Immunizations: Recommendations in Solid Organ Transplant Gwen Nance, PharmD Solid Organ Transplant Pharmacy Resident

Objectives 1. Review and understand vaccinations Identify how vaccinations work Discuss their importance in disease prevention 2. Outline vaccination guidelines for pediatric solid organ transplant (SOT) recipients Review vaccine recommendations Identify recommendations for caregivers of immunocompromised patients 3. Apply our knowledge to patient case example

Vaccinations

Vaccinations: An overview What is a vaccine? “A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease” Can be comprised of: killed microorganisms live attenuated organisms living fully virulent organisms Centers for Disease Control and Prevention. cdc.gov. (2014)

Vaccinations: An overview How does a vaccine work? Stimulate the production of antibodies to provide immunity against one or several diseases The College of Physicians of Philadelphia. historyofvaccines.org. (2016)

Vaccinations: An overview Why are the benefits? Individual immunity Herd immunity Drastic reduction of disease Small pox Polio Diphtheria Measles The College of Physicians of Philadelphia. historyofvaccines.org. (2016) Centers for Disease Control and Prevention. cdc.org. (2016)

Centers for Disease Control and Prevention. cdc.gov. (2011)

Vaccinations: An overview Common Misconceptions Vaccines cause autism MMR Hypothesis Thimerosal Hypothesis Mercury/Aluminum Hypotheses Disappeared diseases Natural immunity is better than vaccine-acquired immunity killed microorganisms live attenuated organisms living fully virulent organisms The College of Physicians of Philadelphia. historyofvaccines.org. (2016) Centers for Disease Control and Prevention. cdc.org. (2016) American Academy of Pediatrics. aap.org. (2013)

Vaccinations: An overview What are the risks? The College of Physicians of Philadelphia. historyofvaccines.org. (2016) Centers for Disease Control and Prevention. cdc.org. (2016)

Vaccinations: An overview Immunogenicity in Solid-Organ Transplant Suboptimal response to vaccines Suppressed humoral and cellular responses Degree of immunosuppression Type of transplant Vaccination pre-transplantation is preferred When vaccines are given post-transplant: Can administer vaccines at 3 - 6 months post-transplant Typically recommend waiting for 6 months The College of Physicians of Philadelphia. historyofvaccines.org. (2016) Centers for Disease Control and Prevention. cdc.org. (2016) American Academy of Pediatrics. aap.org. (2013)

Immunizations Inactivated Vaccines

Immunizations: Influenza Recommendation Yearly vaccination pre- and post-transplantation Age ≥ 6 months For children 6 months to 8 years receiving their 1st vaccination, administer 2 doses (separated by at least 4 weeks) Age ≥ 9 years, administer 1 dose Administer 3 to 6 months post-transplant for best effect Typically recommend ≥ 1 month during flu season Live-attenuated [FluMist®] vs. Inactivated Live-attenuated vaccine is no longer recommended Intradermal IIV = Intramuscular IIV Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Influenza Influenza and Solid-Organ Transplant Kumar D, et al. A 5-year multicenter evaluation of seasonal influenza infection in transplant recipients. Pneumonia at presentation 24.7% Vaccination reduced likelihood [p<0.001] Hospitalized 74.1% ICU care 13.4% Mechanical ventilation 10.8% Kumar D, et al. American Transplant Congress. (2016)

Immunizations: Pneumococcal Recommendation 13-valent conjugated vaccine (PCV13) Age ≥ 6 months Administer a standard 4-dose series (either PCV13 or PCV7) For children 14 to 59 months who received the 7-valent PCV series, administer a single PCV13 supplemental dose 23-valent polysaccharide vaccine (PPSV23) Age ≥ 2 years Administer 2 lifetime doses At least 8 weeks after PCV13 5 years between PPSV23 doses Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Pneumococcal Pneumococcal and Solid-Organ Transplant Increased relative risk for pneumococcal disease 28-36 per 1,000 patients per year Prime-boost strategy Barton M, et al. Seven-valent pneumococcal conjugate vaccine in pediatric solid organ transplant recipients: a prospective study of safety and immunogenicity. 2 doses of PCV7 induced ≥ 2 fold increases in geometric mean concentrations (GMCs) in all organ groups Select organ groups benefited from a 3rd dose of PCV7 Boosting with PPSV23 provided increases in GMCs Barton M, et al. Pediatr Infect Dis. (2009)

Immunizations: Human Papillomavirus Recommendation 3-dose series administered once Age 9 to 26 years Boys and girls Gardisil-9®: covers HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 HPV and Solid Organ Transplant HPV can cause of cervical cancer, throat cancers, and other cancers as well as genital warts in both men and women Increase in the likelihood of HPV-related disease in SOT Effect of immunosuppression on cancer surveillance Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Human Papillomavirus HPV and Solid Organ Transplant Diminished response to HPV vaccine post-transplant when compared to patients with CKD and undergoing dialysis Nelson, et al. Clin J Am Soc Nephol. (2016)

Immunizations: Hepatitis B Recommendation 3 or 4 dose series 1st dose is typically given at birth Hepatitis B antibodies should be quantified prior to transplant Post-vaccination anti-HB concentration goal ≥ 10 mIU/mL If the result is less than goal, a 2nd 3-dose Hep B series should be given Hepatitis B and Solid Organ Transplant HBV reactivation has been observed in SOT Hep B vaccine has a lower efficacy in end-stage renal and liver disease Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Hepatitis A Recommendation 2 dose series Age ≥ 12 months Administer series between 12 and 23 months Separate doses by 6 to 18 months Minimum interval between the 2 doses is 6 months For age ≥ 2 years without Hep A series, 2 doses of can be administered if hepatitis A immunity is desired Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Polio Recommendation 4 dose series Age ≥ 6 weeks Doses are typically given at ages 2, 4, 6 through 18 months and 4 through 6 years Oral polio vaccine is a live vaccination and not recommended after transplant Not available in the United States currently Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Meningococcal Recommendation Routine vaccination: 1 dose at 11-12 years, booster dose at 16 years [Menactra® or Menveo®] Age ≥ 6 weeks Serotype A, C, Y, and W Special recommendations for high-risk persons, including: Children with anatomic or functional asplenia (including sickle cell) Children with persistent complement component deficiency (or those receiving eculizumab [Soliris®]) Children who travel to or reside in countries which meningococcal disease is endemic or epidemic Children at risk during a community outbreak attributable to a vaccine serogroup Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Haemophilus influenzae type b (Hib) Recommendation 4 dose series Age ≥ 6 weeks 3 dose primary series typically administered at 2, 4, and 6 months of age Booster dose administered at 12 through 15 months For patients at high risk of Hib disease (chemotherapy recipients, asplenia, HIV infected, immunoglobulin deficiency, or early component complement deficiency) accelerated schedules and special recommendations exist Not routinely recommended for patients ≥ 5 years Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Diphtheria, Tetanus, and Pertussis Recommendation 5 dose series Age ≥ 6 weeks for DTap vaccine; Age ≥ 10 years for Tdap vaccine Administer DTap vaccine at ages 2, 4, 6, 15, through 18 months, and 4 through 6 years Administer 1 dose of Tdap vaccine to all adolescents aged 11 through 12 years Booster Td [tetanus and diphtheria] is given every 10 years Can be given earlier if indicated Tdap can be given again in place of Td Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations Live Vaccines

Immunizations: Live vaccinations Recommendation Live virus vaccines (i.e. MMR, VAR) are recommended prior to transplant When possible plan to give these vaccinations ≥ 4 weeks before transplant Post-transplant live vaccinations are contraindicated and should not be given to SOT recipients Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Measles, Mump, Rubella Recommendation 2 dose series Age ≥ 6 months Administer 2 dose series at ages 12 through 15 months and 4 through 6 years Minimum time between doses is 4 weeks Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Varicella Recommendation 2 dose series Age ≥ 6 months Administer doses at ages 12 through 15 months and 4 through 6 years Minimum time between doses is 3 months All persons aged 7 through 18 years without evidence of immunity should receive 2 doses of varicella vaccine Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Immunizations: Rotavirus Recommendation 2 or 3 dose series Age ≥ 6 weeks 2 dose series of Rotarix® [RV1] is administered at 2 and 4 months of age 3 dose seres of RotaTeq® [RV5] is administered at 2, 4, and 6 months Maximum age to initiate series is 15 weeks Maximum age for final dose of the series is 8 months Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

International Travel and Vaccines Immunizations International Travel and Vaccines

Immunizations: International Travel and Vaccines Recommendations Inactivated vaccinations indicated for travel are recommended Live vaccinations are not recommended in immunocompromised patients Avoid oral vaccines such as oral typhoid and oral polio Avoid yellow fever vaccine (live-attenuated) Immunization to yellow fever prior to transplant can provide long-term protection Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014) Kumar D. Curr Opin Infect Dis. (2014)

Caregivers and Living Donors Immunizations Caregivers and Living Donors

Immunizations: Caregivers and Living Donors Immunocompetent individuals should receive vaccinations (both live and inactivated) according to the CDC annual schedule Yellow fever vaccine and oral typhoid vaccine should be received prior to travel in relevant areas If skins lesions develop after receipt of varicella or zoster vaccines, avoid direct contact with immunocompromised persons until the lesions clear Living Donors Vaccinations should be up-to-date Avoid live vaccines within 4 weeks of organ donation Vaccination solely for recipient’s benefit is generally not recommended Centers for Disease Control and Prevention. cdc.gov. (2016) Rubin LG, et al. Clin Infect Dis. (2014)

Patient Case

Patient Case: GM 14 year old female, presents to kidney clinic for transplant evaluation. Immunization record: DTP/aP: 5 of 5 HepA: 2 of 2 Hep B: 3 of 3 Hib: 4 of 4 Polio: 5 of 5 Last flu: 9/20/2015 MMR: 2 of 2 PCV7/13: 4 of 4 PPSV23: 1 of 1 Rubella: 2 of 2 Varicella: 2 of 2

Patient Case: GM What vaccinations would you recommend? PPSV-23 PCV-13 and HPV Influenza and HPV Influenza and PPSV-23

Patient Case: GM What vaccinations would you recommend? PPSV-23 PCV-13 and HPV Influenza and HPV Influenza and PPSV-23

Patient Case: GM Mom tells you her daughter is not sexually active and asks you why she should receive HPV vaccine. What do you say? We encourage our potential transplant recipients to receive all appropriate vaccinations prior to transplant in order to produce a stronger immune response and provide longer lasting immunity. There is a higher burden of HPV-related disease in kidney transplant recipients and evidence that HPV vaccination after a solid-organ transplant produces a diminished response.

Patient Case: GM Mom and GM agree to the immunizations you recommended today. GM says the last time she received her flu shot, her arm was red and sore for a few days. She asks you what the chance is that she will have a severe reaction to the flu shot this time. How do you respond? <1 in 1,000,000 chance 1 in 1,000,000 chance 10 in 1,000,000 chance 100 in 1,000,000 chance

Patient Case: GM Mom and GM agree to the immunizations you recommended today. GM says the last time she received her flu shot, her arm was red and sore for a few days. She asks you what the chance is that she will have a severe reaction to the flu shot this time. How do you respond? <1 in 1,000,000 chance 1 in 1,000,000 chance 10 in 1,000,000 chance 100 in 1,000,000 chance

Questions?? https://sandwichlearnstogether.org/2015/02/05/raising-awareness-of-the-importance-of-immunizations-update-from-our-school-nurses/#prettyPhoto

References Vaccines and immunizations. CDC website. www.cdc.gov/vaccines/index.html. Updated August 31, 2016. Accessed September 20, 2016. The history of vaccines. The College of Physicians of Philadelphia website. www.historyofvaccines.org. Accessed October 2, 2016. Immunization: vaccine preventable diseases and policy. American Academy of Pediatrics website. http://www.aap.org. Updated June 2016. Accessed September 20, 2016. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 59(1):144. Kim YJ, Kim SI. Vaccination strategies in patients with solid organ transplant: evidences and future perspectives. Clin Exp Vaccine Res. 2016; 5:125-131. Kumar D. Immunizations following solid-organ transplantation. Curr Opin Infect Dis. 2014; 27:329-335. Kumar D, Cordero E, Blumberg E, et al. A 5-year multicenter evaluation of seasonal influenza infection in transplant recipients. American Transplant Congress. 2016. Nelson DR, Neu AM, Abraham A, et al. Immunogenicity of human papillomavirus recombinant vaccine in children with CKD. Clin J Am Soc Nephol. 2016; 11:776-784.