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Bordetella pertussisBordetella pertussis
http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm
Jill Angelosanto
Bio 360
OutlineOutline
Bordetella PertussisBordetella Pertussis microbiology microbiologyWhooping Cough/Pertussis Whooping Cough/Pertussis VaccineVaccineCurrent problems with Current problems with B. pertussisB. pertussis
Bordetella pertussisBordetella pertussis Basics Basics
Aerobic, Gram negative coccobacillusAerobic, Gram negative coccobacillusAlcaligenaceae Alcaligenaceae FamilyFamilySpecific to HumansSpecific to HumansColonizes the respiratory tract Colonizes the respiratory tract
Whooping Cough (Pertussis)Whooping Cough (Pertussis)
http://microvet.arizona.edu/Courses/MIC420/lecture_notes/bordetella_pertussis/gram_pertussis.html
TransmissionTransmissionVery ContagiousVery ContagiousTransmission occurs via respiratory Transmission occurs via respiratory
dropletsdroplets
http://www.ratbags.com/rsoles/history/2000/12december.htmhttp://www.universityscience.ie/imgs/scientists/whoopingcough.gif
VirulenceVirulence
Steele, R.W. Pertussis: Is Eradication Achievable. Pediatric Annals. Aug 2004. 33(8):525-534
AdhesionsAdhesions
Filamentous hemagglutininFilamentous hemagglutininPertactinPertactinFimbriaeFimbriae
http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpghttp://www.my-pharm.ac.jp/~yishibas/research/Pertussis1.jpg
ToxinsToxins
Pertussis ToxinPertussis ToxinAdenylate Cyclase ToxinAdenylate Cyclase ToxinTracheal cytotoxinTracheal cytotoxinDermonecrotic toxinDermonecrotic toxinHeat-labile toxinHeat-labile toxin
www.ibl.fr/u447/u447.htm
Pertussis ToxinPertussis Toxin
Colonizing factor and endotoxinColonizing factor and endotoxinCell bound and extracellularCell bound and extracellular
gsbs.utmb.edu/ microbook/ch031.htm www.med.sc.edu:85/ ghaffar/pertussis.jpg
Adenylate Cyclase ToxinAdenylate Cyclase Toxin
Invasive toxinInvasive toxinActivated by host cell calmodulinActivated by host cell calmodulin Impairment of immune effector cellsImpairment of immune effector cells
Babu et al., 2001
The The bvgbvg locus locus
Controls expression of Controls expression of virulence factorsvirulence factors
Encodes BvgA, BvgS Encodes BvgA, BvgS and BvgRand BvgRBvgA-BvgS signal BvgA-BvgS signal
transduction systemtransduction system
Babu et al., 2001
Whooping CoughWhooping Cough
Also known as PertussisAlso known as PertussisOutbreaks first described in the 16Outbreaks first described in the 16thth
CenturyCenturyMajor cause of childhood fatality prior to Major cause of childhood fatality prior to
vaccinationvaccination
paaap.org/immunize/ course/slide27.html
Clinical Features Clinical Features
Incubation period 4-21 daysIncubation period 4-21 days3 Stages3 Stages
11stst Stage- Catarrhal Stage 1-2 weeks Stage- Catarrhal Stage 1-2 weeks22ndnd Stage- Paroxysmal Stage 1-6 weeks Stage- Paroxysmal Stage 1-6 weeks33rdrd Stage- Covalescent Stage weeks-months Stage- Covalescent Stage weeks-months
http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf
Pertussis InfectionPertussis Infection
gsbs.utmb.edu/ microbook/ch031.htm
DiagnosisDiagnosis
Isolation by cultureIsolation by culturePCRPCRDirect fluorescent antibodyDirect fluorescent antibodySerological testingSerological testing
http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg
TreatmentTreatment
Antibiotic therapyAntibiotic therapyErythromycinErythromycinAzithromycin and clarithromycinAzithromycin and clarithromycin
http://www.aboutthatbug.com/AboutThatBug/files/CCLIBRARYFILES/FILENAME/0000000032/033_lg.jpg http://www.vet.purdue.edu/bms/courses/lcme510/chmrx/macrohd.htm
Pertussis VaccinePertussis Vaccine
1st Pertussis vaccine- whole cell1st Pertussis vaccine- whole cellAcellular vaccine now usedAcellular vaccine now usedCombination vaccinesCombination vaccines
http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html
http://www.tdh.state.tx.us/immunize/providers.htm
Increase in Pertussis casesIncrease in Pertussis cases
Incidence of disease increasing in Incidence of disease increasing in countries with high vaccination levelscountries with high vaccination levelsUS- MassachusettsUS- MassachusettsNetherlandsNetherlandsFranceFranceFinlandFinland
http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf
Cases in 2003Cases in 2003
http://www.pertussis.com/digest/index.html
MassachusettsMassachusetts
Yih et al., 2000
Substantial increase in the number of cases Substantial increase in the number of cases in adolescents and adults since 1980’sin adolescents and adults since 1980’s
NetherlandsNetherlands
Mismatch between Mismatch between vaccine strains and vaccine strains and circulating strains circulating strains played role in played role in reemergencereemergence
Mooi et al., 2001
Strain VariationStrain Variation
B. pertussisB. pertussis population has changed population has changed significantly since vaccine introductionsignificantly since vaccine introductionAdaptation to vaccineAdaptation to vaccineAntigenic divergenceAntigenic divergence
Mooi et al., 2001
Vaccine problemsVaccine problems
Complications/SafetyComplications/SafetyMultiple administration Multiple administration Waning adolescent and adult immunityWaning adolescent and adult immunityStrain VariabilityStrain Variability
http://www.healthcareforhoosiers.com/Member/vaccineschedule.html
ConclusionsConclusions
Reemerging in adult and adolescent Reemerging in adult and adolescent populations as worldwide vaccination rates populations as worldwide vaccination rates increaseincreaseHigh vaccination rates not enoughHigh vaccination rates not enoughBetter vaccine development neededBetter vaccine development needed
ReferencesReferencesAhuja, N., Kumar, P., Bhatnagar, R. The Adenylate Cyclase Toxins. Critical Reviews in
Microbiology. 2004; 30(3): 187-196.Babu, MM., Bhargavi, J., Singh Saund, R., Singh, S.K. Virulence Factors in Bordetella pertussis.
Current Science. June 2001; 80(12): 1512-1522.Coote, JG. Environmental Sensing Mechanisms in Bordetella. Advances in Microbial Physiology.
2001; 44: 141-181.Dalet, K., Weber, C., Guillemot, L., Njamkepo, E., Guiso, N. Characterization of Adenylate Cyclase-
Hemolysin Gene Duplication in a Bordetella pertussis isolate. Infection and Immunity. Aug 2004; 72(8): 4874-4877.
Forsyth, K.D., Campins-Marti, M., Caro, J., Cherry, J.D., Greenberg, D., Guiso, N., Heininger, U., Schellenkens, J., Tan, T., von Konig, C., Plotkin, S. New Pertussis Vaccination Strategies beyond Infancy: Recommendations by the Global Pertussis Initiative. Clinical Infectious Diseases. Dec 2004: 39: 1802-1809.
Hardwick, T.H., Cassiday, P., Weyant, R.S., Bisgard, K.M., Sanden, G.N. Changes in the Predominance and Diversity of Genomic Subtypes of Bordetella pertussis Isolated in the United States, 1935-1999. Emerging Infectious Diseases. Jan 2002; 8(1): 44-49.
Mattoo, S., Foreman-Wykert, A., Cotter, P., Miller, J. Mechanisms of Bordetella Pathogenesis. Frontiers in Bioscience. Nov 2001; 6: E168-186
Merkel, T.J., Stibitz, S., Keith, J.M., Leef, M., Shahin, R. Contribution of Regulation by the bvg Locus to Respiratory Infection of Mice by Bordetella pertussis. Infection and Immunity. Sept 1998; 66(9): 4367-4373.
Reference cont.Reference cont.Mooi, F.R., van Loo, I.H.M., King, A.J. Adaptation of Bordetella pertussis to Vaccination: A Cause for
Its Reemergence? Emerging Infectious Disease. June 2001; 7(No. 3 Supplement): 526-528.Pishko, E.J., Betting, D.J., Hutter, C.S., Harvill, E.T. Bordetella pertussis Aquires Resistance to
Complement Mediated Killing In Vivo. Infection and Immunity. Sept 2003; 71(9): 4936-4942.Robbins, J.B., Schneerson, R., Trollfors, B., Sato, H., Sato, Y., Rappuoli, R., Keith., J.M. The
Diphtheria and Pertussis Components of the Diphtheria-Tetanus Toxoids-Pertussis Vaccine Should Be Genetically Inactivated Mutant Toxins. The Journal of Infectious Diseases. 2005;191: 81-88.
Schouls, L.M., van der Heide, H.G.J., Vauterin, L., Vaurerin, P., Mooi, F.R. Multiple-Locus Variable-Number Tandem Repeat Analysis of Dutch Bordetella pertussis Strains Reveals Rapid Genetic Changes with Clonal Expansion during the Late 1990s. Journal of Bacteriology. Aug 2004; 186(16): 5496-5505.
Shumilla, J.A., Lacaille, V., Hornell, M.C., Haung, J., Narasimhan, S., Relman, D.A., Mellins, E.D. Bordetella Pertussis Infection of Primary Human Monocytes Alters HLA-DR Expression. Infection and Immunity. Mar 2004; 72(3): 1450-1462.
Steele, RW. Pertussis: Is Eradication Achievable? Pediatric Annals. Aug 2004; 33(8): 525-534.Veal-Carr, W., Stibitz, S. Demonstration of differential virulence gene promoter activation in vivo in
Bordetella pertussis using RIVET. Molecular Microbiology. 2005; 55(3): 788-798.Yih, W.K., Lett, S.M., des Vignes, F.N., Garrison, K.M., Sipe, P.L., Marchant, C.D. The Increasing
Incidence of Pertussis in Massachusetts Adolescents and Adults, 1989-1998. The Journal of Infectious Diseases. 2000; 182: 1409-1416.