1. Tale of Two Adolescent Vaccine-Preventable Diseases: Pertussis and Meningococcal Disease Amanda Cohn, MD National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention

2. Presentation overview
Epidemiology and Transmission
Vaccine properties and immunogenicity
Advisory Committee on Immunization Practices (ACIP) recommendations
Next steps

3. Wuthering Heights: Reported pertussis cases, United States, 1990-2006
> 18 yrs
Licensure and widespread use of pertussis vaccines in the United States had a major impact on the reported number of cases. During the pre-vaccine era, the number of pertussis cases culminated to about 270,000 in the mid 1930s, with more than 10,000 deaths. Since the introduction of DTP vaccine in the late 1940s, the number of reported pertussis cases has fallen dramatically -- more than a 99% decrease in reported cases. However, despite this dramatic decrease, pertussis continues to be endemic in the United States and the number of reported pertussis cases continues to peak every 3-4 years.
Since 1980, there has been an increase in the number of reported cases from approximately 2 thousand cases per year to 7 thousand cases per year, which is shown in the insert graph.
11-18 yrs
< 11 yrs **

4. Gone With the Wind: Meningococcal disease incidence, United States, 1980-2006
This slide uses our national passive surveillance system, known as NETSS, which receives case reports from all 50 states and provides the numbers you see in the MMWR.
This graph shows the incidence of meningococcal disease in the United States from in green. Notice the cyclical waxing and waning pattern of disease with peaks that typically occur every 8-10 years. The case fatality rate, shown here as the orange hatched line, decreased in the 1970’s but has remained stable at around 10% since the 1980’s % of survivors of meningococcal disease have serious sequealae, including limb loss, hearing loss, and neurological problems.
NETSS data

5. Cases of meningococcal disease by serogroup and age group, 1996-2005
Cases of Meningococcal Disease by Age and Serogroup from
- Serogroup is associated with age. B disease is predominant in the <1 age group, whereas serogroup Y causes the majority of disease in the 65 and older age group.
- Focusing in again on the age group, serogroups C and Y (which are both covered in the conjugate vaccine) cause the largest number of cases
ABCs data excluding OR

6. Age Distribution of Reported Pertussis
Cases – U.S., 2006
The graph represents the age distribution of pertussis cases in 2001 among 7580 cases with known age, the most recent year of complete data. The bars indicate the number of cases reported in each age group and the blue line indicates the age-specific incidence rate.
The incidence is by far the highest among infants < 1 year of age (49.78/100,000). This falls dramatically among preschool and young school-aged children, increases slightly among the year age group, and decreases with age thereafter.
Please remember that these are reported cases, and that a reporting bias is likely present. As you know, pertussis is less often suspected, diagnosed, and reported among older age groups. With that in mind, note that slightly over half (55%) of the cases were reported among persons 10 years of age or older.

7. Steps in reporting, meningococcal disease and pertussis
Hmmm, I just read an article about pertussis…
What does this result mean?
Hi, I’m calling from your health department
Cough, Cough
Chemoprophylaxis
Medical encounter
Clinical Recognition
Reliable Diagnostics
Report to Health Department

8. Pertussis transmission
Coughing Adolescent
Lots of coughing adolescents = +
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

9. Meningococcal disease transmission
Asymptomatic Carriers
Invasive Disease = +
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

10. Meningococcal Disease and Pertussis Epidemiology
Endemic diseases
Cases in all age groups, higher rates in infants and adolescents
Clinical presentations lead to very different recognition and reporting patterns

11. Meningococcal Conjugate Vaccine (MCV4) and Acellular Pertussis Vaccine (Tdap)

12. Meningococcal Conjugate Vaccine Composition
Serogroups A,C,Y,W-135
4μg of each capsular polysaccharide
Same as meningococcal polysaccharide vaccine (MPSV4)
MCV4 conjugated to 48μg diphtheria toxoid
Potential licensure in 2009 of MenACYW-Crm
Same age indication as MCV4

13. Tdap Vaccine composition
Tetanus and diphtheria toxoids ~ Td
Acellular pertussis antigens same as DTaP except some antigens present in lower quantity
BOOSTRIX® ~ INFANRIX®: PT, FHA, PRN
ADACEL® ~ DAPTACEL®: PT, FHA, PRN, Fimbrae 2/3
*BOOSTRIX® and INFANRIX®: pertussis toxin (PT); filamentous haemagglutinin (FHA);
pertactin (PRN)
†ADACEL® and DAPTACEL®: PT, FHA, PRN and Fimbrae 2/3

14. Measure for Measure: 4-fold rises in SBA titer by serogroup, MCV4 vs MPSV4
92%
82%
*CDC, MMWR, RR, 2005
FDA Clinical Briefing Document, VRBPAC 09/22/04
Study MTA-02

15. Vaccine effectiveness of MPSV4
VE of MPSV4 among 2- to 29-year-olds= 85% (95% CI, 27%-97%) against serogroup C disease
Presumed advantages of conjugate vaccines
T cell-dependent response
Longer duration of protection
Primes for immunologic memory
Protects from acquisition of carriage

16. The Bridge to Terabithia: Tdap Immunogenicity
Efficacy for licensure inferred from immungenicity data
Serologic bridge
Immune responses in adolescents and adults after 1 dose Tdap not inferior to response in infants after 3 doses DTaP during pertussis efficacy trials
Infant vaccine efficacy approx. 85%
INFANFRIX®: 89% (95% CI: 77%, 95%)*
DAPTACEL®: 85% (95% CI: 80%, 89%)**
But say last bullet not quantitated
*Schmitt HJ et al. JAMA 1996;275:37-41
**Gustafsson LH et al. NEJM 1996;334:

17. Clinical Efficacy of Adult Acellular Pertussis Vaccine*
Vaccine Efficacy = 92% (95% CI: 32%, 99%)
*Ward et al. NEJM 2005; 353(15):
‡Pertussis defined as a cough illness lasting ≥ 5 days with laboratory evidence of pertussis by culture, PCR, and/or serologic testing results

18. MCV4 and Tdap
Lack of known protective antibody level for both diseases
Good vaccines, but not perfect
We have a lot to learn
Ability to reduce transmission to unvaccinated groups
Duration of protection
These properties make it very difficult to know what to do in the situation where children have been vaccinated (chemoprophylaxis)

19. ACIP Recommendations and Implementation Issues

20. The Three Musketeers: Recommended Adolescent Vaccines

21. Sense and Sensibility: The art of risk-benefit decisions
Based on little data about risk or benefit
Intervals between Td and Tdap
Use of Tdap in pregnant adolescents
Increasing evidence about risk
Guillian-Barre Syndrome (GBS) and MCV4

22. Intervals between Td and Tdap
A 5 year interval between Td and Tdap is encouraged to reduce risk for local and systemic reactions
Theoretical risk with multiple doses of tetanus and diphtheria toxoids (including MCV4)
Shorter intervals may be used if the benefit outweighs the risk of vaccination

23. Tdap during pregnancy No data on safety or effectiveness
ACIP does not recommend vaccination of pregnant women with Tdap
Not a contraindication, may be useful in certain situations
AAP recommends that pregnant adolescents be given the same considerations for immunization as nonpregnant adolescents. If Tdap or Td vaccine is indicated, administer in the second or third trimester

24. Guillian-Barre Syndrome (GBS) and MCV4
Vaccine Adverse Event Reporting system
33 reported cases of GBS after MCV4
No increase in risk in year-olds
Possible small increase in risk in year-olds
Vaccine Safety Datalink (VSD)
One case of GBS pending confirmation, no other cases identified
Over 640,000 doses in VSD <= 1 case expected
Ongoing risk of meningococcal disease
History of GBS a precaution to receiving MCV4
ACIP, February 2009

25. ACIP Recommendations
All adolescents years should receive a dose of Tdap and MCV4
Preferably at year-old visit
More data on safety in special situations (pregnancy, intervals) needed and may come with time

26. Next Steps: Maximizing Prevention Strategies

27. Great Expectations: Td/Tdap and MCV4 NIS-Teen 2007

28. Outbreak Management Susceptible group = 1- (VE * Coverage)
1- (0.85 * 0.75)= 47%
1- (0.85*0.95)= 20% - herd immunity?
Response to vaccine takes 7-14 days
Vaccination does not replace chemoprophylaxis of close contacts but may reduce transmission

29. Do you need to give chemoprophylaxis to a vaccinated close contact?
Meningococcal disease
Chemoprophylaxis often given before serogroup data available
Pertussis
Adolescents often exposed multiple times in school outbreaks
Long exposure period

30. Will we have to revaccinate with Tdap and/or MCV4?
Duration of protection unknown
Waning immunity of pertussis vaccines
Memory response may not be enough to protect against meningooccal disease
Disease risk continues
Pre-teen girls will become mothers (hopefully after adolescence!)
Pre-teens will become college freshmen

31. All’s Well that Ends Well: Preventing Meningococcal Disease and Pertussis
Both endemic with transmission among adolescents, different disease patterns
Susceptible populations remain; increasing coverage will reduce disease in the target population and may increase herd immunity across all age groups, e.g. high-risk infants
Safety and effectiveness data are emerging and may help refine recommendations
Intervals, revaccination

32. Acknowledgements Jessica MacNeil Stacey Martin Tami Skoff Stanley Wei
Thomas Clark
Nancy Messonnier
Nihdi Jain
Shannon Stokely
Elaine Miller
Eric Weintraub
John Iskander

33. Thank You!
Contact Info:
Amanda Cohn
Centers for Disease Control and Prevention
1600 Clifton Rd MS C-09
Atlanta, GA 30333
Phone: (404)