1. Amanda Faulkner, MPH Meningitis and Vaccine Preventable Diseases Branch Centers for Disease Control and Prevention September 25, 2012 Responding to the Rise in Pertussis CT AAP CME Program National Center for Immunization and Respiratory Diseases Division of Bacterial Diseases Kathy Kudish, DVM, MSPH Immunization Program Connecticut Department of Public Health

2. 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

3. Clinical Course (in weeks) -302128 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. 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

5. 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. 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. 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. 8 LABORATORY TESTING

9. 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. 10 Diagnostic Needs Clinical vs. Public Health  Clinical setting  Optimizes sensitivity  Rapid turnover  Public health setting  Optimizes specificity  Confirmation of etiology  Prevention and control measures

11. 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. 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

13. 13 Real-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

14. Falsely-positive PCR Results during Outbreak Investigations  Hospital: NH, 2006  Community: CO, 2009  Community: NY, 2010 14

15. 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. 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. 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 collectionwww.cdc.gov/pertussis

18. 18 02128 Culture Serology 46 Cough Onset 10 PCR Optimal Timing in Weeks for Diagnostic Testing

19. 19 EPIDEMIOLOGY AND VACCINATION

20. 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. 21 Reported Pertussis Cases by Diagnosis ±, 1990-2010 ±Data collection for PCR and Epi-Link began in 1995 Source: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System, 2010

22. 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

23. Reported NNDSS pertussis cases: 1922-2011 DTP 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

24. DTaP Coverage among Children Aged 19 through 35 months — 2004-2011 CDC National Immunization Survey 24

25. Reported pertussis incidence by age group: 1990-2011 SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System 25

26. 26 Annual Incidence by State, 2010 Incidence is per 100,000 population Source : CDC National Notifiable Disease Surveillance System, *2010 data accessed July 22, 2011 CDC 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. 27 Annual incidence by State, 2011 Incidence is per 100,000 population Source : CDC National Notifiable Disease Surveillance System, 2011 2010 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. 28 Tdap IMPLEMENTATION AND IMPACT

29. 29 Tdap Vaccine Effectiveness  Bridging studies of ADACEL and BOOSTRIX 1  85-89%  APERT study 2  92% (95% CI: 32.0-99.0)  Australia 3 – screening method  78.0% (95% CI: 60.7-87.6)  St. Croix outbreak 4  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;334:349-355 2 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.

30. Tdap Coverage among Adolescents Aged 13–17 years — 2006–2010 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 20072008 Percentage (%) 2009 2010 30

31. Incidence of Reported Pertussis — 1990–2010 Tdap CDC unpublished data 31

32. 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

33. 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) 52.155.40.64 Skoff et al. Arch Pediatr Adolesc Med. 2012 Jan 11. [ePub ahead of print] 33

34. 34 EMERGENCE OF DISEASE AMONG CHILDREN AGED 7 – 10 YEARS

35. 35

36. 36 Pertussis Cases by Age – 2002-2005

37. 37 Pertussis Cases by Age – 2006-2009

38. 38 EVALUATION OF DTaP VACCINE EFFECTIVENESS (VE) AND DURATION OF PROTECTION

39. 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. 40 Pertussis Disease among Unvaccinated compared to Vaccinated Children Pertussis Vaccination StatusCaseControl OR (95% CI) * Unvaccinated 53198.9 (4.9 – 16.1) 5 DTaP doses6291,997 * Accounting for clustering by county and provider

41. 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 dose5319Ref-- 5 doses6291,99788.779.4 – 93.8 Time since 5 th dose 0 doses5319Ref-- < 12 months1935498.196.1 – 99.1 12 – 23 months5139195.391.2 – 97.5 24 – 35 months7936692.386.6 – 95.5 36 – 47 months 10830487.376.2 – 93.2 48 – 59 months 14129482.868.7 – 90.6 60+ months 23128871.245.8 – 84.8

42. 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 dose5319Ref-- 5 doses6291,99788.779.4 – 93.8 Time since 5 th dose 0 doses5319Ref-- < 12 months1935498.196.1 – 99.1 12 – 23 months5139195.391.2 – 97.5 24 – 35 months7936692.386.6 – 95.5 36 – 47 months 10830487.376.2 – 93.2 48 – 59 months 14129482.868.7 – 90.6 60+ months 23128871.245.8 – 84.8

43. 43 Tdap and DTaP Studies Summary 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. 44 2012 U.S. PERTUSSIS ACTIVITY

45. Reported NNDSS pertussis cases: 1922-2012* DTP Tdap DTaP SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and 1922-1949, passive reports to the Public Health Service 45

46. 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

47. Pertussis cases by age — United States, 2012 47

48. 48 PREVENTION AND CONTROL GUIDELINES

49. 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. 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. 51 PERTUSSIS SURVEILLANCE— CONNECTICUT, 2006–2012

52. 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

53. 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

54. 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

55. 55 Percent of Cases by Confirmation Type— Connecticut, 2006–2012 * Through 9/1/2012 58% 10%

56. Pertussis Incidence by Age Group — Connecticut, 2006–2011 56

57. 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. 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. 59 VACCINATION STRATEGIES TO PROTECT INFANTS

60. 60 Pregnancy and Cocooning ACIP 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. 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 PregnancyPostpartum

62. CONNECTICUT ACTIVITIES TO COMBAT PERTUSSIS 62

63. 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 http://www.ct.gov/dph/immunizations 63

64. 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

65. 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

66. 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

67. Emerging Infection Program Network Sites Working on Pertussis Areas CO (5 counties) CA (state) CT (state) MN (state) NM (state) NY (15 counties) OR (3 counties) 67

68. 68 Enhanced Pertussis Surveillance (EPS) Overview  Builds upon existing pertussis surveillance infrastructure at state  Improved completeness and quality of data  Augmented data collection  Objectives  1 0 - Collect epidemiologic information and isolates, when available, on cases of B. pertussis  2 0 - Collect epidemiologic information and isolates, when available, on other Bordetella species (B. parapertussis, B. bronchiseptica, and B. holmesii)

69. 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. 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. 71 Web Resources  CDC Pertussis Website  www.cdc.gov/pertussis 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 www.cdc.gov/vaccines/conv ersations  Materials created by CDC, AAP, and AAFP