by Aneesh K. Kautilya Mehta, M.D., Rachel Jacqueline Friedman-Moraco, M.D., and George Marshall Lyon III, M.D.
Infections remain a major source of morbidity in solid organ transplant (SOT) recipients. Many of these infections may be prevented by appropriate vaccination of SOT patients, their family members and their healthcare providers.
Since vaccine responses may be significantly diminished after transplantation due to immunosuppressive medications, efforts should be made to evaluate immunity status and vaccinate patients prior to receiving immunosuppres- sion (1, 2) However, SOT recipients can benefit from vac- cination after transplantation as well, and most vaccines are safe to administer to SOT patients without increased risk of organ rejection (3, 4). This review will cover general guidelines for vaccination of SOT candidates and recipients, and their close contacts, as well as recommendations for pertinent vaccines.
General Principles
The vaccination status of potential SOT candidates should be reviewed at the time of initial consideration for transplantation, and a plan for immunizations should be formulated at that time (4). In general, live vaccines are contraindicated in immunosuppressed patients, therefore any need for these vaccines should be evaluated and given prior to transplantation. Transplantation should be delayed for at least four weeks after live viral vaccinations (4). In addition to obtaining a vaccine history, transplant candidates should be screened for immunity to vaccine-preventable diseases, including serologies for Hepatitis-A, Hepatitis-B and varicella-zoster virus (VZV), and potentially rubella in pediatric patients and those unsure of childhood immunizations. Some patients may need to proceed for transplantation before sufficient opportunity to vaccinate them. These patients generally require three to six months for their immunosuppression to stabilize in order to restart a vaccination schedule.
Specific Recommendations
Influenza vaccination
Influenza vaccination is recommended annually for all Americans greater than six months old, including transplant recipients (5, 6). While rates change yearly, influenza is estimated to infect between 1 percent and 4 percent of SOT patients annually and can cause up to 50 percent of upper and lower respiratory tract infections in SOT recipients during influenza season (1, 7, 8). Transplant patients experience more prolonged shedding and more severe disease than immunocompetent patients. Particularly susceptible are lung transplant recipients, in whom influenza may induce organ rejection and bronchiolitis obliterans syndrome (1, 7-10). The immunogenicity of influenza vaccinations in SOT has been thoroughly reviewed by Kumar et al(1), essentially demonstrating that influenza vaccines are effective, though less so than in immunocompetent individuals, and safe in SOT patients. Thus, these data indicate the importance of annual vaccination for influenza.
While data guiding the optimal time for vaccination after transplant is lacking, most transplant centers will vaccinate transplant candidates at the earliest opportunity and will begin vaccinating recipients one to six months post-transplant(11). While live-attenuated nasal vaccines may be used for transplant candidates who are unlikely to be transplanted within the following month, generally the inactivated intramuscular or intradermal immunization is used for most transplant candidates and for all recipients. While the high-dose inactivated vaccine has not been studied in SOT recipients, we believe it is reasonable to administer this vaccine in SOT patients 65 years old and older.
Pneumococcal vaccination
Most indications for transplantation are also indications for pneumococcal vaccination. Currently there are two available formulations of the pneumococcal vaccinations: the 13-valent pneumococcal conjugate vaccine (PCV- 13) and 23-valent pneumococcal polysaccharide vaccine (PPSV-23). The PPSV-23 vaccine covers more serotypes of Streptococcous pneumonia but utilizes T-cell independent mechanisms to develop immunity, and therefore is not effective in young children. PCV-13 initiates a T-cell dependent response, allowing for its utility in young children (5, 12).
Recently, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended the use of PCV-13 for adults aged 19 years and older with specified immunocompromising conditions(13). However, to date there are no studies of PCV-13 in immunocompromised patients, though there is an ongoing trial in pediatric SOT patients. This recommendation was based largely on studies of the older PCV-7 vaccine in HIV+ individuals (13). The CDC’s cost-effectiveness model demonstrated significant benefit to patients with HIV or on dialysis, with much less predicted benefit in SOT recipients (13). Thus, we recommend that transplant candidates who are HIV positive, have functional or anatomic asplenia, have CSF leaks or cochlear implants receive a PCV-13 if they have not already received one. For candidates without these conditions and not update to pneumococcal vaccinations, we recommend PPSV-23 until further data is available for PCV-13. For SOT recipients who need a pneumococcal vaccine, we recommend PPSV-23 until studies of PCV-13 in immunosuppressed patients is available. However, PCV- 13 is likely safe in SOT and therefore may be used at the discretion of the provider. Any adult who receives PCV- 13 and has not received PPSV-23 should receive a dose of PPSV-23, but not until at least eight weeks later (13).
Tetanus, diphtheria, pertussis vaccinations
The ACIP currently recommends that all Americans older than 10 years should receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) regardless of the interval since the last non-pertussis tetanus/diphtheria-toxoid vaccine (14). Thus, all transplant candidates should receive a Tdap. SOT patients who were not vaccinated prior to transplant should receive a Tdap vaccine once they are stable and greater than three months post-transplant. Thereafter, SOT patients should continue with tetanus toxoid/reduced diphtheria toxoid (Td) booster every 10 years.
Hepatitis A virus (HAV) vaccination
All transplant candidates should be screened for protective levels of HAV total or IgG antibodies. Non- immune candidates should receive one dose of the vaccine as soon as possible, then another dose six to twelve months later. Patients may receive a combined HAV and HBV vaccine if lacking immunity to both, dosed at zero, one and six months. SOT recipients who did not complete the series prior to transplantation may complete once stable post-transplant.
Hepatitis B virus (HBV) vaccination
All transplant candidates should be evaluated for active HBV infection with HBV surface antigen and screened for protective levels of HBV surface antibodies. Non-immune patients should receive one dose of the vaccine as soon as possible, a second dose one month later, and a third dose six to 12 months after the initial vaccine. Patients may receive a combined HAV and HBV vaccine if lacking immunity to both, dosed as above. Adult transplant candidates receiving dialysis or with significant immunocompromising conditions should receive either 40 μg/mL doses on the same three-dose schedule above or on a four-dose schedule at zero, one, two and six months. SOT recipients who did not complete the series prior to transplantation may complete once stable post-transplant with the 40 μg/mL dose.
Varicella and Zoster vaccinations
Both the varicella and zoster vaccines are live-attenuated viral vaccines and thus are contraindicated in SOT recipients. All transplant candidates should be screened for varicella-zoster virus (VZV) immunity by antibody titers. If the candidate is VZV seronegative and not in need of an urgent transplant, then he/she should receive two doses of the varicella vaccine, spaced apart by at least four weeks. If the candidate is VZV seropositive, is 50 years old or older and not in need of an urgent transplant, then he/she should receive one dose of the Zoster vaccine. We recommend checking antibody titers after the varicella vaccine series to ensure efficacy (usually > 4 weeks after second immunization), but this is not necessary for the zoster vaccine.
Human papillomavirus (HPV) vaccination
The ACIP recommends that both males and females 11 to 26 years of age should receive three doses of a HPV vaccine (5, 6). All transplant candidates in this age category should be screened for previous HPV vaccination and complete the series if not previously done. If the patient proceeds to transplant prior to completing the HPV series, then he/she may complete the series after transplant. We recommend that quadrivalent HPV vaccine (HPV4) be used for all SOT candidates and recipients.
Measles, mumps, rubella (MMR) vaccination
All persons born after 1956 should have documentation of one or more doses of MMR vaccine, documentation of previous disease or immunity, or an established medical contraindication (14). The MMR is live-attenuated vaccine and contraindicated in SOT. Thus, transplant candidates should be questioned about previous MMR vaccinations, and testing serologies should be considered in candidates raised in a foreign country, planning to live in a foreign country, planning or possible to become pregnant post-transplant, or with unknown childhood vaccine compliance. If deemed non-immune to any component of the vaccine, one dose of MMR should be administered and transplantation delayed for four weeks if possible.
Meningococcal vaccination
Transplant candidates with asplenia or significant complement deficiencies should receive two doses of quadrivalent meningococcal conjugate vaccine at least two months apart. Candidates and recipients who are likely travel to or live in countries with endemic meningococcal disease or those planning on living in dormitories should receive one dose.
Recommendations for healthcare workers and close contacts
Given that SOT recipients have a diminished response to vaccines, it is imperative that healthcare workers, household members and other close contacts be fully immunized according to the ACIP recommendations (http://www.cdc.gov/vaccines/pubs/ACIP-list.htm). There are often concerns regarding exposure of SOT recipients to contacts receiving vaccines. For inactivated vaccines (Table 1) there are no concerns; however, with live- attenuated vaccines (Table 1), there is at least a theoretical concern with some vaccines. For oral polio vaccinations (not used in the U.S.), SOT patients should avoid contact for seven days after vaccination. For recipients of the Rotavirus vaccine, SOT recipients should avoid changing diapers or contact with stool for seven to 14 days. SOT patients need to avoid contact with varicella (chickenpox or zoster) vaccinees only if vaccinee has respiratory symptoms or a rash after vaccine. For most other live viral vaccines, there are no other restrictions needed as the risk of contracting wild-type disease far outweighs any exposure from the vaccinee. Any concerns about exposure of an SOT patient to a vaccinee should be discussed with an Infectious diseases specialist.
Infectious complications continue to contribute significant morbidity in solid organ transplant patients. Most vaccines are safe and efficacious in SOT patients. Therefore, developing and implementing immunization strategies for transplant candidates and recipients, and their contacts, can significantly decrease the frequency of these infectious events in SOT recipients.
References
1. Kumar D, Blumberg EA, Danziger-Isakov L, Kotton CN, Halasa NB, Ison MG, et al. Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations†. American Journal of Transplantation. 2011;11(10):2020-30.
2. Blumberg EA, Brozena SC, Stutman P, Wood D, Phan HM, Musher DM. Immunogenicity of Pneumococcal Vaccine in Heart Transplant Recipients. Clinical Infectious Diseases. 2001;32(2):307-10.
3. Avery RK, Michaels M. Update on Immunizations in Solid Organ Transplant Recipients: What Clinicians Need to Know. American Journal of Transplantation. 2008;8(1):9-14.
4. Danzinger-Isakov L, Kumar D, the ASTIDCoP. Guidelines for Vaccination of Solid Organ Transplant Candidates and Recipients. American Journal of Transplantation. 2009;9:S258-S62.
5. CDC. Recommended immunization schedules for persons aged 0 through 18 Years – United States, 2012. MMWR Morbidity and mortality weekly report. 2012;61(5):1-4.
6. CDC. Recommended Adult Immunization Schedule: United States, 2012*. Annals of Internal Medicine. 2012;156(3):211-7.
7. Gottlieb J, Schulz TF, Welte T, Fuehner T, Dierich M, Simon AR, et al. Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study. Transplantation. 2009;87(10):1530-7.
8. Vilchez RA, McCurry K, Dauber J, Iacono A, Griffith B, Fung J, et al. Influenza Virus Infection in Adult Solid Organ Transplant Recipients. American Journal of Transplantation. 2002;2(3):287-91.
9. Khalifah AP, Hachem RR, Chakinala MM, Schechtman KB, Patterson GA, Schuster DP, et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. American journal of respiratory and critical care medicine. 2004;170(2):181-7.
10. Garantziotis S, Howell DN, McAdams HP, Davis RD, Henshaw NG, Palmer SM. Influenza pneumonia in lung transplant recipients: clinical features and association with bronchiolitis obliterans syndrome. Chest. 2001;119(4):1277-80.
11. Chon WJ, Kadambi PV, Harland RC, Thistlethwaite JR, West BL, Udani S, et al. Changing attitudes toward influenza vaccination in U.S. Kidney transplant programs over the past decade. Clinical journal of the American Society of Nephrology : CJASN. 2010;5(9):1637-41.
12. Nuorti JP, Whitney CG, Centers for Disease C, Prevention. Prevention of pneumococcal disease among infants and children – use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine – recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control. 2010;59(RR-11):1-18.
13. CDC. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbidity and mortality weekly report. 2012;61(40):816-9.
14. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory
Committee on Immunization Practices, 2010. MMWR Morbidity and mortality weekly report. 2011;60(1):13-5.
Aneesh K. Mehta, M.D., is a transplant infectious diseases consultant and researcher at the Emory University School of Medicine and serves as the Assistant Director of Transplant Infectious Diseases at the Emory Transplant Center. He received his medical degree from the University of Oklahoma and trained in Internal Medicine, Infectious Diseases and Transplantation at Emory. His research interests are in exploring viral and vaccine immunology in the setting of immunosuppression.
Rachel Jacqueline Friedman-Moraco, M.D., recently joined the Division of Infectious Diseases at Emory University focused on transplant infections and HIV care and is an Assistant Professor of Medicine at Emory University School of Medicine. She completed her undergraduate education at the University of Michigan and medical school and Wayne State University in Detroit. She completed post-graduate training at Emory University.
George Lyon, III, M.D., attended Marshall University School of Medicine, followed with a fellowship at Massachusetts General Hospital and Brigham and Women’s Hospital. He started practicing at Emory University Hospital in 2003. Dr. Lyon is board certified in Infectious Disease and Internal Medicine, and his areas of clinical interest are AIDS, infectious disease and Lyme disease.
