1	Advances in Pertussis Control Through Expanded Immunization Barbara P. Yawn, MD MSc Director of Research Olmsted Medical Center Rochester, MN
2	Pertussis Disease Manifestations
3	Pertussis Stages, Period of Communicability
4	Reported Pertussis Cases by Year United States, 1922 – 2000
5	Reports of Pertussis United States, 1980 – 2004
6	Waning of Vaccine-Induced Immunity
7	Estimated Duration of Immunity After Infection or Vaccination
8	Common Clinical Manifestations of Adolescent-Adult Pertussis Cough 97% ³ 3 weeks, 52% ³ 9 weeks Paroxysms ³ 3 weeks in 73% Whoop in 69% Post-tussive emesis in 65% Teens missed average 5 days of school; Adults missed average 7 days of work Average 14 days of disrupted sleep
9	Complications of Adolescent – Adult Pertussis Complications common in adolescents (16%) and adults (28%) Cyanosis found in 6% of adolescents and 9% of adults Pneumonia occurs in 2% of patients <30 years old and 5% to 9% of older patients Hospitalization of adolescents and adults at 1.4% and 3.5%, respectively
10	Complications of Pertussis in Infants United States, 1997-2000
11	Infant Pertussis Deaths 1980-1989
12	CDC Study – Infant Pertussis: Who Was the Source? 774 infant cases from 4 states 264 cases had source identified Sources:
13	Age of Pertussis Source* for Infants
14	Case Study #1 8 week old child admitted in October with 8 day history of coughing spells associated with cyanosis, vomiting, nasal congestion and low grade fever of 100^oF Patient seen by his family physician in the office and had a visit to the ER before admission; diagnosed with URI; no antibiotics given Pertussis PCR was positive Youngest of 5 children; ages 2, 4, 9, and 11 years, all fully immunized for age
15	Case Study #1 11 y/o sibling had persistent cough for 3 wk before the infant’s first symptom 26 y/o mother began with paroxysmal cough 10 days before infant’s first symptom The 2 y/o sibling began with mild cough 2 days before the infant’s first symptom The 4 y/o sibling, initially asymptomatic, had a positive pertussis PCR, and later developed a coughing illness that lasted > 2 weeks
16	Case Study #1
17	Case Study #1: Possible Transmission Routes
18	Take Home Messages Difficult to determine transmission patterns Household with multiple children Reasons for negative PCRs Long duration of cough, and poor specimen collection and processing Difference in severity in adolescents/adults vs. children Importance of protecting against all severities of pertussis, including mild disease Importance of chemoprophylaxis
19	Healthcare Professionals Involved in Transmission of Pertussis Physicians 1912 Schwenkenbecher Nurses 1972 Kurt et al Physicians 1992 Etkind et al Nurses 1995 Christie et al Nurses 1997 Matlow et al Nurses and Physicians 2005 CDC
20	Bordetella pertussis Major Antigens and Virulence Factors Pertussis toxin (PT), also known as lymphocytosis- promoting factor (LPF) Filamentous hemagglutinin (FHA) Pertactin (PRN), also known as 69 kilodalton protein Fimbrial agglutinogens (FIM)
21	Components of U.S. DTaP Vaccines
22	Antigenic Components of Selected Diphtheria, Tetanus, and Acellular Pertussis Vaccines
23	Vaccine Formulation
24	ADACEL™ Clinical Development Program Demonstration of non-inferiority for: Safety Comparison to standard of care (Td adsorbed vaccine) Immunogenicity Comparison to standard of care (Td adsorbed vaccine) for diphtheria and tetanus Comparison to efficacious 5 component DTaP vaccine for pertussis Concomitant administration with hepatitis B (HB) or influenza vaccine
25	ADACEL™ Clinical Trial: Tetanus Seroprotection ³ 0.1 IU/mL
26	ADACEL™ Clinical Trial: Diphtheria Seroprotection ³ 0.1 IU/mL
27	ADACEL™ Clinical Trial: Pertussis Post-Vaccination GMTs, Adolescents
28	ADACEL™ Clinical Trial: Pertussis Post-Vaccination GMTs, Adults, vs. Sweden I
29	ADACEL™ Clinical Trial: Solicited Local Reactions, Days 0-14, Adolescents
30	ADACEL™ Clinical Trial: Solicited Local Reactions, Days 0-14, Adults
31	ADACEL™ Post-Marketing Experience Over 6 million doses of ADACEL-containing vaccines distributed Approximately 5 million doses used in Europe, majority ADACEL + IPV Nearly 1 million doses used in Canada
32	ADACEL™ Experience in Canada ADACEL licensed in Canada – May 1999 NACI issued a supportive statement, but at that time did not give a recommendation for universal routine use 3 provinces or territories launched ADACEL vaccination programs
33	Pertussis Incidence and Vaccine Use, 1993 – 2004 Canada’s Northwest Territories
34	Incidence of Pertussis, 1986 – 2003 Canada vs. Newfoundland
35	Long-Term Follow-Up, Adults and Adolescents D and T Seroprotection (³ 0.01 IU/mL)
36	ADACEL™ after Td Vaccination Prescribing information for ADACEL specifies 5-year minimum interval following Td administration Large study concerning safe dosing interval for ADACEL recently completed on Prince Edward Island No serious adverse events related to vaccination reported No clinically important differences in reactogenicity found among those who received ADACEL 2 to 9 versus 10 years after Td / DT vaccination Investigators concluded that ADACEL can be safely administered at intervals > 2 years since previous Td / DT vaccine
37	Pertussis Summary Reports of pertussis, which have increased dramatically in recent years, represent only fraction of actual cases Largest increases in reported cases are among adolescents and adults Pertussis immunity, following disease or vaccination, wanes over time Disease in adolescents and adults associated with significant morbidity and complications, and with transmission to infants Infant pertussis is often severe, leading to hospitalization and mortality; deaths continue to increase among infants too young to be fully vaccinated
38	ADACEL™ Assessment Disease Prevention Potential Provides tetanus and diphtheria immunogenicity similar to current standard of care, Td Added protection against pertussis in adolescents and adults Potential to reduce pertussis disease in general population and prevent transmission of pertussis from adolescents and adults to infants Reactogenicity Slight increase in reactogenicity in adolescents compared to Td
39
40	CDC Advisory Committee on Immunization Practices (ACIP) Provisional Recommendation – Adolescent Pertussis On June 30, 2005, the ACIP voted to recommend that: Adolescents 11 and 18 years of age (who have not received Td) be given Tdap in place of the tetanus-diphtheria (Td) booster. Preferred age is 11-12 years. Adolescents 11 to 18 who have already been vaccinated with Td are encouraged to receive a dose of Tdap to further protect against pertussis. 5 year interval is recommended although shorter intervals may be used. These comments are revised to incorporate January 2006 updates. These will become final when published.
41	CDC Advisory Committee on Immunization Practices (ACIP) Provisional Recommendation – Adult Pertussis On October 26, 2005, the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC) voted unanimously to recommend routine Tdap vaccination to protect against Pertussis in adults 19 through 64 years of age. Specifically, the ACIP recommended the following: Routine Tdap immunization for adults: Adults who have not received a Td immunization during the last 10 years should receive a single dose of Tdap vaccine. Those not previously given Tdap vaccine may be given Tdap vaccine at shorter intervals (< 10 years) following last Td immunization in settings of wound management and increased risk (including pertussis outbreaks and contact with infants).
42	"Tdap immunization of adults to..." Tdap immunization of adults to prevent pertussis exposure in infants: Adults who anticipate having close contact with infants (eg parents, health-care givers and daycare givers) should receive a single dose of Tdap vaccine to protect against Pertussis if they have not received Tdap vaccine. Ideally these adults should receive Tdap vaccine at least one month before beginning close contacts with infants.