Bordetella pertussis

http://www.hhmi.princeton.edu/sw/2002/psidelsk/Microlinks.htm

Dr. M. Noofeli
 Outline

 Bordetella Pertussis microbiology

 Whooping Cough/Pertussis
 Vaccine
 Current problems with B. pertussis

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 Bordetella pertussis Basics
 Aerobic, Gram negative coccobacillus
 Alcaligenaceae Family
 Specific to Humans
 Colonizes the respiratory tract
 Whooping Cough (Pertussis)

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http://microvet.arizona.edu/Courses/MIC420/lecture_notes/bordetella_pertussis/
gram_pertussis.html
 What is Pertussis?
Whooping cough, “The Cough of 100 Days”

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 Transmission
 Very Contagious
 Transmission occurs via respiratory droplets

http://www.universityscience.ie/imgs/scientists/whoopingcough.gif 5
http://www.ratbags.com/rsoles/history/2000/12december.htm
Spread of Pertussis: Then vs. Now

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 Virulence Factors

 Adhesions
 Filamentous hemagglutinin (FHA)

 Pertactin

 Fimbriae

*Filamentous hemagglutinin is an adhesin that allows the bacterium

to adhere to galactose residues of the glycolipids on the membrane
of ciliated epithelial cells of the respiratory tract.

*Pertussis toxin also functions as an adhesin. One subunit of the

pertussis toxin remains bound to the bacterial cell wall while another
subunit binds to the glycolipids on the membrane of ciliated epithelial
cells of the respiratory tract.
Colonization of tracheal epithelial cells
by Bordetella pertussis 7
*B. Pertussis also produces an adhesin called pertactin that further
enables the bacterium to adhere to cells.
 Virulence Factors Cont..
 Toxins
 Pertussis Toxin (PTX)

 Colonizing factor

 Cell Bound

 Extracellular

 Adenylate Cyclase Toxin (CYA)

 Invasive toxin

 Activated by host cell calmodulin

 Tracheal Cytotoxin (TCT)

 Disaccharide tetrapeptide

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 Adhesions
 Filamentous hemagglutinin
 Pertactin
 Fimbriae

http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpg
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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
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 Pertussis Toxin
 Colonizing factor and endotoxin
 Cell bound and extracellular

gsbs.utmb.edu/ microbook/ch031.htm
www.med.sc.edu:85/ ghaffar/pertussis.jpg

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 Adenylate Cyclase Toxin
 Invasive toxin
 Activated by host cell calmodulin
 Impairment of immune effector cells

Babu et al., 2001

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13
 The bvg locus

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

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 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 15
 Pertussis Among Adolescents and
Adults
 Disease often milder than in infants and children
 Infection may be asymptomatic, or may present
as classic pertussis
 Persons with mild disease may transmit the
infection
 Older persons often source of infection for
children

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 Clinical Features
 Incubation period 4-21 days
 3 Stages
 1st Stage- Catarrhal Stage 1-2 weeks
 2nd Stage- Paroxysmal Stage 1-6 weeks
 3rd Stage- Convalescent Stage weeks-months

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http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf
 Incubation period 4-21 days
 3 Stages
 1st Stage- Catarrhal Stage 1-2 weeks

 runny nose, sneezing, low fever, and a mild cough (common mistaken for cold)
 2nd Stage- Paroxysmal Stage 1-6 weeks
 whooping cough, which consists of bursts or paroxysms of numerous, rapid coughs,
severity of the infection is at its greatest
 3rd Stage- Covalescent Stage weeks-months
 gradual recovery starts

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 Pertussis Complications*

Condition Percent reported

Pneumonia 4.9
Seizures 0.7
Encephalopathy 0.1
Hospitalization 16
Death 0.2

*Cases reported to CDC 2001-2003 (N=28,998) 19

 Diagnosis
 Isolation by culture
 PCR
 Direct fluorescent antibody
 Serological testing

http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg
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Test only patients with signs and symptoms of pertussis 
Within 3 weeks of cough onset 
Nasopharyngeal swab or aspirate 

Prepare and administer vaccines in areas separate from 

pertussis specimen collection
Wear gloves immediately before and during specimen 
collection or vaccine preparation and administration with
immediate disposal of gloves after the procedure, and
Clean surfaces using a 10% bleach solution to reduce the 
amount of nucleic acids in the clinic environment.

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 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

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 Pertussis Vaccine
 1st Pertussis vaccine- whole cell
 Acellular vaccine now used
 Combination vaccines

http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html
http://www.tdh.state.tx.us/immunize/providers.htm
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 Pertussis-containing Vaccines
 DTaP (pediatric)
 approved for children 6 weeks through 6 years (to
age 7 years)

 Tdap (adolescent and adult)

 approved for persons 10 through 64 years
(Boostrix) and 11 through 64 years (Adacel)

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 Vaccine Schedule:
Expanded to Adults!
 DTaP
 2, 4, 6 months
 15-18 months
 4-6 years
 Tdap
 11-12 years
 One dose between 19-
64 (instead of Td)
 Any adult in contact
with infant <1 y.o.
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New School Entry Requirements,
2012-2013

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27
 Pertussis Vaccination of
(Teens and) Adults
Who What
Pregnant or post- • one dose of Tdap during the third trimester or late second
partum women not trimester*
previously • One dose of Tdap in the immediate postpartum period before
vaccinated with discharge from hospital or birthing center if not previously
Tdap vaccinated with Tdap or status unknown*
Healthcare personnel • A single dose of Tdap is recommended for health care
who have not personnel and who have direct patient contact*
previously received • Prioritize those who have direct contact with infants
Tdap as an adult

*can be administered regardless of interval since the previous Td dose. Shorter

intervals may be appropriate if your patient is at high risk for contracting pertussis,
or has close contact with infants.
28
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 DTaP Clinical Trials

Product Location VE (95% CI)

Daptacel Sweden 85% (80-89)
Tripedia Germany 80% (59-90)
Infanrix Italy 84% (76-89)

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 Routine DTaP Primary Vaccination
Schedule
Minimum
Dose Age Interval
Primary 1 2 months ---
Primary 2 4 months 4 wks
Primary 3 6 months 4 wks
Primary 4 15-18 months 6 mos
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 DTaP Adverse Reactions
 Local reactions 20%-40%
(pain, redness, swelling)
 Temp of 101oF 3%-5%
or higher
 More severe adverse reactions
not common
 Local reactions more common following 4th
and 5th doses 31
Adverse Reactions Following the 4th
and 5th DTaP Dose

 Local adverse reactions and fever increased with

4th and 5th doses
of DTaP
 Reports of swelling of entire limb
 Extensive swelling after 4th dose NOT a
contraindication to 5th dose

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 DTaP Contraindications

 Severe allergic reaction to vaccine

component or following a prior dose
 Encephalopathy not due to another
identifiable cause occurring within 7 days
after vaccination

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 DTaP Precautions

 Moderate or severe acute illness

 Temperature >105°F (40.5°C) or higher within 48
hours with no other identifiable cause
 Collapse or shock-like state (hypotonic
hyporesponsive episode) within 48 hours
 Persistent, inconsolable crying lasting >3 hours,
occurring within 48 hours
 Convulsions with or without fever occurring within 3
days
*may consider use in outbreaks 34
 Pertussis Among Adolescents
and Adults
 Prolonged cough (3 months or longer)
 Post-tussive vomiting
 Multiple medical visits and extensive medical evaluations
 Complications
 Hospitalization
 Medical costs
 Missed school and work
 Impact on public health system
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 Recommendations for Tdap
Vaccination of Adolescents
 Adolescents 11 or 12 years of age should receive a
single dose of Tdap instead of Td*
 Adolescents 13 through 18 years who have not
received Tdap should receive a single dose of Tdap
as their catch-up booster instead of Td*

*if the person has completed the recommended childhood

DTaP/DTP vaccination series, and has not yet received a
Td booster
MMWR 2006;55(RR-3):1-43. 36
 Tdap Vaccination of Adults
19 Through 64 Years of Age

 Single dose of Tdap to replace a single dose of Td

 May be given at an interval less than 10 years
since receipt of last tetanus toxoid-containing
vaccine
 Special emphasis on adults with close contact with
infants (e.g., childcare and healthcare personnel,
and parents)

MMWR 2006;55(RR-17):1-37. 37
 Increase in Pertussis cases
 Incidence of disease increasing in countries
with high vaccination levels
 US- Massachusetts
 Netherlands
 France
 Finland

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http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf
 Why is the Incidence of Pertussis
Increasing?

 Increased awareness and reporting

 Better tests
 Waning immunity in adults

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Cases in 2003

http://www.pertussis.com/digest/index.html
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 Pertussis—United States, 1980-2007
30000

25000

20000
Cases

15000

10000

5000

0
1980 1985 1990 1995 2000 2005

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Year
 Reported Pertussis by Age Group,
1990-2007
<11 11-18 >18
30000
25000
20000
Cases

15000
10000
5000
0
1990 1995 2000 2005
Year 42
 Netherlands
 Mismatch between
vaccine strains and
circulating strains
played role in
reemergence

43
Mooi et al., 2001
 Strain Variation
 B. pertussis population has changed
significantly since vaccine introduction
 Adaptation to vaccine
 Antigenic divergence

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Mooi et al., 2001
 Vaccine problems
 Complications/Safety
 Multiple administration
 Waning adolescent and adult immunity
 Strain Variability

http://www.healthcareforhoosiers.com/Member/vaccineschedule.html

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Live attenuated pertussis vaccines
Are they the future of
pertussis control ?

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Live attenuated B. pertussis for intranasal
administration
Mucosal administration

Ease of administration
Induction of systemic and mucosal immune responses

Persistence of the bacteria in the host

Long-lived immune responses
Reduced number of administrations to induce
protection
Potential as a multivalent vaccine

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

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 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 Cyclase-
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4373.

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 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
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 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
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 Yih, W.K., Lett, S.M., des Vignes, F.N., Garrison, K.M., Sipe, P.L., Marchant, C.D. The Increasing
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