The safety and effectiveness of vaccines in people with immune deficiency are determined by the nature and degree of immunosuppression. Immunocompromised people vary in their degree of immunosuppression and susceptibility to infection. Immunocompromised children represent a heterogeneous population with regard to immunization. Immunodeficiency conditions can be grouped into primary and secondary (acquired) disorders. Primary disorders of the immune system generally are inherited, usually as single-gene disorders; may involve any part of the immune defenses, including B-lymphocyte (humoral) immunity, T-lymphocyte (cell)-mediated immunity, complement, and phagocytic function as well as other, unique abnormalities of innate immunity; and share the common feature of susceptibility to infection.¹ Secondary disorders of the immune system are acquired and occur in people with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) or malignant neoplasms; people who have undergone transplantation or splenectomy; people receiving immunosuppressive, antimetabolic, or radiation therapy; and people with a variety of other illnesses, such as severe malnutrition, protein loss, and uremia (see Table 1.14). Published studies of experience with vaccine administration in immunocompromised children are limited. In most situations, theoretical considerations are the primary guide to vaccine administration, because experience with specific vaccines in people with a specific disorder is lacking. However, considerable experience in HIV-infected children provides reassurance about the low risk of adverse events in these children after immunization.

Table 1-14

Live Vaccines

In general, people who are severely immunocompromised or in whom immune status is uncertain should not receive live vaccines, either viral or bacterial, because of the risk of disease caused by the vaccine strains. Although precautions, contraindications, and suboptimal efficacy of immunizations in less severely immunocompromised children and adolescents are of concern, benefits may outweigh risks for use of routinely recommended live vaccines.

Inactivated Vaccines And Passive Immunization

Inactivated vaccines and Immune Globulin (IG) preparations should be used when appropriate, because the risk of complications from these preparations is not increased in immunocompromised people. However, immune responses of immunocompromised children to inactivated vaccines (eg, DTaP, Tdap, hepatitis B, hepatitis A, IPV, Hib, pneumococcal, meningococcal, and influenza) may be inadequate. In children with secondary immunodeficiency, the ability to develop an adequate immunologic response depends on the presence of immunosuppression during or within 2 weeks of immunization. In children in whom immunosuppressive therapy is discontinued, an adequate response usually occurs between 3 months and 1 year after discontinuation. Inactivated influenza vaccine should be given yearly to immunosuppressed children 6 months of age and older before each influenza season. In children with malignant neoplasms, if possible, inactivated influenza immunization should be given no sooner than 3 to 4 weeks after a course of chemotherapy is discontinued and when peripheral granulocyte and lymphocyte counts >1000 cells/μL (1.0 X 10⁹/L) are achieved.

All children and adolescents with primary and secondary immunodeficiencies should receive an annual age-appropriate influenza vaccine to prevent influenza and secondary bacterial infections associated with influenza disease.

Primary Immunodeficiencies

Measles and varicella vaccines should be considered for children with B-lymphocyte disorders. However, optimal antibody response may not occur because of the underlying disease and because the patient may be receiving Immune Globulin Intravenous (IGIV) periodically. Oral poliovirus (OPV) vaccine, which no longer is available in the United States, is contraindicated, because it has been associated with an increased incidence of paralytic disease in people with B-lymphocyte or combined immunodeficiency disorders. Other live vaccines also are contraindicated for most patients with B-lymphocyte defects except immunoglobulin A deficiency. Live vaccines are contraindicated for all patients with T-lymphocyte-mediated disorders of immune function (see Table 1.14). Fatal or chronic poliomyelitis, measles, and vaccinia after smallpox immunization have occurred in children with disorders of T-lymphocyte function after administration of the respective live-virus vaccines. Inactivated poliovirus vaccine should be administered. Live-attenuated influenza vaccine (LAIV) should not be given to children or adolescents with immunodeficiencies. These patients should be given trivalent inactivated influenza vaccine. Children with deficiency in antibody-synthesizing capacity may be incapable of developing an antibody response to vaccines and may benefit from regular doses of IG (usually IGIV) to provide passive protection against many infectious diseases. Specific immune globulins are available for postexposure prophylaxis for some infections . Children with milder B-lymphocyte and antibody deficiencies have an intermediate degree of vaccine responsiveness and may require monitoring of postimmunization antibody concentrations to confirm vaccine immunogenicity.

The live-attenuated vaccines for rotavirus are of unproven safety in infants with immunodeficiencies, including primary and acquired immunodeficiency conditions, infants with blood dyscrasias, infants on immunosuppressive therapy, or infants who are HIV exposed or infected. Because these vaccines are recommended for infants beginning at 6 weeks of age, some recipients will have these as-yet undiagnosed diseases and have the potential for prolonged shedding and systemic illness. Health care professionals should consider the potential risks and benefits of administering rotavirus vaccine to infants with known or suspected altered immunocompetence (see Rotavirus).¹

Most experts believe that live-virus vaccines are safe to administer to children with complement deficiencies and disorders of phagocyte function. Children with early or late complement deficiencies can receive all immunizations, including live vaccines. Children with phagocytic function disorders, including chronic granulomatous disease and leukocyte adhesion defects, can receive all immunizations except live-bacteria vaccines (bacille Calmette-Guérin [BCG] and Ty21a Salmonella typhi ).

Secondary (Acquired) Immunodeficiencies

Several factors should be considered in immunization of children with secondary immunodeficiencies, including the underlying disease, the specific immunosuppressive regimen (dose and schedule), and the infectious disease and immunization history of the person. Live vaccines generally are contraindicated because of an increased risk of serious adverse effects. Exceptions are children 1 through 8 years of age with HIV infection who are in CDC clinical categories N, A, and B, in whom measles-mumps-rubella (MMR) vaccine is recommended (see Human Immunodeficiency Virus Infection) and in whom varicella vaccine should be considered if CD4+ T-lymphocyte counts are 15% or greater than expected for age (see Varicella-Zoster Infections). Immunization with MMR and varicella vaccines of people 9 years of age and older who have CD4+ T-lymphocyte counts 200 cells/mm³ or greater can be considered.¹ The use of varicella vaccine in children with acute lymphocytic leukemia in remission should be considered, because the risk of natural varicella disease outweighs the risk associated with the live-attenuated vaccine virus (see Varicella-Zoster Infections).

Live-virus vaccines usually are withheld for an interval of at least 3 months after immunosuppressive cancer chemotherapy has been discontinued. For corticosteroid therapy (see Corticosteroids), the interval is based on the assumption that immune response will have been restored in 3 months and that the underlying disease for which immunosuppressive therapy was given is in remission or under control. Immunodeficiency that follows use of recombinant human proteins with antiinflammatory properties, including tumor necrosis factor alpha antagonists (eg, adalimumab, infliximab, and etanercept) or anti-B-lymphocyte monoclonal antibodies (eg, rituximab), appears to be prolonged. The interval until immune reconstitution varies with the intensity and type of immunosuppressive therapy, radiation therapy, underlying disease, and other factors. Therefore, often it is not possible to make a definitive recommendation for an interval after cessation of immunosuppressive therapy when live-virus vaccines can be administered safely and effectively.

Other Considerations

Because patients with congenital or acquired immunodeficiencies may not have an adequate response to an immunizing agent, they may remain susceptible despite having received an appropriate vaccine. If there is an available test for a known antibody correlate of protection, specific serum antibody titers should be determined 4 to 6 weeks after immunization to assess immune response and guide further immunization and management of future exposures.

People with certain immune deficiencies may benefit from specific immunizations directed at preventing infections by organisms to which they are particularly susceptible. Examples include administration of pneumococcal and meningococcal vaccines to people with splenic dysfunction, asplenia (see Children With Asplenia), and complement deficiencies, because they are at increased risk of infection with encapsulated bacteria. Also, annual inactivated influenza immunization is indicated for children 6 months of age and older with immune deficiencies, including splenic dysfunction, asplenia, and phagocyte function deficiencies, to prevent influenza and decrease the risk of secondary bacterial infections (see Influenza).

Household Contacts

Immunocompetent siblings and other household contacts of people with an immunologic deficiency should not receive smallpox vaccine or OPV vaccines, because vaccine virus may be transmitted to immunocompromised people. However, siblings and household contacts should receive MMR, varicella, and rotavirus vaccines if indicated, because transmission of the vaccine viruses rarely occurs. Household contacts 6 months of age and older should receive yearly inactivated influenza vaccine to prevent infection and subsequent transmission to the immunocompromised person. Limited data are available assessing the risk of transmission of LAIV virus from vaccine recipients to immunosuppressed contacts, although this appears to be a rare event. Inactivated influenza vaccine is recommended for immunizing household members of immunosuppressed people. Varicella vaccine is recommended for susceptible contacts of immunocompromised children, because transmission of varicella vaccine virus from healthy people is rare, and vaccine-associated illness, if it develops, is mild. No precautions need to be taken after immunization unless the vaccine recipient develops a rash, particularly a vesicular rash. In such instances, the vaccine recipient should avoid direct contact with immunocompromised, susceptible hosts for the duration of the rash. If contact occurs inadvertently, risk of transmission is low. Therefore, administration of Varicella-Zoster Immune Globulin (VariZIG) or IGIV is not indicated. Also, when transmission has occurred, the virus has maintained its attenuated characteristics. In most instances, antiviral therapy is not necessary but can be initiated if illness occurs (see Varicella-Zoster Infections).