phenylephrine-hydrochloride and Whooping-Cough

Topics: Ampicillin; Anti-Bacterial Agents; Bordetella pertussis; Child; Chloramphenicol; Erythromycin; Female; Humans; Immunization, Passive; Male; Nose; Oxytetracycline; Pharynx; Whooping Cough

Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (T

Topics: Animals; Bordetella pertussis; CD4-Positive T-Lymphocytes; Cell Movement; Immunization; Interleukin-17; Lung; Mice; Nose; Pertussis Vaccine; T-Lymphocyte Subsets; Whooping Cough

BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization. However, transfer of nasal washes from BPZE1-vaccinated mice resulted in protection against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor-deficient mice, indicating that it depends on secretory IgA (SIgA) induction induced in the nose. BPZE1-induced protection against nasal colonization was long-lived despite the relatively rapid decay of SIgA, indicating a potent BPZE1-induced local memory response, likely due to CD4

Topics: Animals; Bordetella pertussis; Cells, Cultured; Humans; Immunoglobulin A, Secretory; Interleukin-17; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nose; Pertussis Vaccine; Receptors, Cell Surface; Vaccines, Attenuated; Whooping Cough

Current acellular pertussis (aP) vaccines induce strong antibody and Th2 responses but fail to protect against nasal colonization and transmission of Bordetella pertussis. Furthermore, immunity wanes rapidly after immunization. We have developed a novel adjuvant combination (called LP-GMP), comprising c-di-GMP, an intracellular receptor stimulator of interferon genes (STING) agonist, and LP1569, a TLR2 agonist from B. pertussis, which synergistically induces production of IFN-β, IL-12 and IL-23, and maturation of dendritic cells. Parenteral immunization of mice with an experimental aP vaccine formulated with LP-GMP promoted Th1 and Th17 responses and conferred protection against lung infection with B. pertussis. Intranasal immunization with the same aP vaccine-induced potent B. pertussis-specific Th17 responses and IL-17-secreting respiratory tissue-resident memory (T

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Bordetella pertussis; Cells, Cultured; Humans; Immunity, Cellular; Immunologic Memory; Interleukin-17; Mice; Mice, Inbred C57BL; Nose; Pertussis Vaccine; Th1 Cells; Th17 Cells; Vaccination; Whooping Cough

The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in which no virulence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using transcriptomic approaches. Recombinant BP-BvgΔ65, which is in the Bvgi phase by default and can be up-modulated to the Bvg+ phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg+-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-BvgΔ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvgi and Bvg+-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions.

Topics: Animals; Bacterial Proteins; Bordetella pertussis; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Lung; Mice; Mutation; Nose; Protein Engineering; Sequence Analysis, RNA; Transcription Factors; Virulence; Whooping Cough

Pertussis, or whooping cough, caused by the obligate human pathogen

Topics: Animals; Bacterial Adhesion; Biofilms; Bordetella pertussis; Disease Models, Animal; Epithelial Cells; Humans; Mice; Nose; Trachea; Virulence; Whooping Cough

 Advances in molecular laboratory techniques are changing the landscape of Bordetella pertussis illness diagnosis. Polymerase chain reaction (PCR) assays have greatly improved the sensitivity detection and the turnaround time to diagnosis compared to culture. Moreover, different respiratory specimens, such as flocked nasopharyngeal swabs (NPSs), nasopharyngeal aspirates (NPAs), and induced sputum, have been used for B. pertussis detection, although there is limited head-to-head comparison to evaluating the PCR yield from the 3 sampling methods..  Hospitalized infants <6 months of age who fulfilled a broad syndromic criteria of respiratory illness were tested for B. pertussis infection by PCR on paired NPSs and NPAs; or paired NPSs and induced sputum. An exploratory analysis of B. pertussis culture was performed on induced sputum specimens and in a subset of NPSs..  From November 2014 to May 2015, 484 infants with paired NPSs and NPAs were tested; 15 (3.1%) PCR-confirmed pertussis cases were identified, 13 of which were PCR positive on both samples, while 1 each were positive only on NPS or NPA. From March to October 2015, 320 infants had NPSs and induced sputum collected, and 11 (3.4%) pertussis cases were identified by PCR, including 8 (72.7%) positive on both samples, 1 (9.1%) only positive on NPS, and 2 (18.2%) only positive on induced sputum. The 3 types of specimens had similar negative predictive value >99% and sensitivity >83%. Compared to PCR, culture sensitivity was 60% in induced sputum and 40% in NPSs..  Flocked nasopharyngeal swabs, nasopharyngeal aspirates, and induced sputum performed similarly for the detection of B. pertussis infection in young infants by PCR.

Topics: Bordetella pertussis; Coinfection; Female; HIV Infections; Hospitalization; Humans; Infant; Infant, Newborn; Male; Nasopharynx; Nose; Population Surveillance; Sputum; Whooping Cough

Two hundred and fourteen patients who had a cough illness lasting at least 2 weeks were studied to investigate Bordetella pertussis as a cause of prolonged cough in adolescents and adults. Medical history and nasopharyngeal swab specimens for culture and polymerase chain reaction (PCR) were obtained at presentation. Three (1·4%) patients were B. pertussis culture-positive; 15 (7%) were B. pertussis PCR-positive (including the culture-positive patients) and 11 (5·1%) were Bordetella spp. PCR-positive. Symptom combinations were significantly high both in patients with pertussis and patients with indeterminate results (P < 0·05). We conclude that B. pertussis should be considered among differential diagnoses of prolonged cough in adolescents and adults and PCR and culture should be used to detect these cases and facilitate public health response.

Topics: Adolescent; Adult; Bordetella pertussis; Child; Chronic Disease; Cough; DNA, Bacterial; Female; Humans; Male; Medical History Taking; Nose; Pharynx; Turkey; Vomiting; Whooping Cough; Young Adult

Many respiratory pathogens establish persistent infection or a carrier state in the human nasopharynx without overt disease symptoms but the presence of these in the lungs usually results in disease. Although the anatomy and microenvironments between nasopharynx and lungs are different, a virulence factor with an organ-specific function in the colonization of the nasopharynx is unknown. In contrast to the severity of pertussis and mortality in non-vaccinated young children, Bordetella pertussis results in milder and prolonged cough in vaccinated adolescents and adults. Individuals harbouring bacteria in the nasopharynx serve as reservoirs for intrafamilial and nosocomial transmission. We show that the Bps polysaccharide of B. pertussis is critical for initial colonization of the mouse nose and the trachea but not of the lungs. Our data reveal a biofilm lifestyle for B. pertussis in the nose and the requirement of Bps in this developmental process. Bps functions as an adhesin by promoting adherence of B. pertussis and Escherichia coli to human nasal but not to human lung epithelia. Patient serum specifically recognized Bps suggesting its expression during natural human infections. We describe the first bacterial factor that exhibits a differential role in colonization and adherence between the nasopharynx and the lungs.

Topics: Adhesins, Bacterial; Animals; Bacterial Adhesion; Biofilms; Bordetella pertussis; Carrier State; Cell Line; Escherichia coli; Gene Deletion; Genetic Complementation Test; Humans; Lung; Mice; Mice, Inbred C57BL; Nose; Polysaccharides, Bacterial; Whooping Cough

This study examined the ability of the adenylate cyclase toxin (CyaA) of Bordetella pertussis to act as a mucosal adjuvant for other antigens when co-administered by the intranasal route in mice. Two forms of CyaA were used: the cell-invasive, enzymically active form and a cell-invasive toxin lacking adenylate cyclase enzymic activity (CyaA*). Co-administration intranasally (i/n) of CyaA or CyaA* with ovalbumin (Ova) significantly enhanced (P<0.05) anti-Ova IgG and IgA antibody responses in the serum and anti-Ova IgA responses in lung and nasal secretions compared to those generated by immunisation i/n with Ova alone. The effects were greater with CyaA*. Administration of CyaA* with Ova induced priming of Ova-specific T cells in vivo to a greater extent than that obtained after immunisation with Ova alone. Co-administration of CyaA or CyaA* with pertactin (Prn) significantly enhanced (P<0.05) the serum anti-Prn IgG responses and immunisation with Prn and CyaA* significantly increased the anti-Prn IgA responses in the lungs compared with responses after immunisation with Prn alone. Immunisation i/n with Prn alone partially protected mice (P<0.05) against challenge i/n with B. pertussis. Co-administration of CyaA or CyaA* with pertactin (Prn) significantly increased protection (P<0.05) against challenge compared to that obtained with Prn alone. These effects were particularly apparent with CyaA* as the adjuvant.

Topics: Adenylate Cyclase Toxin; Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Bacterial; Bacterial Outer Membrane Proteins; Bordetella pertussis; Female; Immunization; Lung; Mice; Mice, Inbred BALB C; Nose; Ovalbumin; Pertussis Vaccine; T-Lymphocytes; Virulence Factors, Bordetella; Whooping Cough

Mice have been infected by intranasal instillation of Bordetella pertussis and the infection monitored by determining numbers of bacteria isolated from the lungs. Outer membrane proteins, filamentous hemagglutinin, toxoided-lymphocytosis promoting factor and agglutinogens (fimbriae) actively protect mice against intranasal infection and antibodies of the antigens neutralize infectivity. The neutralization of infection by agglutinins is serospecific. In general, antigens that actively protect mice against intracerebral infections also protect against intranasal infections but some antigens, such as filamentous hemagglutinin and agglutinogens, protect only against intranasal infections. The intranasal protective potency of antigens can be enhanced by including low levels of active lymphocytosis promoting factor in the preparations. The relevance of the intranasal test to the potency testing of pertussis vaccines is discussed.

Topics: Animals; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Bordetella pertussis; Disease Models, Animal; Fimbriae, Bacterial; Hemagglutinins; Lung; Mice; Nose; Pertussis Toxin; Pertussis Vaccine; Respiratory Tract Infections; Virulence Factors, Bordetella; Whooping Cough

Topics: Bacteriological Techniques; Bordetella pertussis; Humans; Nose; Whooping Cough

Topics: Bordetella pertussis; Child; Humans; Nose; Specimen Handling; Whooping Cough

To define the role of adenoviruses in the pertussis syndrome, a study was done of a group of 134 children with clinical pertussis and a healthy control population of similar age, race, sex, and socioeconomic status. Adenovirus infections occurred in 30 (22.4%) of 134 patients with the pertussis syndrome and 5 (4.9%) of 101 control subjects (p smaller than 0.001). B. pertussis was recovered from 46 (34.3%) patients, and from 18 (39.1%) of these patients adenoviruses were also isolated. Although adenovirus infections also occurred in patients with the pertussis syndrome with negative cultures for B. pertussis, the rate, 12 of 88 patients (13.6%), was significantly lower (p smaller than 0.001). The clinical course was similar irrespective of the results of bacterial or viral cultures. These data substantiate the frequent association of adenoviruses with the pertussis syndrome, It would appear that adenoviruses do not usually have an independent role in the pathogenesis of the pertussis syndrome since we found them so commonly to be one agent in a mixed infection.

Topics: Adenoviridae; Adenoviridae Infections; Animals; Antibodies, Viral; Bordetella pertussis; Female; Humans; Infant; Leukocyte Count; Macaca mulatta; Male; Nose; Syndrome; Whooping Cough

Topics: Adolescent; Adult; Bordetella pertussis; Carrier State; Child; Child, Preschool; Culture Media; Fluorescent Antibody Technique; Humans; Infant; Nose; Penicillins; Pharynx; Whooping Cough

Topics: Antibodies; Fluorescent Antibody Technique; Humans; Immunoglobulins; Nasopharynx; Nose; Staining and Labeling; Whooping Cough