 years of age. Serum IgA responses to pertussis toxin (PT, filamentous heamagglutinin (FHA and pertactin (Prn were measured with a fluorescent multiplex bead-based immuno-assay. An ELISPOT-assay was used for the detection of IgA-memory B-cells specific to these antigens. Serum IgA levels to all pertussis vaccine antigens were significantly higher in infected children compared with healthy children. High correlations between anti-PT, anti-FHA or anti-Prn IgA and IgG levels were found in infected children and to some degree in wP primed children, but not at all in aP primed children. Highest numbers of IgA-pertussis-specific memory B-cells were observed after infection and generally comparable numbers were found after wP and aP vaccination. CONCLUSIONS: This study provides new insight in the diagnostic role for serum IgA responses against PT in vaccinated children. Since aP vaccines induce high serum IgG levels that interfere with pertussis diagnostics, serum IgA-PT levels will provide an additional diagnostic role. High levels of serum IgA for PT proved specific for recent pertussis infection with reasonable

  10. Bordetella pertussis infection or vaccination substantially protects mice against B. bronchiseptica infection.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Goebel

    Full Text Available Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state.

  11. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants

    Science.gov (United States)

    Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa

    2017-01-01

    ABSTRACT We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2–3–4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18–24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1–3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile. PMID:27768515

  12. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    Science.gov (United States)

    ... the throat. It can lead to breathing problems, paralysis, heart failure, and death.PERTUSSIS (Whooping Cough) causes severe coughing spells, which can cause difficulty breathing, vomiting and disturbed sleep. It can also lead to weight loss, incontinence, ...

  13. Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity.

    Science.gov (United States)

    Raeven, René H M; van der Maas, Larissa; Tilstra, Wichard; Uittenbogaard, Joost P; Bindels, Tim H E; Kuipers, Betsy; van der Ark, Arno; Pennings, Jeroen L A; van Riet, Elly; Jiskoot, Wim; Kersten, Gideon F A; Metz, Bernard

    2015-07-02

    The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail. The purpose of this study was to determine the antigen composition of omvPV and to elucidate the immunogenicity of the individual antigens. Quantitative proteome analysis revealed the complex composition of omvPV. The omvPV immunogenicity profile in mice was compared to those of classic whole cell vaccine (wPV), acellular vaccine (aPV), and pertussis infection. Pertussis-specific antibody levels, antibody isotypes, IgG subclasses, and antigen specificity were determined after vaccination or infection by using a combination of multiplex immunoassays, two-dimensional immunoblotting, and mass spectrometry. The vaccines and infection raised strong antibody responses, but large quantitative and qualitative differences were measured. The highest antibody levels were obtained by omvPV. All IgG subclasses (IgG1/IgG2a/IgG2b/IgG3) were elicited by omvPV and in a lower magnitude by wPV, but not by aPV (IgG1) or infection (IgG2a/b). The majority of omvPV-induced antibodies were directed against Vag8, BrkA, and LPS. The broad and balanced humoral response makes omvPV a promising pertussis vaccine candidate.

  14. Adaptive immune response to whole cell pertussis vaccine reflects vaccine quality : A possible complementation to the Pertussis Serological Potency test

    NARCIS (Netherlands)

    Hoonakker, M E; Verhagen, L M; van der Maas, L; Metz, B; Uittenbogaard, J P; van de Waterbeemd, B; van Els, C A C M; van Eden, W; Hendriksen, C F M; Sloots, A; Han, W G H

    2016-01-01

    Whole cell Bordetella pertussis (wP) vaccines are still used in many countries to protect against the respiratory disease pertussis. The potency of whole-cell pertussis vaccine lots is determined by an intracerebral challenge test (the Kendrick test). This test is criticized due to lack of immunolog

  15. Global population structure and evolution of Bordetella pertussis and their relationship with vaccination.

    Science.gov (United States)

    Bart, Marieke J; Harris, Simon R; Advani, Abdolreza; Arakawa, Yoshichika; Bottero, Daniela; Bouchez, Valérie; Cassiday, Pamela K; Chiang, Chuen-Sheue; Dalby, Tine; Fry, Norman K; Gaillard, María Emilia; van Gent, Marjolein; Guiso, Nicole; Hallander, Hans O; Harvill, Eric T; He, Qiushui; van der Heide, Han G J; Heuvelman, Kees; Hozbor, Daniela F; Kamachi, Kazunari; Karataev, Gennady I; Lan, Ruiting; Lutyńska, Anna; Maharjan, Ram P; Mertsola, Jussi; Miyamura, Tatsuo; Octavia, Sophie; Preston, Andrew; Quail, Michael A; Sintchenko, Vitali; Stefanelli, Paola; Tondella, M Lucia; Tsang, Raymond S W; Xu, Yinghua; Yao, Shu-Man; Zhang, Shumin; Parkhill, Julian; Mooi, Frits R

    2014-04-22

    Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis

  16. Complete Genome Sequences of Bordetella pertussis Vaccine Reference Strains 134 and 10536

    Science.gov (United States)

    Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Burroughs, Mark; Johnson, Taccara; Juieng, Phalasy; Rowe, Lori; Tondella, M. Lucia; Williams, Margaret M.

    2016-01-01

    Vaccine formulations and vaccination programs against whooping cough (pertussis) vary worldwide. Here, we report the complete genome sequences of two divergent Bordetella pertussis reference strains used in the production of pertussis vaccines. PMID:27635001

  17. Complete Genome Sequences of Bordetella pertussis Vaccine Reference Strains 134 and 10536.

    Science.gov (United States)

    Weigand, Michael R; Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Burroughs, Mark; Johnson, Taccara; Juieng, Phalasy; Rowe, Lori; Tondella, M Lucia; Williams, Margaret M

    2016-09-15

    Vaccine formulations and vaccination programs against whooping cough (pertussis) vary worldwide. Here, we report the complete genome sequences of two divergent Bordetella pertussis reference strains used in the production of pertussis vaccines.

  18. Vaccination of health care workers against pertussis: meeting the need for safety within hospitals.

    Science.gov (United States)

    Heininger, U

    2014-08-27

    Pertussis outbreaks in hospitals are reason for substantial concern as they do cause significant morbidity amongst patients and physical and emotional stress and absence from work amongst affected staff. Further, there is a substantial financial burden for the concerned institution. For these reasons, health care institutions should implement prophylactic measures, i.e. pertussis immunisation for their staff. Diphtheria-tetanus-acellular pertussis component combination vaccines with reduced antigen content ("Tdap") have a proven acceptable tolerability with reactogenicity and safety profiles not substantially different from Td vaccines without the pertussis component. Further, excellent immunogenicity after a single dose with an estimated duration of protection for 10 years has been shown in adults. In high risk situations, e.g. in pregnant health care workers and those in contact with infants workers. Local programmes based on education, conviction and common sense should be implemented for health care workers rather than mandatory pertussis immunisation. In addition, health care workers need to be informed and regularly reminded about the impact of exposure to pertussis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.

    Science.gov (United States)

    Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban

    2011-02-24

    The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

  20. Mouse and pig models for studies of natural and vaccine-induced immunity to Bordetella pertussis.

    Science.gov (United States)

    Mills, Kingston H G; Gerdts, Volker

    2014-04-01

    The increasing incidence of whooping cough in many developed countries has been linked with waning immunity induced after immunization with acellular pertussis (aP) vaccines. The rational design of an improved aP vaccine requires a full understanding of the mechanism of protective immunity and preclinical studies in animal models. Infection of mice and pigs with Bordetella pertussis has many features of the infection seen in humans and has already provided valuable information on the roles of innate and adaptive immune responses in protection. Recent findings in these models have already indicated that it may be possible to develop an improved aP vaccine based on a formulation that includes a Toll-like receptor agonist as an adjuvant.

  1. A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

    2013-05-01

    This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

  2. Tetanus, Diphtheria, and Pertussis Vaccines - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Taw) Thiab Pertussis (Hnoos Ntev) - Hmoob (Hmong) PDF Immunization Action Coalition; Centers for Disease Control and Prevention Tetanus, Diphtheria (Td) Vaccine English Tshuaj Txhaj Tiv Thaiv Kab ...

  3. Pertussis: herd immunity and vaccination coverage in St Lucia.

    Science.gov (United States)

    Cooper, E; Fitch, L

    1983-11-12

    In a single complete epidemic in St Lucia, an island too small to support constant clinical pertussis, the pertussis case rates in small communities (villages and small towns) with differing levels of vaccination coverage of young children were compared. The association between greater vaccination coverage and greater herd immunity was clear, despite the imperfect protection given to individuals. An analysis in terms of population dynamics is evidence against the theory that endemic subclinical pertussis maintains transmission in a highly vaccinated population. We suggest that with a homogeneous vaccination coverage of 80% of 2-year-old children pertussis might be eradicated from the island, and that this is a practicable experiment.

  4. Tetanus, Diphtheria, and Pertussis Vaccines

    Science.gov (United States)

    ... nose and throat. Whooping cough causes uncontrollable coughing. Vaccines can protect you from these diseases. In the U.S., there are four combination vaccines: DTaP prevents all three diseases. It is for ...

  5. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

    DEFF Research Database (Denmark)

    Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

    2015-01-01

    (diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis vaccine). METHODS: This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5mL dose of 9vHPV vaccine...

  6. Importance of (antibody-dependent) complement-mediated serum killing in protection against Bordetella pertussis.

    Science.gov (United States)

    Geurtsen, Jeroen; Fae, Kellen C; van den Dobbelsteen, Germie P J M

    2014-10-01

    Pertussis is a highly contagious respiratory disease that is caused by Bordetella pertussis. Despite being vaccine preventable, pertussis rates have been rising steadily over the last decades, even in areas with high vaccine uptake. Recently, experiments with infant baboons indicated that although vaccination with acellular pertussis vaccines prevented disease, no apparent effect was observed on infection and transmission. One explanation may be that current acellular pertussis vaccines do not induce high levels of opsonophagocytic and/or bactericidal activity, implying that engineering of vaccines that promote bacterial killing may improve efficacy. Here, we discuss the importance of complement-mediated killing in vaccine-induced protection against B. pertussis. We first examine how B. pertussis may have evolved different complement evasion strategies. Second, we explore the benefits of opsonophagocytic and/or bactericidal killing in vaccine-induced protection and discuss whether or not inclusion of new opsonophagocytic or bactericidal target antigens in pertussis vaccines may benefit efficacy.

  7. Characterization of the immune response induced by pertussis OMVs-based vaccine.

    Science.gov (United States)

    Bottero, D; Gaillard, M E; Zurita, E; Moreno, G; Martinez, D Sabater; Bartel, E; Bravo, S; Carriquiriborde, F; Errea, A; Castuma, C; Rumbo, M; Hozbor, D

    2016-06-14

    For the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wP) or after infection should be used as a reference point. We have recently identified a vaccine candidate based on outer membrane vesicles (OMVs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. Here we characterized OMVs-mediated immunity and the safety of our new candidate. We also deepen the knowledge of the induced humoral response contribution in pertussis protection. Regarding the safety of the OMVs based vaccine (TdapOMVsBp,) the in vitro whole blood human assay here performed, showed that the low toxicity of OMVs-based vaccine previously detected in mice could be extended to human samples. Stimulation of splenocytes from immunized mice evidenced the presence of IFN-γ and IL-17-producing cells, indicated that OMVs induces both Th1 and Th17 response. Interestingly TdapOMVsBp-raised antibodies such as those induced by wP and commercial acellular vaccines (aP) which contribute to induce protection against Bordetella pertussis infection. As occurs with wP-induced antibodies, the TdapOMVsBp-induced serum antibodies efficiently opsonized B. pertussis. All the data here obtained shows that OMVs based vaccine is able to induce Th1/Th17 and Th2 mixed profile with robust humoral response involved in protection, positioning this candidate among the different possibilities to constitute the third generation of anti-pertussis vaccines.

  8. Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.

    Science.gov (United States)

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2015-11-17

    Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent. In this study, we used an in vivo competition assay in mice immunised with ACV and in naïve (control) mice to compare the proportion of colonisation with recent clinical Prn positive and Prn negative B. pertussis strains from Australia. The Prn negative strain colonised the respiratory tract more effectively than the Prn positive strain in immunised mice, out-competing the Prn positive strain by day 3 of infection. However, in control mice, the Prn positive strain out-competed the Prn negative strain. Our findings of greater ability of Prn negative strains to colonise ACV-immunised mice are consistent with reports of selective advantage for these strains in ACV-immunised humans.

  9. Side effects of cellular and acellular DPT vaccine in children aged from 3 months to 5 years

    Directory of Open Access Journals (Sweden)

    Durmišević Smajil

    2004-01-01

    Full Text Available Introduction Both mild and severe local and systemic postvaccination reactions are seen more rarely in infants immunized with DTPa than in those immunized with DTPw vaccine. Material and methods By analysis of medical records and follow-up of patients, the authors searched for sings of adverse effects of DPT vaccines, comparing cellular and acellular vaccines in children aged from three months to five years. The results of investigation were analyzed using X2. Results Out of the total number of 940 applied vaccines, 329 were cellular and 611 were acellular. Body temperature over 38.5oC occurred in 3% of children immunized with cellular DTPw, and vomiting occurred in 0.8% of those immunized with acellular DTPa vaccine. Vomiting occurred (more than five times in 0.9% of children immunized with DPTw and in 0.32% of children immunized with DPTa. Other undesirable symptoms like swelling, redness and pain in the arm were found in 0.6% of children immunized with DPTw, and in 0.32% of children immunized with DPTa; prolonged crying (three hours or longer was registered in 0.3% of cases immunized with DPTw, and in 0.16% of immunized with DPTa vaccine. Convulsions and collapse appeared only in 0.3% of children immunized with DPTw. Discussion Our investigation shows that local and generalized undesirable postvaccination reactions occurred in 5.4% of children immunized with DPTw and in 1.64 of children immunized with DPTa. The latest clinical investigations show that acellular pertussis vaccines are successful in prevention of pertussis and that they are quite safe for infants; in our investigations, local and generalized reactions were markedly rare in children immunized with DPTa. Conclusion Undesirable postvaccination reactions after application of acellular DPT vaccines are less frequent than it is described in relevant references. The most frequent postvaccination reactions was raised body temperature (38.5oC. Convulsions and collapses were not

  10. Pertussis vaccinations in Dutch children: memory immune responses

    NARCIS (Netherlands)

    Hendrikx, L.H.

    2011-01-01

    Despite high pertussis vaccination coverage, pertussis is reemerging in the Netherlands since 1996. In attempt to improve protection against whooping cough, two major changes in the national immunization program have been made; the introduction of a preschool booster vaccination in children 4 years

  11. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough.

    Directory of Open Access Journals (Sweden)

    Nathalie Mielcarek

    2006-07-01

    Full Text Available Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.

  12. Modelling the effect of changes in vaccine effectiveness and transmission contact rates on pertussis epidemiology.

    Science.gov (United States)

    Pesco, P; Bergero, P; Fabricius, G; Hozbor, D

    2014-06-01

    The incidence of the highly infectious respiratory disease named pertussis or whooping cough has been increasing for the past two decades in different countries, as in much of the highly vaccinated world. A decrease in vaccine effectiveness over time, especially when acellular vaccines were used for primary doses and boosters, and pathogen adaptation to the immunity conferred by vaccines have been proposed as possible causes of the resurgence. The contributions of these factors are not expected to be the same in different communities, and this could lead to different epidemiological trends. In fact, differences in the magnitude and dynamics of pertussis outbreaks as well as in the distribution of notified cases by age have been reported in various regions. Using an age-structured mathematical model designed by us, we evaluated how the changes in some of the parameters that could be related to the above proposed causes of disease resurgence - vaccine effectiveness and effective transmission rates - may impact on pertussis transmission. When a linear decrease in vaccine effectiveness (VE) was assayed, a sustained increase in pertussis incidence was detected mainly in infants and children. On the other hand, when changes in effective transmission rates (βij) were made, a dynamic effect evidenced by the presence of large peaks followed by deep valleys was detected. In this case, greater incidence in adolescents than in children was observed. These different trends in the disease dynamics due to modifications in VE or βij were verified in 18 possible scenarios that represent different epidemiological situations. Interestingly we found that both incidence trends produced by the model and their age distribution resemble the profiles obtained from data reported in several regions. The implications of these correlations are discussed.

  13. DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

    Science.gov (United States)

    ... DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by bacteria . ...

  14. Pertactin-negative variants of Bordetella pertussis in New York State: a retrospective analysis, 2004-2013.

    Science.gov (United States)

    Quinlan, Tammy; Musser, Kimberlee A; Currenti, Salvatore A; Zansky, Shelley M; Halse, Tanya A

    2014-08-01

    The first report of pertactin-negative variants of Bordetella pertussis in the United States has raised questions about the role of acellular pertussis vaccines in the recent increase of pertussis cases. Our laboratory utilized a sequence-based method to identify mutations in the pertactin gene responsible for these variants and assessed vaccination status from the associated cases.

  15. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injurie

  16. [Optimization of the pertussis vaccine production process].

    Science.gov (United States)

    Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

    1995-01-01

    The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased.

  17. Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence.

    Science.gov (United States)

    Sealey, Katie L; Belcher, Thomas; Preston, Andrew

    2016-06-01

    Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation.

  18. Serologic Evidence of Pertussis Infection in Vaccinated Iranian Children

    Directory of Open Access Journals (Sweden)

    Anahita Sanaei Dashti

    2012-12-01

    Full Text Available Background: It seems that the incidence of pertussis-like illnesses is considerably increasing despite the wide coverage of immunization with the whole cell pertussis vaccine. We aimed to investigate the occurrence of pertussis in vaccinated children by measuring anti-pertussis antibodies. Methods: In this cross-sectional study, blood samples were taken from vaccinated children aged 2, 4, 6, 12, 18, and 72 months. Anti-pertussis IgG and IgA were measured by ELISA. P<0.05 was considered significant.Results: 725 children were enrolled in the study. Geometric mean titers for IgG that showed a slight decease after 2 months of age and increased distinctly in children aged 72 months. The frequency of the individuals whose IgG was above the determined cut-off (derived from mean+2SD was observed in 1% of the 2, 4, and 6-month-old infants, 6% of the 12 and 18-month-olds and 12% of the 6-year -old children. Positive IgA titers were detected in 5, 9, 6, 23, 11, and 8% of children aged 2, 4, 6, 12, 18, and 72 months, respectively.Conclusion: Since a considerable percentage of children had high levels of anti-pertussis IgG antibodies (≥2 SD, positive anti-pertussis IgA, and most importantly an increased level of anti-pertussis IgG geometric mean titer at 6 years of age, further investigations regarding the protection provided by the presently used pertussis vaccine seems necessary.

  19. Dynamic models for health economic assessments of pertussis vaccines : what goes around comes around ...

    NARCIS (Netherlands)

    Rozenbaum, M.H.; De Cao, E.; Westra, T.A.; Postma, M.J.

    2012-01-01

    Despite childhood vaccination programs, pertussis remains endemic. To reduce the burden of pertussis, various extended pertussis vaccination strategies have been suggested. The aim of this article is to evaluate dynamic models used to assess the cost-effectiveness of vaccination. In total, 16 studie

  20. Contribution of pertussis toxin to the pathogenesis of pertussis disease.

    Science.gov (United States)

    Carbonetti, Nicholas H

    2015-11-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease.

  1. Analysis of Bordetella pertussis pertactin and pertussis toxin types from Queensland, Australia, 1999–2003

    Directory of Open Access Journals (Sweden)

    Slack Andrew T

    2006-03-01

    Full Text Available Abstract Background In Australia two acellular Bordetella pertussis vaccines have replaced the use of a whole cell vaccine. Both of the licensed acellular vaccines contain the following three components; pertussis toxoid, pertussis filamentous haemagglutinin and the 69 kDa pertactin adhesin. One vaccine also contains pertussis fimbriae 2 and 3. Various researchers have postulated that herd immunity due to high levels of pertussis vaccination might be influencing the makeup of endemic B. pertussis populations by selective pressure for strains possessing variants of these genes, in particular the pertactin gene type. Some publications have suggested that B. pertussis variants may be contributing to a reduced efficacy of the existing vaccines and a concomitant re-emergence of pertussis within vaccinated populations. This study was conducted to survey the pertactin and pertussis toxin subunit 1 types from B. pertussis isolates in Queensland, Australia following the introduction of acellular vaccines. Methods Forty-six B. pertussis isolates recovered from Queensland patients between 1999 and 2003 were examined by both DNA sequencing and LightCycler™ real time PCR to determine their pertactin and pertussis toxin subunit 1 genotypes. Results Pertactin typing showed that 38 isolates possessed the prn1 allele, 3 possessed the prn2 allele and 5 possessed the prn3 allele. All forty-six isolates possessed the pertussis toxin ptxS1A genotype. Amongst the circulating B. pertussis population in Queensland, 82.5% of the recovered clinical isolates therefore possessed the prn1/ptxS1A genotype. Conclusion The results of this study compared to historical research on Queensland isolates suggest that B. pertussis pertactin and pertussis toxin variants are not becoming more prevalent in Queensland since the introduction of the acellular vaccines. Current prevalences of pertactin variants are significantly different to that described in a number of other countries

  2. Cellular and humoral immunity after infection with B. pertussis : the role of age, antigen and vaccination history

    NARCIS (Netherlands)

    van Twillert, I

    2017-01-01

    Pertussis (whooping cough), is a bacterial disease of the respiratory tract, caused by the human pathogen Bordetella pertussis. Vaccination against pertussis has dramatically lowered pertussis incidence and mortality rates; however pertussis still occurs. The duration of immunity to B. pertussis aft

  3. Vaccination against tetanus, diphtheria, pertussis and poliomyelitis in adult travellers.

    Science.gov (United States)

    Gautret, Philippe; Wilder-Smith, Annelies

    2010-05-01

    This paper reviews the risk and vaccine recommendations for tetanus, diphtheria, pertussis and poliomyelitis for adult travellers. The travel clinic presents a unique opportunity to evaluate whether routine vaccinations are up-to-date. Tetanus, diphtheria and pertussis occur worldwide but are more common in low resource countries due to incomplete childhood vaccination coverage, environmental and socio-economic factors. Diphtheria has been reported in travellers without adequate protection. A booster against tetanus and diphtheria is recommended for all adult travellers, regardless of travel destination and duration. The incidence of pertussis in general adult travellers has been poorly studied. Extrapolating from the reported high incidence in travellers to the Hajj, the risk may be more substantial than thought. There are no universal recommendations for pertussis vaccination for adult travellers, and studies are needed to develop evidence based guidelines. Poliomyelitis is well controlled and now only occurs in a small number of countries. Travellers to and from endemic and re-infected countries should be fully vaccinated against poliomyelitis.

  4. Improving pertussis vaccination: central role of CD4 T cell programming

    NARCIS (Netherlands)

    Brummelman, J.

    2016-01-01

    The introduction of whole-cell pertussis (wP) vaccines in the 1950s led to a massive decrease in pertussis incidence and mortality. However, since a few decades, resurgence of pertussis is observed in highly vaccinated populations. Several explanations have been proposed to underlie the resurgence o

  5. Improving pertussis vaccination: central role of CD4 T cell programming

    NARCIS (Netherlands)

    Brummelman, J.

    2016-01-01

    The introduction of whole-cell pertussis (wP) vaccines in the 1950s led to a massive decrease in pertussis incidence and mortality. However, since a few decades, resurgence of pertussis is observed in highly vaccinated populations. Several explanations have been proposed to underlie the resurgence

  6. Bordetella pertussis evolution in the (functional) genomics era.

    Science.gov (United States)

    Belcher, Thomas; Preston, Andrew

    2015-11-01

    The incidence of whooping cough caused by Bordetella pertussis in many developed countries has risen dramatically in recent years. This has been linked to the use of an acellular pertussis vaccine. In addition, it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape. Genomics-based approaches have revolutionized the ability to resolve the fine structure of the global B. pertussis population and its evolution during the era of vaccination. Here, we discuss the current picture of B. pertussis evolution and diversity in the light of the current resurgence, highlight import questions raised by recent studies in this area and discuss the role that functional genomics can play in addressing current knowledge gaps.

  7. Monospecific antibody against Bordetella pertussis Adenylate Cyclase protects from Pertussis

    Directory of Open Access Journals (Sweden)

    Yasmeen Faiz Kazi

    2012-06-01

    Full Text Available Objectives: Acellular pertussis vaccines has been largely accepted world-wide however, there are reports about limitedantibody response against these vaccines suggesting that multiple antigens should be included in acellular vaccinesto attain full protection. The aim of present study was to evaluate the role of Bordetella pertussis adenylate cyclase as aprotective antigen.Materials and methods: Highly mono-specific antibody against adenylate cyclase (AC was raised in rabbits usingnitrocellulose bound adenylate cyclase and the specificity was assessed by immuoblotting. B.pertussis 18-323, wasincubated with the mono-specific serum and without serum as a control. Mice were challenged intra-nasally and pathophysiolgicalresponses were recorded.Results: The production of B.pertussis adenylate cyclase monospecific antibody that successfully recognized on immunoblotand gave protection against fatality (p< 0.01 and lung consolidation (p <0.01. Mouse weight gain showedsignificant difference (p< 0.05.Conclusion: These preliminary results highlight the role of the B.pertussis adenylate cyclase as a potential pertussisvaccine candidate. B.pertussis AC exhibited significant protection against pertussis in murine model. J Microbiol InfectDis 2012; 2(2: 36-43Key words: Pertussis; monospecific; antibody; passive-protection

  8. Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth > For Parents > ... child outweigh the potential risks. Caring for Your Child After Immunization Your child may have a fever, soreness, and ...

  9. Adaptive immune response to whole cell pertussis vaccine reflects vaccine quality: A possible complementation to the Pertussis Serological Potency test.

    Science.gov (United States)

    Hoonakker, M E; Verhagen, L M; van der Maas, L; Metz, B; Uittenbogaard, J P; van de Waterbeemd, B; van Els, C A C M; van Eden, W; Hendriksen, C F M; Sloots, A; Han, W G H

    2016-08-17

    Whole cell Bordetella pertussis (wP) vaccines are still used in many countries to protect against the respiratory disease pertussis. The potency of whole-cell pertussis vaccine lots is determined by an intracerebral challenge test (the Kendrick test). This test is criticized due to lack of immunological relevance of the read-out after an intracerebral challenge with B. pertussis. The alternative in vivo test, which assesses specific antibody levels in serum after wP vaccination, is the Pertussis Serological Potency test (PSPT). Although the PSPT focuses on a parameter that contributes to protection, the protective immune mechanisms after wP vaccination includes more elements than specific antibody responses only. In this study, additional parameters were investigated, i.e. circulating pro-inflammatory cytokines, antibody specificity and T helper cell responses and it was evaluated whether they can be used as complementary readout parameters in the PSPT to assess wP lot quality. By deliberate manipulation of the vaccine preparation procedure, a panel of high, intermediate and low quality wP vaccines were made. The results revealed that these vaccines induced similar IL-6 and IP10 levels in serum 4h after vaccination (innate responses) and similar antibody levels directed against the entire bacterium. In contrast, the induced antibody specificity to distinct wP antigens differed after vaccination with high, intermediate and low quality wP vaccines. In addition, the magnitude of wP-induced Th cell responses (Th17, Th1 and Th2) was reduced after vaccination with a wP vaccine of low quality. T cell responses and antibody specificity are therefore correlates of qualitative differences in the investigated vaccines, while the current parameter of the PSPT alone was not sensitive enough to distinguish between vaccines of different qualities. This study demonstrates that assessment of the magnitude of Th cell responses and the antigen specificity of antibodies induced by w

  10. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): www. ... statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: June ...

  11. From pertussis to meningococcal disease and back.

    Science.gov (United States)

    Gorringe, Andrew

    2011-04-01

    From pertussis to meningococcal disease and back represents nearly 30 years of research at Porton, first at the Centre for Applied Microbiology and Research and latterly as part of the Health Protection Agency. I joined the group lead by Andy Robinson developing an acellular pertussis vaccine and was part of an exciting period that encompassed basic antigen characterisation and pathogenesis studies with the development of an acellular vaccine containing fimbriae. Research then changed to focus on serogroup B meningococcal disease, studying the vaccine potential of iron-regulated proteins and then Neisseria lactamica. The resurgence of pertussis seen in some countries alerted me to the lack of understanding of protective immune responses to Bordetella pertussis infection and disease and this is now an active area of research.

  12. Bordetella pertussis, B. parapertussis, vaccines and cycles of whooping cough.

    Science.gov (United States)

    Bouchez, Valérie; Guiso, Nicole

    2015-10-01

    Whooping cough is a vaccine-preventable disease due to Bordetella pertussis and B. parapertussis. This highly contagious respiratory disease occurs through epidemic cycles every 3-5 years and vaccination did not change this frequency. Models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. However, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine pressure might also play an important role. These parameters are discussed in this review.

  13. [Development studies of lyophilized standard diphtheria-tetanus-pertussis vaccines].

    Science.gov (United States)

    Ozcengiz, Erkan; Unver, Derya; Cayan, H Hüseyin; Atakan Ablay, Pinar; Kanik, Esin

    2007-04-01

    In this study, diphtheria, tetanus and pertussis vaccine components were prepared as the formulations of diphtheria-tetanus-pertussis (DTP), diphtheria-tetanus (DT) for children, diphtheria-tetanus (Td) for adults, and tetanus toxoid (TT), respectively. Alhydrogel-adsorbed vaccines prepared to contain the stabilizing substances were lyophilized and the immunogenicity tests were carried out both in vivo and in vitro. The potencies of the tetanus component of the vaccines were obtained by the lethal challenge test in mice. The values were found as 144.86 IU/ml for lyophilized adsorbed (LA)-DTP, 116.5 IU/ml for LA-DT, 98.25 IU/ml for LA-Td and 96.2 IU/ml for LA-TT. Anti-tetanus IgG and anti-diphteria IgG levels determined by ELISA method were found high in the sera taken from the mice immunized with the above-mentioned vaccines. Anti-B.pertussis fimbria IgG antibody levels were also high by both ELISA and microagglutination tests. The test preparations were then compared to adsorbed liquid vaccines and it was shown that the components were quite stable in the lyophilized formulations. It was concluded that the formulations prepared in this study can be used as standard vaccines after being calibrated against World Health Organization standards.

  14. [Pertussis (Whooping cough)--an update].

    Science.gov (United States)

    Stock, Ingo

    2015-12-01

    Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy.

  15. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing;

    2010-01-01

    %. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  16. Modelling the return on investment of preventively vaccinating healthcare workers against pertussis

    NARCIS (Netherlands)

    Tariq, Luqman; Mangen, Marie-Josee J.; Hovels, Anke; Frijstein, Gerard; de Boer, Hero

    2015-01-01

    Background: Healthcare workers (HCWs) are at particular risk of acquiring pertussis and transmitting the infection to high-risk susceptible patients and colleagues. In this paper, the return on investment (ROI) of preventively vaccinating HCWs against pertussis to prevent nosocomial pertussis outbre

  17. Modelling the return on investment of preventively vaccinating healthcare workers against pertussis

    NARCIS (Netherlands)

    Tariq, Luqman; Mangen, Marie-Josee J.; Hovels, Anke; Frijstein, Gerard; de Boer, Hero

    2015-01-01

    Background: Healthcare workers (HCWs) are at particular risk of acquiring pertussis and transmitting the infection to high-risk susceptible patients and colleagues. In this paper, the return on investment (ROI) of preventively vaccinating HCWs against pertussis to prevent nosocomial pertussis

  18. Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations.

    Science.gov (United States)

    Launay, Odile; Toneatti, Christine; Bernède, Claire; Njamkepo, Elisabeth; Petitprez, Karine; Leblond, Annie; Larnaudie, Sylvie; Goujon, Catherine; Ungeheuer, Marie-Noelle; Ajana, Faïza; Raccurt, Christian; Beytout, Jean; Chidiac, Christian; Bouhour, Damien; Guillemot, Didier; Guiso, Nicole

    2009-05-01

    In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases--tetanus, diphtheria and pertussis--among 331 adults (aged 18-60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18-29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

  19. Attitudes, knowledge and perceptions towards whooping cough and pertussis vaccine in hospitalized adults.

    Science.gov (United States)

    Ridda, Iman; Gao, Zhanhai; Macintyre, C Raina

    2014-02-19

    Whooping cough or pertussis is a major cause of morbidity and mortality for adults and children around the world. There has been a rise in pertussis-related deaths in the elderly; pertussis vaccination is not currently routinely recommended in adults, excepting new parents and other adults household members including grandparents and care-givers of young children. Currently, there is lack of clear vaccine recommendations after the age of 50 years. Given the increase in adult pertussis, adult vaccine recommendations are a policy consideration. The study surveyed a convenience sample of patients previously recruited in a case control study designed to examine the burden of influenza with and without AMI in adults aged ≥ 40 years. Our findings showed that only 9.6% had received the pertussis vaccination within the past five years and 79.4% of participants had no knowledge of the pertussis adult booster vaccine, and 30.7% of participants who had regular contact with children under the age of two years in the past 12 months. The results showed that even though there is general acceptance of prevention by vaccines, there is low awareness about pertussis vaccination. This lack of knowledge presents a barrier against pertussis vaccination thus it is imperative that any future adult immunisation policy recommendations around pertussis vaccine include awareness programs in the target population.

  20. Diagnosis of pertussis in vaccinated children of Khairpur, Sindh, Pakistan by Cough Plate Method

    Directory of Open Access Journals (Sweden)

    Syed Habib Bukhari

    2011-09-01

    Full Text Available Objectives: Pertussis or whooping cough is a communicable infection of upper respiratory tract that mainly affects children. Reports regarding resurgence of pertussis in vaccinated children mainly motivated us to document pertussis in the children. The aim of the study was to explore pertussis in vaccinated children using an alternative method for pertussis diagnosis.Materials and methods: A total of 700 clinical samples were collected during study period (2006-2009, from suspected whooping cough cases of Diphtheria-tetanus- whole cell pertussis (DTwP vaccinated children both male and female aged from 6 months to 84 months The classical ‘Cough Plate Method’ instead of Nasopharyngeal Swab was used for sampling to find out its potential in diagnosis of pertussis.Results: Present study reports the presence of pertussis in vaccinated children using Cough Plate Method. The method successfully isolated Bordetella pertussis from suspected patients of pertussis. A total of 28 culture confirmed cases were detected among 700 samples tested. (Total Isolation rate: 4%.The peak incidence age under risk was 48 months. However, pertussis was detected in children aged as young as 6 and 12 months.Conclusion: The ‘Cough plate’ method used for isolation proved successful and simple instead of nasopharyngeal swabs that is difficult to perform and children may be reluctant to this sampling method when tried. J Microbiol Infect Dis 2011;1 (2 : 68-72

  1. Epidemiology of whooping cough & typing of Bordetella pertussis.

    Science.gov (United States)

    Hegerle, Nicolas; Guiso, Nicole

    2013-11-01

    Bordetella pertussis is a Gram-negative human-restricted bacterium that evolved from the broad-range mammalian pathogen, Bordetella bronchiseptica. It causes whooping cough or pertussis in humans, which is the most prevalent vaccine-preventable disease worldwide. The introduction of the pertussis whole-cell vaccination for young children, followed by the introduction of the pertussis acellular vaccination (along with booster vaccination) for older age groups, has affected the bacterial population and epidemiology of the disease. B. pertussis is relatively monomorphic worldwide, but nevertheless, different countries are facing different epidemiological evolutions of the disease. Although it is tempting to link vaccine-driven phenotypic and genotypic evolution of the bacterium to epidemiology, many other factors should be considered and surveillance needs to continue, in addition to studies investigating the impact of current clinical isolates on vaccine efficacy.

  2. Assessment of a mandatory tetanus, diphtheria, and pertussis vaccination requirement on vaccine uptake over time.

    Science.gov (United States)

    Weber, David J; Consoli, Stephanie A; Sickbert-Bennett, Emily; Rutala, William A

    2012-01-01

    Tetanus, diphtheria, and pertussis (Tdap) vaccine is recommended for all healthcare personnel who provide direct patient care unless medically contraindicated. Our university hospital made employment conditional upon receipt of Tdap vaccine. Implementation for newly hired employees quickly resulted in complete compliance, but achieving adherence among current workers required setting a termination date for noncompliance.

  3. Virulence of pertactin-negative Bordetella pertussis isolates from infants, France.

    Science.gov (United States)

    Bodilis, Hélène; Guiso, Nicole

    2013-03-01

    Bordetella pertussis isolates that do not express pertactin (PRN) are increasing in regions where acellular pertussis vaccines have been used for >7 years. We analyzed data from France and compared clinical symptoms among infants <6 months old infected by PRN-positive or PRN-negative isolates. No major clinical differences were found between the 2 groups.

  4. Desensitization with DTP (diphtheria, tetanus and pertussis vaccine

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2003-01-01

    Full Text Available Immunization with DTP vaccine (diphtheria, tetanus and pertussis is a part of the vaccination calendar offered in childhood. Adverse allergic reactions vary from minimal urticarial reactions to life-threatening anaphylaxis. In infancy these reactions usually interrupt the vaccination calendar, but immunization in these children should be done. At the University Children's Hospital of Belgrade, a group of 137 children with suspected allergic anaphylactic reaction to DTP, DT, TT and monopertussis vaccine was studied for the last six years. Skin (prick and intradermal tests were performed with corresponding vaccine. If both tests were negative, the vaccine could be given as a single dose of 0.5 ml. If one of these tests were positive desensitization with vaccine could be done (according to the protocol described by Carey and Meltzer. In one group of 52 children three days before desensitization, premedication with antihistamines, was done, whereas in the other group of 52 children premedication was not done. Two (3.8% children in a group of 52 children with premedication had a minor (local reaction after vaccination and 50 children (96.2% had no reaction after vaccination, whereas no children (0% had systemic reaction after desensitization.

  5. A Proteomic Characterization of Bordetella pertussis Clinical Isolates Associated with a California State Pertussis Outbreak

    Directory of Open Access Journals (Sweden)

    Yulanda M. Williamson

    2015-01-01

    Full Text Available Bordetella pertussis (Bp is the etiologic agent of pertussis (whooping cough, a highly communicable infection. Although pertussis is vaccine preventable, in recent years there has been increased incidence, despite high vaccine coverage. Possible reasons for the rise in cases include the following: Bp strain adaptation, waning vaccine immunity, increased surveillance, and improved clinical diagnostics. A pertussis outbreak impacted California (USA in 2010; children and preadolescents were the most affected but the burden of disease fell mainly on infants. To identify protein biomarkers associated with this pertussis outbreak, we report a whole cellular protein characterization of six Bp isolates plus the pertussis acellular vaccine strain Bp Tohama I (T, utilizing gel-free proteomics-based mass spectrometry (MS. MS/MS tryptic peptide detection and protein database searching combined with western blot analysis revealed three Bp isolates in this study had markedly reduced detection of pertactin (Prn, a subunit of pertussis acellular vaccines. Additionally, antibody affinity capture technologies were implemented using anti-Bp T rabbit polyclonal antisera and whole cellular proteins to identify putative immunogens. Proteome profiling could shed light on pathogenesis and potentially lay the foundation for reduced infection transmission strategies and improved clinical diagnostics.

  6. Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia.

    Science.gov (United States)

    Lam, Connie; Octavia, Sophie; Ricafort, Lawrence; Sintchenko, Vitali; Gilbert, Gwendolyn L; Wood, Nicholas; McIntyre, Peter; Marshall, Helen; Guiso, Nicole; Keil, Anthony D; Lawrence, Andrew; Robson, Jenny; Hogg, Geoff; Lan, Ruiting

    2014-04-01

    Acellular vaccines against Bordetella pertussis were introduced in Australia in 1997. By 2000, these vaccines had replaced whole-cell vaccines. During 2008-2012, a large outbreak of pertussis occurred. During this period, 30% (96/320) of B. pertussis isolates did not express the vaccine antigen pertactin (Prn). Multiple mechanisms of Prn inactivation were documented, including IS481 and IS1002 disruptions, a variation within a homopolymeric tract, and deletion of the prn gene. The mechanism of lack of expression of Prn in 16 (17%) isolates could not be determined at the sequence level. These findings suggest that B. pertussis not expressing Prn arose independently multiple times since 2008, rather than by expansion of a single Prn-negative clone. All but 1 isolate had ptxA1, prn2, and ptxP3, the alleles representative of currently circulating strains in Australia. This pattern is consistent with continuing evolution of B. pertussis in response to vaccine selection pressure.

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

    Science.gov (United States)

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

    2008-08-18

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

  8. Immunoproteomic analysis of human serological antibody responses to vaccination with whole-cell pertussis vaccine (WCV.

    Directory of Open Access Journals (Sweden)

    Yong-Zhang Zhu

    Full Text Available BACKGROUND: Pertussis (whooping cough caused by Bordetella pertussis (B.p, continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE, immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight

  9. The effect of pertussis toxin and whole-cell pertussis vaccine on haemodynamics and autonomic responsiveness in the rat depends on route of administration and age.

    Science.gov (United States)

    van Amsterdam, J G; te Biesebeek, J D; van de Kuil, T; van der Laan, J W; Wemer, J; de Wildt, D J; Vleeming, W

    1998-04-01

    Vaccination of children with Diphtheria, Tetanus, Poliomyelitis and pertussis vaccine (DTPoP-vaccine) containing the whole-cell pertussis component is known to be associated with manifestation of side-effects such as acute encephalopathy, convulsions and hypotensive-hyporesponsive episodes. In young and adult rats the effects of pertussis toxin and DTPoP-vaccine on haemodynamics and autonomic responsiveness are evaluated following treatment with high dose via different routes of administration (s.c., i.p. and i.v.). The effect of pertussis toxin is dose-dependent (between 1 and 20 micrograms kg-1) and largest responses are observed after i.v. administration. At 20 micrograms kg-1, i.v. pertussis toxin decreases baseline diastolic blood pressure and increases baseline heart rate by 31% and inhibits autonomic responsiveness (salbutamol-induced increase in diastolic blood pressure and arecoline-induced decrease in heart rate). In adult rats DTPoP-vaccine induces generally more prominent effects than in young rats. In adult rats DTPoP-vaccine reduces baseline diastolic blood pressure by 25% while no response is observed in young rats. In adult rats DTPoP inhibits the adrenergic response though less compared to treatment of pertussis toxin. After treatment with DTPoP-vaccine (single or twice) only minor differences are observed between young and adult rats. Present results show that adult rats are more sensitive to pertussis toxin and pertussis vaccine than young rats and that the responses depend on the route of administration.

  10. Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

    Science.gov (United States)

    van Twillert, Inonge; Bonačić Marinović, Axel A.; Kuipers, Betsy; van Gaans-van den Brink, Jacqueline A. M.; Sanders, Elisabeth A. M.; van Els, Cécile A. C. M.

    2017-01-01

    Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality. PMID:28091579

  11. Protecting newborns from pertussis: The role of partner vaccination in the era of maternal immunization.

    Science.gov (United States)

    Krishnaswamy, Sushena; Wallace, Euan M; Cheng, Allen C; Buttery, Jim; Giles, Michelle L

    2017-07-25

    While antenatal vaccination is the most effective strategy to reduce newborn pertussis infection and its associated morbidity and mortality, uptake has consistently been reported to be suboptimal. "Cocooning" or vaccination of the close contacts of newborns therefore remains an important strategy for protecting newborns when maternal vaccination has not occurred or with insufficient time for antibody transfer. This study assesses the uptake of pertussis vaccination by parents and close contacts of newborns providing insight into the vulnerability of newborns to pertussis upon discharge from hospital to their primary carers. The study was conducted at three public and two private hospitals in Melbourne, Australia. A survey was administered to 689 women and/or their partners admitted on maternity wards of participating hospitals after delivery of a healthy newborn between August and December 2016. The main outcomes measured were reported vaccination rates and factors associated with uptake of pertussis vaccination. Kappa statistic and logistic regression were used to determine factors associated with vaccination. 70% of women and 66% of partners reported pertussis vaccination according to national recommendations. Significantly 22% of newborns were discharged to a household where neither parent reported vaccination. Compared to when maternal vaccination did occur, in families where it didn't there were low rates of vaccination of partners (83% vs 26%) and other carers, particularly carers usually resident overseas (76% vs 18.5%). While the majority of mothers and partners reported pertussis vaccination in accordance with recommended guidelines, concerningly nearly a quarter of newborns were discharged to a home where neither parent was vaccinated. When maternal vaccination did not occur, rates of vaccination of the other close contacts was poor. Educating women to encourage vaccination of partners and carers particularly those coming from overseas, prior to their

  12. Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand.

    Science.gov (United States)

    Blackwood, Julie C; Cummings, Derek A T; Broutin, Hélène; Iamsirithaworn, Sopon; Rohani, Pejman

    2013-06-01

    Pertussis is a highly infectious respiratory disease that is currently responsible for nearly 300,000 annual deaths worldwide, primarily in infants in developing countries. Despite sustained high vaccine uptake, a resurgence in pertussis incidence has been reported in a number of countries. This resurgence has led to critical questions regarding the transmission impacts of vaccination and pertussis immunology. We analyzed pertussis incidence in Thailand--both age-stratified and longitudinal aggregate reports--over the past 30 y. To dissect the contributions of waning pertussis immunity and repeat infections to pertussis epidemiology in Thailand following a pronounced increase in vaccine uptake, we used likelihood-based statistical inference methods to evaluate the support for multiple competing transmission models. We found that, in contrast to other settings, there is no evidence for pertussis resurgence in Thailand, with each model examined pointing to a substantial rise in herd immunity over the past 30 y. Using a variety of empirical metrics, we verified our findings by documenting signatures of changing herd immunity over the study period. Importantly, this work leads to the conclusion that repeat infections have played little role in shaping pertussis epidemiology in Thailand. Our results are surprisingly emphatic in support of measurable impact of herd immunity given the uncertainty associated with pertussis epidemiology.

  13. Global population structure and evolution of Bordetella pertussis and their relationship with vaccination

    NARCIS (Netherlands)

    Bart, M.J.; Harris, S.R.; Advani, A.; Arakawa, Y.; Bottero, D.; Bouchez, V.; Cassiday, P.K.; Chiang, C.S.; Dalby, T.; Fry, N.K.; Gaillard, M.E.; Gent, M. van; Guiso, N.; Hallander, H.O.; Harvill, E.T.; He, Q.; Heide, H.G. van der; Heuvelman, K.; Hozbor, D.F.; Kamachi, K.; Karataev, G.I.; Lan, R.; Lutylska, A.; Maharjan, R.P.; Mertsola, J.; Miyamura, T.; Octavia, S.; Preston, A.; Quail, M.A.; Sintchenko, V.; Stefanelli, P.; Tondella, M.L.; Tsang, R.S.; Xu, Y.; Yao, S.M.; Zhang, S.; Parkhill, J.; Mooi, F.R.

    2014-01-01

    Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-ce

  14. Strain variation among Bordetella pertussis isolates in finland, where the whole-cell pertussis vaccine has been used for 50 years.

    Science.gov (United States)

    Elomaa, Annika; Advani, Abdolreza; Donnelly, Declan; Antila, Mia; Mertsola, Jussi; Hallander, Hans; He, Qiushui

    2005-08-01

    Pertussis is an infectious disease of the respiratory tract caused by Bordetella pertussis. Despite the introduction of mass vaccination against pertussis in Finland in 1952, pertussis has remained an endemic disease with regular epidemics. To monitor changes in the Finnish B. pertussis population, 101 isolates selected from 1991 to 2003 and 21 isolates selected from 1953 to 1982 were studied together with two Finnish vaccine strains. The analyses included serotyping of fimbriae (Fim), genotyping of the pertussis toxin S1 subunit (ptxA) and pertactin (prn), and pulsed-field gel electrophoresis (PFGE) after digestion of B. pertussis genomic DNA with XbaI restriction enzyme. Strains isolated before 1977 were found to harbor the same ptxA as the strains used in the Finnish whole-cell pertussis vaccine, and strains isolated before 1982 harbored the same prn as the strains used in the Finnish whole-cell pertussis vaccine. All recent isolates, however, represented genotypes distinct from those of the two vaccine strains. A marked shift of predominant serotype from Fim serotype 2 (Fim2) to Fim3 has been observed since the late 1990s. Temporal changes were seen in the genome of B. pertussis by PFGE analysis. Three PFGE profiles (BpSR1, BpSR11, and BpSR147) were distinguished by their prevalence between 1991 and 2003. The yearly emergence of the three profiles was distributed periodically. Our study stresses the importance of the continuous monitoring of emerging strains of B. pertussis and the need to obtain a better understanding of the relationship of the evolution of B. pertussis in vaccinated populations.

  15. Strain Variation among Bordetella pertussis Isolates in Finland, Where the Whole-Cell Pertussis Vaccine Has Been Used for 50 Years

    Science.gov (United States)

    Elomaa, Annika; Advani, Abdolreza; Donnelly, Declan; Antila, Mia; Mertsola, Jussi; Hallander, Hans; He, Qiushui

    2005-01-01

    Pertussis is an infectious disease of the respiratory tract caused by Bordetella pertussis. Despite the introduction of mass vaccination against pertussis in Finland in 1952, pertussis has remained an endemic disease with regular epidemics. To monitor changes in the Finnish B. pertussis population, 101 isolates selected from 1991 to 2003 and 21 isolates selected from 1953 to 1982 were studied together with two Finnish vaccine strains. The analyses included serotyping of fimbriae (Fim), genotyping of the pertussis toxin S1 subunit (ptxA) and pertactin (prn), and pulsed-field gel electrophoresis (PFGE) after digestion of B. pertussis genomic DNA with XbaI restriction enzyme. Strains isolated before 1977 were found to harbor the same ptxA as the strains used in the Finnish whole-cell pertussis vaccine, and strains isolated before 1982 harbored the same prn as the strains used in the Finnish whole-cell pertussis vaccine. All recent isolates, however, represented genotypes distinct from those of the two vaccine strains. A marked shift of predominant serotype from Fim serotype 2 (Fim2) to Fim3 has been observed since the late 1990s. Temporal changes were seen in the genome of B. pertussis by PFGE analysis. Three PFGE profiles (BpSR1, BpSR11, and BpSR147) were distinguished by their prevalence between 1991 and 2003. The yearly emergence of the three profiles was distributed periodically. Our study stresses the importance of the continuous monitoring of emerging strains of B. pertussis and the need to obtain a better understanding of the relationship of the evolution of B. pertussis in vaccinated populations. PMID:16081896

  16. Sequence Variation of the Pertussis Toxin S1 Subunit Encoding Gene in the Clinical Isolates of Bordetella pertussis in Iran

    Directory of Open Access Journals (Sweden)

    Hosseinpour

    2015-08-01

    Full Text Available Background Whooping cough (pertussis is an acute respiratory disease caused by Bordetella pertussis (B. pertussis. Pertussis toxin is an important virulence factor of B. pertussis and plays a major role in the immune and inflammatory responses. Likewise, allelic variations in the genes of virulence factors have led to the non-responsiveness of the new strains to both whole-cell and acellular vaccines. Given the importance of pertussis vaccine, we sought to address the lack of fundamental studies on the polymorphisms of the virulence genes of B. pertussis in Iran. Objectives The aim of this study was to identify the polymorphisms of the pertussis toxin S1 subunit (ptxS1 gene in the circulating strains and compare them to the vaccine strain. Patients and Methods In this study, 50 strains of B. pertussis isolated from patients with pertussis were investigated in the pertussis reference laboratory of Pasteur institute of Iran. Cultivation, biochemical tests, and the specific antisera were used to confirm B. pertussis. The sequencing of the polymerase chain reaction products was performed to determine the ptxS1 alleles, and B. pertussis 134 was studied as the vaccine strain. Results The results showed that all the strains had the dominant allele ptxS1A. There were differences between the alleles of the clinical strains and the vaccine strain. Conclusions In recent years, a significant increase in the incidence of pertussis has been reported worldwide. Our findings regarding the allelic shift of the ptxS1 gene are similar to those reported in many European and American countries showing the difference of the dominant allele of ptxS1 between the circulating isolates and the vaccine strains.

  17. [Present status of vaccines in 1989].

    Science.gov (United States)

    Roussey, M; Dabadie, A

    1989-01-01

    The authors describe 2 new vaccines now available in France: one is the GenHevac, an hepatitis B vaccine, the first virus recombinant vaccine; the other one is the Typhim Vi, a polysaccharide typhoid vaccine. Three other vaccines are currently used in foreign countries and will be soon available: the Hemophilus influenzae vaccine, the acellular pertussis vaccine and the varicella vaccine. Rotavirus and Cytomegalovirus vaccines are studied for their clinical efficacy.

  18. The WHO Review of the Possible Nonspecific Effects of Diphtheria-Tetanus-Pertussis Vaccine

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Benn, Christine S

    2016-01-01

    BACKGROUND: World Health Organization recently reviewed the possible nonspecific effects of diphtheria-tetanus-pertussis (DTP) vaccine. The results were considered inconsistent though most studies suggested deleterious effects. We examined whether inconsistencies in results reflected differences...

  19. Vaccine independence, local competences and globalisation: lessons from the history of pertussis vaccines.

    Science.gov (United States)

    Blume, Stuart; Zanders, Mariska

    2006-10-01

    In the context of global vaccine politics 'vaccine independence' has been defined as the assumption of financial responsibility for vaccine procurement. This paper suggests 'the possibility of vaccine choice' as an alternative meaning for the term. How far does local competence in vaccine development and production provide that possibility? Coupled to the national vaccination programme, such competence enabled the Netherlands to make use of a polio vaccine (Inactivated Polio Vaccine, or IPV) that it was felt best met national needs even though the rest of the world had switched to the alternative attenuated vaccine (generally known as Oral Polio Vaccine, or OPV); by the 1970s IPV was no longer commercially available. Over the past 20 years major changes in vaccine politics have occurred. Does the earlier conclusion regarding local competence still hold? The more recent example of pertussis (or whooping cough) vaccines, where again controversy surrounds the relative merits of alternative vaccines, permits the question to be posed anew. Results of our analysis from the Netherlands suggest, first, that the pressure to conform has become greater, and second, that the taken-for-granted globalism of today's vaccine system is in need of critical examination.

  20. Side-effects of pertussis toxin, pertussis vaccines and haemoinfluenza type B vaccine

    NARCIS (Netherlands)

    van Amsterdam JGC; te Biesebeek JD; van de Kuil A; Vleeming W; van der Laan JW; Spruyt B; Wemer J; de Wildt DJ; LEO; LGM

    1997-01-01

    Doel van de studie is de bijwerkingen van vaccins nader te bestuderen ter onderbouwing van voor te stellen richtlijnen. Bedoelde richtlijnen stellen eisen aan het verrichten van pre-klinische veiligheids-farmacologie van vaccins. Dit rapport beschrijft de cardiovasculaire en autonome effecten, die

  1. Side-effects of pertussis toxin, pertussis vaccines and haemoinfluenza type B vaccine

    NARCIS (Netherlands)

    van Amsterdam JGC; te Biesebeek JD; van de Kuil A; Vleeming W; van der Laan JW; Spruyt B; Wemer J; de Wildt DJ; LEO; LGM

    1997-01-01

    Doel van de studie is de bijwerkingen van vaccins nader te bestuderen ter onderbouwing van voor te stellen richtlijnen. Bedoelde richtlijnen stellen eisen aan het verrichten van pre-klinische veiligheids-farmacologie van vaccins. Dit rapport beschrijft de cardiovasculaire en autonome effecten, die

  2. Cross-sectional study on factors associated with influenza vaccine uptake and pertussis vaccination status among pregnant women in Germany.

    Science.gov (United States)

    Bödeker, Birte; Walter, Dietmar; Reiter, Sabine; Wichmann, Ole

    2014-07-16

    Pregnant women and their newborns are at increased risk for influenza-related complications; the latter also have an increased risk for pertussis-related complications. In Germany, seasonal influenza vaccination is recommended for pregnant women since 2010. A dose of pertussis-containing vaccine has been recommended since 2004 for women of childbearing age if they have not been vaccinated within the past 10 years. We conducted a nationwide cross-sectional survey among pregnant women in February/March 2013 to assess knowledge, attitudes, and practices related to influenza vaccination during pregnancy and to identify factors associated with their pertussis vaccination status. In total, 1025 pregnant women participated and provided information through a self-administered questionnaire. Of these, 23.2% were vaccinated against seasonal influenza during the 2012/13 season; 15.9% during their pregnancy. Major reasons for being unvaccinated (n=686 respondents) were lack of confidence in the vaccine (60.4%) and the perception that vaccination was not necessary (40.3%). Influenza vaccination during pregnancy was independently associated with having received influenza vaccine in the previous season, having received a recommendation from a physician, a high level of vaccine-related knowledge and of perceived disease severity. In contrast, knowledge of the recommendation for regular hand-washing to prevent influenza and the perception that vaccine-related side effects were likely to occur or likely to be severe were negatively associated with vaccine uptake. Receipt of a pertussis vaccine in the past 10 years was reported by 22.5% of participants. Pertussis vaccine uptake was independently associated with living in the Eastern federal states and receiving seasonal influenza vaccination annually, while a migration background was associated with a lower uptake. To enhance vaccine uptake in pregnant women and women of childbearing age, special efforts must be undertaken to improve

  3. Lower risk of atopic disorders in whole cell pertussis-vaccinated children

    NARCIS (Netherlands)

    R.M.D. Bernsen (Roos); J.C. de Jongste (Johan); J.C. van der Wouden (Hans)

    2003-01-01

    textabstractThis study addressed whether whole cell pertussis-vaccinated children have a different risk of atopic disorders compared with children who did not receive this vaccination. Data on vaccination status, atopic disorders and child and family characteristics of the children

  4. Control of pertussis in the world.

    Science.gov (United States)

    Galazka, A

    1992-01-01

    Available data indicate that pertussis remains an important disease during infancy and childhood, particularly among those who are inadequately immunized. Over the past 15 years, successful immunization programmes have been implemented in most countries in the world. Some problems have arisen in the industrialized world where pertussis had been well controlled previously. The underlying causes of these problems are apathy and complacency on the part of physicians and parents, negative attitudes to immunization spread by anti-immunization pressure groups and litigation over liability for alleged vaccine-related injures. In developing countries, immunization coverage with primary series of three doses of DPT vaccine in infants exceeds 80%, but there are considerable differences in coverage rates between regions and between and within countries. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak management of immunization services, missing opportunities to immunize eligible children and ineffective information and motivation of mothers to return to complete the immunization series. To effectively control pertussis in the world, all countries should use available pertussis vaccines in immunization programmes for children. Since acellular pertussis vaccines are not generally available, the widespread use of DPT vaccine containing the whole-cell pertussis component should be continued. All efforts should be directed to increase or maintain high immunization coverage with DPT immunization at the level of at least 90% in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and ideally, pertussis should be a reportable disease. More information on the present epidemiological pattern of pertussis, especially age distribution of pertussis cases in developing countries, is needed to develop the policy of booster doses of DPT vaccine in children > 1 year.

  5. [Pertussis in fully vaccinated infants and children. Are new vaccination strategies required?].

    Science.gov (United States)

    Moraga-Llop, Fernando A; Mendoza-Palomar, Natàlia; Muntaner-Alonso, Antoni; Codina-Grau, Gemma; Fàbregas-Martori, Anna; Campins-Martí, Magda

    2014-04-01

    To analyse the vaccination status of children diagnosed with pertussis and to compare the clinical manifestations of fully vaccinated with unvaccinated, or incompletely-vaccinated, children. The clinical histories and vaccination cards of patients under 16years of age seen in the Emergency Room of the University Hospital Vall d'Hebron, Barcelona (Spain), for pertussis confirmed by a microbiological study were reviewed. The study period lasted from January 1, 2009 to December 31, 2011. Two hundred and twelve cases were studied: 35 in 2009, 28 in 2010 and 149 in 2011. RT-PCR was positive in 210 patients, and 73 had a positive culture. Infants under 6months of age account for 36.8% of all cases. Forty-four patients (21.5%) were not vaccinated. Forty-four (21.5%) children were between 2 and 5months of age and had received 1-2vaccine doses. One hundred and seventeen (57%) children were fully vaccinated; 76.9% (90cases) had received the last dose less than 4years ago. When clinical manifestations of the fully vaccinated patients were compared with those of the non-vaccinated or incompletely-vaccinated children, only cyanosis was found with a higher frequency in the latter group (P<.001). The age-adjusted probability of hospitalisation was significantly associated with non-vaccination (P=.001). The case mortality rate among inpatients was 1.3%. The number of pertussis cases seen in our centre has risen significantly in the last year. More than half (57%) of the patients were fully vaccinated, and 76.9% had received the last dose in the previous 4years. Other vaccination strategies, such as vaccination of adolescents, adults, and pregnant women, as well as a cocoon strategy are required to protect infants under 6months of age. More effective vaccines need to be developed. Copyright © 2012 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Relative Stability of Pertussis Vaccine Preserved with Merthiolate, Benzethonium Chloride, or the Parabens1

    Science.gov (United States)

    Gardner, Roberta A.; Pittman, Margaret

    1965-01-01

    When stored at 4 C, or heated at 22 or 35 C followed by storage at 4 C, the potency of pertussis vaccines preserved with Merthiolate was more stable than the potency of vaccines preserved with benzethonium chloride or the parabens (methyl- and propyl-p-hydroxybenzoate). Without preservative, potency was more stable than in the presence of benzethonium chloride or the parabens, but less stable than when Merthiolate was present. The histamine-sensitizing factor of the vaccines likewise decreased with the loss of potency. The deleterious effect of benzethonium chloride and the absence of the stabilizing effect of Merthiolate were contributing factors, if not the sole cause, for the instability of pertussis vaccine in quadruple antigen vaccine (diphtheria and tetanus toxoids and pertussis and poliomyelitis vaccines). Images Fig. 2 PMID:14339263

  7. Tetanus, diphtheria, pertussis vaccination coverage before, during, and after pregnancy - 16 States and New York City, 2011.

    Science.gov (United States)

    Ahluwalia, Indu B; Ding, Helen; D'Angelo, Denise; Shealy, Kristen H; Singleton, James A; Liang, Jennifer; Rosenberg, Kenneth D

    2015-05-22

    In June 2011, the Advisory Committee on Immunizations Practices (ACIP) recommended 1 dose of a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy for women who had not received Tdap previously. Before 2011, Tdap was recommended for unvaccinated women either before pregnancy or postpartum. In October 2012, ACIP expanded the 2011 recommendation, advising pregnant women to be vaccinated with Tdap during each pregnancy to provide maternal antibodies for each infant. The optimal time for vaccination is at 27-36 weeks' gestation as recommended by ACIP. In response to ACIP's Tdap recommendation for pregnant women in 2011, CDC added a supplemental question to the Pregnancy Risk Assessment Monitoring System (PRAMS) survey to determine women's Tdap vaccination status before, during, or after their most recent delivery. This report describes overall and state-specific Tdap vaccination coverage around the time of pregnancy using data from 6,852 sampled women who delivered a live-born infant during September-December 2011 in one of 16 states or New York City (NYC). Among the 17 jurisdictions, the median percentage of women with live births who reported any Tdap vaccination was 55.7%, ranging from 38.2% in NYC to 76.6% in Nebraska. The median percentage who received Tdap before pregnancy was 13.9% (range = 7.7%-20.1%), during pregnancy was 9.8% (range = 3.8%-14.2%), and after delivery was 30.9% (range = 13.6%-46.5%). The PRAMS data indicate a wide variation in Tdap vaccination coverage among demographic groups, with generally higher postpartum coverage for non-Hispanic white women, those who started prenatal care in the first trimester, and those who had private health insurance coverage. This information can be used for promoting evidence-based strategies to communicate the importance of ACIP guidelines related to Tdap vaccination coverage to women and their prenatal care providers.

  8. Clinical and Epidemiological Features of Pertussis in Children at Incomplete Vaccination Coverage

    Directory of Open Access Journals (Sweden)

    A.I. Bobrovitskaia

    2015-04-01

    Conclusions. Stabilization of the epidemic situation with pertussis has been promoted by a number of preventive measures: a the development of legislative documents to improve the surveillance system; b monitoring of changes in serotypes of the pathogen; c improvement of laboratory diagnosis of diseases by introducing modern methods of research; d annual sufficient supply of regions with pertussis vaccines in accordance with the requests; e timely and complete vaccination coverage according to the annual plan of immunization; f professional training of primary health care practitioners. Prevention of involvement in the epidemic process of young children and schoolchildren is possible by maintaining stable high immunization coverage of children in decreed terms by using an effective vaccine, availability of affordable and informative methods of immunity evaluation, as well as a reliable bacteriological diagnosis of pertussis. Currently, along with increased coverage of routine vaccination, surveillance of this infection is particularly important, which enables to carry out antiepidemic measures in the form of early diagnosis of pertussis in exposed children. In modern conditions, the classic symptoms of the disease still remain in vaccinated and unvaccinated children, but there are differences in the severity of pertussis in children with poor premorbid background. Diagnosis of pertussis, especially among infants, remains a challenge for practical public health.

  9. Differences in the genomic content of Bordetella pertussis isolates before and after introduction of pertussis vaccines in four European countries.

    Science.gov (United States)

    Kallonen, Teemu; Gröndahl-Yli-Hannuksela, Kirsi; Elomaa, Annika; Lutyńska, Anna; Fry, Norman K; Mertsola, Jussi; He, Qiushui

    2011-12-01

    Resurgence of pertussis has been observed in many countries with high vaccination coverage and clonal expansion of certain Bordetella pertussis strains has been associated with recent epidemics in Europe. It is known that vaccinations have selected strains which are different from those used for vaccine production. However, little is known about the differences in genomic content of strains circulating before the vaccination was introduced. In this study, we compared the genomes of 39 vaccine strains and old clinical isolates (isolated 1941-1984) collected from Finland (n = 5), Poland (n = 14), Serbia (n = 10) and the UK (n = 10). The analysis included genotyping, pulsed-field gel electrophoresis (PFGE) and comparative genomic hybridisation (CGH). Compared to the strain Tohama I, the European isolates analyzed have lost three major regions of difference (RD3, 5 and 29). However, difference in frequency of the absent RDs 3 (BP0910A-BP0934), 5 (BP1135-BP1141) or 29 (BP1225) was observed among isolates from the four countries. Of the isolates with absent RD5, half had also a duplicated region in the genome. All four RDs (RD22 (BB0535-BB0541), 23 (BB0916-BB0921), 24 (BB1140-BB1158) and 26 (BB4880-BB4888)) absent in Tohama I were present in majority of the tested isolates. Results obtained from PFGE analysis correlated well with those of CGH. Recently a novel pertussis toxin promoter allele (ptxP3) was described. Isolates with ptxP3 have replaced resident ptxP1 isolates in the countries where this was investigated. When the recent isolates, collected in 2000-2004, selected from the four countries were examined, the ptxP3 allele was found in all countries except Poland. Our result indicates that at least three clusters of B. pertussis circulated in Europe in pre- and early vaccine era and their genomes were distinct from that of the reference strain Tohama I. Although progressive gene loss occurs in B. pertussis population with time, difference in frequency of the lost

  10. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing

    2010-01-01

    We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children...... had received three doses of vaccine. PT IgA responders did not have significantly longer coughing episodes than PT IgA non-responders. Since an IgA antibody response occurs in only approximately 50% of infected children, the actual infection rate in our cohort is estimated to approximately 10......%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  11. [Acellular vaccines (DTPa/dTpa) against whooping cough, protection duration].

    Science.gov (United States)

    Rigo-Medrano, M Vicenta; Mendoza-García, José L; Gimeno-Gascón, Adelina; Roda-Ramón, Jorge; Cremades-Bernabeú, Israel; Antequera-Rodríguez, Pedro; Alcalá-Minagorre, Pedro J; Ortiz-de la Tabla, Victoria; Rodríguez-Díaz, Juan Carlos

    2016-01-01

    An increase in whooping cough in most of the developed countries has been detected in the last decade. To determine whether the administration of dTpa vaccine instead of DTPa fifth dose is contributing to the appearance of these cases. A descriptive study based on cases of whooping cough reported during an epidemic period in the city of Alicante in the first 5 months of 2014. Only pertussis cases confirmed by PCR were included in the study, and only those vaccinated with 5 doses were included in the analysis of the period of protection. A total of 104 cases of pertussis confirmed by PCR were reported, with 85 cases (82%) having had 5 doses of vaccine. The mean time and standard deviation (SD) of protection was 2.1±1.1 years with dTpa, and 5.1±1.5 years with DTPa (p<.001). In the protection, adjusted for age, it was observed that, after 3 years, only 47.6% of people vaccinated with dTpa were still protected, while people vaccinated with DTPa were 100% protected (P<.001). This study found that people who were properly vaccinated against pertussis and received their last re-vaccination dose with dTpa had a shorter period of protection than those who were vaccinated with DTPa. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: increased female mortality?

    Science.gov (United States)

    Benn, Christine Stabell; Aaby, Peter

    2012-10-01

    In low-income countries, children should receive 3 doses of diphtheria-tetanus-pertussis vaccine (DTP) at 6, 10 and 14 weeks of age, and measles vaccine at 9 months of age. However, there is often a delay in administering the vaccines, and DTP is often given after measles vaccine. Previous observations suggest that this practice is associated with increased mortality for female, but not for male children. Within a vitamin A trial in Guinea-Bissau, vaccination status was registered at the time of measles vaccination at 9 months; 141 (31%) of 455 children were missing 1 or more DTP vaccines and were likely to receive them afterward. We examined whether missing DTP vaccine at this time point was associated with sex-differential effects on mortality. In female children, missing DTP was associated with 3.55 (95% confidence interval: 1.23-10.26) times higher risk of dying before 36 months of age, whereas it made no difference in male children (0.97 [0.34-2.80]). The result supports that receiving DTP after measles vaccine affects female children negatively.

  13. Examining the role of different age groups, and of vaccination during the 2012 Minnesota pertussis outbreak.

    Science.gov (United States)

    Worby, Colin J; Kenyon, Cynthia; Lynfield, Ruth; Lipsitch, Marc; Goldstein, Edward

    2015-08-17

    There is limited information on the roles of different age groups during pertussis outbreaks. Little is known about vaccine effectiveness against pertussis infection (both clinically apparent and subclinical), which is different from effectiveness against reportable pertussis disease, with the former influencing the impact of vaccination on pertussis transmission in the community. For the 2012 pertussis outbreak in Minnesota, we estimated odds ratios for case counts in pairs of population groups before vs. after the epidemic's peak. We found children aged 11-12y, 13-14y and 8-10y experienced the greatest rates of depletion of susceptible individuals during the outbreak's ascent, with all ORs for each of those age groups vs. groups outside this age range significantly above 1, with the highest ORs for ages 11-12y. Receipt of the fifth dose of DTaP was associated with a decreased relative role during the outbreak's ascent compared to non-receipt [OR 0.16 (0.01, 0.84) for children aged 5, 0.13 (0.003, 0.82) for ages 8-10y, indicating a protective effect of DTaP against pertussis infection. No analogous effect of Tdap was detected. Our results suggest that children aged 8-14y played a key role in propagating this outbreak. The impact of immunization with Tdap on pertussis infection requires further investigation.

  14. Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis.

    Science.gov (United States)

    Xu, Yinghua; Liu, Bin; Gröndahl-Yli-Hannuksila, Kirsi; Tan, Yajun; Feng, Lu; Kallonen, Teemu; Wang, Lichan; Peng, Ding; He, Qiushui; Wang, Lei; Zhang, Shumin

    2015-08-18

    Herd immunity can potentially induce a change of circulating viruses. However, it remains largely unknown that how bacterial pathogens adapt to vaccination. In this study, Bordetella pertussis, the causative agent of whooping cough, was selected as an example to explore possible effect of vaccination on the bacterial pathogen. We sequenced and analysed the complete genomes of 40 B. pertussis strains from Finland and China, as well as 11 previously sequenced strains from the Netherlands, where different vaccination strategies have been used over the past 50 years. The results showed that the molecular clock moved at different rates in these countries and in distinct periods, which suggested that evolution of the B. pertussis population was closely associated with the country vaccination coverage. Comparative whole-genome analyses indicated that evolution in this human-restricted pathogen was mainly characterised by ongoing genetic shift and gene loss. Furthermore, 116 SNPs were specifically detected in currently circulating ptxP3-containing strains. The finding might explain the successful emergence of this lineage and its spread worldwide. Collectively, our results suggest that the immune pressure of vaccination is one major driving force for the evolution of B. pertussis, which facilitates further exploration of the pathogenicity of B. pertussis.

  15. Waning and aging of cellular immunity to Bordetella pertussis.

    Science.gov (United States)

    van Twillert, Inonge; Han, Wanda G H; van Els, Cécile A C M

    2015-11-01

    While it is clear that the maintenance of Bordetella pertussis-specific immunity evoked both after vaccination and infection is insufficient, it is unknown at which pace waning occurs and which threshold levels of sustained functional memory B and T cells are required to provide long-term protection. Longevity of human cellular immunity to B. pertussis has been studied less extensively than serology, but is suggested to be key for the observed differences between the duration of protection induced by acellular vaccination and whole cell vaccination or infection. The induction and maintenance of levels of protective memory B and T cells may alter with age, associated with changes of the immune system throughout life and with accumulating exposures to circulating B. pertussis or vaccine doses. This is relevant since pertussis affects all age groups. This review summarizes current knowledge on the waning patterns of human cellular immune responses to B. pertussis as addressed in diverse vaccination and infection settings and in various age groups. Knowledge on the effectiveness and flaws in human B. pertussis-specific cellular immunity ultimately will advance the improvement of pertussis vaccination strategies.

  16. Resurgence of pertussis at the age of vaccination: clinical, epidemiological, and molecular aspects

    Directory of Open Access Journals (Sweden)

    Rosângela S.L.A. Torres

    2015-08-01

    Full Text Available OBJECTIVE: Report the incidence, epidemiology, clinical features, death, and vaccination status of patients with whooping cough and perform genotypic characterization of isolates of B. pertussis identified in the state of Paraná, during January 2007 to December 2013.METHODS: Cross-sectional study including 1,209 patients with pertussis. Data were obtained through the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação - SINAN and molecular epidemiology was performed by repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab(r, bioMerieux, France.RESULTS: The incidence of pertussis in the state of Paraná increased sharply from 0.15-0.76 per 100,000 habitants between 2007-2010 to 1.7-4.28 per 100,000 between 2011-2013. Patients with less than 1 year of age were more stricken (67.5%. Fifty-nine children (5% developed pertussis even after receiving three doses and two diphtheria-tetanus-pertussis (DTP boosters vaccine. The most common complications were pneumonia (14.5%, otitis (0.9%, and encephalopathy (0.7%. Isolates of B. pertussis were grouped into two groups (G1 and G2 and eight distinct patterns (G1: P1-P5 and G2: P6-P8.CONCLUSION: The resurgence of pertussis should stimulate new research to develop vaccines with greater capacity of protection against current clones and also encourage implementation of new strategies for vaccination in order to reduce the risk of disease in infants.

  17. Using age-stratified incidence data to examine the transmission consequences of pertussis vaccination

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    J.C. Blackwood

    2016-09-01

    Full Text Available Pertussis is a highly infectious respiratory disease that has been on the rise in many countries worldwide over the past several years. The drivers of this increase in pertussis incidence remain hotly debated, with a central and long-standing hypothesis that questions the ability of vaccines to eliminate pertussis transmission rather than simply modulate the severity of disease. In this paper, we present age-structured case notification data from all provinces of Thailand between 1981 and 2014, a period during which vaccine uptake rose substantially, permitting an evaluation of the transmission impacts of vaccination. Our analyses demonstrate decreases in incidence across all ages with increased vaccine uptake – an observation that is at odds with pertussis case notification data in a number of other countries. To explore whether these observations are consistent with a rise in herd immunity and a reduction in bacterial transmission, we analyze an age-structured model that incorporates contrasting hypotheses concerning the immunological and transmission consequences of vaccines. Our results lead us to conclude that the most parsimonious explanation for the combined reduction in incidence and the shift to older age groups in the Thailand data is vaccine-induced herd immunity.

  18. Pertussis infections and vaccinations in Bolivia, Brazil and Mexico from 1980 to 2009.

    Science.gov (United States)

    McCormick, Colleen M; Czachor, John S

    2013-01-01

    Global coverage with three doses of the diphtheria, tetanus and pertussis vaccine (DTP3) increased from less than 5% in 1974 to 82% in 2009 due to worldwide focus on universal vaccination. Nonetheless, pertussis remains the fifth-leading cause of vaccine-preventable deaths. This study examines DTP3 vaccination from 1980 through 2009 in three countries within Latin America, Bolivia, Brazil and Mexico, selected for their distinct health care systems and vaccination strategies. Similar to global trends, these nations have achieved dramatic improvements in pertussis immunization. In Bolivia, immunization rates increased from 11% to 85%; in Brazil, rates increased from 37% to 97%; and in Mexico, the immunization rates increased from 44% to 72%. Pertussis infections have concomitantly decreased from 1980 to 2009. In Bolivia, cases decreased from 44.4 per 100,000 people to zero reported cases. In Brazil, the incidence decreased from 37.6 to 0.5 cases per 100,000. The incidence in Mexico decreased from 8.2 to 0.5 cases per 100,000. In order to increase vaccination rates further, health systems must continue to raise awareness about disease prevention, expand health surveillance systems, and improve access to health services. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

    Science.gov (United States)

    Tanriover, Mine Durusu; Soyler, Canan; Ascioglu, Sibel; Cankurtaran, Mustafa; Unal, Serhat

    2014-07-01

    Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital. Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values. A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis. We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of "lifelong vaccination" should be implemented and every encounter with the patient should be regarded as a chance for catch-up. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  20. B-cell responses after intranasal vaccination with the novel attenuated Bordetella pertussis vaccine strain BPZE1 in a randomized phase I clinical trial.

    Science.gov (United States)

    Jahnmatz, Maja; Amu, Sylvie; Ljungman, Margaretha; Wehlin, Lena; Chiodi, Francesca; Mielcarek, Nathalie; Locht, Camille; Thorstensson, Rigmor

    2014-06-05

    Despite high vaccination coverage, pertussis is still a global concern in infant morbidity and mortality, and improved pertussis vaccines are needed. A live attenuated Bordetella pertussis strain, named BPZE1, was designed as an intranasal vaccine candidate and has recently been tested in man in a phase I clinical trial. Here, we report the evaluation of the B-cell responses after vaccination with BPZE1. Forty-eight healthy males with no previous pertussis-vaccination were randomized into one of three dose-escalating groups or into a placebo group. Plasma blast- and memory B-cell responses were evaluated by ELISpot against three different pertussis antigens: pertussis toxin, filamentous haemagglutinin and pertactin. Seven out of the 36 subjects who had received the vaccine were colonized by BPZE1, and significant increases in the memory B-cell response were detected against all three tested antigens in the culture-positive subjects between days 0 and 28 post-vaccination. The culture-positive subjects also mounted a significant increase in the filamentous haemagglutinin-specific plasma blast response between days 7 and 14 post-vaccination. No response could be detected in the culture-negatives or in the placebo group post-vaccination. These data show that BPZE1 is immunogenic in humans and is therefore a promising candidate for a novel pertussis vaccine. This trial is registered at ClinicalTrials.gov (NCT01188512).

  1. Genomic content of Bordetella pertussis clinical isolates circulating in areas of intensive children vaccination.

    Directory of Open Access Journals (Sweden)

    Valérie Bouchez

    Full Text Available BACKGROUND: The objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the world where newborns and infants are highly vaccinated. METHODOLOGY: The analysis was performed using DNA microarray on 15 isolates, PCR on 111 isolates as well as GS-FLX sequencing technology on 3 isolates and the B. pertussis reference strain, Tohama I. PRINCIPAL FINDINGS: Our analyses demonstrate that the current circulating isolates are continuing to lose genetic material as compared to isolates circulating during the pre-vaccine era whatever the area of the world considered. The lost genetic material does not seem to be important for virulence. Our study confirms that the use of whole cell vaccines has led to the control of isolates that were similar to vaccine strains. GS-FLX sequencing technology shows that current isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era and that the sequenced strain Tohama I is not representative of the isolates. Furthermore, this technology allowed us to observe that the number of Insertion Sequence elements contained in the genome of the isolates is temporally increasing or varying between isolates. CONCLUSIONS: B. pertussis adaptation to humans is still in progress by losing genetic material via Insertion Sequence elements. Furthermore, recent isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era. Herd immunity, following intensive vaccination of infants and children with whole cell vaccines, has controlled isolates similar to the vaccine strains without modifying significantly the virulence of the isolates. With the replacement of whole cell vaccines by subunit vaccines, containing only few bacterial antigens targeting the virulence of the bacterium, one could hypothesize the circulation of isolates

  2. Immunization of teenagers with a fifth dose of reduced DTaP-IPV induces high levels of pertussis antibodies with a significant increase in opsonophagocytic activity.

    Science.gov (United States)

    Aase, Audun; Herstad, Tove Karin; Merino, Samuel; Bolstad, Merete; Sandbu, Synne; Bakke, Hilde; Aaberge, Ingeborg S

    2011-08-01

    Waning vaccine-induced immunity against Bordetella pertussis is observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir for B. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity against B. pertussis antigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to live B. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P antibodies against FHA and PRN contribute the most to the OPA and IgG binding.

  3. Modelling the impact of extended vaccination strategies on the epidemiology of pertussis

    NARCIS (Netherlands)

    Rozenbaum, M.H.; De Vries, R.; Le, H.H.; Postma, M.J.

    2012-01-01

    The aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the

  4. Pertussis booster vaccine for adolescents and young adults in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Angela Carvalho Freitas

    2011-12-01

    Full Text Available OBJECTIVE: To develop a model to assess different strategies of pertussis booster vaccination in the city of São Paulo. METHODS: A dynamic stationary age-dependent compartmental model with waning immunity was developed. The "Who Acquires Infection from Whom" matrix was used to modeling age-dependent transmission rates. There were tested different strategies including vaccine boosters to the current vaccination schedule and three of them were reported: (i 35% coverage at age 12, or (ii 70% coverage at age 12, and (iii 35% coverage at age 12 and 70% coverage at age 20 at the same time. RESULTS: The strategy (i achieved a 59% reduction of pertussis occurrence and a 53% reduction in infants while strategy (ii produced 76% and 63% reduction and strategy (iii 62% and 54%, respectively. CONCLUSION: Pertussis booster vaccination at age 12 proved to be the best strategy among those tested in this study as it achieves the highest overall reduction and the greatest impact among infants who are more susceptible to pertussis complications.

  5. Update on pertussis and pertussis immunization

    Directory of Open Access Journals (Sweden)

    Jung Yun Hong

    2010-05-01

    Full Text Available Pertussis is a highly contagious respiratory tract disease caused by Bordetella pertussis infection. The clinical manifestation of this infection can be severe enough to cause death. Although pertussis has been supposed to be a vaccine-preventable disease ever since the widespread vaccination of children against pertussis was started, since the 1990s, cases of pertussis and related fatalities are on the rise, especially in countries with high vaccination coverage. In Korea, there have been no deaths due to pertussis since 1990, and the vaccination rate continues to be approximately 94%. However, the number of pertussis cases reported to the Korea Center for Disease Control and Prevention has tended to increase in the 2000s, and in 2009, there was an obvious increase in the number of pertussis cases reported. This review aims to present the latest information about the pathogenesis, diagnosis, treatment, and prevention of pertussis.

  6. Attenuated Bordetella pertussis BPZE1 as a live vehicle for heterologous vaccine antigens delivery through the nasal route.

    Science.gov (United States)

    Li, Rui; Lim, Annabelle; Alonso, Sylvie

    2011-01-01

    Whereas the great majority of the current vaccines are delivered through the parenteral route, mucosal administration has been increasingly considered for controlling infection and preventing disease. Mucosal vaccination can trigger both humoral and cell-mediated protection, not only at the targeted mucosal surface, but also systemically. In this regard, nasal vaccination has shown great potential. The live attenuated strain of Bordetella pertussis, BPZE1, is particularly attractive and promising as a nasal vaccine delivery vector of heterologous antigen vaccine candidates. BPZE1 was originally developed as a live nasal pertussis vaccine candidate, and is currently undergoing phase I clinical trial in human (http://www.child-innovac.org). Highly adapted to the human respiratory tract and offering several potential protein carriers for presentation of the heterologous antigen vaccine candidates, BPZE1 represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious disease(s).

  7. Construction of Bordetella pertussis strains with enhanced production of genetically-inactivated Pertussis Toxin and Pertactin by unmarked allelic exchange

    Directory of Open Access Journals (Sweden)

    Buasri Wasin

    2012-04-01

    Full Text Available Abstract Background Acellular Pertussis vaccines against whooping cough caused by Bordetella pertussis present a much-improved safety profile compared to the original vaccine of killed whole cells. The principal antigen of acellular Pertussis vaccine, Pertussis Toxin (PT, must be chemically inactivated to obtain the corresponding toxoid (PTd. This process, however, results in extensive denaturation of the antigen. The development of acellular Pertussis vaccines containing PTd or recombinant PT (rPT with inactivated S1, Filamentous Hemagglutinin (FHA, and Pertactin (PRN has shown that the yield of PRN was limiting, whereas FHA was overproduced. To improve antigen yields and process economics, we have constructed strains of Bordetella pertussis that produce enhanced levels of both rPT and PRN. Results Three recombinant strains of Bordetella pertussis were obtained by homologous recombination using an allelic exchange vector, pSS4245. In the first construct, the segment encoding PT subunit S1 was replaced by two mutations (R9K and E129G that removed PT toxicity and Bp-WWC strain was obtained. In the second construct, a second copy of the whole cluster of PT structural genes containing the above mutations was inserted elsewhere into the chromosome of Bp-WWC and the Bp-WWD strain was obtained. This strain generated increased amounts of rPT (3.77 ± 0.53 μg/mL compared to Bp-WWC (2.61 ± 0.16 μg/mL and wild type strain (2.2 μg/mL. In the third construct, a second copy of the prn gene was inserted into the chromosome of Bp-WWD to obtain Bp-WWE. Strain Bp-WWE produced PRN at 4.18 ± 1.02 μg/mL in the cell extract which was about two-fold higher than Bp-WWC (2.48 ± 0.10 μg/mL and Bp-WWD (2.31 ± 0.17 μg/mL. Purified PTd from Bp-WWD at 0.8-1.6 μg/well did not show any toxicity against Chinese hamster ovary (CHO cell whereas purified PT from WT demonstrated a cell clustering endpoint at 2.6 pg/well. Conclusions We have constructed Bordetella

  8. Adult vaccination strategies for the control of pertussis in the United States: an economic evaluation including the dynamic population effects.

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    Laurent Coudeville

    Full Text Available BACKGROUND: Prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. Using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. METHODS: We assessed the impact of different pertussis vaccination strategies using a dynamic compartmental model able to consider pertussis transmission. We then combined the results with economic data to estimate the relative cost-effectiveness of pertussis immunization strategies for adolescents and adults in the US. The analysis compares combinations of programs targeting adolescents, parents of newborns (i.e. cocoon strategy, or adults of various ages. RESULTS: In the absence of adolescent or adult vaccination, pertussis incidence among adults is predicted to more than double in 20 years. Implementing an adult program in addition to childhood and adolescent vaccination either based on 1 a cocoon strategy and a single booster dose or 2 a decennial routine vaccination would maintain a low level of pertussis incidence in the long run for all age groups (respectively 30 and 20 cases per 100,000 person years. These strategies would also result in significant reductions of pertussis costs (between -77% and -80% including additional vaccination costs. The cocoon strategy complemented by a single booster dose is the most cost-effective one, whereas the decennial adult vaccination is slightly more effective in the long run. CONCLUSIONS: By providing a high level of disease control, the implementation of an adult vaccination program against pertussis appears to be highly cost-effective and often cost-saving.

  9. Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

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    Saliou Pierre

    2005-11-01

    Full Text Available Abstract Background Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi, stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP vaccines. Methods In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+ every two weeks for seven months or no chemoprophylaxis (CH-. After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05. The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05 and 77% and 91% for tetanus toxoid (P > 0.05. In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05. While analysis for pertussis showed a 43% (CH+ and 67% (CH- response (P Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

  10. Pertussis (Whooping Cough)

    Science.gov (United States)

    ... babies less than a year old. The best way to protect against pertussis is by getting vaccinated. English | en Español About Pertussis Causes and transmission, signs and symptoms, complications... Pertussis Vaccination Information on getting vaccinated, provider resources... Pregnancy and Whooping ...

  11. Comparison of lipopolysaccharide structures of Bordetella pertussis clinical isolates from pre- and post-vaccine era.

    Science.gov (United States)

    Albitar-Nehme, Sami; Basheer, Soorej M; Njamkepo, Elisabeth; Brisson, Jean-Robert; Guiso, Nicole; Caroff, Martine

    2013-08-30

    Endotoxins are lipopolysaccharides (LPS), and major constituents of the outer membrane of Gram-negative bacteria. Bordetella pertussis LPS were the only major antigens, of this agent of whooping-cough, that were not yet analyzed on isolates from the pre- and post-vaccination era. We compared here the LPS structures of four clinical isolates with that of the vaccine strain BP 1414. All physico-chemical analyses, including SDS-PAGE, TLC, and different MALDI mass spectrometry approaches were convergent. They helped demonstrating that, on the contrary to some other B. pertussis major antigens, no modification occurred in the dodecasaccharide core structure, as well as in the whole LPS molecules. These results are rendering these major antigens good potential vaccine components. Molecular modeling of this conserved LPS structure also confirmed the conclusions of previous experiments leading to the production of anti-LPS monoclonal antibodies and defining the main epitopes of these major antigens.

  12. Cost-effectiveness of Tdap vaccination of adults aged ≥65 years in the prevention of pertussis in the US: a dynamic model of disease transmission.

    Directory of Open Access Journals (Sweden)

    Lisa J McGarry

    Full Text Available OBJECTIVES: In February 2012, the Advisory Committee on Immunization Practices (ACIP advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap, expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to "baseline" practice [full-strength DTaP administered from 2 months to 4-6 years, and one dose of Tdap at 11-64 years replacing decennial Td booster], using a dynamic model. METHODS: We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care and quality-adjusted life-years (QALYs associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. RESULTS: For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective and $44.8 million (payer perspective. From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs versus baseline. Results are robust to sensitivity analyses and alternative

  13. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB).

    Science.gov (United States)

    Bar-On, Edna S; Goldberg, Elad; Hellmann, Sarah; Leibovici, Leonard

    2012-04-18

    doses differed significantly between the studies. Heterogeneous interventions, study location, healthcare environment and combining research across disparate geographical locations, may have lead to bias. The risk of bias was unclear across most of the included studies. Comparisons found little heterogeneity. In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and hepatitis B. Serious adverse events were comparable with mainly hospitalisation and acute bronchiolitis cases. Minor adverse events such as pain and redness were more common in children given the combined vaccine. Overall, the direction shown by the results is in favour of the DTPw (diptheria-tetanus-whole cell pertussis)-HBV-HIB vaccine rather than the DTPa (diptheria-tetanus-acellular pertussis)-HBV-HIB vaccine when compared to the separate vaccines (size of effect: risk ratio (RR) 1.43; 95% confidence interval (CI) 0.98 to 2.10, for 5269 participants). We could not conclude that the immune responses elicited by the combined vaccine were different from or equivalent to the separate vaccines. There was significantly less immunological response for HIB and tetanus and more local reactions in the combined injections. However, these differences rely mostly on one study each. Studies did not use an intention-to-treat (ITT) analysis and we were uncertain about the risk of bias in many of the studies. These results are therefore inconclusive. Studies addressing clinical end points whenever possible, using correct methodology and a large enough sample size should be conducted.

  14. Comparison of five commercial enzyme-linked immunosorbent assays for detection of antibodies to Bordetella pertussis.

    Science.gov (United States)

    Kösters, K; Riffelmann, M; Dohrn, B; von König, C H

    2000-05-01

    Measuring antibodies to Bordetella pertussis antigens is mostly done by enzyme-linked immunosorbent assays (ELISAs). We compared the performance of five commercially available ELISA kits with the help of 65 serum specimens which were repetitively tested for evaluation of the kits. The specimens contained 20 paired serum samples from patients with clinical pertussis, 15 samples were from children vaccinated with a diphtheria-tetanus-acellular pertussis vaccine, seven specimens were taken from an interlaboratory comparison of ELISAs, and there were three reference preparations from the Food and Drug Administration's (FDA's) Laboratory of Pertussis and from our laboratory. Reference values were obtained from the FDA or from results obtained with an in-house ELISA. Commercial ELISAs were compared with respect to their reproducibility and variability, their ability to detect significant titer rises in paired serum samples, their ability to detect an immune response after vaccination, and the comparability of semiquantitative and quantitative results. Reproducibility was generally good (>89%), intra-assay variation ranged from 2.4 to 28.7%, and indeterminate results were recorded in up to 18.5% of all specimens. Most kits correctly identified the antibody response to an acellular pertussis vaccine. None of the commercial kits identified all cases of pertussis correctly, and the sensitivity ranged between 60 and 95%. All five commercial ELISAs showed great discrepancies when comparing semiquantitative results and contained obviously different antigen preparations. Our data suggest that the five commercial ELISAs tested here need further improvement and standardization.

  15. Pertussis Immunization for Adolescents: What Are We Waiting for?

    Directory of Open Access Journals (Sweden)

    SA Halperin

    2001-01-01

    Full Text Available Immunization against pertussis (whooping cough has been part of the routine childhood immunization program for over 50 years. Until 1997, a whole cell pertussis vaccine was used, most often combined with diphtheria and tetanus toxoids; in some jurisdictions it was combined with inactivated poliovirus vaccine and later with Haemophilus influenzae type b (Hib-conjugate vaccine. Vaccine doses were given at two, four, six and 18 months of age, and again at four to six years of age. Use of the whole cell vaccine in children seven years of age and older was not recommended because "the incidence and severity of the disease greatly decrease with age, and because adverse reactions are (may be more common in older children and adults..." (1-3. Over a one-year period in 1997/98, all provinces in Canada began using an acellular pertussis vaccine, again combined with diphtheria and tetanus toxoids, inactivated poliovirus vaccine and Hib-conjugate vaccine. In 1999, an acellular pertussis vaccine that was combined with tetanus and diphtheria toxoids (TdaP (Adacel, Aventis Pasteur, Canada was licensed for use in individuals 12 to 54 years of age in Canada. In Germany, a similar adolescent and adult TdaP was licensed in 2000 (Boostrix, SmithKline Beecham, Belgium. With the availability of a TdaP product in Canada, should routine universal immunization against pertussis be provided for all adolescents and adults? Some of the key issues to be considered when answering this question are addressed in the questions and answers that follow. The focus of the present paper is on the adolescent population; however, similar issues about adult immunization need to be addressed by internal medicine and family practice practitioners.

  16. Impact of vaccination and birth rate on the epidemiology of pertussis: a comparative study in 64 countries.

    Science.gov (United States)

    Broutin, H; Viboud, C; Grenfell, B T; Miller, M A; Rohani, P

    2010-11-01

    Bordetella pertussis infection remains an important public health problem worldwide despite decades of routine vaccination. A key indicator of the impact of vaccination programmes is the inter-epidemic period, which is expected to increase with vaccine uptake if there is significant herd immunity. Based on empirical data from 64 countries across the five continents over the past 30-70 years, we document the observed relationship between the average inter-epidemic period, birth rate and vaccine coverage. We then use a mathematical model to explore the range of scenarios for duration of immunity and transmission resulting from repeat infections that are consistent with empirical evidence. Estimates of pertussis periodicity ranged between 2 and 4.6 years, with a strong association with susceptible recruitment rate, defined as birth rate × (1 - vaccine coverage). Periodicity increased by 1.27 years on average after the introduction of national vaccination programmes (95% CI: 1.13, 1.41 years), indicative of increased herd immunity. Mathematical models suggest that the observed patterns of pertussis periodicity are equally consistent with loss of immunity that is not as rapid as currently thought, or with negligible transmission generated by repeat infections. We conclude that both vaccine coverage and birth rate drive pertussis periodicity globally and that vaccination induces strong herd immunity effects. A better understanding of the role of repeat infections in pertussis transmission is critical to refine existing control strategies.

  17. Primary Immunization with a Triple Diphtheria-Tetanus-Whole Cell Pertussis Vaccine in Iranian Infants: An Analysis of Antibody Response

    Directory of Open Access Journals (Sweden)

    Zarei Saeed

    2009-06-01

    Full Text Available Universal vaccination of neonates and children against diphtheria, tetanus and pertussis has had a tremendous impact on the control of these infectious diseases worldwide. Immunization by the triple diphtheria, tetanus and whole cell pertussis vaccine (DTwP has been applied in Iran for almost 50 years. Periodic assessment of immunogenicity of this vaccine is an important aspect of successful mass vaccination programs. The present study was performed to assess the antibody response against tetanus, diphtheria and pertussis in a group of Iranian infants vaccinated with a local DTwP vaccine. In this prospective study, 330 infants received primary vaccination at 2, 4 and 6 months of age with DTwP vaccine manufactured by Razi Institute of Iran. Blood samples were taken 2-4 weeks after the third dose to assess seroprotection and geometric mean titers (GMT of specific antibodies. Among the 283 infants who completed the vaccination course, 98.2% and 100% developed antibodies against diphtheria and tetanus, respectively. The GMT of antibodies to tetanus, diphtheria and pertussis, were 2.09 IU/ml, 2.08 IU/ml and 8.73 EU/ml, respectively. Comparison of the results obtained from this study with those from previous studies performed in other countries revealed a similar GMT and protection rates for diphtheria and tetanus components. In the absence of well-established serological criteria, judgment about protection rate against pertussis has not been possible. A prospective vaccination study using the local DTwP vaccine in parallel to a WHO approved standard vaccine, could enable assessment of immunogenicity of the pertussis component.

  18. Seroprevalence of pertussis in the Gambia : evidence for continued circulation of bordetella pertussis despite high vaccination rates

    NARCIS (Netherlands)

    Scott, Susana; van der Sande, Marianne; Faye-Joof, Tisbeh; Mendy, Maimuna; Sanneh, Bakary; Barry Jallow, Fatou; de Melker, Hester; van der Klis, Fiona; van Gageldonk, Pieter; Mooi, Frits; Kampmann, Beate

    2015-01-01

    BACKGROUND: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa. METHODS: We evaluated antibody responses to pertussis toxin

  19. Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin.

    Science.gov (United States)

    Hegerle, N; Paris, A-S; Brun, D; Dore, G; Njamkepo, E; Guillot, S; Guiso, N

    2012-09-01

    Bordetella pertussis and Bordetella parapertussis are closely related bacterial agents of whooping cough. Whole-cell pertussis (wP) vaccine was introduced in France in 1959. Acellular pertussis (aP) vaccine was introduced in 1998 as an adolescent booster and was rapidly generalized to the whole population, changing herd immunity by specifically targeting the virulence of the bacteria. We performed a temporal analysis of all French B. pertussis and B. parapertussis isolates collected since 2000 under aP vaccine pressure, using pulsed-field gel electrophoresis (PFGE), genotyping and detection of expression of virulence factors. Particular isolates were selected according to their different phenotype and PFGE type and their characteristics were analysed using the murine model of respiratory infection and in vitro cell cytotoxic assay. Since the introduction of the aP vaccines there has been a steady increase in the number of B. pertussis and B. parapertussis isolates collected that are lacking expression of pertactin. These isolates seem to be as virulent as those expressing all virulence factors according to animal and cellular models of infection. Whereas wP vaccine-induced immunity led to a monomorphic population of B. pertussis, aP vaccine-induced immunity enabled the number of circulating B. pertussis and B. parapertussis isolates not expressing virulence factors to increase, sustaining our previous hypothesis.

  20. Analysis of Bordetella pertussis clinical isolates circulating in European countries during the period 1998-2012.

    Science.gov (United States)

    van Gent, M; Heuvelman, C J; van der Heide, H G; Hallander, H O; Advani, A; Guiso, N; Wirsing von Kőnig, C H; Vestrheim, D F; Dalby, T; Fry, N K; Pierard, D; Detemmerman, L; Zavadilova, J; Fabianova, K; Logan, C; Habington, A; Byrne, M; Lutyńska, A; Mosiej, E; Pelaz, C; Gröndahl-Yli-Hannuksela, K; Barkoff, A M; Mertsola, J; Economopoulou, A; He, Q; Mooi, F R

    2015-04-01

    Despite more than 50 years of vaccination, pertussis is still an endemic disease, with regular epidemic outbreaks. With the exception of Poland, European countries have replaced whole-cell vaccines (WCVs) by acellular vaccines (ACVs) in the 1990s. Worldwide, antigenic divergence in vaccine antigens has been found between vaccine strains and circulating strains. In this work, 466 Bordetella pertussis isolates collected in the period 1998-2012 from 13 European countries were characterised by multi-locus antigen sequence typing (MAST) of the pertussis toxin promoter (ptxP) and of the genes coding for proteins used in the ACVs: pertussis toxin (Ptx), pertactin (Prn), type 2 fimbriae (Fim2) and type 3 fimbriae (Fim3). Isolates were further characterised by fimbrial serotyping, multi-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). The results showed a very similar B. pertussis population for 12 countries using ACVs, while Poland, which uses a WCV, was quite distinct, suggesting that ACVs and WCVs select for different B. pertussis populations. This study forms a baseline for future studies on the effect of vaccination programmes on B. pertussis populations.

  1. Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis

    Science.gov (United States)

    Mohammadpour Dounighi, Naser; Razzaghi-Abyane, Mehdi; Nofeli, Mojtaba; Zolfagharian, Hossein; Shahcheraghi, Fereshteh

    2016-01-01

    Background Whooping cough is caused by Bordetella pertussis, and it remains a public health concern. Whole-cell pertussis vaccines have been commonly employed for expanded immunization. There is no doubt of the efficacy of whole cell pertussis vaccine, but it is necessary to improve the vaccine to decrease its toxicity. Objectives In this study, an inactivation process of dealing with pertussis bacteria is optimized in order to decrease the bacteria content in human doses of vaccines and reduce the vaccine’s toxicity. Materials and Methods The bacterial suspensions of pertussis strains 509 and 134 were divided into 21 sample parts from F1 to F21 and inactivated under different conditions. The inactivated suspensions of both strains were tested for opacity, non-viability, agglutination, purity, and sterility; the same formulation samples that passed quality tests were then pooled together. The pool of inactivated suspensions were analyzed for sterility, agglutination, opacity, specific toxicity, and potency. Results The harvest of both bacterial strains showed purity. The opacity of various samples were lost under different treatment conditions by heat from 8% to 12%, formaldehyde 6% to 8%, glutaraldehyde 6% to 8%, and thimerosal 5% to 8%. Tests on suspensions after inactivation and on pooled suspensions showed inactivation conditions not degraded agglutinins of both strains. The samples of F2, F4, F8, F12, F15, and F17 passed the toxicity test. The potency (ED50) of these samples showed following order F17 > F12 > F8 > F15, F4 > F2, and F17 revealed higher potency compared to other formulations. Conclusions It can be concluded that F17 showed desirable outcomes in the toxicity test and good immunogenicity with a low bacterial number content. Consequently, lower adverse effects and good immunogenicity are foreseeable for vaccine preparation with this method. PMID:27679704

  2. Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

    Directory of Open Access Journals (Sweden)

    Iraj Sedighi

    2016-06-01

    Full Text Available Context Universal immunization against Bordetella pertussis has partially controlled the burden of the disease and its transmission. However, according to recent data, the epidemiology of this vaccine-preventable disease has changed. Now, younger infants, adolescents, and adults are at greater risk of infection. This article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention. Evidence Acquisition In this narrative review, the most recently published sources of information on pertussis control measures, consisting of textbooks and articles, have been reviewed. We focused on the more recent data about the changing epidemiology or pertussis in Scopus through the use of the MeSH-term words [pertussis] or [whooping cough] and [epidemiology] or [outbreak] or [resurgence], but our search was not restricted to this particular strategy; we also tried to find all of the most recent available data in the general field through other means. Results Primary and booster doses of the pertussis vaccine seem to partially control transmission of the disease, but despite the different preventive strategies available, pertussis continues to cause mortality and morbidity among high-risk groups. Conclusions Adding booster doses of acellular pertussis vaccine to the current national immunization practices with whole-cell vaccines for young adults and pregnant women seems to be a good option for controlling mortality and morbidity among high-risk groups such as very young infants.

  3. Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

    Science.gov (United States)

    Sedighi, Iraj; Karimi, Abdollah; Amanati, Ali

    2016-01-01

    Context Universal immunization against Bordetella pertussis has partially controlled the burden of the disease and its transmission. However, according to recent data, the epidemiology of this vaccine-preventable disease has changed. Now, younger infants, adolescents, and adults are at greater risk of infection. This article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention. Evidence Acquisition In this narrative review, the most recently published sources of information on pertussis control measures, consisting of textbooks and articles, have been reviewed. We focused on the more recent data about the changing epidemiology or pertussis in Scopus through the use of the MeSH-term words [pertussis] or [whooping cough] and [epidemiology] or [outbreak] or [resurgence], but our search was not restricted to this particular strategy; we also tried to find all of the most recent available data in the general field through other means. Results Primary and booster doses of the pertussis vaccine seem to partially control transmission of the disease, but despite the different preventive strategies available, pertussis continues to cause mortality and morbidity among high-risk groups. Conclusions Adding booster doses of acellular pertussis vaccine to the current national immunization practices with whole-cell vaccines for young adults and pregnant women seems to be a good option for controlling mortality and morbidity among high-risk groups such as very young infants. PMID:27729960

  4. A behavioral economics intervention to increase pertussis vaccination among infant caregivers: A randomized feasibility trial.

    Science.gov (United States)

    Buttenheim, Alison M; Fiks, Alexander G; Burson, Randall C; Wang, Eileen; Coffin, Susan E; Metlay, Joshua P; Feemster, Kristen A

    2016-02-03

    The incidence of pertussis has tripled in the past five years. Infants can be protected by "cocooning," or vaccinating household contacts with the Tdap vaccine. However, Tdap coverage for adult caregivers of infants is low. This study evaluated the feasibility and impact of interventions informed by behavioral economics (retail pharmacy vouchers for Tdap vaccines and a celebrity public service announcement) to increase Tdap vaccination among caregivers of young infants. We conducted a randomized controlled feasibility trial among adults attending newborn well-child visits at an urban Philadelphia pediatric primary care clinic who were not previously vaccinated with Tdap. Participants were randomized to one of four conditions: ($5-off Tdap voucher vs. free voucher)×(watching a 1min video public service announcement (PSA) about Tdap vaccination vs. no PSA). Tdap vaccination was assessed by tracking voucher redemption and following up with participants by phone. Ninety-five adult caregivers of 74 infants were enrolled in the study (mean age 29.3 years; 61% male; relationship to newborn: 54% father, 33% mother, 13% grandparent or other; caregiver insurance status: 35% Medicaid, 34% private insurance, 32% uninsured). Only 1 subject redeemed the retail pharmacy Tdap voucher. Follow-up interviews suggest that, even with the voucher, significant barriers to vaccination remained including: delaying planned vaccination, perceived inconvenient pharmacy locations, and beliefs about pertussis risk and severity. Despite leveraging existing infrastructure for adult vaccination, results suggest that retail pharmacy vouchers delivered during a newborn visit are not an effective strategy for promoting Tdap. Alternate approaches are needed that prioritize convenience and provide an immediate opportunity to vaccinate when motivation is high. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Experimental Study of Interference Between Pertussis Antigens and Salk Poliomyelitis Vaccine

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    H. Mirehamsy

    1962-01-01

    Full Text Available An interference is observed between whooping-cough antigens and Salk polioc vaccine even if the two components are mixed immediately before use. The phenomenon is more evident when flUlid antigens are injected. Pertussis soluble antigen, which gives a good serological response in rabbits, when used alone or combined with DT, is inactivated in the presence of Salk polio vacc:ne

  6. Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine

    DEFF Research Database (Denmark)

    Orntoft, Nikolaj W; Thorsen, Kasper; Benn, Christine S;

    2013-01-01

    Background. Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. Methods. To investigate possible changes in gene expression after DTP vaccination, we...... identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using...... expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. Results. We found very few transcripts to alter...

  7. Proteomics-identified Bvg-activated autotransporters protect against bordetella pertussis in a mouse model.

    Science.gov (United States)

    de Gouw, Daan; Gouw, Daan de; de Jonge, Marien I; Jonge, Marien I de; Hermans, Peter W M; Wessels, Hans J C T; Zomer, Aldert; Berends, Alinda; Pratt, Catherine; Berbers, Guy A; Mooi, Frits R; Diavatopoulos, Dimitri A

    2014-01-01

    Pertussis is a highly infectious respiratory disease of humans caused by the bacterium Bordetella pertussis. Despite high vaccination coverage, pertussis has re-emerged globally. Causes for the re-emergence of pertussis include limited duration of protection conferred by acellular pertussis vaccines (aP) and pathogen adaptation. Pathogen adaptations involve antigenic divergence with vaccine strains, the emergence of strains which show enhanced in vitro expression of a number of virulence-associated genes and of strains that do not express pertactin, an important aP component. Clearly, the identification of more effective B. pertussis vaccine antigens is of utmost importance. To identify novel antigens, we used proteomics to identify B. pertussis proteins regulated by the master virulence regulatory system BvgAS in vitro. Five candidates proteins were selected and it was confirmed that they were also expressed in the lungs of naïve mice seven days after infection. The five proteins were expressed in recombinant form, adjuvanted with alum and used to immunize mice as stand-alone antigens. Subsequent respiratory challenge showed that immunization with the autotransporters Vag8 and SphB1 significantly reduced bacterial load in the lungs. Whilst these antigens induced strong opsonizing antibody responses, we found that none of the tested alum-adjuvanted vaccines - including a three-component aP - reduced bacterial load in the nasopharynx, suggesting that alternative immunological responses may be required for efficient bacterial clearance from the nasopharynx.

  8. Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis?

    Science.gov (United States)

    Pancer, Katarzyna Wanda

    2015-01-01

    The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires' disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre-absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children tests. As a preliminary, we posed a hypothesis of a potential impact of an anti-pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children.

  9. Pertussis vaccination and epilepsy--an erratic history, new research and the mismatch between science and social policy.

    Science.gov (United States)

    Shorvon, Simon; Berg, Anne

    2008-02-01

    For over 50 years, concerns have been raised about the risk of pertussis vaccine-induced childhood encephalopathy and epilepsy. This article reviews the scientific literature, and the social and historical context in which the scientific, public health and societal views have not always been aligned. Large-scale studies of this issue have produced conflicting results, although the recent consensus is that the risk of vaccine-induced encephalopathy and/or epilepsy, if it exists at all, is extremely low. Risk estimates in the literature have included: risk of a febrile seizure 1 per 19,496 vaccinations; risk of an afebrile seizure 1 per 76,133 vaccinations; risk of encephalopathy after pertussis infection nil-3 cases per million vaccinations. A recent study showed that encephalopathy in 11 out of the 14 children studied, although previously attributed to vaccination, was in fact due an inherited genetic defect of the SCNIA gene that codes for the voltage gated neuronal sodium channel. This study is important because it provides a solid alternative explanation for the perceived pertussis vaccine-encephalopathy association. The interesting possibility is raised that the encephalopathy apparently due to pertussis itself may, in some cases, be due to an SCNIA mutation. It may also, by analogy, shed some light on the continuing debate about other serious long-term adverse effects of vaccination in general.

  10. Pertussis (Whooping Cough) Outbreaks

    Science.gov (United States)

    ... CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  11. Pertussis (Whooping Cough) Complications

    Science.gov (United States)

    ... CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  12. Assessing the Evidence for Maternal Pertussis Immunization: A Report From the Bill & Melinda Gates Foundation Symposium on Pertussis Infant Disease Burden in Low- and Lower-Middle-Income Countries.

    Science.gov (United States)

    Sobanjo-Ter Meulen, Ajoke; Duclos, Philippe; McIntyre, Peter; Lewis, Kristen D C; Van Damme, Pierre; O'Brien, Katherine L; Klugman, Keith P

    2016-12-01

    Implementation of effective interventions has halved maternal and child mortality over the past 2 decades, but less progress has been made in reducing neonatal mortality. Almost 45% of under-5 global mortality now occurs in infants <1 month of age, with approximately 86% of neonatal deaths occurring in low- and lower-middle-income countries (LMICs). As an estimated 23% of neonatal deaths globally are due to infectious causes, maternal immunization (MI) is one intervention that may reduce mortality in the first few months of life, when direct protection often relies on passively transmitted maternal antibodies. Despite all countries including pertussis-containing vaccines in their routine childhood immunization schedules, supported through the Expanded Programme on Immunization, pertussis continues to circulate globally. Although based on limited robust epidemiologic data, current estimates derived from modeling implicate pertussis in 1% of under-5 mortality, with infants too young to be vaccinated at highest risk of death. Pertussis MI programs have proven effective in reducing infant pertussis mortality in high-income countries using tetanus-diphtheria-acellular pertussis (Tdap) vaccines in their maternal and infant programs; however, these vaccines are cost-prohibitive for routine use in LMICs. The reach of antenatal care programs to deliver maternal pertussis vaccines, particularly with respect to infants at greatest risk of pertussis, needs to be further evaluated. Recognizing that decisions on the potential impact of pertussis MI in LMICs need, as a first step, robust contemporary mortality data for early infant pertussis, a symposium of global key experts was held. The symposium reviewed current evidence and identified knowledge gaps with respect to the infant pertussis disease burden in LMICs, and discussed proposed strategies to assess the potential impact of pertussis MI. © The Author 2016. Published by Oxford University Press for the Infectious Diseases

  13. Complete Genome Sequence of Bordetella pertussis Strain VA-190 Isolated from a Vaccinated 10-Year-Old Patient with Whooping Cough

    Science.gov (United States)

    Eby, Joshua C.; Turner, Lauren; Nguyen, Bryan; Kang, June; Neville, Carly

    2016-01-01

    The number of cases of pertussis has increased in the United States despite vaccination. We present the genome of an isolate of Bordetella pertussis from a vaccinated patient from Virginia. The genome was sequenced by long-read methodology and compared to that of a clinical isolate used for laboratory studies, D420. PMID:27634997

  14. Complete Genome Sequence of Bordetella pertussis Strain VA-190 Isolated from a Vaccinated 10-Year-Old Patient with Whooping Cough.

    Science.gov (United States)

    Eby, Joshua C; Turner, Lauren; Nguyen, Bryan; Kang, June; Neville, Carly; Temple, Louise

    2016-09-15

    The number of cases of pertussis has increased in the United States despite vaccination. We present the genome of an isolate of Bordetella pertussis from a vaccinated patient from Virginia. The genome was sequenced by long-read methodology and compared to that of a clinical isolate used for laboratory studies, D420.

  15. Short Term Reactogenicity of a Triple Diphtheria-Tetanus-Whole Cell Pertussis Vaccine in Iranian Infants

    Directory of Open Access Journals (Sweden)

    S Zarei

    2009-03-01

    Full Text Available "nBackground: Immunization against diphtheria, tetanus and pertussis (DTP has long been applied in Iran using whole cell vac­cine. Despite the role of whole cell DTP (DTwP vaccine in reduction of mortality as a result of disastrous diseases such as diphtheria, tetanus, and pertussis, serious local and systemic complications have been attributed to these vaccines. This study was performed to determine the complications of DTwP vaccine in infants attending some of the health centers of Te­hran in 2006-2007."nMethods:  In this prospective study, 330 infants were injected with DTwP vaccine manufactured by Razi Institute of Iran. All subjects received DTwP vaccine at 2, 4, and 6 months of age following the national vaccination schedule of Iran. Re­actogenicity was assessed by the parents for 7 days post-vaccination using diary cards."nResults: Of the 279 infants who completed the vaccination study, pain was the most frequent local reaction after the pri­mary vaccination (68.1-75.3%. The mean diameters of the redness and swelling at first day post-vaccination were 2.81±6.91 and 2.60±7.93 mm in the first dose, 2.40±6.25 and 1.94±5.74 mm in the second dose and 2.24±5.66 and 2.16±6.03 in the third dose, respectively. Fever (axillary temperature >37.5° C was the most frequently reported systemic re­action during the pri­mary vaccination (53.8-58.8%. All systemic reactions observed after each dose were either reduced or completely disap­peared during a week."nConclusion: The high incident of complications observed following vaccination with this cellular triple vaccine may be re­lated to the formulation or the bacterial cell fragments used in vaccine production.

  16. Cloning of Bordetella pertussis putative outer protein D (BopD) and Leucin/Isoleucine/Valin binding protein (LivJ)

    Science.gov (United States)

    Öztürk, Burcu Emine Tefon

    2017-04-01

    Whooping cough also known as pertussis is a contagious acute upper respiratory disease primarily caused by Bordetella pertussis. It is known that this disease may be fatal especially in infants and recently, the number of pertussis cases has been increased. Despite the fact that there are numbers of acellular vaccines on the market, the current acellular vaccine compositions are inadequate for providing sustainable immunity and avoiding subclinical disease cases. Hence, exploring novel proteins with high immune protective capacities is essential to enhance the clinical efficacy of current vaccines. In this study, genes of selected immunogenic proteins via -omics studies, namely Putative outer protein D (BopD) and Leucin/Isoleucine/Valin Binding Protein (LivJ) were first cloned into pGEM-T Easy vector and transformed to into E. coli DH5α cells and then cloned into the expression vector pET-28a(+) and transformed into E. coli BL21 (DE3) cells to express the proteins.

  17. Pertussis immunization in the global pertussis initiative North American region: recommended strategies and implementation considerations.

    Science.gov (United States)

    Tan, Tina; Halperin, Scott; Cherry, James D; Edwards, Kathryn; Englund, Janet A; Glezen, Paul; Greenberg, David; Rothstein, Edward; Skowronski, Danuta

    2005-05-01

    In North America, children currently receive 5 doses of a combined diphtheria-tetanus-acellular pertussis vaccine between the ages of 2 months and 6 years. Although this schedule has reduced the incidence of childhood pertussis, it has not led to the development of herd immunity in the total population, largely because pertussis immunity wanes with time. The time course over which immunity wanes is uncertain; however, high pertussis antibody titers in adolescents and adults indicate unrecognized infection in these groups. There is evidence that this group serves as a source of infection for young infants who are not fully immunized. Therefore, of the potential strategies reviewed by the North American Global Pertussis Initiative group, universal adolescent immunization would in theory reduce the risk of pertussis in this age group and may reduce transmission to young infants. However, because immunity probably wanes at the same rate in adolescents and children, the burden of disease will likely shift to older age groups, including young adults (parents of vulnerable infants). Therefore the ideal would be immunization of adolescents and adults, particularly those who are in contact with young infants. Adolescent immunization is already recommended in Austria, France, Germany and Canada, and participants in the Global Pertussis Initiative recommend that this strategy be implemented across North America with a view to eventually extending immunization to include adults. The final decision to implement such a strategy will depend on pertussis surveillance studies and analysis of the effectiveness and tolerability of adolescent and adult pertussis immunization as well as program considerations related to feasibility and economics.

  18. Pertussis as health care workers infectious disease – The clinical case with a commentary

    Directory of Open Access Journals (Sweden)

    Ernest Kuchar

    2013-10-01

    Full Text Available We discuss the changing epidemiological situation of pertussis observed in recent years, with a focus on the shift of cases from young children to older age groups, teenagers and adults. Whooping cough may affect healthcare workers who belong to a high-risk group and cause hospital infections. We present a case report of pertussis in a nurse and the recommended prophylactic measures in healthcare workers. The current definition and diagnosis of pertussis is also discussed. The clinical course of pertussis can be significantly alleviated and highly non-specific, with no typical coughing and vomiting in people vaccinated against whooping cough a few years earlier. Pertussis should be considered in the differential diagnosis of cough lasting more than fourteen days. Improvement of the epidemiological situation requires, besides immunization of infants, regular and universal booster immunization for adolescents and adults. Vaccinations for health care workers of neonatal and pediatric wards are recommended in the National Program of Immunization for 2013. It seems that booster vaccination of health care workers with a triple vaccine against diphtheria, tetanus and acellular pertussis (dTpa of the reduced quantity of antigens, particularly of health workers caring for infants, children and the elderly, may be the most effective way to reduce the risk of pertussis transmission in the health care environment. Med Pr 2013;64(5:731–739

  19. Effectiveness and acceptance of a health care-based mandatory vaccination program.

    Science.gov (United States)

    Leibu, Rachel; Maslow, Joel

    2015-01-01

    To decrease the risk of transmission of hospital-associated transmission of influenza and pertussis through mandatory vaccination of staff. A mandatory influenza and toxoid-diphtheria toxoid-acellular pertussis program was implemented systemwide. A structured vaccine exemption program was implemented for those requesting a medical and/or religious/moral/ethical exemption. Systemwide influenza vaccination rates increased from 67% historically, 76.2% in the 2012 to 2013 influenza season, to 94.7% in 2013 to 2014 with an overall compliance rate of 97.8%. Toxoid-diphtheria toxoid-acellular pertussis vaccination rates systemwide reached 94.9%, with an overall compliance rate of 98%. Higher rates were experienced at individual hospital facilities compared with the corporate location. Successful vaccination campaign outcomes can be achieved through diligent enforcement of mandatory vaccination, masking, and other infection prevention procedures.

  20. Predictors of Low Uptake of Prenatal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Immunization in Privately Insured Women in the United States.

    Science.gov (United States)

    Butler, Anne M; Layton, J Bradley; Li, Dongmei; Hudgens, Michael G; Boggess, Kim A; McGrath, Leah J; Weber, David J; Becker-Dreps, Sylvia

    2017-04-01

    To examine the uptake of prenatal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) immunization among pregnant women in the United States. Using MarketScan data, we conducted a historical cohort study among pregnant women with employer-based commercial insurance in the United States who delivered between January 1, 2010, and December 31, 2014. We examined temporal trends of uptake, predictors of uptake, and timing of Tdap immunization. Among 1,222,384 eligible pregnancies in 1,147,711 women, receipt of prenatal Tdap immunization increased from 0.0% of women who delivered in January 2010 to 9.8% who delivered in October 2012 (the date of the recommendation by the Advisory Committee on Immunization Practices for Tdap during every pregnancy) to 44.4% who delivered in December 2014. Among women who received Tdap during pregnancy, the majority were immunized between 27 weeks and 36 6/7 weeks of gestation per the Advisory Committee on Immunization Practices recommendation. In multivariable analyses among women who delivered between November 2012 and December 2014, rates of prenatal Tdap immunization were lower for women younger than 25 years of age (eg, 20-24 compared with 30-34 years rate ratio [RR] 0.83, 95% confidence interval [CI] 0.85-0.88), with other children (eg, three compared with zero children: RR 0.86, 95% CI 0.84-0.88), residing in the South compared with the Midwest (RR 0.81, 95% CI 0.80-0.82), or with emergency department visits in early pregnancy (RR 0.93, 95% CI 0.92-0.95). The proportion of pregnant women who received prenatal Tdap increased with increasing gestational age at birth. By the end of 2014, fewer than half of pregnant women in the United States were receiving prenatal Tdap immunization. Implementation and dissemination strategies are needed to increase Tdap coverage among pregnant women, especially those who are young, have other children, or reside in the South.

  1. Bordetella pertussis.

    Science.gov (United States)

    Nieves, Delma J; Heininger, Ulrich

    2016-06-01

    Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of human illness is caused by Bordetella pertussis, and some is caused by Bordetella parapertussis. Bordetella is a Gram-negative, pleomorphic, aerobic coccobacillus. In the past several years, even countries with high immunization rates in early childhood have experienced rises in pertussis cases. Reasons for the resurgence of reported pertussis may include molecular changes in the organism and increased awareness and diagnostic capabilities, as well as lessened vaccine efficacy and waning immunity. The most morbidity and mortality with pertussis infection is seen in infants too young to benefit from immunization. Severe infection requiring hospitalization, including in an intensive care setting, is mostly seen in those under 3 months of age. As a result, research and public health actions have been aimed at better understanding and reducing the spread of Bordetella pertussis. Studies comparing the cost benefit of cocooning strategies versus immunization of pregnant women have been favorable towards immunizing pregnant women. This strategy is expected to prevent a larger number of pertussis cases, hospitalizations, and deaths in infants <1 year old while also being cost-effective. Studies have demonstrated that the source of infection in infants usually is a family member. Efforts to immunize children and adults, in particular pregnant women, need to remain strong.

  2. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, Henrik; Samb, Badara

    2003-01-01

    Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...

  3. Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine.

    Science.gov (United States)

    Raeven, René H M; Brummelman, Jolanda; Pennings, Jeroen L A; van der Maas, Larissa; Tilstra, Wichard; Helm, Kina; van Riet, Elly; Jiskoot, Wim; van Els, Cécile A C M; Han, Wanda G H; Kersten, Gideon F A; Metz, Bernard

    2016-12-01

    The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines. Both vaccines stimulated a mixed systemic Th1/Th2/Th17 response. Remarkably, omvPV evoked higher IgG levels, lower systemic pro-inflammatory cytokine responses and enhanced splenic gene expression than wPV. The omvPV-induced transcriptome revealed gene signatures of the IFN-signaling pathway, anti-inflammatory signatures that attenuate LPS responses, anti-inflammatory metabolic signatures, and IgG responses. Upon intranasal challenge, both immunized groups were equally efficient in clearing Bordetella pertussis from the lungs. This study importantly shows that immunization with omvPV provides a milder inflammatory responses but with equal protection to bacterial colonization and induction of protective antibody and Th1/Th17 type immune responses compared to wPV. These results emphasize the potential of omvPV as a safe and effective next-generation pertussis vaccine.

  4. Antibodies to BrkA augment killing of Bordetella pertussis.

    Science.gov (United States)

    Oliver, D C; Fernandez, R C

    2001-10-12

    BrkA is a Bvg-regulated Bordetella pertussis protein that mediates serum resistance and adherence. It shares sequence identity with another B. pertussis virulence factor called pertactin, and it is a member of the diverse group of proteins found in Gram-negative bacteria that are secreted by an autotransporter mechanism. Sera, either from individuals who have been vaccinated with acellular pertussis vaccines, or from individuals who have no re-collection of recent infection with B. pertussis fail to kill wild-type B. pertussis, but kill brkA mutant strains very well. We examined whether BrkA could be neutralised in serum fitting this profile. BrkA is synthesised as a 103kDa precursor that is processed into a surface-associated N-terminal 73kDa passenger domain, and an outer-membrane embedded C-terminal 30kDa transporter moiety. Polyclonal antibodies were raised to a recombinant, re-folded histidine-tagged fusion protein representing the 73kDa passenger region. These anti-BrkA antibodies were shown to boost the existing bactericidal capacity of human serum against B. pertussis by neutralising BrkA.

  5. Antibody level of New Zealand children immunized with the triple vaccine DTP (diphtheria-tetanus-pertussis).

    OpenAIRE

    Lau, R. C.

    1988-01-01

    Enzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components we...

  6. Production and characterization of recombinant pertactin, fimbriae 2 and fimbriae 3 from Bordetella pertussis

    Directory of Open Access Journals (Sweden)

    Hou Qiming

    2009-12-01

    Full Text Available Abstract Background Bordetella pertussis is a causative agent of pertussis or whooping cough in humans. Pertactin (Prn, fimbriae 2 (Fim2 and fimbriae 3 (Fim3 of B. pertussis are important virulence factors and immunogens which have been included in some acellular pertussis vaccines. In this present study, we cloned, expressed and purified Prn, Fim2 and Fim3, respectively. The immunogenicity and protective efficacy of the three recombinant proteins (rPrn, rFim2 and rFim3 were investigated in mouse model. Results Three recombinant proteins with amount of 12 to 25 mg/L were produced. Compared to the control mice only immunized with adjuvant, serum IgG antibody responses were significantly induced in the mice immunized with rPrn, rFim2 or rFim3 (P P B. pertussis (P Conclusions We have developed an efficient method to produce large amounts of rPrn, rFim2, and rFim3 from B. pertussis. The three recombinant proteins induced both humoral and cellular immune responses in mice. Immunization with rPrn also conferred protection against pertussis in mouse infection models. Our results indicated that the recombinant proteins still retain their immunological properties and highlighted the potential of the recombinant proteins for the future development of the B. pertussis vaccines.

  7. Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review.

    Science.gov (United States)

    Amirthalingam, G; Gupta, S; Campbell, H

    2013-09-19

    This review summarises the epidemiology and control of pertussis in England and Wales since the introduction of routine immunisation and considers the implications for future control. Routine infant immunisation with a whole-cell pertussis (wP) vaccine was introduced in 1957 and had a marked impact on the overall disease burden. Following a fall in vaccine coverage during the 1970s and 80s linked to a safety scare with wP vaccine, there was an extended period of high coverage and pertussis incidence fell dramatically. Incidence continued to decrease with the introduction of an acellular pertussis vaccine in the pre-school booster in November 2001 and in the primary United Kingdom (UK) schedule in September 2004 but has increased since July 2011. In response to a high rate of pertussis in infants, a temporary vaccination programme for pregnant women was introduced in October 2012. The key aim of the programme is to protect vulnerable infants from birth in the first months of life, before they can be fully protected by routine infant immunisation. A review of the UK adolescent immunisation programme is currently ongoing and the inclusion of a pertussis booster is being considered.

  8. Cost-effectiveness of adolescent pertussis vaccination for the Netherlands: using an individual-based dynamic model.

    Directory of Open Access Journals (Sweden)

    Robin de Vries

    Full Text Available BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years. In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY and €6371/QALY (range: 4139-9549 € per QALY for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in

  9. The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community

    DEFF Research Database (Denmark)

    Mogensen, Søren Wengel; Andersen, Andreas; Rodrigues, Amabelia

    2017-01-01

    Background We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s. Methods The child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV...

  10. Vaccine independence, local competences and globalisation: lessons from the history of pertussis vaccines

    NARCIS (Netherlands)

    Blume, S.; Zanders, M.

    2006-01-01

    In the context of global vaccine politics ‘vaccine independence’ has been defined as the assumption of financial responsibility for vaccine procurement. This paper suggests ‘the possibility of vaccine choice’ as an alternative meaning for the term. How far does local competence in vaccine developmen

  11. [PERSISTENCE OF BORDETELLA PERTUSSIS BACTERIA AND A POSSIBLE MECHANISM OF ITS FORMATION].

    Science.gov (United States)

    Karataev, G I; Sinyashina, L N; Medkova, A Yu; Semin, E G

    2015-01-01

    A growth of pertussis morbidity is observed in many countries of the world against the background of mass vaccindtion. Forms of the disease course have changed. Atypical forms of pertussis occur predominately in adolescents and adults. Asymptomatic carriage of the causative agent has been established. Infection of infants with. BordetelIa pertussis bacteria in more than 90% of cases occurs from parents and relatives. A prolonged persistence of the causative agent has been identified. Morbidity increase in developed countries is associated with the use of acellular vaccines, that do not protect from the infection, but reduce severity of the disease. A change of genotypes of the circulating bacteria strains is observed ubiquitously. Formation of a persistent form of B. pertussis is possible due to a reversible integration of IS-elements into bvgAS operon and other virulence genes. The results of studies of invasion and survival of B. pertussis bacteria in eukaryotic cells, a change in B. pertussis bacteria population after experimental infection of laboratory mice and monkeys are presented, accumulation of avirulent insertion Bvg mutants of B. pertussis was detected. The data obtained are in accordance with the results of analysis of causative agent population in patients with typical and atypical forms of pertussis in humans. More than 50% of the population of B. pertussis bacteria in practically healthy carriers was shown to be presented by avirulent insertion Bvg mutants. B. pertussis virulence reducing as a result of inactivation of single or several virulence genes probably provide long-term persistence of bacteria in host organism and formation of apparently healthy vehicles. Follow-up studies on that front would help to formulate new attitudes to preventive measures of pertussis and lead to development of fundamentally new pharmaceuticals (vaccines) preventing formation of bacterial persistence.

  12. Health-state valuations for pertussis: methods for valuing short-term health states

    Directory of Open Access Journals (Sweden)

    LeBaron Charles W

    2005-03-01

    Full Text Available Abstract Background The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1 to describe patient valuations of pertussis disease and vaccination; and (2 to compare valuations for short-term and long-term health states associated with pertussis. Methods We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO and contingent valuation (CV techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test. Results Three hundred three (59% and 309 (60% respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise. Conclusion Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.

  13. Prophylactic antipyretics for prevention of febrile seizures following vaccination.

    Science.gov (United States)

    Monfries, Nicholas; Goldman, Ran D

    2017-02-01

    Question Parents of a 12-month-old boy are bringing their son in to my family practice clinic for his well-baby visit. As the infant is due for his 12-month vaccine series, the parents are concerned after hearing about the association between certain vaccinations and an increased risk of febrile seizures, and are wondering if they should administer prophylactic antipyretics to decrease the risk of febrile seizure. What vaccinations are associated with increased risk of febrile seizure, and is there evidence supporting prophylactic administration of antipyretics to prevent febrile seizures? Answer Vaccinations associated with increased risk of febrile seizure include the following: the measles-mumps-rubella vaccine; the measles-mumps-rubella-varicella vaccine; the combined diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b vaccine; the whole-cell pertussis vaccine; the 7-valent pneumococcal conjugate vaccine; and concomitant administration of the trivalent inactivated influenza vaccine with either the 7-valent pneumococcal conjugate vaccine or the diphtheria, tetanus, and acellular pertussis vaccine. Despite being a higher-risk group, children receiving these vaccinations should not receive prophylactic antipyretics, as no statistically significant reduction in the rate of febrile seizures has been documented, and prophylactic antipyretic use potentially decreases the immune response to certain vaccines. Copyright© the College of Family Physicians of Canada.

  14. Bordetella pertussis isolates in Finland: Serotype and fimbrial expression

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    Mertsola Jussi

    2008-09-01

    Full Text Available Abstract Background Bordetella pertussis causes whooping cough or pertussis in humans. It produces several virulence factors, of which the fimbriae are considered adhesins and elicit immune responses in the host. B. pertussis has three distinct serotypes Fim2, Fim3 or Fim2,3. Generally, B. pertussis Fim2 strains predominate in unvaccinated populations, whereas Fim3 strains are often isolated in vaccinated populations. In Finland, pertussis vaccination was introduced in 1952. The whole-cell vaccine contained two strains, 18530 (Fim3 since 1962 and strain 1772 (Fim2,3 added in 1976. After that the vaccine has remained the same until 2005 when the whole-cell vaccine was replaced by the acellular vaccine containing pertussis toxin and filamentous hemagglutinin. Our aims were to study serotypes of Finnish B. pertussis isolates from 1974 to 2006 in a population with > 90% vaccination coverage and fimbrial expression of the isolates during infection. Serotyping was done by agglutination and serotype-specific antibody responses were determined by blocking ELISA. Results Altogether, 1,109 isolates were serotyped. Before 1976, serotype distributions of Fim2, Fim3 and Fim2,3 were 67%, 19% and 10%, respectively. From 1976 to 1998, 94% of the isolates were Fim2 serotype. Since 1999, the frequency of Fim3 strains started to increase and reached 83% during a nationwide epidemic in 2003. A significant increase in level of serum IgG antibodies against purified fimbriae was observed between paired sera of 37 patients. The patients infected by Fim3 strains had antibodies which blocked the binding of monoclonal antibodies to Fim3 but not to Fim2. Moreover, about one third of the Fim2 strain infected patients developed antibodies capable of blocking of binding of both anti-Fim2 and Fim3 monoclonal antibodies. Conclusion Despite extensive vaccinations in Finland, B. pertussis Fim2 strains were the most common serotype. Emergence of Fim3 strains started in 1999 and

  15. Pertussis in the Era of New Strains of Bordetella pertussis.

    Science.gov (United States)

    Souder, Emily; Long, Sarah S

    2015-12-01

    Despite implementation of a successful vaccination program, pertussis remains a significant health problem. Although the incidence of pertussis in the United States is reduced by approximately 80% compared with incidence before the introduction of vaccination in the 1940s, deaths still occur and the unrecognized disease burden remains high, with 1 million Bordetella pertussis infections annually in the United States estimated by serologic surveys. Reasons for the resurgence and current prevalence of pertussis may be multifactorial and include waning vaccine-induced protection as well as lower vaccine effectiveness, failure to vaccinate, and changes in the organism itself.

  16. Bordetella pertussis transmission.

    Science.gov (United States)

    Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J

    2015-11-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission.

  17. Risk factors of delay proportional probability in diphtheria-tetanus-pertussis vaccination of Iranian children; Life table approach analysis

    Directory of Open Access Journals (Sweden)

    Mohsen Mokhtari

    2015-01-01

    Full Text Available Despite success in expanded program immunization for an increase in vaccination coverage in the children of world, timeliness and schedule of vaccination remains as one of the challenges in public health. This study purposed to demonstrate the related factors of delayed diphtheria-tetanus-pertussis (DTP vaccination using life table approach. A historical cohort study conducted in the poor areas of five large Iran cities. Totally, 3610 children with 24-47 months old age who had documented vaccination card were enrolled. Time of vaccination for the third dose of DTP vaccine was calculated. Life table survival was used to calculate the proportional probability of vaccination in each time. Wilcoxon test was used for the comparison proportional probability of delayed vaccination based on studies factors. The overall median delayed time for DTP3 was 38.52 days. The Wilcoxon test showed that city, nationality, education level of parents, birth order and being in rural areas are related to the high probability of delay time for DTP3 vaccination (P 0.05. Being away from the capital, a high concentration of immigrants in the city borders with a low socioeconomic class leads to prolonged delay in DTP vaccination time. Special attention to these areas is needed to increase the levels of parental knowledge and to facilitate access to the health services care.

  18. Infectious bovine keratoconjunctivitis: enhancement of Moraxella bovis pili immunogenicity with diphtheria-tetanus toxoids and pertussis vaccine.

    Science.gov (United States)

    Pugh, G W; Kopecky, K E; McDonald, T J

    1984-04-01

    A study was conducted to determine whether diphtheria-tetanus-toxoids and pertussis vaccine (DPT) would enhance the immunogenicity of homologous Moraxella bovis pili fractions. Thirty-six calves were divided into 4 groups (I, II, III, and IV) of 9 calves each. Calves in group I were not vaccinated and served as controls. Calves in group II were vaccinated with pili fractions only. Calves in group III were vaccinated with DPT only. Calves in group IV were vaccinated with DPT and pili. Vaccination consisted of 2 inoculations, 21 days apart. Fourteen days after the last vaccinal inoculation was done, the eyes of all calves were exposed to a hemolytic homologous strain of M bovis. The percentage of eyes with disease was significantly less in calves given DPT and pili (P less than 0.001) and calves given pili only (P less than 0.05) than in calves given DPT only or nonvaccinated calves. The lesions were less severe in calves vaccinated with pili only than in calves not vaccinated with pili. Serologic results also showed a positive relationship between the development of serum antibodies against pili and immunity. The results indicate that DPT enhanced the immune response and if used as an adjuvant, might be useful in the development of a vaccine against infectious bovine keratoconjunctivitis.

  19. In vitro innate immune cell based models to assess whole cell Bordetella pertussis vaccine quality: a proof of principle.

    Science.gov (United States)

    Hoonakker, M E; Verhagen, L M; Hendriksen, C F M; van Els, C A C M; Vandebriel, R J; Sloots, A; Han, W G H

    2015-03-01

    Lot release testing of vaccines is primarily based on animal models that are costly, time-consuming and sometimes of questionable relevance. In order to reduce animal use, functional in vitro assays are being explored as an alternative approach for the current lot release testing paradigm. In this study, we present an evaluation of APC platforms assessing innate immune activation by whole cell Bordetella pertussis (wP) vaccines. Primary monocytes, monocyte-derived DC (moDC) and human monocyte/DC cell lines (MonoMac6 and MUTZ-3) were compared for their capacity to respond to wP vaccines of varying quality. To produce such vaccines, the production process of wP was manipulated, resulting in wP vaccines covering a range of in vivo potencies. The responses of MUTZ-3 cells and primary monocytes to these vaccines were marginal and these models were therefore considered inappropriate. Importantly, moDC and MonoMac6 cells responded to the wP vaccines and discriminated between vaccines of varying quality, although slight variations in the responses to wP vaccines of similar quality were also observed. This study provides a proof of principle for the use of in vitro APC platforms as part of a new strategy to assess wP vaccine lot consistency, though careful standardisation of assay conditions is necessary.

  20. Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

    Directory of Open Access Journals (Sweden)

    Reinaldo de Menezes Martins

    2008-11-01

    Full Text Available A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK, which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (>0.15 µg/mL with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

  1. Immunogenicity and reactogenicity of two diphtheria-tetanus-whole cell pertussis vaccines in Iranian pre-school children, a randomized controlled trial.

    Science.gov (United States)

    Zarei, Saeed; Jeddi-Tehrani, Mahmood; Mehdi Akhondi, Mohammad; Zeraati, Hojjat; Ferydonfar, Amir Ali; Nasernia, Jalaledin; Tavangar, Banafsheh; Shokri, Fazel

    2013-06-01

    The present study was undertaken to compare the immunogenicity and reactogenicity of two diphtheria-tetanus-whole cell pertussis (DTwP) vaccines administered to Iranian preschool children. In this randomized, double-blind and multicenter prospective study, 672 children aged 4-6 y were administered with either a local DTwP vaccine (DTwP-Local) (n = 337) or a commercial vaccine (DTwP-Pasteur) (n = 335). All subjects received DTwP vaccine at 4-6 y of age, following the national immunization schedule of Iran. Blood samples were collected before and 2-4 weeks after the vaccination. Immunogenicity of each vaccine was assessed by ELISA using commercial kits. Reactogenicity was assessed by the parents for seven days post-booster using diary cards. The geometric mean titers (GMTs) of the antibodies induced against diphtheria and tetanus by DTwP-Local were 7.7 and 9.4 IU/ml and those of DTwP-Pasteur were 8.2 and 8.6 IU/ml, respectively. There was no significant difference between the immunogenicity of the two vaccines against diphtheria and tetanus. The GMTs of antibodies produced against pertussis were 30.2 EU/ml for DTwP-Local and 47.9 EU/ml for DTwP-Pasteur vaccines (p37.5°C) were the most frequent local and systemic reactions observed after the vaccination. All local and systemic reactions observed after vaccination were significantly higher in subjects immunized with DTwP-Local vaccine. Immunogenicity against diphtheria and tetanus was similar for the two vaccines, but immunogenicity of the local vaccine against pertussis was significantly less efficient than that of DTwP-Pasteur. This difference and the higher side effects of the DTwP-Local vaccine could be due to the bacterial strain or the preparation or formulation protocol of the local pertussis vaccine.

  2. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Roth, Adam Anders Edvin

    2012-01-01

    Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

  3. Impaired autonomic responsiveness of the cardiovascular system of the rat induced by a heat-labile component of Bordetella pertussis vaccine.

    Science.gov (United States)

    de Wildt, D J; Kreeftenberg, H G; Nijkamp, F P

    1983-01-01

    Bordetella pertussis vaccination induces severe impairment of the autonomic responsiveness of the cardiovascular system in rats. The vasodilation after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic action induced by the muscarinic receptor stimulant arecoline were inhibited 4 days after vaccination. Moreover, basal blood pressure values appeared to be significantly lower in B. pertussis-vaccinated rats compared with control animals. These effects were dependent upon the bacterial strain used. Differences in pharmacological activity due to strain differences paralleled variations in the content of lymphocytosis-promoting factor of the vaccine. The inhibitory effects were absent after the administration of vaccine heated for 1 h at 80 degrees C, implicating an important role for a heat-labile component, e.g., lymphocytosis-promoting factor, and not for a heat-stable constituent, e.g., endotoxin (lipopolysaccharide). Previous studies indicate that some early biological effects elicited by B. pertussis vaccine can be attributed to lipopolysaccharide, whereas late induced effects are mainly brought about by lymphocytosis-promoting factor. For that reason a role for lipopolysaccharide might be excluded because 5 h after vaccination no disturbances of the autonomic nervous system were observed. We conclude that B. pertussis vaccination induces autonomic hyporesponsiveness due to a heat-labile component that is assumed to be lymphocytosis-promoting factor. PMID:6307869

  4. Assessment of serologic immunity to diphtheria-tetanus-pertussis after treatment of Korean pediatric hematology and oncology patients.

    Science.gov (United States)

    Kwon, Hyo Jin; Lee, Jae-Wook; Chung, Nak-Gyun; Cho, Bin; Kim, Hack-Ki; Kang, Jin Han

    2012-01-01

    The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination.

  5. Plasticity of fimbrial genotype and serotype within populations of Bordetella pertussis: analysis by paired flow cytometry and genome sequencing.

    Science.gov (United States)

    Vaughan, Thomas E; Pratt, Catherine B; Sealey, Katie; Preston, Andrew; Fry, Norman K; Gorringe, Andrew R

    2014-09-01

    The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its -10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection.

  6. Two injections of diphtheria-tetanus-pertussis-polio vaccine as the backbone of a simplified immunization schedule in developing countries.

    Science.gov (United States)

    Cohen, H; Nagel, J

    1984-01-01

    From studies of antibody levels induced against poliovirus types 1, 2, and 3 and against diphtheria and tetanus toxins as well as from epidemiologic studies comparing the protective effect in children of two and three doses of diphtheria-tetanus-pertussis (DTP) vaccine, respectively, it can be concluded that two injections of DTP-polio vaccine administered at least four months apart will induce immunity against the four diseases. An immunization schedule can be built up in which bacille Calmette-Guérin (BCG) vaccine is given simultaneously with the first DTP-polio injection at the age of three to eight months and vaccination against measles and--if needed--yellow fever is performed simultaneously with the second DTP-polio immunization at the age of nine to 14 months.

  7. Expression and purification of the Bordella Pertussis toxin S1 subunit mutant in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Xiao L. Zhang; Quan M. Zou

    2007-01-01

    Bordella pertussis is the causative agent of whooping cough.Traditional vaccines against this disease are inherently reactogenic, thus research is currentlly focussed on the production of less reactive,acellular vaccines.Expression of candidate antigens for these vaccines in Escherichia coli would be preferable. Pertussis toxin S1 subunit plays a critical role in the bacterium-host interplay.The mutant(rS1) containing two key amino acids substitution(Arg9-Lys/Glu129-Gly)is nontoxin and immunogenic and while retaining the protective epitopes. In this study, the immunoprotective S1 fragment of pertussis toxin fusion was verified by restriction endonuclease analysis and Western immunoblotting. Escherichia coli carrying the recombinant plasmid(pQE-rS1)produced a 26 kDa protein that was recognized by antibodies specific to the S1. Expressed rS1 in E. coli was purified from the inclusion bodies. The N-terminal 6 histidines could easily be captured by Ni-NTA affinity chromatography. Then, the rS1 of interest was purified to 92% homogeneity. Antisera generated against the purified S1 mutant protein recognized the native toxin indicating that some, if not all, of the native epitope were conserved. Thus, this vaccine preparation is potentially applicable for the production of novel vaccines against B. pertussis infection.

  8. Systematic review of human papillomavirus vaccine coadministration.

    Science.gov (United States)

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  9. Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine.

    Science.gov (United States)

    Griffin, M R; Ray, W A; Livengood, J R; Schaffner, W

    1988-09-01

    To evaluate recent immunization against diphtheria, tetanus, and pertussis (DTP) as a possible risk factor for sudden infant death syndrome (SIDS), we studied the rates of SIDS after the administration of DTP vaccine in a cohort of 129,834 children who were born in four urban Tennessee counties during the period from 1974 through 1984. All the children received at least one DTP immunization in the first year of life at county health-department clinics or from Medicaid providers. Computerized immunization records from these sources were linked with Tennessee birth and death certificates to establish the cohort, ascertain the timing of immunization, and identify cases of SIDS. These children represented 42 percent of the births in the four counties. Among these children, 204 deaths occurred at the ages of 29 to 365 days; 109 deaths were classified as due to SIDS. We estimated the risk of SIDS according to the length of time, up to 30 days, since DTP immunization and compared it with the risk 31 days or more after immunization to calculate the relative risk. With control for age, the relative risk from 0 to 3 days after DTP immunization was 0.18 (95 percent confidence interval, 0.04 to 0.8); from 4 to 7 days, 0.17 (95 percent confidence interval, 0.04 to 0.7); from 8 to 14 days, 0.75 (95 percent confidence interval, 0.4 to 1.5); and from 15 to 30 days, 1.0 (95 percent confidence interval, 0.6 to 1.6). A multivariate analysis in which we controlled for age, sex, race, year, birth weight, and Medicaid enrollment, produced similar results. We conclude that in this large population of children there was no increase in the risk of SIDS after immunization with the DTP vaccine.

  10. Caspase-1-independent interleukin-1β is required for clearance of Bordetella pertussis infections and whole-cell vaccine-mediated immunity.

    Directory of Open Access Journals (Sweden)

    David E Place

    Full Text Available Whooping cough remains a significant disease worldwide and its re-emergence in highly vaccinated populations has been attributed to a combination of imperfect vaccines and evolution of the pathogen. The focus of this study was to examine the role of IL-1α/β and the inflammasome in generation of the interleukin-1 (IL-1 response, which is required for the clearance of Bordetella pertussis. We show that IL-1β but not IL-1α is required for mediating the clearance of B. pertussis from the lungs of mice. We further found that IL-1β and IL-1R deficient mice, compared to wild-type, have similar but more persistent levels of inflammation, characterized by immune cell infiltration, with significantly increased IFNγ and a normal IL-17A response during B. pertussis infection. Contrary to expectations, the cleavage of precursor IL-1β to its mature form did not require caspase-1 during primary infections within the lung despite being required by bone marrow-derived macrophages exposed to live bacteria. We also found that the caspase-1 inflammasome was not required for protective immunity against a B. pertussis challenge following vaccination with heat-killed whole cell B. pertussis, despite IL-1R signaling being required. These findings demonstrate that caspase-1-independent host factors are involved in the processing of protective IL-1β responses that are critical for bacterial clearance and vaccine-mediated immunity.

  11. Caspase-1-independent interleukin-1β is required for clearance of Bordetella pertussis infections and whole-cell vaccine-mediated immunity.

    Science.gov (United States)

    Place, David E; Muse, Sarah J; Kirimanjeswara, Girish S; Harvill, Eric T

    2014-01-01

    Whooping cough remains a significant disease worldwide and its re-emergence in highly vaccinated populations has been attributed to a combination of imperfect vaccines and evolution of the pathogen. The focus of this study was to examine the role of IL-1α/β and the inflammasome in generation of the interleukin-1 (IL-1) response, which is required for the clearance of Bordetella pertussis. We show that IL-1β but not IL-1α is required for mediating the clearance of B. pertussis from the lungs of mice. We further found that IL-1β and IL-1R deficient mice, compared to wild-type, have similar but more persistent levels of inflammation, characterized by immune cell infiltration, with significantly increased IFNγ and a normal IL-17A response during B. pertussis infection. Contrary to expectations, the cleavage of precursor IL-1β to its mature form did not require caspase-1 during primary infections within the lung despite being required by bone marrow-derived macrophages exposed to live bacteria. We also found that the caspase-1 inflammasome was not required for protective immunity against a B. pertussis challenge following vaccination with heat-killed whole cell B. pertussis, despite IL-1R signaling being required. These findings demonstrate that caspase-1-independent host factors are involved in the processing of protective IL-1β responses that are critical for bacterial clearance and vaccine-mediated immunity.

  12. Vaccine-Mediated Activation of Human TLR4 Is Affected by Modulation of Culture Conditions during Whole-Cell Pertussis Vaccine Preparation

    Science.gov (United States)

    Hoonakker, Marieke E.; Verhagen, Lisa M.; Pupo, Elder; de Haan, Alex; Metz, Bernard; Hendriksen, Coenraad F. M.; Han, Wanda G. H.; Sloots, Arjen

    2016-01-01

    The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity. The protein compositions and in vivo potencies of the vaccines were BvgASR dependent, with the vaccine containing the highest amount of virulence proteins having the highest in vivo potency. Here, the capacities of these vaccines to stimulate human Toll-like receptors (hTLR) 2 and 4 and the role these receptors play in wP vaccine-mediated activation of antigen-presenting cells in vitro were studied. Prolonged BvgASR suppression was associated with a decreased capacity of vaccines to activate hTLR4. In contrast, no significant differences in hTLR2 activation were observed. Similarly, vaccine-induced activation of MonoMac-6 and monocyte-derived dendritic cells was strongest with the highest potency vaccine. Blocking of TLR2 and TLR4 showed that differences in antigen-presenting cell activation could be largely attributed to vaccine-dependent variation in hTLR4 signalling. Interestingly, this BvgASR-dependent decrease in hTLR4 activation coincided with a reduction in GlcN-modified lipopolysaccharides in these vaccines. Accordingly, expression of the lgmA-C genes, required for this glucosamine modification, was significantly reduced in bacteria exposed to sulfate. Together, these findings demonstrate that the BvgASR status of bacteria during wP vaccine preparation is critical for their hTLR4 activation capacity and suggest that including

  13. Non-specific effects of diphtheria-tetanus-pertussis and measles vaccinations? An analysis of surveillance data from Navrongo, Ghana.

    Science.gov (United States)

    Welaga, Paul; Nielsen, Jens; Adjuik, Martin; Debpuur, Cornelius; Ross, David A; Ravn, Henrik; Benn, Christine S; Aaby, Peter

    2012-12-01

    Studies from low-income countries have suggested that routine vaccinations may have non-specific effects on child mortality; measles vaccine (MV) is associated with lower mortality and diphtheria-tetanus-pertussis (DTP) with relatively higher mortality. We used data from Navrongo, Ghana, to examine the impact of vaccinations on child mortality. Vaccination status was assessed at the initiation of a trial of vitamin A supplementation and after 12 and 24 months of follow-up. Within the placebo group, we compared the mortality over the first 4 months and the full 2 years of follow-up for different vaccination status groups with different likelihoods of additional vaccinations during follow-up. The frequency of additional vaccinations was assessed among children whose vaccination card was seen at 12 and 24 months of follow-up. Among children with a vaccination card, more than 75% received missing DTP or MV during the first 12 months of follow-up, whereas only 25% received these vaccines among children with no vaccination card at enrollment. Children without a card at enrollment had a significant threefold higher mortality over the 2-year follow-up period than those fully vaccinated. The small group of children with DTP3-4 but no MV at enrollment had lower mortality than children without a card and had the same mortality as fully vaccinated children. In contrast, children with 1-2 DTP doses but no MV had a higher mortality during the first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared with the fully vaccinated children, they had significantly higher mortality after 4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)]. Children with 0-2 DTP doses at enrollment had higher mortality after 4 months (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than children who had all three doses of DTP at enrollment. As hypothesised, DTP vaccination was associated with higher child mortality than measles

  14. The effect of vitamin A supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model

    DEFF Research Database (Denmark)

    Jørgensen, Mathias Jul; Hein-Kristensen, Line; Hempel, Casper

    2011-01-01

    Abstract Background: Vitamin A supplementation (VAS) decreases overall child mortality in low-income countries. For logistical reasons, VAS has been linked to routine childhood immunizations. However, several recent studies have indicated that VAS may increase mortality and morbidity from...... infectious diseases when given with the diphtheria-tetanus-pertussis (DTP) vaccine. The immunological effects of combining the 2 treatments are unknown. Methods: We studied the effect of treating C57BL/6 mice with VAS and DTP, 1 week prior to infection with Plasmodium berghei ANKA. The progression of disease...

  15. Stability of EIA kits for determination of pertussis antigens and their application in the production process of pertussis vaccine%检测百日咳抗原的系列酶免疫测定试剂盒的稳定性及其在百日咳疫苗生产中的应用

    Institute of Scientific and Technical Information of China (English)

    潘殊男; 张霖阳; 王玲; 夏德菊; 王宇星; 肖詹蓉

    2014-01-01

    目的 评估检测百日咳毒素(pertussis toxin,PT)、丝状血凝素(filamentous haemagglutinin,FHA)和黏着素(pertactin,Prn)的3种酶免疫测定试剂盒的稳定性及其在无细胞百日咳疫苗(acellular pertussis vaccine,aPV)生产质量控制中的应用.方法 对3种酶免疫测定试剂盒进行热加速试验(37℃放置3 d)和长期稳定性试验(4℃放置6月),根据试剂盒的标准曲线相关系数、最高浓度标准品与阴性对照的吸光度值之比(P/N)值、质控品回收率评估试剂盒的稳定性.将3种试剂盒用于aPV生产的发酵、纯化、吸附阶段的PT、FHA、Prn定量检测,以确定3种试剂盒对aPV生产质量控制的可行性.结果 3种酶免疫测定试剂盒的37℃热加速试验和4℃长期稳定性试验的各项质量参数均符合相关要求.采用试剂盒定量各生产阶段的百日咳抗原含量显示:百日咳杆菌的发酵终点在第42~46 h;各3批PT、FHA和Prn组分液的纯化回收率分别为49.24%、56.12%和63.65%,68.75%、55.60%和49.76%、75.73%、60.63%和50.10%.采用单独吸附的铝佐剂抗原吸附率高于采用混合吸附,但单独和混合吸附方式制备的疫苗的效力无差异.结论 检测PT、FHA和Prn的3种酶免疫测定试剂盒具有良好的稳定性,可用于aPV生产的质量控制.%Objective To evaluate the stability of 3 kinds of EIA kits for detecting pertussis toxin (PT),filamentous haemagglutinin (FHA) and pertactin (Prn) and their application in the quality control of acellular pertussis vaccine (aPV) production.Methods The stability of EIA kits were evaluated by heat accelerated test (37 ℃ for 3 days) and long-term stability test (4 ℃ for 6 months),using the correlation coefficient of standard curve,the P/N value and the recovery of the quality control material.The contents of PT,FHA and Prn in the fermentation,purification and adsorption stages during the production process of aPV were detected by these 3 kinds

  16. Tdap Vaccine (Tetanus, Diphtheria and Pertussis): What You Need to Know

    Science.gov (United States)

    ... It can lead to breathing problems, heart failure, paralysis, and death. PERTUSSIS (Whooping Cough) causes severe coughing spells, which can cause difficulty breathing, vomiting and disturbed sleep. • It can also lead to weight loss, incontinence, ...

  17. Tdap (tetanus, diphtheria and pertussis) vaccine - what you need to know

    Science.gov (United States)

    ... It can lead to breathing problems, heart failure, paralysis, and death. PERTUSSIS (Whooping Cough) causes severe coughing spells, which can cause difficulty breathing, vomiting, and disturbed sleep. It can also lead to weight loss, incontinence, ...

  18. Granulocyte-macrophage colony-stimulating factor DNA prime-protein boost strategy to enhance efficacy of a recombinant pertussis DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Qing-tian LI; Yong-zhang ZHU; Jia-you CHU; Ke DONG; Ping HE; Chun-yan FENG; Bao-yu HU; Shu-min ZHANG; Xiao-kui GUO

    2006-01-01

    Aim: To investigate a new strategy to enhance the efficacy of a recombinant pertussis DNA vaccine. The strategy is co-injection with cytokine plasmids as prime, and boosted with purified homologous proteins. Method: A recombinant pertussis DNA vaccine containing the pertussis toxin subunit 1 (PTS1), fragments of the filamentous hemagglutinin (FHA) gene and pertactin (PRN) gene encoding filamentous hemagglutinin and pertactin were constructed. Balb/c mice were immunized with several DNA vaccines and antigen-specific antibodies anti-PTSl, anti-PRN, anti-FHA, cytokines interleukin (IL)-10, IL-4, IFN-γ, TNF-oc, and spleno-cyte-proliferation assay were used to describe immune responses. Results: The recombinant DNA vaccine could elicit similar immune responses in mice as that of separate plasmids encoding the 3 fragments, respectively. Mice immunized with DNA and boosted with the corresponding protein elicited more antibodies than those that received DNA as boost. In particular, when the mice were co-immunized with murine granulocyte-macrophage colony-stimulating factor plasmids and boosted with proteins, all 4 cytokines and the 3 antigen-specific antibodies were significantly increased compared to the pVAXl group. Anti-PTSl, anti-FHA, IL-4 and TNF-α elicited in the colony stimulating factor (CSF) prime-protein boost group showed significant increase compared to all the other groups. Conclusion: This prime and boost strategy has proven to be very useful in improving the immunogenicity of DNA vaccines against pertussis.

  19. [Vaccination coverage against pertussis in pregnant women of Catalonia in the first year of implementation of the immunisation program].

    Science.gov (United States)

    Fernández-Cano, María Isabel; Espada-Trespalacios, Xavier; Reyes-Lacalle, Azahara; Manresa Domínguez, Josep Maria; Armadans-Gil, Lluís; Campins-Martí, Magda; Falguera-Puig, Gemma; Toran Monserrat, Pere

    2016-10-18

    The re-emergence of pertussis and the severity of its complications in infants younger than 3 months, were determining factors for starting a vaccination program for pregnant women in the third trimester of gestation in Catalonia in February 2014. This was the first autonomous community to introduce it in Spain. The aim of the study was to estimate the coverage of the program in its first year of implementation. A retrospective analysis was performed on the data from the Primary Care Centre computerised medical records of pregnant women attending Sexual and Reproductive Health Care centres of the Metropolitan Nord area of the province of Barcelona, part of the Catalan Institute of Health. The overall coverage was estimated, as well as the sociodemographic variables of Tdap vaccination of women who had registered a delivery of a live birth between August 2014 and August 2015. A total of 6,697 deliveries of live births were recorded, and 1,713 pregnant women were vaccinated, which represented an overall coverage of 25.6% (95% CI; 24.1-26.1). Vaccination coverage was higher in pregnant women under 18 years and Spanish women (P=.018 and P=.036, respectively). The estimation of vaccine coverage against pertussis in pregnant women in the third trimester of pregnancy, after the first year of implementation of the program in a health area of Catalonia was lower than the objective set. Strategies need to be designed in order to improve program coverage. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Colonization of Bordetella pertussis clinical isolates that differ by pulsed field gel electrophoresis types in the lungs of naïve mice or mice immunized with the whole-cell pertussis vaccine used in Poland.

    Science.gov (United States)

    Polak, Maciej; Zawadka, Monika; Mosiej, Ewa; Rabczenko, Daniel; Augustynowicz, Ewa; Guiso, Nicole; Lutyńska, Anna

    2015-04-01

    The goal of our study was to compare the elimination of Bordetella pertussis clinical isolates that differ according to pulsed field gel electrophoresis (PFGE), serotypes and genes encoding virulence factors from the lungs of naïve mice or mice immunized with commercial diphtheria-tetanus-whole-cell pertussis vaccine used in Poland. When a mixture of four isolates, given in equal proportions and harboring different PFGE profiles, serotypes, and alleles encoding virulence factors, was used to infect non-immunized mice, a single isolate, characterized by PFGE type IVγ, Fim2 phenotype and ptxA1-prn2-tcfA2-fim2-1-ptxP1-ptxC1-fim3-1 alleles, was found to be significantly predominant compared to the others. This PFGE profile is commonly found in B. pertussis isolates circulating in some European countries since the late 1990s, confirming its high fitness. The Polish commercial whole-cell pertussis vaccine induced an immunity effective at eliminating the B. pertussis isolates from the lungs. However, the elimination of the isolate harboring PFGE type C profile, Fim2,3 phenotype and ptxA1-prn1-tcfA2-fim2-1-ptxP1-ptxC1-fim3-1 alleles was delayed as compared to the others, suggesting phenotypic differences with the other isolates and vaccine strains. Nevertheless, the same isolate, when challenged into mice in the defined mixture of strains, lost the competition with the others, as measured by lung colonization efficiency. This PFGE profile represents 15 % of the isolates circulating in Poland between 2001 and 2012.

  1. Effect of vaccinations on seizure risk and disease course in Dravet syndrome.

    Science.gov (United States)

    Verbeek, Nienke E; van der Maas, Nicoline A T; Sonsma, Anja C M; Ippel, Elly; Vermeer-de Bondt, Patricia E; Hagebeuk, Eveline; Jansen, Floor E; Geesink, Huibert H; Braun, Kees P; de Louw, Anton; Augustijn, Paul B; Neuteboom, Rinze F; Schieving, Jolanda H; Stroink, Hans; Vermeulen, R Jeroen; Nicolai, Joost; Brouwer, Oebele F; van Kempen, Marjan; de Kovel, Carolien G F; Kemmeren, Jeanet M; Koeleman, Bobby P C; Knoers, Nine V; Lindhout, Dick; Gunning, W Boudewijn; Brilstra, Eva H

    2015-08-18

    To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific. © 2015 American Academy of Neurology.

  2. Fully liquid DTaP-IPV-Hib pediatric combination vaccine (Pediacel): a review of 18 years of clinical experience.

    Science.gov (United States)

    Reynolds, Donna L; Vidor, Emmanuel

    2014-08-01

    Safe and effective combination pediatric vaccines are necessary to simplify complex immunization schedules and to improve coverage and protection for children worldwide. We provide an overview of the 18 years of clinical and worldwide experience with DTaP-IPV-Hib (Pediacel(®)), a unique fully liquid pentavalent vaccine (diphtheria [D], tetanus [T], acellular pertussis, inactivated poliovirus [IPV], Haemophilus influenzae type b [Hib]). Pediacel has demonstrated good and lasting immunogenicity in many populations, with differing primary series and booster schedules, and with a variety of coadministered vaccines. The acellular pertussis antigens have proven efficacy and real-world effectiveness. Clinical and post-marketing studies confirm the safety of Pediacel. Pediacel can be used for primary series and toddler booster doses, as well as in mixed pediatric vaccine schedules.

  3. Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination: diffusion-weighted imaging and proton MR spectroscopy findings

    Energy Technology Data Exchange (ETDEWEB)

    Aydin, Hale; Ozgul, Esra; Agildere, Ahmet Muhtesem [Baskent University Hospital, Department of Radiology, Ankara (Turkey)

    2010-07-15

    We present a previously healthy 6-month-old boy who was admitted to our hospital with lethargy, hypotonia and focal clonic seizures 6 days following diptheria, tetanus toxoid and whole-cell pertussis vaccination. A diagnosis of acute necrotising encephalopathy was made with the aid of MRI, including diffusion-weighted imaging and proton MR spectroscopy. (orig.)

  4. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    Science.gov (United States)

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract.

  5. Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.

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    Tjeerd G Kimman

    Full Text Available BACKGROUND: Activation of the Toll-like receptor (TLR signaling pathway through TLR4 may be important in the induction of protective immunity against Bordetella pertussis with TLR4-mediated activation of dendritic and B cells, induction of cytokine expression, and reversal of tolerance as crucial steps. We examined whether single nucleotide polymorphisms (SNPs in genes of the TLR4 pathway and their interaction are associated with the response to whole-cell vaccine (WCV pertussis vaccination in 490 one-year-old children. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed associations of 75 haplotype-tagging SNPs in genes in the TLR4 signaling pathway with pertussis toxin (PT-IgG titers. We found significant associations between the PT-IgG titer and SNPs in CD14, TLR4, TOLLIP, TIRAP, IRAK3, IRAK4, TICAM1, and TNFRSF4 in one or more of the analyses. The strongest evidence for association was found for two SNPs (rs5744034 and rs5743894 in TOLLIP that were almost completely in linkage disequilibrium, provided statistically significant associations in all tests with the lowest p-values, and displayed a dominant mode of inheritance. However, none of these single gene associations would withstand correction for multiple testing. In addition, Multifactor Dimensionality Reduction Analysis, an approach that does not need correction for multiple testing, showed significant and strong two and three locus interactions between SNPs in TOLLIP (rs4963060, TLR4 (rs6478317 and IRAK1 (rs1059703. CONCLUSIONS/SIGNIFICANCE: We have identified significant interactions between genes in the TLR pathway in the induction of vaccine-induced immunity. These interactions underline that these genes are functionally related and together form a true biological relationship in a protein-protein interaction network. Practically all our findings may be explained by genetic variation in directly or indirectly interacting proteins at the extra- and intracytoplasmic sites of the cell

  6. Epidemiology, reemergence of pertussis and vaccine development in Latin America: an overview

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    Celso Pérez-Bolaños

    2011-01-01

    Full Text Available Pertussis o tosferina es una enfermedad bacteriana aguda del tracto respiratorio, causada principalmente por Bordetella pertussis y en menor medida por Bordetella parapertussis. Bordetella pertussis ocupa el quinto lugar en la lista de muertes atribuidas a enfermedades prevenibles por vacunas en niños menores de cinco años en todo el mundo. Se ha reportado que provoca morbilidad y mortalidad significativa, tanto en países desarrollados como en países en desarrollo. La enfermedad es más severa en niños pequeños, pero su prevalencia ha sido observada en todo el mundo en todos los grupos de edad, aún después del desarrollo de vacunas a partir de células completas contra pertussis en los años cuarenta del pasado siglo. Desde la última década ha sido reportada una re-emergencia de pertussis en muchos países desarrollados, incluidos aquellos con una elevada cobertura de vacunación por años. Varios factores pudieran provocar la re-emergencia de pertussis, por ejemplo, una mayor conciencia del problema, un mejor diagnóstico mediante la implementación de técnicas de PCR, disminución de la cobertura de vacunación, la utilización de vacunas de baja protección, baja inmunidad inducida por vacunas y adaptación del patógeno. Este trabajo revisa el estado actual de la epidemiología y la re-emergencia de la enfermedad en América Latina y enfoca la situación actual en Cuba, para dar un panorama de la aplicación de estrategias novedosas en el desarrollo de vacunas futuras, así como medidas generales, recomendadas para el tratamiento de la enfermedad.

  7. Direct molecular typing of Bordetella pertussis from nasopharyngeal specimens in China in 2012-2013.

    Science.gov (United States)

    Du, Q; Wang, X; Liu, Y; Luan, Y; Zhang, J; Li, Y; Liu, X; Ma, C; Li, H; Wang, Z; He, Q

    2016-07-01

    Data on the molecular epidemiology of Bordetella pertussis are limited in developing countries where whole-cell pertussis vaccines (WCVs) have been used. The aim of this study was to determine the genotypes of circulating B. pertussis in China by direct molecular typing of clinical specimens. DNA extracts of 122 nasopharyngeal swabs (NPs) positive for B. pertussis by polymerase chain reaction (PCR) (targeting IS481 and ptx-Pr) from 2012 to 2013 were used for typing using the multiple-locus variable number tandem repeat analysis (MLVA) and also by PCR-based multilocus sequence typing (MLST) of B. pertussis virulence genes (ptxP, prn, and fim3). One hundred and eight DNA extracts (89 %) generated a complete MLVA type (MT). Among the 18 MTs obtained, MT55 (52 %) and MT104 (13 %) were the most common. MT27, which is linked to the ptxP3 allele and is prevalent in many developed countries using acellular pertussis vaccines (ACVs), was only found in 7 (6 %) DNA extracts. Eighty-seven DNA extracts (71 %) produced a complete multiantigen sequence typing (MAST) type. Of them, 77 (89 %) had the ptxP1/prn1/fim3-1 allele profile. Four DNA extracts (5 %) had the ptxP3/prn2/fim3-2 profile and 3 (4 %) had the ptxP3/prn1/fim3-2 allele profile. These seven DNA extracts also harbored MT27. Our result shows that B. pertussis circulating in China was different from those found in countries where ACVs have been in use, supporting the notion that selection pressure induced by WCVs and ACVs on the bacterial population differs.

  8. Prevalence and molecular characterization of pertactin-deficient Bordetella pertussis in the United States.

    Science.gov (United States)

    Pawloski, L C; Queenan, A M; Cassiday, P K; Lynch, A S; Harrison, M J; Shang, W; Williams, M M; Bowden, K E; Burgos-Rivera, B; Qin, X; Messonnier, N; Tondella, M L

    2014-02-01

    Pertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s. Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive). The first prnIS481-positive isolate was found in 1994, and the next prnIS481-positive isolates were not detected until 2010. The prevalence of pertactin-deficient isolates increased substantially to more than 50% of collected isolates in 2012. Sequence analysis of pertactin-deficient isolates revealed various types of mutations in the prn gene, including two deletions, single nucleotide substitutions resulting in a stop codon, an inversion in the promoter, and a single nucleotide insertion resulting in a frameshift mutation. All but one mutation type were found in prn2 alleles. CDC 013 was a predominant pulsed-field gel electrophoresis (PFGE) profile in the pertactin-positive isolates (203/994) but was found in only 5% (16/306) of the pertactin-deficient isolates. Interestingly, PFGE profiles CDC 002 and CDC 237 represented 55% (167/306) of the identified pertactin-deficient isolates. These results indicate that there has been a recent dramatic increase in pertactin-deficient B. pertussis isolates throughout the United States.

  9. Re-emergence of diphtheria and pertussis: implications for Nigeria.

    Science.gov (United States)

    Sadoh, A E; Oladokun, R E

    2012-11-26

    In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

  10. Purification of heat labile toxin from Bordetella pertussis vaccine strain 134 employed indigenous technology

    Directory of Open Access Journals (Sweden)

    K.C. Shivanandappa

    2016-06-01

    Conclusion: The B. pertussis HLT could be purified through two phase with G50 and DEAE, cost effective techniques, the G50 purification has reduced the bioburden problems during DEAE purification and at the same time the quality of the product was high.

  11. Manufacturing Vaccines: An Illustration of Using PAT Tools for Controlling the Cultivation of Bordetella pertussis

    NARCIS (Netherlands)

    Sprang, van E.N.M.; Streefland, M.; Ramaker, H.J.; Pol, van der L.A.; Beuvery, E.C.; Smilde, A.K.

    2007-01-01

    An illustration of the operational consistency of the upstream part of a biopharmaceutical process is given. For this purpose four batch cultivations of Bordetella pertussis have been executed under identical conditions. The batches have been monitored by means of two fundamentally different process

  12. Manufacturing Vaccines: An Illustration of Using PAT Tools for Controlling the Cultivation of Bordetella pertussis

    NARCIS (Netherlands)

    Sprang, van E.N.M.; Streefland, M.; Ramaker, H.J.; Pol, van der L.A.; Beuvery, E.C.; Smilde, A.K.

    2007-01-01

    An illustration of the operational consistency of the upstream part of a biopharmaceutical process is given. For this purpose four batch cultivations of Bordetella pertussis have been executed under identical conditions. The batches have been monitored by means of two fundamentally different process

  13. Differential effect of TLR2 and TLR4 on the immune response after immunization with a vaccine against Neisseria meningitidis or Bordetella pertussis.

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    Floris Fransen

    Full Text Available Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2-/- mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required.

  14. Systems vaccinology : molecular signatures of immunity to Bordetella pertussis

    NARCIS (Netherlands)

    Raeven, R.H.M.

    2016-01-01

    The worldwide resurgence of whooping cough (pertussis), even in highly vaccinated populations, demands improved pertussis vaccines. In this thesis a systems vaccinology approach is applied to deepen knowledge of the immune responses evoked by different pertussis vaccines and compare this with a Bord

  15. Immunogenicity of live attenuated B. pertussis BPZE1 producing the universal influenza vaccine candidate M2e.

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    Hana Kammoun

    Full Text Available BACKGROUND: Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration. However, using this delivery route for inactivated vaccines usually requires the use of potent mucosal adjuvants, and no such adjuvant has yet been approved for human use. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a live attenuated Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to present the universal influenza virus epitope M2e to the mouse respiratory tract to prime for protective immunity against viral challenge. Three copies of M2e were genetically fused to the N-terminal domain of filamentous hemagglutinin (FHA and produced in recombinant BPZE1 derivatives in the presence or absence of endogenous full-length FHA. Only in the absence of FHA intranasal administration of the recombinant BPZE1 derivative induced antibody responses to M2e and effectively primed BALB/c mice for protection against influenza virus-induced mortality and reduced the viral load after challenge. Strong M2e-specific antibody responses and protection were observed after a single nasal administration with the recombinant BPZE1 derivative, followed by a single administration of M2e linked to a virus-like particle without adjuvant, whereas priming alone with the vaccine strain did not protect. CONCLUSIONS/SIGNIFICANCE: Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the universal influenza M2e peptide linked to virus-like particles for boosting may constitute a promising approach for needle-free and adjuvant-free nasal vaccination against influenza.

  16. Prevalence of high antibody titers of pertussis in Turkey: reflection of circulating microorganism and a threat to infants.

    Science.gov (United States)

    Esen, Berrin; Coplu, Nilay; Kurtoglu, Demet; Gozalan, Aysegul; Akin, Levent

    2007-01-01

    Acute pertussis infection among adults can cause its transmission to the larger population, especially to infants and young children, who can develop severe disease. In order to determine an age-dependent pertussis immune response, anti-pertussis toxin (PT) antibody was detected by the indirect enzyme-linked immunosorbent assay (ELISA) method in serum samples from 2,085 healthy subjects ranging in age from 6 months to > or = 60 years. Also included in the evaluation were responses to a questionnaire including sociodemographic characteristics, vaccination, and infection history. Titers of 50-99 ELISA units (EU)/mL and of > or = 100 EU/mL were accepted as indicative for recent exposure or infection. In addition, 30 EU/mL was estimated to be a sufficient titer in women of childbearing age to protect their newborns until administration of their first dose of pertussis vaccine. After the age of 4-5 years, presence of high-titered antibodies that increase with age might be a reflection of circulating infection and indicate the magnitude of the threat to infants. According to the questionnaires, in the groups younger than 15 years old, three to four doses of diphtheria toxoid-whole cell pertussis-tetanus toxoid (DwPT) were administered in 47.2 to 77.4%, 91.2 to 100.0%, and 83.5 to 100.0% of participants in Diyarbakir, Samsun, and Antalya, respectively. In addition, up to half of the expectant mothers we studied lacked a sufficient level of estimated antibody titers. To protect infants from life-threatening pertussis infection, improving vaccination coverage to ensure herd immunity and uniformly establishing coverage throughout the country are essential. Furthermore, revaccination with acellular vaccine for schoolchildren as well as for the households of pregnant women is recommended.

  17. A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.

    Science.gov (United States)

    Sugai, Toshiyuki; Mori, Masaaki; Nakazawa, Masatoshi; Ichino, Motohide; Naruto, Takuya; Kobayashi, Naoki; Kobayashi, Yoshinori; Minami, Mutsuhiko; Yokota, Shumpei

    2005-11-16

    Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.

  18. Preparation and evaluation of alginate nanoparticles containing pertussis toxin as a particulate delivery system

    Directory of Open Access Journals (Sweden)

    Hamid Reza Goudarzi

    2016-04-01

    Full Text Available During the last decades, research on different kinds of nanoparticles (NPs has been increased to prepare various medical applications, for instance in vaccine and gene delivery and as new generation of adjuvant candidates. The aim of the present study was to prepare sodium alginate nanoparticles (Alg-NPs containing pertussis toxin (PTX as an candidate acellular vaccine. Formulation of antigen loaded Alg-NPs were assessed for immunological activities and their role as potential immunological adjuvant. Alg-Nps were prepared using mild ionic gelation method. Optimal formulation was obtained by concentration of 0.2%w/v sodium alginate, 0.1%w/v CaCl2 solution and magnetically homogenization condition of 45 min and rate of 2000 rpm. Obtained Alg-NPs showed average size of 88 nm and zeta potential of -32mV in blank and 72 nm and -29 mV in PTX entrapped nanoparticles, respectively. A Loading efficiency of more than 90% was determined for PTX. The antigen loaded nanoparticles showed 75.3% of release within 144 h in in vitro release studies. The immunological evaluation in female Balb/c mice groups revealed that the Alg-NPs formulation induced significantly higher serum antibody titers (p < 0.01 as compared with commercial acellular pertussis vaccine and conventional alum-adjuvanted antigen administered by subcutaneous route. The results showed the potential of Alg-NPS to be a simplex and efficient delivery system. This study also indicated the potential of Alg-NPs as new generation of immunostimulant adjuvant to boost the antigenecity of the antigens in a cellular pertussis vaccines.

  19. In vitro characterization of pertussis vaccines : Functional analysis as part of the Consistency Approach

    NARCIS (Netherlands)

    Hoonakker, M.E.

    2017-01-01

    The current paradigm in vaccine lot release testing is that each final lot of vaccine produced is unique, due to the considerable inherent variation in the preceding biological production process. Consequently, each individual vaccine lot needs to be tested for safety and potency, frequently

  20. In vitro characterization of pertussis vaccines : Functional analysis as part of the Consistency Approach

    NARCIS (Netherlands)

    Hoonakker, M.E.

    2017-01-01

    The current paradigm in vaccine lot release testing is that each final lot of vaccine produced is unique, due to the considerable inherent variation in the preceding biological production process. Consequently, each individual vaccine lot needs to be tested for safety and potency, frequently involvi

  1. Early BCG and pertussis vaccination and atopic diseases in 5- to 7-year-old preschool children from Augsburg, Germany: results from the MIRIAM study.

    Science.gov (United States)

    Möhrenschlager, Matthias; Haberl, Victoria M; Krämer, Ursula; Behrendt, Heidrun; Ring, Johannnes

    2007-02-01

    The role of immunization in the development of atopic disorders is still under debate. One reason might be, that because of high vaccination coverage in most countries only few and selected children are not immunized, leading to unstable and often biased effect estimates. In Germany, the situation was different between 1985 and 1991: bacillus Calmette-Guérin (BCG) and pertussis vaccination were not officially recommended leading to high numbers of non-vaccinated children in the 1990s. We report on a cross-sectional study with 1673 participants among 5- to 7-year-old preschool children conducted in 1996. We found no hint that BCG vaccination or whole-cell pertussis (WCP) vaccination may lead to higher prevalences of asthma, allergic rhinitis, eczema or allergic sensitization at preschool age. None of the associations was significantly positive. WCP vaccination may be protective against asthma OR 0.55 (95% CI: 0.31-0.98) and against symptoms of eczema in boys.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Sekura, R.D.; Moss, J.; Vaughan, M.

    1985-01-01

    This book contains 13 selections. Some of the titles are: Genetic and Functional Studies of Pertussis Toxin Substrates; Effect of Pertussis Toxin on the Hormonal Responsiveness of Different Tissues; Extracellular Adenylate Cyclase of Bordetella pertussis; and GTP-Regulatory Proteins are Introcellular Messagers: A Model for Hormone Action.

  4. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012.

    Science.gov (United States)

    Zeddeman, A; van Gent, M; Heuvelman, C J; van der Heide, H G; Bart, M J; Advani, A; Hallander, H O; Wirsing von Konig, C H; Riffelman, M; Storsaeter, J; Vestrheim, D F; Dalby, T; Krogfelt, K A; Fry, N K; Barkoff, A M; Mertsola, J; He, Q; Mooi, F

    2014-08-21

    Pathogen adaptation has been proposed to contribute to the resurgence of pertussis. A striking recent example is the emergence of isolates deficient in the vaccine component pertactin (Prn). This study explores the emergence of such Prn-deficient isolates in six European countries. During 2007 to 2009, 0/83 isolates from the Netherlands, 0/18 from the United Kingdom, 0/17 Finland, 0/23 Denmark, 4/99 Sweden and 5/20 from Norway of the isolates collected were Prn-deficient. In the Netherlands and Sweden, respectively 4/146 and 1/8 were observed in a later period (2010–12). The Prn-deficient isolates were genetically diverse and different mutations were found to inactivate the prn gene. These are indications that Prn-deficiency is subject to positive selective pressure. We hypothesise that the switch from whole cell to acellular pertussis vaccines has affected the balance between ‘costs and benefits’ of Prn production by Bordetella pertussis to the extent that isolates that do not produce Prn are able to expand. The absence of Prn-deficient isolates in some countries may point to ways to prevent or delay the spread of Prn-deficient strains. In order to substantiate this hypothesis, trends in the European B. pertussis population should be monitored continuously.

  5. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... the herd dr. offit's testimony not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  6. One Family's Struggles with Pertussis (Whooping Cough)

    Science.gov (United States)

    ... the herd dr. offit's testimony not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  7. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... not vaccinating the abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room ...

  8. Costs and effectiveness of extended vaccination strategies against pertussis and pneumococcal disease

    NARCIS (Netherlands)

    Rozenbaum, Mark Hermannes

    2013-01-01

    Omdat het Nederlandse Rijksvaccinatieprogramma al intensief is en de gezondheidszorg kampt met gelimiteerde budgetten, zijn de mogelijkheden voor opname van nieuwe vaccins in het Rijksvaccinatieprogramma beperkt. Naast vele andere factoren, hebben doelmatigheidsuitkomsten een groot effect op de besl

  9. Pertussis toxins, other antigens become likely targets for genetic engineering

    Energy Technology Data Exchange (ETDEWEB)

    Marwick, C.

    1990-11-14

    Genetically engineered pertussis vaccines have yet to be fully tested clinically. But early human, animal, and in vitro studies indicate effectiveness in reducing toxic effects due to Bordetella pertussis. The licensed pertussis vaccines consists of inactivated whole cells of the organism. Although highly effective, they have been associated with neurologic complications. While the evidence continues to mount that these complications are extremely rare, if they occur at all, it has affected the public's acceptance of pertussis immunization.

  10. Adverse events following primary and secondary immunisation with whole-cell pertussis: a systematic review protocol

    Science.gov (United States)

    Patterson, Jenna; Kagina, Benjamin M; Gold, Michael; Hussey, Gregory D; Muloiwa, Rudzani

    2017-01-01

    Introduction Pertussis is a contagious respiratory illness caused by the bacterium Bordetella pertussis. Two types of vaccines are currently available against the disease: whole-cell pertussis (wP) and acellular pertussis (aP). With the shift of high-income countries from wP to aP as a result of adverse events following immunisation (AEFI), an upsurge in reported cases of pertussis has been noticed. Owing to this, it is proposed to use wP as a prime and aP for boost vaccination strategy. However, a comparison of the AEFI with the first doses of wP and aP are not clearly documented. Methods and analysis The primary outcomes of interest are AEFI with dose 1 of wP, subsequent doses of wP and dose 1 of aP. As a secondary outcome frequency of AEFI with wP will be compared with the AEFI of doses 2 and 3 of wP and dose 1 of aP. Electronic databases will be searched and two authors will screen the titles and abstracts of the output. Full texts will then be independently reviewed by the first author and two other authors. Qualifying studies will then be formally assessed for quality and risk of bias using a scoring tool. Following standardised data extraction, statistical analysis will be carried out using STATA. Where data are available, subgroup analyses will be performed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed in reporting the findings of the systematic review and meta-analysis. Ethics and dissemination No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal. Trial registration number This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42016035809. PMID:28122832

  11. Human dendritic cell maturation and cytokine secretion upon stimulation with Bordetella pertussis filamentous haemagglutinin.

    Science.gov (United States)

    Dirix, Violette; Mielcarek, Nathalie; Debrie, Anne-Sophie; Willery, Eve; Alonso, Sylvie; Versheure, Virginie; Mascart, Françoise; Locht, Camille

    2014-07-01

    In addition to antibodies, Th1-type T cell responses are also important for long-lasting protection against pertussis. However, upon immunization with the current acellular vaccines, many children fail to induce Th1-type responses, potentially due to immunomodulatory effects of some vaccine antigens, such as filamentous haemagglutinin (FHA). We therefore analysed the ability of FHA to modulate immune functions of human monocyte-derived dendritic cells (MDDC). FHA was purified from pertussis toxin (PTX)-deficient or from PTX- and adenylate cyclase-deficient Bordetella pertussis strains, and residual endotoxin was neutralized with polymyxin B. FHA from both strains induced phenotypic maturation of human MDDC and cytokine secretion (IL-10, IL-12p40, IL-12p70, IL-23 and IL-6). To identify the FHA domains responsible for MDDC immunomodulation, MDDC were stimulated with FHA containing a Gly→Ala substitution at its RGD site (FHA-RAD) or with an 80-kDa N-terminal moiety of FHA (Fha44), containing its heparin-binding site. Whereas FHA-RAD induced maturation and cytokine production comparable to those of FHA, Fha44 did not induce IL-10 production, but maturated MDDC at least partially. Nevertheless, Fha44 induced the secretion of IL-12p40, IL-12p70, IL-23 and IL-6 by MDDC, albeit at lower levels than FHA. Thus, FHA can modulate MDDC responses in multiple ways, and IL-10 induction can be dissociated from the induction of other cytokines.

  12. Spotlight on DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa).

    Science.gov (United States)

    Dhillon, Sohita

    2010-10-01

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titers. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive

  13. DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa): A Review of its Use as Primary and Booster Vaccination.

    Science.gov (United States)

    Dhillon, Sohita

    2010-05-28

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive

  14. IMMUNOGENICITY AND SAFETY OF QUINVAXEM® (DIPHTHERIA, TETANUS, WHOLE-CELL PERTUSSIS, HEPATITIS B AND HAEMOPHILUS INFLUENZAE TYPE B VACCINE) GIVEN TO VIETNAMESE INFANTS AT 2 TO 4 MONTHS OF AGE.

    Science.gov (United States)

    Huu, Tran Ngoc; Phuong, Nguyen Thi Minh; Toan, Nguyen Trong; Thang, Ho Vinh

    2015-07-01

    Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem® vaccine in children. A total of 131 infants received the Quinvaxem® vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP ≥ 0.15 µg/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP ≥ 0.15 µg/ml). The Quinvaxem® vaccine was well tolerated and has a low rate of adverse events. Quinvaxem® given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam.

  15. Negative Correlation between Circulating CD4(+)FOXP3(+)CD127(-) Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria-Tetanus-Pertussis Vaccine Implies a Regulatory Role.

    Science.gov (United States)

    Ndure, Jorjoh; Noho-Konteh, Fatou; Adetifa, Jane U; Cox, Momodou; Barker, Francis; Le, My Thanh; Sanyang, Lady C; Drammeh, Adboulie; Whittle, Hilton C; Clarke, Ed; Plebanski, Magdalena; Rowland-Jones, Sarah L; Flanagan, Katie L

    2017-01-01

    Regulatory T cells (Tregs) play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4(+)FOXP3(+)CD127(-) Tregs in controlling immunity in infant males and females to vaccination with diphtheria-tetanus-whole cell pertussis (DTP) and/or measles vaccine (MV). We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

  16. Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

    Directory of Open Access Journals (Sweden)

    Jorjoh Ndure

    2017-08-01

    Full Text Available Regulatory T cells (Tregs play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP and/or measles vaccine (MV. We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

  17. Report of the Task Force on Pertussis and Pertussis Immunization--1988.

    Science.gov (United States)

    American Academy of Pediatrics, Elk Grove Village, IL.

    Pertussis is a severe epidemic and endemic disease with significant morbidity and mortality. The use of whole-cell pertussis vaccines in the United States has been effective in controlling the disease but not in decreasing the circulation of the organism. Whole-cell vaccines commonly cause reactions in children, and in addition, they are often…

  18. Dismantling the Taboo against Vaccines in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maurizio de Martino

    2016-06-01

    Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

  19. Dismantling the Taboo against Vaccines in Pregnancy

    Science.gov (United States)

    de Martino, Maurizio

    2016-01-01

    Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

  20. Interaction of Bordetella pertussis filamentous hemagglutinin with human TLR2: identification of the TLR2-binding domain.

    Science.gov (United States)

    Asgarian-Omran, Hossein; Amirzargar, Ali Akbar; Zeerleder, Sacha; Mahdavi, Marzieh; van Mierlo, Gerard; Solati, Shabnam; Jeddi-Tehrani, Mahmood; Rabbani, Hodjatallah; Aarden, Leucien; Shokri, Fazel

    2015-02-01

    Filamentous hemagglutinin (FHA) is a major adhesion and virulence factor of Bordetella pertussis and also a main component of acellular pertussis vaccines. Interaction of FHA with different receptors on human epithelial and immune cells facilitates entrance and colonization of bacteria as well as immunomodulation of the host immune response. Three overlapping segments of the FHA gene were cloned in a prokaryotic expression vector and the recombinant proteins were purified. These recombinant fragments along with the native FHA protein were employed to assess their potential Toll-like receptor (TLR) stimulatory effects and to localize the TLR binding region. TLR stimulation was monitored by applying HEK293-Blue cell lines cotransfected with TLR2, 4, or 5 and a NF-κB reporter gene. Culture supernatants were checked for secretion of the reporter gene product and IL-8 as indicators of TLR stimulation. Native FHA was found to strongly stimulate TLR2, but not TLR4 or TLR5 transfected cells. Among recombinant FHA fragments only the fragment spanning amino acid residues 1544-1917 was able to exhibit the TLR2 stimulating property of FHA. Interaction of FHA with TLR2 suggests its involvement in induction of the innate immune system against Bordetella pertussis. The TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.

  1. What do Parents Learn by Reading a DPT Vaccine Information Form?

    Directory of Open Access Journals (Sweden)

    Ronald Gold

    1994-01-01

    Full Text Available Objective: Information forms are commonly used to inform parents about childhood vaccination. This study assessed the knowledge of mothers about pertussis and pertussis vaccine before and after reading a form about diphtheria-pertussis-tetanus (dpt vaccine.

  2. Induction and maintenance of Bordetella pertussis specific immune responses

    NARCIS (Netherlands)

    Stenger, R.M.

    2010-01-01

    Pertussis, also referred to as whooping cough, is a serious respiratory disease mainly caused by the gram-negative bacterium Bordetella pertussis. The disease is most severe in neonates and children under the age of 1. Before childhood vaccination was introduced in the 1950s, pertussis was an import

  3. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants

    Directory of Open Access Journals (Sweden)

    Spady Donald W

    2006-06-01

    Full Text Available Abstract Background Adverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B (DTP-IPV-Hib immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study. Methods Infants with gestational age of ≤ 32 weeks who received their first DTP-IPV-Hib immunization prior to discharge from two Edmonton Neonatal Intensive Care Units January 1, 1996 to November 30, 2000 were eligible for the study. Each immunized infant was matched by gestational age to one control infant. The number of episodes of apnea, bradycardia, and/or desaturations (ABD and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort or at the same post-natal age (for controls was recorded. Results Thirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1% and 36 control infants (29.0% had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51 as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%. Eighteen immunized infants (14.5% and 51 control infants (41.1% had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39. The need for therapy of ABD in the immunized

  4. RESULTS OF ADMINISTRATION OF COMBINED VACCINE AGAINST DIPHTHERIA, PERTUSSIS, TETANUS, POLIOMYELITIS AND HAEMOPHILIC INFECTION TYPE B IN CHILDREN WITH CONCOMITANT DISEASES

    Directory of Open Access Journals (Sweden)

    N. F. Snegova

    2011-01-01

    Full Text Available The article summarizes data on methods and opportunities of frequently ailing children rehabilitation. Authors mark a leading role of vaccination against pneumotropic infections. Questions of successful interaction between doctor and frequently ailing child’s parents are highlighted. The observation of 94 children 3 months — 3 years old (patients had different types of initial immune insuffiiency, neurological pathology, recurrent obstructive bronchitis, or were included in group of frequently ailing children vaccinated with Pentaxim was performed. 94% of children showed asymptomatic postvaccinal period. Fever up to 39°C occurred in 2.3% of patients. Local reactions (diameter was not over 3–5 cm developed in 1.7% of children. There was no any case of postvaccinal complication. Evaluation of vaccine’s reactogenity proves its safety and reasonability in immunization against pertussis, diphtheria, tetanus, poliomyelitis, Haemophilis influenzae type b in children of different health state including those with concomitant diseases.

  5. Genetic Variation of Bordetella pertussis in Austria

    NARCIS (Netherlands)

    Wagner, B.; Melzer, H.; Freymuller, G.; Stumvoll, S.; Rendi-Wagner, P.; Paulke-Korinek, M.; Repa, A.; Mooi, F.R.; Kollaritsch, H.; Mittermayer, H.; Kessler, H.H.; Stanek, G.; Steinborn, R.; Duchene, M.; Wiedermann, U.

    2015-01-01

    In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunit

  6. Pertussis: the return of a bad penny.

    Science.gov (United States)

    Mathis, R D; Shoaf, B; Weiner, T I

    1993-08-01

    We describe two related cases of pertussis infection ("whooping cough"). This disease entity was almost completely eradicated through successful mass immunization programs. In the past decade it has demonstrated a steady rise in incidence. The epidemiology, clinical manifestations, treatment, and current vaccines for pertussis infection are reviewed.

  7. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    Energy Technology Data Exchange (ETDEWEB)

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. (Medical College of Wisconsin, Milwaukee (USA))

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  8. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  9. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally

    NARCIS (Netherlands)

    de Gouw, Daan; Hermans, Peter W M; Bootsma, Hester J; Zomer, Aldert; Heuvelman, Kees; Diavatopoulos, Dimitri A; Mooi, Frits R

    2014-01-01

    Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promo

  10. 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.

    Science.gov (United States)

    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.

  11. Association of Interacting Genes in the Toll-Like Receptor Signaling Pathway and the Antibody Response to Pertussis Vaccination

    NARCIS (Netherlands)

    Kimman, Tjeerd G.; Banus, Sander; Reijmerink, Naomi; Reimerink, Johan; Stelma, Foekje F.; Koppelman, Gerard H.; Thijs, Carel; Postma, Dirkje S.; Kerkhof, Marjan

    2008-01-01

    Background: Activation of the Toll-like receptor (TLR) signaling pathway through TLR4 may be important in the induction of protective immunity against Bordetella pertussis with TLR4-mediated activation of dendritic and B cells, induction of cytokine expression, and reversal of tolerance as crucial s

  12. Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands : Using an Individual-Based Dynamic Model

    NARCIS (Netherlands)

    de Vries, Robin; Kretzschmar, Mirjam; Schellekens, Joop F P; Versteegh, Florens G A; Westra, Tjalke A; Roord, John J; Postma, Maarten J

    2010-01-01

    BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an indivi

  13. Bordetella pertussis isolates from Argentinean whooping cough patients display enhanced biofilm formation capacity compared to Tohama I reference strain

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    Laura eArnal

    2015-12-01

    Full Text Available Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines since the 1950´s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE coupled with mass spectrometry (MS, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host.

  14. Bordetella pertussis Isolates from Argentinean Whooping Cough Patients Display Enhanced Biofilm Formation Capacity Compared to Tohama I Reference Strain.

    Science.gov (United States)

    Arnal, Laura; Grunert, Tom; Cattelan, Natalia; de Gouw, Daan; Villalba, María I; Serra, Diego O; Mooi, Frits R; Ehling-Schulz, Monika; Yantorno, Osvaldo M

    2015-01-01

    Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines, since the 1950s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host.

  15. Whooping Cough (Pertussis) - Fact Sheet for Parents

    Science.gov (United States)

    ... Teen Vaccine Resources Related Links Vaccines & Immunizations Whooping Cough and the Vaccine (Shot) to Prevent It Language: ... and adults is called Tdap. What is whooping cough? Whooping cough—or pertussis—is a very serious ...

  16. Pattern of functional antibody activity against Haemophilus influenzae type b (Hib in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine

    Directory of Open Access Journals (Sweden)

    D.C.S. Matos

    2009-12-01

    Full Text Available We evaluated the functional activity of Haemophilus influenzae B (Hib antibodies elicited in a group of infants immunized with the diphtheria-tetanus-pertussis vaccine combined with an Hib vaccine produced totally in Brazil after technological transfer of Hib vaccine production from Glaxo SmithKline, Belgium. Blood samples from immunized infants (N = 985 were collected for the determination of Hib antibodies. Total Ig and IgM and IgG subclasses of antibodies against polyribosyl ribitol phosphate (PRP were analyzed by ELISA. Almost all vaccinees (97.56%, 961/985 developed a strong anti-PRP IgG antibody response (≥1.0 μg/mL, while an anti-PRP IgM response was observed in 64.24% (634/985 of them (≥0.15 μg/mL. Only 18.88% (186/985 of the infants in the group with high PRP antibody IgG concentrations (≥1.0 μg/mL developed a high IgM antibody response. Anti-PRP IgG antibody levels were significantly higher than anti-PRP IgM. These results demonstrate the predominance of IgG antibodies over IgM antibodies in response to PRP, with a ratio of 17:1. IgG antibodies were predominantly of the IgG1 subclass. An increase in IgG avidity was also observed during the course of immunization.

  17. Pattern of functional antibody activity against Haemophilus influenzae type B (Hib) in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine.

    Science.gov (United States)

    Matos, D C S; Silva, A M V; Neves, P C C; Martins, R M; Homma, A; Marcovistz, R

    2009-12-01

    We evaluated the functional activity of Haemophilus influenzae B (Hib) antibodies elicited in a group of infants immunized with the diphtheria-tetanus-pertussis vaccine combined with an Hib vaccine produced totally in Brazil after technological transfer of Hib vaccine production from Glaxo SmithKline, Belgium. Blood samples from immunized infants (N = 985) were collected for the determination of Hib antibodies. Total Ig and IgM and IgG subclasses of antibodies against polyribosyl ribitol phosphate (PRP) were analyzed by ELISA. Almost all vaccinees (97.56%, 961/985) developed a strong anti-PRP IgG antibody response (>or=1.0 microg/mL), while an anti-PRP IgM response was observed in 64.24% (634/985) of them (>or=0.15 microg/mL). Only 18.88% (186/985) of the infants in the group with high PRP antibody IgG concentrations (>or=1.0 microg/mL) developed a high IgM antibody response. Anti-PRP IgG antibody levels were significantly higher than anti-PRP IgM. These results demonstrate the predominance of IgG antibodies over IgM antibodies in response to PRP, with a ratio of 17:1. IgG antibodies were predominantly of the IgG1 subclass. An increase in IgG avidity was also observed during the course of immunization.

  18. A retrospective study of acute pertussis in Hasan Sadikin Hospital–Indonesia

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2015-06-01

    Conclusions: Mostly patients were admitted on paroxysmal phase when no more active B. pertussis could be found from nasopharyngeal secret. A rigorous history taking particularly excessive cough, posttussive vomitting, and pertussis vaccination status need to be taken into account.

  19. Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

    Science.gov (United States)

    Isaka, Masanori; Komiya, Takako; Takahashi, Motohide; Yasuda, Yoko; Taniguchi, Tooru; Zhao, Yanqiu; Matano, Keiko; Matsui, Hideyuki; Maeyama, Jun-Ichi; Morokuma, Kazunori; Ohkuma, Kunio; Goto, Norihisa; Tochikubo, Kunio

    2004-08-13

    Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine.

  20. c-di-GMP enhances protective innate immunity in a murine model of pertussis.

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    Shokrollah Elahi

    Full Text Available Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required.

  1. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

    Science.gov (United States)

    Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

    2012-10-05

    To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Neurologic manifestations of diphtheria and pertussis.

    Science.gov (United States)

    Sanghi, Viraj

    2014-01-01

    Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

  3. Bordetella pertussis filamentous hemagglutinin itself does not trigger anti-inflammatory interleukin-10 production by human dendritic cells.

    Science.gov (United States)

    Villarino Romero, Rodrigo; Hasan, Shakir; Faé, Kellen; Holubova, Jana; Geurtsen, Jeroen; Schwarzer, Martin; Wiertsema, Selma; Osicka, Radim; Poolman, Jan; Sebo, Peter

    2016-01-01

    Filamentous hemagglutinin (FHA) is an important adhesin of the whooping cough agent Bordetella pertussis and is contained in most acellular pertussis vaccines. Recently, FHA was proposed to exert an immunomodulatory activity through induction of tolerogenic IL-10 secretion from dendritic cells. We have re-evaluated the cytokine-inducing activity of FHA, placing specific emphasis on the role of the residual endotoxin contamination of FHA preparations. We show that endotoxin depletion did not affect the capacity of FHA to bind primary human monocyte-derived dendritic cells, while it abrogated the capacity of FHA to elicit TNF-α and IL-10 secretion and strongly reduced its capacity to trigger IL-6 production. The levels of cytokines induced by the different FHA preparations correlated with their residual contents of B. pertussis endotoxin. Moreover, FHA failed to trigger cytokine secretion in the presence of antibodies that block TLR2 and/or TLR4 signaling. The TLR2 signaling capacity appeared to be linked to the presence of endotoxin-associated components in FHA preparations and not to the FHA protein itself. These results show that the endotoxin-depleted FHA protein does not induce cytokine release from human dendritic cells.

  4. Immunogenicity and Reactogenicity of DTPa-IPV/Hib Vaccine Co-administered With Hepatitis B Vaccine for Primary and Booster Vaccination of Taiwanese Infants

    Directory of Open Access Journals (Sweden)

    Pei-Lan Shao

    2011-06-01

    Full Text Available Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib conjugate vaccine (DTPa-IPV/Hib, Infanrix™-IPV + Hib was assessed when co-administered with hepatitis B (HBV vaccine. Seventy healthy infants received DTPa-IPV/Hib at 1.5, 3.5, 6 and 15–18 months, and HBV at birth, 1.5, 6 and 15–18 months of age. Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis seroprotection/seropositivity rates were 100% after primary vaccination. Post-primary immune responses to poliovirus could not be evaluated for technical reasons. However, after the booster dose, seroprotection/seropositivity rates, including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post-booster geometric mean antibody concentrations/titers (GMC/GMTs rose from 14-fold to 45-fold, indicating effective priming against all antigens, including polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV. No serious adverse events were considered related to vaccination. Primary and booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well tolerated. Combination vaccines enable vaccine providers to conveniently provide routine pediatric immunizations, with minimal discomfort.

  5. A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Stanley A. Plotkin

    2012-01-01

    Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

  6. Genetic diversity and population dynamics of Bordetella pertussis in China between 1950-2007.

    Science.gov (United States)

    Xu, Yinghua; Zhang, Liu; Tan, Yajun; Wang, Lichan; Zhang, Shumin; Wang, Junzhi

    2015-11-17

    Pertussis is an acute respiratory infectious disease caused by the bacterium Bordetella pertussis. Although pertussis vaccination was introduced in the 1960s, pertussis is still an endemic disease in China. To better understand the genetic diversity of the Chinese B. pertussis population, we characterized 115 clinical isolates obtained in China during 1950-2007 using multilocus variable-number tandem repeat analysis (MLVA). Forty-six different B. pertussis MLVA profiles (MTs) were identified, of which 13 were new MTs. Analysis using a minimum-spanning tree showed that distinct MTs were prevalent during different periods, suggesting that a dynamic change in B. pertussis MTs occurred over time in China. The predominant MTs in recent isolates from China were different from those of many developed countries. A decreasing trend in genetic diversity of the B. pertussis population was observed following the introduction of pertussis vaccines. Similar to the pertactin 2 (prn2) allele, the novel pertussis toxin promoter (ptxP3) allele first emerged in 2000, but unlike trends elsewhere, ptxP1 remained predominant among the isolates, further reflecting the unique temporal trends in the B. pertussis population in China. Our results suggest that temporal changes in the B. pertussis population may be closely associated with vaccination coverage and the vaccine types used. These data may lead to an improved understanding of the virulence mechanism of B. pertussis and facilitate new strategies for controlling this infectious disease.

  7. A retrospective study of acute pertussis in Hasan Sadikin Hospital-Indonesia

    Institute of Scientific and Technical Information of China (English)

    Heda Melinda Nataprawira; Evelyn Phangkawira

    2015-01-01

    Objective: To describe the representation of pertussis diagnosis in children. Methods: A retrospective observational study was performed on pediatric pertussis and pertussis-like syndrome registry for children <14 years of age documented from October 2008 to December 2014 in Hasan Sadikin Hospital, Indonesia. Demographic data, signs and symptoms at presentation, case definition (probable, confirmed), possible pertussis contact, pertussis vaccination status, results of Bordetella pertussis (B. pertussis) culture, complications, and outcome were recorded. Results:Sixty-one probable and two confirmed pertussis were documented. Male and female ratio was 1:1, mostly presented with shortness of breath, 24 (38%) subjects had posttussive vomiting, 10 (16%) had whooping-cough. Ten patients (16%) were reported to have adult possible pertussis contact. Only 2 infants had previous pertussis vaccination. All subjects presented in the second week of illness were all diagnosed as bronchopneumonia but two. The mean age was 6 months, ranging from 0−50 months. One subject required mechanical ventilation. B. pertussis culture was performed only in 35 (56%) subjects but positive only in two. There were no fatal cases, 55 (87%) including the subject who need mechanical ventilation had good outcome. Conclusions: Mostly patients were admitted on paroxysmal phase when no more active B. pertussis could be found from nasopharyngeal secret. A rigorous history taking particularly excessive cough, posttussive vomitting, and pertussis vaccination status need to be taken into account.

  8. Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

    Directory of Open Access Journals (Sweden)

    Alexander Doroshenko

    2016-08-01

    Full Text Available Background Pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. Multiple outbreaks have been reported in different ages worldwide. For certain outbreaks, public health authorities can launch an outbreak response immunization (ORI campaign to control pertussis spread. We investigated effects of an outbreak response immunization targeting young adolescents in averting pertussis cases. Methods We developed an agent-based model for pertussis transmission representing disease mechanism, waning immunity, vaccination schedule and pathogen transmission in a spatially-explicit 500,000-person contact network representing a typical Canadian Public Health district. Parameters were derived from literature and calibration. We used published cumulative incidence and dose-specific vaccine coverage to calibrate the model’s epidemiological curves. We endogenized outbreak response by defining thresholds to trigger simulated immunization campaigns in the 10–14 age group offering 80% coverage. We ran paired simulations with and without outbreak response immunization and included those resulting in a single ORI within a 10-year span. We calculated the number of cases averted attributable to outbreak immunization campaign in all ages, in the 10–14 age group and in infants. The count of cases averted were tested using Mann–Whitney U test to determine statistical significance. Numbers needed to vaccinate during immunization campaign to prevent a single case in respective age groups were derived from the model. We varied adult vaccine coverage, waning immunity parameters, immunization campaign eligibility and tested stronger vaccination boosting effect in sensitivity analyses. Results 189 qualified paired-runs were analyzed. On average, ORI was triggered every 26 years. On a per-run basis, there were an average of 124, 243 and 429 pertussis cases averted across all age

  9. Absence of Bordetella pertussis Among Infants Hospitalized for Bronchiolitis in Finland, 2008-2010.

    Science.gov (United States)

    Korppi, Matti; Kivistö, Juho; Koponen, Petri; Lehtinen, Pasi; Remes, Sami; Piippo-Savolainen, Eija; Piedra, Pedro A; Espinola, Janice A; Camargo, Carlos A; Jartti, Tuomas

    2016-02-01

    In 169 Finnish infants hospitalized for bronchiolitis at age Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with respiratory syncytial virus), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005.

  10. Long-term immunogenicity assessment of a DTaP-IPV//PRP-T vaccine given at 2, 4, 6 and 18-19 months of age, and immunogenicity and safety of a DTaP-IPV vaccine given as a booster dose at 4 to 6 years of age in Thai children.

    Science.gov (United States)

    Pancharoen, Chitsanu; Chotpitayasunondh, Tawee; Chuenkitmongkol, Sunate; Ortiz, Esteban

    2012-05-01

    Booster vaccination of infants aims to further reduce the burden of childhood infectious diseases. This study assessed the antibody persistence induced by a primary series vaccination at 2, 4, 6 months of age and a first booster at 18-19 months of age with a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b combined vaccine (DTaP-IPV//PRP-T) in 4-6 year-old Thai children (N=123). The safety and immunogenicity of a tetravalent acellular pertussis combined vaccine (containing the same DTaP-IPV antigens as the previous vaccine) given as a second booster at 4 to 6 years of age was also evaluated. Seroprotective antibody levels against diphtheria (> or = 0.01 IU/ml), tetanus (> or = 0.10 IU/ml), and polioviruses (> or = 8 1/dil) were maintained 4-6 years after primary-vaccination and first booster by > or = 92.7% of children, and anti-pertussis antibodies > or = 5 EU/ml were observed in the majority of children. The second booster with DTaP-IPV elicited a strong response for all antigens. GMT or GMC ratios for all antigens at the pre- and post-booster samples were from 4.7 to 52.5. Primary vaccination at 2, 4, 6 and a booster at 18-19 months of age with the DTaP-IPV//PRP-T vaccine induced satisfactory antibody persistence at 4-6 years of age. A second booster with DTaP-IPV induced a strong immune response and was well tolerated.

  11. Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines.

    Science.gov (United States)

    Schilling, Andrea; Parra, Mercedes Macias; Gutierrez, Maricruz; Restrepo, Jaime; Ucros, Santiago; Herrera, Teobaldo; Engel, Eli; Huicho, Luis; Shew, Marcia; Maansson, Roger; Caldwell, Nicole; Luxembourg, Alain; Ter Meulen, Ajoke Sobanjo

    2015-09-01

    This study in 11- to 15-year-old boys and girls compared the immunogenicity and safety of GARDASIL 9 (9-valent human papillomavirus [9vHPV] vaccine) administered either concomitantly or nonconcomitantly with 2 vaccines routinely administered in this age group (Menactra [MCV4; Neisseria meningitidis serotypes A/C/Y/W-135] or Adacel [Tdap; diphtheria/tetanus/acellular pertussis]). Participants received 9vHPV vaccine at day 1 and months 2 and 6; the concomitant group (n = 621) received MCV4/Tdap concomitantly with 9vHPV vaccine at day 1; the nonconcomitant group (n = 620) received MCV4/Tdap at month 1. Antibodies to HPV-, MCV4-, and Tdap-relevant antigens were determined. Injection-site and systemic adverse events (AEs) were monitored for 15 days after any vaccination; serious AEs were monitored throughout the study. The geometric mean titers for all HPV types in 9vHPV vaccine 4 weeks after dose 3, proportion of subjects with a fourfold rise or greater in titers for 4 N meningitidis serotypes 4 weeks after injection with MCV4, proportion of subjects with antibody titers to diphtheria and tetanus ≥0.1 IU/mL, and geometric mean titers for pertussis antigens 4 weeks after injection with Tdap were all noninferior in the concomitant group compared with the nonconcomitant group. Injection-site swelling occurred more frequently in the concomitant group. There were no vaccine-related serious AEs. Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually. Copyright © 2015 by the American Academy of Pediatrics.

  12. Competition, coinfection and strain replacement in models of Bordetella pertussis.

    Science.gov (United States)

    Nicoli, Emily J; Ayabina, Diepreye; Trotter, Caroline L; Turner, Katherine M E; Colijn, Caroline

    2015-08-01

    Pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. Recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. Interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. In particular, if we are to understand the role strain replacement plays in vaccinated settings, it will be essential to understand how strains or variants of pertussis interact. Here we explore under what conditions we would expect strain replacement to be of concern in pertussis. We develop a dynamic transmission model that allows for coinfection between Bordetella pertussis (the main causative agent of pertussis) and a strain or variant unaffected by the vaccine. We incorporate both neutrality (in the sense of ecological/population genetic neutrality) and immunity into the model, leaving the specificity of the immune response flexible. We find that strain replacement may be considerable when immunity is non-specific. This is in contrast to previous findings where neutrality was not considered. We conclude that the extent to which models reflect ecological neutrality can have a large impact on conclusions regarding strain replacement. This will likely have onward consequences for estimates of vaccine efficacy and cost-effectiveness.

  13. Bordetella pertussis: why is it still circulating?

    Science.gov (United States)

    Guiso, Nicole

    2014-01-01

    Bordetella pertussis is the causal agent of whooping cough, a highly contagious respiratory disease that is life-threatening in infants under the age of three months and may also be very severe in pregnant women and seniors. This disease can be prevented by vaccination but it remains a public health problem in many developed and developing countries.(1) So, why is B. pertussis still circulating? We need to consider several aspects of this vaccine-preventable disease when answering this question: (i) the history of the disease and the historical context in which the vaccine was developed; (ii) the type of vaccine used; (iii) the vaccination strategy and coverage; (iv) the disease surveillance after the introduction of generalized vaccination and (v) the surveillance for the causal agent of the disease.

  14. Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Sørup, Signe; Stensballe, Lone Graff;

    2015-01-01

    -confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. RESULTS: The study......BACKGROUND: The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association...... was strongest for admissions with lower respiratory infections. OBJECTIVE: To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. METHODS: Nationwide cohort study of laboratory...

  15. Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

    NARCIS (Netherlands)

    van Twillert, Inonge; Bonačić Marinović, Axel A; Kuipers, Betsy; van Gaans-van den Brink, Jacqueline A M; Sanders, Elisabeth A M; van Els, Cécile A C M

    2017-01-01

    Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis

  16. The potential role of subclinical Bordetella Pertussis colonization in the etiology of multiple sclerosis.

    Science.gov (United States)

    Rubin, Keith; Glazer, Steven

    2016-04-01

    It is established that (1) subclinical Bordetella pertussis colonization of the nasopharynx persists in highly vaccinated populations, and (2) B. pertussis toxin is a potent adjuvant that, when co-administered with neural antigens, induces neuropathology in experimental autoimmune encephalomyelitis, the principle animal model of multiple sclerosis. Building on these observations with supporting epidemiologic and biologic evidence, we propose that, contrary to conventional wisdom that subclinical pertussis infections are innocuous to hosts, B. pertussis colonization is an important cause of multiple sclerosis.

  17. Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine S;

    2016-01-01

    and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

  18. Humoral immunity of dTap-IPV vaccine (REPEVAX®) administered one month after dT-IPV vaccine (REVAXIS®) in adults with unknown vaccination history.

    Science.gov (United States)

    Larnaudie, Sylvie; Guiso, Nicole; Baptiste, Charles; Desaint, Corinne; Desforges, Lionel; Lebon, Pierre; Soubeyrand, Benoit; Launay, Odile

    2010-10-01

    This study was to assess the humoral immune response induced by a vaccination schedule routinely used in France in 18-50 year old adults with unknown vaccination history. In this monocentric, prospective study, subjects received one dose of REVAXIS® (dT-IPV, diphtheria, tetanus and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)) (Visit 1) followed by one dose of REPEVAX® (dTap-IPV, diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed, reduced antigen(s) content)) one month later (Visit 2). Antibodies against diphtheria, tetanus, poliomyelitis types 1, 2 and 3, and pertussis toxin (PT) were measured one month after the administration of REPEVAX® (Visit 3). A total of 136 subjects were included in the study, but blood samples were available for only 73 subjects. Their mean age at inclusion was 33.2 ± 7.3 years. 49.3% of the 73 subjects originated from the WHO African Region, 6.8% from the WHO Western Pacific Region and 5.5% from the WHO European Region. One month after REPEVAX® administration, all subjects had seroprotective antibody titers against diphtheria and tetanus (≥0.1 IU/mL), poliomyelitis types 2 and 3 (≥ 8 1/dil); one subject (1.4%) did not have antibodies against poliomyelitis type 1. The rate of anti-PT seropositivity (≥8 EU/mL) was 94.4%. One dose of REPEVAX® administered one month after a dose of REVAXIS® in subjects with unknown vaccination history induced a high humoral response. These results validate a vaccination schedule routinely used for years that rapidly elicits effective immunization against diphtheria, tetanus, poliomyelitis and pertussis.

  19. Age-appropriate versus up-to-date coverage of routine childhood vaccinations among young children in Israel.

    Science.gov (United States)

    Stein-Zamir, Chen; Israeli, Avi

    2017-09-02

    Routine childhood vaccinations schedules recommend that children receive the vaccine doses at specific ages. Vaccination coverage data are conventionally reported by the up-to-date method. We aimed to assess vaccination timeliness by the age-appropriate method and compare with the up-to-date vaccination coverage. Assessment of age-appropriate and up-to-date vaccination coverage among children born in Israel in 2009 and followed to age 48 months (national representative sample, n = 3892). The vaccinations included: Hepatitis B vaccine (HBV), Diphtheria-Tetanus-acellular Pertussis-Polio-Haemophilus-influenzae-b (DTaP-IPV-Hib), Pneumococcal conjugate vaccine (PCV), Measles-mumps-rubella-varicella vaccine (MMR/MMRV) and Hepatitis A vaccine (HAV). The categories defined: age-appropriate (at the recommended age and up to 1 month), delayed less than 6 months, delayed 6 months and above and unvaccinated (48 months). The age-specific vaccinations assessment showed considerable delay in receipt of routine vaccination. While most (96%, 95%, 91%, 96%, 94% and 86%) children were vaccinated up-to-date for HBV3, DTaP-IPV-Hib4, PCV3, MMR/MMRV1, HAV1and HAV2 vaccine doses; only 26%, 29%, 47%, 64%, 55% and 12% were vaccinated age-appropriate. Vaccination delay was more common in vaccines with multiple doses. Vaccination delay was associated with high child's birth order, low socio-economic rank, ethnicity (delay more common in Jews vs. Arabs), season of birth (winter) and delayed receipt of DTaP-IPV-Hib vaccine 1st dose. This study assessed age-appropriate childhood vaccination coverage in a national cohort of children. While the overall vaccination coverage stands in line with the WHO goals, vaccination timeliness and equity are inadequate and targeted public health intervention programs aimed at vaccination timeliness are necessary.

  20. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

    Science.gov (United States)

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

  1. Pertussis in Latin America: epidemiology and control strategies.

    Science.gov (United States)

    Falleiros Arlant, Luiza Helena; de Colsa, Agustín; Flores, Dario; Brea, José; Avila Aguero, Maria L; Hozbor, Daniela Flavia

    2014-10-01

    Pertussis is a serious respiratory disease in infants that can also affect children and adults. Vaccination against pertussis was introduced in the 1950s and in the 1990s a resurgence of pertussis was observed worldwide. The aim of this work is to summarize the recent data concerning pertussis disease in different countries of Latin America. In this geographic region, pertussis is nationally notifiable and cases should be reported to the appropriate health department/Ministry. Though the surveillance systems are not the same among Latin America countries, over recent decades an increasing number of cases have been detected. Most of these cases correspond to patients younger than 6 months old who received fewer than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Latin America countries, several explanations have been proposed.

  2. DTaP-IPV-Hep B-Hib vaccine (Hexaxim®) : a review of its use in primary and booster vaccination.

    Science.gov (United States)

    McCormack, Paul L

    2013-02-01

    Hexaxim(®) (DTaP-IPV-Hep B-Hib) is a new, thiomersal-free, fully liquid, hexavalent combination pediatric vaccine containing diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, recombinant hepatitis B virus surface antigen produced in the yeast Hansenula polymorpha, and Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) conjugated to tetanus toxoid. It is currently registered in markets outside of the EU for primary vaccination of infants from 6 weeks of age and for booster vaccination up to 24 months of age. In randomized controlled trials, primary vaccination of infants with Hexaxim(®) using various immunization schedules was highly immunogenic for all vaccine component antigens regardless of the administration schedule, producing high levels of seroprotection or seroconversion for each antigen. Hexaxim(®) was as immunogenic as the comparator DTwP- or DTaP-based vaccines in these studies. The serological responses were generally sustained at high levels over a follow-up of ≈1 year, and booster vaccination at 15-18 months further enhanced the immune response. Hexaxim(®) was less reactogenic than a DTwP-based combination vaccine, and displayed a tolerability profile similar to those of the comparator DTaP-based combination vaccines. Thus, Hexaxim(®) provides effective seroprotection or seroconversion against six major childhood diseases simultaneously, both as primary and booster vaccination, and offers the benefits and convenience of a fully liquid, ready-to-use vaccine.

  3. Seroprevalence of pertussis in Senegal: a prospective study.

    Directory of Open Access Journals (Sweden)

    Lobna Gaayeb

    Full Text Available BACKGROUND: Pertussis, also known as whooping cough, is a vaccine-preventable respiratory disease caused by Bordetella pertussis infection, against which Senegalese children are immunized with the diphtheria-tetanus-whole cell pertussis vaccine (DTwP. Seroepidemiology of pertussis has been widely described in industrialized countries, but rare are the studies referring to it in developing countries. METHODS: We conducted a longitudinal survey in Northern Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG antibody (Ab response against pertussis toxin (PT. A cohort of 410 children aged 1 to 9 from five villages in the Middle Senegal River Valley were followed-up for 18 months. During that period, five visits were made to assess the immunological status of the children. PRINCIPAL FINDINGS: PT-specific IgG responses were significantly different according to age. Until the age of 3, there was a decrease in the Ab response, which then increased in the older groups. Assessment of IgG antibodies to PT (IgG-PT suggested evidence of recent exposures to the pathogen. Surprisingly, in one of the five villages the average Ab response to PT was very low at all ages during the first 6 months of the study. At the third visit, IgG-PT concentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed. CONCLUSIONS: Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs.

  4. Seroprevalence of Pertussis in Senegal: A Prospective Study

    Science.gov (United States)

    Gaayeb, Lobna; Sarr, Jean Biram; Ndiath, Mamadou O.; Hanon, Jean-Baptiste; Debrie, Anne-Sophie; Seck, Modou; Schacht, Anne-Marie; Remoué, Franck; Hermann, Emmanuel; Riveau, Gilles

    2012-01-01

    Background Pertussis, also known as whooping cough, is a vaccine-preventable respiratory disease caused by Bordetella pertussis infection, against which Senegalese children are immunized with the diphtheria-tetanus-whole cell pertussis vaccine (DTwP). Seroepidemiology of pertussis has been widely described in industrialized countries, but rare are the studies referring to it in developing countries. Methods We conducted a longitudinal survey in Northern Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG antibody (Ab) response against pertussis toxin (PT). A cohort of 410 children aged 1 to 9 from five villages in the Middle Senegal River Valley were followed-up for 18 months. During that period, five visits were made to assess the immunological status of the children. Principal Findings PT-specific IgG responses were significantly different according to age. Until the age of 3, there was a decrease in the Ab response, which then increased in the older groups. Assessment of IgG antibodies to PT (IgG-PT) suggested evidence of recent exposures to the pathogen. Surprisingly, in one of the five villages the average Ab response to PT was very low at all ages during the first 6 months of the study. At the third visit, IgG-PT concentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed. Conclusions Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs. PMID:23119090

  5. Financial barriers to the adoption of combination vaccines by pediatricians.

    Science.gov (United States)

    Gidengil, Courtney A; Dutta-Linn, M Maya; Messonnier, Mark L; Rusinak, Donna; Lieu, Tracy A

    2010-12-01

    To describe the prevalence of combination vaccine use and the associated financial barriers faced by pediatric practices, and to identify determinants of adoption of combination vaccines. Mailed national survey. Pediatric practices during the period from August through October 2008. Pediatricians randomly selected from the American Medical Association Masterfile. Use of 1 of 2 infant combination vaccines (the diphtheria and tetanus toxoids and acellular pertussis, hepatitis B virus, and inactivated poliovirus [DTaP-HepB-IPV] vaccine or the DTaP, IPV, and Haemophilus influenzae type b [DTaP-IPV/Hib] vaccine). We received 629 responses (response rate, 67%). Four hundred ninety-two pediatricians (78%) reported using 1 or both of the infant combination vaccines of interest (ie, the DTaP-HepB-IPV or DTaP-IPV/Hib vaccine). More than half of the respondents said their practice did not receive adequate reimbursement for the purchase and administration of vaccines in general. More than one-fifth reported not using 1 or more of the combination vaccines because of inadequate reimbursement for the cost of vaccine doses (23% of respondents) and/or vaccine administration (20% of respondents). The infant combination vaccines studied were less likely to be used by smaller practices, by those with a lower proportion of publicly insured patients, and by those with less inclusive state vaccine financing policies. One in 5 pediatricians reported that inadequate reimbursement prevented their using 1 or more combination vaccines. Practice size as well as the proportion of children whose vaccinations are paid for by public funds appear to be important determinants of the adoption of combination vaccines.

  6. Vaccination coverage among children in kindergarten - United States, 2013-14 school year.

    Science.gov (United States)

    Seither, Ranee; Masalovich, Svetlana; Knighton, Cynthia L; Mellerson, Jenelle; Singleton, James A; Greby, Stacie M

    2014-10-17

    State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children.

  7. Vaccination Coverage Among Children in Kindergarten - United States, 2014-15 School Year.

    Science.gov (United States)

    Seither, Ranee; Calhoun, Kayla; Knighton, Cynthia L; Mellerson, Jenelle; Meador, Seth; Tippins, Ashley; Greby, Stacie M; Dietz, Vance

    2015-08-28

    State and local jurisdictions require children to be vaccinated before starting school to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. State vaccination requirements, which include school vaccination and exemption laws and health department regulations, permit medical exemptions for students with a medical contraindication to receiving a vaccine or vaccine component and may allow nonmedical exemptions for religious reasons or philosophic beliefs. To monitor state and national vaccination coverage and exemption levels among children attending kindergarten, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage estimates in 49 states and the District of Columbia (DC) and vaccination exemption estimates in 46 states and DC that reported the number of children with at least one exemption among kindergartners during the 2014-15 school year. Median vaccination coverage* was 94.0% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 94.2% for the local requirements for diphtheria, tetanus, and acellular pertussis vaccine (DTaP); and 93.6% for 2 doses of varicella vaccine among the 39 states and DC with a 2-dose requirement. The median percentage of any exemptions† was 1.7%. Although statewide vaccination coverage among kindergartners was high during the 2014-15 school year, geographic pockets of low vaccination coverage and high exemption levels can place children at risk for vaccine-preventable diseases. Appropriate school vaccination coverage assessments can help immunization programs identify clusters of low coverage and develop partnerships with schools and communities to ensure that children are protected from vaccine-preventable diseases.

  8. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  9. Paediatric surveillance of pertussis in 1998

    NARCIS (Netherlands)

    Melker HE de; Neppelenbroek SN; Schellekens JFP; Suijkerbuijk AWM; Conyn- van Spaendonck MAE; CIE; LIS

    2000-01-01

    Objective: To gain insight into the severity of pertussis in hospitalised cases. Methods: In 1998, hospitalisation data were collected through paediatric surveillance. Results: From 115 hospitalisation admissions collected, 55% of the patients were younger than 3 months of age and not vaccinated; 12

  10. Recognizing and Preventing Whooping Cough 2 (Pertussis)

    Centers for Disease Control (CDC) Podcasts

    2010-09-16

    This podcast encourages everyone to get vaccinated against whooping cough (pertussis), especially those who will have close contact with an infant.  Created: 9/16/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/16/2010.

  11. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  12. A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers.

    Science.gov (United States)

    Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion

    2012-03-01

    As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.

  13. Toward a mechanism-based in vitro safety test for pertussis toxin.

    NARCIS (Netherlands)

    Vaessen, S.F.; Bruysters, M.W.; Vandebriel, R.J.; Verkoeijen, S.; Bos, R.; Krul, C.A.M.; Akkermans, A.M.

    2014-01-01

    Pertussis vaccines are routinely administered to infants to protect them from whooping cough. Still, an adequate safety test for pertussis toxin (PT), one of the main antigens in these vaccines, is not available. The histamine sensitization test is currently the only assay accepted by regulatory

  14. Vaccination Coverage Disparities Between Foreign-Born and U.S.-Born Children Aged 19-35 Months, United States, 2010-2012.

    Science.gov (United States)

    Varan, Aiden K; Rodriguez-Lainz, Alfonso; Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Li, Qian

    2016-08-01

    Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35 months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed.

  15. Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

    Science.gov (United States)

    Vermeulen, Françoise; Dirix, Violette; Verscheure, Virginie; Damis, Eliane; Vermeylen, Danièle; Locht, Camille; Mascart, Françoise

    2013-04-01

    Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

  16. A randomised controlled study with whole-cell or acellular pertussis vaccines in combination with regular DT-IPV vaccine and a new poliomyelitis (IPV vero) component in children 4 years of age in the Netherlands

    NARCIS (Netherlands)

    Berbers GAM; Lafeber AB; Labadie J; Vermeer-de Bondt PE; Bolscher DJA; Plantinga AD; LVO; Stichting Thuiszorg Oost-Veluwe

    1999-01-01

    In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere

  17. A randomised controlled study with whole-cell or acellular pertussis vaccines in combination with regular DT-IPV vaccine and a new poliomyelitis (IPV vero) component in children 4 years of age in the Netherlands

    NARCIS (Netherlands)

    Berbers GAM; Lafeber AB; Labadie J; Vermeer-de Bondt PE; Bolscher DJA; Plantinga AD; LVO; Stichting Thuiszorg Oost-Veluwe

    1999-01-01

    In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere

  18. The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study.

    Science.gov (United States)

    Cherry, J D

    1984-02-01

    Pertussis is a common serious illness of childhood that can be controlled by immunization. It is a unique disease in that it is clinically manifested more often in females than in males. In the 20th century the mortality from pertussis has decreased steadily in both the United Kingdom and the United States. This decline in death rate was well underway prior to the introduction of pertussis vaccine but was accelerated after vaccine use became widespread. In recent years the case fatality rate in the United States has been considerably greater than that in the United Kingdom. One obvious reason for this difference is the difference in age-specific attack rates in the two nations. Available data also suggest that recent pertussis deaths in infants in England and Wales may frequently be reported as due to respiratory diseases other than pertussis. Although it is frequently suggested by some observers, there is no evidence that the incidence of pertussis was declining prior to the widespread use of vaccine. All available evidence indicates that pertussis vaccine use in both the United Kingdom and the United States was responsible for a drastic reduction in the magnitude of both endemic and epidemic pertussis. Decreased utilization of pertussis vaccine in England and Wales beginning in 1975 resulted in two major epidemics of pertussis in 1977-1979 and 1982-1983. Moderate local and systemic reactions commonly occur following pertussis immunization. These reactions appear to be less common and less severe in the United Kingdom than in the United States, but in contrast to recent studies in the United States, there are no recent quantitative studies in the United Kingdom. There are virtually no data available in the United States on the incidence of serious neurologic disease resulting from pertussis immunization. In contrast, the recently published findings of the NCES, a case-control study of national scope, have allowed attributable risk estimates of serious neurologic

  19. The intention of Dutch general practitioners to offer vaccination against pneumococcal disease, herpes zoster and pertussis to people aged 60 years and older

    NARCIS (Netherlands)

    Lehmann, Birthe A.; Eilers, Renske; Mollema, Liesbeth; Ferreira, Jose; de Melker, Hester E.

    2017-01-01

    Background: Increasing life expectancy results in a larger proportion of older people susceptible to vaccine preventable diseases (VPDs). In the Netherlands, influenza vaccination is routinely offered to people aged 60 years and older. Vaccination against pneumococcal disease, herpes zoster and

  20. Economic evaluation of the 7-vaccine routine childhood immunization schedule in the United States, 2001.

    Science.gov (United States)

    Zhou, Fangjun; Santoli, Jeanne; Messonnier, Mark L; Yusuf, Hussain R; Shefer, Abigail; Chu, Susan Y; Rodewald, Lance; Harpaz, Rafael

    2005-12-01

    To evaluate the economic impact of the routine US childhood immunization schedule: diphtheria and tetanus toxoids and acellular pertussis; tetanus and diphtheria toxoids; Haemophilus influenzae type b conjugate; inactivated poliovirus; measles, mumps, and rubella; hepatitis B; and varicella vaccines. Decision tree-based analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported for 1995-2001. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and time lost. All costs were inflated to 2001 US dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2001 US birth cohort of 3,803,295 infants was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine immunization. Routine childhood immunization with the 7 vaccines was cost saving from the direct cost and societal perspectives, with net savings of 9.9 billion dollars and 43.3 billion dollars, respectively. Without routine vaccination, direct and societal costs of diphtheria, tetanus, pertussis, H influenzae type b, poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, hepatitis B, and varicella would be 12.3 billion dollars and 46.6 billion dollars, respectively. Direct and societal costs for the vaccination program were an estimated 2.3 billion dollars and 2.8 billion dollars, respectively. Direct and societal benefit-cost ratios for routine childhood vaccination were 5.3 and 16.5, respectively. Regardless of the perspective, the current routine childhood immunization schedule results in substantial cost savings.

  1. Research on the safety of the absorbed diphtheria, tetanus,and acellular pertusis combined vaccine(DTaP)%吸附无细胞百白破联合疫苗安全性研究

    Institute of Scientific and Technical Information of China (English)

    凌罗亚; 陈海平; 戚小华; 杨云铠; 陈恩富

    2012-01-01

    Objective To evaluate the safety of the absorbed diphtheria,tetanus and acellular pertusis combined vaccine(DTaP),and provide the evidence for decision-making on National Immunization Program (NIP).Methods There were 3235 aged 3-5 months healthy children and 3198 aged 18-24 months healthy children in four counties in Zhejiang Province selected to immunize the DTaP according to the schedule of NIP.Adverse Events Following Immunization (AEFI) for each vaccinated child was observed.Results The incidence rates of AEFI for three primary doses and one boost dose were 6.28%,6.39%,6.26% and 14.57%,respectively.There was no statistical difference among the rates of 3 primary doses vaccinated children,and the rate of one boost dose vaccinated children was significant higher than the average rate(6.31% ) of basic vaccinated children ( x2 =1049,P < 0.01 ).Most of the AEFI happened in 30 minutes after vaccinated.The main clinical character were fever,tetter and pain.Most of the AEFI were mild.There were not any rare,sever AEFI or new AEFI detected.Conclusions The reported AEFIs for DTaP were mild in this study.DTaP have a good immunization safety.%目的 研究吸附无细胞百白破联合疫苗在人群中应用的安全性,为评价纳入国家免疫规划疫苗安全性提供依据.方法 在浙江省4个县(市、区)选择3~5月龄的初免儿童3235人,18~24月龄加强免疫儿童3198名,按照免疫程序接种本次研究观察的无细胞百白破疫苗,进行接种后安全性观察.结果 初免儿童3剂次基础免疫总不良反应发生率分别为6.28%、6.39%、6.26%,差异无统计学意义(x2=0.05,P> 0.05).基础免疫平均不良反应发生率为6.31%,与加强免疫的总体不良反应发生率14.57%比较差异有统计学意义( x2=1049,P<0.01).大部分不良反应发生在接种后30 min内.全身不良反应以发热和皮疹为主,局部反应以注射处触痛为主.各剂次不良反应发生程度均以轻度和

  2. Genetic Variation of Bordetella pertussis in Austria.

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    Birgit Wagner

    Full Text Available In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32, Linz (n = 63 and Graz (n = 15 by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis (n = 77, by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin gene (n = 110, and by amplification refractory mutation system quantitative PCR (ARMS-qPCR (n = 110 to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB, a fimbrial adhesin (fimD, tracheal colonisation factor (tcfA, and the virulence sensor protein (bvgS. Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517. The major part of the samples (93% displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.

  3. Genetic Variation of Bordetella pertussis in Austria.

    Science.gov (United States)

    Wagner, Birgit; Melzer, Helen; Freymüller, Georg; Stumvoll, Sabine; Rendi-Wagner, Pamela; Paulke-Korinek, Maria; Repa, Andreas; Mooi, Frits R; Kollaritsch, Herwig; Mittermayer, Helmut; Kessler, Harald H; Stanek, Gerold; Steinborn, Ralf; Duchêne, Michael; Wiedermann, Ursula

    2015-01-01

    In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.

  4. An Infant with Benign Isolated Abducens Palsy After Vaccination

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    Celebi Kocaoglu

    2014-02-01

    Full Text Available Benign isolated abducens palsy is a self-improving clinical entity characterized by esotropia and diplopia led by the deficiency of abduction, and accompanied by no other neurological findings. The entity may occur after experiencing minor fever episodes, viral infection. The pathophysiological mechanism of cellular injury remains unclear. Hypotheses involve damage arising from autoimmune mediation or direct viral invasion causing demyelination, localized arteritis or genetic predisposition, which could increase susceptibility to such nerve palsies. Diagnosed with benign isolated abducens palsy, a 19-month-old girl infant admitted to our outpatient clinic with an acute onset of esotropia in the right eye developing two weeks after the vaccination of diphtheria, acellular pertussis, tetanus, inactivated polio and Haemophilus influenzae type b (DTPa-IP-Hib was presented in this report.

  5. Parental delay or refusal of vaccine doses, childhood vaccination coverage at 24 months of age, and the Health Belief Model.

    Science.gov (United States)

    Smith, Philip J; Humiston, Sharon G; Marcuse, Edgar K; Zhao, Zhen; Dorell, Christina G; Howes, Cynthia; Hibbs, Beth

    2011-01-01

    We evaluated the association between parents' beliefs about vaccines, their decision to delay or refuse vaccines for their children, and vaccination coverage of children at aged 24 months. We used data from 11,206 parents of children aged 24-35 months at the time of the 2009 National Immunization Survey interview and determined their vaccination status at aged 24 months. Data included parents' reports of delay and/or refusal of vaccine doses, psychosocial factors suggested by the Health Belief Model, and provider-reported up-to-date vaccination status. In 2009, approximately 60.2% of parents with children aged 24-35 months neither delayed nor refused vaccines, 25.8% only delayed, 8.2% only refused, and 5.8% both delayed and refused vaccines. Compared with parents who neither delayed nor refused vaccines, parents who delayed and refused vaccines were significantly less likely to believe that vaccines are necessary to protect the health of children (70.1% vs. 96.2%), that their child might get a disease if they aren't vaccinated (71.0% vs. 90.0%), and that vaccines are safe (50.4% vs. 84.9%). Children of parents who delayed and refused also had significantly lower vaccination coverage for nine of the 10 recommended childhood vaccines including diphtheria-tetanus-acellular pertussis (65.3% vs. 85.2%), polio (76.9% vs. 93.8%), and measles-mumps-rubella (68.4% vs. 92.5%). After adjusting for sociodemographic differences, we found that parents who were less likely to agree that vaccines are necessary to protect the health of children, to believe that their child might get a disease if they aren't vaccinated, or to believe that vaccines are safe had significantly lower coverage for all 10 childhood vaccines. Parents who delayed and refused vaccine doses were more likely to have vaccine safety concerns and perceive fewer benefits associated with vaccines. Guidelines published by the American Academy of Pediatrics may assist providers in responding to parents who may delay

  6. Is pertussis actually reemerging? Insights from an individual-based model.

    Science.gov (United States)

    Codeço, C T; Luz, P M

    2001-01-01

    In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc.), human population structure (individual risk, age structure, interaction matrices, immune response, etc.), as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  7. Is pertussis actually reemerging? Insights from an individual-based model

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    Codeço Cláudia Torres

    2001-01-01

    Full Text Available In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc., human population structure (individual risk, age structure, interaction matrices, immune response, etc., as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  8. Is pertussis actually reemerging? Insights from an individual-based model

    Directory of Open Access Journals (Sweden)

    Cláudia Torres Codeço

    2001-06-01

    Full Text Available In this paper, we introduce a spatially explicit, individual-based model developed to simulate the dynamics of pertussis in a small population. With this simulation approach, complex epidemic systems can be built using information on parasite population structure (strain diversity, virulence diversity, etc., human population structure (individual risk, age structure, interaction matrices, immune response, etc., as well as mechanisms of evolution and learning. We parameterized our model to describe pertussis in an age-structured community. Pertussis or whooping cough is an acute infection of the respiratory tract caused by Bordetella pertussis. Despite wide-scale vaccination in many countries, this disease is reemerging throughout the world in both adults and children. Emergence has been explained by many factors: wane of vaccine and natural immunity, increase of asymptomatic carriers, and/or natural selection of non-vaccine strains. Here, we model these hypotheses and analyze their potential impact on the observed increase of pertussis notification.

  9. ADVERSE EVENTS POST-DTAP AND DTwP VACCINATION IN THAI CHILDREN.

    Science.gov (United States)

    Fortuna, Librada; Sirivichayakul, Chukiat; Watanaveeradej, Veerachai; Soonthornworasiri, Ngamphol; Sitcharungsi, Raweerat

    2015-07-01

    We conducted a prospective study to compare the development of fever (axillary T ≥ 37.9 °C) within 4 hours of vaccination, determine the proportion of children who develop high fever (T ≥ 39°C) and evaluate parental days missed from work due to their children's vaccination with either the diphtheria-tetanus-whole cell pertussis (DTwP) or diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The results of this study can help physicians and parents decide whether to have their child vaccinated with the DTwP or more expensive DTaP vaccine. We studied 140 healthy Thai children aged 2 months to 6 years from December 2011 to March 2012 who presented for vaccination. Parents recorded their child's temperature, local and systemic adverse reactions and missed days from work due to these adverse events on a diary card. Of the 140 participants, 72 received the DTwP vaccine and 68 received the DTaP vaccine. The median (IQR) age was 4 (2-6) months and the median weight was 7.1 (5.6-8.7) kg. Twenty children developed fever (axillary T ≥ 37.9°C) within 4 hours following vaccination, 17 (23.6%) had received the DTwP vaccine and 3 (4.4%) had received the DTaP vaccine (p = 0.040). One child (1.4%) who had received the DTwP vaccine and none who received the DTaP vaccine developed high fever (T ≥ 39°C) within 4 hours of vaccination (p = 0.329). Parents of two children who received the DTwP vaccine and one child who received the DTaP vaccine missed work following vaccination (p = 0.059). In conclusion, children who received the DTwP vaccines were more likely to have early post-vaccination fever and higher fever but there was no significant difference between the two groups in parental days lost from work.

  10. Bordetella pertussis attachment to respiratory epithelial cells can be impaired by fimbriae-specific antibodies

    NARCIS (Netherlands)

    Rodriguez, ME; Hellwig, SMM; Vidakovics, MLAP; Berbers, GAM; van de Winkel, JGJ

    2006-01-01

    Bordetella pertussis attachment to host cells is a crucial step in colonization. In this study, we investigated the specificity of antibodies, induced either by vaccination or infection, capable of reducing bacterial adherence to respiratory epithelial cells. Both sera and purified anti-B. pertussis

  11. Pertussis in north-central and northwestern regions of Algeria.

    Science.gov (United States)

    Benamrouche, Nabila; Tali Maamar, Hassiba; Lazri, Malika; Hasnaoui, Sonia; Radoui, Abdelkarim; Lafer, Ourida; Boukari, Rachida; Kaddache, Chawki; Arrada, Zakia; Rahal, Kheira

    2016-11-24

    Pertussis outbreaks continue to occur in many countries despite high vaccination coverage. Under-diagnosed cases in adolescents and adults may result in increased transmission to infants, who are at risk of severe pertussis. Additional measures to protect both groups should be considered. Nasopharyngeal samples and sera were collected from patients and household contacts with clinically suspected pertussis. Diagnoses were confirmed by culture, real-time polymerase chain reaction (PCR), and serology. Bordetella pertussis isolates were characterized by antimicrobial sensitivity and fimbrial serotyping. Of 392 participants, 134/248 patients (54%) and 66/144 contacts (45.8%) had confirmed pertussis infections. B. parapertussis was not detected. All B. pertussis isolates were sensitive to the antibiotics tested, and all expressed the Fim3, not the Fim2, fimbrial serotype. Most patients (81.2%) were Algeria. Most infections occur in unvaccinated infants <6 months of age, with mothers as the main source of infection. An adolescent/adult booster should be considered. Adoption of sensitive and specific laboratory tests would improve pertussis diagnosis and surveillance.

  12. Observation on Adverse Reaction of Diphtheria, Tetanus and Acellular Pertusis Combined Vaccine and Diphtheria, Tetanus and Whole-cell Pertusis Combined Vaccine%无细胞和全细胞百白破疫苗接种不良反应观察

    Institute of Scientific and Technical Information of China (English)

    杨洁; 何梅英; 单芙香; 旷翠萍

    2011-01-01

    目的 比较接种吸附无细胞百白破疫苗(DTaP)与全细胞百自破疫苗(DTwP)后发生疑似预防接种异常反应的差异.方法 对2009年1月-2010年12月在辖区内预防接种门诊接种百白破疫苗出现疑似预防接种异常反应进行回顾性分析.结果 62 214名接种DTaP者发生疫苗疑似预防接种异常反应8例,反应率12.86/10万;62 182名接种DTwP者发生疫苗疑似预防接种异常反应54例,反应率86.84/10万;DTwP反应发生率高于DTaP,差异有统计学意义(P<0.01).结论 DTaP的接种副反应较DTwP低、安全性好,接种百白破联合疫苗时最好使用吸附无细胞百白破疫苗(DTaP).%Objective To compare the difference abnormal reaction in preventive vaccination between absorbed diphtheria, tetanus and acellular pertusis combined vaccine(DTaP) and absorbed diphtheria, tetanus and whole - cell pertusis combined vaccine( DTwP). Methods Retrospective analysis on suspected adverse events following immunization (AEFI) of diphtheria, tetanus and pertusis combined vaccine in Luohu Distric during Jan 2009 - Dec 2010. Results Eight AEFI cases were observed in 62 214 cases vaccinated with DTaP. The reaction rate was 12.86/100,000. In 62 182 cases vaccinated with DTwP, 54 AEFI cases were observed. The reaction rate was 86.84/100,000. The reaction rate in DTwP group was higher than the DTaP group (with statistical significance, P<0.01). Conclusions The adverse reaction rate of DTaP is comparatively lower. DTaP is safe and recommended for vaccination.

  13. Infectious Disease Report: Bordetella pertussis Infection in Patients With Cancer.

    Science.gov (United States)

    Yacoub, Abraham; Nanjappa, Sowmya; Janz, Tyler; Greene, John N

    2016-04-01

    We illustrate 2 cases of pneumonia associated with Bordetella pertussis infection in 72-year-old and 61-year-old patients with cancer receiving myelosuppressive therapy after hematopoietic stem cell transplantation. Bacterial infections are a significant cause of morbidity and mortality in patients with cancer, and those receiving hematopoietic stem cell transplant, solid organ transplant, or myelosuppressive therapy are at increased risk. The infection was detected and the 2 patients had good outcomes following azithromycin treatment. Pertussis, also known as whooping cough, is a contagious respiratory illness that has become a public health challenge due to decreased immunity of the pertussis vaccine. Therefore, it is critical to recognize pertussis early in the course of the disease.

  14. Pertussis-like syndrome or pertussis: a delay diagnosis

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    Heda Melinda Nataprawira

    2012-01-01

    Full Text Available Background Recent reports of pertussis epidemiology from Asia, Africa and South America have been limited, but the World Health Organization estimates indicate that these regions have the highest disease burden. Difficulty in estimating the prevalence of pertussis is due to lack of access to diagnostic methods, misdiagnoses, under-reporting, and different countries’ reporting criteria. A syndrome characterized by severe episodes of coughing resembling whooping cough (pertussis has also been defined as pertussis-like syndrome. Objective To report eleven cases of pertussis or pertussis-like syndrome in the pediatric ward of Hasan Sadikin Hospital. Methods This retrospective study was conducted by reviewing medical records from 2008–2010. Characteristics of 11 pertussis-like syndrome patients were documented including age, gender, history of pertussis immunization, clinical manifestations, laboratory findings, initial diagnosis, treatment and clinical response. Isolation of Bordetella pertussis using Bordet-Gengou agar was also noted. Pertussis diagnoses were grouped based on two classifications: probable and confirmed. Results Eleven patients were diagnosed with pertussis-like syndrome, including 5 boys and 6 girls. Mmost subjects were less than 6 months of age. Only one subject had received previous pertussis immunization. Dyspnea, paroxysmal cough, and fever were the most common symptoms. All were initially diagnosed to have had severe bacterial pneumonia, and later changed to probable pertussis. Three subjects exhibited post-tussive vomiting and cyanosis, while none had apneic symptoms. All B. pertussis isolations yielded negative results. Ampicillin or cephalosporin was initially administered. Patients receiving subsequent clarithromycin showed good clinical responses. Conclusion All infants were likely considered to have pertussis, as most had no pertussis immunizations. However, B. pertussis isolation was unsuccessful in all cases. As

  15. Safety and immunogenicity of an investigational fully liquid hexavalent DTaP-IPV-Hep B-PRP-T vaccine at two, four and six months of age compared with licensed vaccines in Latin America.

    Science.gov (United States)

    Macías, Mercedes; Lanata, Claudio F; Zambrano, Betzana; Gil, Ana I; Amemiya, Isabel; Mispireta, Monica; Ecker, Lucie; Santos-Lima, Eduardo

    2012-08-01

    This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 μg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators. Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3. The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine. This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.

  16. PENETAPAN STANDAR NASIONAL DARI VAKSIN DPT: Penetapan Standar Nasional Vaksin Pertussis

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    Muljanti Prijanto

    2012-09-01

    Full Text Available To check the potency of DPT vaccine, standard preparations of the components, namely Adsorbed Diphtheria Toxoid, Pertussis Vaccine, and Adsorbed Tetanus Toxoid are necessary. Since WHO International Standard Preparations are distributed only in limited amounts, WHO has suggested that each member country shold develop a National Standard, which is to be matched with International Standard Preparations. An Indonesian National Standard of DPT vaccine (lot 1 has been prepared and lyophilized at the National Institute of Health in Tokyo. The potency of the National Standard of Pertussis Vaccine was determined by Active Mouse Protection Test (AMPT. After several experiments, the potency of the National Standard of Pertussis Vaccine has been decided of being 12 IU/ml. Using the same standard preparations, namely the National Standards, it is hoped that from a lot of DPT vaccine, similar results of potency could be achieved when determined by Government Vaccine Quality Control laboratory and the Manufacturer's laboratory.

  17. PENETAPAN STANDAR NASIONAL DARI VAKSIN DPT: Penetapan Standar Nasional Vaksin Pertussis

    Directory of Open Access Journals (Sweden)

    Muljanti Prijanto

    2012-09-01

    Full Text Available To check the potency of DPT vaccine, standard preparations of the components, namely Adsorbed Diphtheria Toxoid, Pertussis Vaccine, and Adsorbed Tetanus Toxoid are necessary. Since WHO International Standard Preparations are distributed only in limited amounts, WHO has suggested that each member country shold develop a National Standard, which is to be matched with International Standard Preparations. An Indonesian National Standard of DPT vaccine (lot 1 has been prepared and lyophilized at the National Institute of Health in Tokyo. The potency of the National Standard of Pertussis Vaccine was determined by Active Mouse Protection Test (AMPT. After several experiments, the potency of the National Standard of Pertussis Vaccine has been decided of being 12 IU/ml. Using the same standard preparations, namely the National Standards, it is hoped that from a lot of DPT vaccine, similar results of potency could be achieved when determined by Government Vaccine Quality Control laboratory and the Manufacturer's laboratory.

  18. A phase III, randomized controlled study to assess the safety and immunogenicity of a semi-synthetic diphtheria, tetanus and whole-cell pertussis vaccine in Indian infants.

    Science.gov (United States)

    Sharma, Hitt; Patil, Vishwanath; Sharma, Dharambhushan; Kapre, Subhash; Jadhav, Suresh; Ravetkar, Satish; Kumar, Rakesh; Bahl, Sunil; Parekh, Sameer; Chakravarty, Anita

    2012-09-21

    Reactions to DTwP vaccine are well known and are a matter of great concern, much for the development of next generation combination vaccines. To avoid such reactions which occur from foreign compounds, WHO suggested manufacture of DTwP vaccine using semi-synthetic medium. The phase III trial reported here was conducted to assess the immunogenicity, tolerability and safety of a new DTwP vaccine manufactured using semi-synthetic medium for both tetanus and diphtheria toxoids in comparison with the routinely manufactured DTwP vaccine. In all, 331 infants aged 6-8 weeks were enrolled, out of which 308 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly amongst the two study groups. Though, the immunogenicity results were comparable between the two vaccines, the incidence of adverse events was comparatively low in semi-synthetic vaccine as against the routine vaccine group for all the three doses. The semi-synthetic DTwP vaccine was immunogenic and showed a significant lower incidence of local adverse events in comparison to the routine vaccine. This vaccine is now being used in the routine vaccination programme both as a triple antigen (DTwP alone) as well as a combination with Hepatitis B and/or Haemophilus influenzae type b vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

    Science.gov (United States)

    Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

    2010-04-19

    This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.

  20. Whooping cough in Pakistan: Bordetella pertussis vs Bordetella parapertussis in 2005-2009.

    Science.gov (United States)

    Bokhari, Habib; Said, Fahad; Syed, Muhammad A; Mughal, Amjad; Kazi, Yasmeen F; Heuvelman, Kees; Mooi, Frits R

    2011-10-01

    Pertussis, or whooping cough, is an acute respiratory disease mainly affecting infants and children and is caused by Bordetella pertussis and Bordetella parapertussis. The aim of this study was to investigate the share of Bordetella species from potential whooping cough cases during 2005-2009. Eight hundred and two samples from suspected pertussis cases were collected, mainly from 2 provinces of Pakistan. Bacterial culture, identification, DNA extraction and routinely used polymerase chain reaction (PCR) methods using IS1001, IS1002 and IS481 were used to identify the Bordetella species. The results were unexpected, because all of the isolates collected from the different cities were identified as B. parapertussis (7.4%); B. pertussis was not isolated from any sample. However, PCR results indicated the presence of a small percentage (0.6%) of B. pertussis among the total cases studied. This study suggests that vaccines to protect against both B. pertussis and B. parapertussis should be considered.

  1. Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

    Institute of Scientific and Technical Information of China (English)

    Fiorella Orellana-Peralta; Michelle Jacinto; Maria J Pons; Cludia Gomes; Carlos Bada; Isabel Reyes; Juana del Valle Mendoza; Joaquim Ruiz

    2015-01-01

    Objective:To characterize two Achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program. Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR. Results:Two Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was evaluated by disk-diffusion method and by PCR. Conclusions:Although more detailed studies are needed, the present data highlight the possibility that Achromobacter xylosoxidans, closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella, might also result in cases of whooping cough. Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.

  2. Seroepidemiology of Bordetella pertussis infections in the twin cities of Pakistan

    Directory of Open Access Journals (Sweden)

    Fahad Said

    2009-12-01

    Full Text Available Background: Bordetella pertussis is the cause of whooping cough occurring mainly in children. The prevalence of this disease has been reduced largely due to worldwide mass vaccination with DTP vaccine. However, the immunity produced by the vaccination wanes by the passage of time. Still this disease kills around 2-4 million children annually. Adults may be a source of infection for infants and children. Furthermore, Bordetella pertussis has also been found to be associated with cases of persistent cough in adults in many countries. Aim: The aim of this study was to study the exposure of the adult population to the Bordetella pertussis by detecting IgG antibodies. Materials and Methods: We performed Seroepidemiology of Bordetella pertussis infections in multiethnic twin cities of Pakistan (Rawalpindi and Islamabad using a commercially available ELISA kit to have a picture of epidemiology of Bordetella pertussis in Pakistan. We targeted adults of age between 18-45 years (mean age 29.64 years. Results: The results of our study show a high percentage of seropositivity to Bordetella pertussis (89 percent, which indicates higher exposure to this organism and risk of infection to infants, children, adolescents and adults. Conclusion: A high percentage of seropositive individuals are alarming to health care professionals as well as policy makers. Bordetella pertussis infections may be associated with their atypical manifestation in Pakistan. Adult vaccination with DTP is recommended to reduce the risk of infection in infants and children through adult reservoirs.

  3. Seroepidemiology of Bordetella pertussis infections in the twin cities of Pakistan

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Syed

    2009-01-01

    Full Text Available Background: Bordetella pertussis is the cause of whooping cough occurring mainly in children. The prevalence of this disease has been reduced largely due to worldwide mass vaccination with DTP vaccine. However, the immunity produced by the vaccination wanes by the passage of time. Still this disease kills around 2-4 million children annually. Adults may be a source of infection for infants and children. Furthermore, Bordetella pertussis has also been found to be associated with cases of persistent cough in adults in many countries. Aim: The aim of this study was to study the exposure of the adult population to the Bordetella pertussis by detecting IgG antibodies. Materials and Methods: We performed Seroepidemiology of Bordetella pertussis infections in multiethnic twin cities of Pakistan (Rawalpindi and Islamabad using a commercially available ELISA kit to have a picture of epidemiology of Bordetella pertussis in Pakistan. We targeted adults of age between 18-45 years (mean age 29.64 years. Results: The results of our study show a high percentage of seropositivity to Bordetella pertussis (89 percent, which indicates higher exposure to this organism and risk of infection to infants, children, adolescents and adults. Conclusion: A high percentage of seropositive individuals are alarming to health care professionals as well as policy makers. Bordetella pertussis infections may be associated with their atypical manifestation in Pakistan. Adult vaccination with DTP is recommended to reduce the risk of infection in infants and children through adult reservoirs.

  4. Timeliness and completeness of routine childhood vaccinations in children by two years of age in Alberta, Canada.

    Science.gov (United States)

    Saini, Vineet; MacDonald, Shannon E; McNeil, Deborah A; McDonald, Sheila W; Kellner, James D; Edwards, Sarah A; Stagg, Victoria; Tough, Suzanne

    2017-06-16

    Assessing timeliness and completeness of vaccine administration is important for evaluating the effectiveness of immunization programs. Few studies have reported timeliness, particularly in Canada. The objective of this study was to examine timeliness of the receipt of vaccination for each routine childhood recommended vaccine by 24 months of age among children in a community-based pregnancy cohort in Calgary, Alberta. Survey data from a community-based pregnancy cohort in Alberta were linked to Public Health vaccination records of children (n = 2763). The proportion of children receiving early, timely, delayed, or no vaccination was calculated. A dose was considered early if it was administered before the recommended age in days as per the vaccination schedule, timely if administered at any time from start of recommended age in days to age in days when delay counts were initiated, and delayed if it was administered on or after age in days when delay counts were initiated. Series completion rates were also calculated. For multi-dose vaccines, over 80% of children had timely doses at 2, 4 and 6 months. By 12 months, this proportion decreased to 65% (95% CI: 63%-66%) for meningococcal conjugate group C, 61% (95% CI: 59%-62%) for measles antigen-containing vaccines and 64% (95% CI: 62%-65%) for varicella antigen-containing vaccines. At 18 months, only 55% (95% CI: 53%-56%) of the children had a timely 4th dose of diphtheria, acellular pertussis, tetanus, polio, and Haemophilus influenzae type b vaccine. Eventual series completion rate for all recommended vaccines was 77% (95% CI: 75%-79%). The timeliness and completeness of routine childhood vaccination in preschool children in this community-based pregnancy cohort is lower than provincial targets. Data on timeliness of vaccination can inform further work on barriers and enablers to vaccination in order to meet provincial targets.

  5. Pertussis: clinical and bacteriological diagnosis of six cases

    Directory of Open Access Journals (Sweden)

    Arellano Penagos Mario

    2014-07-01

    Full Text Available ertussis is an endemic disease in our population. Every 3 to 4 years, pertussis has an epidemic pattern even in countries with good health conditions. Antipertussis vaccine first dose is adminis- tered at the age of 2 months; a second and third dose are given at 4 and 6 months of age. This vaccine has an 8 to 10 year protective effect, for which reason it is suggested that pregnant women in the third trimester should be vaccinated in order to prevent pertussis in newborns. It should also be administered to older people to avoid turning them into asymptomatic carriers. Clinic manifestations are easily identifiable due to respiratory symptoms, especially to the particular characteristics of the cough. The diagnosis is supported by the presence of leukocytosis (predominantly lymphocytes and by certain thoracic radiologic findings. The diagnosis is confirmed with a positive culture for Bordetella pertussis or with a polymerase chain reaction (PCR. In a non complicated clinic course macrolides are still the best therapeutic choice. Nonetheless clinic observation is highly recom- mended in order to avoid complications. Redefinition of vaccine programs against Bordetella pertussis in Mexican population is recommended and also to notify the presence of the disease to the corresponding health authorities.

  6. Simultaneous vaccination of Chinese applicants for a United States immigrant visa.

    Science.gov (United States)

    Hua, Li; Hongtao, He; Shunqin, Wang; Jinping, Gao; Jiandong, Chen; Zhaoliang, Lei; Xinwen, Feng

    2008-05-01

    Simultaneous vaccination is still uncommon in China, and many Chinese people are quite concerned about the adverse reactions because few data regarding the adverse reactions of simultaneous vaccination in Chinese people have been reported. The objective of this study was to evaluate the safety of simultaneous vaccination and the frequency of adverse reactions following simultaneous vaccinations in Chinese applicants for a United States immigrant visa. We conducted a prospective observational study in 772 applicants receiving required vaccination in Guangdong International Travel Healthcare Center. The vaccines required for vaccination included diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), adult formulation tetanus and diphtheria toxoids (Td), haemophilus influenzae type-b conjugate vaccine (Hib), oral polio vaccine (OPV), hepatitis B vaccine (HepB), combined measles mumps rubella vaccine (MMR), varicella vaccine (Var), and influenza vaccine (Inf), pneumococcal polysaccharide vaccine (PPV). Data on adverse reactions were collected by questionnaires. Seven hundred and seventy-two participants have received a total of 2533 doses of different vaccines, and 49.6% of the participants reported adverse reactions within 7 days following vaccination, with 39.8%(307/772) local reactions and 20.2%(156/772) systemic reactions. There were no allergic reactions. Only one vaccinee visited hospital seeking treatment due to fever, and recovered well. The most frequent local reaction was pain at the injection site (260/772, 33.7%), especially in the case of PPV vaccination, 61.2% (63/103) vaccinees who received PPV complained of pain at the site of injection, while the most frequent systemic reaction was fever (84/772, 10.9%). Pain and fever were all temporary reactions and resolved within 72h. Logistic regression analysis found that females experienced adverse reactions more frequently than males [(local reactions: female:male=41.7%(187/448):37%(120/324), p

  7. Phase variation and microevolution at homopolymeric tracts in Bordetella pertussis

    Directory of Open Access Journals (Sweden)

    Cummings Craig A

    2007-05-01

    Full Text Available Abstract Background Bordetella pertussis, the causative agent of whooping cough, is a highly clonal pathogen of the respiratory tract. Its lack of genetic diversity, relative to many bacterial pathogens, could limit its ability to adapt to a hostile and changing host environment. This limitation might be overcome by phase variation, as observed for other mucosal pathogens. One of the most common mechanisms of phase variation is reversible expansion or contraction of homopolymeric tracts (HPTs. Results The genomes of B. pertussis and the two closely related species, B. bronchiseptica and B. parapertussis, were screened for homopolymeric tracts longer than expected on the basis of chance, given their nucleotide compositions. Sixty-nine such HPTs were found in total among the three genomes, 74% of which were polymorphic among the three species. Nine HPTs were genotyped in a collection of 90 geographically and temporally diverse B. pertussis strains using the polymerase chain reaction/ligase detection reaction (PCR/LDR assay. Six HPTs were polymorphic in this collection of B. pertussis strains. Of note, one of these polymorphic HPTs was found in the fimX promoter, where a single base insertion variant was present in seven strains, all of which were isolated prior to introduction of the pertussis vaccine. Transcript abundance of fimX was found to be 3.8-fold lower in strains carrying the longer allele. HPTs in three other genes, tcfA, bapC, and BP3651, varied widely in composition across the strain collection and displayed allelic polymorphism within single cultures. Conclusion Allelic polymorphism at homopolymeric tracts is common within the B. pertussis genome. Phase variability may be an important mechanism in B. pertussis for evasion of the immune system and adaptation to different niches in the human host. High sensitivity and specificity make the PCR/LDR assay a powerful tool for investigating allelic variation at HPTs. Using this method

  8. Pertactin-negative Bordetella pertussis strains in Canada: characterization of a dozen isolates based on a survey of 224 samples collected in different parts of the country over the last 20 years

    Directory of Open Access Journals (Sweden)

    Raymond S.W. Tsang

    2014-11-01

    Conclusions: As reported elsewhere, pertactin-negative B. pertussis has emerged in Canada in recent years, notably in 2012. This coincided with an increase in pertussis activity in Canada. A further systematic study with a larger geographical representative sample is required to determine how these vaccine-negative strains may contribute to the overall changing epidemiology of pertussis in Canada.

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

    Science.gov (United States)

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

    2011-02-01

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

  10. Pertussis: Disease Villain!

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about pertussis, or whooping cough-what it is and how to protect yourself from it.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  11. Preventing Pertussis (Whooping Cough)

    Science.gov (United States)

    ... will get pertussis becomes very small. Journal of Midwifery & Women’s Health 1526-9523/09/$36.00 doi: ... reproduction is sub- ject to the Journal of Midwifery & Women’s Health’s approval. The information and recommendations appearing ...

  12. Travelers' Health: Pertussis

    Science.gov (United States)

    ... in an Area with Zika? Find a Clinic Yellow Fever Vaccinations Clinics FAQ Disease Directory Resources Resources for ... CE Courses and Training Presentations for Health Professionals Yellow Fever Vaccine Course About the Yellow Fever Vaccine Course ...

  13. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... meningitis Stiletto and Extremus posters videos mono pertussis Silence the Sounds of Pertussis Acalla los Sonidos de ... someone you know has hbv/hcv standard precautions Silence the Sounds of Pertussis spokespeople who we are ...

  14. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... and Extremus posters videos mono pertussis Silence the Sounds of Pertussis Acalla los Sonidos de la Tos ... know has hbv/hcv standard precautions Silence the Sounds of Pertussis spokespeople who we are Your Choice! ...

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Loss of multi-epitope specificity in memory CD4(+ T cell responses to B. pertussis with age.

    Directory of Open Access Journals (Sweden)

    Wanda G H Han

    Full Text Available Pertussis is still occurring in highly vaccinated populations, affecting individuals of all ages. Long-lived Th1 CD4(+ T cells are essential for protective immunity against pertussis. For better understanding of the limited immunological memory to Bordetella pertussis, we used a panel of Pertactin and Pertussis toxin specific peptides to interrogate CD4(+ T cell responses at the epitope level in a unique cohort of symptomatic pertussis patients of different ages, at various time intervals after infection. Our study showed that pertussis epitope-specific T cell responses contained Th1 and Th2 components irrespective of the epitope studied, time after infection, or age. In contrast, the breadth of the pertussis-directed CD4(+ T cell response seemed dependent on age and closeness to infection. Multi-epitope specificity long-term after infection was lost in older age groups. Detailed knowledge on pertussis specific immune mechanisms and their insufficiencies is important for understanding resurgence of pertussis in highly vaccinated populations.

  17. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

    Science.gov (United States)

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-01

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care.

  18. National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19-35 Months - United States, 2014.

    Science.gov (United States)

    Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Singleton, James A; Kolasa, Maureen

    2015-08-28

    The reduction in morbidity and mortality associated with vaccine-preventable diseases in the United States has been described as one of the 10 greatest public health achievements of the first decade of the 21st century. A recent analysis concluded that routine childhood vaccination will prevent 322 million cases of disease and about 732,000 early deaths among children born during 1994-2013, for a net societal cost savings of $1.38 trillion. The National Immunization Survey (NIS) has monitored vaccination coverage among U.S. children aged 19-35 months since 1994. This report presents national, regional, state, and selected local area vaccination coverage estimates for children born from January 2011 through May 2013, based on data from the 2014 NIS. For most vaccinations, there was no significant change in coverage between 2013 and 2014. The exception was hepatitis A vaccine (HepA), for which increases were observed in coverage with both ≥1 and ≥2 doses. As in previous years, children received no vaccinations. National coverage estimates indicate that the Healthy People 2020 target* of 90% was met for ≥3 doses of poliovirus vaccine (93.3%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.5%), ≥3 doses of hepatitis B vaccine (HepB) (91.6%), and ≥1 dose of varicella vaccine (91.0%). Coverage was below target for ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), the full series of Haemophilus influenzae type b (Hib) vaccine, hepatitis B (HepB) birth dose,† ≥4 doses pneumococcal conjugate vaccine (PCV), ≥2 doses of HepA, the full series of rotavirus vaccine, and the combined vaccine series.§ Examination of coverage by child's race/ethnicity revealed lower estimated coverage among non-Hispanic black children compared with non-Hispanic white children for several vaccinations, including DTaP, the full series of Hib, PCV, rotavirus vaccine, and the combined series. Children from households classified as below the federal

  19. Review of the neutrophil response to Bordetella pertussis infection.

    Science.gov (United States)

    Eby, Joshua C; Hoffman, Casandra L; Gonyar, Laura A; Hewlett, Erik L

    2015-12-01

    The nature and timing of the neutrophil response to infection with Bordetella pertussis is influenced by multiple virulence factors expressed by the bacterium. After inoculation of the host airway, the recruitment of neutrophils signaled by B. pertussis lipooligosaccharide (LOS) is suppressed by pertussis toxin (PTX). Over the next week, the combined activities of PTX, LOS and adenylate cyclase toxin (ACT) result in production of cytokines that generate an IL-17 response, promoting neutrophil recruitment which peaks at 10-14 days after inoculation in mice. Arriving at the site of infection, neutrophils encounter the powerful local inhibitory activity of ACT, in conjunction with filamentous hemagglutinin. With the help of antibodies, neutrophils contribute to clearance of B. pertussis, but only after 28-35 days in a naïve mouse. Studies of the lasting, antigen-specific IL-17 response to infection in mice and baboons has led to progress in vaccine development and understanding of pathogenesis. Questions remain about the mediators that coordinate neutrophil recruitment and the mechanisms by which neutrophils overcome B. pertussis virulence factors.

  20. Development and Validation of ELISA Assays for Determination of Serum Antibody against Pertussis Toxin, Filamentous Hemagglutinin, Pertactin of Bordetella Pertussis%百日咳毒素丝状血凝素和百日咳黏附素血清抗体检测方法的建立及验证

    Institute of Scientific and Technical Information of China (English)

    徐颖华; 骆鹏; 王丽婵; 卫辰; 侯启明; 张庶民

    2011-01-01

    目的 建立定量检测抗百日咳毒素抗体(Antibody to Pertussis Toxin,Anti-PT)、抗丝状血凝素抗体(Antibody to Filamentous Haemagglutinin,Anti-FHA)和抗百日咳黏附素抗体(Antibody to Pertactin,Anti-Prn)的酶联免疫吸附试验(Enzyme-linked Immunosorbent Assay,ELISA)方法.方法 分别应用纯化的百日咳毒素(PT)、丝状血凝素(FHA)和百日咳黏附素(Prn)作为包被抗原,百日咳血清抗体国际参考品为标准品,建立定量检测Anti-PT、Anti-FHA、Anti-Prn的ELISA方法.结果 建立了三种定量检测ELISA方法,并进行方法学验证.结果 显示,定量检测Anti-PT的ELISA方法的最低检测限度为1.31IU/ml(国际单位/毫升),批内和批间变异系数(Coefficient of Variability,CV)分别为9.99%和11.55%,回收率为97.19%;检测Anti-FHA方法的最低检测限度为1.02IU/ml,批内和批间CV分别为11.01%和12.76%,回收率为101.20%;检测Anti-Prn方法的最低检测限度为0.511U/ml,批内和批间CV分别为9.00%和11.18%,回收率为107.83%.用建立的ELISA方法与国外同类方法对30份血清样本进行分析,检测结果差异无统计学意义.应用上述建立的三种ELISA方法,检测分析了三组份无细胞百日咳疫苗(Acellular Pertussis Vaccine,aP)基础免疫后免疫原性.结论 所建立的百日咳血清抗体检测ELISA方法,准确度高和重复性好,无需特殊仪器,适合于一般实验室开展,可用于接种aP后血清学效果观察和百日咳流行病学研究.%Objective To develop three Enzyme-linked Immunosorbent Assay (ELISA ) methods for quantitative determination of IgG antibody against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin(Prn)in human serum, respectively. Method Purified PT, FHA and Prn and international reference pertussis serum were used as coating antigen and standard for development of three ELISA assays. Results Three ELJSA assays had been established for determining anti-PT, FHA and Prn antibody, respectively

  1. Estimated incidence of pertussis in people aged <50 years in the United States

    Science.gov (United States)

    Chen, Chi-Chang; Balderston McGuiness, Catherine; Krishnarajah, Girishanthy; Blanchette, Christopher M.; Wang, Yuanyuan; Sun, Kainan; Buck, Philip O.

    2016-01-01

    ABSTRACT The introduction of pertussis vaccination in the United States (US) in the 1940s has greatly reduced its burden. However, the incidence of pertussis is difficult to quantify, as many cases are not laboratory-confirmed or reported, particularly in adults. This study estimated pertussis incidence in a commercially insured US population aged models; (3) using the fraction of cough illness (ICD-9 033.0, 033.9, 484.3, 786.2, 466.0, 466.1, 487.1) attributed to laboratory-confirmed pertussis, estimated by time series linear regression models. Method 1 gave a projected annual incidence of diagnosed pertussis of 9/100,000, which was highest in those aged <1 year. Method 2 gave an average annual projected incidence of 21/100,000. Method 3 gave an overall regression-estimated weighted annual incidence of pertussis of 649/100,000, approximately 58–93 times higher than method 1 depending on the year. These estimations, which are consistent with considerable underreporting of pertussis in people aged <50 years and provide further evidence that the majority of cases go undetected, especially with increasing age, may aid in the development of public health programs to reduce pertussis burden. PMID:27246119

  2. [Whooping cough in Spain. Current epidemiology, prevention and control strategies. Recommendations by the Pertussis Working Group].

    Science.gov (United States)

    Campins, Magda; Moreno-Pérez, David; Gil-de Miguel, Angel; González-Romo, Fernando; Moraga-Llop, Fernando A; Arístegui-Fernández, Javier; Goncé-Mellgren, Anna; Bayas, José M; Salleras-Sanmartí, Lluís

    2013-04-01

    A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups. Adolescents and adults immunization must be a priority. In the first group, strategy is easy to implement, and with a very low additional cost (to replace dT vaccine by dTap one). Adult vaccination may be more difficult to implement; dT vaccine decennial booster should be replaced by dTap. The immunization of household contacts of newborn infants (cocooning) is the strategy that has a most important impact on infant pertussis. Recently, pregnant women vaccination (after 20weeks of gestation) has been recommended in some countries as the most effective way to protect the newborn.

  3. A field study of household attack rates and the effectiveness of macrolide antibiotics in reducing household transmission of pertussis.

    Science.gov (United States)

    Terry, Janet B; Flatley, Christopher J; van den Berg, Debra J; Morgan, Geoffrey G; Trent, Marianne; Turahui, John A; Greenwood, Michelle C; Corben, Paul W; Bell, Greg J

    2015-03-31

    Bordetella pertussis (whooping cough) is an endemic, highly contagious bacterial respiratory infection, which is notifiable to Australian state and territory health departments. Between 2008 and 2011 there was a substantial outbreak in New South Wales with an initial increase in cases occurring in North Coast New South Wales from late 2007. During September and October 2011 the North Coast Public Health Unit conducted a household study of secondary attack rates to assess the effectiveness of pertussis vaccination as well as the timely use of antibiotics in preventing household transmission. At the time the study was commenced, notified cases included a large proportion of individuals with a documented history of vaccination against pertussis. We found lower attack rates amongst vaccinated compared with non-vaccinated subjects in all age groups, with the exception of the 5-11 years age group, who were also primarily responsible for the introduction of pertussis into the household. There was an increased risk of pertussis transmission from the household first primary case to contacts when antibiotic treatment was commenced later than 7 days after the onset of symptoms compared with within 7 days. This protective effect of timely antibiotic treatment in relation to transmission highlights the need to control for antibiotic treatment in field studies of pertussis. The benefits of timely diagnosis and use of antibiotics in preventing household transmission underscore the importance of early presentation and diagnosis of pertussis cases, particularly in households with susceptible occupants.

  4. Characterisation of the Bordetella pertussis secretome under different media.

    Science.gov (United States)

    Luu, Laurence Don Wai; Octavia, Sophie; Zhong, Ling; Raftery, Mark; Sintchenko, Vitali; Lan, Ruiting

    2017-03-31

    Our understanding of the Bordetella pertussis secretome remains limited including the role of different growth conditions in the secretome. In this study the secretome of L1423, a clinical isolate from the 2008-2012 Australian epidemic, cultured on Stainer-Scholte (SS) and Thalen-IJssel (THIJS) media for 12h was characterised using liquid chromatography-mass spectrometry (LC-MS/MS). In the supernatant, LC-MS/MS identified 260 proteins with 143 bioinformatically predicted to be secreted. Eighty percent of proteins were identified in both media. Proteins secreted were functionally associated with cell surface (41%), pathogenicity (16%) and transport (17%). The most abundant proteins identified were pathogenic proteins including toxins (PtxA and CyaA), adhesins (TcfA) and type III secretion (T3SS) proteins. There were 46 proteins found uniquely in THIJS including 8 virulence associated proteins. These included T3SS proteins, adhesins (FhaL and FhaS) and a putative toxin (BP1251). Nine proteins were found uniquely in SS and these were metabolic and transport-related proteins. None of the unique proteins detected in SS were known to be virulence associated. This study found that THIJS promotes secretion of virulence factors based on the number of unique virulence proteins found and may be a growth media of choice for the study of B. pertussis virulence and vaccine development. Over the past two decades, the number of B. pertussis notifications has risen despite vaccination. There is a greater need to understand the biology behind B. pertussis infections. The secretome of B. pertussis in two different media was characterised using LC-MS/MS. The results showed that THIJS promotes secretion of importance virulence factors which may be important for the development of vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Increasing provision of adolescent vaccines in primary care: a randomized controlled trial.

    Science.gov (United States)

    Gilkey, Melissa B; Dayton, Amanda M; Moss, Jennifer L; Sparks, Alicia C; Grimshaw, Amy H; Bowling, James M; Brewer, Noel T

    2014-08-01

    To assess the effectiveness of in-person and webinar-delivered AFIX (Assessment, Feedback, Incentives, and eXchange) consultations for increasing adolescent vaccine coverage. We randomly assigned 91 primary care clinics in North Carolina, serving 107 443 adolescents, to receive no consultation or an in-person or webinar AFIX consultation. We delivered in-person consultations in April through May 2011 and webinar consultations in May through August 2011. The state's immunization registry provided vaccine coverage data for younger patients (ages 11-12 years) and older patients (ages 13-18 years) for 3 adolescent vaccines: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap); meningococcal; and human papillomavirus (HPV) vaccines (≥1 dose, females only). At the 5-month follow-up, AFIX consultations increased vaccine coverage among younger adolescents. Patients in the in-person arm experienced coverage changes that exceeded those in the control arm for Tdap (3.4% [95% confidence interval (CI): 2.2 to 4.6]), meningococcal (4.7% [95% CI: 2.3 to 7.2], and HPV (1.5% [95% CI: 0.3 to 2.7]) vaccines. Patients in the webinar versus control arm also experienced larger changes for these vaccines. AFIX did little to improve coverage among older adolescents. At 1 year, the 3 arms showed similar coverage changes. The effectiveness of in-person and webinar consultations was not statistically different at either time point (all, P >.05). Webinar AFIX consultations were as effective as in-person consultations in achieving short-term increases in vaccine coverage for younger adolescents. AFIX consultations for adolescents need improvement to have a stronger and more durable impact, especially for HPV vaccine. Copyright © 2014 by the American Academy of Pediatrics.

  6. Genome-wide gene expression analysis of Bordetella pertussis isolates associated with a resurgence in pertussis: elucidation of factors involved in the increased fitness of epidemic strains.

    Science.gov (United States)

    King, Audrey J; van der Lee, Saskia; Mohangoo, Archena; van Gent, Marjolein; van der Ark, Arno; van de Waterbeemd, Bas

    2013-01-01

    Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.

  7. Population diversity among Bordetella pertussis isolates, United States, 1935-2009.

    Science.gov (United States)

    Schmidtke, Amber J; Boney, Kathryn O; Martin, Stacey W; Skoff, Tami H; Tondella, M Lucia; Tatti, Kathleen M

    2012-08-01

    Since the 1980s, pertussis notifications in the United States have been increasing. To determine the types of Bordetella pertussis responsible for these increases, we divided 661 B. pertussis isolates collected in the United States during 1935-2009 into 8 periods related to the introduction of novel vaccines or changes in vaccination schedule. B. pertussis diversity was highest from 1970-1990 (94%) but declined to ≈ 70% after 1991 and has remained constant. During 2006-2009, 81.6% of the strains encoded multilocus sequence type prn2-ptxP3-ptxS1A-fim3B, and 64% were multilocus variable number tandem repeat analysis type 27. US trends were consistent with those seen internationally; emergence and predominance of the fim3B allele was the only molecular characteristic associated with the increase in pertussis notifications. Changes in the vaccine composition and schedule were not the direct selection pressures that resulted in the allele changes present in the current B. pertussis population.

  8. A national reference for inactivated polio vaccine derived from Sabin strains in Japan.

    Science.gov (United States)

    Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji

    2014-09-08

    As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan.

  9. Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.

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    Hyun-Ja Han

    Full Text Available BACKGROUND: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s involved in the type shift. METHODOLOGY/PRINCIPAL FINDING: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. CONCLUSION/SIGNIFICANCE: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.

  10. Eventos adversos pós-vacina contra a difteria, coqueluche e tétano e fatores associados à sua gravidade Adverse events following diphtheria, pertussis and tetanus vaccinations and factors associated with severity

    Directory of Open Access Journals (Sweden)

    Fabiana Ramos Martin de Freitas

    2007-12-01

    Full Text Available OBJETIVO: Avaliar os eventos adversos pós-vacina contra a difteria, coqueluche e tétano (EAPV-DPT e os fatores associados à sua gravidade. MÉTODOS: Estudo transversal com componente descritivo e analítico, abrangendo os eventos adversos pós-vacina DPT notificados no Estado de São Paulo, de 1984 a 2001, entre crianças menores de sete anos de idade. A definição de caso foi a adotada pela vigilância de EAPV-DPT; os dados obtidos foram originados da vigilância passiva desses eventos. No cálculo das taxas, o numerador foram os EAPV e o denominador o número de doses aplicadas. A associação entre a gravidade dos EAPV-DPT e as exposições de interesse foi investigada pelas estimativas não ajustadas e ajustadas da odds ratio, com os respectivos intervalos de 95% de confiança, usando regressão logística não condicional. RESULTADOS: Identificaram-se 10.059 EAPV-DPT relativos a 6.266 crianças, apresentando um ou mais EAPV, 29,5% foram internadas e em 68,2% houve contra-indicação das doses subseqüentes de DPT. Cerca de 75% dos eventos ocorreram nas primeiras seis horas após a aplicação da vacina. Os eventos mais freqüentes foram: febreOBJECTIVE: To analyze adverse events following vaccinations against diphtheria, pertussis and tetanus (AEFV-DPT and to investigate factors associated with event severity. METHODS: A cross-sectional study was carried out with a descriptive and analytical component covering AEFV-DPT that were notified in the State of São Paulo, Brazil, between 1984 and 2001, among children less than seven years old. Cases were defined as used in AEFV-DPT surveillance; the data source was AEFV-DPT passive surveillance. In calculating the rates, the numerator was the number of AEFV-DPT and as denominator was the number of doses applied. The association between severity of AEFV-DPT and the exposures of interest was investigated by means of non-adjusted and adjusted estimates of odds ratios, with their respective 95

  11. Perfil epidemiológico da coqueluche no Rio Grande do Sul, Brasil: estudo da correlação entre incidência e cobertura vacinal Epidemiological profile of pertussis in Rio Grande do Sul State, Brazil: a study of the correlation between incidence and vaccine coverage

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    Sarina Trevizan

    2008-01-01

    Full Text Available No Estado do Rio Grande do Sul, Brasil, foi constatado que a coqueluche apresentou uma tendência crescente desde o ano 2000, levando à deflagração de alerta epidêmico em 2004, conforme boletins epidemiológicos emitidos pelos órgãos governamentais de saúde. Nosso objetivo neste estudo foi identificar o perfil epidemiológico da coqueluche nesse estado; para tanto, utilizamos a incidência da notificação da doença entre janeiro de 1995 e dezembro de 2004, a porcentagem de cobertura vacinal e a caracterização da população afetada. Construiu-se um diagrama de controle para determinar a magnitude da doença em 2004; para a análise da correlação entre incidência e cobertura vacinal foi estabelecida a oscilação entre as curvas de cobertura vacinal e de notificação de casos nos últimos dez anos. No Rio Grande do Sul, a coqueluche esteve em nível epidêmico em 2004, representando importante causa de morbimortalidade em crianças menores de um ano, apesar da disponibilidade de vacinas eficazes e de altas taxas de cobertura vacinal informadas nos últimos anos. Portanto, serão necessários estudos sobre o comportamento da doença nos próximos anos e determinação de possíveis fatores envolvidos nesse ressurgimento.An upward trend was observed in pertussis incidence in the State of Rio Grande do Sul, Brazil, since 2000, leading to an epidemic alert in 2004, based on epidemiological bulletins issued by government health agencies. Our objective in the current study was to identify the epidemiological profile of pertussis in the State. We used the incidence of reports of the disease from January 1995 to December 2004, the percentage of vaccine coverage, and characterization of the affected population. A control diagram was constructed to determine the magnitude of the disease in 2004. To analyze the correlation between incidence and vaccine coverage, we established the fluctuation between the vaccine coverage and case reporting in

  12. Comparative genomic profiling of Dutch clinical Bordetella pertussis isolates using DNA microarrays: Identification of genes absent from epidemic strains

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    van Gent Marjolein

    2008-06-01

    Full Text Available Abstract Background Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many countries despite vaccination. Several studies have shown that significant shifts have occurred in the B. pertussis population resulting in antigenic divergence between vaccine strains and circulating strains and suggesting pathogen adaptation. In the Netherlands, the resurgence of pertussis is associated with the rise of B. pertussis strains with an altered promoter region for pertussis toxin (ptxP3. Results We used Multi-Locus Sequence Typing (MLST, Multiple-Locus Variable Number of Tandem Repeat Analysis (MLVA and microarray-based comparative genomic hybridization (CGH to characterize the ptxP3 strains associated with the Dutch epidemic. For CGH analysis, we developed an oligonucleotide (70-mers microarray consisting of 3,581 oligonucleotides representing 94% of the gene repertoire of the B. pertussis strain Tohama I. Nine different MLST profiles and 38 different MLVA types were found in the period 1993 to 2004. Forty-three Dutch clinical isolates were analyzed with CGH, 98 genes were found to be absent in at least one of the B. pertussis strains tested, these genes were clustered in 8 distinct regions of difference. Conclusion The presented MLST, MLVA and CGH-analysis identified distinctive characteristics of ptxP3 B. pertussis strains -the most prominent of which was a genomic deletion removing about 23,000 bp. We propose a model for the emergence of ptxP3 strains.

  13. Comparison of nasopharyngeal culture, polymerase chain reaction (PCR) and serological test for diagnosis of pertussis.

    Science.gov (United States)

    Cengiz, Ali Bülent; Yildirim, Inci; Ceyhan, Mehmet; Seçmeer, Gülten; Gür, Deniz; Kara, Ateş

    2009-01-01

    This prospective study, which was designed to compare nasopharyngeal culture, polymerase chain reaction (PCR) and serology in the diagnosis of pertussis, covered 35 children aged between 0 and 16 who were admitted to Hacettepe University Ihsan Doğramaci Children's Hospital between 1 March 2005 and 31 August 2006 with coughing for 7 days or longer, paroxysmal cough of any duration, or cough with inspiratory whoop and/or vomiting (or apnea) after coughs. The demographic data and vaccination history of the patients were recorded. During the initial examination, samples were taken from the posterior nasopharynx for Bordetella pertussis (B. pertussis) culture and PCR analysis. In order to determine antibody positivity and antibody levels against B. pertussis antigens, serum samples were taken during the initial examination (acute phase) and two weeks later (convalescent phase). In the first serum sample, immunoglobulin M (IgM) was determined against pertussis toxin. In the first and second samples, IgA and IgG antibodies were evaluated against pertussis toxin and filamentous hemagglutinin. Culture yielded negative results in all of the patients. PCR was positive in two cases (5.7%). In the PCR-positive patients, IgM, IgA and IgG type anti-pertussis antibodies were found to be positive in the first serum samples, and IgA and IgG antibodies were found to be positive in the second serum samples. Therefore, it was considered that serology could be as sensitive as PCR when type IgM, IgA and IgG antibodies were found to be positive against a minimum of two antigens of B. pertussis. In conclusion, both PCR and serologic tests--if evaluating all types of antibodies to a minimum of two antigens of B. pertussis obtained in both acute and convalescent sera--could be more sensitive than culture in the diagnosis of pertussis.

  14. The seroepidemiology of Immunoglobulin G antibodies against pertussis toxin in China: a cross sectional study

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    Zhang Qi

    2012-06-01

    Full Text Available Abstract Background Pertussis is a reported vaccine-preventable respiratory disease in China. Because the routine laboratory methods for diagnosis are not in use, the reported cases are mainly in infants with classical paroxysmal cough and the true incidence related to pertussis is most likely under estimated. In China, however, few studies have attempted to address this issue. The purpose of this cross sectional study was to estimate the incidence rates using the method of sero-epidemiology of immunoglobulin (Ig G antibodies against pertussis toxin (PT among healthy populations in China. Methods Blood samples were obtained from 1313 healthy individuals aged 0 to 95 years in Guangdong province of China throughout September 2010. Serum IgG antibodies against PT were determined by commercial ELISA kits. Subjects with concentration of anti-PT IgG higher than 30 IU/mL were indicated to have recent Bordetella pertussis infection, if they have not received a booster dose of pertussis vaccine within one year. Results Of the 1313 study subjects, 117 (8.91% were found to have anti-PT antibodies higher than 30 IU/mL. The estimated incidence of recent infection was thus 9395 per 100,000 for individuals older than 7 years. Peaks of the estimated incidence rate of recent infection were found to be 11561 per 100,000 in age group of 41–50 years and 11428 per 100,000 in the group aged 13–19 years. Conclusions Our study indicated that B.pertussis infections are considerablely common, particularly in adolescents and adults in China. The study also stresses the importance of laboratory diagnosis for pertussis and employment of booster dose of pertussis vaccine in adolescents and adults in this country.

  15. 水痘减毒活疫苗与百白破疫苗联合免疫的安全性和免疫原性观察%Safety and immunogenicity of co-immunization with varicella vaccine and the triple vaccine against diphtheria, pertussis and tetanus

    Institute of Scientific and Technical Information of China (English)

    唐学雯; 马相虎; 邓璇; 尹志英; 马燕丽; 李羽敏; 黄清霄; 陈丹丹; 刘小琴

    2016-01-01

    目的 了解水痘减毒活疫苗与百白破联合疫苗(DTP)联合接种的安全性和免疫原性,为科学制定相关免疫策略提供依据.方法 2013—2014年在浙江省衢州市、丽水市选择734名约18月龄儿童,分为联合接种组、单独接种水痘减毒活疫苗组和单独接种DTP组.接种后研究人员定期开展主动随访评价疫苗安全性,并采集免疫前、免疫后35 d血清采用膜抗原荧光抗体法和酶联免疫吸附试验分别检测水痘和百白破抗体水平,评价疫苗免疫原性.结果 3组对象接种后仅有红肿、低热发生(发生比例<3%),均无严重异常反应发生.单独接种水痘疫苗组与联合接种组比,免疫后水痘抗体阳性率(100%vs 100%)、阳转率(56.13%vs 61.01%,P=0.311)、几何抗体滴度水平(20.55 IU/ml vs 23.69 IU/ml,P=0.118),差异均无统计学意义.单独接种DTP组与联合接种组比,白喉、破伤风和百日咳的抗体阳性率均大于95%,两组比较差异无统计学意义(P=0.23;P=0.16);但联合接种组百日咳抗体阳转率略高(41.9%vs 90.6%,P<0.001),单独接种组白喉阳转率略高(89.53%vs 77.36%,P<0.001),而破伤风抗体阳转率(18.02%vs 14.47%,P=0.381)差异无统计学意义;单独接种DTP组的白喉与破伤风的抗体滴度水平显著高于同时接种组(2.04 vs 1.32,P<0.001;3.48 vs 2.62,P<0.001).结论 适龄儿童联合接种或单独接种水痘减毒活疫苗与DTP具有较好的安全性和免疫原性.%Objective To evaluate the safety and immunogenicity of co-immunization with varicel-la vaccine and the triple vaccine against diphtheria, tetanus and pertussis ( DPT) .Methods A total of 734 infants aged about 18 months were recruited in Quzhou and Lishui areas of Zhejiang Province and allocated into three groups including co-immunization group, DPT vaccine immunization group and varicella vaccine immunization group ( respectively abbreviated to CI group, DPT group and VV group) .Active follow-up ob-servation was

  16. Is the current pertussis incidence only the results of testing? A spatial and space-time analysis of pertussis surveillance data using cluster detection methods and geographically weighted regression modelling

    Science.gov (United States)

    Kauhl, Boris; Heil, Jeanne; Hoebe, Christian J. P. A.; Schweikart, Jürgen; Krafft, Thomas; Dukers-Muijrers, Nicole H. T. M.

    2017-01-01

    Background Despite high vaccination coverage, pertussis incidence in the Netherlands is amongst the highest in Europe with a shifting tendency towards adults and elderly. Early detection of outbreaks and preventive actions are necessary to prevent severe complications in infants. Efficient pertussis control requires additional background knowledge about the determinants of testing and possible determinants of the current pertussis incidence. Therefore, the aim of our study is to examine the possibility of locating possible pertussis outbreaks using space-time cluster detection and to examine the determinants of pertussis testing and incidence using geographically weighted regression models. Methods We analysed laboratory registry data including all geocoded pertussis tests in the southern area of the Netherlands between 2007 and 2013. Socio-demographic and infrastructure-related population data were matched to the geo-coded laboratory data. The spatial scan statistic was applied to detect spatial and space-time clusters of testing, incidence and test-positivity. Geographically weighted Poisson regression (GWPR) models were then constructed to model the associations between the age-specific rates of testing and incidence and possible population-based determinants. Results Space-time clusters for pertussis incidence overlapped with space-time clusters for testing, reflecting a strong relationship between testing and incidence, irrespective of the examined age group. Testing for pertussis itself was overall associated with lower socio-economic status, multi-person-households, proximity to primary school and availability of healthcare. The current incidence in contradiction is mainly determined by testing and is not associated with a lower socioeconomic status. Discussion Testing for pertussis follows to an extent the general healthcare seeking behaviour for common respiratory infections, whereas the current pertussis incidence is largely the result of testing. More

  17. Vaccinations

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

  18. The Diagnostic Value of ELISA Method for Pertussis in Children

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    O. P. Popova

    2016-01-01

    Full Text Available Because of low effectiveness of laboratory methods for diagnosing pertussis it is important to look for new ways of verification of this infection. The article presents the analysis of the diagnostic value of ELISA method, which involves the identification of antibodies of different isotypes (IgM, IgG, IgA to pertussis toxoid (PT and filamentous haemagglutinin (FHA. The study included 279 children: 114 were under 1 year of age, 165 — older than 1 year. The pertussis was confirmed in 74.3 ± 2.6% of patients by using ELISA method. A significant proportion of seronegative patients (46.1 ± 6.2 per cent was revealed in the group of patients under 1 year. The pattern of production of antibodies in unvaccinated children was different. It depended on the age of the children and timing of illness. A low proportion of diagnostically significant indicators of IgM-antibodies at 2—3 weeks of illness was typical for patients under 1 year of age (e.g. 6.7 ± 6.5% as compared to 20.0 ± 7.9% and 50.0 ± 15.3 — 1—3 and 4—6 years of age. The diagnosis of pertussis in children under 1 year of age was confirmed mainly by the detection of IgG, starting from the 4th week of the disease. In the examination of vaccinated children diagnostically significant levels of IgA and IgG were identified (even in the late stages of the disease. Thus, the results of the analysis show special significance of using ELISA method for the diagnosis of pertussis in vaccinated children.

  19. Acellular nerve allograft promotes selective regeneration

    Institute of Scientific and Technical Information of China (English)

    Haili Xin; Guanjun Wang; Xinrong He; Jiang Peng; Quanyi Guo; Wenjing Xu

    2011-01-01

    Acellular nerve allograft preserves the basilar membrane tube and extracellular matrix, which pro-motes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetyl-choline esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive senso-ry nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.

  20. Changes in genetic diversity of the Bordetella pertussis population in Serbia between 1953 and 2011

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    Plješa Tatjana

    2014-01-01

    Full Text Available Mass vaccination has significantly reduced the incidence of pertussis, however, the disease is re-emerging, even in some countries with high vaccination coverage. In Serbia, whole cell pertussis vaccine was introduced in 1957. To monitor changes in bacterial population, 77 isolates collected from 1953 to 2011 were studied. The methods included serotyping of fimbriae (Fim, genotyping of pertactin (prn and pertussis toxin S1 subunit (ptxA. A shift from ptxA2 to ptxA1 has been observed in isolates since the late of 1960s. In the period 1961-1979, the genotype ptxA1 became as common as genotype ptxA2. After that, during the period 1980-1989, the predominant ptx genotype was ptxA1. The reappearance of the ptxA2 allele followed an addition of the two strains harboring ptxA1 in the vaccine in 1985. The allele prn1 was predominant among the Serbian isolates, though prn3 and prn11 have been detected since 1981. The prn2 allele was only found in one strain isolated in 1984, two of the four strains isolated in 2000 and in three isolated strains from 2011. Serotype Fim2.3 disappeared before 1980 and serotype Fim2 became predominant thereafter. The results of this study indicate that the B. pertussis population in Serbia is different from other vaccinated populations and that this difference may be related to the vaccine used.

  1. The historical association between measles and pertussis: A case of immune suppression?

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    Stephen Coleman

    2015-12-01

    Full Text Available Objectives: According to historical medical reports, many children with measles subsequently contracted pertussis, often with fatal results. The likelihood of a child contracting pertussis after a measles infection is increased by its immune-suppressing effects. This research aims to verify the historical reports. Methods: The analysis examines statistically the historical relationship between average measles and pertussis incidence rates in the United States from 1938 to 1954 at the state level and in average weekly rates. Analysis of incidence rates is cross-sectional at the state level using public health data. Results: The results show that, on average and over time, states with higher measles rates have higher pertussis rates, and the peaks and nadirs of average weekly incidence rates of pertussis lag measles by a delay of about 3–4 weeks, well within the duration of immune suppression. Measles and pertussis have similar geographical distributions. Conclusion: The research tentatively supports the hypothesis that because of its immune-suppressing effects, measles causes an increase in pertussis, but other factors may be involved. Epidemic models should give more attention to the possibility of immune suppression for diseases such as measles where that might be a risk factor. The findings reemphasize the importance of measles vaccination for the prevention of other diseases.

  2. Adverse events following vaccination in the French armed forces: An overview of surveillance conducted from 2002 to 2010.

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    Mayet, A; Haus-Cheymol, R; Bouaiti, E A; Decam, C; Simon, F; Mérens, A; Spiegel, A; Meynard, J B; Deparis, X; Migliani, R

    2012-06-14

    French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to describe vaccine adverse events (VAE) reported from 2002 to 2010 in armed forces. VAE are routinely surveyed by the military Centre for epidemiology and public health. For each case, military practitioners fill a notification form, providing patient characteristics, clinical information and vaccines administered. For this study, VAE following influenza A(H1N1)pdm09 vaccination were excluded. Among the 473 cases retained, 442 (93%) corresponded to non-severe VAE,including local, regional and systemic events, while 31 corresponded to severe VAE, with two leading to significant disability. The global VAE reporting rate (RR) was 14.0 per 100,000 injections. While stationary from 2002 to 2008, the RR increased from 2009. The most important observations were a marked increase of VAE attributed to Bacillus Calmette-Guérin (BCG) vaccine from 2005 to 2008, a high RR observed with the inactivated diphtheria-tetanus (toxoids)-poliovirus vaccine combined with acellular pertussis vaccine (dTap-IPV) from 2008 and an increase in RR for seasonal influenza vaccine VAE in 2009. Our RR for severe VAE (1.1 VAEper 100,000) appears comparable with rates observed among United States civilians and military personnel. The increase observed from 2009 could be partly explained by the influenza A(H1N1)pdm09 pandemic which increased practitioner awareness towards VAE. In conclusion, the tolerance of the vaccines used in French armed forces appears acceptable.

  3. Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines.

    Science.gov (United States)

    Bergfors, Elisabet; Björkelund, Cecilia; Trollfors, Birger

    2005-11-01

    Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria-tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.

  4. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

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    Valentina Marcellini

    2017-09-01

    Full Text Available Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies.

  5. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

    Science.gov (United States)

    Marcellini, Valentina; Piano Mortari, Eva; Fedele, Giorgio; Gesualdo, Francesco; Pandolfi, Elisabetta; Midulla, Fabio; Leone, Pasqualina; Stefanelli, Paola; Tozzi, Alberto Eugenio; Carsetti, Rita; Agricola, E.

    2017-01-01

    Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies. PMID:28966622

  6. 百日咳杆菌黏着素的纯化及生物学特性研究%Study on purification and biological characteristics of pertactin from Bordetella pertussis

    Institute of Scientific and Technical Information of China (English)

    王玲; 肖詹蓉; 叶娟; 韩俊杰; 孙翔宇

    2012-01-01

    目的 建立从天然百日咳杆菌中提纯百日咳杆菌黏着素( pertactin,PRN)的方法,研究PRN的生物学特性并确定PRN在无细胞百日咳疫苗中的作用.方法 百日咳杆菌CS株于发酵罐培养后,经热浸提、硫酸铵分级沉淀及离子交换层析得到纯化PRN,根据《中华人民共和国药典》2005年版三部的要求,对纯化PRN进行纯度检测及生物学特性研究.结果 各项检测显示,纯化PRN的纯度在95%以上,其相对分子质量和等电点与标准PRN一致.纯化PRN对小鼠具有保护效力,且其保护效力随PRN免疫浓度的增加而增强.未检出纯化PRN的特异性毒性和异常毒性.结论 建立了从天然百日咳杆菌中提纯PRN的方法,而且纯化PRN具有免疫原性和保护效力.%Objective To establish a method for purifying pertactin from Bordetella pertussis,study its biological characteristics and confirm its role in acellular pertussis vaccine.Methods Bordetella pertussis CS strain was cultured in a fermenter,and purified pertactin was obtained by hot lixiviation,ammonium sulfate fractional precipitation and ion-exchange chromatography.Purity and biological characteristics of the purified pertactin were studied according to requirements of Pharmacopoeia of the People's Republic of China 2005 Volume Ⅲ.Results The purity of the purified pertactin was above 95%,relative molecular mass and isoelectric point of the purified pertactin were identical with those of standard pertactin.Protective potency of the purified pertactin was observed in mice and enhanced with increase of its concentrations.No specific and abnormal toxicities were detected.Conclusions The method for purifying pertactin from Bordetella pertussis is established,and purified pertactin has immunogenicity and protective potency.

  7. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally.

    Science.gov (United States)

    de Gouw, Daan; Hermans, Peter W M; Bootsma, Hester J; Zomer, Aldert; Heuvelman, Kees; Diavatopoulos, Dimitri A; Mooi, Frits R

    2014-01-01

    Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel

  8. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally.

    Directory of Open Access Journals (Sweden)

    Daan de Gouw

    Full Text Available Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR. The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by

  9. Purification of pertussis toxin, filamentous haemagglutinin and pertactin%百日咳毒素、丝状血凝素和黏附素的纯化

    Institute of Scientific and Technical Information of China (English)

    田阳; 史秋明; 隋礼丽

    2013-01-01

    Objective To isolate and purify the pertussis toxin (PT),filamentous haemagglutinin (FHA) and pertactin (PRN) of acellular pertussis vaccine by using a novel chromatography medium.Methods The pH value and conductivity of fermentation liquid of PT and FHA were adjusted,based on which PT was purified by Capto SP ImpRes and Capto MMC chromatography,while FHA by Capto SP ImpRes chromatography.The purified samples were identified by 4% ~12% NuPAGE and analyzed for purity by ImageQ and for protein mass spectrum by LC-MASS (Thermo LTQ Velas).PT and FHA were analyzed quantitatively by BiaCore T200,and calucated for recovery rates at various steps.Results The purities of PT,FHA and PRN reached more than 95%.The total recovery rates of PT and FHA were about 30%.LCMASS showed high homologies of bands of the three components on electrophoretic profile to those in databank.Conclusion The PT,FHA and PRN components of acellular pertusis vaccine were purified effectively by novel chromatography media,while the antigen purities increased,and the time for production was shortened remarkably.%目的 采用新型层析介质对无细胞百日咳疫苗百日咳毒素(pertussis toxin,PT)、丝状血凝素(filamen-tous hemagglutinin,FHA)和黏附素(pertactin,PRN)3组分进行分离纯化.方法 调整PT和FHA发酵液上清的pH值和电导后,PT经Capto SP ImpRes和Capto MMC进行两步层析,FHA经Capto SP ImpRes进行一步层析;PRN热处理原液经Capto Adhere和Capto SP ImpRes进行两步层析.纯化产物经4%~12% NuPAGE进行鉴定,ImageQ分析纯度;LC-MASS(Thermo LTQ Velas)进行蛋白质的质谱检测;PT和FHA经BiaCore T200进行定量分析,并计算各步回收率.结果 纯化后,无细胞百日咳疫苗3组分纯度均达95%以上;PT和FHA的总回收率均在30%左右;电泳图谱上的各组分条带经LC-MASS鉴定,均与Uniprot Bordetella pertussis数据库数据高度同源.结论 采用新型层析介质有效纯化了无细胞百

  10. Pertussis Reinfection in an Adult: A Cause of Persistent Cough Not to Be Ignored

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    Theocharis Koufakis

    2017-01-01

    Full Text Available Pertussis is traditionally considered as a disease of the childhood; however, accumulating evidence suggests a stable increase of its incidence among adults and adolescents, during the last decades. Despite the fact that reinfection after natural disease or vaccination is not uncommon, the index of clinical suspicion of pertussis diagnosis in adults remains low. In this article, we report a case of pertussis reinfection 30 years after natural infection, which was complicated by pneumonia, and we discuss our diagnostic and therapeutic approach, aiming to raise clinicians’ degree of suspicion regarding pertussis diagnosis in adults. Prompt recognition and appropriate therapy of adult patients can result in the effective control of the symptoms, prevention of severe complications, and spread of the infection to children; thus, they are of great clinical and public health importance.

  11. Development and clinical application of new polyvalent combined paediatric vaccines.

    Science.gov (United States)

    André, F E

    1999-03-26

    , conjugated Haemophilus influenzae type b polysaccharide and hepatitis B surface antigen to the diphtheria-tetanus-pertussis vaccine either in its 'classical' (whole-cell) or more purified (acellular) formulations. Experience is showing that the development of combined vaccines involves much more than the simple mixing of existing antigens. Possible incompatibilities or mutual interferences between the antigens themselves, or between excipients, preservatives, adjuvants, residual contaminants, stabilisers and suspending fluids make it mandatory that each formulation be thoroughly tested for quality, stability, efficacy and safety. Furthermore the ability to produce and control it consistently must be established before it can be licensed for commercial use. The progress being made in this field is reviewed.

  12. Surveillance of Vaccination Coverage among Adult Populations - United States, 2015.

    Science.gov (United States)

    Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Kim, David K; Grohskopf, Lisa A; Pilishvili, Tamara; Skoff, Tami H; Nelson, Noele P; Harpaz, Rafael; Markowitz, Lauri E; Rodriguez-Lainz, Alfonso; Fiebelkorn, Amy Parker

    2017-05-05

    Overall, the prevalence of illness attributable to vaccine-preventable diseases is greater among adults than among children. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults is low. August 2014-June 2015 (for influenza vaccination) and January-December 2015 (for pneumococcal, tetanus and diphtheria [Td] and tetanus and diphtheria with acellular pertussis [Tdap], hepatitis A, hepatitis B, herpes zoster, and human papillomavirus [HPV] vaccination). The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. The survey objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Compared with data from the 2014 NHIS, increases in vaccination coverage occurred for influenza vaccine among adults aged ≥19 years (a 1.6 percentage point increase compared with the 2013-14 season to 44.8%), pneumococcal vaccine among adults aged 19-64 years at increased risk for pneumococcal disease (a 2.8 percentage point increase to 23.0%), Tdap vaccine among adults aged ≥19 years and adults aged 19-64 years (a 3.1 percentage point and 3.3 percentage point increase to 23.1% and to 24.7%, respectively), herpes zoster vaccine among adults aged ≥60 years and adults aged ≥65 years (a 2.7 percentage point and 3.2 percentage point increase to 30.6% and to 34.2%, respectively), and hepatitis B vaccine among health care personnel (HCP) aged

  13. Pertussis prevalence and its determinants among children with persistent cough in urban Uganda.

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    Vincent Kayina

    Full Text Available We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR and ELISA serology tests.Pertussis prevalence was 67 (15% (95% Confidence Interval (CI: 12-18 and 81 (20% (95% CI: 16-24 by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30% had a coughing household member and 316 (70% did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR 7.16 (95% CI: 1.24-41.44. Among the 316 children that did not have a coughing household member, age 40 years of age were the factors associated with pertussis. Age 59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.

  14. Measuring Immunoglobulin G Antibodies to Tetanus Toxin, Diphtheria Toxin, and Pertussis Toxin with Single-Antigen Enzyme-Linked Immunosorbent Assays and a Bead-Based Multiplex Assay▿

    OpenAIRE

    Reder, Sabine; Riffelmann, Marion; Becker, Christian; Wirsing von König, Carl Heinz

    2008-01-01

    Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a vaccine study. The multianalyte bead assa...

  15. Existing antibacterial vaccines.