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.

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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.