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Pertussis – evolving epidemiology and strategies for prevention

Pertussis – evolving epidemiology and strategies for prevention. Dr Dave Graham Community and General Paediatrician Waikato. Declaration of conflict of interest. GlaxoSmithKline invited speaker Conference attendance supported by GSK. Additional conflicts/comments

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Pertussis – evolving epidemiology and strategies for prevention

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  1. Pertussis – evolving epidemiology and strategies for prevention Dr Dave Graham Community and General Paediatrician Waikato

  2. Declaration of conflict of interest • GlaxoSmithKline invited speaker • Conference attendance supported by GSK Additional conflicts/comments Not an infectious disease specialist Clinical and research interests in population immunisation strategies, general and developmental paediatrics, and optimised acute care practice

  3. Pertussis is back • Take home messages • It’s a bad bug • It’s most common and most severe in babies • Standard vaccination protocols are insufficient • We need some innovative strategies • Read “the book”

  4. Pertussis How serious is the burden of disease?

  5. New Zealand: notifications rising in 2011-12 Institute for Environmental Surveillance and Research. Pertussis Report. March 2012. Weeks 8-9: 18 Feb – 2 Mar 2012. Wellington: ESR; 2012. http://www.surv.esr.cri.nz/surveillance/PertussisRpt.php

  6. Pertussis cases and rates 2012 Institute for Environmental Surveillance and Research. Pertussis Report. March 2012. Weeks 10-11: 3 – 16 Mar 2012. Wellington: ESR; 2012. http://www.surv.esr.cri.nz/surveillance/PertussisRpt.php

  7. Pertussis is most severe in babies Australia: children admitted to hospital with pertussis, 2009–2010 44% of children hospitalised for pertussis were aged <2 months Marshall H et al. Presentation at Pertussis Workshop: National Centre for Immunisation Research; Sydney: 25-26 August 2011. http://www.ncirs.edu.au/news/past-news-events/Day%201/Marshall-Severity-of-pertussis-PertussisWS-25_26Aug11.pdf

  8. Pertussis still causes significant global mortality... Deaths in children younger than 5 years from vaccine-preventable diseases in 2008 Pertussis: 195,000 deaths per year (20%) WHO. 2010. http://www.who.int/immunization_monitoring/diseases/en/

  9. ... and morbidity “I have attached a recording of Ella coughing she does this all night and it has been going on 5 weeks now. I have had her at the gp 3 times . She has been on a course of antibiotic and now is on ventolin which I don't think is working…”

  10. Symptoms differ according to age Adolescents and adults have asymptomatic, mild or atypical disease Usually unsuspected, undiagnosed, untreated and not reported, especially in older individuals 1 Cherry J et al. Pediatr Infect Dis J 2005;24(5):S25–34. 2 Brooks DA, Clover R. J Am Board Fam Med 2006; 19: 603–11. 3 Wirsing von König CH et al. Lancet Infect Dis 2002;2:744–50. 4 Postels-Multani Set al. Infection 1995;23:139–42.

  11. Why? • The vaccination doesn’t work? • The vaccine isn’t being given? • Infectivity risk factors have changed? • The bacteria has changed? • The vaccine doesn’t last?

  12. Immunisation programmes have decreased the incidence of pertussis • 1980: • almost 2 million reported cases • low (~20%) vaccination coverage • 2010: • ~91,000 reported cases • High (~80%) vaccination coverage Vaccination coverage (%) (3 primary DTP doses) Number of cases WHO. IVB; 2010. http://whqlibdoc.who.int/hq/2010/WHO_IVB_2010_eng.pdf (accessed July 2011)

  13. Immunisation history of pertussis vaccination in hospitalised patients Percentage Goh A et al. Vaccine 2011;29:2503-07.

  14. Vaccine doesn’t work? • Overall the vaccine is effective • 84% efficacy (95% CI: 76-90%) after three infant doses • Sustained efficacy to 6 years of age • Adult vaccination is also effective, antibodies persist after 5 years but protection wanes over time • BUT – we still see regional epidemic cycles Ministry of Health. Immunisation Handbook. Wellington: 2011. http://www.health.govt.nz/publication/immunisation-handbook-2011

  15. Vaccine not being given? • Immunisation coverage has been variable • 1991-1992 national survey, 1996 northern region survey • 80-90% received three-dose primary series • Only 50-60% completed within 4 weeks of due date Parr A et al. The Northern Region health survey 1996/97. Auckland: Health Funding Authority 1998. Ministry of Health, A Portrait of Health. Key Results of the 2006/07 New Zealand Health Survey. Wellington: Ministry of Health; 2008.

  16. Current immunisation rates National Immunisation Coverage – 12 month reporting period ending June 2011 Ministry of Health. National and DHB immunisation data. Available at http://www.health.govt.nz/our-work/preventative-health-wellness/immunisation/immunisation-coverage/national-and-dhb-immunisation-data

  17. Immunisation coverage at 24 months Reporting Period: 12 month period ending September 2011 Ministry of Health. National and DHB immunisation data. Available at http://www.health.govt.nz/our-work/preventative-health-wellness/immunisation/immunisation-coverage/national-and-dhb-immunisation-data

  18. Immunisation coverage at 6 months Reporting Period: 12 month period ending September 2011 Ministry of Health. National and DHB immunisation data. Available at http://www.health.govt.nz/our-work/preventative-health-wellness/immunisation/immunisation-coverage/national-and-dhb-immunisation-data

  19. Vaccine not being given? • Pretty good at age 2 years • Poor at age 6 months • Dramatic ethnic disparity at 6 months • Delayed immunisation is a specific risk factor for admission to hospital with pertussis • No good quality data for older children or adults Grant CC et al. Delayed immunisation and risk of pertussis in infants: unmatched case-control study. BMJ (Clinical Research Ed). 2003; 326: 852-53.

  20. Has pertussis epidemiology changed?

  21. California: pertussis from 1947–2011* Cases Rate per 100,000 10,000 120 Previous peak in 1947 Number of cases:9,394 9,000 9,146 cases 100 8,000 23.4/100,000 7,000 80 6,000 dTap adolescent booster (ACIP rec) Previous peak in 1958 Incidence: 26.0/100,000 Number of cases Cases per 100,000 5,000 60 4,000 DTaP in primary infant series (doses 1–3) 40 3,000 DTaP as 4th and 5th childhood booster 2,000 20 1,000 0 0 1947 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 Year *As of September 2011 http://www.cdph.ca.gov/programs/immunize/Documents/PertussisReport20119.pdf (accessed November 2011); http://www.cdc.gov/vaccines/pubs/acip-list.htm (accessed November 2011)

  22. Demographic trends • Both parents in workforce • Older parents • More children in early childcare • And remember… • Immunoprotection wanes over time • True for both wild infection and immunisation

  23. Social contacts and spread of infectious diseases Contact Rates: White = high Green = intermediate Blue = low Mossong J et al. PLoS Med 2008;5(3):e74

  24. Transmission from older adults to unvaccinated infants Primary immunisation and preschool booster1 Infant <6 months Waning Immunity1,2,3 Adolescent booster1 Potential source of transmission1 1 Australian Government. Immunisation Handbook.9th edn, 2008. 2 Wood N et al. J Paediatr Child Health 2008;44(4):161-5. 3 Edelman K et al. Clin Infect Dis 2007;44:1271–77.

  25. We have designed a system where… • Young infants are unprotected • Older infants are under-immunised • Adults are effective disease vectors • Intensive co-mingling of disease-bearing adults, and vulnerable infants • We tolerate anti-science denialism • The system does what it was designed to do… • Episodic disease break-outs • Greatest morbidity and mortality burden in the very young Specter M. Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives. Penguin Press, New York, NY, USA, 2009

  26. Pertussis What can we do to reduce the burden of disease?

  27. Strategies for prevention • Universal infant pertussis vaccination has reduced disease incidence and mortality • But to reduce the burden of disease we may need to reinforce and expand current immunisation strategies: • Childhood vaccination (infants, toddlers, pre-school) • Adolescent booster dose • Adult vaccinations to ‘cocoon’ high-risk infants by vaccinating families, healthcare workers and childcare workers • Decennial boosting for all adults • Pregnant women and newborns?? • A better vaccine? 1 Forsyth K et al. Pediatr Infect Dis J 2005;24:S69–74. 2 Zepp F et al. Lancet Infect Dis 2011; 11: 557–70.

  28. Pertussis vaccines DTPw(diphtheria, tetanus, whole-cell pertussis) • Introduced in 1940s and still used in many countries DTPa/DTaP(diphtheria, tetanus, acellularpertussis) – e.g. Infanrix-hexa • Introduced in 1980s • Antigenic components of B. pertussis • Reduced reactogenicity1,2 but some swelling after fourth and fifth doses3 • Consistent 85–90% efficacy2 • Immunity persists for 5–10 years2 dTpa/dTap(diphtheria, tetanus, acellularpertussis) – e.g.Boostrix • Introduced 2000 • Reduced antigen formulations • Immunogenic and well tolerated in adolescents and adults1 1 Mattoo S, Cherry D. Clin Microbiol Rev 2005;18:326-82. 2 Zhang L et al. Cochrane Database Syst Rev 2011;1: CD001478 . 3 Marshall H et al. Pediatrics 2006;118:1501-09.

  29. Reinforce current infant and toddler immunisation strategies Coverage of immunisation programmes and timeliness of vaccine delivery are crucial • In 2010 in NZ, only 70% of children aged 6 months had completed their age-appropriate immunisations • 76% of European, 56% of Māori, and 67% of Pacific Island children1 • Infants for whom any of the three doses of the primary infant immunisation series were delayed had a five-fold increased risk of being hospitalised with pertussis.2 1 Ministry of Health. Immunisation coverage at milestone age: 6 months to September 2011. Wellington: 2011. Available at: http://www.health.govt.nz/our-work/preventative-health-wellness/immunisation/immunisation-coverage/national-and-dhb-immunisation-data 2 Grant CC, et al. Brit Med J 2003;326:852-53

  30. NZ Immunisation Handbook on pertussis • 6.5 Recommended immunisation schedule • A primary course of pertussis vaccine is given as DTaP-IPV-HepB/Hib (Infanrix-hexa) at ages six weeks, three months and five months, followed by a dose of DTaP-IPV (Infanrix-IPV) at age four years, prior to school entry, to extend the duration of protection during the school years. • A further booster is given at age 11 years (school Year 7) as Tdap (Boostrix). • Recommended but not funded • Tdap is recommended but not funded by the Ministry for: • Lead maternity carers (LMCs) and other health care personnel who work in neonatal units and other clinical settings where they are exposed to infants, especially those with respiratory, cardiac, neurological or other co-morbid conditions (a booster dose at 10-yearly intervals) • Household contacts of newborns, including update vaccination of older siblings (funded), adult household and other contacts during pregnancy, and maternal immunisation shortly after delivery • Early childhood service personnel (a booster dose at 10-yearly intervals) although the priority is to ensure all children attending childcare have received age-appropriate vaccination. Ministry of Health. Immunisation Handbook. Wellington: 2011. http://www.health.govt.nz/publication/immunisation-handbook-2011

  31. US recommendations for use of Tdap vaccines - Advisory Committee on Immunization Practices, 2010 • General Recommendations – • For routine use, adolescents aged 11-18 yrs who have completed the recommended childhood DTP / DTaP vaccination series, and adults aged 19 – 64 yrs and older should receive a single dose of Tdap. Adolescents should preferably receive Tdap at the 11 to 12 year-old preventive health-care visit. • Timing of Tdap - • Can be administered regardless of interval since last T or Td vaccine. • Adults Aged > 65 yrs – • Those with close contact to an infant <12 m old should receive a dose of Tdap. • Other adults ages 65 years and older may also be given a single dose of Tdap. • Children Aged 7 Through 10 Years - • Those not fully vaccinated against pertussis* and for whom no contraindication to pertussis vaccine exists should receive a single dose of Tdap. • Those never vaccinated against T, D or P or who have unknown vaccination status should receive a series of three vaccinations containing T & D. The first of these three doses should be Tdap. • * Fully vaccinated is defined as 5 doses of DTaP or 4 doses of DTaP if 4th dose administered on or after 4th BD.

  32. California: control measures 2010-2011 • Expanded use of Tdap (new recommendations) • Legal requirement for Tdap immunisation of adolescents • 7th- to 12th-graders in 2011-2012, 7th-graders in future years • Pregnant mothers or immediate postpartum immunisation • Family members (cocoon strategy to protect infants) • All close contacts of young infants • Under-immunised persons 7-9 years and 65 years and older • No specified interval for Tdap after prior Td dose • Routine wound management dT Tdap • Note: Vaccination during pregnancy is not recommended in New Zealand. CDPH Immunization Branch (unpublished)

  33. Pre-pregnancy booster dose Mothers Infants Seropositivity (%) Seropositivity (%) Pre-maternal booster Post-maternal booster n=24 *n=22 n=14 n=22 Interim analysis *Mean interval between vaccinating and delivery = 12.7 months Samples taken at 1 month post birth Leuridan et al. Pediatr Infect Dis J 2011; 30

  34. Pertussis vaccines in pregnancy – US ACIP ACIP Provisional Recommendations for Pregnant Women on Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap) Date of ACIP vote: June 22, 2011 Date of posting of provisional recommendations: August 5, 2011 “Women’s health care providers should implement a Tdap vaccination program for pregnant women who previously have not received Tdap. Health care providers should administer Tdap during pregnancy, preferably during the third or late second trimester. Alternatively, if not administered during pregnancy, Tdap should be administered immediately postpartum.“ • Note: Vaccination during pregnancy is not recommended in New Zealand. ACIP Provisional Recommendations. http://www.cdc.gov/vaccines/recs/provisional/default.htm (accessed November 2011)

  35. Maternal immunisation with Tdap: effect on cord blood antibody levels (US data) *cut-off levels: DT, 0.10 IU/mL; TT, 0.10 IU/mL; PT, 5 enzyme-linked immunosorbent assay (U ELU/mL); FHA, 3 ELU/mL; PRN, 5 ELU/mL; and FIM 2/3, 5 ELU/mL. aSignificantat 0.05 level. FIM= Fimbriae. PT=pertussistoxoid. FHA= filamentous haemagglutinin. PRN=pertactin(PRN). Proportions of women with antibody above possible cut-off level for protective level • Note: Vaccination during pregnancy is not recommended in New Zealand. Gall et al. Am J ObstetGynecol2011; 204: 334.e1–5.

  36. Immunogenicity of decennial dose of dTpa in adults Anti-PT Anti-FHA • One month after the decennial dTpa booster dose, all subjects were seropositive for antibodies against PT, FHA and PRN • 100% of subjects in the dTpa group and at least 99.3% in the Td + pa group had antibody concentrations associated with seroprotection against diphtheria and tetanus Anti-PRN GMC, geometric mean concentration; pa, reduced antigen content acellular pertussis; Td, tetanus & reduced antigen content diphtheria Booy et al. Vaccine 2011; 29: 45–50 (Figure reproduced with kind permission from Elsevier)

  37. Conclusions: evolving epidemiology • Pertussis is still endemic in many countries 1 • Periodic outbreaks across all age groups and high mortality in infants 1 • Newborns and partially vaccinated infants are most susceptible and at risk of severe disease2-6 • Pertussis is under-diagnosed and under-reported, with a wide range of symptoms • Older children and adults act as a reservoir for transmission to susceptible infants2-6 1 NCIRS. Vaccine Preventable Diseases in Australia, 2005 to 2007. CommDisIntell2010; 34: Supplement. 2 Quinn HE, McIntyre P. CommDisIntell2007;31(2):205-15. 3 NZ Immunisation Handbook, 2011. 4 NCIRS. Pertussis Fact Sheet. November 2009. 5 Chuk LR et al. CommDisIntell2008;32:449-56. 6 Elliot E et al. Pediatr Infect Dis J 2004;23:246–52

  38. Conclusions: evolving strategies for prevention • Available vaccines are immunogenic and effective1 • Timely childhood vaccination is important2 • Immunity is not life-long – levels of antibody wane with all vaccines3 • Cocooning strategies vaccinate parents and close contacts to protect vulnerable infants 3-6 • Decennial booster vaccination is well-tolerated and immunogenic • Adult vaccination should protect whole communities via reduced circulation and herd immunity3 1 Zhang L et al. Cochrane Database Syst Rev 2011, Issue 1. Art.No.: CD001478 . 2 Grant CC et al. Brit Med J 2003;326:852-53 . 3 Zepp F et al. Lancet Infect Dis2011; 11: 557–70. 4 Chuk LR et al. Comm Dis Intell2008;32(4):449-56. 5 Elliot E et al. Pediatr Infect Dis J 2004;23:246–52. 6 McIntyre P, Wood N. Curr Opin Infect Dis2009;22:215-23.

  39. Boostrix® Combined diphtheria-tetanus-acellular pertussis (dTpa) vaccine • Boostrix is the only dTpa vaccine available in a pre-filled syringe1,2 • Boostrix is well tolerated; in clinical trials, common side effects were mild and transient. They included fever, malaise, fatigue, headache, irritability, loss of appetite, vomiting, diarrhoea, dizziness, and local reactions such as pain, redness, bruising, itching, or swelling at the injection site.1 1 GlaxoSmithKline New Zealand. Boostrix® Data Sheet. GSK NZ; 2011. Available at www.medsafe.govt.nz/profs/datasheet/b/Boostrixinj.pdf 2 Sanofi-aventis New Zealand. Adacel Data Sheet. Sanofi-aventis NZ; 2007. Available at www.medsafe.govt.nz/profs/datasheet/a/adacelinj.pdf

  40. Boostrix®(combined diphtheria-tetanus-acellular pertussis (dTpa) vaccine) is available as an injection. A 0.5 mL dose contains not less than 2.5 LfU of diphtheria toxoid, not less than 5 LfU of tetanus toxoid, and three purified Bordetella pertussis antigens (8mcg of pertussis toxoid, 8 mcg of filamentous haemagglutinin, and 2.5 mcg of 69 kDa outer membrane protein). Boostrixis a private-purchase prescription medicine for booster vaccination against diphtheria, tetanus, and pertussis of individuals aged 10 years and older – a prescription charge will apply. Contraindications: known hypersensitivity to any component of the vaccine, encephalopathy after previous pertussis vaccination, or transient thrombocytopenia or neurological complications after previous vaccination against diphtheria and/or tetanus. Precautions: do not administer intravenously; ensure medical treatment is readily available in case of rare anaphylactic reaction following administration. Common side effects include fever,malaise, fatigue, headache, irritability, loss of appetite, vomiting, diarrhoea, and local reactions such as pain, redness, bruising, itching, or swelling at the injection site. Before prescribing Boostrix, please review the full Data Sheet at www.medsafe.govt.nz. Boostrix is a registered trade mark of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. DA4512TS/12MA/083

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