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Canadian Immunization Guide
Seventh Edition - 2006

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Part 3
Recommended Immunization

Immunization of Immunocompromised Persons

The number of immunocompromised people in Canadian society is steadily increasing for a variety of reasons. These include our increased understanding of "normal" and altered immunity; recognition of the subtle immunodeficiencies associated with chronic illnesses (e.g., liver disease, renal disease); increased numbers of individuals with absent or dysfunctional spleens; the expanding range of illnesses treated with immunomodulatory agents (e.g., autoimmune diseases, inflammatory conditions); the HIV pandemic; increased numbers of long-term survivors after organ transplantation; and the increased use of ablative therapy for cancer and other conditions.

The number of immunizations to which immunocompromised people are likely to be exposed is also increasing. There is an ever-enlarging spectrum of vaccines available, and an increasing number of vaccines are included in routine programs. Efforts are under way to fully immunize adolescents, adults and the elderly. As well, individuals with significant illness can now travel with relative ease, for example, people infected with HIV. For more information, please visit http://www.phac-aspc.gc.ca/tmp-pmv/catmat-ccmtmv/index.html.

Therefore, the frequency and complexity of questions dealing with immunization in immunocompromised hosts will only increase with time. Still further complexity is added by the fact that the relative degree of immunodeficiency varies over time in many people. The decision to recommend for or against any particular vaccine will depend upon a careful, case-by-case analysis of the risks and benefits. Consultation with a specialist with expertise in vaccination should be considered when immunizing immunocompromised persons.

There is potential for serious illness and death in the underimmunization of immunocompromised people, and every effort should be made to ensure adequate protection through immunization. However, the inappropriate use of live vaccines can cause serious adverse events in some immunocompromised hosts as a result of uncontrolled replication of the virus or bacterium. Children with a known or suspected family history of congenital or hereditary immunodeficiency that is a contraindication to vaccination with live virus should not receive live vaccines unless their immune competence has been established. As many congenital immunodeficiencies are autosomal recessive, the history of immunodeficiency may not be present in first-degree relatives. Vaccine providers should also be alert to such clues as multiple neonatal or infant deaths in a family. Although questioning about personal or family history of immunodeficiency is recommended before any live vaccine is administered, the family history is of paramount importance if such vaccines are to be given before 1 year of age, as signs or symptoms of congenital immunodeficiency may not be present in younger children. Immunization of those with significant immunodeficiency should be performed only in consultation with experts.

General principles

Several general principles apply to the immunization of immunocompromised individuals:

  • Maximize benefit while minimizing harm;
  • Make no assumptions about susceptibility or protection
    • A history of childhood infection or previous immunization may be irrelevant;
  • Immunize at the time when maximum immune response can be anticipated
    • Immunize early, before immunodeficiency begins, if possible
    • Delay immunization if the immunodeficiency is transient (if this can be done safely)
    • Stop or reduce immunosuppression to permit better vaccine response, if appropriate;
  • Consider the immunization environment broadly
    • Vaccinate household contacts when appropriate (see below for specific recommendations)
    • Consider the immunization status of both the donor and/or recipient in the setting of hematopoietic stem cell transplantation;
  • Avoid live vaccines, unless
    • Data are available to support their use
    • The risk of natural infection is greater than the risk of immunization;
  • Monitor vaccinees carefully and boost aggressively
    • The magnitude and duration of vaccine-induced immunity are often reduced in immunocompromised individuals.

Approach to vaccination of immunodeficient individuals

Chronic liver disease

Hepatitis A and B immunizations are recommended in people with chronic liver disease, since they are at risk of fulminant hepatitis. Vaccination should be done early in the course of the disease, as the immune response to vaccine is suboptimal in advanced liver disease. For more information, please refer to the hepatitis A and B chapters.

Chronic renal disease and patients undergoing dialysis

Bacterial and viral infections are a major cause of morbidity and mortality in patients who have renal disease or who are undergoing chronic dialysis. Many of these infections are vaccine preventable. All the standard immunizations are required (see Recommended Immunization Schedules).

Particular attention should be paid to ensuring that there is optimal protection against varicella, hepatitis B, influenza and pneumococcal diseases. Influenza immunization is recommended yearly; household members should also be vaccinated. The schedule proposed for immunization against pneumococcal disease in patients with splenic disorders (see below) should be followed for people with chronic renal disease and for dialysis patients. Some data suggest that there is a poor response to hepatitis B vaccine in the dialysis population and that hepatitis B surface antibody levels might decline rapidly. In adults, immunization with a higher dosage is recommended (see the Hepatitis B Vaccine chapter for details). Data on alternative vaccination schedules for children undergoing hemodialysis are limited. The antibody level to hepatitis B surface antigen should be measured yearly and booster doses should be given if the level decreases to less than 10 IU/L (see the Hepatitis B Vaccine chapter for details). Varicella vaccine should be given to susceptible transplant candidates before transplantation because varicella is a significant cause of morbidity and mortality, but the vaccine is contraindicated in immunosuppressed patients after transplantation (see below). See section on solid organ transplantation for renal transplant recipients.

Splenic disorders

Asplenia or hyposplenism may be congenital, surgical or functional. A number of conditions can lead to functional hyposplenism. These include sickle cell anemia, thalassemia major, essential thrombocytopenia, celiac disease and inflammatory bowel disease. There are no contraindications to the use of any vaccine for patients known to be functionally or anatomically hyposplenic. Particular attention should be paid to providing optimal protection against encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae type b [Hib], Neisseria meningitidis), to which these individuals are highly susceptible. They should also receive all routine immunizations and yearly influenza vaccination. Careful attention should be paid to immunization status when "elective" surgical splenectomy is planned so that all of the necessary vaccines can be delivered at least 2 weeks before removal of the spleen. In the case of an emergency splenectomy, vaccines should be given 2 weeks after the splenectomy. If the patient is discharged earlier and there is a concern that he/she might not return, vaccination should be given before discharge.

The following immunization schedule is recommended for hyposplenic and asplenic individuals.
  • Meningococcal disease:

    • Children < 2 years of age with asplenia or hyposplenia should be vaccinated with Men-C-C as described in the routine infant schedule (please refer to the Recommended Immunization Schedules chapter, and then receive quadrivalent Men-P-ACYW at 2 years of age and at least 2 weeks after the Men-C-C.
    • Children > 2 years of age and adults should receive both the Men-C-C and the Men-P-ACYW. The Men-C-C should be given first and the Men-P-ACYW at least 2 weeks later. If the Men-P-ACYW vaccine is given first, an adequate response to Men-C-C has been observed after a delay of 6 months in adults, and this remains the recommended interval until further data are available.
    • A booster dose of Men-P-ACYW is recommended every 2 to 5 years depending on the age at immunization. Please refer to the meningococcal chapter for more information on recommended usage.
  • Pneumococcal disease:

    • Children ≤ 23 months of age: Pneu-C-7 is recommended as described in the routine infant schedule (please refer to the Recommended Immunization Schedules chapter). They should receive the Pneu-P-23 at 2 years of age and ≥ 8 weeks after the last dose of Pneu-C-7.
    • Children 24 to 59 months not previously vaccinated: two doses of Pneu-C-7, administered 2 months apart, followed by one dose of Pneu-P-23 administered ≥ 8 weeks after the second dose of Pneu-C-7.
    • Children 24 to 59 months who have completed the Pneu-C-7 vaccination series before age 2: one dose of Pneu-P-23 (≥ 8 weeks after the last dose of Pneu-C-7).
    • Children aged 24 to 59 months who have already received Pneu-P-23 but not Pneu-C-7: two doses of Pneu-C-7 administered 2 months apart. Vaccination with Pneu-C-7 should be initiated ≥ 8 weeks after vaccination with Pneu-P-23.
    • Children ≥ 5 years of age and adults who have not previously received pneumococcal vaccines should be vaccinated with Pneu-P-23. Pneu-C-7 is not contraindicated in children ≥ 5 years of age with high-risk conditions. When circumstances permit, some experts suggest that the conjugate vaccine may be given as the initial dose followed by the polysaccharide vaccine, as this may theoretically improve antibody response and immunologic memory. However, the polysaccharide vaccine is the vaccine of choice for these individuals, and if only one vaccine can be provided it should be the polysaccharide vaccine.
    • A single booster with Pneu-P-23 is recommended after 5 years in those aged > 10 years at the time of initial immunization and after 3 years for those who received their initial vaccine when they were ≤ 10 years.
  • Haemophilus influenzae type b:

    • Vaccination with the age-appropriate primary series of Hib conjugate vaccine should be completed (if not already complete) for all children < 5 years of age with asplenia. Despite limited efficacy data and the low overall risk of Hib sepsis in individuals > 5 years of age, especially in the era of high Hib immunization coverage in the population, some experts recommend that all asplenic individuals > 5 years of age receive a single dose of conjugate Hib vaccine, regardless of previous Hib immunization.

Congenital immunodeficiency states

This is a varied group of conditions that includes defects in antibody production (e.g., agammaglobulinemia, isotype and IgG subclass deficiencies, common variable immunodeficiency), complement deficiencies, defects in one or more aspects of cell-mediated immunity and mixed deficits. Individuals with defects in antibody and complement have unusual susceptibility to the encapsulated bacteria and members of the Enteroviridae family (e.g., polio, coxsackie and echoviruses), and individuals with mixed and T cell defects are particularly susceptible to intracellular pathogens (virtually all viruses and some bacteria, fungi and parasites). Although the defects and susceptibility patterns are very different, the approach to immunization is quite similar for these individuals. Component and inactivated vaccines can and should be administered in all of these conditions, despite the fact that many vaccinees will respond poorly, if at all. Live vaccines are generally not recommended for these patients, although some exceptions exist (see below).

  • Antibody defects:
    Immune response to a vaccine might be decreased and antibody levels might decrease more quickly in people with congenital B cell deficiency. As a general rule, people with antibody defects can be protected from many of the vaccine-preventable infections with the use of intravenous immunoglobulin (IVIg) or pathogen-specific Ig preparations. However vaccination is recommended in these people to increase the level of protection. Particular attention should be given to ensuring that individuals with these conditions are immunized against pneumococcal, meningococcal and Hib diseases. Yearly influenza vaccine is also recommended. Although oral poliovirus vaccine (OPV) is no longer used in Canada, it remains an approved product and is used in many other countries. OPV should not be used in the affected individual or any of his or her family members. Measles (available as MMR) and varicella vaccines should be considered if the patient is not receiving regular Ig replacement therapy (which may affect the efficacy of the vaccines); but all other live vaccines are contraindicated (except in isolated IgA deficiency).
  • T cell, natural killer and mixed cell-mediated antibody defects:
    All live vaccines are contraindicated. Inadvertent live vaccine administration and exposure to natural infections can be dealt with by rapid administration of serum Ig or pathogen-specific Ig with or without appropriate antiviral or antibacterial treatment. Yearly influenza vaccine is recommended.
  • Phagocytic defects:
    Live bacterial vaccines (BCG [Bacille Calmette-Guirin] and oral typhoid vaccine) are contraindicated. Yearly influenza vaccine is recommended.
  • Complement deficiency:
    There are no contraindications to the use of any vaccine. However, immunity can decrease over time. Measurement of antibody titres and re-immunization, if needed, should be considered. Individuals with complement deficiency should receive meningococcal vaccine because of increased susceptibility to this pathogen (see the section on high-risk groups in the meningococcal chapter for details). Immunizations against common bacterial pathogens such as pneumococcus and Hib are also recommended.
  • Household contact:
    Even if contraindicated for the patients, household contacts can receive MMR vaccine if indicated. Varicella vaccine is recommended for susceptible contacts of immunocompromised individuals. No precautions need to be taken after vaccination unless the recipient develops a rash. In such circumstances, the rash should be covered and the vaccine recipient should avoid direct contact with the immuncompromised person for the duration of the rash. Yearly influenza vaccination and up-to-date routine immunizations are also recommended for household contacts of immunocompromised individuals

Immunosuppressive therapy

Long-term immunosuppressive therapy (e.g., long-term steroids [discussed below], cancer chemotherapy, radiation therapy/azathioprine, cyclosporine, cyclophosphamide/infliximab) is used for organ transplantation and an increasing range of chronic infectious and inflammatory conditions (e.g., inflammatory bowel disease, psoriasis, systemic lupus erythematosis). These therapies have their greatest impact on cell-mediated immunity, although T cell-dependent antibody production can also be adversely affected.

There is no contraindication to the use of any inactivated vaccine in these people, and particular attention should be paid to the completion of childhood immunizations, annual influenza immunization and pneumococcal immunization (with a booster after 3-5 years). Ideally, all appropriate vaccines or boosters should be administered to these individuals at least 14 days before the initiation of therapy. If this cannot be done safely, a period of at least 3 months should elapse after immunosuppressive drugs have been stopped before administration of both inactivated and component vaccines (to establish immunogenicity, although inactivated vaccines can be administered if required for post-exposure or outbreak management) and live vaccines (to reduce the risk of dissemination). However, the interval may vary with the intensity of the immunosuppressive therapy, underlying disease and other factors. If immunosuppressive therapy cannot be stopped, inactivated or component vaccines should be given when the therapy is at the lowest possible level. Live vaccines are generally contraindicated, although the risk-to-benefit ratio for several of these vaccines can favour immunization if only low doses of immunosuppressive drugs are required and there is significant risk of wild-type infection (e.g., varicella vaccine in seronegative individuals).

Children with acute lymphocytic leukemia may be vaccinated with the varicella vaccine if the disease has been in remission for ≥ 12 months, the patient's total lymphocyte count is ≥ 1.2 x 109/L, the patient is not receiving radiation therapy, and maintenance chemotherapy can be withheld for at least 1 week before to 1 week after immunization. Two doses of the vaccine are recommended, 1-3 months apart, since North American studies suggest that two doses are more immunogenic than a single dose in these patients. For more information refer to the Varicella Vaccine chapter.
  • High dose steroids:
    High-dose, systemic steroids (e.g., a prednisone dose of ≥ 2 mg/kg per day or ≥ 20 mg per day for ≥ 14 days) can interfere with vaccine-induced immune responses. Of course, reasonable clinical judgment must be exercised in the risk-to-benefit review of each case. Topical, inhaled and locally injected (intra-articular, bursal or tendon injection) steroids do not have an impact on vaccines unless there is clinical or laboratory evidence of immunosuppression from such therapy. A period of at least 1 month should elapse between high-dose steroid use and the administration of both inactivated and component vaccines (to establish immunogenicity, unless needed for post-exposure or outbreak management) and live vaccines (to reduce the risk of dissemination). Children with adrenogenital syndrome and those receiving physiologic replacement doses of glucocorticoids can follow the routine immunization schedule without restriction.

Hematopoietic stem cell transplantation

If time permits, careful consideration must be given to the pre-ablation immunization status of the patient and, in the case of allogenic bone marrow transplantation (BMT), the donor. It is well established that disease and immunization histories in both the host and the donor (i.e., in adoptive transfer) can influence immunity after ablation or transplantation. Antibody titres to vaccine-preventable diseases decline after allogenic or autologous hematopoietic stem cell transplantation if the recipient is not re-vaccinated. Hematopoietic stem cell transplant recipients are at increased risk of certain vaccine-preventable diseases (e.g., pneumococcal and Hib infections).

Recommendations for post-transplantation immunizations in this setting include the following:

  • DTaP (< 7 years old) or one dose of Tdap followed by two doses of Td (persons ≥ 7 years old) should be given starting 12 months after transplantation. Three doses are required, at 12, 14 and 24 months after transplantation.
  • Hib vaccine is recommended 12 months after transplantation. Three doses are required (12, 14 and 24 months after transplantation).
  • Inactivated polio vaccine (IPV) should be given 12 months after transplantation. Three doses are required, 12, 14 and 24 months after transplantation.
  • Pneumococcal vaccine is recommended for all persons 12 months after transplantation. Adults and children > 5 years of age should receive the Pneu-P-23. Children < 5 years should be immunized with the Pneu-C-7 according to the recommended schedule for their age, as if they had not been previously immunized. Children 2 to 5 years of age should receive both conjugate and polysaccharide vaccine (see Pneumococcal Vaccine chapter for recommended schedules). Because antibody response to pneumococcal vaccination is known to be poor in these patients, some experts recommend that all transplant patients > 2 years of age receive a booster dose of polysaccharide vaccine 1 year after their initial Pneu-P-23 immunization.
  • Meningococcal vaccine should be given 12 months after transplantation if indicated (see meningococcal chapter for age-specific recommendation). At this time, there are a number of choices for immunization to prevent meningococcal disease, and new conjugate vaccines are being developed (see NACI Web site for future updates).
  • Inactivated influenza vaccine should be given annually during early autumn, starting at least 6 months after transplantation.
  • Hepatitis B vaccine should be given to all patients. Vaccination should be started 12 months after transplantation, and three doses are required, at 12, 14 and 24 months after transplantation.
  • MMR should be given at least 2 years after the transplantation and only if the recipient is deemed to be immunocompetent by the transplant specialist. It should not be given to those with chronic graft-versus-host disease or those taking immunosuppressive therapy for chronic-graft-versus host disease. A second dose should be given 6-12 months later.
  • Varicella vaccination of recipients at ≥ 2 years after transplantation may be considered, provided there is minimal immunosuppression and no graft-versus-host disease. Until further data are available, the same age-appropriate dosage schedule as for healthy children may be followed. Currently, the only varicella vaccine approved in Canada for use in select immunocompromised people is Varilrix®.
  • Other live vaccines (BCG, yellow fever and oral typhoid vaccine) are usually contraindicated in hematopoietic stem cell recipients with active graft-versus-host diseases or immunosuppression. If such vaccines are required, consultation with a specialist is recommended.
  • Non-immune household contacts should be immunized against measles, mumps, rubella, varicella and influenza. IPV and hepatitis A vaccine should be administered if indicated.

Solid organ transplantation

The ideal is to immunize all recipients before transplantation. However, many children undergo solid organ transplantation before completion of their immunization schedule. Solid organ recipients usually receive lifelong immunosuppression. No formal recommendations have been developed about when to resume immunization. In general, vaccination should not be re-initiated until at least 6-12 months after transplantation.

Recommendations in this setting include the following:

Other live vaccines are usually contraindicated after transplantation. However, if some live vaccines are needed, consultation with a specialist is recommended. Household contacts who do not have immunity should be immunized against Hib, measles, mumps, rubella, varicella and influenza. IPV, hepatitis A and hepatitis B and any other vaccines should be administered if indicated.

Illnesses that progressively weaken the immune system
(e.g., Human Immunodeficiency Virus (HIV), myelodysplasia)

With the exception of BCG, there are no contraindications to the use of any vaccine (including MMR) early in the course of these illnesses. With progression of these conditions, the risk of using live vaccines increases. Therefore, the risks and benefits of a particular vaccine (and the alternative therapies available) need to be carefully considered.

Early immunization is not only safer but is also more effective in these conditions. There is no contraindication to the use of inactivated or component vaccines at any time. Particular attention should be paid to the completion of childhood immunizations, pneumococcal immunization (see Pneumococcal Vaccine chapter), annual influenza immunization and possibly booster doses against Hib. In the case of HIV, consensus "cut-offs" have been determined for the use of some live vaccines. Infants infected with HIV who are asymptomatic should receive routine MMR vaccination. In addition, MMR is recommended for most symptomatic HIV-infected persons, including children who are symptomatic without evidence of severe immunosuppression. Please consult an infectious disease specialist/immunologist for more specific advice on MMR immunization for HIV-infected people.

Varicella vaccine should be considered in children > 12 months of age with asymptomatic or mildly symptomatic HIV infection (CDC class N1 or A1) and with age-specific CD4 percentages of > 25%. Two doses need to be given 3 months apart. Although theoretical concerns have been raised about increases (probably transient) in HIV viral load, which can occur after a number of routine immunizations, these changes are transient and should not influence the decision regarding immunization.

Immunocompromised travellers

Although the degree and range of infectious disease risks can increase dramatically when an immunocompromised individual travels to other countries or continents, the basic principles already outlined still apply. Evidence is accumulating to suggest that several live vaccines (including yellow fever vaccine) can be considered for people with HIV infection whose CD4+ T cell count is > 200/mm3. However, the risks and benefits of each live vaccine must be carefully evaluated for every traveler. When a certificate of yellow fever vaccination is required but this vaccine is contraindicated, a letter of deferral should be supplied to the patient.

Table 8. Vaccination of Individuals with Immunodeficiency

Selected references

American Society of Transplantation. Guidelines for vaccination of solid organ transplant candidates and recipients. American Journal of Transplantation 2004;4(Suppl 10): S160-63.

Ballout A, Goffin E, Yombi JC et al. Vaccinations for adult solid organ transplant recipients: current recommendations. Transplantation Proceedings 2005;37(6):2826-27.

Campbell AL, Herold BC. Immunization of pediatric solid-organ transplantation candidates: immunizations in transplant candidates. Pediatric Transplantation 2005;9(5):652-61.

Castagnola E, Fioredda F. Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. European Journal of Haematology 2003;71(5):319-26.

Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Morbidity and Mortality Weekly Report 2000;49(RR-10):1-125.

Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence. Morbidity and Mortality Weekly Report 1993;42(RR-4):1-18.

Committee to Advise on Tropical Medicine and Travel. Statement on travellers and HIV/ AIDS. Canada Communicable Disease Report 1994;20(17):147-49.

Duchini A, Goss JA, Karpen A et al. Vaccinations for adult solid-organ transplant recipients: current recommendations and protocols. Clinical Microbiology Reviews 2003;16(3):357-64.

Fivush BA, Neu AM. Immunization guidelines for pediatric renal disease. Seminars in Nephrology 1998;18(3):256-63.

Gershon AA, Steinberg SP. Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine. New England Journal of Medicine 1989;320(14):892-97.

Keeffe EB. Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination. American Journal of Medicine 2005;118(Suppl 10A):S21-27.

LaRussa P, Steinberg S, Gershon AA. Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada. Journal of Infectious Diseases 1996;174(Suppl 3):S320-23.

McFarland E. Immunizations for the immunocompromised child. Pediatric Annals 1999;28(8):487-96.

Melles DC, de Marie S. Prevention of infections in hyposplenic and asplenic patients: an update. Netherlands Journal of Medicine 2004;62(2):45-52.

Mileno MD, Bia FJ. The compromised traveler. Infectious Disease Clinics of North America 1998;12(2):369-412.

Molrine DC. Recommendations for immunizations in stem cell transplantation. Pediatric Transplantation 2003;7(Suppl 3):S76-85

Molrine DC, Hibberd PL. Vaccines for transplant recipients. Infectious Disease Clinics of North America 2001;15(1):273-305.

National Advisory Committee on Immunization. Statement on recommended use of meningococcal vaccines. Canada Communicable Disease Report 2001;27(ACS-6):2-36.

National Advisory Committee on Immunization. Statement on recommended use of pneumococcal conjugate vaccines. Canada Communicable Disease Report 2002;28(ACS-2):1-32.

Neuhauss TJ. Immunization in children with chronic renal failure: a practical approach. Pediatric Nephrology 2004;19(12):1334-39.

Rangel MC, Coronado VG, Euler GL et al. Vaccine recommendations for patients on chronic dialysis. Seminars in Dialysis 2000;13(2):101-107.

Sartori AM. A review of the varicella vaccine in immunocompromised individuals. International Journal of Infectious Diseases 2004;8(5):259-70.

Somani J, Larson RA. Reimmunization after allogeneic bone marrow transplantation. American Journal of Medicine 1995;98(4):389-98.

Weber DJ, Rutala WA. Immunization of immunocompromised persons. Immunology and Allergy Clinics of North America 2003;23(4):605-34.

Yeung CY, Liang DC. Varicella vaccine in children with acute lymphoblastic leukemia and non Hodgkins lymphoma. Pediatric Hematology and Oncology 1992;9(1):29-34.

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