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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.
Several general principles apply to the immunization of immunocompromised 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.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).
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.
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.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:
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
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