Immunization in Special Clinical Circumstances. Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2009:72– 86
General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention. MMWR Morbid Mortal Wkly Rep. 2006;55 (No.RR-15):24– 29OpenUrl
With improving survival rates after treatment of childhood malignancy, an increase in hematopoietic stem cell (HSCT) and solid organ transplantation, and the use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infections, the population of immunocompromised children who have special vaccination needs is burgeoning. Understanding the degree of immune recovery of these children is important in guiding vaccine administration. Inactivated vaccines can be administered safely to persons who have altered immunocompetence, but the effectiveness of such vaccines may be suboptimal. Inactivated influenza immunization should be administered annually to immunosuppressed children 6 months of age and older before each influenza season. In general, severely immunocompromised children should not receive live vaccines, either viral or bacterial, because of the risk of disease caused by vaccine strains. Oral polio virus vaccine and live bacterial vaccines, such as bacillus Calmette-Guérin (BCG) and Salmonella typhi Ty21, are contraindicated for immunocompromised patients as well as their household contacts. Household contacts and other close contacts of persons who have altered immunocompetence, however, should receive all other age-appropriate vaccines, including the live oral rotavirus vaccines.
Although many children who undergo HSCT acquire the immunity of the donor, some lose serologic evidence of immunity. Studies indicate that administration of diphtheria and tetanus toxoids to the donor before organ harvest and to the recipient after transplantation can facilitate response to these antigens. Similar results are expected with other inactivated vaccine antigens. Healthy survivors can be immunized with inactivated vaccines 1 year after HSCT and can receive measles, mumps, and rubella (MMR) and varicella vaccines 2 years after transplantation. Inactivated influenza vaccination, however, can be given as soon as 6 months after HSCT. Some experts elect to reimmunize all children after HSCT; others base the decision on inadequate serologic titers obtained 1 year posttransplantation.
Children being considered for solid organ transplantation should receive age-recommended immunizations prior to transplantation. Vaccines generally are more immunogenic at this time because posttransplant immunosuppressive medications often interfere with T- and B-lymphocyte activity. Live virus vaccines should be administered at least 4 weeks before organ transplantation to minimize the potential for posttransplant vaccine-related illness. It is reasonable to evaluate serum concentrations of antibodies to measles, mumps, rubella, and varicella to determine if these vaccines are needed.
Monovalent measles vaccination or if not available, MMR, may be administered before transplantation in children as young as 6 months of age if the transplantation is anticipated before the child reaches 1 year of age. Because of the increased mortality associated with hepatitis A infection in liver transplant recipients, hepatitis A vaccination should be considered in this population. Similarly, liver transplant recipients experience a more rapid and severe course compared with immunocompetent individuals if infected with hepatitis B. Therefore, all liver transplant candidates should receive hepatitis B vaccination if adequate protective antibodies are not present. Most experts recommend waiting at least 6 months after transplantation for the resumption of immunization schedules.
For children who will be receiving chemotherapy, the administration of all routinely recommended vaccinations prior to initiation of chemotherapy is optimal, and revaccination with these agents is not necessary. During active chemotherapy and shortly thereafter, antibody responses to vaccines are impaired. However, improvement in antibody production occurs rapidly, and immunization as early as 3 months after cessation of chemotherapy, including with live virus vaccines, is reasonable.
A dosage equivalent to at least 2 mg/kg per day of prednisone or equivalent to a total of at least 20 mg/day for children who weigh more than 10 kg, when administered for more than 14 days, is considered sufficient to raise concern about the safety of immunization with live virus vaccine. Therefore, vaccine schedules should be postponed until corticosteroids have been discontinued for at least 3 months. The safety and efficacy of live-attenuated vaccines administered concurrently with recombinant human immune mediators and anti-B-lymphocyte monoclonal antibodies is unknown. Until additional information becomes available, avoidance of live vaccines while receiving immunomodulators generally is recommended.
Studies suggest that antibody responses, although frequently improved in the presence of HAART, still are lower than in HIV-uninfected populations, suggesting that immune reconstitution with HAART varies among people and may be incomplete. An inverse relationship between vaccine response and HIV viral load has been found for a number of vaccines. This information suggests that vaccinations optimally should be administered when patients are on stable HAART, have good CD4 response, and have maximally suppressed viremia. It may be reasonable to delay vaccination until these endpoints are reached or to consider reimmunization.
Inactivated vaccines generally pose no harm to the HIV-infected patient and are recommended according to the routine schedules. Accumulating data suggest that measles and varicella vaccinations also are safe for HIV-infected children who have mild clinical disease and adequate CD4 counts (CD4 percentage, ≥15%). Measles immunization is especially important because wild-type measles can result in severe disease in HIV-infected children.
Live vaccines are contraindicated for all patients who have T-lymphocyte-mediated disorders. Measles and varicella vaccines should be considered for children who have B-lymphocyte disorders, but other live viral vaccines are contraindicated, except in immunoglobulin A deficiency. Many experts believe that live-virus vaccines are safe to administer to children who have disorders of phagocyte or complement function.
Children who have deficiencies in antibody-synthesizing capacity may be incapable of developing an antibody response to vaccines and should receive regular doses of gamma globulin as passive protection. Children receiving gamma globulin may not respond to live virus vaccines due to the continued presence of neutralizing antibody. Depending on the dose of gamma globulin administered, measles and varicella vaccinations need to be delayed for several months. If gamma globulin must be given within 14 days of measles or varicella vaccination, readministration of these vaccines should be considered. (See Table 3.34 of the 2009 Red Book for additional details.)
Children and adolescents who have anatomic or functional asplenia are at an increased risk of invasive infections with encapsulated bacteria and should receive protection with the 7-heptavalent conjugate pneumococcal vaccine and, after 2 years of age, the 23-valent pneumococcal polysaccharide vaccine as well meningococcal vaccination. A single dose of Haemophilus influenzae type B (Hib) vaccine also can be considered for asplenic older children who did not receive the childhood Hib vaccine series. Of note, children who have all of the aforementioned immunosuppressive conditions are at increased risk of invasive pneumococcal disease and are candidates for the 23-valent pneumococcal polysaccharide vaccine.
As the number of children who have altered immunity continues to grow, understanding which immunizations should be administered and when they can be provided safely with maximal benefit is increasingly important to protect some of the most vulnerable children against significant but preventable illnesses.
Pranita Tamma, MD
Johns Hopkins University School of Medicine
Understanding immunization principles and strategies for children who are immunocompromised is critically important to maximize protection against preventable diseases. Dr Tamma reviews important concepts and principles. One strategy worth emphasizing is the immunization of household contacts, particularly other children and adolescents in the family. This procedure is essential to try to minimize exposure of the immunocompromised patient to household contacts who might contract vaccine-preventable illnesses. Pediatric health-care clinicians need to update and review the vaccine status of all siblings and pediatric-age household members. Annual influenza vaccination of all family members with inactivated influenza vaccine is recommended in addition to ensuring routine immunization of all other recommended vaccines.
MMR, varicella, and rotavirus vaccines, although live viral vaccines, are recommended for immunocompetent household contacts because transmission of the virus is rare. The lack of viral shedding with MMR eliminates concern regarding transmission. Because the varicella virus rarely can be shed through a postimmunization vesicular rash that may develop, recommendations include avoiding contact until the rash resolves. For the rotavirus vaccine, avoidance of contact with the stools by the immunocompromised patient and good hand hygiene measures by all family members for at least 1 week after vaccination should be implemented. Note, however, that oral polio vaccine, BCG, and typhoid vaccine Ty21 are contraindicated for household contacts.
The resources that Dr Tamma provides are helpful for answering specific questions, and clinicians may want to review guidelines in special circumstances.
Janet R. Serwint, MD
Drs Tamma and Serwint have disclosed no financial relationships relevant to this In Brief. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
- Copyright © 2010 by the American Academy of Pediatrics