Ms Kim Hunter. Clinical Nurse Coordinator Immunisation Population Health Waikato District Health Board

Ms Kim Hunter Clinical Nurse Coordinator Immunisation Population Health Waikato District Health Board 11:30-12:00 A Hitchhiker's Guide to Vaccine Preventable Disease

Hitchhikers Guide to Vaccines and Preventable Disease Kim Hunter Medical Science Liaison - Vaccines

Presentation Overview Varicella vaccination key points to note Pertussis vaccination strategies and goals

Varicella virus the causative agent Varicella zoster virus (VZV) Primary infection with VZV results in: varicella (chickenpox) latency Reactivation results in: herpes zoster (HZ / shingles) 1. Heininger U et al. Lancet 2006;368:1365 76. Electron micrograph of VZV courtesy of Professor Anne Gershon

Varicella causes substantial illness in NZ Figure 21.1: Hospitalisations for varicella, 1970 2013 rates continue to rise Every year in NZ ~60,000 people get chickenpox; several hundred are admitted to hospital. 1 Maori and Pacific Island are 3 and 4 times more likely to be hospitalised than European children 2 1. Ministry of Health. 2017 Draft Immunisation Handbook wording; Personal correspondence. Wellington: Ministry of Health 2. Wen SC et al. J Paediatr Child Health 2015;51:078-83. Image by www.kiwiemoji.co.nz

Serious financial and social burden associated with varicella Mild, uncomplicated varicella can last for up to two weeks with: 1-3 Substantial medical costs from treating the disease and its complications Societal costs due to absence from work Parents can suffer stress, sleep deprivation, family breakdown and loss of income 4 1. Heininger U et al. Lancet 2006;368:1365-1376. 2. Banz K et al. Eur J Health Econ 2004;5:46-53. 3. Coupeville L et al. Value Health 2005;8:209-222. 4. Soarez PC et al. Cad Saude Publica 2009;25(3):S401-14.

Varilrix live attenuated varicella vaccine 1 10 vials of lyophilised vaccine with 10 syringes of diluent (reconstitute) 1 dose at 15 months: 2 o Those born on or after 1 st April 2016 1 dose for those turning 11 yrs old on or after 1 st July 2017, if: o Unvaccinated o No history of varicella 2 Given alongside MMR, Hib, and PCV 2 High risk criteria will remain the same 2 1. GlaxoSmithKline New Zealand. Varilrix Data Sheet. GSK NZ;2016. Available at http://www.medsafe.govt.nz/profs/datasheet/v/varilrixinj.pdf Accessed August 2016. 2. Pharmaceutical Management Agency New Zealand. Changes to the National Immunisation Schedule. Available at https://www.pharmac.govt.nz/news/consultation-2016-12-09-nis/ Accessed February 2017

Varilrix is a well established vaccine Varilrix has been available for over 30 years and is currently licensed in over 96 countries 1 Used in funded programmes in Australia, the United States, and Germany 1 Available in NZ since 1996 and has been funded for the high risk population since 2014 2 1. GlaxoSmithKline New Zealand Data on file 2016. 2. Pharmaceutical Management Agency New Zealand. Changes to the National Immunisation Schedule. Available at http://www.pharmac.govt.nz/news/notification-2016-07-28-immunisation-schedule/ Accessed August 2016.

One dose is highly effective at preventing moderate to severe cases resulting in fewer hospitalisations 1 One dose: 1 86-94% effective in preventing moderate to severe cases of chickenpox 57-72% effective in preventing all chickenpox Two doses: 1 97-100% effective in preventing moderate to severe cases of chickenpox 92-97% effective in preventing all chickenpox Breakthrough disease: 2 Can occur following a single dose Disease is generally milder than an unvaccinated child resulting in fewer skin lesions 1. GlaxoSmithKline New Zealand. Varilrix Data Sheet. GSK NZ;2016. Available at http://www.medsafe.govt.nz/profs/datasheet/v/varilrixinj.pdf Accessed August 2016. 2. Seward JF et al. JAMA 2004;292:704-8.

1. Heywood AE et al. Bull World Health Organ 2014;92(8):593-604. 2. Quian J et al. Arch Dis Child 2008;93:845-850. 3. Guris D et al. J Infect Dis 2008;197: S71-5. 4. Marin M et al. J Infect Dis 2008;197:S94-S100. 5. Marin M et al. Pediatrics 2008;22:e744-51. 6. WHO. Position Paper Varicella and Zoster. [Online] 2014. www.who.int/wer/2014/wer8925.pdf?ua=1 Accessed June 2016. 7. SAGE Working Group on Varicella and Herpes Zoster Vaccines. Background Paper on Varicella Vaccine. April 2014 www.who.int/immunization/sage/meetings/2014/april/1_sage_varicella_background_paper_final.pdf Accessed June 2016. High coverage is crucial to effectively protect with a one-dose schedule 1 Rapid, high (> 80%) and sustained coverage with a one dose varicella universal mass vaccination (UMV) schedule is critical for: Herd protection 1 Reducing the risk of transmission to others 2-5 Avoiding an upward age shift of varicella disease which is more severe in adults 1,6,7

Duration of Protection When chickenpox continues to circulate, giving opportunities for regular boosting of vaccine-induced immunity, protection lasts for at least 20 years. 1 One dose 2 Unknown whether waning immunity after one dose is evident Breakthrough disease does not become more severe with age Reductions in circulating disease may reduce duration of protection Two doses 3 Appears to be very long term for most people immunised It is not known if it is lifelong 1. Takahashi, M. Paediatri Drugs. 2001;3:85-92. 2. SAGE WHO; 2014 Available from: http://www.who.int/immunization/sage/meetings/2014/april/presentations_background_docs/en/ 3. IMAC. Chickenpox factsheet. http://www.immune.org.nz/sites/default/files/resources/diseasevaricellaimac20151218v02final.pdf Accessed July 2016.

Herd effect seen in Australia following varicella universal vaccination programme Following introduction of 1-dose universal vaccination programme in Australia: Vaccine administered at 18 months of age: 60% decline in hospitalisation rates for infants aged <1 year, demonstrating that unvaccinated infants also benefit from routine childhood vaccination Varicella hospitalisations decreased in all age groups 1.Heywood AE et al. Bull World Health Organ 2014;92(8):593-604.

14 1.Heywood AE et al. Bull World Health Organ 2014;92(8):593-604.

No increase in Herpes Zoster (HZ) seen in the USA and Australia Concerns regarding an increased HZ rate associated with varicella vaccination programmes appear to be unfounded 1 US experience 1 No difference in the slope of increase in HZ incidence rate before and after the introduction of varicella vaccine Australian experience 2 HZ hospitalisations rate did not increase over time Despite high varicella vaccination coverage in Australia for almost five years 1. WHO. Position Paper Varicella and Zoster. [Online] 2014. http://www.who.int/wer/2014/wer8925.pdf?ua=1 Accessed June 2016. 2. Heywood AE et al. Bull World Health Organ 2014;92(8):593-604.

Varicella high-risk funding criteria unchanged A max of 2-doses of Varilrix for the following people: For non-immune patients: with chronic liver disease who may in future be candidates for transplantation; or with deteriorating renal function before transplantation; or prior to solid organ transplant; or prior to any elective immunosuppression* For patients at least 2 years after bone marrow transplantation, on advice of their specialist For patients at least 6 months after completion of chemotherapy, on advice of their specialist Ministry of Health. 2017. Immunisation Handbook 2017; Wellington: Ministry of Health. Available at http://immunisation.book.health.govt.nz/ Accessed July 2017.

Varicella high-risk funding criteria For HIV positive non immune to varicella with mild or moderate immunosuppression on advice of HIV specialist Individuals with inborn errors of metabolism at risk of major metabolic decompensation, with no clinical history of varicella For household contacts (with no history of varicella) of paediatric patients who are immunocompromised, or undergoing a procedure leading to immune compromise For household contacts (with no history of varicella) of adult patients who have no clinical history of varicella and who are severely immunocompromised, or undergoing a procedure leading to immune compromise Ministry of Health. 2017. Immunisation Handbook 2017; Wellington: Ministry of Health. Available at http://immunisation.book.health.govt.nz/ Accessed July 2017.

Varilrix prescribing information Varilrix (live attenuated varicella vaccine) is available as an injection, 0.5mL per dose. Varilrix is a private-purchase prescription medicine for immunisation and prophylaxis against varicella (chickenpox) in adults and children older than 9 months. A prescription charge will apply. Varilrix is also funded for certain high-risk groups and their contacts. From July 2017, one dose of Varilrix will be fully funded on the National Immunisation Schedule at 15 months of age and for previously unvaccinated children turning 11 years old who have not previously had a varicella infection. Children aged 13 years and older need two doses with an interval between doses of at least 6 weeks. Two doses at least 6 weeks apart are also recommended for children aged between 9 months and 12 years, to provide optimal immune responses against varicella virus. Contraindications: acute severe febrile illness, lack of cellular immunity (e.g. leukaemia, lymphoma, HIV infection, or immunosuppressive therapy), known systemic hypersensitivity to neomycin or any component of the vaccine, or pregnancy. Pregnancy should also be avoided for 3 months after vaccination. Precautions: do not administer intradermally or intravenously. Ensure medical treatment is readily available in case of fainting or rare anaphylactic reaction following administration. Use caution in patients with serious chronic diseases (such as chronic renal failure, autoimmune diseases, collagen diseases, or severe bronchial asthma). Avoid salicylates for 6 weeks after vaccination. Vaccination should be delayed for at least 3 months after a patient has received immunoglobulins or a blood transfusion. If a measles vaccine is not given at the same time as Varilrix, it should be delayed by at least 1 month. Alcohol and other disinfecting agents must be allowed to evaporate from the skin before injection of the vaccine. Common side effects include mild rash; pain, redness and swelling at the injection site; and small numbers of papulo-vesicular eruptions. Uncommon side effects include fever, headache, cough, vomiting, lymphadenopathy, and arthralgia. Before prescribing Varilrix, please review the full Data Sheet at www.medsafe.govt.nz. Varilrix is a registered trade mark of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on 0800 808 500.

Pertussis vaccination - strategies and goals

Pertussis is highly contagious It is estimated that in an immune-naïve population, 1 primary case of pertussis can cause approximately 12 to 17 new cases 1,2 The reproductive values for pertussis are close to measles, and higher than mumps, polio, rubella or smallpox 2 1. Schellekens J et al. Pediatr Infect Dis J 2005;24:S19 S24; 2. Fine PE: Epidemiol Rev 1993;15:265 302 20

Higher numbers of pertussis cases reported to date in 2017 versus 2016 https://surv.esr.cri.nz/pdf_surveillance/pertussisrpt/2017/pertussisreport27june2017_24&25.pdf. Accessed August 2017

The highest rates are among the <1 year and 1 4 years age groups (43.9 and 35.9 per 100,000) ESR Pertussis Report: https://surv.esr.cri.nz/pdf_surveillance/pertussisrpt/2017/pertussisreport19july2017_24-27.pdf Acessed August 2017

Pertussis containing vaccines spaced effectively across immunisation schedule 23

EPIC study shows Infanrix hexa is highly effective in preventing pertussis in NZ infants Radke et al. / Vaccine 35 (2017) 177 183. vac http://dx.doi.org/10.1016/j.vaccine.2016.11.004 24

Percentage of total source contacts with pertussis Mothers are the most common source of pertussis infection 60 Sources of infant pertussis cases by contact category (%) 54.4 50 40 37.3 30 26.8 20 17.6 14.9 10 0 4.2 Any parent Mother Father Sibling Grandparent Other Pooled data from a maximum of 7 studies which included case infants less than 6 months old Data derived from Wiley KE et al. Vaccine 2013;31:618 625 25

Immunisation strategies are needed to protect the most vulnerable Strategies proposed include: Maternal immunisation: targeting the most common source of infant infections 1 with the potential to provide protection to the foetus and newborn infant 2 1. Wiley KE et al. Vaccine 2013; 31:618 625; 2. Chu HY et al. Clin Infect Dis 2014; 59:560 568; 3. Zepp F et al. Lancet Infect Dis 2011; 11:557 570. 26

Immunisation strategies are needed to protect the most vulnerable Strategies proposed include: Maternal Cocooning: immunisation: immunising all close targeting contacts of the most common vulnerable source infantsof infant infections 1 with the potential to provide protection to the foetus and newborn infant 2 1. Wiley KE et al. Vaccine 2013; 31:618 625; 2. Chu HY et al. Clin Infect Dis 2014; 59:560 568; 3. Zepp F et al. Lancet Infect Dis 2011; 11:557 570. 27

Immunisation strategies are needed to protect the most vulnerable Strategies proposed : include: Booster Maternal Cocooning: immunisation of immunisation: immunising older children, all close targeting contacts adolescents of the and most common vulnerable adults with source infants the of infant overall infections aim of 1 with the reducing potential morbidity to in provide target populations protection to the and foetus increasing and herd newborn protectioninfant 3 2 1. Wiley KE et al. Vaccine 2013; 31:618 625; 2. Chu HY et al. Clin Infect Dis 2014; 59:560 568; 3. Zepp F et al. Lancet Infect Dis 2011; 11:557 570. 28

NZ Immunisation Handbook 2017 Pertussis Recommendations The goal of the pertussis immunisation programme is to protect those most at risk of developing severe disease, that it, infants in the first year of life. 1 Two key strategies for reducing the burden of disease in infants are: 1. Vaccination during pregnancy 28 to 38 weeks gestation, every pregnancy, to protect the mother and so antibodies can pass to the fetus 2. More complete and timely delivery of the current infant immunisation schedule 1 Post partum maternal vaccination will reduce the risk of the mother infecting her baby but does not have the added benefit of providing passive antibodies 1 NZ recommendations in line with both the Advisory Committee on Immunisation Practices (ACIP) 2012 and WHO 2015 Key Position 2,3 Ministry of Health. 2017. Immunisation Handbook 2017; Wellington: Ministry of Health. Available at http://immunisation.book.health.govt.nz/ Accessed July 2017. 2. CDC. MMWR 2013; 62(7):131 135. 3. World Health Organization. Pertussis vaccines: WHO position paper August 2015. Wkly Epidemiol Rec 2015;90:433 60

The Immunisation Handbook recommends a pertussis booster for people in contact with infants - not funded Ministry of Health. 2017. Immunisation Handbook 2017; Wellington: Ministry of Health. Available at http://immunisation.book.health.govt.nz/ Accessed July 2017.

Increase vaccination Barriers and enablers for Tdap vaccine uptake during pregnancy/post-partum Predictors/enablers Vaccination against influenza during pregnancy 1,10 Incorporating maternal immunisation into routine obstetric care 2 Younger age of mothers 3 In-hospital vaccine ordering procedures 4 Deployment of clinical decision support systems 5 Barriers/inhibiters Lack of recommendation from HCP 6,7 Lack of knowledge of risk and consequences of neonatal pertussis infection 8 Lack of trust or confidence in the vaccine 9 Concerns about safety 8 Delivering pre-term 1 Prevent vaccination 1. Goldfarb IT, et al. Am J Obstet Gynecol 2014; 211:299.e1 5. 2. Webb H, et al. Hum Vaccin Immunother 2014;10(4):1114-21 3. Donnan EJ, et al. BMC Public Health 2013; 13:676. 4. Yeh S, et al. Am J Obstet Gynecol 2014; 210:237.e1e 6. 5. Trick WE, et al. Obstet Gynecol 2010; 116:515 7.6. Urwyler P, et al. BMC Infect Dis 2014; 14:397. 7. Wiley KE, et al. Vaccine 2013; 31:3972 3978. 8. Moniz MH, et al. Hum Vaccin Immunother 2014;10:2562 70.9. Cheng PJ, et al. Vaccine 2010; 28:5641 5647. 10. Bodeker B, 31

Infant outcomes after exposure to Boostrix in pregnancy Objective: Collecting information to evaluate the safety of Boostrix for infants exposed during pregnancy A prospective observational study in New Zealand. 470 women who had received Boostrix during pregnancy were recruited. Infants were followed for 6 and 12 months after birth. Follow up data was obtained from 403 women on 408 infants (403 singleton infants, 6 sets of twins and one stillbirth). There were no significant differences in birth weight, gestational age at birth, congenital anomalies, or infant growth as compared to baseline population data. Walls T, Graham P, Petousis-Harris H, et al.bmj Open 2016;6:e009536.doi:10.1136/ bmjopen-2015-009536 32

Safety outcomes after exposure to Boostrix in pregnancy Objective: Actively recruit and follow pregnant women receiving a dose of Boostrix for 4 weeks after vaccination. A prospective observational study conducted in two NZ regions. 793 women in their 28th 38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Boostrix administration. Outcomes measured were injection site reactions, systemic symptoms and serious adverse events (SAEs) Vaccination with Boostrix in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Petousis-Harris H, Walls T, Watson D, et al.bmj Open 2016;6:e010911.doi:10.1136/bmjopen-2015-010911 33

1. PHARMAC. Changes to the National Immunisation Schedule. Available at http://www.pharmac.govt.nz/news/notification-2016-07-28-immunisation-schedule/ Accessed August 2016 2. GlaxoSmithKline New Zealand. Boostrix Data Sheet. GSK NZ; 2016. Available at http://www.medsafe.govt.nz/profs/datasheet/b/boostrixinj.pdf Accessed January 2017 3. Ministry of Health. 2017. Immunisation Handbook 2017; Wellington: Ministry of Health. Available at http://immunisation.book.health.govt.nz/ Accessed July 2017 Boostrix Diphtheria, Tetanus, Pertussis No change to NIS 1 No concerns with co-administration 2 Updated data sheet now included on NZ pregnant women study one of the first in the world 2 Recommendations for pregnant women is to have a dose with every pregnancy between 28 and 38 weeks gestation 1 Recommended but not funded for adults in contact with infants for work or household contacts 3

Boostrix prescribing information Boostrix (combined diphtheria-tetanus-acellular pertussis (dtpa or Tdap) 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). Boostrix is government funded for 11 year olds as part of the national immunisation schedule, and for pregnant women between 28 and 38 weeks gestation. (Category B1). It is also available as a private-purchase prescription medicine for booster vaccination against diphtheria, tetanus, and pertussis in individuals aged 4 years and older a prescription charge will apply. A trained pharmacist can also administer Boostrix to a person aged 18 years and older. Safety data where Boostrix was administered to pregnant women during the third trimester indicate no vaccine related adverse effect on pregnancy or on the health of the foetus/newborn child. Boostrix may be used during pregnancy when the possible advantages outweigh the possible risks for the foetus. 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 Ltd, Auckland. Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on 0800 808 500.

Infanrix hexa prescribing information Infanrix hexa (combined diphtheria-tetanus-acellular pertussis, hepatitis B, enhanced inactivated polio vaccine and Haemophilus influenzae type b vaccine) is available as an injection. This vaccine should be administered by deep intramuscular injection. Each 0.5 ml dose of the vaccine contains not less than 30 IU of diphtheria toxoid, 40 IU of tetanus toxoid, 25 mcg of pertussis toxoid, 25 mcg of filamentous haemagglutinin, 8 mcg of pertactin, and 10 mcg of recombinant HBsAg protein, all adsorbed on hydrated aluminium hydroxide. Each 0.5 ml dose also contains inactivated polio virus: 40 D-antigen units of type 1 (Mahoney), 8 D-antigen units of type 2 (MEF-1), and 32 D-antigen units of type 3 (Saukett). It also contains 10 mcg of adsorbed purified capsular polysaccharide of H. influenzae type b (Hib) polyribosylribitol phosphate, conjugated to 20-40 mcg of tetanus toxoid. Infanrix hexa is funded on the National Immunisation Schedule. Contraindications: encephalopathy following previous pertussis vaccination, or transient thrombocytopenia or neurological complications following earlier immunisation against diphtheria and/or tetanus. Precautions: do not administer intravenously; ensure medical treatment is readily available in case of rare anaphylactic reaction following administration; review medical history for progressive neurological disorders or any instances of reactions to previous vaccinations with pertussis; High incidence of fever (> 39.5 C), increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed in infants receiving Infanrix hexa and Prevenar compared to infants receiving the hexavalent vaccine alone. Common side effects include malaise, fatigue, headache, fever, irritability, loss of appetite, vomiting, diarrhoea, and local reactions such as pain, redness and swelling at the injection site; very rarely reported reactions include allergic reactions including anaphylactoid reactions. Before prescribing Infanrix hexa, please review the full Data Sheet at www.medsafe.govt.nz. Infanrix hexa is a registered trade mark of the GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. 11/08/2017 36