Pertussis: Trends, Prevention and Challenges Flor M. Munoz, MD Associate Professor Pediatric Infectious Diseases
Disclosure I do not have any relevant conflicts of interest to disclose. Page 1 xxx00.#####.ppt 1/23/2015 2:17:54 PM
Objectives 1. Epidemiology of Pertussis in US and Texas 2. Current Pertussis Prevention Strategies and Vaccine Coverage 3. Update on Disease Prevention Strategies: Maternal Immunization 4. Challenges and Future Direction of Pertussis Prevention in the US Page 2 xxx00.#####.ppt 1/23/2015 2:17:55 PM
Pertussis Whooping cough Starts with a mild URI without fever (Catarrhal stage), then Paroxysmal Cough, Whoop, Post- Tussive Emesis for >2-3 weeks. Affects infants, children, adolescents, adults ~48.5 million cases per year worldwide ~ 295,000 deaths Infants < 6 mo have the highest attack rate, morbidity and mortality. Diagnosis often delayed. Source: CA Dept.of Health website Grandparents 6% Caretakers 2% Friends & Cousins 10% Children, adolescents and adults: Often misdiagnosed. Up to 20% of prolonged coughing illnesses in adults are due to pertussis. Reservoirs. Complications. Aunts & Uncles 10% Siblings 16% Parents 55% Wendelboe, A, et al PIDJ. 2007;26:293-99. Page 3 xxx00.#####.ppt 1/23/2015 2:17:57 PM
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~49,000 cases Page 5 xxx00.#####.ppt 1/23/2015 2:17:59 PM
Pertussis in U.S. 2014 20,284 cases nationwide (as of 09/20/14) Reported in 50 states and Washington, D.C. 30% increase from same time last year California has declared an epidemic Over 8,000 cases (as of 9/15/14) 3.5% of cases have required hospitalization One death (5 week old) Page 6 xxx00.#####.ppt 1/23/2015 2:18:00 PM
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Source: CDC.gov Page 9 xxx00.#####.ppt 1/23/2015 2:18:04 PM
2009 2009 2013 2005 Page 11 xxx00.#####.ppt 1/23/2015 2:18:04 PM
Pertussis in Texas DSHS reported 3,986 pertussis cases in 2013. The annual total surpassed the recent high of 3,358 cases in 2009. There were 5 pertussis-related deaths in 2013; All infants too young to be vaccinated and none of the mothers were vaccinated with Tdap during pregnancy. From 2000-2013, a total of 48 deaths were attributed to pertussis In 2014, 2,045 cases have been reported as of Nov 3, 2014; 2 deaths (< 3 months, unvaccinated mother; teen with comorbidities); and a 11% hospitalization rate (80% < 1 year old) http://www.dshs.state.tx.us/idcu/disease/pertussis/ Page 12 xxx00.#####.ppt 1/23/2015 2:18:06 PM
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Pertussis Prevention Strategies - ACIP 1997 DTaP 2,4,6 mo + 12-18 mo and 4-6 yr 2005 Tdap Adolescents 11-12 yr and catch up 13-18 yr 2006 Tdap Adults 18-64 yr Health care workers Tdap not Td for tetanus post-exposure prophylaxis MMWR 2011-13 Page 14 xxx00.#####.ppt 1/23/2015 2:18:07 PM
Pertussis Prevention Strategies - ACIP 2008 Post-partum women and close contacts of infants (cocoon strategy) Breastfeeding NOT a contraindication 2011 Pregnant women 2 nd -3 rd trimest. if no previous Tdap Use Tdap without concern for interval since last TT People > 65 yrs in contact with infants 2012 Pregnant women 27-36 wks gest EVERY pregnancy Page 15 xxx00.#####.ppt 1/23/2015 2:18:07 PM MMWR 2011-13
Resurgence despite high vaccine coverage Page 16 xxx00.#####.ppt 1/23/2015 2:18:08 PM
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Tdap Effectiveness wanes within 3-4 years Page 21 xxx00.#####.ppt 1/23/2015 2:18:11 PM
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Antibodies post Tdap Rapidly decline in first 1-2 years Slower decline over 5-10 years Close to pre-vaccination at 10 years Note: No defined level of antibody correlates absolutely with protection! Increase in disease after ~5 years correlates with decrease in antibody concentrations Page 24 xxx00.#####.ppt 1/23/2015 2:18:13 PM
Tdap Effectiveness and Revaccination Response to booster vaccination is robust to all pertussis antibodies after 5 or 10 years Data available for a second dose only, not subsequent doses (ie. decennial Tdap) Page 25 xxx00.#####.ppt 1/23/2015 2:18:13 PM
Infant DTaP Effectiveness and Duration of Protection Page 26 xxx00.#####.ppt 1/23/2015 2:18:14 PM
Pertussis Hospitalizations in Infants and Vaccine Coverage Page 27 xxx00.#####.ppt 1/23/2015 2:18:15 PM
Waning protection after 5 th dose of DTaP Protection from the 5 th dose of DTaP wanes substantially during the 5 years after vaccination in children who received only DTaP Risk of pertussis increased by an average of 42% per year after vaccination Vaccine effectiveness decreases over time and duration of protection depends on initial effectiveness Klein NP. Et al NEJM 2012;367:1042-9 Page 28 xxx00.#####.ppt 1/23/2015 2:18:16 PM
Comparative Effectiveness of Acellular vs. Whole-Cell Pertussis Vaccines in Teenagers Increasing number of DTaP doses from 0 to 4 was significantly associated with increasing % of positive PCR Risk of pertussis: 4DTaP vs 4DTwP OR 5.63 Mixed vs 4DTwP OR 3.77 If no Tdap booster: 4DTaP vs 4DTwP OR 9.92 With Tdap booster: 4DTaP vs 4 DTwP OR 4.85 Percentage of pertussis PCR tests with a positive result in the study population by pertussis vaccine type for the first 4 doses received between 1 and 24 months of age, Jan 2010 to Dec 2011. * Those given whole-cell pertussis vaccines in childhood were more protected than those given acellular pertussis vaccines * Tdap booster remains best means currently available to protect teens Klein NP, et al 2013;131:e1716 e1722 Page 29 xxx00.#####.ppt 1/23/2015 2:18:17 PM
Summary: Immune responses to Pertussis vaccines DTaP and Tdap yield high specific antibody titers after imm Whole cell and acelllular vaccines elicit different priming response: DTwP (and natural infection) produce Th1 cytokine response DTaP elicit mixed Th1/Th2 responses, skewed toward Th2, at 6 months and probably until the 5 th dose Immunity and protection wane faster than anticipated (3-5 y) Data not supportive for change in schedule (more doses) in adults (HCP) Ausiello CM et al. Infect Immun 1997;65(6):2188; Mascart F et al. Vaccine 2007;25(2):391 Ryan M et al. Immunology 1998;93(1):1-10; Ausiello Page CM et 30 al. Infect Immun 1999;67(8):4064 Dirix V et al. Vaccine 2009;27(43):6042; Hendrikx LK et al.vaccine 2011;29(40):6874 xxx00.#####.ppt 1/23/2015 2:18:18 PM
Current Pertussis Prevention Strategies On time and on schedule vaccination Improve coverage in adults, including HCP Maternal Immunization Recommended since 2012 coverage remains low ~16-18% in US Recommended in UK, Australia, other countries based on epidemiology Most direct and effective method to protect infants against pertussis Page 31 xxx00.#####.ppt 1/23/2015 2:18:19 PM
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Maternal Immunization with Tdap Study Maternal immunization with Tdap* is safe and will boost maternal antibodies to pertussis antigens, which can be efficiently transferred transplacentally Infants born to mothers vaccinated during pregnancy will have higher concentrations of pertussis specific antibodies that could protect them during the first 2 months of life, a period of vulnerability, high morbidity and mortality Maternal immunization with Tdap should NOT interfere with infant responses to primary and booster vaccination with DTaP** *Adacel (SP) contains PT (2.5 ug), FHA (5 ug), PRN (3 ug), FIM 1-2 (5 ug), DT (2LfU) and TT (5LfU) **Pentace l (SP) contains PT, FHA, PRN, FIM1, FIM2, Tetanus and Diphtheria Toxoids / Hib / IPV Page 33 xxx00.#####.ppt 1/23/2015 2:18:20 PM
Maternal Immunization with Tdap Study Design Arm Group N= Single dose administered to pregnant women with crossover design Postpartum Antepartum Intervention 1 32 Tdap Saline Control 2 16 Saline Tdap Single dose administered to non-pregnant women Control 3 32 Tdap vaccine Page 34 xxx00.#####.ppt 1/23/2015 2:18:21 PM
Munoz FM et al. JAMA May 7, 2014 Page 35 xxx00.#####.ppt 1/23/2015 2:18:21 PM
Safety: Proportion of Subjects with ANY Injection Site or Systemic Reaction by Day and Study Group Injection Site Reactions Systemic Reactions Antepartum dose Postpartum dose Antepartum dose Postpartum dose Tdap Saline Tdap Saline Saline Tdap Saline Tdap Tdap Tdap Page 36 xxx00.#####.ppt 1/23/2015 2:18:22 PM
Safety Outcomes V. Antepartum (N-33) V. Post-Partum (N-15) C-section delivery 9 (27.27%) 9 (60%) Infant Preterm Del (<37 wk) 3 (9.1%) 1 (6.7%) Infant AGA SGA 27 (84.4%) 1 (3.1%) 13 (86.7%) 0 Infant Weight Mean (SD) Median 3.2 Kg (0.5) 3.2 Kg 3.5 Kg (0.7) 3.3 Kg Infant APGAR scores (Median at 1/5 minutes) 8 / 9 8 / 9 No significant differences in infant exam findings and neonatal course, growth and development, and Bailey developmental exam No documented cases of pertussis in mothers or infants No deaths, no vaccine-related SAEs Page 37 xxx00.#####.ppt 1/23/2015 2:18:24 PM
Transplacental Antibody Transfer Page 38 xxx00.#####.ppt 1/23/2015 2:18:25 PM
Immunogenicity (GMC) Pertussis Antibodies in Mothers and Infants Page 39 xxx00.#####.ppt 1/23/2015 2:18:26 PM
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Donegan K, et al, UK Tdap Safety in Pregnancy Observational cohort study UK Clinical Practice Research Datalink Pop: 20,074 pregnant women with a median age of 30 yr who received Tdap-IPV (SP) in the 3 rd trimester (28-38 wk) since October 2012 and a matched historical unvaccinated control group Primary Outcome: Adverse events identified from clinical diagnoses during pregnancy with additional data from the matched child record identified through mother-child linkage. The primary event of interest was stillbirth (Def: intrauterine death after 24 weeks gestation). Donegan K, et al. BMJ 2014;349:g4219 Page 45 xxx00.#####.ppt 1/23/2015 2:18:30 PM
Tdap Safety in Pregnancy There was no increased risk of stillbirth in the 14 days after vaccination (incidence rate ratio 0.69, 95% CI 0.23 to 1.62) or later in pregnancy (0.85, 0.44 to 1.61) compared with historical national rates. There was no evidence that vaccination accelerated the time to delivery (hazard ratio 1.00 0.97 to 1.02) There was no evidence of an increased risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, hemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, Cesarean delivery, low birth weight, or neonatal renal failure, all serious events that can occur naturally in pregnancy. Congenital anomalies not sought (registries). UK Yellow Card no increase in pregnancy complications Donegan K, et al. BMJ 2014;349:g4219 Page 46 xxx00.#####.ppt 1/23/2015 2:18:33 PM
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US VSD Coverage and Safety of Tdap during pregnancy (Kharbanda et al. 2014) Coverage during pregnancy ~ 15-18% 2007-2012 Safety cohort study 2010-12, observational Outcomes: Hypertensive disorders, Chorioamnionitis Preterm delivery (<37 wk), SGA (< 10%) Page 48 xxx00.#####.ppt 1/23/2015 2:18:36 PM
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Maternal Vaccination Prevents Leukocytosis, not Colonization Page 52 xxx00.#####.ppt 1/23/2015 2:18:40 PM
Summary Childhood and adolescent Pertussis disease has increased despite high DTaP and Tdap coverage and effective vaccines (vaccines do protect!) Pertussis epidemiology changed since switch to less reactogenic acellular pertussis vaccines Factors involved: Rapidely waning immunity, awareness and improved diagnostic methods, unvaccinated groups, incomplete reservoir elimination (adults, close contacts, HCW), changes in pathogen? Potential Solutions: Short term: Maternal immunization to protect most vulnerable infants, Tdap vaccination of adolescents and adults; Improved coverage and On Time vaccination Long term: Need new pertussis vaccines! Page 53 xxx00.#####.ppt 1/23/2015 2:18:41 PM
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