Immunization of the immunocompromised child: Key principles

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Children who are immunocompromised, either by congenital immune deficits or an immunosuppressive illness or therapy, are at increased risk for severe illness from many vaccine-preventable infections. The goal of immunization for an immunocompromised child is to provide the maximum possible protection while minimizing harm [1]–[4].

Primary care providers and specialists who care for immunocompromised patients share responsibility for ensuring that appropriate vaccinations are administered to immunocompromised patients and their households. If a vaccine is given inappropriately, it may not work; if it is a ‘live’ vaccine, it may cause adverse effects. When in doubt, consult an institution or a physician with experience in managing patients with the specific immunocompromising condition of concern.

Detailed guidelines for the immunization of immunocompromised individuals, outlining vaccines that are recommended or contraindicated for various immunocompromised states, are presented in the current online version of the Canadian Immunization Guide (CIG) [1]. The purpose of this practice point is to raise awareness of the CIG recommendations. General principles are outlined here. Provincial/territorial guidelines are also available in some jurisdictions.

• Indirect protection is provided by ensuring that all household members and other close contacts are immunized against infections that they may transmit to the immunocompromised child (i.e., all routine vaccines and yearly influenza vaccine) [1]–[4]. Household pets should also receive all routine vaccines [4].
• Inactivated vaccines may be given safely to immunocompromised patients, but responses may be diminished or absent, and increases in dose or in number of doses may be indicated (e.g., hepatitis B, conjugate pneumococcal vaccines) [1]–[4].
• Live vaccines may cause disease by uncontrolled replication and are usually contraindicated in immunocompromised individuals, with the exception of those with isolated IgA deficiency, IgG subclass deficiency, complement deficiency, or anatomical or functional asplenia. Another exception is that live viral vaccines are safe for most children with phagocyte or neutrophil disorders (including chronic granulomatous disease) but live bacterial vaccines (e.g., BGG, live typhoid vaccine) are contraindicated [1][3]. Live vaccines may be given to individuals with HIV infection who are not severely immunocompromised [1]–[3].
• Additional vaccines: Immunocompromised children may require vaccines that are not routinely recommended for all children (e.g., 23-valent pneumococcal polysaccharide), or not routinely given beyond a certain age (e.g., Haemophilus influenzae type b).
• The duration of the immune response may be diminished, necessitating extra booster doses (e.g., children at ongoing risk of hepatitis B exposure should undergo annual testing for hepatitis B antibody and receive booster doses if indicated) [2].
• Timing: Vaccines should be given at the time when maximum immune response can be anticipated:
  • If a disease process is such that immune function may deteriorate over time, vaccinate early (e.g., asymptomatic HIV infection; some forms of congenital immunodeficiency).
  • If immunosuppression is planned (e.g., a nonurgent solid organ transplant or start of immunosuppressive therapy for an inflammatory condition) and time permits, provide all live and inactivated vaccines before immunosuppression. Inactivated vaccines should be given at least two weeks and live vaccines must be given at least four weeks before onset of immunosuppressive therapy. To facilitate pretransplant immunization, measles, mumps, rubella and varicella vaccines may be given to solid organ transplant candidates as early as 6 months of age, if necessary.
  • If immunosuppression is urgent but temporary, defer immunizations until the immune system has recovered. If the risk of exposure to a specific infection is high, inactivated vaccines may be given although the response may be diminished; doses given during immunosuppression should be repeated when the immune system has recovered.
  • In general, live vaccines may be given 1 month after discontinuation of high dose steroid therapy, 3 months or more after completion of other immunosuppressive chemotherapy, or 6 months after treatment with anti-B-cell antibodies, provided that the underlying disease is not immunosuppressive or is no longer active. (N.B. ‘High dose steroid therapy is defined as systemic treatment with the equivalent of prednisone ≥2 mg/kg/day or ≥20 mg/day if weight >10 kg for ≥14 days. Live vaccines are not contraindicated with lower doses or shorter durations of treatment or with topical, inhaled or locally injected steroid therapy [1].
  • Vaccination after hematopoietic stem cell transplantation is complex. Recipients are no longer immune to conditions for which they received vaccines pretransplant, so require reimmunization with all routine vaccines. Reimmunization with inactivated vaccines is started 3 to 12 months post-transplant. Reimmunization with live vaccines is started 24 months post-transplant, assuming that there is no evidence of chronic graft versus host disease, immunosuppression has been discontinued for at least 3 months, and the transplant specialist considers the patient to be immunocompetent [1][3].
  • When long-term immunosuppression is required, inactivated vaccines are given when the patient is on the lowest anticipated dose of immunosuppressive agents. Also, if feasible, immunosuppression is held or reduced temporarily to maximize response.
  • For solid organ transplants, inactivated vaccines are initiated 3 to 6 months post-transplant if baseline immunosuppression levels are attained. Live vaccines are generally contraindicated but are occasionally given under special circumstances if recommended by transplant specialists [1]–[4].
  • Donors of hematopoietic stem cells and solid organs should receive all age-appropriate routine vaccines. However, parenteral live vaccines should not be administered within four weeks of stem cell or organ harvest [3].
• Response to a vaccine should not be assumed:
  • The response to vaccines is variable and influenced by the underlying disease and the specific immunosuppressive drugs used.
  • When assays are available (for hepatitis B, measles, mumps, rubella, varicella, tetanus and diphtheria and, in some locations, others), measure antibody response to the vaccine. In general, tests should be done within 1 to 3 months of vaccination.
  • If antibody response cannot be determined, other protective measures may be required in the event of an exposure (e.g., immune globulin) or outbreak (e.g., exclusion from school).
• Travel: Immunocompromised patients who are travelling may face infection risks that are higher or different from those in Canada. They should be advised to seek advice pretravel about exposure risks and vaccines that are indicated or contraindicated.
• Immune globulin: People with defective antibody production can be protected from some vaccine-preventable infections with regular infusions of replacement immune globulin. Pathogen-specific immune globulins are indicated after exposure to varicella or hepatitis B, or after an injury with a tetanus risk. Administration of parenteral live vaccines must be deferred for 3 to 11 months after receiving immune globulin because this may interfere with the immune response to these vaccines. No delay is required for live oral or intranasal vaccines or for inactivated vaccines [5].

Acknowledgements

This practice point was reviewed by the Community Paediatrics Committee of the Canadian Paediatric Society.

CPS INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE

Members: Natalie A Bridger MD; Shalini Desai MD; Ruth Grimes MD (Board Representative); Charles Hui (past member); Nicole Le Saux MD (Chair); Timothy Mailman MA; Joan L Robinson MD (Past Chair); Marina Salvadori MD (past member); Otto G Vanderkooi MD

Liaisons: Upton D Allen MBBS, Canadian Pediatric AIDS Research Group; Tobey Audcent MD, Committee to Advise on Tropical Medicine and Travel (CATMAT), Public Health Agency of Canada; Carrie Byington MD, Committee on Infectious Diseases, American Academy of Pediatrics; Fahamia Koudra MD, College of Family Physicians of Canada; Rhonda Kropp BScN MPH, Public Health Agency of Canada; Marc Lebel MD, Immunization Monitoring Program, ACTive (IMPACT); Jane C McDonald MD, Association of Medical Microbiology and Infectious Disease Canada; Dorothy L Moore MD, National Advisory Committee on Immunization (NACI)

Consultant: Noni E MacDonald MD

Principal author: Dorothy L Moore MD

References

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.