W. Michael Brown, MD, FAAP

Director of Pediatrics

Associate Director Family Medicine Residency

Bayfront Medical Center

St. Petersburg, Florida

Pertussis AwarenessPertussis AwarenessAnd PreventionAnd Prevention

Pertussis Awareness and Prevention: Pertussis Awareness and Prevention: ObjectivesObjectives

• Increase awareness and prevention of pertussis in the United States

• Educate health care professionals on epidemiology and diagnosis of pertussis

• Discuss importance of pertussis immunization

• Discuss important strategies for improving control of pertussis

• Increase awareness and prevention of pertussis in the United States

• Educate health care professionals on epidemiology and diagnosis of pertussis

• Discuss importance of pertussis immunization

• Discuss important strategies for improving control of pertussis

PERTUSSIS (WHOOPING COUGH)PERTUSSIS (WHOOPING COUGH)

• Acute respiratory tract infection by Bordetella pertussis

• highly communicable

• 80% secondary attack rates among susceptible persons

• Significant morbidity and mortality in infants

• Milder nonspecific upper respiratory tract infection in adolescents and adults

• Difficult to diagnose

• Referred to by the Chinese as “the cough of 100 days”

• Acute respiratory tract infection by Bordetella pertussis

• highly communicable

• 80% secondary attack rates among susceptible persons

• Significant morbidity and mortality in infants

• Milder nonspecific upper respiratory tract infection in adolescents and adults

• Difficult to diagnose

• Referred to by the Chinese as “the cough of 100 days”

Prolonged Cough Illness in Adolescents Prolonged Cough Illness in Adolescents and Adults Due to and Adults Due to Bordetella PertussisBordetella Pertussis

Source Locale Year(s) % of cough illnesses

Jackson et al Seattle 1983-87 15%Robertson et al New S Wales 1985-86 26%Mink et al Los Angeles 1986-89 26%Schmitt-Grohé et al Germany 1992-94 32%Wright et al Nashville 1992-94 21%Wirsing v Köenig et al Germany 1992-94 31%Rosenthal et al Chicago 1993-94 26%Jansen et al San Diego 1993-94 17%Nennig et al San Francisco 1994-95 12%Strebel et al Minn-St Paul 1995-96 13%Birbeback et al Denmark 1995-97 17%Vicent et al Korea 1997-98 50%Gilberg et al Paris 1999 52%

Pertussis Disease ManifestationsPertussis Disease Manifestations

• Incubation period -- 7 - 10 days (range 4 - 21)

• Stages• Catarrhal: runny nose,

sneezing, low-grade fever, mild cough

• Paroxysmal: severe spasms of cough, thick mucus, whoops, vomiting, exhaustion

• Convalescent: gradual recovery with less frequent & less severe coughing

Photograph courtesy of the WHO

Why Is Pertussis Increasing?Why Is Pertussis Increasing?

• Ascertainment…awareness and better diagnostic tests

• Incomplete immunization of children

• Variable vaccine efficacy

• Waning immunity• ~ 15 years after active disease• ~ 5-10 years after vaccination

• Under diagnosis, especially in adolescents and adults

• Lack of an adolescent/adult booster vaccine

UNTIL NOW

• Ascertainment…awareness and better diagnostic tests

• Incomplete immunization of children

• Variable vaccine efficacy

• Waning immunity• ~ 15 years after active disease• ~ 5-10 years after vaccination

• Under diagnosis, especially in adolescents and adults

• Lack of an adolescent/adult booster vaccine

UNTIL NOW

DECLINE IN VACCINE-PREVENTABLE DISEASEDECLINE IN VACCINE-PREVENTABLE DISEASE

Disease Maximum Cases %

cases in 2003 change

_____________________________________________________________________________________

Diphtheria 296,939 in 1921 1 99.99%

_____________________________________________________________________________________

Tetanus 1,560 in 1923 20 98.5%

_____________________________________________________________________________________

Pertussis 265,269 in 1934 11647 92.1%

_____________________________________________________________________________________

Measles 894,134 in 1941 56 99.98%

_____________________________________________________________________________________

Paralytic polio 21,269 in 1952 0 100%

3,100 died

_______________________ _____________________________________________________________

Mumps 152,209 in 1968 231 99.80%

_____________________________________________________________________________________

Rubella 57,686 in 1969 7 99.9%

_____________________________________________________________________________________

HIB 20,000 prior to 1985 259 98.7%

_____________________________________________________________________________________

From Centers for Disease Control and Prevention. MMWR 2004

Disease Maximum Cases %

cases in 2003 change

_____________________________________________________________________________________

Diphtheria 296,939 in 1921 1 99.99%

_____________________________________________________________________________________

Tetanus 1,560 in 1923 20 98.5%

_____________________________________________________________________________________

Pertussis 265,269 in 1934 11647 92.1%

_____________________________________________________________________________________

Measles 894,134 in 1941 56 99.98%

_____________________________________________________________________________________

Paralytic polio 21,269 in 1952 0 100%

3,100 died

_______________________ _____________________________________________________________

Mumps 152,209 in 1968 231 99.80%

_____________________________________________________________________________________

Rubella 57,686 in 1969 7 99.9%

_____________________________________________________________________________________

HIB 20,000 prior to 1985 259 98.7%

_____________________________________________________________________________________

From Centers for Disease Control and Prevention. MMWR 2004

Efficacy of Acellular Pertussis VaccinesEfficacy of Acellular Pertussis VaccinesRandomized, Blinded Trials*Randomized, Blinded Trials*

Study Vaccine

Efficacy (%)(Confidence

Interval)†

(WHO)†

StockholmGustafsson L et al. N Engl J Med. 1996;334:349-355.

DAPTACEL™ 85 (81-89)

Connaught DTP 48 (37-58)

ItalyGreco D et al. N Engl J Med. 1996;334(6):341-348.

Infanrix® 84 (76-89)

Connaught DTP 36 (14-52)

*Shows results for vaccines available in the United States for 3-dose infant immunization series; effects of any booster dose are not included.

†The definition closest to the standard WHO case definition (Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344).

*Shows results for vaccines available in the United States for 3-dose infant immunization series; effects of any booster dose are not included.

†The definition closest to the standard WHO case definition (Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344).

Source: CDC. Pertussis --- United States, 1997--2000. MMWR 2002;51:73-76.

Reported Pertussis Cases by YearReported Pertussis Cases by YearUnited States, 1922 – 2000United States, 1922 – 2000

Routine pertussisRoutine pertussisimmunization begins immunization begins

Ca

ses

(T

ho

us

and

s)

Ca

ses

(T

ho

us

and

s)

YearYear

00

5050

100100

150150

200200

250250

300300

19221922 19301930 19401940 19501950 19601960 19701970 19801980 19901990 20002000

0

2000

4000

6000

8000

10,000

12,000

14,000

16,000

18,000

20,000

1980 1990 1995 1999 2000 2001 2002 2003 2004

All Patients

25,827

11,647

9,771

7,867

7,580

7,2885,137

4,570

1,730

11,647

25,827

73%5,795

3,355

122%

Children 4 yrs. of age

5,795

3,355

The Growing Disease Reservoir The Growing Disease Reservoir Increases Exposure to PertussisIncreases Exposure to Pertussis

22,000

24,000

26,000

Reports of Pertussis in the U.S.Reports of Pertussis in the U.S.

Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. MMWRMMWR. 2002;51:73-76; . 2002;51:73-76; GGüüririşş et al. et al. Clin Infect DisClin Infect Dis. 1999;28:1230-1237.. 1999;28:1230-1237.

National Immunization Program, Bacterial Vaccine Preventable Diseases Branch. National Immunization Program, Bacterial Vaccine Preventable Diseases Branch. Pertussis Surveillance Report, August 6, 2004Pertussis Surveillance Report, August 6, 2004

00

500500

10001000

15001500

20002000

25002500

30003000

35003500

<1 yr<1 yr 1-4 yrs1-4 yrs 5-9 yrs5-9 yrs 10-19 yrs10-19 yrs 20+ yrs20+ yrs

Av

era

ge

Nu

mb

er

Av

era

ge

Nu

mb

er

of

Ca

ses

/ Y

ear

of

Ca

ses

/ Y

ear

1990-1993 1990-1993 1994-1996 1994-1996 1997-2000 1997-2000 2001-20032001-2003

552%552%

490%490%

……there are between there are between ~800,000 and 3.3 million ~800,000 and 3.3 million cases per year in the United States.cases per year in the United States.

Estimated Duration of Immunity After Infection or Vaccination

Source of Immunity Duration Reference

Natural infection 15 years Wirsing Von Konig, 1995

Whole-cell vaccine

UK 6 years Jenkinson, 1988

Finland 6 years He, 1994

Germany > 6 years Lugauer, 2002

Acellular vaccine

Italy 6 years Salmaso, 2001

Germany > 6 years Lugauer, 2002

Wirsing Von Konig et al. Lancet ID 2002:2:774-750

Consequences of Waning ImmunityConsequences of Waning Immunity

• Increased transmission of pertussis disease to unimmunized and underimmunized infants and children1

• Considerable pertussis-related morbidity and economic cost in families2

• Increased incidence of pertussis disease among adolescents and adults1,3

• Increased transmission of pertussis disease to unimmunized and underimmunized infants and children1

• Considerable pertussis-related morbidity and economic cost in families2

• Increased incidence of pertussis disease among adolescents and adults1,3

1. Edwards KM et al. In: Plotkin SA et al, eds. 1. Edwards KM et al. In: Plotkin SA et al, eds. VaccinesVaccines. 1999;293-344. . 1999;293-344. 2. Lee LH et al. 2. Lee LH et al. Arch Fam MedArch Fam Med. 2000;9:989-996.. 2000;9:989-996.3. Centers for Disease Control and Prevention. 3. Centers for Disease Control and Prevention. MMWRMMWR. 2002;51:73-76. . 2002;51:73-76.

Reported Pertussis Cases Are the Reported Pertussis Cases Are the Tip of the IcebergTip of the Iceberg

Not Reported

Under- reporting

Atypical forms

Wide disease variability

Inconsistent case definitions

Underdiagnosis

Low physician awareness

Underconsultation

Reported

• Nationwide, an estimated Nationwide, an estimated 12%12% of pertussis cases are actually reported of pertussis cases are actually reported• Underreporting may be greatest among adolescents and adultsUnderreporting may be greatest among adolescents and adults

Güriş et al. Clin Infect Dis. 1999;28:1230. 16

Pertussis Cases Reported in 2002Pertussis Cases Reported in 2002Each Dot Represents One CaseEach Dot Represents One Case

The total number of cases and incidence rate for each state represent provisional numbers, which may change as states report more cases for 2002Source: Bacterial Vaccine Preventable Diseases Branch, National Immunization Program, CDC.

Sharp demarcation at state borders illustrates inconsistent reporting.

75% Of Suspected Sources For Infant Pertussis 75% Of Suspected Sources For Infant Pertussis Cases Were Family MembersCases Were Family Members

47% Mom or Dad

Mom32%

Dad15%

Sibling20%

Grandparent8%

Other25%

20% Other Adults

33% Other Children

Bisgard, K. et al. Ped Infect Dis J. 2004;23:985-989.

The Cycle of Pertussis Susceptibility The Cycle of Pertussis Susceptibility Promotes Transmission & DiseasePromotes Transmission & Disease

Primary vaccination:

Protected

Booster vaccination: Prolonged protection

No additional booster: Immunity

wanes

Unvaccinated orpartially vaccinated infants: Susceptible

Susceptible adolescents and

adults: Reservoir of B pertussis

Break the Pertussis Cycle: Vaccinate

• Reduce morbidity in all age groups

• Reduce reservoir of Pertussis disease

• Prevent transmission of Pertussis disease between adolescents and adults, and from adolescents and adults to infants

Supported by multiple publications. See notes

Pertussis: Clinical PresentationPertussis: Clinical Presentation In Infants In Infants

Severe vs Mild PertussisSevere vs Mild Pertussis

1. Scott PT et al. Am Fam Physician. 1997;56:1121-1128. 2. Strebel P. Infect Med. 1996;13:S33-S41. 3. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.

1. Scott PT et al. Am Fam Physician. 1997;56:1121-1128. 2. Strebel P. Infect Med. 1996;13:S33-S41. 3. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.

SevereSevere** MildMild

• More common in infantsMore common in infants

• Occurs in nonimmune Occurs in nonimmune individualsindividuals

• Paroxysmal cough (Paroxysmal cough (>>21 days’ 21 days’ duration) with heavy inspiration duration) with heavy inspiration (whoops) accompanied by (whoops) accompanied by vomiting and gaggingvomiting and gagging

• Characteristic symptoms Characteristic symptoms (eg, whoop) often absent(eg, whoop) often absent11

• An important mechanism of An important mechanism of transmission to infantstransmission to infants

• Estimated to represent 21% to Estimated to represent 21% to 26% of acute cough illness in 26% of acute cough illness in adultsadults2,32,3

• Often unrecognized, Often unrecognized, underdiagnosedunderdiagnosed

* World Health Organization (WHO) definition.* World Health Organization (WHO) definition.

Common Clinical Manifestations of Common Clinical Manifestations of Adolescent-Adult PertussisAdolescent-Adult Pertussis

• Cough 97% 3 weeks, 52% 9 weeks

• Paroxysms 3 weeks in 73%

• Whoop in 69%

• Post-tussive emesis in 65%

• Teens missed average 5 days of school; Adults missed average 7 days of work

• Average 14 days of disrupted sleep

De Serres et al. J Infect Dis. 2000;182:174–9.De Serres et al. J Infect Dis. 2000;182:174–9.

PERTUSSIS DEATHS BY AGE, UNITED STATES PERTUSSIS DEATHS BY AGE, UNITED STATES (1980-1999)(1980-1999)

Pertussis Complications By AgePertussis Complications By Age

Diagnostic Laboratory Findings In PertussisDiagnostic Laboratory Findings In Pertussis

• Marked lymphocytosis with leukocyte counts often exceeding 50,000 cells/mm3

• Generally afebrile with no elevation of ESR or other acute phase reactions

• CXR with a “shaggy heart” produced by bilateral perihilar infiltrates, edema, and atelectasis

• Culture of posterior NP swab may take 2 weeks, but negative cultures are common especially after 4 weeks of illness

• Direct immunofluorescent assay of NP secretions had variable sensitivity and low specificity

• Serologic tests to measure immunglobin antibody to pertusis toxin (IgG, IgM, IgA).

• DNA by PCR of NP secretions is the most sensitive and rapid test but may not always be available

*Most cases of Pertussis are diagnosed clinically!

Period Of Communicability Of PertussisPeriod Of Communicability Of Pertussis

-2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

Weeks of cough

Catarrhal stage

Paroxysmal stage

Convalescent stage

Cough onset

Period of communicability

• Persons with pertussis are most infectious during the catarrhal period starting Persons with pertussis are most infectious during the catarrhal period starting as early as one day of cough as early as one day of cough

• Some individuals, such as infants who remain culture-positive for several Some individuals, such as infants who remain culture-positive for several weeks, may be infectious for a longer periodweeks, may be infectious for a longer period

Diagnostic Laboratory Findings in PertussisDiagnostic Laboratory Findings in Pertussis

Adapted from Mortimer EA. In: Krugman’s Infectious Diseases of Children. 10th ed. Mosby Year Book, Inc; 1998:335-349. Adapted from Mortimer EA. In: Krugman’s Infectious Diseases of Children. 10th ed. Mosby Year Book, Inc; 1998:335-349.

10

30

50

1-21-2 2-52-5 5-12+5-12+

Time After Onset of Symptoms (weeks)Time After Onset of Symptoms (weeks)

CatarrhalCatarrhal ParoxysmalStage

ParoxysmalStage

ConvalescentConvalescent

Lym

ph

ocy

te C

ou

nt

(th

ou

san

ds

)L

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Co

un

t (t

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usa

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s)

Po

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ve

Cu

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reP

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tiv

eC

ult

ure

DiagnosisDiagnosis

•Culture 1-3 weeks cough

•PCR 1-4

•Serology 3 weeks or longer

• IFA never

•Culture 1-3 weeks cough

•PCR 1-4

•Serology 3 weeks or longer

• IFA never

TREAMENT OF PERTUSSISTREAMENT OF PERTUSSIS

• Infants younger than 6 months generally require hospitalization

• Antibiotic Therapy:

• Erythromycin 40 to 50 mg/kg/day given QID x 14 days

• Azythromycin 10 to 12 mg/kg/day given Qday X 5 days

• Clarithromycin 15 to 20 mg/kg/day given BID X 7 days

• Bactrim or Septra 8 mg TMP/ 40 mg SMX per kg per day in two divided doses for 14 days if allergic to macrolides

• *Treatment with antibiotics does not effect duration or severity of clinical course

• Cough suppressants

MMWR Jan. 2005

• Infants younger than 6 months generally require hospitalization

• Antibiotic Therapy:

• Erythromycin 40 to 50 mg/kg/day given QID x 14 days

• Azythromycin 10 to 12 mg/kg/day given Qday X 5 days

• Clarithromycin 15 to 20 mg/kg/day given BID X 7 days

• Bactrim or Septra 8 mg TMP/ 40 mg SMX per kg per day in two divided doses for 14 days if allergic to macrolides

• *Treatment with antibiotics does not effect duration or severity of clinical course

• Cough suppressants

MMWR Jan. 2005

• Pertussis toxin (PT), also knownas “lymphocytosis-promoting factor” (systemic action)

• Filamentous hemagglutinin (FHA)

• Pertactin (PRN) or 69 kD* protein

• Fimbrial agglutinogens (FIM)(1-4 serotypes)

• Pertussis toxin (PT), also knownas “lymphocytosis-promoting factor” (systemic action)

• Filamentous hemagglutinin (FHA)

• Pertactin (PRN) or 69 kD* protein

• Fimbrial agglutinogens (FIM)(1-4 serotypes)

FIM

PT

PRN

FHA

Antigenic Components of Antigenic Components of B pertussisB pertussis

*kD = kilodalton. *kD = kilodalton. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.

Currently licensed in US

Tripedia® Infanrix®* Daptacel™ Boostrix™ Adacel®

Indicated Age Group

Infants/Children†

Infants/Children†

Infants/Children† Adolescents

‡ (10-18 years)

Adults/Adolescents

‡ (11-64 years)

AntigenicComponents§

PT (µg)FHA (µg) PRN (µg)FIM 2 + 3 (µg) D (Lf) T (Lf)

23.423.4——6.75

25258—2510

10535

155

88

2.5—2.55

2.553525

Diphtheria, Tetanus, andDiphtheria, Tetanus, andAcellular Pertussis VaccinesAcellular Pertussis Vaccines

Comparison of Tdap VaccinesComparison of Tdap Vaccines

Adacel Boostrix

Company Sanofi GSK

Age 11-64 10-18

Efficacy 21d 85% 84%

7d 78% 71%

Components 4 (fimbrae) 3

Diphtheria LF 2 2.5

Adacel Boostrix

Company Sanofi GSK

Age 11-64 10-18

Efficacy 21d 85% 84%

7d 78% 71%

Components 4 (fimbrae) 3

Diphtheria LF 2 2.5

The Adacel Program in NewfoundlandThe Adacel Program in Newfoundland

• Replaced Td in 1999 school year

• Adacel delivered in a Grade 9 (14 year olds) school-based program

• Approximately 25,000 doses given by June 2004

Incidence of Pertussis in Newfoundland, 1993-2003

1993 94 95 96 97 98 99 2000 01 02 03

Time Periods

Inc

ide

nc

e p

er

10

0,0

00

Po

pu

lati

on

0

10

20

30

40

50

60 Introduction of adolescent dTaP5

CCDR Notifiable Disease Annual Summaries

70

****

**** Pertussis outbreak confined to persons not immunized with dTaP5

Pertussis Incidence and Vaccine Use, 1993 Pertussis Incidence and Vaccine Use, 1993 – – 20042004Canada’s Northwest TerritoriesCanada’s Northwest Territories

Kandola, K. Abstract in Kandola, K. Abstract in Can J Infect Dis Med Microbiol.Can J Infect Dis Med Microbiol. 2004;15:351. Manuscript in preparation. 2004;15:351. Manuscript in preparation.

Adacel Adacel begunbegun

Switch to Switch to PentacelPentacel

00

22

44

66

88

1010

1212

1993-19961993-1996 1997-20001997-2000 2001-20022001-2002 2003-20042003-2004

Time PeriodsTime Periods

Av

era

ge

Yea

rly

Av

era

ge

Yea

rly

Ca

ses

/ 1

0,0

00

Ca

ses

/ 1

0,0

00

United States Licensure Trial:United States Licensure Trial:Summary of ImmunogenicitySummary of Immunogenicity

Pre Post PostPre

Diphtheria Tetanus

Data reported for sera collected one month after vaccination.Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.

Diphtheria and Tetanus Seroprotection ≥0.1 IU/mL With Adacel™ vs Td

0

20

40

60

80

100

Sero

pro

tecti

on

Rate

(%

)

Tdap Adolescents(N = 1175)

Td Adolescents (N = 787)

Tdap Adults (N = 1698)

Td Adults (N = 561)

Diphtheria and Tetanus Seroprotection ≥0.1 IU/mL With Adacel™ vs Td

0

20

40

60

80

100

Sero

pro

tecti

on

Rate

(%

)

Tdap Adolescents(N = 1175)

Td Adolescents (N = 787)

Tdap Adults (N = 1698)

Td Adults (N = 561)

Incidence of Systemic Reactions With Adacel™ vs Td

0

20

40

60

80

Perc

en

tag

e (

%)

Tdap Adol (N = 1175)

Td Adol (N = 787)

Tdap Adults (N = 1698)

Td Adults (N = 561)

Incidence of Systemic Reactions With Adacel™ vs Td

0

20

40

60

80

Perc

en

tag

e (

%)

Tdap Adol (N = 1175)

Td Adol (N = 787)

Tdap Adults (N = 1698)

Td Adults (N = 561)

Fever Headache GeneralizedBody Ache

Tiredness Sore JointsChills

United States Licensure Trial:United States Licensure Trial:Summary of Solicited Systemic ReactionsSummary of Solicited Systemic Reactions

Data collected from days 0-14.Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.

United States Licensure Trial:United States Licensure Trial:Summary of Solicited Local ReactionsSummary of Solicited Local Reactions

No significant difference was observed between Tdap and Td recipients for any safety parameters measured with the exception of pain in adolescents which was marginally more frequent in Tdap recipients.Data collected from days 0-3.*≥35 mm; †Severe local pain: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.

Incidence of Injection Site Erythema, Swelling, and Pain With Adacel™ vs Td

0

20

40

60

80

Perc

en

tag

e (

%)

Tdap Adol (N = 1175)

Td Adol (N = 787)

Tdap Adults(N = 1698)

Td Adults (N = 561)

Incidence of Injection Site Erythema, Swelling, and Pain With Adacel™ vs Td

0

20

40

60

80

Perc

en

tag

e (

%)

Tdap Adol (N = 1175)

Td Adol (N = 787)

Tdap Adults(N = 1698)

Td Adults (N = 561)

Severe Erythema*

Erythema Severe Swelling*

Swelling Severe Local Pain†

Local Pain

Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.

Adolescents = 11-17 years. Adults = 18-64 years.

Adequacy, Efficacy, & Safety Data for Tdap Adequacy, Efficacy, & Safety Data for Tdap VaccinesVaccines

• Age Indications: Adacel 11- 64 years, Boostrix 10-18 years

• Both vaccines met all agreed non-inferiority criteria

• For Diphtheria and Tetanus antigens, at least as immunogenic as US – licensed Td vaccines

• Pertussis booster response induced an immune response at least as immunogenic as Daptacel and Infanrix

• Can be used concomitantly with other vaccines

• Safety profile comparable to US-licensed Td Vaccine

• Age Indications: Adacel 11- 64 years, Boostrix 10-18 years

• Both vaccines met all agreed non-inferiority criteria

• For Diphtheria and Tetanus antigens, at least as immunogenic as US – licensed Td vaccines

• Pertussis booster response induced an immune response at least as immunogenic as Daptacel and Infanrix

• Can be used concomitantly with other vaccines

• Safety profile comparable to US-licensed Td Vaccine

FDA Vaccine Advisory CommitteeFDA Vaccine Advisory Committee

• Unanimous vote March 2005– Adacel safe and effective age 11-64 years of age– Boostrix safe and effective 10-18 years of age

• Licensure… May, June 2005

• CDC ACIP

• July 2005 11-12 yr Universal Immunization, catch up 5 yrs from last Td Oct 2005 Universal Adult Immunization,10 yrs from Td

• Unanimous vote March 2005– Adacel safe and effective age 11-64 years of age– Boostrix safe and effective 10-18 years of age

• Licensure… May, June 2005

• CDC ACIP

• July 2005 11-12 yr Universal Immunization, catch up 5 yrs from last Td Oct 2005 Universal Adult Immunization,10 yrs from Td

Rationale for Vaccinating Adolescents Rationale for Vaccinating Adolescents and Adults: and Adults: Bordetella PertussisBordetella Pertussis Reservoirs Reservoirs

1. Sheretz et al. Emerg Infect Dis. 2001;7:241-244. 2. Izurieta et al. Clin Infect Dis. 1996;22:503-507.3. Postels-Multani et al. Infection. 1995;23:139-142.4. Crowcroft et al. Arch Dis Child. 2003;88:802-806.

Adolescents and Adults Are Primary Sources for Infant TransmissionAdolescents and Adults Are Primary Sources for Infant Transmission

Health Care ProvidersHealth Care ProvidersMost hospital outbreaks of Most hospital outbreaks of pertussis disease involve pertussis disease involve transmission from health transmission from health care workers to pediatric care workers to pediatric patientspatients11

Adults/ParentsAdults/ParentsIn Chicago, young In Chicago, young mothers with a cough mothers with a cough >7 days were shown to >7 days were shown to be a significant source of be a significant source of pertussis disease pertussis disease transmission transmission to their young infantsto their young infants22

GrandparentsGrandparentsIn 15% of families, an In 15% of families, an adult patient was adult patient was identified as the identified as the source of infection for source of infection for other household other household members. Fifteen members. Fifteen percent of these percent of these adults were adults were grandparents or great-grandparents or great-grandparents of an grandparents of an affected childaffected child33

Adolescents/SiblingsAdolescents/SiblingsFor 27% of infants For 27% of infants hospitalized with pertussis hospitalized with pertussis disease in London disease in London between 1998 and 2000, between 1998 and 2000, an older, fully vaccinated an older, fully vaccinated sibling was the source of sibling was the source of infectioninfection44

Advisory Committee On Immunization Practices (ACIP) Recommendations For Tdap Vaccine In Adolescents

• Recommendations of the ACIP (CDC) for the use of Tdap vaccines:

• Adolescents 11 to 12 years of age be given Tdap in place of the Td booster currently being used

• Tdap vaccine should be given to adolescents 13 to 18 years who missed the 11 to 12 year dose of Td

• Adolescents 11 to 18 years of age who have already been vaccinated with Td are encouraged to receive a dose of Tdap to further protect against pertussis

• Adolescents can and should receive Tdap and the meningococcal conjugate vaccine (menactra) at the same visit

ACIP Recommendations for Tdap Vaccine Use in ACIP Recommendations for Tdap Vaccine Use in AdultsAdults

• Adults who have not received a Td immunization during the last 10 years should receive a single dose of Tdap Vaccine

• Those not previously given Tdap vaccine may be given Tdap vaccine at shorter intervals (< 10 years) following last Td immunizations in settings of wound management and increased risk (including pertussis outbreaks and contact with infants

• Adults who anticipate having close contact with infants (ie: parents, healthcare workers and daycare workers) should receive a single dose of Tdap vaccine to protect against pertussis if they have not received Tdap vaccine. Ideally these adults should receive Tdap vaccine at least one month before beginning close contact with infants

• Adults who have not received a Td immunization during the last 10 years should receive a single dose of Tdap Vaccine

• Those not previously given Tdap vaccine may be given Tdap vaccine at shorter intervals (< 10 years) following last Td immunizations in settings of wound management and increased risk (including pertussis outbreaks and contact with infants

• Adults who anticipate having close contact with infants (ie: parents, healthcare workers and daycare workers) should receive a single dose of Tdap vaccine to protect against pertussis if they have not received Tdap vaccine. Ideally these adults should receive Tdap vaccine at least one month before beginning close contact with infants

Other ACIP Recommendations for Adult Tdap UseOther ACIP Recommendations for Adult Tdap Use

• Women should receive Tdap vaccine immediately post partum if not previously immunized

• Women are encouraged to receive Tdap vaccine before conception

• Tdap vaccine is encouraged over Td vaccine in the wound care setting for those who have not previously received Tdap vaccine

• Pregnancy is not a contraindication to Tdap and may be considered in the 2nd and 3rd trimester

• Women should receive Tdap vaccine immediately post partum if not previously immunized

• Women are encouraged to receive Tdap vaccine before conception

• Tdap vaccine is encouraged over Td vaccine in the wound care setting for those who have not previously received Tdap vaccine

• Pregnancy is not a contraindication to Tdap and may be considered in the 2nd and 3rd trimester

ACIP Recommendations for Tdap ACIP Recommendations for Tdap Use In Healthcare WorkersUse In Healthcare Workers

• There are 8-10 million workers employed in hospital and ambulatory settings.

• The risk of contracting pertussis from healthcare workers is nearly 2 times greater than the general population.

• For each decade the immunization of healthcare workers could prevent as many as 100, 000 cases of pertussis and save up to $151 million in direct and indirect costs.

• Therefore it is recommended that all healthcare workers and anyone who works in a healthcare setting receive Tdap.

• There are 8-10 million workers employed in hospital and ambulatory settings.

• The risk of contracting pertussis from healthcare workers is nearly 2 times greater than the general population.

• For each decade the immunization of healthcare workers could prevent as many as 100, 000 cases of pertussis and save up to $151 million in direct and indirect costs.

• Therefore it is recommended that all healthcare workers and anyone who works in a healthcare setting receive Tdap.

Strategies to Control Pertussis…Strategies to Control Pertussis…

• Improve immunization coverage

• Ensure immunization of all appropriate infants

• Prevent mild disease

• Improve surveillance and reporting

• Implement Tdap vaccines for adolescents and adults

• Eliminate reservoirs of infection in general population

• Reduce transmission to vulnerable infants

SUMMARYSUMMARY

• Epidemiology of pertussis disease has changed with the spectrum of illness shifting to a milder form in all age groups

• B. pertussis infections in the adolescent and adult populations are common and endemic accounting for more of the disease seen today

• Immunity after natural infection or vaccinations is not life long and wanes rapidly after 5 – 8 years

• Pertussis acounts for up to 25% of acute cough illnesses in the adolescent and adult populations

• The adolescent and adult populations serve as a major resevoir of disease transmission to the young infant population

• Immunizing the infant population on time and implementing a booster vaccine program in the adolescent and adult populations will have the greatest impact on decreasing the amount of disease seen

• Epidemiology of pertussis disease has changed with the spectrum of illness shifting to a milder form in all age groups

• B. pertussis infections in the adolescent and adult populations are common and endemic accounting for more of the disease seen today

• Immunity after natural infection or vaccinations is not life long and wanes rapidly after 5 – 8 years

• Pertussis acounts for up to 25% of acute cough illnesses in the adolescent and adult populations

• The adolescent and adult populations serve as a major resevoir of disease transmission to the young infant population

• Immunizing the infant population on time and implementing a booster vaccine program in the adolescent and adult populations will have the greatest impact on decreasing the amount of disease seen

……a universal program of adolescent and adult boosters a universal program of adolescent and adult boosters would decrease the circulation of would decrease the circulation of B pertussisB pertussis… and … and possibly could lead to the elimination of the organism…possibly could lead to the elimination of the organism…

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