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

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

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 **

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 1970-2005 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. 10-20% of survivors of meningococcal disease have serious sequealae, including limb loss, hearing loss, and neurological problems. NETSS data

Cases of meningococcal disease by serogroup and age group, 1996-2005 Cases of Meningococcal Disease by Age and Serogroup from 1996-2005. - 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 11-19 age group, serogroups C and Y (which are both covered in the conjugate vaccine) cause the largest number of cases ABCs data excluding OR

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 10-19 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.

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

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

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

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

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

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

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

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

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

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;334:349-355

Clinical Efficacy of Adult Acellular Pertussis Vaccine* Vaccine Efficacy = 92% (95% CI: 32%, 99%) *Ward et al. NEJM 2005; 353(15):1555-63. ‡Pertussis defined as a cough illness lasting ≥ 5 days with laboratory evidence of pertussis by culture, PCR, and/or serologic testing results

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)

ACIP Recommendations and Implementation Issues

The Three Musketeers: Recommended Adolescent Vaccines

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

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

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

Guillian-Barre Syndrome (GBS) and MCV4 Vaccine Adverse Event Reporting system 33 reported cases of GBS after MCV4 No increase in risk in 11-19 year-olds Possible small increase in risk in 15-19 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

ACIP Recommendations All adolescents 11-18 years should receive a dose of Tdap and MCV4 Preferably at 11-12 year-old visit More data on safety in special situations (pregnancy, intervals) needed and may come with time

Next Steps: Maximizing Prevention Strategies

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

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

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

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

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

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

Thank You! Contact Info: Amanda Cohn Centers for Disease Control and Prevention 1600 Clifton Rd MS C-09 Atlanta, GA 30333 Phone: (404) 639-6039 E-mail: acohn@cdc.gov