Effectiveness of adolescent and adult pertussis (Tdap) vaccine. Roger Baxter, Joan Bartlett, Ali Rowhani-Rahbar, Bruce Fireman, Nicola Klein

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1 Effectiveness of adolescent and adult pertussis (Tdap) vaccine Roger Baxter, Joan Bartlett, Ali Rowhani-Rahbar, Bruce Fireman, Nicola Klein

2 Disclosures I receive research grants from Sanofi Pasteur and GSK 2

3 Background: Despite widespread use of childhood pertussis vaccines, outbreaks of whooping cough are increasing. Tdap (tetanus, diphtheria and reduced dose acellular pertussis) was licensed in 2005 for adolescents and adults, based mostly on immunogenicity data compared to infant formulations Effectiveness data is needed, especially in persons vaccinated with acellular vaccines as infants 3

4 Pertussis (Rate per 100,000) In response to the California pertussis outbreak in 2010, we examined the relationship between Tdap vaccination and a positive test for pertussis 7.0 PCR-confirmed pertussis 2006 to 2011 Rates per 100,000 members per month

5 Study population Kaiser Permanente Northern California (KPNC) is a large, integrated health care delivery system with a membership in 2010 of 3.2 million. The KPNC population is diverse with regard to age, sex, race, and socioeconomic status and has similar demographics to the region except for the extremes of wealth and poverty. 5

6 Study population Study period: January 2006 through June 2011 PCR (amplified nucleic acid testing) was used to identify pertussis cases. No clinical criteria were used. Excluded: Persons younger than 11 years because Tdap vaccination rates were very low at these ages. Tdap recipients within 7 days of the PCR date 6

7 Methods - Case control design The risk of pertussis was assessed in relation to ever having had a Tdap vaccine We compared the vaccination history of persons testing positive for pertussis with two groups of controls: 1.Persons testing negative for pertussis and 2.Persons selected from the entire KPNC population. 7

8 Case control analyses For both study populations, we fit a conditional logistic regression model to estimate the association between PCRconfirmed pertussis and Tdap vaccination status after controlling for the same set of confounders. The model specification differed between the two study populations. 8

9 2 control groups PCR-negative controls: Matched for calendar time (date of PCR testing), and controlled for age, sex, race/ethnicity, and medical center KPNC controls: matched closely on calendar time, age, sex, race/ethnicity, and medical center 9

10 Why the 2 control groups? PCR negatives: to control for utilization and unmeasured confounding KPNC population: to more closely control for all the potential confounders we measured (sex, age, location and race/ethnicity) 10

11 Acellular Analysis: Tdap effectiveness in persons vaccinated with only acellular vaccines as children Identified the subset of persons for whom all 5 doses in the primary series were confirmed as acellular. Performed same analyses 11

12 Vaccine Effectiveness VE= (1 - odds ratio) Where the odds ratio equals: odds of positive pertussis test in vaccinated odds of positive pertussis test in unvaccinated 12

13 Results: PCR testing was performed on 27,631 members during the study period. 1,512 tests (5.47%) were positive for B. pertussis. 23.3% of PCR-positive cases had received Tdap vs. 30.3% of PCR-negative cases 13

14 Rate per 100,000 person-years Rates of PCR-confirmed pertussis by age in years Increased starting at age 5, peaked at 10 and declined by Age in years 14

15 Pertussis rate (per 100,000 person-years) PCR-confirmed pertussis rates and Tdap vaccination percent By age in years in % 90% 80% Age in years Percent vaccinated with Tdap 70% 60% 50% 40% 30% 20% 10% 0% 15

16 Results: PCR-negative controls The odds ratio of a positive pertussis test in vaccinated vs. not was Control Type Cases N Controls N Odds Ratio 95% CI P-value PCR Negative 566 9, <0.001 KPNC Pop , <0.001 VE: For the PCR-negative control analysis, calculated vaccine effectiveness was 55.2% (95% CI %, p<0.001). 16

17 VE: For the KPNC controls analysis Calculated vaccine effectiveness was 62.7% (95% CI ) Very little change when stratification for race, medical office location, or both were removed from the model KPNC Pop controls Cases Controls Odds Ratio 95% CI P value Age, sex, race, and mob , <0.001 Age, sex, and mob , <0.001 Age, sex, and race , <0.001 Age and sex 567 2,067, <

18 Acellular subanalysis 487 persons 5.0% of the main analysis 96 cases 17.0% of all cases All persons are 11 to 18 years of age 97% are 11 to 13 18

19 Acellular analysis Control Type Cases N Controls N Odds Ratio 95% CI PCR Negative ,0.818 KPNC Pop ,1.522 For PCR-negative controls, VE was 55% (vs. 55% in full study) For KPNC controls, VE was 70% (vs.63% in full study) 19

20 Conclusions: Tdap was modestly effective (~55%) at preventing PCR-confirmed pertussis among KPNC adolescents and adults, most of whom had received whole cell vaccines as infants. A secondary analysis of the population vaccinated exclusively with acellular vaccines had the same VE (in the PCR-negative control analysis). 20

21 Limitations We did not use clinical criteria for pertussis Most persons in the study had received Tdap within the last 3 years. If there is waning over time, this could affect VE 21

22 Thank You! See also: Late Breaker Presentation # LB-6 Pertussis Vaccine effectiveness and the California 2010 pertussis outbreak 22

23 Results: Tdap waning Odds ratio of the risk of a pertussis test in relation to each year since vaccination: Control Type Cases N Controls N Odds Ratio 95% CI P-value PCR negative 177 3, KPNC pop 177 4, There was no clear evidence of waning. 23