Download Pertussis Awareness

Pertussis Awareness
And Prevention
W. Michael Brown, MD, FAAP
Director of Pediatrics
Associate Director Family Medicine Residency
Bayfront Medical Center
St. Petersburg, Florida
Pertussis Awareness and Prevention:
Objectives
• 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)
• 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
and Adults Due to Bordetella Pertussis
Source
Jackson et al
Robertson et al
Mink et al
Schmitt-Grohé et al
Wright et al
Wirsing v Köenig et al
Rosenthal et al
Jansen et al
Nennig et al
Strebel et al
Birbeback et al
Vicent et al
Gilberg et al
Locale
Year(s)
% of cough
illnesses
Seattle
New S Wales
Los Angeles
Germany
Nashville
Germany
Chicago
San Diego
San Francisco
Minn-St Paul
Denmark
Korea
Paris
1983-87
1985-86
1986-89
1992-94
1992-94
1992-94
1993-94
1993-94
1994-95
1995-96
1995-97
1997-98
1999
15%
26%
26%
32%
21%
31%
26%
17%
12%
13%
17%
50%
52%
Pertussis 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?
• 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 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
Efficacy of Acellular Pertussis Vaccines
Randomized, Blinded Trials*
Efficacy (%)
(Confidence
Interval)†
Study
Stockholm
Gustafsson L et al. N Engl J
Med.
1996;334:349-355.
Italy
Greco D et al. N Engl J Med.
1996;334(6):341-348.
Vaccine
(WHO)†
DAPTACEL™
85 (81-89)
Connaught DTP
48 (37-58)
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).
Reported Pertussis Cases by Year
United States, 1922 – 2000
Cases (Thousands)
300
Routine pertussis
immunization begins
250
200
150
100
50
0
1922
1930
1940
1950
1960
1970
Year
Source: CDC. Pertussis --- United States, 1997--2000. MMWR 2002;51:73-76.
1980
1990
2000
The Growing Disease Reservoir
Increases Exposure to Pertussis
26,000
25,827
24,000
22,000
122%
20,000
25,827
18,000
All Patients
16,000
Children  4 yrs. of age
14,000
11,647
11,647
12,000
9,771
10,000
7,867
5,795
8000
5,137
6000
4,570
7,580
5,795
7,288
4000
73%
3,355
1,730
3,355
2000
0
1980
1990
1995
1999
2000
2001
2002
2003
2004
Reports of Pertussis in the U.S.
1990-1993
1994-1996
1997-2000
2001-2003
Average Number
of Cases / Year
3500
3000
552%
2500
2000
490%
1500
1000
500
0
<1 yr
1-4 yrs
5-9 yrs
10-19 yrs
20+ yrs
Centers for Disease Control and Prevention. MMWR. 2002;51:73-76;
Güriş et al. Clin Infect Dis. 1999;28:1230-1237.
National Immunization Program, Bacterial Vaccine Preventable Diseases Branch.
Pertussis Surveillance Report, August 6, 2004
…there are between ~800,000 and 3.3 million
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
Germany
6 years
> 6 years
Salmaso, 2001
Lugauer, 2002
Wirsing Von Konig et al. Lancet ID 2002:2:774-750
Consequences 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
1. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.
2. Lee LH et al. Arch Fam Med. 2000;9:989-996.
3. Centers for Disease Control and Prevention. MMWR. 2002;51:73-76.
Reported Pertussis Cases Are the
Tip of the Iceberg
• Nationwide, an estimated 12% of pertussis cases are actually reported
• Underreporting may be greatest among adolescents and adults
Reported
Atypical forms
Not Reported
Wide disease
variability
Underconsultation
Low physician
awareness
Güriş et al. Clin Infect Dis. 1999;28:1230.
Underreporting
Underdiagnosis
Inconsistent case
definitions
16
Pertussis Cases Reported in 2002
Each Dot Represents One Case
Sharp
demarcation at
state borders
illustrates
inconsistent
reporting.
The total number of cases and incidence rate for each state represent provisional numbers, which may change as states report
more cases for 2002
Source: Bacterial Vaccine Preventable Diseases Branch, National Immunization Program, CDC.
75% Of Suspected Sources For Infant Pertussis
Cases Were Family Members
Other
25%
20% Other Adults
Mom
32%
Grandparent
8%
Sibling
20%
Dad
15%
47% Mom or Dad
33% Other Children
Bisgard, K. et al. Ped Infect Dis J. 2004;23:985-989.
The Cycle of Pertussis Susceptibility
Promotes Transmission & Disease
Unvaccinated or
partially vaccinated
infants: Susceptible
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
Susceptible
adolescents and
adults:
Reservoir of
B pertussis
Supported by multiple publications. See notes
No additional
booster:
Immunity
wanes
Primary
vaccination:
Protected
Booster
vaccination:
Prolonged
protection
Pertussis: Clinical Presentation
In Infants
Severe vs Mild Pertussis
Severe*
• More common in infants
• Occurs in nonimmune
individuals
• Paroxysmal cough (>21 days’
duration) with heavy inspiration
(whoops) accompanied by
vomiting and gagging
Mild
• Characteristic symptoms
(eg, whoop) often absent1
• An important mechanism of
transmission to infants
• Estimated to represent 21% to
26% of acute cough illness in
adults2,3
• Often unrecognized,
underdiagnosed
* World Health Organization (WHO) definition.
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.
Common Clinical Manifestations of
Adolescent-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.
PERTUSSIS DEATHS BY AGE, UNITED STATES
(1980-1999)
Pertussis Complications By Age
Diagnostic 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 Pertussis
Period of communicability
Cough onset
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
Weeks of cough
Catarrhal
stage
Paroxysmal
stage
Convalescent
stage
• Persons with pertussis are most infectious during the catarrhal period starting
as early as one day of cough
• Some individuals, such as infants who remain culture-positive for several
weeks, may be infectious for a longer period
Positive
Culture
Diagnostic Laboratory Findings in Pertussis
Lymphocyte Count
(thousands)
Catarrhal
Paroxysmal
Stage
Convalescent
50
30
10
1-2
2-5
5-12+
Time After Onset of Symptoms (weeks)
Adapted from Mortimer EA. In: Krugman’s Infectious Diseases of Children. 10th ed. Mosby Year Book, Inc; 1998:335-349.
Diagnosis
• Culture
1-3 weeks cough
• PCR
1-4
• Serology
3 weeks or longer
• IFA
never
TREAMENT 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
Antigenic Components of
B pertussis
FIM
FHA
PT
• Pertussis toxin (PT), also known
as “lymphocytosis-promoting factor”
(systemic action)
• Filamentous hemagglutinin (FHA)
• Pertactin (PRN) or 69 kD* protein
PRN
• Fimbrial agglutinogens (FIM)
(1-4 serotypes)
*kD = kilodalton.
Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.
Diphtheria, Tetanus, and
Acellular Pertussis Vaccines
Tripedia®
Infanrix®*
Daptacel™
Indicated Age
Group
Infants/
Children†
Infants/
Children†
Infants/
Children†
Antigenic
Components§
PT (µg)
FHA (µg)
PRN (µg)
FIM 2 + 3 (µg)
D (Lf)
T (Lf)
23.4
23.4
—
—
6.7
5
25
25
8
—
25
10
10
5
3
5
15
5
Currently
licensed in US
Boostrix™
Adacel®
Adults/
Adolescents Adolescents
‡ (10-18
‡ (11-64
years)
years)
8
8
2.5
—
2.5
5
2.5
5
3
5
2
5
Comparison of Tdap Vaccines
Adacel
Boostrix
Company
Sanofi
Age
11-64
10-18
Efficacy 21d
85%
84%
7d
78%
71%
Components
4 (fimbrae)
Diphtheria LF
2
GSK
3
2.5
The 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
Incidence per 100,000 Population
70
60
Introduction of
adolescent dTaP5
50
40
30
**** Pertussis outbreak
confined to persons not
immunized with dTaP5
20
10
****
0
1993
94
95
96
97
98
99
2000
01
02
03
Time Periods
CCDR Notifiable Disease Annual Summaries
Pertussis Incidence and Vaccine Use, 1993 – 2004
Canada’s Northwest Territories
12
Switch to
Pentacel
Adacel
begun
Average Yearly
Cases / 10,000
10
8
6
4
2
0
1993-1996
1997-2000
2001-2002
2003-2004
Time Periods
Kandola, K. Abstract in Can J Infect Dis Med Microbiol. 2004;15:351. Manuscript in preparation.
United States Licensure Trial:
Summary of Immunogenicity
Seroprotection Rate (%)
Diphtheria and Tetanus Seroprotection ≥0.1 IU/mL
With Adacel™ vs Td
Tdap Adolescents
(N = 1175)
100
80
Td Adolescents
(N = 787)
60
Tdap Adults
(N = 1698)
40
Td Adults
(N = 561)
20
0
Pre
Post
Diphtheria
Data reported for sera collected one month after vaccination.
Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.
Pre
Post
Tetanus
United States Licensure Trial:
Summary of Solicited Systemic Reactions
Incidence of Systemic Reactions With Adacel™ vs Td
Tdap Adol (N = 1175)
Td Adol (N = 787)
Tdap Adults (N = 1698)
Td Adults (N = 561)
Percentage (%)
80
60
40
20
0
Fever
Chills
Headache GeneralizedB
ody Ache
Data collected from days 0-14.
Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.
Tiredness
Sore Joints
United States Licensure Trial:
Summary of Solicited Local Reactions
Incidence of Injection Site Erythema, Swelling, and Pain
With Adacel™ vs Td
Tdap Adol
Percentage (%)
80
(N = 1175)
Td Adol
(N = 787)
Tdap Adults
(N = 1698)
Td Adults
(N = 561)
Adolescents = 11-17 years.
Adults = 18-64 years.
60
40
20
0
Erythema
Severe
Erythema*
Swelling
Severe
Swelling*
Local Pain
Severe
Local Pain†
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.
Data on file, Td 506, Aventis Pasteur Limited, Toronto, Canada.
Adequacy, Efficacy, & Safety Data for Tdap
Vaccines
• 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 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
Rationale for Vaccinating Adolescents
and Adults: Bordetella Pertussis Reservoirs
Adolescents and Adults Are Primary Sources for Infant Transmission
Health Care Providers
Most hospital outbreaks of
pertussis disease involve
transmission from health
care workers to pediatric
patients1
Adults/Parents
In Chicago, young
mothers with a cough
>7 days were shown to
be a significant source of
pertussis disease
transmission
to their young infants2
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.
Grandparents
In 15% of families, an
adult patient was
identified as the
source of infection for
other household
members. Fifteen
percent of these
adults were
grandparents or greatgrandparents of an
affected child3
Adolescents/Siblings
For 27% of infants
hospitalized with pertussis
disease in London
between 1998 and 2000,
an older, fully vaccinated
sibling was the source of
infection4
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
Adults
• 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 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
ACIP Recommendations for Tdap
Use 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.
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
SUMMARY
• 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
would decrease the circulation of B pertussis… and
possibly could lead to the elimination of the organism…
Questions