Pertussis C. Mary Healy, M.D. Center for Vaccine Awareness and Research, Texas Children’s Hospital Ben Taub General Hospital Baylor College of Medicine, Houston, Texas C Mary Healy MD, 11/30/09. St. David's Medical Center

Disclosures Research Grant : Sanofi Pasteur Advisory Board for Novartis Vaccines

Pertussis: The “pernicious” or “100 day” cough Recognized since the middle ages – “The kink” or “kindhoest” 1640: Clinical description of the 1578 Paris epidemic 1905: Bordetella pertussis isolated 1925: Vaccine protection reported Incubation Period 7-10 days (4-21) Catarrhal Stage “Cold” Paroxysmal Stage “Whooping” Convalescent Stage “weeks to months”   

Dermal necrosis and vasoconstriction Attach to ciliae; important immunogen; activates cAMP, histamine sensitizing factor, lymphocyte promoting factor and islet-activating protein; stimulates IL-4 and IgE; interferes with phagocytosis; hemolytic; may be neurotoxic Adhesion and immunomodulation Causes fever Adhesion and immunogen Dermal necrosis and vasoconstriction OMP that mediates adherence and resists complement Ciliostasis; inhibits DNA synthesis; kills cilial epithelial cells Activates cAMP; interferes with leucocytes; hemolytic Lancet 2006; 367: 1926-36

Pertussis Vaccination: A Success Story DTP  Pre-vaccination > 180,000 cases 4000 deaths Vaccination reduced number of cases and deaths by >95% DTaP  CDC

Incidence of Pertussis, U.S. DTP  No. of Cases CDC

Pertussis in Texas 13.5 cases/100,000 pop www.dshs.state.tx.us

Pertussis in Texas : not the whole story www.wcchd.org

Pertussis in Texas : not the whole story www.wcchd.org

Why Pertussis is a Problem Pertussis is highly contagious Pertussis vaccine protection wears off after age 10 years There is an epidemic of pertussis in the U.S. in adolescents and adults Pertussis may be atypical or asymptomatic in adolescents and young adults who then spread the infection widely Pertussis may be severe and fatal in young infants

Pertussis: an evolving story Rate/100,000 DTP  No. of Cases DTaP  CDC

Pertussis Threatens Infants Infants too young to be immunized (< 6 months) have up to 20 times higher risk of pertussis Two thirds of these are admitted to hospital Pneumonia, seizures, brain damage Pertussis causes ~ 20 deaths per year, almost all in very young infants Infants of Hispanic ethnicity are at increased risk Message points: This photo illustrates the effects of pertussis on infants. You’ll notice that the lung on the left, the infected infant’s lung, is deflated and not receiving air. Pertussis causes 40 to 80 infant deaths each year in the U.S. Since 1990, 87-100% of annual pertussis-related deaths occur in infants under six months of age. Normal Chest x-ray Baby with Pertussis C Mary Healy MD, 11/30/09. St. David's Medical Center 12

Pertussis in Texas 4 deaths in 2008; 3 in 2009 All occurred in infants < 3 mo of age Haleigh Throgmorton; age 6 weeks Just how close to home is the threat of pertussis? Pictured here are two Texas parents, the Throgmortons, whose infant died as a result of pertussis. This tragic death occurred four years ago, before the pertussis Tdap booster vaccine for adults was available. Trying to keep other families from a similar tragedy, the Throgmortons share their story to encourage other families to vaccinate against pertussis. We thank them for letting us share their story today. Personal Communication: Texas Dept Health 13

California 2010 7-fold increase in the pertussis incidence rate compared with 2009 Highest number of cases in 50 years Highest rate of disease in Hispanic infants < 6 months (172 cases/100,000) 9 deaths All in infants too young to complete have completed their immunizations 7 of Hispanic ethnicity Emergency interventions in place Personal Communication, CDPH

Prevention of Infant Pertussis Treatment and Antimicrobial Prophylaxis Azithromycin or Erythromycin (all age groups) Clarithromycin or TMP-SMX (not for young infants) Tdap vaccine (tetanus, diphtheria, acellular pertussis) Natural and vaccine induced immunity wanes One time dose for adolescents and adults Part of pre-conceptual health Targeted immunization-cocooning Postpartum women before hospital discharge Immunize all contacts of infants < 1 year Immunize healthcare providers No outcome data but estimated to have a strong indirect effect:70%  in 0 - 3 mo old cases Red Book: 2009 Report of COID, pp. 504-19 MMWR 2008; 57(RR-4):1-51 Global Pertussis Initiative Vaccine 2007:2634-42 Vaccine 2007:2634-42

Who Infects Infants? Household contacts in > 75% of cases Pediatr Infect Dis J. 2004;23:985-9. Pediatr Infect Dis J. 2007;26:293-9.

Interrupt Transmission to Infants “Cocooning” Infants Interrupt Transmission to Infants In 2006, CDC recommended Tdap booster vaccine for contacts of young infants: All postpartum women before hospital discharge All contacts of infants < 1 year Healthcare providers for infants < 1 year N Engl J Med 2005;352:1215-1222 MMWR 2008; 57:1-51; Vaccine 2007:2634-42

Challenges with Cocooning Pertussis awareness Healthcare providers Population at large New immunization platform No infrastructure in place Need to target two populations Postpartum women Families New immunization providers Reimbursement

Implementation of Cocooning Parents of infants in NICU (N=598) Immunized 72% of all parents 86.9% of parents who had been screened Uptake higher in infants with stays > 3 days No adverse reactions observed Doctor’s Office, North Carolina (N=200) Approached parents attending for routine neonatal care 51.2% of parents immunized 40% of those immunized consented to Tdap on the second visit Dylag et al. Pediatrics 2008;122:e;550-5 Walter et al. Acad Pediatr 2009; 9:344-7

The Cocoon Strategy: Aim: the phased implementation of pertussis cocooning at Ben Taub General Hospital (BTGH), Houston, Texas Phase 1: postpartum immunization Phase 2: immunization of household contacts Ben Taub General Hospital One of two public, tax-supported hospitals in Harris County Hospital District ~5000 deliveries per year Predominantly Hispanic (>90%), medically underserved and underinsured population High risk for pertussis illness No infrastructure for cocooning in place

Raising Awareness Healthcare Providers (HCP) educated by Grand Rounds and small group in-services Obstetricians, Family Practitioners Midwives, Nursing Personnel Translators Posters and literature in antenatal and postnatal areas Pertussis information packets for families Information on other means to access low or no-cost vaccines Available to answer questions

Phase 1: Postpartum Women Starting January 2008, standing order for postpartum Tdap unless maternal contraindication is present* Tdap administered on hospital discharge concurrent with rubella vaccine (if needed) * 2 year minimum interval since prior tetanus-containing vaccine observed Jan 2008-May 2009; no minimum interval required June 2009-Jan 2010

Phase 1: Postpartum women 150 HCPs completed pertussis in-service Since Jan 7th, 2008 through Sept 20th, 2010, 10,450 postpartum women received Tdap prior to discharge Well-accepted No adverse events reported June 2009 - Jan 2010 92% of postpartum women are protected 86% immunized by us 6% previously had Tdap 87% of those by our program with a prior baby Healy et al. National Immunization Conference, 2010

Phase 2: Household Contacts Starting June 2009, contacts of newborn infants offered Tdap Where possible, postpartum women were interviewed to ascertain the number of additional contacts eligible and recommended to receive Tdap Pertussis education was provided Consenting eligible contacts were immunized on-site in the “Tdap Cocoon Clinic” (Mon-Fri; 10am-7pm)

Phase 2: Household Contacts Two Thirds of Mothers Interviewed Average of 3 contacts per infant eligible for Tdap (range 1-11) Average of 2 contacts per infant received Tdap (range 0-10) 58% of families had ≥ 1 contact immunized 1860 contacts immunized Timing of immunization 91% before or the day of infant discharge 8% day 1-7 post infant discharge Healy et al. National Immunization Conference, 2010 C Mary Healy MD, 11/30/09. St. David's Medical Center

Contact Relationship to Infant 87% lived in the infant’s household 98% would be in daily contact with infant Healy et al. National Immunization Conference, 2010

Challenges Identified Education Start early and often Takes time and effort, different groups have different perceptions Convenient, out of hours service Readily accessible immunization records Financial constraints Vaccine costs Requires multiple personnel Multi-disciplinary approach Prepare for the unexpected !

Other Texas Initiatives Texas Medical Association Postpartum immunization program in Williamson County hospitals Strongly encourage contacts to avail of vaccines at a variety of locations Educational initiatives Pamphlets, Webinar Texas Pediatric Society Immunization Partnership Adopted promotion of pertussis cocooning as a goal for current year

For the Future Maternal Immunization Neonatal Immunization Anecdotal evidence from pre-vaccine era Studies in the 1940s - 1950s demonstrated infant protection High levels of maternal antibody did not interfere with infant response to DTaP Transfer of pertussis antibodies from mother to infants occurs and antibody persist Neonatal Immunization Variable results Interfered with response to other vaccines Disease may precede immune response

In Summary: The disease burden from pertussis is considerable and very young infants are at high risk of life-threatening illness Pertussis immunity wears off within 10 years of vaccination and booster Tdap vaccine is required Targeted immunization strategies such as cocooning are recommended to prevent infants becoming infected with pertussis by family and household contacts

In Summary: Finally, let us remember why this is important ………. Cocooning needs initial and sustained educational efforts and novel initiatives to build this new immunization platform All immunization providers in a variety of settings should work together to form the “protective cocoon” around the vulnerable infants Finally, let us remember why this is important ……….

Protect Our Infants

Acknowledgements Center for Vaccine Awareness and Research Carol J. Baker, MD Julie A. Boom, MD Amy B. Middleman, MD Betsy H. Mayes, RN Baylor College of Medicine Marcia A. Rench, RN Baylor Methodist Community Health Fund Harris County Hospital District Foundation Williamson County Health Dept. Ben Taub General Hospital Kenneth Mattox, MD Harold Miller, MD Amy Young, MD Joseph Garcia Prats, MD Francis Kelly, RN Sara Ruppelt, PharmD City of Houston Health Dept. Immunization Partnership Sanofi Pasteur Texas Dept of Health All HCPs who care for pregnant women and their newborn infants Finally I’d like to acknowledge our associates and funding sources for this study. 33 33