Sample records for circulating bordetella pertussis

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

    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.


    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 mu...

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

    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


    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. PMID:25527446

  3. Laboratory Maintenance of Bordetella pertussis.

    Hulbert, Robin R; Cotter, Peggy A


    The causative agent of the respiratory disease whooping cough, Bordetella pertussis, is a nutritionally fastidious microorganism but can be grown with relative ease in research laboratories. Stainer-Scholte synthetic broth medium and Bordet-Gengou blood agar both support growth of B. pertussis and are commonly used. B. pertussis prefers aerobic conditions and a temperature range of 35 degrees to 37 degrees C. Appropriate laboratory safety protocols are required to prevent the generation of aerosols, which could potentially spread this highly infectious agent. PMID:19885941

  4. Bordetella pertussis diagnosed by polymerase chain reaction

    Birkebaek, N H; Heron, I; Skjødt, K


    The object of this work was to test the polymerase chain reaction (PCR) for demonstration of Bordetella pertussis (BP) in nasopharyngeal secretions. The method was applied to patients with recently diagnosed pertussis, as verified by BP culture. In order to test the sensitivity and specificity of...

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

    Slack Andrew T


    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

  6. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    Valérie Bouchez


    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.

  7. Prevalence of Bordetella pertussis and Bordetella parapertussis in Samples Submitted for RSV Screening

    Walsh, Paul


    Full Text Available BACKGROUND: The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV; however, management differs.HYPOTHESIS: First, the prevalence of B. pertussis is less than 2% among patients screened for RSV, and second the prevalence of B. parapertussis is also less than 2% among these patients.METHODS: Nasal washings submitted to a clinical laboratory for RSV screening were tested for B. pertussis and B. parapertussis, using species-specific real-time polymerase chain reaction (PCR assays. These were optimized to target conserved regions within a complement gene and the CarB gene, respectively. A Bordetella spp. genus-specific real-time PCR assay was designed to detect the Bhur gene of B. pertussis, B. parapertussis, and B. bronchiseptica. RSV A and B subtypes were tested by reverse transcription-PCR.RESULTS: Four hundred and eighty-nine clinical samples were tested. There was insufficient material to complete testing for one B. pertussis, 10 RSV subtype A, and four RSV subtype B assays. Bordetella pertussis was detected in 3/488 (0.6% (95% CI 0.1% to 1.8%, while B. parapertussis was detected in 5/489 (1.0% (95% CI 0.3% to 2.4%. Dual infection of B. pertussis with RSV and of B. parapertussis with RSV occurred in two and in three cases respectively. RSV was detected by PCR in 127 (26.5%.CONCLUSION: The prevalence of B. pertussis in nasal washings submitted for RSV screening was less than 2%. The prevalence of parapertussis may be higher than 2%. RSV with B. pertussis and RSV with B. parapertussis coinfection do occur.

  8. The Bordetella pertussis protein Pertactin: role in immunity and immune evasion

    Hijnen, Marcel


    Pertussis is a highly contagious infectious disease of the respiratory tract which is caused by Bordetella pertussis. Before widespread introduction of vaccination against pertussis, almost every child contracted pertussis. The disease is most severe in neonates and children under the age of 1. Intr

  9. Suppression of Platelet Aggregation by Bordetella pertussis Adenylate Cyclase Toxin

    Iwaki, Masaaki; Kamachi, Kazunari; Heveker, Nikolaus; Konda, Toshifumi


    The effect of Bordetella pertussis adenylate cyclase toxin (ACT) on platelet aggregation was investigated. This cell-invasive adenylate cyclase completely suppressed ADP (10 μM)-induced aggregation of rabbit platelets at 3 μg/ml and strongly suppressed thrombin (0.2 U/ml)-induced aggregation at 10 μg/ml. The suppression was accompanied by marked increase in platelet intracellular cyclic AMP (cAMP) content and was diminished by the anti-ACT monoclonal antibody B7E11. A catalytically inactive p...

  10. Severe infantile Bordetella pertussis pneumonia in monozygotic twins with a congenital C3 deficiency

    Kurvers, R.A.J.; Westra, D.; Heijst, A.F.J. van; Walk, T.L.M.; Warris, A.; Kar, N.C.A.J. van de


    Bordetella pertussis or whooping cough is a vaccine-preventable disease that still remains a serious infection in neonates and young infants. We describe two young infants, monozygotic twins, with a severe B. pertussis pneumonia of whom one needed extracorporeal membrane oxygenation. Diagnostic work

  11. Recovery of Bordetella pertussis from PCR-positive nasopharyngeal samples is dependent on bacterial load.

    Vestrheim, Didrik F; Steinbakk, Martin; Bjørnstad, Martha L; Moghaddam, Amir; Reinton, Nils; Dahl, Mette L; Grude, Nils; Sandven, Per


    Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load. PMID:23035189

  12. Recovery of Bordetella pertussis from PCR-Positive Nasopharyngeal Samples Is Dependent on Bacterial Load

    Vestrheim, Didrik F.; Steinbakk, Martin; Bjørnstad, Martha L.; Moghaddam, Amir; Reinton, Nils; Dahl, Mette L.; Grude, Nils; Sandven, Per


    Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load.

  13. Identification and characterization of iron-regulated Bordetella pertussis alcaligin siderophore biosynthesis genes.

    Kang, H.Y.; Brickman, T J; Beaumont, F C; Armstrong, S K


    Bordetella bronchiseptica mutants BRM1, BRM6, and BRM9 fail to produce the native dihydroxamate siderophore alcaligin. A 4.5-kb BamHI-Smal Bordetella pertussis genomic DNA fragment carried multiple genes required to restore alcaligin production to these siderophore-deficient mutants. Phenotypic complementation analysis using subclones of the 4.5-kb genomic region demonstrated that the closely linked BRM1 and BRM9 mutations were genetically separable from the BRM6 mutation, and both insertions...

  14. Detection of IgG antibodies against Bordetella pertussis with 125I-protein A

    A method for the detection of IgG antibodies against Bordetella pertussis is described, based on the principle of 'sandwich' radioimmunoassay. 125I protein A is used as radioactive tracer. The influence of amounts of antigen, antibody, radioactive tracer, incubation time and temperature were tested and the optimal conditions for the assay are described. The procedure offers a simple, quick, and sensitive method for detecting antibodies against B. pertussis. Application and limitation of the test are discussed. (orig.)

  15. Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics

    Bowden, Katherine E.; Weigand, Michael R.; Peng, Yanhui; Cassiday, Pamela K.; Sammons, Scott; Knipe, Kristen; Rowe, Lori A.; Loparev, Vladimir; Sheth, Mili; Weening, Keeley; Tondella, M. Lucia


    ABSTRACT During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome

  16. Real-time PCR-based detection of Bordetella pertussis and Bordetella parapertussis in an Irish paediatric population.

    Grogan, Juanita A


    Novel real-time PCR assays targeting the Bordetella pertussis insertion sequence IS481, the toxin promoter region and Bordetella parapertussis insertion sequence IS1001 were designed. PCR assays were capable of detecting ≤10 copies of target DNA per reaction, with an amplification efficiency of ≥90 %. From September 2003 to December 2009, per-nasal swabs and nasopharyngeal aspirates submitted for B. pertussis culture from patients ≤1 month to >15 years of age were examined by real-time PCR. Among 1324 patients, 76 (5.7 %) were B. pertussis culture positive and 145 (10.95 %) were B. pertussis PCR positive. Of the B. pertussis PCR-positive patients, 117 (81 %) were aged 6 months or less. A total of 1548 samples were examined, of which 87 (5.6 %) were culture positive for B. pertussis and 169 (10.92 %) were B. pertussis PCR positive. All culture-positive samples were PCR positive. Seven specimens (0.5 %) were B. parapertussis culture positive and 10 (0.8 %) were B. parapertussis PCR positive, with all culture-positive samples yielding PCR-positive results. A review of patient laboratory records showed that of the 1324 patients tested for pertussis 555 (42 %) had samples referred for respiratory syncytial virus (RSV) testing and 165 (30 %) were positive, as compared to 19.4 % of the total 5719 patients tested for RSV in this period. Analysis of the age distribution of RSV-positive patients identified that 129 (78 %) were aged 6 months or less, similar to the incidence observed for pertussis in that patient age group. In conclusion, the introduction of the real-time PCR assays for the routine detection of B. pertussis resulted in a 91 % increase in the detection of the organism as compared to microbiological culture. The incidence of infection with B. parapertussis is low while the incidence of RSV infection in infants suspected of having pertussis is high, with a similar age distribution to B. pertussis infection.

  17. Bordetella pertussis acquires resistance to complement-mediated killing in vivo.

    Pishko, Elizabeth J; Betting, David J; Hutter, Christina S; Harvill, Eric T


    In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genus Bordetella includes three closely related species that differ in their ability to resist complement-mediated killing. Bordetella parapertussis and Bordetella bronchiseptica resist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen. Bordetella pertussis lacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized that B. pertussis may have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain of B. pertussis observed were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However, B. pertussis rapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired by B. parapertussis and B. bronchiseptica mutants lacking O antigen. This B. pertussis-specific mechanism of complement resistance does not appear to be dependent on either brkA or other genes expressed specifically in the Bvg(+) phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by which B. pertussis evades complement-mediated killing. PMID:12933835

  18. Expresión episomal de toxina de pertussis genéticamente inactivada en Bordetella pertussis

    Ernesto Marcos


    Full Text Available Bordetella pertussis es una bacteria Gram negativa, la cual constituye el agente etiologico de la tos ferina. La enfermedad se desencadena por el efecto conjunto de una serie de factores de virulencia expresados por la bacteria, los cuales se encuentran regulados por el sistema bvg. Uno de los factores de virulencia mas importantes es la toxina de pertussis, razon por la cual, se emplea de forma inactivada como el componente principal de las vacunas acelulares contra la enfermedad. La toxina de pertussis posee una estructura del tipo A-B compuesta por seis polipeptidos codificados en un operon unico. El polipeptido S1 constituye la subunidad enzimaticamente activa, la cual cataliza la transferencia de ADP-ribosa del NAD a la subunidad ALPHA de las proteinas G en celulas eucariotas, lo cual genera una serie de efectos biologicos dentro de los que se incluye: sensibilizacion a histamina, incremento de la secrecion de insulina y efectos inmunoestimuladores e inmunosupresores. El presente trabajo describe los procedimientos realizados para la obtencion de cepas de Bordetella pertussis productoras de elevadas concentraciones de toxina pertusica atenuada geneticamente. Para esto, se realizaron las sustituciones aminoacidicas Arg9 por Lys y Glu129 por Gly de la subunidad S1. El operon de la toxina de pertussis mutada se clono en un vector de amplio rango de hospedero bajo la regulacion de un promotor de expresion temprana (fhaB. Los clones obtenidos pudieran ser empleados como sistemas de expresion para produccion de vacunas acelulares en Cuba.

  19. SNP-based typing: a useful tool to study Bordetella pertussis populations

    Gent, M. van; Bart, M.J.; Heide, H.G. van der; Heuvelman, K.J.; Kallonen, T.; He, Q.; Mertsola, J.; Advani, A.; Hallander, H.O.; Janssens, K.; Hermans, P.W.M.; Mooi, F.R.


    To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed a

  20. Attenuated Bordetella pertussis Vaccine Protects against Respiratory Syncytial Virus Disease via an IL-17-Dependent Mechanism

    Sawant, Devika; Schnoeller, Corinna; Roux, Xavier; Openshaw, Peter J.; Olszewska, Wieslawa; Locht, Camille; Raze, Dominique


    Rationale: We attenuated virulent Bordetella pertussis by genetically eliminating or detoxifying three major toxins. This strain, named BPZE1, is being developed as a possible live nasal vaccine for the prevention of whooping cough. It is immunogenic and safe when given intranasally in adult volunteers.

  1. Bordetella pertussis, the Causative Agent of Whooping Cough, Evolved from a Distinct, Human-Associated Lineage of B. bronchiseptica

    Diavatopoulos, Dimitri A; Cummings, Craig A.; Schouls, Leo M.; Brinig, Mary M.; Relman, David A.; Mooi, Frits R.


    Bordetella pertussis, B. bronchiseptica, B. parapertussishu, and B. parapertussisov are closely related respiratory pathogens that infect mammalian species. B. pertussis and B. parapertussishu are exclusively human pathogens and cause whooping cough, or pertussis, a disease that has resurged despite vaccination. Although it most often infects animals, infrequently B. bronchiseptica is isolated from humans, and these infections are thought to be zoonotic. B. pertussis and B. parapertussishu ar...

  2. Evaluation of Amplification Targets for the Specific Detection of Bordetella pertussis Using Real-Time Polymerase Chain Reaction

    Mohammad Rubayet Hasan


    Full Text Available BACKGROUND: Bordetella pertussis infections continue to be a major public health challenge in Canada. Polymerase chain reaction (PCR assays to detect B pertussis are typically based on the multicopy insertion sequence IS481, which offers high sensitivity but lacks species specificity.

  3. Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model.

    Kimura, A; Mountzouros, K T; Relman, D.A.; Falkow, S; Cowell, J L


    Filamentous hemagglutinin (FHA) is a cell surface protein of Bordetella pertussis which functions as an adhesin for this organism. It is a component of many new acellular pertussis vaccines. The proposed role of FHA in immunity to pertussis is based on animal studies which have produced some conflicting results. To clarify this situation, we reexamined the protective activity of FHA in an adult mouse respiratory infection model. Four-week-old BALB/c mice were immunized with one or two doses o...

  4. Detection of Bordetella pertussis by rapid-cycle PCR and colorimetric microwell hybridization.

    Buck, G E


    The use of rapid-cycle PCR combined with colorimetric microwell hybridization for detecting Bordetella pertussis was investigated. Rapid cycling was performed with an air thermocycler (model 1605; Idaho Technology, Idaho Falls, Idaho). Although the instrument was originally designed to be used with capillary tubes, an adapter that allows this instrument to be used with PCR tubes has recently been introduced. Because of the low heat capacity of air, the thermocycler has rapid transition rates ...

  5. Bordetella pertussis adenylate cyclase toxin translocation across a tethered lipid bilayer

    Veneziano, Rémi; Rossi, Claire; Chenal, Alexandre; Devoisselle, Jean-Marie; Ladant, Daniel; Chopineau, Joel


    Many bacterial toxins can cross biological membranes to reach the cytosol of mammalian cells, although how they pass through a lipid bilayer remains largely unknown. Bordetella pertussis adenylate cyclase (CyaA) toxin delivers its catalytic domain directly across the cell membrane. To characterize this unique translocation process, we designed an in vitro assay based on a tethered lipid bilayer assembled over a biosensor surface derivatized with calmodulin, a natural activator of the toxin. C...

  6. Mutations in Cytochrome Assembly and Periplasmic Redox Pathways in Bordetella pertussis

    Feissner, Robert E.; Beckett, Caroline S.; Loughman, Jennifer A.; Kranz, Robert G.


    Transposon mutagenesis of Bordetella pertussis was used to discover mutations in the cytochrome c biogenesis pathway called system II. Using a tetramethyl-p-phenylenediamine cytochrome c oxidase screen, 27 oxidase-negative mutants were isolated and characterized. Nine mutants were still able to synthesize c-type cytochromes and possessed insertions in the genes for cytochrome c oxidase subunits (ctaC, -D, and -E), heme a biosynthesis (ctaB), assembly of cytochrome c oxidase (sco2), or ferroch...

  7. Laboratory-based surveillance of pertussis using multitarget real-time PCR in Japan: evidence for Bordetella pertussis infection in preteens and teens

    K. Kamachi


    Full Text Available Between January 2013 and December 2014, we conducted laboratory-based surveillance of pertussis using multitarget real-time PCR, which discriminates among Bordetella pertussis, Bordetella parapertussis, Bordetella holmesii and Mycoplasma pneumoniae. Of 355 patients clinically diagnosed with pertussis in Japan, B. pertussis, B. parapertussis and M. pneumoniae were detected in 26% (n = 94, 1.1% (n = 4 and 0.6% (n = 2, respectively, whereas B. holmesii was not detected. It was confirmed that B. parapertussis and M. pneumoniae are also responsible for causing pertussis-like illness. The positive rates for B. pertussis ranged from 16% to 49%, depending on age. Infants aged ≤ 3 months had the highest rate (49%, and children aged 1 to 4 years had the lowest rate (16%, p < 0.01 vs. infants aged ≤ 3 months. Persons aged 10 to 14 and 15 to 19 years also showed high positive rates (29% each; the positive rates were not statistically significant compared with that of infants aged ≤ 3 months (p ≥ 0.06. Our observations indicate that similar to infants, preteens and teens are at high risk of B. pertussis infection.

  8. Bordetella pertussis en estudiantes adolescentes de la Ciudad de México Bordetella pertussis em estudantes adolescentes da Cidade do México Bordetella pertussis in adolescents students in Mexico City

    Patricia Tomé Sandoval


    Full Text Available OBJETIVO: Estimar la seroprevalencia a Bordetella pertussis en escolares y sus contactos escolares y familiares. MÉTODOS: Un total de 12.273 estudiantes de 12 a 15 años de edad, de 14 escuelas secundarias públicas de la Ciudad de México fueron estudiados durante los meses de Septiembre 2002 a Marzo 2003. Se tomó muestra de exudado nasofaríngeo en adolescentes con tos de más de 14 días de evolución. La infección fue confirmada por la técnica de reacción en cadena de polimerasa. Se realizó estudio de contactos escolares y familiares. RESULTADOS: La incidencia de tos fue de 5 para 1.000 estudiantes. De los 61 estudiantes con tos incluidos en la muestra, 20 (32,8% fueron positivos para Bordetella. De los 152 contactos escolares, 16 (10,6% resultaron positivos, y ocho tenían tos. Uno de esos contactos fue el director de una de las escuelas responsable de más del 60% de los casos positivos (12/20, quien también dio lecciones a diez de los estudiantes infectados. De los 29 familiares, ocho (27,6% fueron positivos, pertenecientes a tres familias. CONCLUSIONES: Los resultados muestran que la frecuencia de la enfermedad fue similar al comunicado en la población adolescente de otros países. Sin embargo, este trastorno no tiene necesariamente signos clínicos de la tos persistente y está sujeto a la existencia de infectados asintomáticos con Bordetella.OBJETIVO: Estimar a soroprevalência a Bordetella pertussis em escolares e seus contatos. MÉTODOS: Foram examinados 12.273 alunos entre 12 e 15 anos de idade, de 14 escolas secundárias públicas da Cidade do México, de setembro de 2002 a março de 2003. Amostras de exudado nasofaríngeo foram coletadas de adolescentes com tosse por mais de 14 dias. A infecção foi confirmada por reação em cadeia da polimerase. Todos os alunos e funcionários dos colégios dos casos confirmados por reação em cadeia da polimerase e seus familiares foram testados. RESULTADOS: A incidência de tosse

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

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


    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. PMID:26932577

  10. Characterization of fimbrial subunits from Bordetella species

    Mooi, F.R.; Heide, H.G.J. van der; Avest, A.R. ter; Welinder, K.G.; Livey, I.; Zeijst, B.A.M. van der; Gaastra, W.


    Using antisera raised against serotype 2 and 3 fimbrial subunits from Bordetella pertussis, serologically related polypeptides were detected in Bordetella bronchiseptica, Bordetella parapertussis and Bordetella avium strains. The two B. pertussis fimbrial subunits, and three of the serologically rel

  11. Identification of residues essential for catalysis and binding of calmodulin in Bordetella pertussis adenylate cyclase by site-directed mutagenesis.

    Glaser, P; Elmaoglou-Lazaridou, A; Krin, E.; Ladant, D.; Bârzu, O; Danchin, A


    In order to identify molecular features of the calmodulin (CaM) activated adenylate cyclase of Bordetella pertussis, a truncated cya gene was fused after the 459th codon in frame with the alpha-lacZ' gene fragment and expressed in Escherichia coli. The recombinant, 604 residue long protein was purified to homogeneity by ion-exchange and affinity chromatography. The kinetic parameters of the recombinant protein are very similar to that of adenylate cyclase purified from B.pertussis culture sup...


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


    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. PMID:26951000

  13. Research on pharmacological mechanism of the treatment of Asthma by oral Bordetella pertussis

    CHI Shen; SUN Yun; ZHANG Bao-yuan


    Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin (OVA), and explore the possible mechanism. Methods Culture the B. pertussis in Bordet-Gengou agar containing 25 % rabbit blood. Collect the bacteria and inactive them at 80 ℃ for 30 min to get whole killed B. pertussis. 32 BALB/C mice were randomly divided into control group, model-control group, model group and treatment group. The mice were sensitized and challenged with OVA to establish asthma model. Asthma mice in treatment group were orally administrated with B. pertussis 7 days before sensitization. The mice in control group and model-control group were challenged with saline. After 24 hours of last challenge, bronchoaveolar lavage fluid (BALF) and peripheral blood were collected. The total cells and eosinophils were counted in BALF. Results Compared with the control group (2.03±0.42, 0.33±0.82)× 105 mL-1 and model-control group (2.16±0.48,0.16±0.41)×105 mL-1, the total cells (10.13±1.33) ×105mL-1 and eosinophils (11.83±4.573)×105 mL-1 in BALF were more in asthma mice (P<0.01). The number of total cells (5.50±1.55)×105 mL-1 and eosinophils(0.66±0.82)×105 mL-1 in BALF were reduced in asthma mice treated with B. pertussis compared with asthma mice(P<0.01 ). Conclusions Oral B. pertussis can inhabit airway inflammation of asthma mice and has the potential of treating asthma.

  14. Produccion de suspensiones de bordetella pertussis por fermentación

    Algecira N.


    Full Text Available En este trabajo se estudió la producción de suspensión de Bordetella pertussis por fermentación para obtener el ingrediente activo de la vacuna contra tosferina. Se probaron diferentes medios de cultivo para el proceso, seleccionando el medio Stainer-Scholte adicionado con 3 g/L de casaminoacidos, el cual permite obtener altas concentraciones de células y suspensiones de buena calidad. Se estudió también la cinética de consumo de glutamato de sodio, producción de biomasa y evolución del pH. El crecimiento fue descrito por un modelo logístico. Se compara la tecnología de cultivo estacionario con el cultivo en fermentador presentándose esta última como la mejor alternativa de producción.

  15. Extracted protective antigen of Bordetella pertussis. I. Preparation and properties of the solubilized surface of components.

    Helting, T B; Blackkolb, F


    Bordetella pertussis microorganisms were treated with several extracting agents followed by ultracentrifugation to remove particulate matter. Analysis of the resulting supernatants by SDS gel electrophoresis showed one major component after simple salt extraction, and much more complex, although consistent pattern following detergent treatment. The yield of the solubilized protein in detergent extracts exceeded by far the values recorded for salt extracts. In order to prevent irreversible precipitation of the solubilized proteins upon removal of the denaturing agent, a novel procedure was developed. After extraction with urea-salt, the solubilized material was absorbed on a mineral carrier prior to the separation of the denaturing agent. The resulting absorbed vaccine was highly potent in the mouse-protection test, whereas the toxic reactions, elicited upon injection into experimental animals, were reduced in the comparison to the starting material. This diminished reactogenic potential was accompanied by the partial loss of the leukocytosis-promiting factor, whose activity was greatly diminished by urea-salt at alkaline pH-values. The procedure described may be applied to large-scale processing of Bordetella persussis microorganisms. Clinical trials now in progress should confirm or rebut the thesis that increased tolerability of the product, inferred from animal experiments, is reflected by fewer adverse reactions in humans. In the former case, the detergent extract vaccine may constitute a realistic alternative to conventional whole-cell vaccines against whooping-cough. PMID:6266198

  16. Filamentous hemagglutinin has a major role in mediating adherence of Bordetella pertussis to human WiDr cells.

    Urisu, A; Cowell, J L; Manclark, C R


    [35S]methionine-labeled Bordetella pertussis adhered to monolayers of WiDr cells, an epitheliumlike cell line from a human intestinal carcinoma. Adherence was proportional to the density of the WiDr cells and to the concentration of B. pertussis in the assay. Adherence of virulent phase I strains Tohama phase I, 114, and BP338 was much greater than adherence of avirulent strains Tohama phase III and 423 phase IV. Mutants deficient in the production of the filamentous hemagglutinin (FHA) were ...

  17. Amidate Prodrugs of 9-[2-(Phosphonomethoxy)Ethyl]Adenine as Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis

    Šmídková, Markéta; Dvořáková, Alexandra; Tloušťová, Eva; Česnek, Michal; Janeba, Zlatko; Mertlíková-Kaiserová, Helena


    Roč. 58, č. 2 (2014), s. 664-671. ISSN 0066-4804 R&D Projects: GA MV VG20102015046 Grant ostatní: OPPC(XE) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : Bordetella pertussis * adenylate cyclase toxin * ACT * inhibitors * PMEA * amidate prodrugs Subject RIV: CC - Organic Chemistry Impact factor: 4.476, year: 2014

  18. [Serological evaluation of Bordetella pertussis infection in adults with prolonged cough].

    Sönmez, Cemile; Çöplü, Nilay; Gözalan, Ayşegül; Yılmaz, Ülkü; Bilekli, Selen; Demirci, Nilgün Yılmaz; Biber, Çiğdem; Erdoğan, Yurdanur; Esen, Berrin; Çöplü, Lütfi


    Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0

  19. Infección por Bordetella pertussis: Una causa emergente de tos prolongada en adolescentes y adultos Bordetella pertussis infection: An emerging cause of prolonged cough illness in adolescents and adults



    Full Text Available La tos convulsiva o coqueluche está siendo reconocida cada vez con mayor frecuencia como causa de tos prolongada en adolescentes y adultos. La vacunación sistemática de la población pediátrica ha determinado un cambio en el perfl epidemiológico de la enfermedad, aumentando su prevalencia en la población adulta. Se presenta el caso clínico de una paciente de 45 años, fumadora, enfermera de unidad de hemodiálisis, que consulta por malestar general y tos seca de seis semanas de evolución. La radiografía de tórax era normal y la inmunofuorescencia directa de hisopado nasofaríngeo fue positiva para Bordetella pertussis. A propósito de este caso clínico, revisamos las principales causas de tos crónica: asma bronquial, enfermedad rinosinusal y refujo gastroesofágico; el cuadro clínico, evaluación diagnóstica y tratamiento de la infección por B. pertussis en población adulta.Whooping cough is increasingly recognized as a cause of prolonged cough illness in adolescents and adults. Systematic vaccination has changed its epidemiology, with the majority of cases now primarily affecting adolescents and adults. A 45-year-old female, active smoker, nurse, who works in a dialysis service, presented with a 6-week history of bothersome cough and malaise. Thorax x-ray was normal and direct immunofuorescence of nasopharyngeal swab was positive for Bordetella pertussis. This case illustrates pertussis infection in adulthood. We review the main causes of chronic cough in adults: asthma, chronic rhinosinusitis and gastroesophageal refux; the clinical features, prevalence, diagnostic tools, and management of adult patients with B. pertussis infection to increase awareness of this highly contagious disease.

  20. Seroprevalence of Bordetella pertussis in the Mexican population: a cross-sectional study.

    Conde-Glez, C; Lazcano-Ponce, E; Rojas, R; DeAntonio, R; Romano-Mazzotti, L; Cervantes, Y; Ortega-Barría, E


    SUMMARY Serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-95 years (January-October 2010) and analysed to assess the seroprevalence of Bordetella pertussis (BP) in Mexico. Subjects' gender, age, geographical region and socioeconomic status were extracted from the survey and compiled into a subset database. A total of 3344 subjects (median age 29 years, range 1-95 years) were included in the analysis. Overall, BP seroprevalence was 47.4%. BP seroprevalence was significantly higher in males (53.4%, P = 0.0007) and highest in children (59.3%) decreasing with advancing age (P = 0.0008). BP seroprevalence was not significantly different between regions (P = 0.1918) and between subjects of socioeconomic status (P = 0.0808). Women, adolescents and young adults were identified as potential sources of infection to infants. Booster vaccination for adolescents and primary contacts (including mothers) for newborns and infants may provide an important public health intervention to reduce the disease burden. PMID:23734968

  1. Membrane-Pore Forming Characteristics of the Bordetella pertussis CyaA-Hemolysin Domain

    Chattip Kurehong


    Full Text Available Previously, the 126-kDa Bordetella pertussis CyaA pore-forming/hemolysin (CyaA-Hly domain was shown to retain its hemolytic activity causing lysis of susceptible erythrocytes. Here, we have succeeded in producing, at large quantity and high purity, the His-tagged CyaA-Hly domain over-expressed in Escherichia coli as a soluble hemolytically-active form. Quantitative assays of hemolysis against sheep erythrocytes revealed that the purified CyaA-Hly domain could function cooperatively by forming an oligomeric pore in the target cell membrane with a Hill coefficient of ~3. When the CyaA-Hly toxin was incorporated into planar lipid bilayers (PLBs under symmetrical conditions at 1.0 M KCl, 10 mM HEPES buffer (pH 7.4, it produced a clearly resolved single channel with a maximum conductance of ~35 pS. PLB results also revealed that the CyaA-Hly induced channel was unidirectional and opened more frequently at higher negative membrane potentials. Altogether, our results first provide more insights into pore-forming characteristics of the CyaA-Hly domain as being the major pore-forming determinant of which the ability to induce such ion channels in receptor-free membranes could account for its cooperative hemolytic action on the target erythrocytes.

  2. Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.

    Tzvia Abramson

    Full Text Available BACKGROUND: Filamentous hemagglutinin (FHA is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-kappaB transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappaB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection. METHODOLOGY/PRINCIPAL FINDINGS: Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-kappaB pathway, as manifested by the degradation of cytosolic IkappaB alpha, by NF-kappaB DNA binding, and by the subsequent secretion of NF-kappaB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IkappaB alpha, and the failure of TNF-alpha to activate NF-kappaB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells. CONCLUSIONS: These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-kappaB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.

  3. Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.

    Wu, V; Smith, A A; You, H; Nguyen, T A; Ferguson, R; Taylor, M; Park, J E; Llontop, P; Youngman, K R; Abramson, T


    Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough. PMID:26462419

  4. A new assay for invasion of HeLa 229 cells by Bordetella pertussis: effects of inhibitors, phenotypic modulation, and genetic alterations.

    Lee, C. K.; Roberts, A. L.; Finn, T M; Knapp, S; Mekalanos, J J


    Invasion and intracellular survival of Bordetella pertussis in HeLa 229 cells was studied by a new assay that utilizes polymyxin B instead of gentamicin to rapidly kill extracellular organisms. Invasion measured by this assay was time and temperature dependent and was inhibited by the microfilament drug cytochalasin D. The invasion process was also dependent on a functional vir locus (also known as bvg), the positive regulator of virulence gene expression in B. pertussis. Four spontaneous Vir...

  5. A CpG-containing oligodeoxynucleotide adjuvant for acellular pertussis vaccine improves the protective response against Bordetella pertussis

    Asokanathan, Catpagavalli; Corbel, Michael; Xing, Dorothy


    We investigated the adjuvant effect of CpG ODN alone or in combination with aluminum hydroxide on the immune response to the three main antigens presented in current acellular pertussis vaccines: pertussis toxoid, filamentous haemagglutinin and pertactin. The development of protection in mice was investigated for the intra-peritoneal and intra-nasal immunisation routes. The results showed that CpG ODN alone, or in combination with aluminum hydroxide, gave enhancement in anti-pertussis toxin, ...

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

    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


    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. PMID:25166348

  7. Cooperative phenomena in binding and activation of Bordetella pertussis adenylate cyclase by calmodulin.

    Bouhss, A; Krin, E; Munier, H; Gilles, A M; Danchin, A; Glaser, P; Bârzu, O


    The catalytic domain of Bordetella pertussis adenylate cyclase located within the first 400 amino acids of the protein can be cleaved by trypsin in two subdomains (T25 and T18) corresponding to ATP-(T25) and calmodulin (CaM)-(T18) binding sites. Reassociation of subdomains by CaM is a cooperative process, which is a unique case among CaM-activated enzymes. To understand better the molecular basis of this phenomenon, we used several approaches such as partial deletions of the adenylate cyclase gene, isolation of peptides of various size, and site-directed mutagenesis experiments. We found that a stretch of 72 amino acid residues overlapping the carboxyl terminus of T25 and the amino terminus of T18 accounts for 90% of the binding energy of adenylate cyclase-CaM complex. The hydrophobic "side" of the helical region situated around Trp242 plays a major role in the interaction of adenylate cyclase with CaM, whereas basic residues that alternate with acidic residues in bacterial enzyme play a much less important role. The amino-terminal half of the catalytic domain of adenylate cyclase contributes only 10% to the binding energy of CaM, whereas the last 130 amino acid residues are not at all involved in binding. However, these segments of adenylate cyclase might affect protein/protein interaction and catalysis by propagating conformational changes to the CaM-binding sequence which is located in the middle of the catalytic domain of bacterial enzyme. PMID:8420945

  8. Expression of bvg-repressed genes in Bordetella pertussis is controlled by RisA through a novel c-di-GMP signaling pathway

    The BvgAS two component system of Bordetella pertussis controls virulence factor expression. In addition, BvgAS controls expression of the bvg-repressed genes through the action of the repressor, BvgR. The transcription factor RisA is inhibited by BvgR, and when BvgR is not expressed RisA induces th...

  9. Cyclic di-GMP regulation of the bvg-repressed genes and the orphan response regulator RisA in Bordetella pertussis

    Expression of Bordetella pertussis virulence factors is activated by the BvgAS two-component system. Under modulating growth conditions BvgAS indirectly represses another set of genes through the action of BvgR, a bvg-activated protein. BvgR blocks activation of the response regulator RisA which is ...

  10. Bisamidate Prodrugs of 2-Substituted 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA, adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis

    Česnek, Michal; Jansa, Petr; Šmídková, Markéta; Mertlíková-Kaiserová, Helena; Dračínský, Martin; Brust, T. F.; Pávek, P.; Trejtnar, F.; Watts, V. J.; Janeba, Zlatko


    Roč. 10, č. 8 (2015), s. 1351-1364. ISSN 1860-7179 R&D Projects: GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : adenylate cyclase toxin * bisamidates * Bordetella pertussis * nucleosides * phosphonates Subject RIV: CC - Organic Chemistry Impact factor: 2.968, year: 2014

  11. Bordetella pertussis: an underreported pathogen in pediatric respiratory infections, a prospective cohort study

    Brink, van den G.; Wishaupt, J.O.; Douma, J.C.; Hartwig, N.G.; Versteegh, F.G.A.


    Background: The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence has risen higher than the reported cases, suggesting that laboratory tests for pertussis are considered infrequently and that even more pertussis cases are missed. The objective of our study

  12. Murine antibody response to oral infection with live aroA recombinant Salmonella dublin vaccine strains expressing filamentous hemagglutinin antigen from Bordetella pertussis.

    Molina, N C; Parker, C D


    Two plasmids which express either nearly intact or truncated filamentous hemagglutinin (FHA) from Bordetella pertussis and which are marked with a tetracycline resistance (Tcr) gene were transformed into Salmonella dublin SL1438, an aroA deletion mutant intended for use as an attenuated oral vaccine against salmonellosis. These S. dublin recombinants, when fed to mice, induced serum immunoglobulin, immunoglobulin M (IgM), and sometimes IgA antibody responses to FHA and S. dublin. In addition,...

  13. Filamentous hemagglutinin of Bordetella pertussis: a key adhesin with immunomodulatory properties?

    Villarino Romero, Rodrigo; Osička, Radim; Šebo, Peter


    Roč. 9, č. 12 (2014), s. 1339-1360. ISSN 1746-0913 R&D Projects: GA ČR(CZ) P302/11/0580; GA ČR(CZ) GA13-14547S Institutional support: RVO:61388971 Keywords : Bordetella * adhesion * integrins * filamentous hemagglutinin Subject RIV: EE - Microbiology, Virology Impact factor: 4.275, year: 2014

  14. A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation.

    Castillo, Sonsire Fernández; Chovel, Mario Landys; Hernández, Niurka Gutiérrez; González, Lorena Corcho; Blanco, Amaya; Hernández, Daily Serrano; Medina, Mildrey Fariñas; Tito, Maydelis Álvarez; Quiñoy, José Luis Pérez


    In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone. PMID:27489808

  15. Mutation in the β-hairpin of the Bordetella pertussis adenylate cyclase toxin modulates N-lobe conformation in calmodulin

    Springer, Tzvia I.; Goebel, Erich; Hariraju, Dinesh [Department of Microbiology, Miami University, Oxford, OH 45056 (United States); Finley, Natosha L., E-mail: [Department of Microbiology, Miami University, Oxford, OH 45056 (United States); Cell, Molecular, and Structural Biology Program, Miami University, Oxford, OH 45056 (United States)


    Highlights: • Bordetella pertussis adenylate cyclase toxin modulates bi-lobal structure of CaM. • The structure and stability of the complex rely on intermolecular associations. • A novel mode of CaM-dependent activation of the adenylate cyclase toxin is proposed. - Abstract: Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD’s β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD’s β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (R{sub h}) and reduced thermal stability in the mutant complex. Taken

  16. [Cryofractographic study of intercellular junctions in the populations of agar-cultivated Bordetella pertussis].

    Vysotskiĭ, V V; Vaisman, I Sh; Efimova, O G; Chemurzieva, N V


    The characteristic feature of replicas obtained from the freeze-fractures of B. pertussis unfixed cultures developing on casein charcoal agar for 1-7 days is the associative growth of highly polymorphic cells, ensured by the ramified system of intercellular connections (IC) formed by the derivatives of the outer layers of the cell wall. This proves that the associative location of bacterial cells, linked by numerous IC, in the preparation is not the artefact appearing in the process of their chemical fixation. In replicas obtained from the freeze-fractures of B. pertussis cultures, previously fixed with glutaraldehyde, osmic acid and uranyl acetate, oval cells with the cytoplasm having a relatively homogeneous structure and with the smoothed-out three-layer cell wall prevail. As a rule, IC are limited to the sites of direct contacts between individual cells. PMID:2866645

  17. Purification and assay of cell-invasive form of calmodulin-sensitive adenylyl cyclase from Bordetella pertussis

    An invasive form of the CaM-sensitive adenylyl cyclase from Bordetella pertussis can be isolated from bacterial culture supernatants. This isolation is achieved through the use of QAE-Sephadex anion-exchange chromatography. It has been demonstrated that the addition of exogenous Ca2+ to the anion-exchange gradient buffers will affect elution from the column and will thereby affect the isolation of invasive adenylyl cyclase. This is probably due to a Ca2(+)-dependent interaction of the catalytic subunit with another component in the culture supernatant. Two peaks of adenylyl cyclase activity are obtained. The Pk1 adenylyl cyclase preparation is able to cause significant increases in intracellular cAMP levels in animal cells. This increase occurs rapidly and in a dose-dependent manner in both N1E-115 mouse neuroblastoma cells and human erythrocytes. The Pk2 adenylyl cyclase has catalytic activity but is not cell invasive. This material can serve, therefore, as a control to ensure that the cAMP which is measured is, indeed, intracellular. A second control is to add exogenous CaM to the Pk1 adenylyl cyclase preparation. The 45-kDa catalytic subunit-CaM complex is not cell invasive. Although the mechanism for membrane translocation of the adenylyl cyclase is unknown, there is evidence that the adenylyl cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis. Calmodulin-sensitive adenylyl cyclase activity can be removed from preparations of the adenylyl cyclase that have been subjected to SDS-polyacrylamide gel electrophoresis. This property of the enzyme has enabled purification of the catalytic subunit to apparent homogeneity. The purified catalytic subunit from culture supernatants has a predicted molecular weight of 45,000. This polypeptide interacts directly with Ca2+ and this interaction may be important for its invasion into animal cells

  18. Analusis by 252Cf plasma desorption mass spectrometry of Bordetella pertussis endotoxin after nitrous deamination

    Deprun, C.; Karibian, D.; Caroff, M.


    Endotoxic lipopolysaccharides (LPSs) are the major components of Gram-negative bacterial outer membrane. Like many amphipathic molecules, they pose problems of heterogeneity, purity, solubility, and aggregation. Nevertheless, PDMS has recently have been applied to unmodified endotoxins composed of LPS having uip to five sugar units in their saccharide chain. The B. Pertussis LPSs, most of which have a dodecasaccharide domain, ahve been analysed by classical methods and the masses of the separate lipid and saccharide domains determined after rupture of the bond linking them. However, the acid treatment employed for these and most chemical analyses can also modify structures in the vicinity of the bond. In order to investigate this biologically-important region, the endotoxin was treated to nitrous deamination, which shortens the saccharide chain to five sugars, but preserves the acid-labile region of the LPS. The PDM spectrum of this derivative, which required new conditions for its desorption, confirmed the structure analysis and demonstrated the presence of at least four molecular species.

  19. A versatile, non genetically modified organism (GMO)-based strategy for controlling low-producer mutants in Bordetella pertussis cultures using antigenic modulation.

    Goffin, Philippe; Slock, Thomas; Smessaert, Vincent; De Rop, Philippe; Dehottay, Philippe


    The uncontrolled presence of non-producer mutants negatively affects bioprocesses. In Bordetella pertussis cultures, avirulent mutants emerge spontaneously and accumulate. We characterized the dynamics of accumulation using high-throughput growth assays and competition experiments between virulent and avirulent (bvg(-) ) isolates. A fitness advantage of bvg(-) cells was identified as the main driver for bvg(-) accumulation under conditions of high virulence factor production. Conversely, under conditions that reduce their expression (antigenic modulation), bvg(-) takeover could be avoided. A control strategy was derived, which consists in applying modulating conditions whenever virulence factor production is not required. It has a wide range of applications, from routine laboratory operations to vaccine manufacturing, where pertussis toxin yields were increased 1.4-fold by performing early pre-culture steps in modulating conditions. Because it only requires subtle modifications of the culture medium and does not involve genetic modifications, this strategy is applicable to any B. pertussis isolate, and should facilitate regulatory acceptance of process changes for vaccine production. Strategies based on the same concept, could be derived for other industrially relevant micro-organisms. This study illustrates how a sound scientific understanding of physiological principles can be turned into a practical application for the bioprocess industry, in alignment with Quality by Design principles. PMID:26014907

  20. Rediscovering Pertussis

    Zlamy, Manuela


    Pertussis, caused by Bordetella (B.) pertussis, a Gram-negative bacterium, is a highly contagious airway infection. Especially in infants, pertussis remains a major health concern. Acute infection with B. pertussis can cause severe illness characterized by severe respiratory failure, pulmonary hypertension, leucocytosis, and death. Over the past years, rising incidence rates of intensive care treatment in young infants were described. Due to several virulence factors (pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and lipooligosaccharide) that promote bacterial adhesion and invasion, B. pertussis creates a unique niche for colonization within the human respiratory tract. The resulting long-term infection is mainly caused by the ability of B. pertussis to interfere with the host’s innate and adaptive immune system. Although pertussis is a vaccine-preventable disease, it has persisted in vaccinated populations. Epidemiological data reported a worldwide increase in pertussis incidence among children during the past years. Either acellular pertussis (aP) vaccines or whole-cell vaccines are worldwide used. Recent studies did not detect any differences according to pertussis incidence when comparing the different vaccines used. Most of the currently used aP vaccines protect against acute infections for a period of 6–8 years. The resurgence of pertussis may be due to the lack of herd immunity caused by missing booster immunizations among adolescents and adults, low vaccine coverages in some geographic areas, and genetic changes of different B. pertussis strains. Due to the rising incidence of pertussis, probable solution strategies are discussed. Cocooning strategies (vaccination of close contact persons) and immunizations during pregnancy appear to be an approach to reduce neonatal contagiousness. During the past years, studies focused on the pathway of the immune modulation done by B. pertussis to provide a basis for the

  1. Rediscovering Pertussis.

    Zlamy, Manuela


    Pertussis, caused by Bordetella (B.) pertussis, a Gram-negative bacterium, is a highly contagious airway infection. Especially in infants, pertussis remains a major health concern. Acute infection with B. pertussis can cause severe illness characterized by severe respiratory failure, pulmonary hypertension, leucocytosis, and death. Over the past years, rising incidence rates of intensive care treatment in young infants were described. Due to several virulence factors (pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and lipooligosaccharide) that promote bacterial adhesion and invasion, B. pertussis creates a unique niche for colonization within the human respiratory tract. The resulting long-term infection is mainly caused by the ability of B. pertussis to interfere with the host's innate and adaptive immune system. Although pertussis is a vaccine-preventable disease, it has persisted in vaccinated populations. Epidemiological data reported a worldwide increase in pertussis incidence among children during the past years. Either acellular pertussis (aP) vaccines or whole-cell vaccines are worldwide used. Recent studies did not detect any differences according to pertussis incidence when comparing the different vaccines used. Most of the currently used aP vaccines protect against acute infections for a period of 6-8 years. The resurgence of pertussis may be due to the lack of herd immunity caused by missing booster immunizations among adolescents and adults, low vaccine coverages in some geographic areas, and genetic changes of different B. pertussis strains. Due to the rising incidence of pertussis, probable solution strategies are discussed. Cocooning strategies (vaccination of close contact persons) and immunizations during pregnancy appear to be an approach to reduce neonatal contagiousness. During the past years, studies focused on the pathway of the immune modulation done by B. pertussis to provide a basis for the

  2. The Bordetella bhu Locus Is Required for Heme Iron Utilization

    Vanderpool, Carin K.; Armstrong, Sandra K.


    Bordetella pertussis and Bordetella bronchiseptica are capable of obtaining iron from hemin and hemoglobin. Genes encoding a putative bacterial heme iron acquisition system (bhu, for Bordetella heme utilization) were identified in a B. pertussis genomic sequence database, and the corresponding DNA was isolated from a virulent strain of B. pertussis. A B. pertussis bhuR mutant, predicted to lack the heme outer membrane receptor, was generated by allelic exchange. In contrast to the wild-type s...

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


    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 <4 yrs.old, the reduction of anti-B. pertussis IgM by both antigens was higher than for B. pertussis antigen alone. Based on the high difference (≥ 2 times) between reduction by L.pneumophila sg1 and by B. pertussis antigen, legionellosis was confirmed in 8/19 children. The majority of them also indicated IgM positive/borderline results for B. pertussis or M.pneumoniae in routine ELISA 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. PMID:26557032

  4. Crystallization and preliminary X-ray diffraction analysis of two extracytoplasmic solute receptors of the DctP family from Bordetella pertussis

    Sample preparation, crystallization and preliminary X-ray analysis are reported for two B. pertussis extracytoplasmic solute receptors. DctP6 and DctP7 are two Bordetella pertussis proteins which belong to the extracytoplasmic solute receptors (ESR) superfamily. ESRs are involved in the transport of substrates from the periplasm to the cytosol of Gram-negative bacteria. DctP6 and DctP7 have been crystallized and diffraction data were collected using a synchrotron-radiation source. DctP6 crystallized in space group P41212, with unit-cell parameters a = 108.39, b = 108.39, c = 63.09 Å, while selenomethionyl-derivatized DctP7 crystallized in space group P212121, with unit-cell parameters a = 64.87, b = 149.83, c = 170.65 Å. The three-dimensional structure of DctP7 will be determined by single-wavelength anomalous diffraction, while the DctP6 structure will be solved by molecular-replacement methods

  5. A direct pyrophosphatase-coupled assay provides new insights into the activation of the secreted adenylate cyclase from Bordetella pertussis by calmodulin.

    Lawrence, Anthony J; Coote, John G; Kazi, Yasmin F; Lawrence, Paul D; MacDonald-Fyall, Julia; Orr, Barbara M; Parton, Roger; Riehle, Mathis; Sinclair, James; Young, John; Price, Nicholas C


    Continuous recording of the activity of recombinant adenylate cyclase (CyaA) of Bordetella pertussis (EC ) by conductimetric determination of enzyme-coupled pyrophosphate cleavage has enabled us to define a number of novel features of the activation of this enzyme by calmodulin and establish conditions under which valid activation data can be obtained. Activation either in the presence or absence of calcium is characterized by a concentration-dependent lag phase. The rate of formation and breakdown of the activated complex can be determined from an analysis of the lag phase kinetics and is in good agreement with thermodynamic data obtained by measuring the dependence of activation on calmodulin concentration, which show that calcium increases k(on) by about 30-fold. The rate of breakdown of the activated complex, formed either in the presence or absence of calcium, has been determined by dilution experiments and has been shown to be independent of the presence of calcium. The coupled assay is established as a rapid, convenient and safe method which should be readily applicable to the continuous assays of most other enzymes that catalyze reactions in which inorganic pyrophosphate is liberated. PMID:11934879

  6. Conservación por congelación de Bordetella pertussis y Corynebacterium diphtheriae, empleados en la producción de vacunas para uso humano

    Yilian Plasencia,


    Full Text Available En el presente estudio se evaluó el método de congelación a –70ºC para la preservación de Bordetella pertussis y Corynebacterium diphtheriae. Para verificar el sustento de los cultivos se realizó un adecuado control de calidad, que incluyó comprobación de pureza, viabilidad y estabilidad de las propiedades de interés. En este trabajo se probaron diferentes formulaciones. Se seleccionó la que arrojó los mejores resultados y se realizó un estudio de mantenimiento de las características evaluadas durante el tiempo. Para medir determinados parámetros se realizaron procesos a escala industrial, empleándose para esto un biorreactor Chemap de 35 L. Se tomaron como referencia los valores obtenidos por las cepas conservadas por liofilización. De esta forma se buscaron alternativas y soluciones a problemas presentados en su conservación. Los resultados obtenidos sugieren la posible inclusión en el Programa de Mantenimiento establecido.

  7. Pesquisa de antigenos aglutinantes "major" 1, 2 e 3 em cepas de Bordetella pertussis, isoladas de crianças com coqueluche atendidas no Hospital de Isolamento Emílio Ribas de São Paulo, Brasil Determination of 1, 2 and 3 major antigens in Bordetella pertussis strains isolated from Brazilian children with whooping-cough

    Sebastião Timo Iaria


    Full Text Available Em 30 cepas de Bordetella pertussis isoladas de crianças com coqueluche, atendidas no Hospital de Isolamento Emílio Ribas de São Paulo, foram pesquisados os antígenos aglutinantes ''major" 1, 2 e 3. Levando-se em conta a presença combinada dos três antígenos, as provas de soro-aglutinação rápida em lamina revelaram que 25 (83,3% cepas possuiam os fatores 1, 2 e 3, enquanto que 3 (10,0% e 2 (6,7% foram positivas, somente, para 1, 2 e 1, 3, respectivamente. Os resultados foram discutidos, considerando-se a importância deste antígeno no preparo de vacinas.The presence of major antigens, 1, 2 and 3 were determined in 30 strains of B. pertussis isolated from children with whooping-cough hospitalized at the Hospital Emílio Ribas, São Paulo Brazil. The method used was the slide-agglutination test. Tests showed that 25(83.3% of strains were positives for factors 1, 2 and 3. Factores 1 and 3 alone were present in 3 (10% of strains and 1 and 2 alone in 2 (6.7%.

  8. Differences in Purinergic Amplification of Osmotic Cell Lysis by the Pore-Forming RTX Toxins Bordetella pertussis CyaA and Actinobacillus pleuropneumoniae ApxIA: the Role of Pore Size

    Mašín, Jiří; Fišer, Radovan; Linhartová, Irena; Osička, Radim; Bumba, Ladislav; Hewlett, E. L.; Benz, R.; Šebo, Peter


    Roč. 81, č. 12 (2013), s. 4571-4582. ISSN 0019-9567 R&D Projects: GA ČR GAP302/12/0460; GA ČR(CZ) GAP302/11/0580; GA ČR(CZ) GAP207/11/0717; GA AV ČR IAA500200914; GA ČR GA13-14547S Institutional support: RVO:61388971 Keywords : Bordetella pertussis * Actinobacillus pleuropneumoniae * E-coli Subject RIV: EE - Microbiology, Virology Impact factor: 4.156, year: 2013

  9. Tosse convulsa em Portugal: análise retrospetiva de casos clínicos suspeitos de infeção por Bordetella pertussis no período 2010-2014

    Santos, Maria Augusta; Pereira, Brigida; Furtado, Cristina


    Objetivo: Analisar retrospetivamente os resultados laboratoriais dos casos clínicos suspeitos de tosse convulsa enviados ao Laboratório Nacional de Referência de Bordetella pertussis do INSA no Porto para confirmação laboratorial no período 2010-2014, tendo como finalidade alertar não só para a necessidade de conhecer-se melhor a real incidência da tosse convulsa nos grupos etários com idade superior a 13 anos, bem como de caracterizar geneticamente as estirpes circulantes em Portuga...

  10. Genómica funcional de Bordetella pertussis, implicancias sobre una enfermedad considerada reemergente

    Gaillard, María Emilia


    Objetivos generales de la tesis: Con el desarrollo de esta propuesta se espera contribuir al conocimiento que sirva de base para el diseño de una vacuna más efectiva contra pertussis, no sólo en términos generales, sino en lo que se refiere a su efectividad en Argentina, determinando la definición de la/s cepas / componentes a incluir en una nueva formulación. Objetivos específicos de la tesis: En este marco conceptual y tomando como hipótesis la divergencia de la población bacterian...

  11. Crystallization and preliminary X-ray diffraction analysis of the peptidylprolyl isomerase Par27 of Bordetella pertussis

    Par27 from B. pertussis, the prototype of a new group of parvulins has been crystallized in two different crystal forms. Proteins with both peptidylprolyl isomerase (PPIase) and chaperone activities play a crucial role in protein folding in the periplasm of Gram-negative bacteria. Few such proteins have been structurally characterized and to date only the crystal structure of SurA from Escherichia coli has been reported. Par27, the prototype of a new group of parvulins, has recently been identified. Par27 exhibits both chaperone and PPIase activities in vitro and is the first identified parvulin protein that forms dimers in solution. Par27 has been expressed in E. coli. The protein was purified using affinity and gel-filtration chromatographic techniques and crystallized in two different crystal forms. Form A, which belongs to space group P2 (unit-cell parameters a = 42.2, b = 142.8, c = 56.0 Å, β = 95.1°), diffracts to 2.8 Å resolution, while form B, which belongs to space group C222 (unit-cell parameters a = 54.6, b = 214.1, c = 57.8 Å), diffracts to 2.2 Å resolution. Preliminary diffraction data analysis agreed with the presence of one monomer in the asymmetric unit of the orthorhombic crystal form and two in the monoclinic form

  12. Bulk protein biosynthesis of the spleen and some splenic cell populations after induction of splenomegaly by application of Bordetella pertussis

    Autoradiographic studies and liquid scintillation counting were carried out in female NMRI mice just reaching maturity. All animals had received a single injection, either of bovine serum albumin (BSA) or of pertussis organism (PO) or BSA + PO. The animals were sacrificed 4 d and 10 d after this pretreatment. 2 h before decapitation, a single dose of 3H-l phenyl alamine was applied intraperitoneally. The following results were obtained: The splenic index (splenic weight in mg/mouse weight in g) increased as a result of splenomegaly caused by PO. Morphometric data suggested an enlarged cell and nuclear area with enhanced cellular amino acid turnover and migration of RNP-containing matter into the nucleus, especially in the megakaryocytes and in lymphocytoid blastic cells. Incorporation of 3H-l-phenylalanine per unit of dry weight of the spleen is slowed down during the experiment while amiro acid incorporation by the total spleen increases with PO-induced splenomegaly. Incorporation of amino acid per unit of dry weight is constant in all experimental and control animals. The increased amino acid incorporation in lymphocytoid blastic cells is probably caused by the immunological situations during the experiment. An explanation of total cell increase and cell increase of megakaryocytic splenic cells is attempted. (orig./MG)

  13. Adults with pertussis

    MacLean, D. W.


    Eighty adults were diagnosed in one general practice as having infection due to Bordetella pertussis, type 1.3, during a period of 30 months. Their clinical presentation and progress is recorded. A plea is made for attention to be paid to this infection in adults.

  14. BpsR Modulates Bordetella Biofilm Formation by Negatively Regulating the Expression of the Bps Polysaccharide

    Conover, Matt S.; Redfern, Crystal J.; Ganguly, Tridib; Sukumar, Neelima; Sloan, Gina; Mishra, Meenu; Deora, Rajendar


    Bordetella bacteria are Gram-negative respiratory pathogens of animals, birds, and humans. A hallmark feature of some Bordetella species is their ability to efficiently survive in the respiratory tract even after vaccination. Bordetella bronchiseptica and Bordetella pertussis form biofilms on abiotic surfaces and in the mouse respiratory tract. The Bps exopolysaccharide is one of the critical determinants for biofilm formation and the survival of Bordetella in the murine respiratory tract. In...

  15. Extended incubation of culture plates improves recovery of Bordetella spp.

    Katzko, G; Hofmeister, M; Church, D.


    Extended incubation of culture plates was studied to see if the recovery of Bordetella spp. from nasopharyngeal swabs could be improved. Forty-eight Bordetella isolates were recovered from 103 children (overall positive-culture rate, 46.6%) who met the clinical case definition of pertussis. Seven of 44 (16%) B. pertussis isolates and 2 of 4 (50%) B. parapertussis isolates were recovered only after extended incubation of nasopharyngeal cultures up to 12 days.

  16. Tracking Pertussis and Evaluating Control Measures through Enhanced Pertussis Surveillance, Emerging Infections Program, United States.

    Skoff, Tami H; Baumbach, Joan; Cieslak, Paul R


    Despite high coverage with pertussis-containing vaccines, pertussis remains endemic to the United States. There have been increases in reported cases in recent years, punctuated by striking epidemics and shifting epidemiology, both of which raise questions about current policies regarding its prevention and control. Limited data on pertussis reported through the National Notifiable Disease Surveillance System have proved insufficient to answer these questions. To address shortcomings of national pertussis data, the Emerging Infections Program at the US Centers for Disease Control and Prevention launched Enhanced Pertussis Surveillance (EPS), which is characterized by systematic case ascertainment, augmented data collection, and collection of Bordetella pertussis isolates. Data collected through EPS have been instrumental in understanding the rapidly evolving epidemiology and molecular epidemiology of pertussis and have contributed essential information regarding pertussis vaccines. EPS also serves as a platform for conducting critical and timely evaluations of pertussis prevention and control strategies, including targeting of vaccinations and antimicrobial prophylaxis. PMID:26291475

  17. Bordetella pertussis commits human dendritic cells to promote a Th1/Th17 response through the activity of adenylate cyclase toxin and MAPK-pathways.

    Giorgio Fedele

    Full Text Available The complex pathology of B. pertussis infection is due to multiple virulence factors having disparate effects on different cell types. We focused our investigation on the ability of B. pertussis to modulate host immunity, in particular on the role played by adenylate cyclase toxin (CyaA, an important virulence factor of B. pertussis. As a tool, we used human monocyte derived dendritic cells (MDDC, an ex vivo model useful for the evaluation of the regulatory potential of DC on T cell immune responses. The work compared MDDC functions after encounter with wild-type B. pertussis (BpWT or a mutant lacking CyaA (BpCyaA-, or the BpCyaA- strain supplemented with either the fully functional CyaA or a derivative, CyaA*, lacking adenylate cyclase activity. As a first step, MDDC maturation, cytokine production, and modulation of T helper cell polarization were evaluated. As a second step, engagement of Toll-like receptors (TLR 2 and TLR4 by B. pertussis and the signaling events connected to this were analyzed. These approaches allowed us to demonstrate that CyaA expressed by B. pertussis strongly interferes with DC functions, by reducing the expression of phenotypic markers and immunomodulatory cytokines, and blocking IL-12p70 production. B. pertussis-treated MDDC promoted a mixed Th1/Th17 polarization, and the activity of CyaA altered the Th1/Th17 balance, enhancing Th17 and limiting Th1 expansion. We also demonstrated that Th1 effectors are induced by B. pertussis-MDDC in the absence of IL-12p70 through an ERK1/2 dependent mechanism, and that p38 MAPK is essential for MDDC-driven Th17 expansion. The data suggest that CyaA mediates an escape strategy for the bacterium, since it reduces Th1 immunity and increases Th17 responses thought to be responsible, when the response is exacerbated, for enhanced lung inflammation and injury.

  18. Pertussis: Microbiology, Disease, Treatment, and Prevention.

    Kilgore, Paul E; Salim, Abdulbaset M; Zervos, Marcus J; Schmitt, Heinz-Josef


    Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. PMID:27029594

  19. Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

    Fiorella; Orellana-Peralta; Michelle; Jacinto; Maria; J.Pons; Cláudia; Gomes; Carlos; Bada; Isabel; Reyes; Juana; del; Valle; Mendoza; Joaquim; Ruiz


    Objective:To characterize two Achromobaeter 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 Achromobaeter 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 Achromobaeter 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.

  20. Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

    Fiorella Orellana-Peralta; Michelle Jacinto; Maria J Pons; Cludia Gomes; Carlos Bada; Isabel Reyes; Juana del Valle Mendoza; Joaquim Ruiz


    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.

  1. Epithelial cell invasion and survival of Bordetella bronchiseptica.

    SCHIPPER, H; Krohne, G F; R. Gross


    Wild-type Bordetella bronchiseptica and a bvg mutant strain were used for invasion and survival experiments in human Caco-2 and A549 epithelial cells. Both bacterial strains were able to enter and persist within the host cells for at least a week. A significant proportion of the bacteria from both B. bronchiseptica strains but not from Bordetella pertussis were found free in the cytoplasm, suggesting different invasion and survival strategies of the two species in epithelial cells.

  2. Pertussis in young infants: clinical presentation, course and prevention.

    O'Riordan, A; Cleary, J; Cunney, R; Nicholson, A J


    Pertussis is a highly contagious disease caused by the Gram negative aerobic coccobacillus, Bordetella pertussis. It may present with severe symptoms and complications in infants and can pose a diagnostic challenge. This is a vaccine preventable illness covered by the Irish Childhood Immunisation Schedule. In 2011, a retrospective review was conducted of the records of infants, under six months, with a confirmed diagnosis of pertussis, presenting to Temple Street Children's University Hospital (TSCUH). A summery of notifications of pertussis nationally, from 2001 to 2012, was also examined as part of the study. This found that the rate of reported cases of pertussis has been increasing in Ireland. This national increase corresponds with a rising number of cases identified at TSCUH. Patients commonly presented severely ill with cyanosis and apnoea, on a background of prolonged cough. We found that pertussis was diagnosed rapidly in most cases however in all cases there was a delay to commencement of appropriate macrolide therapy. PMID:25226721

  3. Optimizing polymerase chain reaction testing for the diagnosis of pertussis: current perspectives

    Arbefeville S


    Full Text Available Sophie Arbefeville, Patricia Ferrieri Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA Abstract: Nucleic acid testing has revolutionized the diagnosis of pertussis in the clinical microbiology laboratory and has become the main avenue of testing for pertussis infection. Real-time polymerase chain reaction (RT-PCR is an important tool for timely diagnosis of pertussis and is more sensitive than culture. The most commonly amplified targets are the insertion-sequence (IS genes, which are found in multiple copies in the genome of Bordetella species. Some strains of Bordetella pertussis have more than 200 copies of IS481 in their genome. This high number of repeats allows RT-PCR assays to be very sensitive and makes nucleic acid testing two to three times more sensitive than culture. Despite these advantages, RT-PCR can give inaccurate results due to contamination or lack of specificity. Contamination can easily happen during specimen collection, DNA extraction, or nucleic acid amplification steps. To avoid contamination, laboratories need to have quality controls and good workflows in place. The poor specificity of the nucleic acid assays amplifying the IS genes is because they are found in various Bordetella species and, thus, not unique to a specific species. Bordetella holmesii, a more recently described Bordetella species found to be responsible for respiratory symptoms similar to pertussis in adolescents and adults, can be misidentified as B. pertussis in RT-PCR assays that amplify only the IS481 target. Use of multiple targets may improve specificity of RT-PCR assays for pertussis. In the past few years, the US Food and Drug Administration has cleared three commercial assays for the detection of B. pertussis in respiratory specimens. Several commercial assays and analyte-specific reagents, which are not US Food and Drug Administration cleared, are available for the detection of one

  4. The Lymphocytosis-Promoting Agent Pertussis Toxin Affects Virus Burden and Lymphocyte Distribution in the SIV-Infected Rhesus Macaque

    Pauza, C. David; Hinds, Paul W.; Yin, Cheng; McKechnie, Timothy S.; Hinds, Sarah B; Salvato, Maria S.


    Pertussis toxin from the gram-negative bacterium Bordetella pertussis is an ADP-ribosylase that modifies Gi proteins in mammalian lymphocytes and inhibits their capacity to traffic from blood into lymphoid tissues. We used this compound to induce lymphocytosis in rhesus macaques and to study its effects on SIV infection. Pertussis toxin injected at 25 μg/kg induced a transient lymphocytosis that peaked 3–8 days after administration and caused a rapid, transient decrease in the frequency of in...

  5. A retrospective study of acute pertussis in Hasan Sadikin Hospital-Indonesia

    Heda Melinda Nataprawira; Evelyn Phangkawira


    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.

  6. Incidence and reproduction numbers of pertussis: estimates from serological and social contact data in five European countries.

    Mirjam Kretzschmar


    Full Text Available BACKGROUND: Despite large-scale vaccination programmes, pertussis has remained endemic in all European countries and has been on the rise in many countries in the last decade. One of the reasons that have been discussed for the failure of vaccination to eliminate the disease is continued circulation of the pathogen Bordetella pertussis by mostly asymptomatic and mild infections in adolescents and adults. To understand the impact of asymptomatic and undiagnosed infection on the transmission dynamics of pertussis we analysed serological data from five European countries in combination with information about social contact patterns from five of those countries to estimate incidence and reproduction numbers. METHODS AND FINDINGS: We compared two different methods for estimating incidence from individual data on IgG pertussis toxin (PT titres. One method combines the cross-sectional surveys of titres with longitudinal information about the distribution of amplitude and decay rate of titres in a back-calculation approach. The second method uses age-dependent contact matrices and cross-sectional surveys of IgG PT titres to estimate a next generation matrix for pertussis transmission among age groups. The next generation approach allows for computation of basic reproduction numbers for five European countries. Our main findings are that the seroincidence of infections as estimated with the first method in all countries lies between 1% and 6% per annum with a peak in the adolescent age groups and a second lower peak in young adults. The incidence of infections as estimated by the second method lies slightly lower with ranges between 1% and 4% per annum. There is a remarkably good agreement of the results obtained with the two methods. The basic reproduction numbers are similar across countries at around 5.5. CONCLUSIONS: Vaccination with currently used vaccines cannot prevent continued circulation and reinfection with pertussis, but has shifted the bulk

  7. Pertussis (Whooping Cough) Vaccination

    ... Tdap= Tetanus-diphtheria-acellular Pertussis vaccine Pertussis (Whooping Cough) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet Share Compartir Whooping cough — known medically as pertussis — is a ...

  8. Extracellular DNA Is Essential for Maintaining Bordetella Biofilm Integrity on Abiotic Surfaces and in the Upper Respiratory Tract of Mice

    Conover, Matt S.; Mishra, Meenu; Deora, Rajendar


    Bacteria form complex and highly elaborate surface adherent communities known as biofilms which are held together by a self-produced extracellular matrix. We have previously shown that by adopting a biofilm mode of existence in vivo, the Gram negative bacterial pathogens Bordetella bronchiseptica and Bordetella pertussis are able to efficiently colonize and persist in the mammalian respiratory tract. In general, the bacterial biofilm matrix includes polysaccharides, proteins and extracellular...

  9. Protecting Newborns Against Pertussis: Treatment and Prevention Strategies.

    Salim, Abdulbaset M; Liang, Yan; Kilgore, Paul E


    Pertussis is a potentially severe respiratory disease, which affects all age groups from young infants to older adults and is responsible for an estimated 195,000 deaths occurred globally in 2008. Active research is ongoing to better understand the pathogenesis, immunology, and diagnosis of pertussis. For diagnosis, molecular assays (e.g., polymerase chain reaction) for detection of Bordetella pertussis have become more widely available and support improved outbreak detection. In children, pertussis vaccines have been incorporated into routine immunization schedules and deployed for pertussis outbreak control. Lower levels of vaccine coverage are now being observed in communities where vaccine hesitancy is rising. Additionally, recognition that newborn babies are at risk of pertussis in the USA and UK has led to recommendations to immunize pregnant women. Among adolescents and older adults in the USA, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular pertussis (Tdap) Vaccines are recommended, but substantial individual- and system-level barriers exist that will make achieving national Healthy People 2020 targets for immunization challenging. Current antimicrobial regimens for pertussis are focused on reducing the severity of disease, reducing rates of sequelae, and minimizing transmission of infection to susceptible individuals. Continued surveillance for pertussis will be important to identify opportunities for reducing young infants' exposure and reducing the impact of outbreaks among school-aged children. Laboratory-based surveillance for newly emerging strains of B. pertussis will be important to identify strains that may evade protection elicited by currently available vaccines. Efforts to develop new-generation pertussis vaccines should be considered now in anticipation of vaccine development programs, which may require ten or more years to deliver a licensed vaccine. PMID:26542059

  10. Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

    Šebo, Peter; Osička, Radim; Mašín, Jiří


    Roč. 13, č. 10 (2014), s. 1215-1227. ISSN 1476-0584 R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : adenylate cyclase toxin * antigen delivery * Bordetella pertussis Subject RIV: EE - Microbiology, Virology Impact factor: 4.210, year: 2014

  11. A real-time PCR assay with improved specificity for detection and discrimination of all clinically relevant Bordetella species by the presence and distribution of three Insertion Sequence elements

    Ossewaarde Jacobus M


    Full Text Available Abstract Background In Dutch laboratories molecular detection of B. pertussis and B. parapertussis is commonly based on insertion sequences IS481 and IS1001, respectively. Both IS elements are more widely spread among Bordetella species. Both Bordetella holmesii, and B. bronchiseptica can harbour IS481. Also, IS1001 is found among B. bronchiseptica. IS481, and IS1001 based PCR thus lacks specificity when used for detection of specific Bordetella spp. Findings We designed a PCR based on IS1002, another IS element that is present among Bordetella species, and exploited it as a template in combination with PCR for IS481, and IS1001. In combining the PCRs for IS481, IS1001, and IS1002, and including an inhibition control, we were able to detect and discriminate all clinically relevant Bordetella species. Conclusions We developed an improved PCR method for specific detection of B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica.

  12. Clinical presentation of pertussis in fully immunized children in Lithuania

    Bernatoniene Genovaite


    Full Text Available Abstract Background In Lithuania, the vaccination coverage against pertussis is high. Nevertheless, there is a significant increase in pertussis cases in fully immunized children. The aim of our study was to determine the frequency of classical symptoms of laboratory confirmed pertussis and describe its epidemiology in children fully vaccinated against pertussis. Methods From May to December 2001, 70 children aged 1 month to 15 years, suffering from prolonged cough were investigated in the Centre of Paediatrics, Vilnius University Children's Hospital. The collected information included personal data, vaccination history, clinical symptoms of the current illness, and treatment before hospitalization. At the admission to the hospital blood samples were taken from all studied children for Bordetella pertussis IgM and IgA. Results A total of 53 (75.7% of the 70 recruited patients with prolonged cough showed laboratory evidence of pertussis. 32 of them were fully vaccinated with whole cell pertussis vaccine (DTP. The age of fully vaccinated patients varied from 4 to 15 years (average 10.9 ± 3.1; median 11. The time period between the last vaccination dose (fourth and the clinical manifestation of pertussis was 2.6–13 years (average 8.9 ± 3.0; median 9. More than half of the children before the beginning of pertussis were in contact with persons suffering from long lasting cough illness in the family, school or day-care center. The mean duration from onset of pertussis symptoms until hospitalization was 61.4 ± 68.3 days (range, 7 to 270 days; median 30. For 11 patients who had had two episodes (waves of coughing, the median duration of cough was 90 days, and for 21 with one episode 30 days (p Conclusion Fully vaccinated children fell ill with pertussis at the median of 11 years old, 9 years following pertussis vaccination. More than half of the children could catch pertussis at home, at school or day-care center. Clinical picture of pertussis in

  13. The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae

    Schneiker-Bekel Susanne


    Full Text Available Abstract Background Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. Results In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. Conclusion The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches.

  14. Bordetella bronchiseptica Pneumonia in an Infant and Genetic Comparison of Clinical Isolates with Veterinary Kennel Cough Vaccines

    An infant with recurrent episodes of respiratory failure was diagnosed with pertussis based on immunofluorescence testing, but culture revealed macrolide-resistant Bordetella bronchiseptica. Genetic analysis demonstrated that the child was not infected with a kennel cough vaccine strain, although th...

  15. Pertussis (Whooping Cough) Outbreaks

    ... 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 ...

  16. Pertussis (Whooping Cough) Complications

    ... 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 ...

  17. Whooping Cough (Pertussis)

    ... 5 Things to Know About Zika & Pregnancy Whooping Cough (Pertussis) KidsHealth > For Parents > Whooping Cough (Pertussis) Print A A A Text Size What's ... the Doctor en español La tos ferina Whooping cough (pertussis) is an infection of the respiratory system ...

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

    Schure, R.M.


    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

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

    Celso Pérez-Bolaños


    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.

  20. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

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

  1. Bordetella protein toxins

    Mašín, Jiří; Šebo, Peter; Locht, C.

    New York : Elsevier, Academic Press, 2006, s. 291-309. ISBN 978-0-12-088445-2 R&D Projects: GA AV ČR IAA5020406; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50200510 Keywords : pertussis toxin * adenylate cyclase toxin * dermonecrotic toxin Subject RIV: EE - Microbiology, Virology

  2. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels.

    Ahmad, Shaikh Meshbahuddin; Alam, Jahangir; Afsar, Nure Alam; Huda, Nazmul; Kabir, Yearul; Qadri, Firdausi; Raqib, Rubhana; Stephensen, Charles B


    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7-9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy. PMID:27176823

  3. Epidemiological Aspects of Pertussis among Adults and Adolescents in a Korean Outpatient Setting: A Multicenter, PCR-Based Study

    Park, Sunghoon; Lee, Sun Hwa; Seo, Ki-Hyun; SHIN, KYEONG-CHEOL; Park, Yong Bum; Lee, Myung Goo; Yoo, Kwang Ha; Kim, Hui Jung; Park, Jae Seuk; Cho, Jae Hwa; Ko, Yongchun; Lee, Soo-Keol; Cheon, Ki Tae; Kim, Do Il; Ha, Jun Wook


    Epidemiological data of Bordetella pertussis infection among adolescents and adults are limited in Korea. Patients (≥ 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in Korea. Nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and for bacteriologic culture. In total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for B. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age d...

  4. Extracellular DNA is essential for maintaining Bordetella biofilm integrity on abiotic surfaces and in the upper respiratory tract of mice.

    Matt S Conover

    Full Text Available Bacteria form complex and highly elaborate surface adherent communities known as biofilms which are held together by a self-produced extracellular matrix. We have previously shown that by adopting a biofilm mode of existence in vivo, the gram negative bacterial pathogens Bordetella bronchiseptica and Bordetella pertussis are able to efficiently colonize and persist in the mammalian respiratory tract. In general, the bacterial biofilm matrix includes polysaccharides, proteins and extracellular DNA (eDNA. In this report, we investigated the function of DNA in Bordetella biofilm development. We show that DNA is a significant component of Bordetella biofilm matrix. Addition of DNase I at the initiation of biofilm growth inhibited biofilm formation. Treatment of pre-established mature biofilms formed under both static and flow conditions with DNase I led to a disruption of the biofilm biomass. We next investigated whether eDNA played a role in biofilms formed in the mouse respiratory tract. DNase I treatment of nasal biofilms caused considerable dissolution of the biofilm biomass. In conclusion, these results suggest that eDNA is a crucial structural matrix component of both in vitro and in vivo formed Bordetella biofilms. This is the first evidence for the ability of DNase I to disrupt bacterial biofilms formed on host organs.

  5. Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens

    Park Jihye


    Full Text Available Abstract Background The classical Bordetella subspecies are phylogenetically closely related, yet differ in some of the most interesting and important characteristics of pathogens, such as host range, virulence and persistence. The compelling picture from previous comparisons of the three sequenced genomes was of genome degradation, with substantial loss of genome content (up to 24% associated with adaptation to humans. Results For a more comprehensive picture of lineage evolution, we employed comparative genomic and phylogenomic analyses using seven additional diverse, newly sequenced Bordetella isolates. Genome-wide single nucleotide polymorphism (SNP analysis supports a reevaluation of the phylogenetic relationships between the classical Bordetella subspecies, and suggests a closer link between ovine and human B. parapertussis lineages than has been previously proposed. Comparative analyses of genome content revealed that only 50% of the pan-genome is conserved in all strains, reflecting substantial diversity of genome content in these closely related pathogens that may relate to their different host ranges, virulence and persistence characteristics. Strikingly, these analyses suggest possible horizontal gene transfer (HGT events in multiple loci encoding virulence factors, including O-antigen and pertussis toxin (Ptx. Segments of the pertussis toxin locus (ptx and its secretion system locus (ptl appear to have been acquired by the classical Bordetella subspecies and are divergent in different lineages, suggesting functional divergence in the classical Bordetellae. Conclusions Together, these observations, especially in key virulence factors, reveal that multiple mechanisms, such as point mutations, gain or loss of genes, as well as HGTs, contribute to the substantial phenotypic diversity of these versatile subspecies in various hosts.

  6. Pertussis: Disease Villain!


    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.

  7. Pertussis Frequently Asked Questions

    ... and infection . Q: Do pertussis vaccines protect from serious disease? A: If you've been vaccinated and get ... of any age can catch this very contagious disease. But if you've been vaccinated, your infection is usually less serious. If you or your child develops a cold ...

  8. Molecular evolution of the two-component system BvgAS involved in virulence regulation in Bordetella.

    Julien Herrou

    Full Text Available The whooping cough agent Bordetella pertussis is closely related to Bordetella bronchiseptica, which is responsible for chronic respiratory infections in various mammals and is occasionally found in humans, and to Bordetella parapertussis, one lineage of which causes mild whooping cough in humans and the other ovine respiratory infections. All three species produce similar sets of virulence factors that are co-regulated by the two-component system BvgAS. We characterized the molecular diversity of BvgAS in Bordetella by sequencing the two genes from a large number of diverse isolates. The response regulator BvgA is virtually invariant, indicating strong functional constraints. In contrast, the multi-domain sensor kinase BvgS has evolved into two different types. The pertussis type is found in B. pertussis and in a lineage of essentially human-associated B. bronchiseptica, while the bronchiseptica type is associated with the majority of B. bronchiseptica and both ovine and human B. parapertussis. BvgS is monomorphic in B. pertussis, suggesting optimal adaptation or a recent population bottleneck. The degree of diversity of the bronchiseptica type BvgS is markedly different between domains, indicating distinct evolutionary pressures. Thus, absolute conservation of the putative solute-binding cavities of the two periplasmic Venus Fly Trap (VFT domains suggests that common signals are perceived in all three species, while the external surfaces of these domains vary more extensively. Co-evolution of the surfaces of the two VFT domains in each type and domain swapping experiments indicate that signal transduction in the periplasmic region may be type-specific. The two distinct evolutionary solutions for BvgS confirm that B. pertussis has emerged from a specific B. bronchiseptica lineage. The invariant regions of BvgS point to essential parts for its molecular mechanism, while the variable regions may indicate adaptations to different lifestyles. The

  9. Lymphocyte receptors for pertussis toxin

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes

  10. Pertussis outbreak in Papua New Guinea: the challenges of response in a remote geo-topographical setting

    William Lagani


    Full Text Available Introduction: A large outbreak of pertussis was detected during March 2011 in Goilala, a remote district of the Central Province in Papua New Guinea, characterized by rugged topography with no road access from the provincial headquarters. This outbreak investigation highlights the difficulties in reporting and responding to outbreaks in these settings.Method: The suspected pertussis cases, reported by health workers from the Ononge health centre area, were investigated and confirmed for the presence of Bordetella pertussis DNA using the polymerase chain reaction (PCR method.Results: There were 205 suspected pertussis cases, with a case-fatality rate (CFR of 3%. All cases were unvaccinated. The Central Province conducted a response vaccination programme providing 65% of children less than five years of age with diphtheria–pertussis-tetanus-HepB-Hib vaccine at a cost of US$ 12.62 per child.Discussion: The incurred cost of vaccination in response to this outbreak was much higher than the US$ 3.80 per child for routine outreach patrol. To prevent further outbreaks of vaccine-preventable diseases in these areas, local health centres must ensure routine vaccination is strengthened through the “Reaching Every District” initiative of the National Department of Health.

  11. Tetanus, Diphtheria, and Pertussis Vaccines

    Tetanus, diphtheria, and pertussis (whooping cough) are serious bacterial infections. Tetanus causes painful tightening of the muscles, usually all ... older children and adults. DT prevents diphtheria and tetanus. It is for children younger than seven who ...

  12. Tetanus, Diphtheria, and Pertussis Vaccines

    Tetanus, diphtheria, and pertussis (whooping cough) are serious bacterial infections. Tetanus causes painful tightening of the muscles, usually all ... It can lead to "locking" of the jaw. Diphtheria usually affects the nose and throat. Whooping cough ...

  13. Whooping Cough and the Pertussis Vaccine

    ... someone with pertussis, do I need to do anything? Yes, it’s recommended that anyone who comes in ... get very sick with pertussis infection. Is there anything I should ask my health care provider before ...

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

    Full Text Available Immunizations Pertussis (Whooping Cough) One family's struggles with pertussis We provide this video in a variety of ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

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

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

  16. Development of a PCR assay for identification of Bordetella hinzii

    Bordetella hinzii infects primarily poultry and immunocompromised humans. Although initially thought to be nonpathogenic in poultry, it was recently shown that some strains cause disease in turkey poults indistinguishable from the clinical presentation of turkey coryza caused by Bordetella avium. ...

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

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


    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.

  18. Molecular analysis of the bvg-repressed urease of Bordetella bronchiseptica.

    McMillan, D J; Shojaei, M; Chhatwal, G S; Guzmán, C A; Walker, M J


    Bordetella bronchiseptica is a ureolytic mammalian respiratory pathogen. We have investigated the regulation of urease in B. bronchiseptica and the potential role of this enzyme in eukaryotic invasion and intracellular survival. Our results indicate urease is a bordetella virulence repressed gene. Urease activity in virulent B. bronchiseptica BB7865 is up-regulated from basal levels by 5 gl1 magnesium sulphate at 37 degrees C. At 30 degrees C, urease activity remained at basal levels, even in the presence on magnesium sulphate, suggesting a second temperature dependent mechanism of urease regulation was also operating. Urease was not inducible by 10 mM urea nor up-regulated in nitrogen limiting conditions. To evaluate the role of urease in intracellular invasion and survival urease-negative mutants of B. bronchiseptica BB7865 and B. bronchiseptica BB7866 were created by transposon mutagenesis, and compared to the urease-positive parental strains in a HeLa cell invasion assay. We demonstrate that increasing the concentration of urea in the assay increased survival of the urease-positive but not urease-negative strains after 24 h, suggesting that urease does have a role in intracellular survival. Partial DNA sequence analysis of an 11.0 kb EcoRI DNA fragment encoding urease activity revealed an open reading frame containing 50%, 45%, 45%, and 41% homology to the UreA urease subunit protein of Klebsiella aerogenes, Proteus vulgaris, Helicobacter pylori and Proteus mirabilis respectively. We also show Bordetella pertussis to contain sequences homologous with a DNA probe containing the gene encoding UreA of B. bronchiseptica indicating the possible presence of cryptic urease genes in this species. PMID:8938644

  19. Limitaciones del ensayo de toxicidad específica para el componente pertussis de células completas

    Vicente Perdomo


    Full Text Available Las vacunas que contienen células inactivadas de Bordetella pertussis se han utilizado con efectividad en los Programas Nacionales de Inmunización de todo el mundo. Pese a su reconocida eficacia, ellas se caracterizan por su elevada reactogenicidad, atribuible a la presencia de componentes como toxina pertussis y endotoxinas. Paramonitorear la seguridad de estas vacunas existe el ensayo de ganancia en peso en ratones, el cual ha sido criticado por su inespecificidad, poca sensibilidad y alta variabilidad. Basado en lo anterior, el Laboratorio Nacional de Biológicos del Centro Estatal para el Control de de la Calidad de los Medicamentos en Cuba, decidió evaluar la relevancia de esta prueba para la liberación de los lotes de la vacuna DPT. Para ello se estimó la sensibilidad del método para detectar diferentes concentraciones de endotoxinas y toxina pertussis, así como la variabilidad entre ensayos. Los resultados de este trabajo mostraron que sólo altas concentraciones de endotoxinas y toxina pertussis, muy superiores a las habituales en las vacunas DPT, provocan una disminución de la ganancia en peso promedio y un fallo en la especificación de la prueba. Este elemento y la inherente variabilidad de este método resultaron claves en la decisión de no utilizarlo para la liberación nacional de lotes de la vacuna DPT.

  20. Limitaciones del ensayo de toxicidad específica para el componente pertussis de células completas

    Mario Landys Chovel


    Full Text Available Las vacunas que contienen células inactivadas de Bordetella pertussis se han utilizado con efectividad en los Programas Nacionales de Inmunización de todo el mundo. Pese a su reconocida eficacia, ellas se caracterizan por su elevada reactogenicidad, atribuible a la presencia de componentes como toxina pertussis y endotoxinas. Para monitorear la seguridad de estas vacunas existe el ensayo de ganancia en peso en ratones, el cual ha sido criticado por su inespecificidad, poca sensibilidad y alta variabilidad. Basado en lo anterior, el Laboratorio Nacional de Biológicos del Centro Estatal para el Control de de la Calidad de los Medicamentos en Cuba, decidió evaluar la relevancia de esta prueba para la liberación de los lotes de la vacuna DPT. Para ello se estimó la sensibilidad del método para detectar diferentes concentraciones de endotoxinas y toxina pertussis, así como la variabilidad entre ensayos. Los resultados de este trabajo mostraron que sólo altas concentraciones de endotoxinas y toxina pertussis, muy superiores a las habituales en las vacunas DPT, provocan una disminución de la ganancia en peso promedio y un fallo en la especificación de la prueba. Este elemento y la inherente variabilidad de este método resultaron claves en la decisión de no utilizarlo para la liberación nacional de lotes de la vacuna DPT.

  1. European Sero-Epidemiology Network 2: standardisation of immunoassay results for pertussis requires homogeneity in the antigenic preparations.

    Giammanco, Anna; Nardone, Antony; Pebody, Richard; Kafatos, George; Andrews, Nick; Chiarini, Alfredo; Taormina, Susanna; de Ory, Fernando; Prosenc, Katarina; Krize, Bohumir; Hallander, Hans; Ljungman, Margaretha; Marva, Esther; Tsakris, Athanassios; O'Flanagan, Darina; Schneider, François; Griskevicius, Algirdas; Vranckx, Robert; Karacs, Ildiko


    A standardisation process, already developed during the earlier European Sero-Epidemiology Network (ESEN) project, was employed with a more robust algorithm to harmonise results of pertussis serological assays performed in 12 European and non-European countries. Initially, results from each country's own assay were compared with those obtained at the reference laboratory by means of an in-house pertussis toxin (PT)-based ELISA: seven countries used in-house or commercial PT-ELISAs; the other countries used assays based on Bordetella pertussis whole cell extracts (WCE) (three countries) or on combined PT-FHA (filamentous haemagglutinin) antigenic preparations (two countries). The WCE assays, although admitted for diagnostic purposes, confirmed their low correlation with the PT-ELISAs and their results could not be used for standardisation; the PT-FHA ELISAs gave results that were suitable for standardisation in one country but unsatisfactory in the other; the use of purified PT in serological assays confirmed its better reliability than other preparations and all PT-ELISAs results could be calibrated against those of the reference centre. In the standardisation process two high-titre cut-offs indicative of likelihood of recent infection (from within 4 weeks of disease onset up to 1 year after) were included for evaluations as they are suggested to be more useful, for the sero-epidemiological assays of immunity to pertussis, than the cut-off of protection, commonly employed, but still not defined for pertussis. Providing PT-ELISAs are used, standardisation of pertussis assay results is always possible and, when standardisation is performed, evaluation and comparison of the impact of different interventions can be also allowed, by measuring at the distribution of high antibody titres in the populations. PMID:18602434

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

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

  3. La vacunación contra pertussis: Estado actual y perspectivas futuras

    Celso Pérez-Bolaños


    Full Text Available La tosferina o pertussis es una enfermedad producida por la bacteria Gram negativa Bordetella pertussis y constituye actualmente un problema de salud a escala mundial, siendo la población infantil la más vulnerable dentro de los grupos de riesgo. Suele ser fatal en niños menores de un año, debido a que la tos paroxística característica bloquea las vías respiratorias, lo cual provoca la asfixia y la muerte. Adicionalmente, se observan eventos adversos o complicaciones serias de la enfermedad tales como neumonías bacterianas secundarias, epilepsias, encefalopatía, apnea e hipertensión pulmonar. En la actualidad se aplican programas extensivos de vacunación contra pertussis en todo el mundo, de modo que la enfermedad está considerada como relativamente bien controlada. Según informes de la Organización Mundial de la Salud, cerca del 82 % de toda la población infantil mundial recibió las tres dosis de la vacuna de pertussis en 2008. La vacunación global contra pertussis en ese año evitó cerca de 687 000 muertes por la enfermedad. Sin embargo, se ha observado que ocurre un resurgimiento de ella a escala mundial, así como una prevalencia en zonas del mundo donde la vacunación es pobre. El presente trabajo tuvo como objetivo presentar una revisión acerca de los problemas inherentes a la vacunación contra esta enfermedad en el contexto actual de su resurgimiento a escala universal, la forma de enfocarlos y resolverlos, para su aplicación en Cuba en caso necesario. La vacunación contra pertussis necesita de nuevos enfoques dirigidos a la eliminación de un flagelo que afecta primordialmente a la población infantil, que es el futuro de la humanidad. La solución del problema parece ser la búsqueda de nuevas vacunas más eficaces y la extensión de los esquemas de vacunación a la población de adolescentes y adultos que rodean a los infantes, así como a las mujeres en estado de gestación y a los recién nacidos.

  4. Pertussis toxin analog with reduced enzymatic and biological activities is a protective immunogen.

    Kimura, A; Mountzouros, K T; Schad, P A; Cieplak, W; Cowell, J L


    Bordetella pertussis TOX3201 has a 12-base-pair insertion in the S1 subunit gene of pertussis toxin (PTX), which encodes for a 4-amino-acid insertion between residues 107 and 108 of the mature S1 subunit (Black et al., Science 240:656-659, 1988). This mutant strain has been shown to secrete a holotoxin analog of PTX, designated CRM3201, with reduced ADP-ribosyltransferase activity. In the present study, we evaluated the biochemical, biological, and immunoprotective activities of purified CRM3201. Assay of enzymatic activities showed that CRM3201 had 20 to 30% of the ADP-ribosyltransferase activity and 55 to 60% of the NAD glycohydrolase activity of native PTX. CRM3201, however, had only 2 to 6% of the activity of PTX in clustering CHO cells, promoting leukocytosis, inducing histamine sensitization, and potentiating an anaphylactic response to bovine serum albumin. In contrast, activities associated with the B oligomer (binding to fetuin, hemagglutination of goose erythrocytes, and lymphocyte mitogen activity) were comparable to those of native PTX. Injection of BALB/c mice with CRM3201 mixed with Al(OH)3 elicited high titers of antibody to PTX (as measured by enzyme-linked immunosorbent assay), which neutralized a leukocytosis-promoting dose of PTX in these mice and neutralized PTX in a CHO cell assay. Passive transfer of the anti-CRM3201 antibody protected 20-day-old Swiss-Webster mice against a lethal aerosol challenge with B. pertussis 18323. Active immunization with CRM3201 significantly reduced lung colonization in adult BALB/c mice with a B. pertussis respiratory infection. These results demonstrate (i) that the reduced ADP-ribosyltransferase activity of CRM3201 is associated with reductions in certain biological and toxic activities of PTX (the enzymatic and biological activities are not, however, totally concordant); (ii) that CRM3201 possesses a functional B oligomer; and (iii) that CRM3201 can induce toxin-neutralizing antibodies which protect mice

  5. Pertussis Vaccine Trials in the 1990s

    Lambert, Linda C.


    The significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the introduction of inactivated whole-bacterial-cell vaccines in the middle of the 20th century. Although these vaccines were effective in reducing the incidence of pertussis in the countries that implemented their widespread use, increasing concerns about pertussis vaccine–associated adverse events led the development of acellul...

  6. The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

    Bíbová, Ilona; Škopová, Karolína; Mašín, Jiří; Černý, Ondřej; Hot, D.; Šebo, Peter; Večerek, Branislav


    Roč. 81, č. 11 (2013), s. 4081-4090. ISSN 0019-9567 R&D Projects: GA ČR(CZ) GAP302/11/1940; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : ADENYLATE-CYCLASE TOXIN * ISLET-ACTIVATING PROTEIN * ESCHERICHIA-COLI HFQ Subject RIV: EC - Immunology Impact factor: 4.156, year: 2013

  7. Internation of Bordetella pertussis Adenylate Cyclase with CD11b/CD18

    El-Azami-El-Idrisi, M.; Bauche, C.; Loucká, Jiřina; Osička, Radim; Šebo, Peter; Ladant, D.; Leclerc, C.


    Roč. 278, č. 40 (2003), s. 38514-38521. ISSN 0021-9258 R&D Projects: GA AV ČR IPP1050128; GA ČR GA310/01/0934; GA AV ČR IAA5020907 Grant ostatní: GA by National Institutes of Health Grant(XX) 55000334; GA QLK2-CT-1999(XX) 00556 Institutional research plan: CEZ:AV0Z5020903 Keywords : cyaa * rtx * cd11b Subject RIV: EE - Microbiology, Virology Impact factor: 6.482, year: 2003

  8. Inflammasome Activation by Adenylate Cyclase Toxin Directs Th17 Responses and Protection against Bordetella pertussis

    Dunne, A.; Ross, P. J.; Pospíšilová, Eva; Mašín, Jiří; Meaney, A.; Sutton, C. E.; Iwakura, Y.; Tschopp, J.; Šebo, Peter; Mills, K. H. G.


    Roč. 187, č. 3 (2010), s. 1711-1719. ISSN 0022-1767 R&D Projects: GA ČR GA310/08/0447; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : ADAPTIVE IMMUNE-RESPONSES * IL-17-PRODUCING T-CELLS * HOST-DEFENSE Subject RIV: EC - Immunology Impact factor: 5.745, year: 2010

  9. Acylation of lysine 983 is sufficient for toxin activity of Bordetella pertussis adenylate cyclase

    Basar, T.; Havlíček, Vladimír; Bezoušková, Silvia; Hackett, M.; Šebo, Peter


    Roč. 276, č. 1 (2001), s. 348-354. ISSN 0021-9258 R&D Projects: GA ČR GA310/98/0432; GA ČR GV310/96/K102; GA AV ČR IAA5020907; GA MŠk ME 167; GA MŠk VS96149 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EE - Microbiology, Virology Impact factor: 7.258, year: 2001

  10. Phenotypic variation and modulation in Bordetella bronchiseptica.

    Peppler, M S; Schrumpf, M E


    Most of the isolates of Bordetella bronchiseptica obtained by this laboratory possessed a characteristic colonial morphology when grown on Bordet- Gengou agar (BGA) at 37 degrees C. The colonies appeared domed (Dom+) with a smooth colonial surface (Scs+) and a clear zone of hemolysis ( Hly +). From these Dom+ Scs+ Hly + BGA colony types arose flat (Dom-), smooth colonial surface (Scs+) and nonhemolytic ( Hly -) variants at frequencies of 10(-2) to 10(-3). Isogenic pairs of Dom+ Scs+ Hly + and...

  11. A PCR assay for identification of Bordetella hinzii

    Bordetella hinzii infects primarily poultry and immunocompromised humans. Although initially thought to be nonpathogenic in poultry, it was recently shown that some strains cause disease in turkey poults indistinguishable from the clinical presentation of turkey coryza caused by Bordetella avium. B....

  12. Bordetella bronchiseptica and fatal pneumonia of dogs and cats

    Bordetella bronchiseptica frequently causes nonfatal tracheobronchitis, but its role in fatal pneumonia is less well-studied. The objectives of this study were to identify the frequency of Bordetella bronchiseptica infection in fatal cases of bronchopneumonia in dogs and cats and to compare the diag...

  13. Strategies to decrease pertussis transmission to infants.

    Forsyth, Kevin; Plotkin, Stanley; Tan, Tina; Wirsing von König, Carl Heinz


    The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants authority guidelines. These efforts are anticipated to minimize pertussis transmission to vulnerable infants, although real-world effectiveness data are limited. Countries should educate lay and medical communities on pertussis and introduce robust surveillance practices while implementing these protective strategies. PMID:25963002

  14. FastStats: Whooping Cough or Pertussis

    ... Submit What's this? Submit Button NCHS Home Whooping Cough or Pertussis Recommend on Facebook Tweet Share Compartir ... the U.S. Morbidity Reported number of new whooping cough cases: 28,639 (2013) Source: Health, United States, ...

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

    Full Text Available ... One family's struggles with pertussis We provide this video in a variety of formats and lengths for use by your organization free-of-charge. Branded videos contain the "PKIDs.ORG" end slate; unbranded videos ...

  16. Genomic island excisions in Bordetella petrii

    Levillain Erwan


    Full Text Available Abstract Background Among the members of the genus Bordetella B. petrii is unique, since it is the only species isolated from the environment, while the pathogenic Bordetellae are obligately associated with host organisms. Another feature distinguishing B. petrii from the other sequenced Bordetellae is the presence of a large number of mobile genetic elements including several large genomic regions with typical characteristics of genomic islands collectively known as integrative and conjugative elements (ICEs. These elements mainly encode accessory metabolic factors enabling this bacterium to grow on a large repertoire of aromatic compounds. Results During in vitro culture of Bordetella petrii colony variants appear frequently. We show that this variability can be attributed to the presence of a large number of metastable mobile genetic elements on its chromosome. In fact, the genome sequence of B. petrii revealed the presence of at least seven large genomic islands mostly encoding accessory metabolic functions involved in the degradation of aromatic compounds and detoxification of heavy metals. Four of these islands (termed GI1 to GI3 and GI6 are highly related to ICEclc of Pseudomonas knackmussii sp. strain B13. Here we present first data about the molecular characterization of these islands. We defined the exact borders of each island and we show that during standard culture of the bacteria these islands get excised from the chromosome. For all but one of these islands (GI5 we could detect circular intermediates. For the clc-like elements GI1 to GI3 of B. petrii we provide evidence that tandem insertion of these islands which all encode highly related integrases and attachment sites may also lead to incorporation of genomic DNA which originally was not part of the island and to the formation of huge composite islands. By integration of a tetracycline resistance cassette into GI3 we found this island to be rather unstable and to be lost from

  17. Effect of different detoxification procedures on the residual pertussis toxin activities in vaccines.

    Yuen, Chun-Ting; Asokanathan, Catpagavalli; Cook, Sarah; Lin, Naomi; Xing, Dorothy


    Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis and its detoxified form is one of the major protective antigens in vaccines against whooping cough. Ideally, PTx in the vaccine should be completely detoxified while still preserving immunogenicity. However, this may not always be the case. Due to multilevel reaction mechanisms of chemical detoxification that act on different molecular sites and with different production processes, it is difficult to define a molecular characteristic of a pertussis toxoid. PTx has two functional distinctive domains: the ADP-ribosyltransferase enzymatic subunit S1 (A-protomer) and the host cell binding carbohydrate-binding subunits S2-5 (B-oligomer); and in this study, we investigated the effect of different detoxification processes on these two functional activities of the residual PTx in toxoids and vaccines currently marketed worldwide using a recently developed in vitro biochemical assay system. The patho-physiological activities in these samples were also estimated using the in vivo official histamine sensitisation tests. Different types of vaccines, detoxified by formaldehyde, glutaraldehyde or by both, have different residual functional and individual baseline activities. Of the vaccines tested, PT toxoid detoxified by formaldehyde had the lowest residual PTx ADP-ribosyltransferase activity. The carbohydrate binding results detected by anti-PTx polyclonal (pAb) and anti-PTx subunits monoclonal antibodies (mAb) showed specific binding profiles for toxoids and vaccines produced from different detoxification methods. In addition, we also demonstrated that using pAb or mAb S2/3 as detection antibodies would give a better differential difference between these vaccine lots than using mAbs S1 or S4. In summary, we showed for the first time that by measuring the activities of the two functional domains of PTx, we could characterise pertussis toxoids prepared from different chemical detoxification

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

    Aroldo P. de Carvalho


    Full Text Available OBJETIVOS: A utilização da vacina de células inteiras contra coqueluche levou a uma redução significativa na incidência da enfermidade na criança. Essa mudança no perfil epidemiológico resultou em aumento no número de casos em adolescentes e adultos, conseqüente à perda da imunidade conferida pela doença ou por vacina após cerca de 10 anos, e em lactentes não imunizados ou incompletamente imunizados. O licenciamento da vacina tríplice bacteriana contra difteria, tétano e coqueluche acelular, com formulação específica para maiores de 10 anos de idade (dTpa, apontou para a possibilidade do controle da coqueluche na população das faixas etárias mais acometidas nos últimos anos. FONTE DE DADOS: As informações foram coletadas na base de dados MEDLINE. A pesquisa foi limitada ao período compreendido entre janeiro de 1995 a janeiro de 2006. SÍNTESE DOS DADOS: Estão licenciadas em alguns países duas vacinas dTpa para a faixa etária maior de 10 anos de idade, uma delas contendo cinco componentes imunogênicos da Bordetella pertussis: toxina pertússis, hemaglutinina filamentosa, fimbrias 2 e 3 e pertactina, e a outra contendo três componentes: pertactina, hemaglutinina filamentosa e toxina pertússis inativada, sendo esta a única apresentação licenciada até o momento no Brasil. Embora a composição das duas vacinas seja diferente, os estudos mostram que a imunogenicidade e a eficácia são semelhantes. Entretanto, alguns autores enfatizam que existem dificuldades para a realização de uma avaliação mais precisa da resposta imunológica à vacina e sua duração. Vários países já recomendam de rotina o uso da vacina dTpa para adolescentes. O Canadá ampliou a população alvo até 54 anos de idade. A orientação é de que esse grupo receba uma dose da vacina como reforço do esquema básico de imunização. Isso é fundamentado em resultados de estudos que mostram que a duração da imunidade induzida pela

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

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


    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 in-vivo worden waargenomen in jonge en volwassen ratten behandeld met hoge doseringen pertussis toxine, cellulair (DKTP-vaccin) en acellulair pertussis vaccin en Haemoinfluenza type b vaccin. Deze e...

  20. Recognizing and Preventing Whooping Cough 2 (Pertussis)


    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.

  1. Occurrence of Bordetella infection in pigs in northern India.

    Kumar, Sandeep; Singh, Bhoj R; Bhardwaj, Monika; Singh, Vidya


    Bordetella bronchiseptica infection causing atrophic rhinitis in pigs is reported from almost all countries. In the present study, occurrence of Bordetella infection in apparently healthy pigs was determined in 392 pigs sampled to collect 358 serum samples and 316 nasal swabs from Northern India by conventional bacterioscopy, detection of antigen with multiplex polymerase chain reaction (mPCR), and detection of antibodies with microagglutination test (MAT) and enzyme linked immune-sorbent assay (ELISA). Bordetella bronchiseptica could be isolated from six (1.92%) nasal swabs. Although isolates varied significantly in their antimicrobial sensitivity, they had similar plasmid profile. The genus specific and species specific amplicons were detected from 8.2% and 4.4% nasal swabs using mPCR with alc gene (genus specific) and fla gene and fim2 gene (species specific) primers, respectively. Observations revealed that there may be other bordetellae infecting pigs because about 50% of the samples positive using mPCR for genus specific amplicons failed to confirm presence of B. bronchiseptica. Of the pig sera tested with MAT and ELISA for Bordetella antibodies, 67.6% and 86.3% samples, respectively, were positive. For antigen detection mPCR was more sensitive than conventional bacterioscopy while for detection of antibodies neither of the two tests (MAT and ELISA) had specificity in relation to antigen detection. Study indicated high prevalence of infection in swine herds in Northern India. PMID:24688547

  2. Occurrence of Bordetella Infection in Pigs in Northern India

    Sandeep Kumar


    Full Text Available Bordetella bronchiseptica infection causing atrophic rhinitis in pigs is reported from almost all countries. In the present study, occurrence of Bordetella infection in apparently healthy pigs was determined in 392 pigs sampled to collect 358 serum samples and 316 nasal swabs from Northern India by conventional bacterioscopy, detection of antigen with multiplex polymerase chain reaction (mPCR, and detection of antibodies with microagglutination test (MAT and enzyme linked immune-sorbent assay (ELISA. Bordetella bronchiseptica could be isolated from six (1.92% nasal swabs. Although isolates varied significantly in their antimicrobial sensitivity, they had similar plasmid profile. The genus specific and species specific amplicons were detected from 8.2% and 4.4% nasal swabs using mPCR with alc gene (genus specific and fla gene and fim2 gene (species specific primers, respectively. Observations revealed that there may be other bordetellae infecting pigs because about 50% of the samples positive using mPCR for genus specific amplicons failed to confirm presence of B. bronchiseptica. Of the pig sera tested with MAT and ELISA for Bordetella antibodies, 67.6% and 86.3% samples, respectively, were positive. For antigen detection mPCR was more sensitive than conventional bacterioscopy while for detection of antibodies neither of the two tests (MAT and ELISA had specificity in relation to antigen detection. Study indicated high prevalence of infection in swine herds in Northern India.

  3. Confocal microscopy study of pertussis toxin and toxoids on CHO-cells

    Tan, Yajun; Fleck, Roland A.; Asokanathan, Catpagavalli; Yuen, Chun-Ting; Xing, Dorothy; Zhang, Shumin; Wang, Junzhi


    Pertussis toxin in its detoxified form is a major component of all current acellular pertussis vaccines. Here we report the membrane translocation and internalization activities of pertussis toxin and various pertussis toxoids using Chinese hamster ovary cells and confocal microscopy based on indirect immunofluorescence labeling. Chemically detoxified pertussis toxoids were able to translocate/internalize into cells at the concentration about 1,000 times higher than the native toxin. Pertussi...

  4. Strain-specific virulence of Bordetella hinzii in poultry

    Two species of Bordetella, B. avium and B. hinzii, are known to infect avian hosts. B. avium is the etiologic agent of turkey coryza, a disease of high morbidity. B. hinzii, though commonly acquired from the respiratory tracts of diseased poultry, has not been demonstrated to be pathogenic in eith...

  5. The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

    Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay


    Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. PMID:27435387

  6. Efficient Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells by Genetically Detoxified Bordetella pertussis Adenylate Cyclase Antigen Toxodids

    Wilkinson, K. A.; Šimšová, Marcela; Schölvinck, E.; Šebo, Peter; Leclerc, C.; Voredermeier, H. M.; Dickson, S. J.; Brown, J. R.; Davidson, R. N.; Pasvol, G.; Levin, M.; Wilkinson, R. J.


    Roč. 73, č. 5 (2005), s. 2991-2998. ISSN 0019-9567 R&D Projects: GA AV ČR IBS5020311; GA ČR GA310/01/0934 Institutional research plan: CEZ:AV0Z50200510 Keywords : mycobacterium tuberculosis * t cell * CyaA Subject RIV: EE - Microbiology, Virology Impact factor: 3.933, year: 2005

  7. Transcriptional profiling of Bordetella pertussis reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

    Bíbová, Ilona; Hot, D.; Keidel, Kristina; Amman, F.; Slupek, S.; Černý, Ondřej; Gross, R.; Večerek, Branislav


    Roč. 12, č. 2 (2015), s. 175-185. ISSN 1547-6286 R&D Projects: GA ČR(CZ) GAP302/11/1940; GA MŠk(CZ) EE2.3.20.0055; GA MŠk(CZ) EE2.3.30.0003; GA MŠk(CZ) 7AMB14AR028; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Bsp22 * Hfq * infection Subject RIV: CE - Biochemistry Impact factor: 4.974, year: 2014

  8. Mass spectrometric analysis of recombinant adenylate cyclase toxin from Bordetella pertussis strain 18323/pHSP9+

    Havlíček, Vladimír; Higgins, L.; Chen, W.; Halada, Petr; Šebo, Peter; Sakamoto, H.; Hackett, M.


    Roč. 36, - (2001), s. 384-391. ISSN 1076-5174 R&D Projects: GA AV ČR IAA5020907; GA MŠk ME 167; GA MŠk VS96141 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EE - Microbiology, Virology Impact factor: 2.685, year: 2001

  9. The adenylate cyclase toxin from Bordetella pertussis - a novel promising vehicke fer antigen delivery to dendritic cells

    Šimšová, Marcela; Šebo, Peter; Leclerc, C.


    Roč. 293, - (2004), s. 571-576. ISSN 1438-4221 R&D Projects: GA ČR GA310/01/0934; GA AV ČR IAA5020907 Grant ostatní: GA QLK2-CT-1999(XX) 00556 Keywords : cyaa * cellular immune response * antigen delivery Subject RIV: EE - Microbiology, Virology Impact factor: 2.919, year: 2004

  10. A Cough-Based Algorithm for Automatic Diagnosis of Pertussis.

    Pramono, Renard Xaviero Adhi; Imtiaz, Syed Anas; Rodriguez-Villegas, Esther


    Pertussis is a contagious respiratory disease which mainly affects young children and can be fatal if left untreated. The World Health Organization estimates 16 million pertussis cases annually worldwide resulting in over 200,000 deaths. It is prevalent mainly in developing countries where it is difficult to diagnose due to the lack of healthcare facilities and medical professionals. Hence, a low-cost, quick and easily accessible solution is needed to provide pertussis diagnosis in such areas to contain an outbreak. In this paper we present an algorithm for automated diagnosis of pertussis using audio signals by analyzing cough and whoop sounds. The algorithm consists of three main blocks to perform automatic cough detection, cough classification and whooping sound detection. Each of these extract relevant features from the audio signal and subsequently classify them using a logistic regression model. The output from these blocks is collated to provide a pertussis likelihood diagnosis. The performance of the proposed algorithm is evaluated using audio recordings from 38 patients. The algorithm is able to diagnose all pertussis successfully from all audio recordings without any false diagnosis. It can also automatically detect individual cough sounds with 92% accuracy and PPV of 97%. The low complexity of the proposed algorithm coupled with its high accuracy demonstrates that it can be readily deployed using smartphones and can be extremely useful for quick identification or early screening of pertussis and for infection outbreaks control. PMID:27583523

  11. The pertussis enigma: reconciling epidemiology, immunology and evolution.

    Domenech de Cellès, Matthieu; Magpantay, Felicia M G; King, Aaron A; Rohani, Pejman


    Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980-2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies. PMID:26763701

  12. Bordetella bronchiseptica phase variation induced by crystal violet.

    Ishikawa, H.; Isayama, Y


    A method for effective induction of phase variation in Bordetella bronchiseptica by treatment with crystal violet (CV) is presented. When grown in CV-broth, phase I cells dissociated into three serial phases. Appearance of variant cells was observed simultaneously with the beginning of cell multiplication. The maximum effect of CV was obtained at a concentration of 8 micrograms/ml, when the proportion of variants in the population reached 100%. The main factors which affected phase variation ...

  13. Bordetella avium Antibiotic Resistance, Novel Enrichment Culture, and Antigenic Characterization

    Beach, Nathan M; Thompson, Seth; Mutnick, Rachel; Brown, Lisa; Kettig, Gina; Puffenbarger, Robyn; Miyamoto, David; Temple, Louise


    Bordetella avium continues to be an economic issue in the turkey industry as the causative agent of bordetellosis, which often leads to serious secondary infections. This study presents a broad characterization of the antibiotic resistance patterns in this diverse collection of B. avium strains collected over the past thirty years. In addition, the plasmid basis for the antibiotic resistance was characterized. The antibiotic resistance pattern allowed the development of a novel enrichment cul...

  14. Properties of dermonecrotic toxin prepared from sonic extracts Bordetella bronchiseptica.

    Kume, K.; Nakai, T.; Samejima, Y; Sugimoto, C


    A toxin with dermonecrotic activity (DNT) was purified from sonic extracts of Bordetella bronchiseptica L3 of pig origin at phase I by chromatographic and electrophoretic methods. The purification procedure was one developed for obtaining the Pasteurella multocida DNT from sonic extracts with some modifications. Dermonecrotizing activity of B. bronchiseptica-purified DNT was increased by 600-fold compared with that of the crude extract, and the average yield was about 3%. The toxin was homoge...

  15. Cilia-associated bacteria in fatal Bordetella bronchiseptica pneumonia of dogs and cats

    Bordetella bronchiseptica frequently causes nonfatal tracheobronchitis, but its role in fatal pneumonia is less well-studied. The objectives of this study were to identify the frequency of Bordetella bronchiseptica infection in fatal cases of bronchopneumonia in dogs and cats and to compare the diag...

  16. [Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation].

    Echeverri-Toro, Lina; Arango, Andrés; Ospina, Sigifredo; Agudelo, Carlos


    We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia. PMID:26849691

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

    ... Palsy: Shannon's Story" 5 Things to Know About Zika & Pregnancy Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth > For Parents > Your Child's Immunizations: Diphtheria, ...

  18. Pertussis outbreak in northwest Ireland, January - June 2010.

    Barret, A S


    We report a community pertussis outbreak that occurred in a small town located in the northwest of Ireland. Epidemiological investigations suggest that waning immunity and the absence of a booster dose during the second year of life could have contributed to the outbreak. The report also highlights the need to reinforce the surveillance of pertussis in Ireland and especially to improve the clinical and laboratory diagnosis of cases.

  19. Pertussis immunisation and serious acute neurological illness in children.

    Ebrahim, Shah


    The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had be...

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

    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.

  1. Characterization of the N-terminal domain of BteA: a Bordetella type III secreted cytotoxic effector.

    Chen Guttman

    Full Text Available BteA, a 69-kDa cytotoxic protein, is a type III secretion system (T3SS effector in the classical Bordetella, the etiological agents of pertussis and related mammalian respiratory diseases. Currently there is limited information regarding the structure of BteA or its subdomains, and no insight as to the identity of its eukaryotic partners(s and their modes of interaction with BteA. The mechanisms that lead to BteA dependent cell death also remain elusive. The N-terminal domain of BteA is multifunctional, acting as a docking platform for its cognate chaperone (BtcA in the bacterium, and targeting the protein to lipid raft microdomains within the eukaryotic host cell. In this study we describe the biochemical and biophysical characteristics of this domain (BteA287 and determine its architecture. We characterize BteA287 as being a soluble and highly stable domain which is rich in alpha helical content. Nuclear magnetic resonance (NMR experiments combined with size exclusion and analytical ultracentrifugation measurements confirm these observations and reveal BteA287 to be monomeric in nature with a tendency to oligomerize at concentrations above 200 µM. Furthermore, diffusion-NMR demonstrated that the first 31 residues of BteA287 are responsible for the apparent aggregation behavior of BteA287. Light scattering analyses and small angle X-ray scattering experiments reveal a prolate ellipsoidal bi-pyramidal dumb-bell shape. Thus, our biophysical characterization is a first step towards structure determination of the BteA N-terminal domain.

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

    Maria Leonor S Oliveira

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

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

    ... 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 ...

  4. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccines: What You Need to Know

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

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

    ... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

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

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

  7. Perceptions of Tetanus-diphteria-acellular pertussis (Tdap) Vaccination among Korean Women of Childbearing Age

    Kim, In Seon; Seo, Yu Bin; Hong, Kyung-Wook; Noh, Ji Yun; Choi, Won Suk; Song, Joon Young; Cho, Geum Joon; Oh, Min Jeong; Kim, Hai Joong; Hong, Soon Choul; Sohn, Jang Wook; Kim, Woo Joo; Cheong, Hee Jin


    Background The number of cases of pertussis reported has increased gradually in the last decade. Pertussis vaccination is the most effective strategy for the prevention of infection. Despite the fact that young infants are at the highest risk for pertussis, the rate of tetanus-diphtheria-acellular pertussis (Tdap) vaccination is presumed to be very low among women of childbearing age in Korea. The purpose of this study was to investigate the perceptions of women of childbearing age regarding ...

  8. Expression of the S-1 catalytic subunit of pertussis toxin in Escherichia coli.

    Barbieri, J T; Rappuoli, R; Collier, R J


    The S-1 subunit of pertussis toxin was expressed as a fusion protein in a strain of Escherichia coli deficient in protein degradation. The fusion protein reacted with anti-pertussis toxin antibody, and, like authentic pertussis toxin, it ADP-ribosylated a 41,000-molecular-weight membrane protein from human erythrocytes.

  9. Pertussis: A Review of Disease Epidemiology Worldwide and in Italy

    Giovanni Gabutti


    Full Text Available Pertussis continues to be a relevant public-health issue. The high coverage rates achieved have decreased the spread of the pathogen, but the waning of immunity implies a relevant role of adolescents and adults in the infective dynamics as they may represent a significant source of infection for unvaccinated or incompletely immunized newborns. The passive surveillance system is affected by many limitations. The underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived, anyway, the unavailability of comprehensive data should not hamper the adoption of active prophylactic interventions aimed at preventing the impact of waning immunity on pertussis. To avoid an increase of the mean age of acquisition of the infection, a booster dose of low-antigen content combined vaccine should be adopted in adolescents and adults. A decreased risk of infection in newborns can be achieved with the cocoon strategy, although the debate on this aspect is still open and enhanced surveillance and further studies are needed to fine-tune the pertussis prevention strategy.

  10. Polymorphisms influencing expression of dermonecrotic toxin in Bordetella bronchiseptica.

    Keisuke Okada

    Full Text Available Bordetella bronchiseptica is a pathogenic bacterium causing respiratory infections in a broad range of mammals. Recently, we determined the whole genome sequence of B. bronchiseptica S798 strain isolated from a pig infected with atrophic rhinitis and found four single-nucleotide polymorphisms (SNPs at positions -129, -72, +22, and +38 in the region upstream of dnt encoding dermonecrotic toxin (DNT, when compared with a rabbit isolate, RB50. DNT is known to be involved in turbinate atrophy observed in atrophic rhinitis. Immunoblotting, quantitative real-time PCR, and β-galactosidase reporter assay revealed that these SNPs resulted in the increased promoter activity of dnt and conferred the increased ability to produce DNT on the bacteria. Similar or identical SNPs were also found in other pig isolates kept in our laboratory, all of which produce a larger amount of DNT than RB50. Our analysis revealed that substitution of at least two of the four bases, at positions -72 and +22, influenced the promoter activity for dnt. These results imply that these SNPs are involved in the pathogenicity of bordetellae specific to pig diseases.

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

    Gautret, Philippe; Wilder-Smith, Annelies


    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. PMID:20541135

  12. Pertussis Prevalence and Its Determinants among Children with Persistent Cough in Urban Uganda

    Vincent Kayina; Samuel Kyobe; Katabazi, Fred A; Edgar Kigozi; Moses Okee; Beatrice Odongkara; Babikako, Harriet M; Whalen, Christopher C.; Joloba, Moses L.; Musoke, Philippa M.; Ezekiel Mupere


    Background We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control. Methods 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. Results Pertussis prevalence was 67 (15% (95% Confidence Interval (CI): 12–18)) and 81 (20%...

  13. An Introductory Pharmacy Practice Experience to Improve Pertussis Immunization Rates in Mothers of Newborns

    Clarke, Cheryl; Wall, Geoff C.; Soltis, Denise A.


    Objective. To implement an introductory pharmacy practice experience (IPPE) involving discharge counseling on postpartum pertussis immunization recommendations and evaluate its impact on student learning and patient immunization rates.

  14. Seroepidemiology of pertussis in a cross-sectional study of an adult general population in Denmark

    Rønn, P F; Dalby, T; Simonsen, J; Jørgensen, C S; Linneberg, A; Krogfelt, K A


    SUMMARY An increase in pertussis has been observed in several countries over the last decades, especially in adult populations. The seroprevalence of pertussis was determined in a cross-sectional study of the adult population in the Copenhagen area, Denmark, conducted between 2006 and 2008....../1000 person-years. In contrast, an incidence of 0·03/1000 person-years was estimated from the official data of notified cases during the same period. Of the investigated risk factors, only age and education were significantly associated with pertussis infection. This study indicates that pertussis is highly...

  15. Fetal Circulation

    ... Pressure High Blood Pressure Tools & Resources Stroke More Fetal Circulation Updated:Jul 8,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  16. cAMP signalling of Bordetella adenylate cyclase toxin through the SHP-1 phosphatase activates the BimEL-Bax pro-apoptotic cascade in phagocytes.

    Ahmad, Jawid Nazir; Cerny, Ondrej; Linhartova, Irena; Masin, Jiri; Osicka, Radim; Sebo, Peter


    The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) plays a key role in virulence of Bordetella pertussis. CyaA penetrates myeloid cells expressing the complement receptor 3 (αM β2 integrin CD11b/CD18) and subverts bactericidal capacities of neutrophils and macrophages by catalysing unregulated conversion of cytosolic ATP to the key signalling molecule adenosine 3',5'-cyclic monophosphate (cAMP). We show that the signalling of CyaA-produced cAMP hijacks, by an as yet unknown mechanism, the activity of the tyrosine phosphatase SHP-1 and activates the pro-apoptotic BimEL-Bax cascade. Mitochondrial hyperpolarization occurred in human THP-1 macrophages within 10 min of exposure to low CyaA concentrations (e.g. 20 ng ml(-1) ) and was accompanied by accumulation of BimEL and association of the pro-apoptotic factor Bax with mitochondria. BimEL accumulation required cAMP/protein kinase A signalling, depended on SHP-1 activity and was selectively inhibited upon small interfering RNA knockdown of SHP-1 but not of the SHP-2 phosphatase. Moreover, signalling of CyaA-produced cAMP inhibited the AKT/protein kinase B pro-survival cascade, enhancing activity of the FoxO3a transcription factor and inducing Bim transcription. Synergy of FoxO3a activation with SHP-1 hijacking thus enables the toxin to rapidly trigger a persistent accumulation of BimEL, thereby activating the pro-apoptotic programme of macrophages and subverting the innate immunity of the host. PMID:26334669

  17. Bordetella avium antibiotic resistance, novel enrichment culture, and antigenic characterization.

    Beach, Nathan M; Thompson, Seth; Mutnick, Rachel; Brown, Lisa; Kettig, Gina; Puffenbarger, Robyn; Stockwell, Stephanie B; Miyamoto, David; Temple, Louise


    Bordetella avium continues to be an economic issue in the turkey industry as the causative agent of bordetellosis, which often leads to serious secondary infections. This study presents a broad characterization of the antibiotic resistance patterns in this diverse collection of B. avium strains collected over the past thirty years. In addition, the plasmid basis for the antibiotic resistance was characterized. The antibiotic resistance pattern allowed the development of a novel enrichment culture method that was subsequently employed to gather new isolates from diseased turkeys and a healthy sawhet owl. While a healthy turkey flock was shown to seroconvert by four weeks-of-age, attempts to culture B. avium from healthy turkey poults were unsuccessful. Western blot of B. avium strains using pooled serum from diseased and healthy commercial turkey flocks revealed both antigenic similarities and differences between strains. In sum, the work documents the continued exposure of commercial turkey flocks to B. avium and the need for development of an effective, inexpensive vaccine to control spread of the disease. PMID:22721730

  18. Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

    Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R


    Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the

  19. Comparative safety and immunogenicity of an acellular versus whole- cell pertussis component of Diphteria-Tetanus-Pertussis vaccines in senegalese infants

    Simondon, François; Yam, A.; Gagnepain, J.Y.; Wassilak, S.; Danve, B; Cadoz, M.


    A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP), consisting of 25 microg glutaraldehyde-detoxified pertussis toxin (PT) and 25 microg native filamentous hemagglutinin (FHA), was compared with diphtheria and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double-blind manner in 286 Senegalese infants inoculated at two, four, and six months of age. In infants receiving DTaP a significantly lower rate of local reactions, crying and fever was o...

  20. A Type VI secretion system encoding locus is required for Bordetella bronchiseptica immunomodulation and persistence in vivo.

    Laura S Weyrich

    Full Text Available Type VI Secretion Systems (T6SSs have been identified in numerous gram-negative pathogens, but the lack of a natural host infection model has limited analysis of T6SS contributions to infection and pathogenesis. Here, we describe disruption of a gene within locus encoding a putative T6SS in Bordetella bronchiseptica strain RB50, a respiratory pathogen that circulates in a broad range of mammals, including humans, domestic animals, and mice. The 26 gene locus encoding the B. bronchiseptica T6SS contains apparent orthologs to all known core genes and possesses thirteen novel genes. By generating an in frame deletion of clpV, which encodes a putative ATPase required for some T6SS-dependent protein secretion, we observe that ClpV contributes to in vitro macrophage cytotoxicity while inducing several eukaryotic proteins associated with apoptosis. Additionally, ClpV is required for induction of IL-1β, IL-6, IL-17, and IL-10 production in J774 macrophages infected with RB50. During infections in wild type mice, we determined that ClpV contributes to altered cytokine production, increased pathology, delayed lower respiratory tract clearance, and long term nasal cavity persistence. Together, these results reveal a natural host infection system in which to interrogate T6SS contributions to immunomodulation and pathogenesis.

  1. Ca2+ influx and tyrosine kinases trigger Bordetella adenylate cyclase toxin (ACT endocytosis. Cell physiology and expression of the CD11b/CD18 integrin major determinants of the entry route.

    Kepa B Uribe

    Full Text Available Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3, its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca(2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

  2. Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

    Melker, de H.


    In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.In a population-based nationwide sampl

  3. Early Induction of Cytokines in Pigs Coinfected with Swine Influenza Virus and Bordetella bronchiseptica

    Respiratory disease is one of the most important health issues for the swine industry, and coinfection with two or more pathogens is a common occurrence. Bordetella bronchiseptica and swine influenza virus (SIV) are important and common respiratory pathogens of pigs. The effect of coinfection of S...

  4. Identification of Bordetella bronchseptica in fatal pneumonia of dogs and cats

    Infection with Bordetella bronchiseptica is a common cause of tracheobronchitis and upper respiratory disease in dogs and cats, but it can also lead to fatal pneumonia. Identification of this pathogen is important due the risk of transmission to other animals, availability of vaccines and potential...

  5. Bordetella bronchiseptica associated with pulmonary disease in mountain voles (Microtus montanus)

    Jensen, W.I.; Duncan, R.M.


    Bordetella bronchiseptica was isolated from the lungs of all of six mountain voles (Microtus montanus) found dead or dying of pulmonary infection near the Bear River Research Station in northern Utah in January, 1973. The possibility of concomitant viral or mycoplasmal infection was not ruled out.

  6. Evidence for horizontal gene transfer of two antigenically distinct O antigens in Bordetella bronchiseptica

    Antigenic variation is one mechanism pathogens use to avoid immune-mediated competition between closely related strains. Here, we show that two Bordetella bronchiseptica strains, RB50 and 1289, express two antigenically distinct O-antigen serotypes (O1 and O2 respectively). When 18 additional B. b...

  7. Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

    The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment

  8. The contribution of PCR testing to influenza and pertussis notifications in Australia.

    Kaczmarek, M C; Ware, R S; Lambert, S B


    Influenza and pertussis are the two most common vaccine-preventable infections notified in Australia. We assessed the role of polymerase chain reaction (PCR) diagnosis in influenza and pertussis cases notified to the Australian National Notifiable Diseases Surveillance System (NNDSS). There were a total of 2 10 786 notified influenza cases (2001-2013) and 2 55 866 notified pertussis cases (1991-2013). After 1 January 2007, the majority of influenza and pertussis notifications were PCR-based (80·5% and 59·6%, respectively). Before 31 December 2006, PCR-based notifications were limited (29·1% and 11·7%, respectively). By 2013, PCR-based notifications had largely replaced all other diagnostic methods, with the exception of serology-based notifications in pertussis cases in adults aged ⩾ 25 years. PMID:26112983

  9. Canine distemper virus infection with secondary Bordetella bronchiseptica pneumonia in dogs Infecção pelo virus da cinomose com pneumonia secundária por Bordetella bronchiseptica em cães

    Selwyn Arlington Headley; Dominguita Lühers Graça; Mateus Matiuzzi da Costa; Agueda Castagna de Vargas


    Canine distemper virus infection and secondary Bordetella bronchiseptica pneumonia are described in mongrel dogs. Canine distemper was characterised by nonsuppurative demyelinating encephalitis with typical inclusion bodies in astrocytes. B. bronchiseptica was isolated from areas of purulent bronchopneumonia.São descritas as infecções simultâneas do vírus da cinomose canina e Bordetella bronchiseptica em caninos sem raça definida. As lesões de cinomose foram caracterizadas por encefalite desm...

  10. Synthesis of acyclic nucleoside phosphonates bearing (N-methyl)anthraniloyl substituent as potential inhibitors of adenylate cyclase toxin from Bordetella Pertussis

    Břehová, Petra; Šmídková, Markéta; Mertlíková-Kaiserová, Helena; Dračínský, Martin; Janeba, Zlatko

    Praha: Czech Chemical Society, 2015. s. 61. [Liblice 2015. Advances in Organic , Bioorganic and Pharmaceutical Chemistry /50./. 06.11.2015-08.11.2015, Olomouc] R&D Projects: GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * adenylate cyclase toxin * prodrugs Subject RIV: CC - Organic Chemistry

  11. Bordetella pertussis Adenylate Cyclase Toxin Blocks Induction of Bactericidal Nitric Oxide in Macrophages through cAMP-Dependent Activation of the SHP-1 Phosphatase

    Černý, Ondřej; Kamanová, Jana; Mašín, Jiří; Bíbová, Ilona; Škopová, Karolína; Šebo, Peter


    Roč. 194, č. 10 (2015), s. 4901-4913. ISSN 0022-1767 R&D Projects: GA ČR GAP302/12/0460; GA ČR GA13-14547S Institutional support: RVO:61388971 Keywords : CYCLIC-AMP * MURINE MACROPHAGES * IFN-GAMMA Subject RIV: EE - Microbiology, Virology Impact factor: 4.922, year: 2014

  12. Incidence of pertussis in patients of general practitioners in Poland.

    Stefanoff, P; Paradowska-Stankiewicz, I A; Lipke, M; Karasek, E; Rastawicki, W; Zasada, A; Samuels, S; Czajka, H; Pebody, R G


    We estimated the incidence of pertussis in patients consulting general practitioners (GPs). Between July 2009 and April 2011, we conducted a prospective cohort study of patients attending 78 general practices (158 863 persons overall). We included patients aged ≥ 3 years, with cough lasting 2-15 weeks, who gave informed consent. GPs interviewed eligible patients, collected a blood specimen, and a nasopharyngeal swab. At follow-up 30-60 days after the initial visit, physicians collected a second blood specimen and conducted patient interview. Cases were confirmed by specific IgA and/or IgG antibody titre exceeding significantly the general population background level or detection of bacterial DNA by real-time PCR. During the study period, 3864 patients with prolonged cough consulted the participating GPs, of those 1852 met the inclusion criteria, 1232 were recruited, and 288 were confirmed as pertussis cases (4% by PCR, 96% by serology). The adjusted incidence rate was 201.1/100 000 person-years [95% confidence interval (CI) 133.9-302.0], ranging from 456.5 (95% CI 239.3-870.8) in the 15-19 years group to 94.0 (95% CI 33.4-264.5) in the 25-29 years group. The reporting ratio was 61, ranging from 4 in those aged 3-5 years, to 167 in those aged 65-69 years. The study confirmed high incidence of pertussis in all age groups in the general population, in particular in adults, not appropriately documented by the existing surveillance system. PMID:23870166

  13. El Gran Catharro de 1580 ¿gripe o pertussis?

    Camaño Puig, Ramón


    Full Text Available The gran Catharro (1580 is considered the first influenza epidemic. The analysis of various testimonies of the time may offer some doubts about whether or not it was so; and data strongly support that it was a pertussis epidemic.

    El Gran Catharro (1580 es considerado como la primera epidemia de gripe. El análisis conjunto de los datos contenidos en diferentes testimonios, suscita dudas respecto a que se tratara de una epidemia de gripe y apoyan la posibilidad de que se tratara de una de tos ferina.

  14. El Gran Catharro de 1580 ¿gripe o pertussis?

    Camaño Puig, Ramón; Barriendos Vallvé, Mariano; Faus Gabandé, Francisco


    The gran Catharro (1580) is considered the first influenza epidemic. The analysis of various testimonies of the time may offer some doubts about whether or not it was so; and data strongly support that it was a pertussis epidemic.

    El Gran Catharro (1580) es considerado como la primera epidemia de gripe. El análisis conjunto de los datos contenidos en diferentes testimonios, suscita dudas respecto a que se tratara de una epidemia de gripe y apoyan la posibilidad de que se tr...

  15. Lung Circulation.

    Suresh, Karthik; Shimoda, Larissa A


    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897-943, 2016. PMID:27065170

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

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


    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

  17. Pertussis prevalence and its determinants among children with persistent cough in urban Uganda.

    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.

  18. Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

    The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate [Gpp(NH)p] on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed [32P]ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-α/sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-α/sub i/ or anti-α0 antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed

  19. Whooping cough in South-East Romania: a 1-year study.

    Dinu, Sorin; Guillot, Sophie; Dragomirescu, Cristiana Cerasella; Brun, Delphine; Lazăr, Stefan; Vancea, Geta; Ionescu, Biatrice Mariana; Gherman, Mariana Felicia; Bjerkestrand, Andreea-Florina-Dana; Ungureanu, Vasilica; Guiso, Nicole; Damian, Maria


    The incidence of whooping cough in Romania is substantially underestimated, and, as noted by the health authorities, this is mostly due to the lack of both awareness and biological diagnosis. We conducted a 1-year study in Bucharest in order to assess the circulation of Bordetella pertussis, the main etiological agent of whooping cough. Fifty-one subjects suspected of whooping cough were enrolled. Culture, real-time PCR, and enzyme-linked immunosorbent assay were used for laboratory diagnosis. Whooping cough patients (63%) were distributed among all age groups, and most were unvaccinated, incompletely vaccinated, or had been vaccinated more than 5 years previously. Bordetella holmesii DNA was detected in 22% of the bordetellosis cases; these patients included adults; teenagers; and, surprisingly, young children. B. pertussis isolates were similar to the clinical isolates currently circulating elsewhere in Europe. One isolate does not express pertactin, an antigen included in some acellular pertussis vaccines. PMID:24355701

  20. Monoclonal Antibodies Directed Against the Outer Membrane Protein of Bordetella avium

    Liu, Guanhua; Liang, Manfei; Zuo, Xuemei; Zhao, Xue; Guo, Fanxia; Yang, Shifa; Zhu, Ruiliang


    Bordetella avium is the etiologic agent of coryza and rhinotracheitis in poultry. This respiratory disease is responsible for substantial economic losses in the poultry industry. Monoclonal antibodies (MAbs) were produced against the outer membrane proteins (OMPs) of B. avium isolated from diseased chickens. BALB/c mice were immunized with the extracted B. avium OMPs. Then the splenocytes from immunized mice and SP2/0 myeloma cells were fused using PEG 4000. Three stable hybridoma clones (des...

  1. Host Specificity of Ovine Bordetella parapertussis and the Role of Complement.

    Sara E Hester

    Full Text Available The classical bordetellae are comprised of three subspecies that differ from broad to very limited host specificity. Although several lineages appear to have specialized to particular host species, most retain the ability to colonize and grow in mice, providing a powerful common experimental model to study their differences. One of the subspecies, Bordetella parapertussis, is composed of two distinct clades that have specialized to different hosts: one to humans (Bpphu, and the other to sheep (Bppov. While Bpphu and the other classical bordetellae can efficiently colonize mice, Bppov strains are severely defective in their ability to colonize the murine respiratory tract. Bppov genomic analysis did not reveal the loss of adherence genes, but substantial mutations and deletions of multiple genes involved in the production of O-antigen, which is required to prevent complement deposition on B. bronchiseptica and Bpphu strains. Bppov lacks O-antigen and, like O-antigen mutants of other bordetellae, is highly sensitive to murine complement-mediated killing in vitro. Based on these results, we hypothesized that Bppov failed to colonize mice because of its sensitivity to murine complement. Consistent with this, the Bppov defect in the colonization of wild type mice was not observed in mice lacking the central complement component C3. Furthermore, Bppov strains were highly susceptible to killing by murine complement, but not by sheep complement. These data demonstrate that the failure of Bppov to colonize mice is due to sensitivity to murine, but not sheep, complement, providing a mechanistic example of how specialization that accompanies expansion in one host can limit host range.

  2. Bordetella Bronchiseptica in the Immunosuppressed Population – A Case Series and Review

    Yacoub, Abraham T.; Katayama, Mitsuya; Tran, JoAnn; Zadikany, Ronit; Kandula, Manasa; Greene, John


    Organisms that are not known to cause serious infection in the immunocompetent population can, in fact, cause devastating illness in immunosuppressed neutropenic populations especially those who are undergoing hematopoietic stem cell transplantation (HSCT), and solid organ transplantation or a history of malignancy. One organism of interest isolated from immunosuppressed patients at our institution was Bordetella bronchiseptica. It is known to cause respiratory tract disease in the animal pop...

  3. A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study

    Park, Sunghoon; Lee, Myung-Gu; Lee, Kwan Ho; Park, Yong Bum; Yoo, Kwang Ha; Park, Jeong-Woong; Kim, Changhwan; Lee, Yong Chul; Park, Jae Seuk; Kwon, Yong Soo; Seo, Ki-Hyun; Kim, Hui Jung; Kwak, Seung Min; Kim, Ju-Ock; Lim, Seong Yong


    Background Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea. Methods Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and cul...

  4. Hospital-Diagnosed Pertussis Infection in Children and Long-term Risk of Epilepsy

    Olsen, Morten; Thygesen, Sandra K; Østergaard, John R;


    , maternal history of epilepsy, presence of congenital malformations, and gestational age. Unique personal identifiers permitted unambiguous data linkage and complete follow-up for death, emigration, and hospital contacts. RESULTS: We identified 4700 patients with pertussis (48% male), of whom 90 developed......: In Denmark, risk of epilepsy was increased in children with hospital-diagnosed pertussis infections compared with the general population; however, the absolute risk was low....

  5. Immune Boosting Explains Regime-Shifts in Prevaccine-Era Pertussis Dynamics

    Lavine, Jennie; King, Aaron A; Andreasen, Viggo; Bjornstad, Ottar N


    of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that...... permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory for pertussis epidemiology....

  6. [Impact of vaccination on the infectious diseases epidemiology: example of pertussis

    Guiso, Nicole


    Several vaccines are now routinely used since fifty years in different developed countries. Their principal impact has been to decrease morbidity and mortality of the infectious diseases they are targeting. One disease, smallpox, is eradicated, poliomyelitis will be soon, diphteria is controlled in several countries but pertussis is still endemic although an efficacious vaccine was used. Why? Pertussis is an example of an infection for which the immunity of the population has changed after th...


    Aida Borgi


    Background: Critical pertussis is characterized by severe respiratory failure, severe leukocytosis, pulmonary hypertension, septic shock and encephalopathy.Aim: To describe the clinical course of critical pertussis and identify predictors of death at the time of presentation for medical care.Methodology: retrospective study conducted in children’s hospital Tunisian PICU between 01 January and 31 october 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventil...

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

    Rosângela S.L.A. Torres


    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.

  9. Analytical Verification of a PCR Assay for Identification of Bordetella avium

    Register, Karen B.; Yersin, Andrew G.


    Bordetella avium is the etiologic agent of turkey coryza or bordetellosis, a respiratory disease responsible for substantial economic losses to the turkey industry. At present, identification of this bacterium relies on isolation and biochemical testing. Although a PCR for the detection of B. avium was proposed a number of years ago (P. H. Savelkoul, L. E. de Groot, C. Boersma, I. Livey, C. J. Duggleby, B. A. van der Zeijst, and W. Gaastra, Microb. Pathog. 15:207-215, 1993), lack of analytica...

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

    Atanasković-Marković Marina


    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.

  11. PENETAPAN STANDAR NASIONAL DARI VAKSIN DPT: Penetapan Standar Nasional Vaksin Pertussis

    Muljanti Prijanto


    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.

  12. Diphtheria, Tetanus, and Pertussis Immunity in Indian Adults and Immunogenicity of Td Vaccine

    Kulkarni, Prasad S; Raut, Sidram K.; Dhorje, Sanjay P.; Barde, Prajakt J.; Girish Koli; Jadhav, Suresh S.


    Rise of diphtheria cases in adults is a cause of concern worldwide. Pertussis is also now affecting adults. We assessed serum levels of tetanus, diphtheria and pertussis antibodies in 62 adults in Pune, India, who had missed their primary immunization. All adults were then given three doses of tetanus-diphtheria (Td) vaccine at 0, 1, and 6 months. All adults were immune to tetanus but 78% had long-term protection. For diphtheria, 88% were protected but only 9% had long term immunity. Only 60%...

  13. Circulation economics

    Ingebrigtsen, Stig; Jakobsen, Ove


    Purpose - This paper is an attempt to advance the critical discussion regarding environmental and societal responsibility in economics and business. Design/methodology/approach - The paper presents and discusses as a holistic, organic perspective enabling innovative solutions to challenges...... concerning the responsible and efficient use of natural resources and the constructive interplay with culture. To reach the goal of sustainable development, the paper argues that it is necessary to make changes in several dimensions in mainstream economics. This change of perspective is called a turn towards...... presupposes a perspective integrating economic, natural and cultural values. Third, to organize the interplay between all stakeholders we introduce an arena for communicative cooperation. Originality/value - The paper concludes that circulation economics presupposes a change in paradigm, from a mechanistic...

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

    Xiao L. Zhang; Quan M. Zou


    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.

  15. Effects of pertussis toxin on vascular reactivity of femoral arteries in WKY and SHR

    Líšková, Silvia; Kuneš, Jaroslav; Zicha, Josef

    Bratislava : Advent- Orion , 2007 - (Pecháňová, O.), s. 89-94 ISBN 978-80-8071-094-1 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : NA-induced contraction of arteria femorale * pertussis toxin * nifedipine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  16. The effect of pertussis toxin administration on geometry and structure of conduit arteries in SHR

    Kristek, F.; Čačányiová, S.; Kuneš, Jaroslav; Zicha, Josef

    Bratislava : Advent- Orion , 2007 - (Pecháňová, O.), s. 101-106 ISBN 978-80-8071-094-1 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * spontaneously hypertensive rats * geometry and structure of arteria carotis Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  17. Chao Yuanfang: Imperial Physician of the Sui Dynasty and an Early Pertussis Observer?

    Liang, Yan; Salim, Abdulbaset M; Wu, Wendy; Kilgore, Paul E


    Early Chinese texts contain extensive disease descriptions, including various texts that contain descriptions of modern-day conditions. During the Sui Dynasty, a leading scholar, Chao Yuanfang, may have authored a leading treatise 1400 years ago. Although these texts are the subject of ongoing research, evidence suggests that a clinical syndrome consistent with pertussis was observed in ancient China. PMID:26977422

  18. Pyrexia after diphtheria/tetanus/pertussis and diphtheria/tetanus vaccines.

    Waight, P. A.; Pollock, T M; Miller, E.; Coleman, E M


    The temperatures of 587 children were taken before and after diphtheria/tetanus/pertussis (DTP) or diphtheria/tetanus (DT) vaccine. Only slight temperature increases were found but these were notably more frequent after plain than adsorbed DTP vaccine preparations and the frequency increased with each successive dose.

  19. Cost-effectiveness of next-generation vaccines: The case of pertussis.

    Fitzpatrick, Meagan C; Wenzel, Natasha S; Scarpino, Samuel V; Althouse, Benjamin M; Atkins, Katherine E; Galvani, Alison P; Townsend, Jeffrey P


    Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95% CI: $12-$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of $22 per dose for the childhood series (CI: $10-$33) or $12 for the adult booster (CI: $4-$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of $39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown. PMID:27087151

  20. Bordetella bronchiseptica Pneumonia in an Extremely-Low-Birth-Weight Neonate.

    Ting, Yuk Joseph; Ho, Pak-Leung; Wong, Kar-Yin


    Bordetella bronchiseptica, a gram-negative coccobacillus, is a common veterinary pathogen. In both domestic and wild animals, this bacterium causes respiratory infections including infectious tracheobronchitis in dogs and atrophic rhinitis in swine. Human infections are rare and have been documented in immunocompromised hosts. Here, we describe an extremely-low-birth-weight infant with B. bronchiseptica pneumonia. This is the first report that describes the microorganism's responsibility in causing nosocomial infection in a preterm neonate. He recovered uneventfully after a course of meropenem. It is possible that the bacteria colonize the respiratory tracts of our health care workers or parents who may have had contact with pets and then transmitted the bacterium to our patient. Follow-up until 21 months of age showed normal growth and development. He did not suffer from any significant residual respiratory disease. PMID:23705092

  1. Comparative Serological and Random Amplified Polymorphic DNA Typing for Bordetella avium Isolates in China

    Ping-Ping Yang, Rong-De Ma1, Xue Zhao and Rui-Liang Zhu*


    Full Text Available To study the similarity among Bordetella avium isolates in China, antigens and diagnostic antiserum of 22 B. avium isolates were prepared for serotyping, and a set of 20 commercially available primers was screened out to identify suitable primers for random amplified polymorphic DNA fingerprinting (RAPD analysis in this study. Twenty-two B. avium isolates were divided into two serovars (A and B based on their reaction in the plate-agglutination test. Four primers R1, R2, R4 and R10 resulted in informative fingerprints and were used to evaluate the B. avium isolates. Based on their RAPD patterns, a dendrogram allowed the separation of the B. avium isolates into six genetic similarity clusters. However, no direct correlation was observed between serotypes and RAPD typing among the isolates.

  2. Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

    Coursaget, P.; Yvonnet, B.; Relyveld, E. H.; Barres, J L; Diop-Mar, I.; Chiron, J. P.


    We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6...

  3. Outer membrane protein OmpQ of Bordetella bronchiseptica is required for mature biofilm formation.

    Cattelan, Natalia; Villalba, María Inés; Parisi, Gustavo; Arnal, Laura; Serra, Diego Omar; Aguilar, Mario; Yantorno, Osvaldo


    Bordetella bronchiseptica, an aerobic Gram-negative bacterium, is capable of colonizing the respiratory tract of diverse animals and chronically persists inside the hosts by forming biofilm. Most known virulence factors in Bordetella species are regulated by the BvgAS two-component transduction system. The Bvg-activated proteins play a critical role during host infection. OmpQ is an outer membrane porin protein which is expressed under BvgAS control. Here, we studied the contribution of OmpQ to the biofilm formation process by B. bronchiseptica. We found that the lack of expression of OmpQ did not affect the growth kinetics and final biomass of B. bronchiseptica under planktonic growth conditions. The ΔompQ mutant strain displayed no differences in attachment level and in early steps of biofilm formation. However, deletion of the ompQ gene attenuated the ability of B. bronchiseptica to form a mature biofilm. Analysis of ompQ gene expression during the biofilm formation process by B. bronchiseptica showed a dynamic expression pattern, with an increase of biofilm culture at 48 h. Moreover, we demonstrated that the addition of serum anti-OmpQ had the potential to reduce the biofilm biomass formation in a dose-dependent manner. In conclusion, we showed for the first time, to the best of our knowledge, evidence of the contribution of OmpQ to a process of importance for B. bronchiseptica pathobiology. Our results indicate that OmpQ plays a role during the biofilm development process, particularly at later stages of development, and that this porin could be a potential target for strategies of biofilm formation inhibition. PMID:26673448

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

    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.

  5. T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

    Pascal Feunou Feunou; Julie Bertout; Camille Locht


    BACKGROUND: Despite the extensive use of efficacious vaccines, pertussis still ranks among the major causes of childhood mortality worldwide. Two types of pertussis vaccines are currently available, whole-cell, and the more recent acellular vaccines. Because of reduced reactogenicity and comparable efficacy acellular vaccines progressively replace whole-cell vaccines. However, both types require repeated administrations for optimal efficacy. We have recently developed a live attenuated vaccin...

  6. Assessment of Serologic Immunity to Diphtheria-Tetanus-Pertussis After Treatment of Korean Pediatric Hematology and Oncology Patients

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


    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...

  7. Pertussis serological potency test as an alternatively to the intracerebral mouse protection test.

    van der Ark, A; van Straaten-van de Kappelle, I; Hendriksen, C; van de Donk, H


    The current potency test for pertussis vaccines, the intracerebral protection test (MPT), is still the only mandatory laboratory model available. This test, however, is a valid, but inhumane and imprecise test and therefore a good candidate for replacement. Recently we have developed the Pertussis Serological Potency Test (PSPT) as an alternative for the MPT. The PSPT is based on in vitro assessment of the humoral immune response against the whole range of surface -antigens of B. pertussis in mice after immunisation with Whole Cell Vaccine (WCV). We have demonstrated a relationship between the mean pertussis antibody concentration at the day of challenge and the proportion of surviving mice at each vaccine dose in the MPT (R = 0.91). The PSPT is a model in which mice (20-24 g) are immunised i.p. with graded doses of vaccine and bled after four weeks. Sera are titrated in a whole cell ELISA and potency based on the vaccine dose-dependent antibody response is estimated by means of a parallel line analysis. In an in-house validation study 13 WCVs were tested in the PSPT and MPT. Homogeneity of both tests was proven by means of the chi-square test; potencies were significantly similar (p = 0.95). Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice. Additional experiments showed that estimation of WCV-potency in the PSPT based on specific antibody responses against protective antigens (PT, FHA, 69- and 92-kDa OMPS) was not possible or did not correlate with protection in MPT. Sera obtained from the PSPT showed a correlation between pertussis antibody levels and complement-mediated killing by pertussis antibodies in in vitro assays. In conclusion, the PSPT is a promising substitute for the MPT though further validation and additional studies on functional


    Muljati Prijanto


    Full Text Available The objective of this study is to evaluate the serological response against pertussis after completion of both 2 and 3 doses of DPT vaccination. The study has been carried out retrospectively among 766 children under 3 years of age in Tulang-an District, Sidoarjo, East Java. The antibody titres against pertussis were measured by micro agglutination test. The results showed that the percentage of children having antibody titre of 1 : 80 or more, at 1—5 months post vaccination were 80.9% and 88.3% for 2 and 3 doses, respectively. The results do not differ significantly. This insignificance was maintained up to 17 months of the post-vaccination period.

  9. Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation.

    Bell, F.; Martin, A; Blondeau, C.; THORNTON, C; Chaplais, J; A. Finn


    A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to...

  10. Maintenance of biological activity of pertussis toxin radioiodinated while bound to fetuin-agarose.

    Armstrong, G. D.; Peppler, M S


    We developed a method to produce radioiodinated pertussis toxin (PT) which was active in the goose erythrocyte agglutination and CHO cell assay systems. The procedure used fetuin coupled to agarose to prevent inactivation of the toxin during the iodination reaction. Analysis of the labeled PT by affinity chromatography on fetuin-agarose and wheat germ agglutinin-agarose and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that there were minimal amounts of labeled fetuin...

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

    H. Mirehamsy


    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

  12. Changes to the varicella and pertussis immunisation schedule in Germany 2009: Background, rationale and implementation

    Wiese-Posselt, Miriam; Hellenbrand, Wiebke


    In July 2009, the German Standing Committee on Vaccination (STIKO) modified its recommendations for varicella and pertussis vaccination, based on newly available data on disease epidemiology, vaccine effectiveness (VE) and safety, and an evaluation of the feasibility of the recommended immunisation strategy. The recommendation for varicella vaccine now includes a routine two-dose schedule with the administration of the first dose at the age of 11 to 14 months and the second dose at t...

  13. Effects of mutations on enzyme activity and immunoreactivity of the S1 subunit of pertussis toxin.

    Lobet, Y; Cieplak, W; Smith, S. G.; Keith, J M


    By introducing a series of six different substitutions at and around position 9, we investigated the structural requirements of the amino-terminal region of the S1 subunit of pertussis toxin for both enzyme activity and immunoreactivity. All mutant S1 analogs with a substitution at this location exhibited severely decreased ADP-ribosyltransferase activity (range, 400- to 2,500-fold). In contrast, alteration of arginine 58 had considerably less effect. The reactivity of the mutant molecules wi...

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

    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.

  15. Pertussis immunity and epidemiology: mode and duration of vaccine-induced immunity.

    Magpantay, F M G; Domenech DE Cellès, M; Rohani, P; King, A A


    The resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. In particular, major questions surround the nature, degree and durability of vaccine protection. To address these questions, we used mechanistic transmission models to examine regional time series incidence data from Italy in the period immediately following the introduction of acellular pertussis (aP) vaccine. Our results concur with recent animal-challenge experiments wherein infections in aP-vaccinated individuals proved as transmissible as those in naive individuals but much less symptomatic. On the other hand, the data provide evidence for vaccine-driven reduction in susceptibility, which we quantify via a synthetic measure of vaccine impact. As to the precise nature of vaccine failure, the data do not allow us to distinguish between leakiness and waning of vaccine immunity, or some combination of these. Across the range of well-supported models, the nature and duration of vaccine protection, the age profile of incidence and the range of projected epidemiological futures differ substantially, underscoring the importance of the remaining unknowns. We identify key data gaps: sources of data that can supply the information needed to eliminate these remaining uncertainties. PMID:26337864

  16. Pertussis in the central-west region of Brazil: one decade study

    Angelita Fernandes Druzian


    Full Text Available In many parts of the world, numerous outbreaks of pertussis have been described despite high vaccination coverage. In this article we report the epidemiological characteristics of pertussis in Brazil using a Surveillance Worksheet. Secondary data of pertussis case investigations reported from January 1999 to December 2008 recorded in the Information System for Notifiable Diseases (SINAN and the Central Laboratory for Public Health (LACEN-MS were utilized. The total of 561 suspected cases were reported and 238 (42.4% of these were confirmed, mainly in children under six months (61.8% and with incomplete immunization (56.3%. Two outbreaks were detected. Mortality rate ranged from 2.56% to 11.11%. The occurrence of outbreaks and the poor performance of cultures for confirming diagnosis are problems which need to be addressed. High vaccination coverage is certainly a good strategy to reduce the number of cases and to reduce the impact of the disease in children younger than six months.

  17. Cost-effectiveness analysis of Tdap in the prevention of pertussis in the elderly.

    Lisa J McGarry

    Full Text Available OBJECTIVES: Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP recommended expanding Tdap vaccination (one single dose to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. METHODS: We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25-200 cases per 100,000, due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US$ 2010 for each case. Quality-adjusted life-years (QALYs lost to acute disease were calculated by multiplying cases of mild/moderate/severe pertussis by the associated health-state disutility; QALY losses due to death and long-term sequelae were also considered. Incremental costs and QALYs were summed over the cohort to derive incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of alternative plausible parameter estimates on results. RESULTS: At incidence levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario


    Aida Borgi


    Full Text Available Background: Critical pertussis is characterized by severe respiratory failure, severe leukocytosis, pulmonary hypertension, septic shock and encephalopathy.Aim: To describe the clinical course of critical pertussis and identify predictors of death at the time of presentation for medical care.Methodology: retrospective study conducted in children’s hospital Tunisian PICU between 01 January and 31 october 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventilation were included. Predictors of death were studied.Results : A total of 17 patients were included. Median age was 50 days. Mortality was 23%. Predictors  risk of mortality  were high PRISM (p=0,007, shock (p=0,002, tachycardia (p=0,005, seizures (p=0,006, altered mental status(p=0,006, elevated WBC count (p=0,003 and hemodynamic support (p=0022. However difference did not reach statistical significance in comorbidity, pneumoniae, high pulmonary hypertension or exchange transfusion. Concomitant viral or bacterial coinfection wasn’t related to poor outcome.Conclusion: Young infants are at high risk to have critical pertussis. Despite advances in life support and the treatment of organ failure in childhood critical illness, critical pertussis remains difficult to treat.

  19. Time series analysis of temporal trends in the pertussis incidence in Mainland China from 2005 to 2016.

    Zeng, Qianglin; Li, Dandan; Huang, Gui; Xia, Jin; Wang, Xiaoming; Zhang, Yamei; Tang, Wanping; Zhou, Hui


    Short-term forecast of pertussis incidence is helpful for advanced warning and planning resource needs for future epidemics. By utilizing the Auto-Regressive Integrated Moving Average (ARIMA) model and Exponential Smoothing (ETS) model as alterative models with R software, this paper analyzed data from Chinese Center for Disease Control and Prevention (China CDC) between January 2005 and June 2016. The ARIMA (0,1,0)(1,1,1)12 model (AICc = 1342.2 BIC = 1350.3) was selected as the best performing ARIMA model and the ETS (M,N,M) model (AICc = 1678.6, BIC = 1715.4) was selected as the best performing ETS model, and the ETS (M,N,M) model with the minimum RMSE was finally selected for in-sample-simulation and out-of-sample forecasting. Descriptive statistics showed that the reported number of pertussis cases by China CDC increased by 66.20% from 2005 (4058 cases) to 2015 (6744 cases). According to Hodrick-Prescott filter, there was an apparent cyclicity and seasonality in the pertussis reports. In out of sample forecasting, the model forecasted a relatively high incidence cases in 2016, which predicates an increasing risk of ongoing pertussis resurgence in the near future. In this regard, the ETS model would be a useful tool in simulating and forecasting the incidence of pertussis, and helping decision makers to take efficient decisions based on the advanced warning of disease incidence. PMID:27577101

  20. Design of primers for pertussis diagnosis by Real Time PCR and determination of its sensitivity and specificity in comparison with commercial kits.

    Hamidreza Monavari


    Results: Performance of our home made primers for detecting pertussis using Real Time PCR in comparison with those by commercial kit was acceptable based on diagnostic classical guidance (WHO and the (CDC. Conclusions: Real time PCR test with new primers in comparison with culture techniques is more suitable, high sensitivity and can provide more informative values for pertussis detection.

  1. Rapid and sensitive detection of Bordetella bronchiseptica by loop-mediated isothermal amplification (LAMP

    Hui Zhang


    Full Text Available Bordetella bronchiseptica causes acute and chronic respiratory infections in diverse animal species and occasionally in humans. In this study, we described the establishment of a simple, sensitive and cost-efficient loop-mediated isothermal amplification (LAMP assay for the detection of B. bronchiseptica. A set of primers towards a 235 bp region within the flagellum gene of B. bronchiseptica was designed with online software.. The specificity of the LAMP assay was examined by using 6 porcine pathogens and 100 nasal swabs collected from healthy pigs and suspect infected pigs. The results indicated that positive reactions were confirmed for all B. bronchiseptica and no cross-reactivity was observed from other non-B. bronchiseptica. In sensitivity evaluations, the technique successfully detected a serial dilutions of extracted B. bronchiseptica DNA with a detection limit of 9 copies, which was 10 times more sensitive than that of PCR. Compared with conventional PCR, the higher sensitivity of LAMP method and no need for the complex instrumentation make this LAMP assay a promising alternative for the diagnosis of B. bronchiseptica in rural areas and developing countries where there lacks of complex laboratory services.

  2. Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence.

    West, N P; Jungnitz, H; Fitter, J T; McArthur, J D; Guzmán, C A; Walker, M J


    The phosphoglucomutase (PGM)-encoding gene of Bordetella bronchiseptica is required for lipopolysaccharide (LPS) biosynthesis. An insertion mutant of the wild-type B. bronchiseptica strain BB7865 which disrupted LPS biosynthesis was created and characterized (BB7865pgm). Genetic analysis of the mutated gene showed it shares high identity with PGM genes of various bacterial species and forms part of an operon which also encompasses the gene encoding phosphoglucose isomerase. Functional assays for PGM revealed that enzyme activity is expressed in both bvg-positive and bvg-negative strains of B. bronchiseptica and is substantially reduced in BB7865pgm. Complementation of the mutated PGM gene with that from BB7865 restored the wild-type condition for all phenotypes tested. The ability of the mutant BB7865pgm to survive within J774. A1 cells was significantly reduced at 2 h (40% reduction) and 24 h (56% reduction) postinfection. BB7865pgm was also significantly attenuated in its ability to survive in vivo following intranasal infection of mice, being effectively cleared from the lungs within 4 days, whereas the wild-type strain persisted at least 35 days. The activities of superoxide dismutase, urease, and acid phosphatase were unaffected in the PGM-deficient strain. In contrast, the inability to produce wild-type LPS resulted in a reduced bacterial resistance to oxidative stress and a higher susceptibility to the antimicrobial peptide cecropin P. PMID:10899872

  3. Immunoproteomic Analysis ofBordetella bronchisepticaOuter Membrane Proteins and Identiifcation of New Immunogenic Proteins

    JI Quan-an


    Bordetella bronchiseptica is a Gram-negative pathogen that causes acute and chronic respiratory infection in a variety of animals. To identify useful antigen candidates for diagnosis and subunit vaccine ofB. bronchiseptica, immunoproteomic analysis was adopted to analyse outer membrane proteins of it. The outer membrane proteins extracted fromB. bronchiseptica were separated by two-dimensional gel electrophoresis and analyzed by Western blotting for their reactivity with the convalescent serum against two strains. Immunogenic proteins were identiifed by matrix-assisted laser desorption/ionization time of lfight-mass spectrometry (MALDI-TOF-MS), a total of 14 proteins are common immunoreactive proteins, of which 1 was known antigen and 13 were novel immunogenic proteins forB. bronchiseptica. Putative lipoprotein gene was cloned and recombinantly expressed. The recombinant protein induced high titer antibody, but showed low protective indices against challenges with HB (B. bronchiseptica strain isolated from a infected rabbit). The mortality of mice was 80% compared to 100% of positive controls. The identiifcation of these novel antigenic proteins is an important resource for further development of a new diagnostic test and vaccine for B. bronchiseptica.

  4. Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs.

    Ellis, J A; Gow, S P; Waldner, C L; Shields, S; Wappel, S; Bowers, A; Lacoste, S; Xu, Z; Ball, E


    In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty-one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines. PMID:27256028

  5. Crystal violet staining of Bordetella bronchiseptica colonies for differentiation of phase-I strains from variant strains in degraded phases.

    Ishikawa, H.; Isayama, Y


    After 2 days of growth on Brain heart infusion agar (BHIA) at 38 degrees C, phase-I colonies and degraded-phase colonies of Bordetella bronchiseptica could be differentiated by their ability to take up crystal violet (CV). Phase-I colonies in X mode, but not colonies in degraded phases (phases II, III, and rough) bound CV. Phenotypically-altered C-mode colonies (grown at 32 degrees C or lower temperatures) also lacked this ability. CV staining offers an easy method for the recognition of diff...

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

    Zarei Saeed


    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.

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

    Kraan, Heleen; Ten Have, Rimko; van der Maas, Larissa; Kersten, Gideon; Amorij, Jean-Pierre


    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 injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine. The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45°C compared to type 3 in non-lyophilized liquid controls. Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6h at 25°C, which are WHO open vial policy conditions. At 37°C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable. PMID:27470209

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

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


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

    Saliou Pierre


    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. Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study

    Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony


    Objective To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Design Prospective cohort study (November 2010 to December 2012). Setting General practices in Thames Valley, UK. Participants 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks’ duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Main outcome measures Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. Results 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Conclusions Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the