Amanda Faulkner, MPHMeningitis and Vaccine Preventable Diseases Branch

Centers for Disease Control and Prevention

September 25, 2012

Responding to the Rise in PertussisCT AAP CME Program

National Center for Immunization and Respiratory DiseasesDivision of Bacterial Diseases

Kathy Kudish, DVM, MSPHImmunization Program

Connecticut Department of Public Health

2

Pertussis (Whooping Cough)

Highly contagious respiratory disease Severe, debilitating cough illness (“100 day cough”) in

persons of all ages Highest morbidity and mortality among infants Estimated worldwide deaths > 300,000/yr Vaccine-preventable Poorly controlled, despite high vaccine coverage First U.S. pertussis vaccines for adolescents and adults

(Tdap)† licensed in 2005

†Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine

2

Clinical Course (in weeks)

-3 0 2 128

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)

3

4

Clinical Stages

Catarrhal Watery eyes, low-grade fever, malaise, mild eye inflammation, runny

nose, late-phase nonproductive cough Paroxysmal

Paroxysms (bursts of coughing during a single exhalation) followed by an inspiratory "whooping" sound, post-tussive cyanosis, and vomiting

In infants younger than six months (especially those younger than four weeks): apnea, bradycardia, prolonged cough, poor feeding, no paroxysms

Convalescent Paroxysms gradually improve but recur with respiratory infections

www.aafp.prg

4

Infant Pertussis

Young infants at highest risk of disease and complications

Atypical symptoms: Catarrhal stage and cough may be

minimal or absent Apnea (sometimes with seizures) Sneezing Gagging, choking, vomiting Whoop infrequent

Cough illness among close contacts

Presumptive treatment should begin immediately

Source: Shot of Prevention, Brady passed away at just 2 months from pertussis

5

6

Pertussis among Adolescents and Adults

Wide spectrum of presentation Disease often milder than in infants and children May be asymptomatic Can be quite severe and with classic presentation

Clinically difficult to distinguish from other causes of cough illness

Persons with mild disease can transmit infection

7

Pertussis Treatment When to treat

Adults, adolescents, children• Antimicrobials may modify course if given early (reduce duration and

severity of symptoms and lessen communicability)• Treatment >3 weeks after cough onset limited benefit

Infants and pregnant women near term• Treatment up to 6 weeks after cough onset should be considered

Recommended treatment Macrolide / azolide antimicrobial

• 5 day course azithromycin• 7 day course clarithromycin• 14 day course erythromycin

Alternative agent: • 14 day course trimethoprim-sulfamethoxazole (Bactrim)

8

LABORATORY TESTING

9

Diagnostic Challenges

Stage of disease Quality/timely collection of clinical specimen (s) Antimicrobial administration Vaccination status Transport conditions Contamination of clinical specimen Lack of clinically validated/ standardized tests

10

Diagnostic NeedsClinical vs. Public Health

Clinical setting Optimizes sensitivity Rapid turnover

Public health setting Optimizes specificity Confirmation of etiology Prevention and control measures

11

Pertussis Diagnostics at CDC

Culture 100% specific Low sensitivity Incubation time 4-10 days

Multi-target real-time PCR 4 targets Speciate 3 Bordetella spp. Co-infections

IgG anti-PT ELISA Quantitative/qualitative Adolescents and adults Late phase of disease

12

Commercial Pertussis Serologic Assays

Commercial assays are not standardized and clinical accuracy is unknown

CDC is conducting a study to better understand the usefulness of commercially available assays for clinical diagnosis

Not included in CDC/CSTE pertussis case definition CDC ELISA is not commercially available

Tech transfer is ongoing in collaboration with APHL and state public health laboratories

13Real-Time PCR Amplification Plot

R-PCR Assay IS481

Present in three Bordetella spp. 50 to >200 copies in B. pertussis 8 to 10 copies in B. holmesii 0 to 7 copies in B. bronchiseptica

High Ct value could indicate Positive test for B. pertussis False positive Positive for

• B. holmesii• B. bronchiseptica

Falsely-positive PCR Results during Outbreak Investigations

Hospital: NH, 2006 Community: CO, 2009 Community: NY, 2010

14

Falsely-positive PCR Results Use of IS481 as a single target assay

• High Ct values interpreted as positive results Contamination of clinical specimens during collection

• B. pertussis DNA present in some vaccines • Confirmed by environmental sampling of clinics• Key factors likely ungloved hands and use of liquid transport media

+ + +

False Positives

+

15

16

CDC Best Practices Guidance for Healthcare Professionals on the Use of PCR for Diagnosing Pertussis

Target clinicians to optimize the use of PCR Testing patients with signs and symptoms of pertussis Optimal timing and specimen collection for PCR testing Avoiding contamination of clinical specimens with B. pertussis DNA Understanding and interpreting PCR results

Available at:

http://www.cdc.gov/pertussis/clinical/diagnostic-testing/diagnosis-pcr-bestpractices.html

17

Specimen Collection for Pertussis PCR

Acceptable samples: Nasopharyngeal swabs Nasopharyngeal aspirates

Nasal swabs are not acceptable

Visit www.cdc.gov/pertussis for instructions on specimen collection

18

0 2 128

Culture

Serology

4 6

Cough Onset

10

PCR

Optimal Timing in Weeks for Diagnostic Testing

19

EPIDEMIOLOGY AND VACCINATION

20

Pertussis Surveillance and Reporting

Nationally notifiable Clinical (Probable) case

Cough ≥2 weeks AND One among paroxysms, whoop, post-tussive vomiting

Confirmed case Culture OR Clinical case and PCR positive OR Clinical case and epi-linked to confirmed case

21

Reported Pertussis Cases by Diagnosis±, 1990-2010

1990 1995 2000 2005 20100

5000

10000

15000

20000

25000

30000

UnknownSero+(MA)Epi-linkedDFAPCRCulture

Year

Num

ber o

f Cas

es

±Data collection for PCR and Epi-Link began in 1995Source: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System, 2010

22

Pertussis Immunization in the US

Infants/children Widely used since 1940s Transitioned from DTP to DTaP throughout the 1990s DTaP at 2, 4, 6 months; 15-18 months; 4-6 years Children 7 through 10 years not fully immunized against pertussis

should receive a single dose of Tdap

Adolescents/adults Licensed in 2005, recommended in 2006 Single Tdap, preferred at 11-12 years All adolescents/adults who did not receive at 11-12 years should

receive a single dose as soon as feasible (includes those 65 yr and older)

• Tdap can be administered regardless of interval since the previous Td dose

1922

1930

1940

1950

1960

1970

1980

1990

2000

2011

0

50,000

100,000

150,000

200,000

250,000

300,000

Year

Num

ber o

f cas

esReported NNDSS pertussis cases: 1922-2011

DTP

1990

1995

2000

2005

0

5,000

10,000

15,000

20,000

25,000

30,000

Tdap

DTaP

SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and 1922-1949, passive reports to the Public Health Service 23

DTaP Coverage among Children Aged 19 through 35 months — 2004-2011

2004 2005 2006 2007 2008 2009 2010 20117880828486889092949698

3+4+

Year

Cove

rage

%

CDC National Immunization Survey 24

Reported pertussis incidence by age group: 1990-2011

1990

1995

2000

2005

2011

0

20

40

60

80

100

<1 yr1-6 yrs7-10 yrs11-1920+ yrs

Year

Inci

denc

e ra

te

(per

100

,000

)

SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System 25

26

Annual Incidence by State, 2010

Incidence is per 100,000 populationSource : CDC National Notifiable Disease Surveillance System, *2010 data accessed July 22, 2011CDC Wonder Population Estimates (Vintage 2009)

1.1-3.6

3.7-6.5

6.6-10.2

10.3-23.2

Incidence

2010 incidence 9.0(n=27,550)

27

Annual incidence by State, 2011

Incidence is per 100,000 populationSource : CDC National Notifiable Disease Surveillance System, 20112010 Census data used for population estimates

2011 incidence 6.1(n=18,719)

0.7-2.8

2.9-5.1

5.2-9.3

9.4-23.3

Incidence

28

Tdap IMPLEMENTATION AND IMPACT

29

Tdap Vaccine Effectiveness

Bridging studies of ADACEL and BOOSTRIX1

85-89% APERT study2

92% (95% CI: 32.0-99.0) Australia3 – screening method

78.0% (95% CI: 60.7-87.6) St. Croix outbreak4

65.6% (95% CI: -35.8-91.3) MN case-control study

72.3% (95% CI: 38.8-87.4)

1 Schmitt HJ et al. JAMA 1996;275:37-41; Gustafsson LH et al. NEJM 1996;334:349-3552 Ward JI et al. N Engl J Med. 2005 Oct 13;353(15):1555-63.3 Rank C, et al. Pediatr Infect Dis J. 2009 Feb;28(2):152-3. 4 Wei SC, et al. CID 2010; 51(3):315-321.

Tdap Coverage among Adolescents Aged 13–17 years — 2006–2010

Series10

10

20

30

40

50

60

70

80

90

100

10.8

30.4

40.8

55.6

68.7

CDC. National, State, and Local Area Vaccination Coverage Among Adolescents Aged 33-17 Years - United States, 2008. MMWR 2008;58(36);997-1001.CDC. Vaccination Coverage Among Adolescents Aged 13-17 Years – United States, 2007. MMWR 2008;57(40)1100-1103.CDC. Vaccination Coverage Among Adolescents Aged 13-17 Years– United States, 2006. MMWR 2007;56(34) 885-888. CDC. National, State, and Local Area Vaccination Coverage among Adolescents Aged 13-17 Years - United States, 2009 MMWR 2010 ;59(32);1018-1023.

2006 2007 2008

Perc

enta

ge (%

)

2009 2010

30

Incidence of Reported Pertussis — 1990–2010

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

0123456789

10

OverallYear

Case

s/10

0,00

0 Po

pula

tion Tdap

CDC unpublished data

31

Slope = -0.4752, p<.0001

Slope = +0.2225, p<.0001

Accelerated Decline of Pertussis Rate ratios of pertussis incidence among

adolescents 11-18 years, 1990-2009

Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print]

32

Absence of Indirect Effects of Tdap Mean incidence of reported pertussis among infants

1990-2003(pre-peak)

2006-2009(post-peak)

p-value

Mean incidence

(per 100,000)52.1 55.4 0.64

Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print]

33

34

EMERGENCE OF DISEASE AMONG CHILDREN AGED 7 – 10 YEARS

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

0

5

10

15

20

25

Proportion of all Pertussis Cases contributed by Children Aged 7–10 years

Year

Perc

ent

35

36

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

200400600800

10001200140016001800

2004

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

200

400

600

800

1000

1200

1400

1600

2005

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

50100150200250300350400450

2002

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

100200300400500600700800

2003

Age (years)

Case

s

Pertussis Cases by Age – 2002-2005

37

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

200

400

600

800

1000

1200

2008

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

200

400

600

800

1000

1200

1400

1600

2009

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

100200300400500600700800

2006

Age (years)

Case

s

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180

50100150200250300350400450

2007

Age (years)

Case

s

Pertussis Cases by Age – 2006-2009

38

EVALUATION OF DTaP VACCINE EFFECTIVENESS (VE) AND DURATION OF PROTECTION

39

California VE Study

Cases & controls 4-10 yrs at illness onset or enrollment Reported pertussis cases in 15 CA counties Unmatched controls from case-patient providers (3:1) Vaccine histories collected by in-person visits to providers Logistic regression, accounting for clustering 250 provider offices, 4,000 charts abstracted

40

Pertussis Disease among Unvaccinated compared to Vaccinated Children

PertussisVaccination Status Case Control OR (95% CI) *Unvaccinated 53 19 8.9 (4.9 – 16.1)5 DTaP doses 629 1,997

* Accounting for clustering by county and provider

41

Overall VE & Duration of Protection Estimates

* Accounting for clustering by county and provider

Model * Case (n)

Control (n)

VE, % 95% CI

Overall VE, All Ages 0 dose 53 19 Ref -- 5 doses 629 1,997 88.7 79.4 – 93.8

Time since 5th dose 0 doses 53 19 Ref -- < 12 months 19 354 98.1 96.1 – 99.1 12 – 23 months

51 391 95.3 91.2 – 97.5

24 – 35 months

79 366 92.3 86.6 – 95.5

36 – 47 months 108 304 87.3 76.2 – 93.2 48 – 59 months 141 294 82.8 68.7 – 90.6 60+ months 231 288 71.2 45.8 – 84.8

42

Overall VE & Duration of Protection Estimates

* Accounting for clustering by county and provider

Model * Case (n)

Control (n)

VE, % 95% CI

Overall VE, All Ages 0 dose 53 19 Ref -- 5 doses 629 1,997 88.7 79.4 – 93.8

Time since 5th dose 0 doses 53 19 Ref -- < 12 months 19 354 98.1 96.1 – 99.1 12 – 23 months

51 391 95.3 91.2 – 97.5

24 – 35 months

79 366 92.3 86.6 – 95.5

36 – 47 months 108 304 87.3 76.2 – 93.2 48 – 59 months 141 294 82.8 68.7 – 90.6 60+ months 231 288 71.2 45.8 – 84.8

43

Tdap and DTaP StudiesSummary and Conclusions

Tdap program has reduced the burden of pertussis in adolescents

No evidence for “herd immunity” Excellent initial DTaP vaccine effectiveness Modest but immediate waning of immunity from DTaP Pertussis burden in children aged under 10 years appears to

be a “cohort effect” from change to all aP vaccines i.e. a problem of susceptibility despite vaccination

44

2012 U.S. PERTUSSIS ACTIVITY

1922

1930

1940

1950

1960

1970

1980

1990

2000

2012*

0

50,000

100,000

150,000

200,000

250,000

300,000

Year

Num

ber o

f cas

es

* 2012 NNDSS data are provisional and reflect cases reported to NNDSS as of Week 37

Reported NNDSS pertussis cases: 1922-2012*

DTP

1990

1995

2000

2005

2012*

05,000

10,00015,00020,00025,00030,00035,000

Tdap

DTaP

SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and 1922-1949, passive reports to the Public Health Service 4

5

Changes in Pertussis Reporting by State from 2011 to 2012* †

*Data for 2012 are provisional and subject to change. †Cases reported through Week 37 in 2011 were compared with cases reported through Week 37 in 2012; fold-changes were calculated for each state.

Decrease/No change< 2-fold increase

2 to 3-fold increase

> 3-fold increase

46

Pertussis cases by age — United States, 2012

<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 190

5

10

15

20

25

30

35National Incidence without WashingtonNational Incidence

Age (years)

Case

s/10

0,00

0

Acellular Only

3 DTaPs

5th DTaP Tdap

Vaccine Type Re-ceived*

4th DTaP

Transition Period

Whole Cell and Acellular

47

48

PREVENTION AND CONTROL GUIDELINES

49

Revised CDC Guidelines for the Prevention and Control of Pertussis: Objectives

Primary: Preventing death and serious complications in individuals at increased risk of severe and/or complicated disease, including infants <12 months

Secondary: Limit transmission in outbreak setting Limit further spread and duration of transmission within closed

communities Decrease morbidity in affected populations Lower risk of dissemination to unaffected groups within an outbreak

50

Revised CDC Pertussis Outbreak and Control Guidelines: Overview

Emphasis on those at highest risk Lack of evidence of broad-scale prophylaxis

Tiered approach offers flexibility but encourages judicious use of antibiotics

Alternatives to prophylaxis Cough exclusion and “watchful waiting”

Opportunity to increase pertussis vaccine coverage

51

PERTUSSIS SURVEILLANCE—CONNECTICUT, 2006–2012

52

Cumulative Number of Cases by Month Reported—Connecticut, 2006–2012

* Through 9/19/2012; current state-wide incidence is 5.3 cases/100,000 population

Jan Feb MarchApril May June July Aug Sept Oct Nov Dec0

20

40

60

80

100

120

140

2006200720082009201020112012*

Month

Num

ber o

f Cas

es

53

Cumulative Number of Cases by Month Reported— Fairfield County Connecticut, 2006–2012

* Through 9/19/2012; current incidence in Fairfield County is 8.7 cases/100,000 population

Jan Feb March April May June July Aug Sept Oct Nov Dec*0

10

20

30

40

50

60

70

80

2006200720082009201020112012*

Month

Num

ber o

f Cas

es

54

Cumulative Number of Cases by Month Reported— Litchfield County Connecticut, 2006–2012

* Through 9/19/2012; current incidence in Litchfield County is 26.9 cases/100,000 population

Jan Feb March April May June July Aug Sept Oct Nov Dec0

10

20

30

40

50

60

2006200720082009201020112012*

Month

Num

ber o

f Cas

es

55

Percent of Cases by Confirmation Type—Connecticut, 2006–2012

* Through 9/1/2012

2006 2007 2008 2009 2010 2011 20120%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CulturePCREpi linkProbable (no test)

Year

Perc

ent

of C

ases

58%

10%

Pertussis Incidence by Age Group — Connecticut, 2006–2011

<1 1–6 7–10 11–19 >190

5

10

15

20

25

30

3529.7

2.8

7.75.2

1

Age Group

Incid

ence

per

100

,000

Pop

ulati

on

56

57

Culture Submissions to the Department of Public Health (DPH) Laboratory

• Culture is still considered to be the gold standard (100% specific)• The DPH encourages providers to submit cultures alongside PCR,

particularly in situations where a clinical practice is seeing an increase in the number of pertussis diagnoses among patients that share a common setting, such as a school or daycare

• Availability of culture has contracted over the past decade• Culture continues to be available at the DPH Laboratory• Successful culture isolation of the organism declines if the

patient has received prior antibiotic therapy effective against B. pertussis, if specimen collection has been delayed beyond the first 2 weeks of illness or if the patient has been vaccinated

58

Pertussis Culture

• Samples can be sent to the state either directly by healthcare providers or by a hospital laboratory

• If specimen collection is to take place in the office: Specimen collection kits which include the transport media for B.

pertussis may be obtained by calling the DPH Laboratory at (860) 920-6674 or 6675

Kits should be requested ahead of time so they are accessible at the time of specimen collection

Instructions for specimen collection are provided with the kits Transport media has a finite shelf life (3-6 months)

• Once a nasopharyngeal swab has been collected it should be plated directly or placed into transport medium immediately

59

VACCINATION STRATEGIES TO PROTECT INFANTS

60

Pregnancy and CocooningACIP Recommendations

Pregnant women vaccinated preferably during the third or late second trimester. Alternatively, administer Tdap immediately postpartum

Cocooning is the strategy of vaccinating all close contacts of infants with Tdap to reduce the risk of transmission Ideally at least 2 weeks before contact with the infant Parents, siblings, grandparents, child-care providers and health-care

personnel

61

Shifting the timing of mother’s Tdap dose:postpartum to pregnancy

Provides earlier benefit to mother, thereby protecting infant at birth

High levels of transplacental maternal antibodies in infants of mothers vaccinated during pregnancy Likely provides direct immunity to infant

Pregnancy Postpartum

CONNECTICUT ACTIVITIES TO COMBAT PERTUSSIS

62

Tdap Cocoon Program

• Hospital-based program to vaccinate new mothers and family members of newborns with Tdap upon the birth of their child

• Of the 28 birth hospitals in Connecticut, 23 are participating in the DPH Tdap Cocoon Program– Began fall of 2008– Close to 55,000 doses administered through this program,

with the number increasing every year • List of “referral sites” where family members of infants <12

months can receive Tdap on the DPH Immunization Tdap Cocoon Program web page: http://www.ct.gov/dph/immunizations

63

Tdap Cocoon Program Evaluation

• Surveyed birth hospitals in fall 2011 about use of Tdap– 24 (86%) hospitals reported routinely offering Tdap to

postpartum patients – Mean Tdap immunization rate for postpartum patients

where Tdap was offered was 61% (confidence interval 54%–67%; median 63%, range 16%–87%)

– Manuscript submitted for publication

64

Tdap Vaccination Effectiveness for Preventing Infant Pertussis

• Case control study in 6 states participating in the Emerging Infections Program (EIP) to evaluate the effectiveness of the Tdap “cocooning” strategy

• Just getting underway, results probably at least a couple of years away

65

Enhanced Pertussis Surveillance(EPS)

• Part of EIP• Connecticut funded as an EPS site since 2011• One of 6 sites in the U.S.• Similar to previous surveillance activities with some

additional data collection• Collect Bordetella culture isolates where feasible and

forward to CDC for molecular characterization

66

Emerging Infection Program Network SitesWorking on Pertussis

AreasCO (5 counties)CA (state)CT (state)MN (state)NM (state)NY (15 counties)OR (3 counties)

67

68

Enhanced Pertussis Surveillance (EPS)Overview

Builds upon existing pertussis surveillance infrastructure at state Improved completeness and quality of data Augmented data collection

Objectives 10 - Collect epidemiologic information and isolates, when available, on

cases of B. pertussis 20 - Collect epidemiologic information and isolates, when available, on

other Bordetella species (B. parapertussis, B. bronchiseptica, and B. holmesii)

69

Tdap Vaccination Strategies Evaluation: Objectives

Measure effectiveness of vaccination during pregnancy at preventing pertussis among infants <12 months Age-specific effectiveness for infants <2months, and infants 2 - <6 months Determine if infants 6 - <12 months born to women vaccinated during

pregnancy have a higher odds of pertussis compared to infants born to women not vaccinated during pregnancy

Measure effectiveness cocooning at preventing pertussis among infants <2 months Effectiveness of maternal vaccination (at any time) at preventing pertussis

among infants <2 months Effectiveness of vaccination of the infant cocoon (all household contacts and

infant caregivers) at preventing pertussis among infants <2 months

70

Final Thoughts…

Pertussis continues to be a significant public health problem Vaccination is our best prevention tool Goal is no infant deaths

Improve Tdap coverage in adults Remove barriers to vaccination of pregnant women Implement cocooning Focus chemoprophylaxis efforts on high risk

Maintain high levels of coverage with DTaP Continue to evaluate and refine vaccination policy and

prevention and control recommendations

71

Web Resources CDC Pertussis Website

www.cdc.gov/pertussis Disease overview, podcasts, vaccine recommendations,

specimen collection videos, etc.

Provider Resources for Vaccine Conversations with Parents www.cdc.gov/vaccines/conv

ersations Materials created by CDC,

AAP, and AAFP