Bordetella pertussis hhmi.princeton/sw/2002/psidelsk/Microlinks.htm

Bordetella pertussis http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm Jill Angelosanto Bio 360

Outline Bordetella Pertussis microbiology Whooping Cough/Pertussis Vaccine Current problems with B. pertussis

Bordetella pertussis Basics Aerobic, Gram negative coccobacillus Alcaligenaceae Family Specific to Humans Colonizes the respiratory tract Whooping Cough (Pertussis) http://microvet.arizona.edu/Courses/MIC420/lecture notes/bordetella pertussis/ gram pertussis.html

Transmission Very Contagious Transmission occurs via respiratory droplets http://www.universityscience.ie/imgs/scientists/whoopingcough.gif http://www.ratbags.com/rsoles/history/2000/12december.htm

Virulence Steele, R.W. Pertussis: Is Eradication Achievable. Pediatric Annals. Aug 2004. 33(8):525-534

Adhesions Filamentous hemagglutinin Pertactin Fimbriae http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpg http://www.my-pharm.ac.jp/ yishibas/research/Pertussis1.jpg

Toxins Pertussis Toxin Adenylate Cyclase Toxin Tracheal cytotoxin Dermonecrotic toxin Heat-labile toxin www.ibl.fr/u447/u447.htm

Pertussis Toxin Colonizing factor and endotoxin Cell bound and extracellular gsbs.utmb.edu/ microbook/ch031.htm www.med.sc.edu:85/ ghaffar/pertussis.jpg

Adenylate Cyclase Toxin Invasive toxin Activated by host cell calmodulin Impairment of immune effector cells Babu et al., 2001

The bvg locus Controls expression of virulence factors Encodes BvgA, BvgS and BvgR BvgA-BvgS signal transduction system Babu et al., 2001

Whooping Cough Also known as Pertussis Outbreaks first described in the 16th Century Major cause of childhood fatality prior to vaccination paaap.org/immunize/ course/slide27.html

Clinical Features Incubation 3 period 4-21 days Stages 1st Stage- Catarrhal Stage 1-2 weeks 2nd Stage- Paroxysmal Stage 1-6 weeks 3rd Stage- Covalescent Stage weeks-months http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf

Pertussis Infection gsbs.utmb.edu/ microbook/ch031.htm

Diagnosis Isolation by culture PCR Direct fluorescent antibody Serological testing http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg

Treatment Antibiotic therapy Erythromycin Azithromycin 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 Vaccine 1st Pertussis vaccine- whole cell Acellular vaccine now used Combination vaccines http://www.tdh.state.tx.us/immunize/providers.htm http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html

Increase in Pertussis cases Incidence of disease increasing in countries with high vaccination levels US- Massachusetts Netherlands France Finland http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf

Cases in 2003 http://www.pertussis.com/digest/index.html

Massachusetts Yih et al., 2000 Substantial increase in the number of cases in adolescents and adults since 1980’s

Netherlands Mismatch between vaccine strains and circulating strains played role in reemergence Mooi et al., 2001

Strain Variation B. pertussis population has changed significantly since vaccine introduction Adaptation to vaccine Antigenic divergence Mooi et al., 2001

Vaccine problems Complications/Safety Multiple administration Waning adolescent and adult immunity Strain Variability http://www.healthcareforhoosiers.com/Member/vaccineschedule.html

Conclusions Reemerging in adult and adolescent populations as worldwide vaccination rates increase High vaccination rates not enough Better vaccine development needed

References Ahuja, 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 CyclaseHemolysin 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. 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 VariableNumber 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.