Pediatrics

Pertussis “A disease for a lifetime”

Mary Healy, M.D.

Center for Vaccine Awareness & Research

Texas Children’s Hospital

Baylor College of Medicine, Houston, Texas

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Disclosures

•Research Grant

• Sanofi Pasteur

• Novartis Vaccines and Diagnostics

•Advisory Board

•Novartis Vaccines and Diagnostics

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Objectives

•Describe pertussis and the challenge of inducing

durable immunity

•Outline the current epidemiology of pertussis

•Describe the complications of endemic pertussis

or pertussis outbreaks in adults

•Describe the consequences of pertussis disease

•Critically evaluate currently recommended

pertussis prevention strategies

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Pertussis “A poorly controlled vaccine-preventable disease”

•Cyclical incidence with peaks every 3-5 years

•Immunity (natural and vaccine-induced) wanes

•Highly contagious

•Infection may be unrecognized

‐atypical or asymptomatic in adolescents and young adults

•Improved detection methods

•Impact of change to acellular pertussis vaccine?

•Variations in B. pertussis?

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Pertussis: Antigenic and Biologically

Active Components

•Pertussis toxin (PT)

•Filamentous hemagglutinin (FHA)

•Pertactin (PRN)

•Fimbrial proteins (FIM)

•Agglutinogens

•Adenylate cyclase

•Tracheal cytotoxin

4

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Clinical Course (Weeks)

-3 0 2 12 8

Onset

Incubation period

(typically 5-10 days;

max 21 days) Catarrhal stage

(1-2 weeks)

Paroxysmal stage

(1-6 weeks)

Convalescent stage

(weeks to months)

Communicable period

(onset to 3 weeks after

start of paroxysmal cough)

5

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Pertussis

0

50000

100000

150000

200000

250000

300000

1922 1930 1940 1950 1960 1970 1980 1990 2000 2010

DTP

DTaP

Pre-vaccination • > 180,000 cases • 4000 deaths Vaccination reduced number of cases and deaths by >85%

www.cdc.gov JAMA. 2007;298:2155-2163

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Pertussis in the US

●

▲

2012 On target for most cases since 1959

No

. of

Cas

es

0

20

40

60

80

100

120

140

160

2005 2006 2007 2008 2009

<6 mos 6-11 mos

1-4 yrs 5-9 yrs

10-19 yrs 20+ yrs

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Pertussis in Texas: 2012

•1,284 cases as of 9-24-12 (incidence 4.86/100,000)

Personal Communication: Rachel Wiseman MPH

Incidence rate highest in infants < 6 mos 6 deaths (43% of US total) 5 in infants < 3 months 4 in Hispanic infants

Age (years)

% c

ase

s

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Pertussis Outbreaks in Adults • Debilitating

•“100 day cough”

Quebec N=384

Sweden N=155

Germany N=79

UK N=77

Australia N=63

Duration of cough

97% ≥ 3 wks

55% > 9 wks

- 80% ≥ 3 wks

100% ≥ 3 wks

Mean/Median

wks -/12 8/- 7/7.7 - 8.6/-

Range wks - 2-26 Up to 32 wks

3-32 0.5-21

MMWR 2006; 55:1-44

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Pertussis Outbreaks

MMWR 2006; 55:1-44

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Pertussis Outbreaks

• Social effects

‐Missed school or work time

•Economic burden

‐Physician visits and hospitalization

‐Contact investigations

•Non-medical costs account for up to 58% of

total cost in adults

•Societal cost estimated to be ~ $2000 per case

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Pertussis Outbreaks: Who is at risk?

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Waning Immunity

• Protection wanes during the 5 years after 5th DTaP dose

• Odds of acquiring pertussis ↑ ~ 42% per year since 5th DTaP

www.cdph.ca.gov/programs/immunize/Pages/PertussisSummaryReports.aspx Klein et al., NEJM 2012;367:1012-9

Herd immunity is critical

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Pertussis: Who may die?

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Young Infants are Vulnerable •Infants too young to have completed the primary immunization series have up to 20 times higher risk of pertussis

•Complications highest in infants <6 m

‐Deaths almost exclusively in < 3 months

‐Risk of complications and death in infants inversely proportional to number of DTaP doses received

•Infants of Hispanic ethnicity over-represented in pertussis incidence (74% ↑) and deaths (70% in 2007; 90% of deaths in 2010 California outbreak)

JAMA 2003; 290::2968-75 MMWR 2009; 57:1420-1431 Pediatrics 2008;121:484-492

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Vaccinate the Village

Pediatr Infect Dis J. 2004;23:985-9. Pediatr Infect Dis J. 2007;26:293-9. MMWR 2008; 57(RR-4):1-51 Clin Infect Dis 2010;50:1339-45 Clin Infect Dis 2010;50:1346-8

Household contacts infect young infants in 75% of cases

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No Single Strategy to Prevent Pertussis

• Antimicrobial Prophylaxis

• Tdap vaccine (tetanus, diphtheria, acellular pertussis)

‐Natural and vaccine-induced immunity wanes

‐One time dose for adolescents and adults

• New Immunization Platforms ‐2011: Immunization during 3rd or late 2nd trimester of pregnancy preferable to postpartum

‐2006: Targeted immunization – “cocooning”

MMWR 2008; 57(RR-4):1-51 Global Pertussis Initiative Vaccine 2007:2634-42

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Tdap Coverage among Adolescents

Age 13–17 years: 2006–2010

10.8

30.4

40.8

55.6

68.7

0

10

20

30

40

50

60

70

80

90

100

CDC. MMWR 2008;58(36);997-1001. CDC. MMWR 2008;57(40)1100-1103. CDC. MMWR 2007;56(34) 885-888. CDC. MMWR 2010 ;59(32);1018-1023.

2006 2007 2008

Perc

enta

ge (

%)

2009 2010

19

Tdap coverage among adults increased from 2% to 8.2% in the same time period

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•Safe for mother and infant

•Optimal timing

•Biological factors affecting placental transport

‐ IgG1 antibodies superior to other subclasses

•Anecdotal evidence from pre-vaccine era

‐Peak death rates occurred age 2-3 months

•Studies with whole cell pertussis vaccine in the

1940s - 1950s demonstrated infant protection

•High levels of maternal antibody interfered with

infant response to DTP but not DTaP

Maternal Immunization Nature’s Gift

Pediatr Infect Dis J. 2005;24:S62-S65.

Pediatrics 1995; 96:580-84.

Clin Obstet Gynecol. 2012;55:474-86.

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Cocooning • Targeted immunization of infant caregivers

‐Contacts of infants age < 1 yr

‐Healthcare providers (HCPs) of infants age < 1 yr

•No outcome data

•Potential strong indirect effect:70% in <3 mo old cases

•Challenging to implement on a regional/national level

‐New Immunization Platform

‐Education

‐Two populations – pregnant and postpartum women, families

‐New Immunization Providers

‐Reimbursement issues Global Pertussis Initiative Vaccine 2007:2634-42

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Implementation of Cocooning Postpartum

Women

Houston, TX: Jan-Apr 2008

1129 (72%) immunized; 96.5% of those eligible

Chicago, IL: June 2008-Nov 2009

9,540 (78.7%) immunized

NICU Stony Brook, New York

72% of all parents; 89% of “screened” parents

Uptake greater if infant admitted > 3 days

Pediatric

Office

Durham, NC

51% of parents immunized,

60% of these immunized at first postnatal visit

Hospital-based

Cocooning

Houston, TX: June 2009-Jan 2010

92% postpartum women immunized

58% of mothers had additional contact immunized

91% received Tdap before infant discharge

98% in daily contact with infant

Vaccine 2009; 27:5599-602 Jt Comm J Qual Patient Saf. 2010;36:173-8. Pediatrics 2008;122:e550-5. Acad Pediatr. 2009;9:344-7. Clin Infect Dis 2011; 52:157-62

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Lessons Learnt •Postpartum immunization possible through

standing order protocols

•Barriers to the full implementation of

cocooning include:

‐targeted education for new immunization providers

and target populations

‐need for convenient, out of hours service

‐access to reliable immunization records

‐unanticipated societal events

•The necessary infrastructure and education

requires investment of finances and time

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Conclusions •Despite high immunization rates, pertussis

outbreaks are reported

•Pertussis outbreaks cause morbidity and are a

considerable social and economic burden

•The majority of pertussis-related complications and

deaths are in infants too young to be immunized

•Prevention strategies are hampered by waning of

vaccine-induced immunity and limited

implementation of targeted immunization strategies

•As with other infectious diseases, no single or

stand-alone strategy will control pertussis

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Control of Pertussis: 2012 •Administer DTaP as per Infant and Childhood schedule

•Tdap to adolescents at 11-12 years (Middle School Entry)

•All contacts of infants age < 1 year, including adults 65

years and older

•All pregnant women in 3rd or late 2nd trimester

of pregnancy or, if not, postpartum

•Current Questions

‐Each pregnancy?

‐Tdap at age 7 years?

‐Tdap every 5 years?

‐New vaccine?

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Doing Nothing is Unacceptable

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