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Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine  [PDF]
Pádraig J. Ross,Caroline E. Sutton equal contributor,Sarah Higgins equal contributor,Aideen C. Allen,Kevin Walsh,Alicja Misiak,Ed C. Lavelle,Rachel M. McLoughlin,Kingston H. G. Mills
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003264
Abstract: Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells.
Infección por Bordetella pertussis
Archivos argentinos de pediatr?-a , 2010,
Abstract: physiopathological, clinical, and epidemiological aspects of whooping cough, an acute highly contagious respiratory infection caused by bordetella pertussis, are described. different vaccination schedules are mentioned, since the vaccine was introduced, more than 40 years ago, until present; and the outbreacks ocurred in argentina during different periods. moreover, the recrudescense of the disease observed in several countries during last years is highlighted, particularly in preschool children, and even more in adolescents, and young adults.
Epidemiological consequences of an ineffective Bordetella pertussis vaccine  [PDF]
Benjamin M. Althouse,Samuel V. Scarpino
Quantitative Biology , 2014,
Abstract: The recent increase in Bordetella pertussis incidence (whooping cough) presents a challenge to global health. Recent studies have called into question the effectiveness of acellular B. pertussis vaccination in reducing transmission. Here we examine the epidemiological consequences of an ineffective B. pertussis vaccine. Using a dynamic transmission model, we find that: 1) an ineffective vaccine can account for the observed increase in B. pertussis incidence; 2) asymptomatic infections can bias surveillance and upset situational awareness of B. pertussis; and 3) vaccinating individuals in close contact with infants too young to receive vaccine (so called "cocooning" unvaccinated children) may be ineffective. Our results have important implications for B. pertussis vaccination policy and paint a complicated picture for achieving herd immunity and possible B. pertussis eradication.
Seroepidemiology of Bordetella pertussis infections in the twin cities of Pakistan
Muhammad Ali Syed,Fahad Said,S. Habib Ali Bukhari
North American Journal of Medical Sciences , 2009,
Abstract: Background: Bordetella pertussis is the cause of whooping cough occurring mainly in children. The prevalence of this disease has been reduced largely due to worldwide mass vaccination with DTP vaccine. However, the immunity produced by the vaccination wanes by the passage of time. Still this disease kills around 2-4 million children annually. Adults may be a source of infection for infants and children. Furthermore, Bordetella pertussis has also been found to be associated with cases of persistent cough in adults in many countries. Aim: The aim of this study was to study the exposure of the adult population to the Bordetella pertussis by detecting IgG antibodies. Materials and Methods: We performed Seroepidemiology of Bordetella pertussis infections in multiethnic twin cities of Pakistan (Rawalpindi and Islamabad) using a commercially available ELISA kit to have a picture of epidemiology of Bordetella pertussis in Pakistan. We targeted adults of age between 18-45 years (mean age 29.64 years). Results: The results of our study show a high percentage of seropositivity to Bordetella pertussis (89 percent), which indicates higher exposure to this organism and risk of infection to infants, children, adolescents and adults. Conclusion: A high percentage of seropositive individuals are alarming to health care professionals as well as policy makers. Bordetella pertussis infections may be associated with their atypical manifestation in Pakistan. Adult vaccination with DTP is recommended to reduce the risk of infection in infants and children through adult reservoirs.
Comparative genomics of prevaccination and modern Bordetella pertussis strains
Marieke J Bart, Marjolein van Gent, Han GJ van der Heide, Jos Boekhorst, Peter Hermans, Julian Parkhill, Frits R Mooi
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-627
Abstract: The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains.Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation.The genus Bordetella comprises nine species, of which four are exclusively respiratory pathogens of mammalian hosts: Bordetella bronchiseptica, Bordetella parapertussis, Bordetella pertussis and Bordetella holmesii [1]. The first three species are closely related, while B. holmesii forms a distinct branch [2]. B. bronchiseptica causes chronic and often asymptomatic respiratory tract infections in a wide variety of mammals and is only sporadically isolated from humans. B. parapertussis consists of two distinct lineages, designated B. parapertussisHU and B. parapertussisOV, which infect humans and sheep respectively [3,4]. B. parapertussisHU and B. pertussis are exclusive human pathogens and the causative agents of pertussis or whooping cough. Both these species have evolved independently from a B. bronchiseptica-like ancestor, a process which has been accompanied by extensive gene loss [4-6].By far, most cases of whooping cough are caused by B. pertussis. Despite widespread vaccination, pertussis remains a major cause of infant death worldwide [7]. In the 1990s a resurgence of pertussis was observed in several countries with highly vaccinated populati
Prevalence of Bordetella pertussis and Bordetella parapertussis in Samples Submitted for RSV Screening  [cached]
Walsh, Paul,Lim-Overmeyer, Christina,Kimmel, Lauren,Feola, Melanie
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2008,
Abstract: 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.
Monospecific antibody against Bordetella pertussis Adenylate Cyclase protects from Pertussis
Yasmeen Faiz Kazi,Qurban Hussain
Journal of Microbiology and Infectious Diseases , 2012,
Abstract: Objectives: Acellular pertussis vaccines has been largely accepted world-wide however, there are reports about limitedantibody response against these vaccines suggesting that multiple antigens should be included in acellular vaccinesto attain full protection. The aim of present study was to evaluate the role of Bordetella pertussis adenylate cyclase as aprotective antigen.Materials and methods: Highly mono-specific antibody against adenylate cyclase (AC) was raised in rabbits usingnitrocellulose bound adenylate cyclase and the specificity was assessed by immuoblotting. B.pertussis 18-323, wasincubated with the mono-specific serum and without serum as a control. Mice were challenged intra-nasally and pathophysiolgicalresponses were recorded.Results: The production of B.pertussis adenylate cyclase monospecific antibody that successfully recognized on immunoblotand gave protection against fatality (p< 0.01) and lung consolidation (p <0.01). Mouse weight gain showedsignificant difference (p< 0.05).Conclusion: These preliminary results highlight the role of the B.pertussis adenylate cyclase as a potential pertussisvaccine candidate. B.pertussis AC exhibited significant protection against pertussis in murine model. J Microbiol InfectDis 2012; 2(2): 36-43Key words: Pertussis; monospecific; antibody; passive-protection
Small Mutations in Bordetella pertussis Are Associated with Selective Sweeps  [PDF]
Marjolein van Gent, Marieke J. Bart, Han G. J. van der Heide, Kees J. Heuvelman, Frits R. Mooi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046407
Abstract: Bordetella pertussis is the causative agent of pertussis, a highly contagious disease of the human respiratory tract. Despite high vaccination coverage, pertussis has resurged and has become one of the most prevalent vaccine-preventable diseases in developed countries. We have proposed that both waning immunity and pathogen adaptation have contributed to the persistence and resurgence of pertussis. Allelic variation has been found in virulence-associated genes coding for the pertussis toxin A subunit (ptxA), pertactin (prn), serotype 2 fimbriae (fim2), serotype 3 fimbriae (fim3) and the promoter for pertussis toxin (ptxP). In this study, we investigated how more than 60 years of vaccination has affected the Dutch B. pertussis population by combining data from phylogeny, genomics and temporal trends in strain frequencies. Our main focus was on the ptxA, prn, fim3 and ptxP genes. However, we also compared the genomes of 11 Dutch strains belonging to successful lineages. Our results showed that, between 1949 and 2010, the Dutch B. pertussis population has undergone as least four selective sweeps that were associated with small mutations in ptxA, prn, fim3 and ptxP. Phylogenetic analysis revealed a stepwise adaptation in which mutations accumulated clonally. Genomic analysis revealed a number of additional mutations which may have a contributed to the selective sweeps. Five large deletions were identified which were fixed in the pathogen population. However, only one was linked to a selective sweep. No evidence was found for a role of gene acquisition in pathogen adaptation. Our results suggest that the B. pertussis gene repertoire is already well adapted to its current niche and required only fine tuning to persist in the face of vaccination. Further, this work shows that small mutations, even single SNPs, can drive large changes in the populations of bacterial pathogens within a time span of six to 19 years.
Phase variation and microevolution at homopolymeric tracts in Bordetella pertussis
Emily B Gogol, Craig A Cummings, Ryan C Burns, David A Relman
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-122
Abstract: The genomes of B. pertussis and the two closely related species, B. bronchiseptica and B. parapertussis, were screened for homopolymeric tracts longer than expected on the basis of chance, given their nucleotide compositions. Sixty-nine such HPTs were found in total among the three genomes, 74% of which were polymorphic among the three species. Nine HPTs were genotyped in a collection of 90 geographically and temporally diverse B. pertussis strains using the polymerase chain reaction/ligase detection reaction (PCR/LDR) assay. Six HPTs were polymorphic in this collection of B. pertussis strains. Of note, one of these polymorphic HPTs was found in the fimX promoter, where a single base insertion variant was present in seven strains, all of which were isolated prior to introduction of the pertussis vaccine. Transcript abundance of fimX was found to be 3.8-fold lower in strains carrying the longer allele. HPTs in three other genes, tcfA, bapC, and BP3651, varied widely in composition across the strain collection and displayed allelic polymorphism within single cultures.Allelic polymorphism at homopolymeric tracts is common within the B. pertussis genome. Phase variability may be an important mechanism in B. pertussis for evasion of the immune system and adaptation to different niches in the human host. High sensitivity and specificity make the PCR/LDR assay a powerful tool for investigating allelic variation at HPTs. Using this method, allelic diversity and phase variation were demonstrated at several B. pertussis loci.Bordetella pertussis causes whooping cough, a highly communicable disease that killed roughly 279,000 people and infected 17.6 million people globally in a recent typical year [1]. B. pertussis and the closely related human- and sheep-adapted species, B. parapertussis, have diverged independently by genome decay from a putative common ancestor that they share with B. bronchiseptica, which has a broader host range, and unlike the other two species, causes
Rini Pangastuti,Eko Suprijanto,Muljati Prijanto,Dyah W. Isbagio
Bulletin of Health Research , 2012,
Abstract: The antibiotic resistancy of Bordetella pertussis to erythromicin, chloramphenicol and tetracyclin has been examined using Disc diffusion method described by Kirby bauer (1966) on Charcoal agar contains 10% sheep blood. The examination was done on positive culture which had been collected from 233 nasopharyngeal swab specimens. The results showed that no resistant to erythromicin (0%). Mean while there was significant resistancy to chloramphenicol (5,6%) and tetracyclin (25%). Antibiotic treatment should be given rationally to gain efficiency in antibiotic usage, to avoid antibiotic resistancy and to minimize cost of treatment.
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