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Pertussis and Pertussis
Vaccination:
Why All the Whoop-la?
A Summary for South Carolina Medical Providers
Riyadh D. Muhammad, MD, MPH – Pediatrician
Helen L. Huber, MSN - Pediatric Nurse Practitioner
Bureau of Disease Control
South Carolina Department of Health and Environmental Control
Source: W. Orenstein. An overview of Vaccinology; 2009 Clinical Vaccinology Course, Atlanta.
Sounds of Pertussis
Whooping Child
Whooping Adult
Overview
• Pertussis Surveillance Data
• Clinical Considerations
–
–
–
–
–
Background
Clinical Features
Diagnosis
Treatment
Reporting cases to DHEC
• Vaccine
–
–
–
–
Vaccines available
Recommendations
Coverage rates
Safety
Reported Pertussis Cases*
U.S., 1922-2009†
DTP
(1949)
DTaP for
doses 4 & 5
(1992)
DTaP for all
doses
(1997)
Tdap
(2005)
*National Notifiable Diseases Surveillance System (NNDSS)
†2009
data provisional
Ref: S. Roush, NIC 2010
Reported Pertussis Cases*
Tdap
U.S., 1980-2009†
(2005)
1997: PCR
included in case
definition
*National Notifiable Diseases Surveillance System (NNDSS)
†2009
data provisional
Ref: S. Roush, NIC 2010
U.S. Pertussis Cases, 2010
Ref: CDC. Unpublished data.
Rate
South Carolina
S.C. Pertussis Cases, 2010
South Carolina, 2010
South Carolina
Pertussis
• Fastidious gram-negative bacillus,
Bordetella pertussis
• Severe, debilitating cough illness
lasting weeks to months (“100 day
cough”)
• Characterized by paroxysms of cough,
inspiratory whoop, vomiting; apnea in
young infants
Pertussis
• Highly contagious
• Transmission by contact with
secretions, droplets from nose or
mouth
• Vaccine preventable, but poorly
controlled
– Despite high childhood vaccine coverage,
pertussis remains a problem in S.C. and
the U.S.
Pertussis
• Worldwide occurrence
• Affects all ages, even vaccinated persons
• Morbidity and mortality complications most
common among infants
– Transmission from parents, household
members
– Recommendation for cocooning vaccination
approach
• Persistent cough itself can cause
complications
Pertussis Clinical Features
• Incubation period 5-10 days (range 4-21
days)
• Insidious onset, similar to minor URI with
nonspecific cough
• Fever minimal or absent
• Pertussis presentation varies depending
upon age, existing immunity
• Classically characterized by
– Paroxysms of cough
– Inspiratory whoop
– Vomiting
Timeline of Pertussis Symptoms
• Catarrhal stage
1-2 weeks
– Mild URI, progresses to cough
– Most contagious stage
• Paroxysmal
cough stage
1-6 weeks
– Whooping, vomiting
• Convalescence
– Gradual resolution
Weeks to months
Pertussis Epidemiology
• Reservoir
Humans
• Transmission
Respiratory droplets
• Communicability
Maximum in catarrhal stage
Secondary attack rate up to
80%
Pertussis Among Adolescents
and Adults
• Disease often milder compared to infants
and children
– Persons with mild disease may transmit the
infection
• Infection may be asymptomatic, or present
as classic pertussis
– Pertussis is unrecognized, underreported
– Asymptomatic infections are 4 to 22 times more
common than symptomatic infections
– Symptomatic adolescents and adults are the
major source of infection in unvaccinated children
Pertussis Among Infants
• Most severe disease
• Infants under 6 months have an atypical
presentation
– Short catarrhal stage
– Longer period of convalescence
– Absence of whoop
• Prominent symptoms can be
– Gagging
– Gasping
– Apnea
• Can lead to sudden unexplained death
Let’s Protect Our Infants!
Pertussis Deaths in the U.S., 2004-2006
Age at onset
<3 mos
>3 mos
Total
2004
24
3
27
2005
32
7
39
2006
13
3
16
Total
69
13
82
(84%)
(16%)
CDC, unpublished data, 2007
Source of Pertussis Among
Infants
• 616 cases of pertussis in infants
• Source identified in 264 (43%)
– Parents 47%
– Siblings 20%
– Grandparents 8%
– Other 25%
Ref: Bisgard et al. PIDJ 2004;23:985-989.
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)
Pertussis Complications
• Seizures
• Encephalopathy
• Syncope
• Rib Fractures
• Incontinence
Courtesy of T. Schlenker,
Children's Hospital of Wisconsin
Pertussis Diagnosis
• Culture
• Polymerase chain reaction
(PCR)
• Serology
• Direct fluorescent antibody
(DFA)
• DFA and serology might be
clinically useful
– Cannot be used for case
confirmation for reporting
Pertussis Diagnosis
Is currently complicated by:
– Stage of disease (catarrhal, paroxysmal,
convalescent)
– Antimicrobial administration
– Vaccination status
– Quality/timely collection of clinical specimen
– Transport conditions
– Contamination of clinical specimen
– Lack of clinically validated and standardized
tests
26
Optimal Timing for Pertussis
Diagnostic Testing
Communicable Period
Incubation Period Catarrhal Stage
-3
Symptom Onset
0
2
Convalescent
Paroxysmal Stage Stage
8
Weeks
Bacterial Culture
PCR
Serology
12
PCR
Pros
•High sensitivity
•Results can be obtained quickly
•Organism does not need to be viable
•Less affected by immunization and
antibiotics
Cons
•Expensive
•No commercial FDA approved tests or
standardized protocol
•No standardized reagents or
interpretation of results
•Most labs only use single targets
•False positives and contamination
•Still affected by disease phase and
antibiotic treatment
Culture
Pros
Cons
•Gold standard
•100% specific
•False positives not a concern
•Low cost
•Facilitates public health surveillance
•Difficult collection, transport, growth
conditions
•Slow, incubation time up to 10 days
•Lower yield if prior antibiotics
•Low sensitivity
-Generally 30-60%, but can be <10% for
adolescents and adults with prolonged cough
Isolation drastically declines after:
- 2 weeks of cough
- Antimicrobial or vaccine administration
- Inappropriate collection/transport /growth conditions
‘Pseudo’
Outbreaks of
Pertussis: Pitfalls
of PCR
Problems Identified in Pseudo
Pertussis Outbreaks
• Over reliance on PCR
– Single, non-specific DNA targets
– Few cultures were performed
• Testing ill persons without typical pertussis
symptoms
– Viruses, parapertussis, Chlamydia, Mycoplasma, etc
• Contamination of PCR tests via
– Specimens from true cases
– Pertussis vaccines
• Inappropriate specimen handling
Obtain PCR and Culture
• CDC and DHEC recommend culture along
with your PCR
– PCR should be used in conjunction with and not
in place of culture
• Pertussis culture is
– Cheap
– Facilitates validation of PCR results
– Keeps PCR ‘honest’
• False positives
• Contamination
• None are FDA approved
Collecting Pertussis Specimens
• Nasopharyngeal (NP) wash or swab
• Use for culture, PCR
• Throat swabs, cotton-tipped swabs not
acceptable and inhibit growth of B. pertussis
*A video of NP swab collection is available at: http://video.cdc.gov/asxgen/nip/isd/swabdemo.wmv
Collecting NP Swabs for
Pertussis Testing
• Requires 2 Dacron tipped swabs with flexible
shafts per patient
– One placed in Regan Lowe Transport Media at
bedside (used for culturing)
– One placed in a sterile tube without media (used for
PCR)
• Avoid contamination
• Failure to follow these procedures can cause
– False negatives
– False positives
Antibiotic Treatment
• Macrolide antibiotics first-line
– 5-day course of azithromycin, or
– 7-day course of clarithromycin, or
– 14-day course of erythromycin
• Alternative is a14-day course of TMP/SMX
• Treat persons >1 year within 3 weeks of cough
onset (up to 90% clear infection in 3-4 weeks)
• Treat persons <1 year within 6 weeks of cough
onset (infectious longer)
• Postexposure antibiotics to case contacts
within 3 weeks of exposure
Fairfield, Lexington, Newberry, Richland
803-576-2749
Chester, Lancaster, York
803-286-9948
Reporting Pertussis to DHEC
• Providers required to report
– Not the sole responsibility of laboratories
• Report suspected or confirmed cases
– No need to wait for lab confirmation
• DHEC assists providers
– Diagnostic testing
– Outbreak investigation and control
• Identification of source cases
• Contact tracing for antibiotic prophylaxis
• Vaccine resources
Pertussis Case Investigation
• Suspect pertussis infection
– Infant with: initially URI symptoms*, coughing,
apnea, gagging, gasping, hypoxia, seizures; contact
with a coughing individual
– Older child or adult with: cough illness, paroxyms,
whooping, post-tussive vomiting, prolonged cough;
cases may be diagnosed with ‘bronchitis’
• Inform local DHEC county
• Collect specimens
– Culture and PCR (use recommended methods,
materials)
– Begin treatment (do not wait for lab confirmation)
Pertussis Case Investigation
• Identify contacts during infectious period
– Most infectious at cough onset through 21 days
after cough onset
– Close contacts should receive antibiotic
prophylaxis, regardless of vaccination
• Pertussis is highly infectious
• Use standard and droplet precautions
– Consider face masks to all patients with URI
(flu, pertussis, etc)
• Cases must stay home until completion of 5
days of antibiotics
Clinicians and Pertussis
• Use recommended methods to diagnose
and treat suspected cases
– Early diagnosis and treatment will prevent
infant cases and deaths
• Use postpartum cocooning strategies to
vaccinate parents, families of newborns
before mother is discharge
• Ensure patients are appropriately
vaccinated with DTaP and Tdap
Pertussis Vaccines:
Got Tdap?
Pertussis Vaccines
• DTaP
– Infant/childhood vaccine
– Ages 6 weeks to 6 years
• Tdap
– Adolescent/Adult vaccine
– Ages 10 to 64 years
• Group in whom studies were done
• No licensed vaccine for those 7-9 years of age
• Some off label use reported for >64 year olds
Pertussis Vaccines
Ref: Sandora et al. Clin Microbiol Rev. 2008:21(3);426-434.
DTaP Adverse Reactions
• Local reactions
• Temp of 101° or higher
• More severe adverse reactions not
common
• Local reactions and fever more common
following 4th and 5th doses (swelling
involving entire thigh or upper arm has
been reported—NOT a contraindication to
5th dose)
DTaP Precautions
• Moderate or severe acute illness
• Temperature 105° (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 or longer, occurring within 48 hours
• Convulsions with or without fever
occurring within 3 days
DTaP/Tdap Contraindications
• Severe allergic reaction (anaphylaxis) to
vaccine component or following a prior
dose
• Encephalopathy not due to another
identifiable cause occurring within 7 days
after vaccination with a pertussiscontaining vaccine
Tdap in Persons with Adverse
Events after DTaP
• Occurrence of adverse reactions
(precaution) following DTaP vaccine
in childhood is NOT a
contraindication or precaution to
administration of Tdap to an
adolescent or adult
Tdap Precautions
• History of a severe local reaction (Arthus
reaction) following a prior dose of a
tetanus and/or diphtheria toxoid-containing
vaccine
• Progressive neurologic disorder until the
condition has stabilized
• History of Guillain-Barré syndrome within 6
weeks after a prior dose of tetanus toxoidcontaining vaccine
• Moderate or severe acute illness
Tdap Adverse Reactions
• Local reactions
21%-75%
(pain, redness, swelling)
• Temp of 100.4oF
or higher
3%-5%
• Adverse reactions occur at approximately
the same rate as Td alone
Tdap Recommendations
• Approved as a single booster to replace Td in persons
fully vaccinated with pediatric DTaP or DTP
 Routine administration at 11-12 year well visit.
 Adolescents and adults <65 years of age who have
not received a dose of Tdap, or for whom vaccine
status is unknown, should be immunized as soon
as feasible.
• Priority groups
 Health care personnel (HCP)
 Any individual with infant contact (<1 year of age)
• Use Tdap for wound prophylaxis, not Td, if not already
received Tdap
Adolescents/Adults With History of
No/Unknown Tetanus, Diphtheria, or
Pertussis Vaccination
• All adolescents and adults should have documentation of
having received a series of DTaP, DTP, DT, or Td
• Persons without documentation should receive a series of
3 vaccinations
• Preferred schedule:
– Single dose of Tdap*
– Td at least 4 weeks after the Tdap dose
– Second dose of Td at least 6 months after the Td dose
* If not administered as the first dose, Tdap can be
substituted for any of the other doses in the series.
Use of Tdap Among Pregnant Women
• Td is generally preferred during pregnancy
• Women who have not received Tdap should
receive a dose in the immediate post-partum
period
• Any woman who might become pregnant is
encouraged to receive a single dose of Tdap
• Pregnancy is not a contraindication for Tdap
• Clinician may choose to administer Tdap to a
pregnant woman in certain circumstances
– Such as during a community pertussis outbreak
• Tdap OK for lactating women
DTaP Coverage
• 84.9% of children 19-35 months have
received 4 or more doses of
DTaP/DTP/DT
• 93% DTaP coverage among children
entering kindergarten for 2008-2009
school year
Ref: J. Liang, Pertussis Vaccines, CDC ACIP Presentation, June 2010
Tdap coverage among adolescents
13-17 years NIS Teen, U.S. and S.C.
Why aren’t More Teens Getting
Vaccinated?
• Many parents and students still unaware of
disease, vaccine
• Fewer health maintenance visits
– Usually seen only when sick
• Missed immunization opportunities
• Episodic healthcare from healthcare providers in
varied settings
– Gyn offices and EDs that have rarely offered routine
vaccination services to adolescents
• Misperception about vaccine safety
Self-reported Tdap vaccination coverage among
U.S. adults – NHIS, 2008
Ref: B. Miller, Factors influencing Tdap coverage, 2010 NIC Presentation
Barriers to Tdap Vaccination,
Adult 2007 NIS
• Low awareness of vaccine existence
• Relative absence of provider
recommendations
• Low perceived risk among unvaccinated
adults
– Likely have contributed to low coverage
– Despite this, many adults would be receptive
to the idea of being vaccinated with Tdap, if
provider recommends
Ref: B. Miller, Factors influencing Tdap coverage, 2010 NIC Presentation
Minimum Interval Between Tdap
and Td
• ACIP did not define an absolute minimum
interval between Td and Tdap
• Confusing language has caused providers to
delay vaccination and miss opportunities to
vaccinate
Minimum Interval Between Tdap
and Td – Removing a Barrier
Tdap can be given regardless of the
interval since the last Td was given.
(CDC ACIP vote October 2010—expected language)
– Safety data available—reduces concern for AEs due
to frequent, reported exposure to antigens.
– Need to improve vaccination rates and protect
vulnerable infants
Extending Tdap Age Indications
to 7-9 Year olds
• ACIP reviewed adverse event data in 4-8
year olds given Tdap in place of 5th DTaP
--No increased risk of severe local or systemic adverse events
compared to using DTaP 5th dose
• ACIP reviewed immunogenicity data in 4-6
year olds given Tdap in place of 5th DTaP
--No difference between Tdap and DTaP recipients in antibody
response against pertussis antigens
--Immunity similar between Tdap and DTaP recipients 3-5 years
later
Extending Tdap Age Indications
to 7-9 Year olds
• ACIP (expected) language
--Children 7-10 years of age who are not fully
immunized against pertussis (i.e., did not
complete a series of pertussis-containing
vaccine before their seventh birthday) should
receive a one-time dose of Tdap.
Extending Tdap Age Indications
to > 65 year olds
• New recommendation depends on
contact with infant <12 months:
(expected language from ACIP)
--Full recommendation: Adults > 65 years of age
who have or anticipate having contact with infants
(e.g., grandparents, childcare providers, HCWs)
should receive a single dose of Tdap…
--Permissive recommendation: For adults > 65
years of age, a single dose of Tdap may be given…
Have you received your Tdap?
Questions?
Resources
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DHEC pertussis site
http://www.scdhec.gov/health/disease/immunization/pertussis.htm
DHEC 2010 list of reportable conditions
http://www.scdhec.gov/administration/library/CR-009025.pdf
CDC pertussis site www.cdc.gov/pertussis
CDC Recommended Antimicrobial Agents for Treatment and
Postexposure Prophylaxis of Pertussis
http://www.cdc.gov/mmwr/PDF/rr/rr5414.pdf
CDC Prevention of Pertussis, Tetanus, and Diphtheria Among Pregnant
and Postpartum Women and their Infants
http://www.cdc.gov/mmwr/PDF/rr/rr5704.pdf
Additional CDC pertussis vaccine recommendations
http://www.cdc.gov/vaccines/pubs/ACIP-list.htm#pert
CDC Pinkbook, Pertussis
http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/pert.pdf
Immunization Action Coalition http://www.immunize.org/pertussis/
AAP Redbook
Antibiotics for Pertussis
CDC. MMWR : 2005;54:14.
DTaP Vaccine Efficacy
• 85.2% (95% CI: 80.6 to 88.8)
• 88.7% (95% CI: 76.6 to 94.6)
Ref: J. Liang, Pertussis Vaccines, ACIP June 2010
Tdap Impact: Studies, Disease
Rates
• Based on efficacy studies before licensure
– 85%-92%
• Based on effectiveness studies after
licensure
– 66%-78%
– Since Tdap licensure, pertussis rates among
adolescents have declined faster compared to
other age groups
Ref: J. Liang, Pertussis Vaccines, ACIP June 2010
Improving Pertussis Diagnostics:
Current and Future Efforts
• Serologic assay kit
– Revisit the CSTE case definition
• Multi-target PCR assay
• Pertussis Clinical Validation Study
• Public health lab training
– Consider testing at SC DHEC laboratory:
discuss with local DHEC epis first (803576-2749)
Serology
Pros
Cons
•Can be used later in disease
course
•Less affected by antibiotic
treatment
•No standardized test
•May be affected by recent
immunization
•Not useful during first 2 weeks of
illness
•Not currently included in CSTE
case definition
- Not counted for surveillance
purposes