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

2

Bordetella pertussis Basics

Aerobic, Gram negative coccobacillus

Alcaligenaceae Family

Specific to Humans

Colonizes the respiratory tract

Whooping Cough (Pertussis)

3 http://microvet.arizona.edu/Courses/MIC420/lecture_notes/bordetella_pertussis/

gram_pertussis.html

What is Pertussis?

Whooping cough, “The Cough of 100 Days”

4

Transmission

Very Contagious

Transmission occurs via respiratory droplets

5 http://www.ratbags.com/rsoles/history/2000/12december.htm http://www.universityscience.ie/imgs/scientists/whoopingcough.gif

Spread of Pertussis: Then vs. Now

6

7

Virulence Factors

Adhesions

Filamentous hemagglutinin (FHA)

Pertactin

Fimbriae

Colonization of tracheal epithelial cells

by Bordetella pertussis

*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.

*B. Pertussis also produces an adhesin called pertactin that further

enables the bacterium to adhere to cells.

8

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

Adhesions

Filamentous hemagglutinin

Pertactin

Fimbriae

9 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

10 www.ibl.fr/u447/u447.htm

Pertussis Toxin

Colonizing factor and endotoxin

Cell bound and extracellular

11

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

12

Babu et al., 2001

13

The bvg locus

Controls expression of

virulence factors

Encodes BvgA, BvgS and

BvgR

BvgA-BvgS signal

transduction system

14

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

15 paaap.org/immunize/ course/slide27.html

16

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

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

17

http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf

18

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

19

Pertussis Complications*

Condition

Pneumonia

Seizures

Encephalopathy

Hospitalization

Death

Percent reported

4.9

0.7

0.1

16

0.2

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

Diagnosis

Isolation by culture

PCR

Direct fluorescent antibody

Serological testing

20 http://medinfo.ufl.edu/year2/mmid/bms5300/images/d7053.jpg

21

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.

Treatment

Antibiotic therapy

Erythromycin

Azithromycin and clarithromycin

22

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

23 http://www.nfid.org/publications/clinicalupdates/pediatric/pertussis.html

http://www.tdh.state.tx.us/immunize/providers.htm

24

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)

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.

25

26

New School Entry Requirements, 2012-2013

27

28

Pertussis Vaccination of (Teens and) Adults

Who What

Pregnant or post-

partum women not

previously

vaccinated with

Tdap

• one dose of Tdap during the third trimester or late second

trimester*

• One dose of Tdap in the immediate postpartum period before

discharge from hospital or birthing center if not previously

vaccinated with Tdap or status unknown*

Healthcare personnel

who have not

previously received

Tdap as an adult

• A single dose of Tdap is recommended for health care

personnel and who have direct patient contact*

• Prioritize those who have direct contact with infants

28

*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.

29

DTaP Clinical Trials

Product

Daptacel

Tripedia

Infanrix

Location

Sweden

Germany

Italy

VE (95% CI)

85% (80-89)

80% (59-90)

84% (76-89)

30

Routine DTaP Primary Vaccination

Schedule

Dose

Primary 1

Primary 2

Primary 3

Primary 4

Age

2 months

4 months

6 months

15-18 months

Minimum Interval

---

4 wks

4 wks

6 mos

31

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

32

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

33

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

34

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

35

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

36

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.

37

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.

Increase in Pertussis cases

Incidence of disease increasing in countries

with high vaccination levels

US- Massachusetts

Netherlands

France

Finland

38

http://www.cdc.gov/nip/publications/pertussis/chapter1.pdf

Increased awareness and reporting

Better tests

Waning immunity in adults

39

Why is the Incidence of Pertussis

Increasing?

Cases in 2003

40 http://www.pertussis.com/digest/index.html

41

0

5000

10000

15000

20000

25000

30000

1980 1985 1990 1995 2000 2005

Ca

se

sPertussis—United States, 1980-2007

Year

42

Reported Pertussis by Age Group,

1990-2007

0

5000

10000

15000

20000

25000

30000

1990 1995 2000 2005

Year

Cas

es

<11 11-18 >18

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

44 Mooi et al., 2001

Vaccine problems

Complications/Safety

Multiple administration

Waning adolescent and adult immunity

Strain Variability

45

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

46

Live attenuated pertussis vaccines

Are they the future of

pertussis control ?

47

Live attenuated B. pertussis for intranasal

administration

Mucosal administration Induction of systemic and mucosal immune responses

Ease of administration

Persistence of the bacteria in the host

Long-lived immune responses

Reduced number of administrations to induce

protection

Potential as a multivalent vaccine

Conclusions

Reemerging in adult and adolescent

populations as worldwide vaccination rates

increase

High vaccination rates not enough

Better vaccine development needed

48

References

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Reference cont.

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Reemergence? Emerging Infectious Disease. June 2001; 7(No. 3 Supplement): 526-528.

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