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Immunization of the immunocompromised child 

Immunization of the immunocompromised child
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Immunization of the immunocompromised child
DOI:
10.1093/med/9780198729228.003.0018
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date: 04 August 2020

Specific vaccines of relevance to immunocompromised children

The vaccines included in routine immunization schedules used in Europe are outlined in Appendix 3. For details of individual vaccines please refer to specific infection chapter. Some of these need specific consideration in immunocompromised children, including the following.

Rotavirus

Two live vaccines are available: Rotarix® (two doses) and RotaTeq® (three doses). The first dose requires administration before 15 weeks of age (the second dose before 23 weeks and 6 days), therefore before the presentation of most immunocompromising conditions.

Administration is:

  • To be avoided in patients with SCID

  • Safe in patients with HIV on ART

  • Of uncertain efficacy and safety in infants with other immunocompromising illnesses; however, most children are likely to benefit, as natural rotavirus infection is almost unavoidable

  • Advised in infants born into households with an immunocompromised inhabitant, according to the routine infant schedule.

Varicella

Two live attenuated vaccines available, administered as two doses, given 4–8 weeks apart from 12 months of age. Monovalent vaccines preferred to combination vaccines with measles, mumps, rubella, and varicella (MMRV), which have a higher varicella dose.

  • Avoid in children with immunocompromise, with the possible exceptions of seronegative children:

    • With 22Q11 deletion/di George syndrome

    • With HIV if % CD4 >15.

  • Where possible, give a dose 3–4 weeks before commencing immunosuppressive therapy for seronegative children.

  • Use in children already on low-dose immunosuppressants is controversial and should be discussed with paediatric infectious disease clinicians.

  • Efficacy potentially reduced in immunocompromised children.

  • Administer to contacts of immunocompromised; the benefit/risk ratio remains positive, despite case reports of 2° transmission of the vaccine strain.

BCG

Live attenuated vaccine.

  • Do not administer to immunocompromised children.

  • Delay in babies born to HIV-positive mothers until the infant has had two negative HIV PCR tests, one of which is at least 6 weeks after antiretroviral therapy has stopped.

Measles, mumps, rubella

Combination of three live attenuated viruses.

  • Do not administer to children on high-dose immunosuppressants and chemotherapy, and with disorders of T-cell function.

  • Can be given to HIV-positive children and those with di George syndrome ≥12 months of age if CD4% ≥15.

Influenza

  • Annual influenza immunization is appropriate for most immunocompromised children (two doses given 1 month apart in first season for children under 9 years; otherwise a single dose given annually).

  • The live attenuated influenza vaccine (LAIV) is only licensed from 2 years of age, at-risk children younger than this should receive the inactivated vaccine.

  • Inactivated influenza vaccines should be given instead of LAIV for children or adolescents on high-dose immunosuppressants or chemotherapy, or with T- or B-cell immunocompromise.

  • LAIV not contraindicated in children ≥2 years of age with:

    • Stable HIV infection receiving ART

    • Topical/inhaled corticosteroids, low-dose systemic corticosteroids, or corticosteroids for replacement therapy, e.g. for adrenal insufficiency.

  • Immunization of household contacts encouraged; however, shedding of the live attenuated virus in the weeks following immunization creates the theoretical risk of transmission to severely immunocompromised hosts; therefore, close contacts of such children should receive the inactivated influenza vaccine.

Pneumococcus

Children with broad range of immunodeficiencies and chronic illnesses are at increased risk of pneumococcal disease, especially those with haematological malignancy, HIV, and splenic dysfunction. Immunization with one of the two licensed pneumococcal glycoconjugate vaccines (10-valent PCV10 or 13-valent PCV13) is now universal in most European countries, and the resultant herd immunity is expected to reduce the disease burden due to these serotypes, even in immunocompromised children.

  • Administer PCV10 or PCV13 in infancy, according to local routine immunization schedules.

  • For older children, current UK recommendations are:

    • One dose of PCV13 for a child ≥2, but <5 years old if not already given (two doses for splenic dysfunction or immune system impairment)

    • One dose of PCV13 for children ≥5 years old and severely immunocompromised (e.g. bone marrow transplant patients, those with haematological malignancies or primary immunodeficiencies).

Although included in some immunization guidelines for children over 2 years of age, the benefits from an additional 23-valent plain polysaccharide vaccine are uncertain, given concerns regarding immunological hyporesponsiveness with repeated immunization. Disease-specific guidance has been provided for some conditions, e.g. HIV guidelines produced by Children’s HIV Association (CHIVA, Immunization of the immunocompromised child <http://www.chiva.org.uk>), and these should override more general guidelines.

Meningococcus

Specific conditions at increased risk of invasive meningococcal disease (IMD) are asplenia/splenic dysfunction, complement deficiency, and eculizumab therapy.

Serogroups A, C, W, and Y

Two quadrivalent glycoconjugate MenACWY vaccines are licensed in Europe: Nimenrix® (MenACWY-TT, licensed as a single dose from 12 months of age) and Menveo® (MenACWY-CRM, licensed as a single dose from 2 years of age). These vaccines should be used in preference to plain polysaccharide vaccines for all children at increased risk of IMD.

  • Although no glycoconjugate MenACWY vaccine is licensed in Europe for use in <12 months of age, some national guidelines (e.g. UK) suggest using MenACWY as a substitute for monovalent MenC vaccine in infant immunization programmes for children at increased risk of IMD.

  • For children previously immunized with MenC vaccine, give a further dose of MenACWY conjugate vaccine ≥1 month later.

  • Children/adolescents previously receiving a plain polysaccharide MenACWY vaccine should receive a dose of glycoconjugate MenACWY vaccine.

  • Children at increased risk of IMD who are travelling to countries with a high incidence of serogroup A meningococcal infection (e.g. Saudi Arabia and sub-Saharan Africa) should be given a further dose of MenACWY conjugate vaccine, in addition to those recommended above, prior to travel.

Serogroup B

A serogroup B meningococcal vaccine (Bexsero®, 4CMenB) has been licensed in Europe for children ≥2 months old.

This vaccine is recommended for children at increased risk of IMD, according to the following schedules:

  • Three doses at least 1 month apart, with a booster dose in the second year of life if <6 months of age

  • Two doses at least 2 months apart, with a booster after 12–23 months if 6 months to 2 years of age

  • Two doses at least 2 months apart if 2–10 years

  • Two doses at least 1 month apart if 11 years or older.

Polio vaccines

  • Avoid live oral polio vaccine (OPV) in all immunocompromised children and their household contacts.

  • Use inactivated polio vaccines in these circumstances.

Hepatitis B vaccine

  • If not included in the routine vaccine schedule, give to children at increased exposure risk (e.g. dialysis, HIV-positive family member) or with reduced hepatic capacity (e.g. chronic liver disease).

  • Give as 0-, 1-, 6-month course, unless accelerated schedule required for post-exposure prophylaxis (PEP) (e.g. maternal infection), in which case a 0-, 1-, 2-, 12-month immunization course should be given.

  • Check serology 6–8 weeks post-third dose.

    • If >10IU/L, but <100IU/L, offer a booster, and recheck serology after 6–8 weeks.

    • If <10IU/L after the 1° course, repeat the course and serology.

  • Consider combination hepatitis A and B vaccine if over 12 months of age.

Palivizumab

Humanized monoclonal antibody against RSV F protein can protect children at increased risk from RSV infection against hospitalization and severe disease when administered monthly during the RSV season.

  • Licensed for use in children:

    • Born <35 weeks’ gestation who are under 6 months at the onset of the RSV season

    • Under 2 years of age and requiring treatment for bronchopulmonary dysplasia (BPD) within the last 6 months

    • Under 2 years of age with haemodynamically significant cardiovascular disease.

  • Local guidance for use may differ, based on cost-effectiveness calculations. In the UK, its use is targeted at extremely low-birthweight premature infants with chronic lung disease.

Immunizing children with primary immunodeficiencies

See Chapter 17 for a discussion on 1° immunodeficiencies. For all the 1° immunodeficiencies:

  • Passive immunization on exposure to measles, varicella, and tetanus will be required

  • The importance of immunizing immunocompetent family members to reduce transmission should be emphasized.

Combined B-/T-cell immunodeficiency

Examples: SCID, Wiskott–Aldrich Syndrome, hyper IgM/CD40 ligand deficiency, chronic mucocutaneous candidiasis (CMC) (autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) syndrome).

  • Inactivated routine vaccines:

    • Safe; however, effectiveness is doubtful, especially for patients on immunoglobulin replacement therapy (IRT) (providing continual passive immunity).

  • Live vaccines:

    • Avoid all, including rotavirus, MMR, BCG, and LAIV.

  • Additional vaccines:

    • Annual inactivated influenza immunization may be beneficial.

B-cell deficiency

Examples: X-linked agammaglobulinaemia, common variable immunodeficiency, hyper IgE (Jobs) syndrome.

  • Inactivated routine vaccines:

    • Safe; however, effectiveness doubtful, especially following commencement of IRT therapy.

  • Live vaccines:

    • While immunization with MMR and varicella vaccine could potentially provide cellular immunity, safety is uncertain, and any immune response is unlikely if the patient is on IRT

    • Avoid BCG.

  • Additional vaccines:

    • Annual inactivated influenza immunization may be beneficial.

Reduced T-cell numbers

Example: 22q11 deletion/di George syndrome.

  • Inactivated routine vaccines:

    • Administer as per local routine schedule.

  • Live vaccines:

    • Recent case series suggests that MMR and varicella vaccines may be given safely to patients with di George syndrome who have mild to moderate immunocompromise; these should be given at age 12–18 months if CD4 count adequate and normal mitogen response.

    • Other live vaccines (BCG, OPV, yellow fever vaccine, live influenza vaccine) should be avoided.

  • Additional vaccines:

    • Pneumococcal and influenza immunizations.

Minor antibody deficiencies

Examples: IgA and IgG subclass deficiencies, ataxia telangiectasia. Some children will require regular IVIG therapy for recurrent infections, which will potentially interfere with live vaccine immunogenicity (but these should still be given).

  • Inactivated routine vaccines:

    • Administer as per local routine schedule.

  • Live vaccines:

    • Safe; administer as per local routine schedule.

  • Additional vaccines:

    • Pneumococcal and influenza immunizations.

Phagocytic cell deficiencies

Examples: CGD, myeloperoxidase deficiency, and leucocyte adhesion deficiency.

  • Inactivated routine vaccines:

    • Administer as per local routine schedule.

  • Live vaccines:

    • MMR and varicella, and live attenuated influenza vaccines should be administered (varicella vaccine is advised to reduce the risk of 2° bacterial sepsis from natural infection)

    • Avoid BCG or other live bacterial vaccines such as oral typhoid.

  • Additional vaccines:

    • Pneumococcal and influenza immunizations.

Complement deficiency

At increased risk of infection with encapsulated bacteria, particularly Meningococcus.

  • Inactivated routine vaccines:

    • Administer as per local routine schedule (but ensure meningococcal immunization as per specific guidance).

  • Live vaccines:

    • Safe; administer as per local routine schedule.

  • Additional vaccines:

    • Immunize with MenACWY and serogroup B meningococcal vaccines

    • Pneumococcal immunizations should be administered.

Acquired immunodeficiencies

HIV infection

  • Inactivated routine vaccines:

    • Administer as per local schedule

    • If highly active antiretroviral therapy (HAART) indicated, vaccination should be delayed until both viral load <50 copies/mL and CD4 % >15 for 6 months.

  • Live vaccines:

    • Live attenuated influenza vaccine if ≥2 years and infection stable

    • Rotavirus vaccine safe and recommended (usual age limits apply)

    • MMR recommended, unless severe immunosuppression, i.e.:

      • CD4 % <15 (any age), or

      • CD4 count <750 cells/mm3 (<12 months)

      • CD4 count <500 cells/mm3 (>1–5 years)

      • CD4 count <200 cells/mm3 (>6 years)

    • Give two doses of MMR at least 3 months apart (if under 18 months) or at least 1 month apart (if ≥18 months)

    • Give two doses of varicella vaccine 1–2 months apart in VZV seronegative children over 1 year of age and in the absence of severe immunosuppression (as per MMR guidance)

    • Administer MMR and varicella vaccine at least 1 month apart

    • Avoid BCG in HIV-positive children.

  • Additional vaccines:

    • Annual influenza vaccine (consider live vaccine if ≥2 years)

    • All require two doses of pneumococcal glycoconjugate vaccine (PCV13 or PCV10, as used in the local schedule), given 2 months apart (if not given in infancy)

    • Consider including pertussis vaccine in adolescent booster if not included in routine immunization programme

    • Human papillomavirus (HPV) according to routine immunization practice for adolescent girls; consider also administering to adolescent boys

    • Hepatitis B vaccine.

In addition to HBV serology check, consider checking tetanus and measles antibody concentrations post-preschool and adolescent booster vaccine visits. For children immunized prior to commencing ART, consider re-immunizing after immune reconstitution on HAART.

HIV-negative children in a household with an HIV-positive member

  • Routine immunizations, as per national guidelines.

  • MMR and BCG should be given.

  • Varicella immunization for children >1 year, if not already immune.

Immunosuppressive medication

Immunosuppressants

The following medicines/doses are considered ‘high-dose’:

  • Glucocorticoids: high-dose glucocorticoid—pulse therapy or >2mg/kg/day or >20mg per day for 2 weeks.

  • Non-biological immunosuppressants (also known as disease-modifying anti-rheumatic drugs, DMARDs):

    • Methotrexate >15mg/m2/week

    • Ciclosporin >2.5mg/kg/day

    • Azathioprine 1–3mg/kg/day

    • Cyclophosphamide 0.5–2.0mg/kg/day orally

    • Leflunomide 0.25–0.5mg/kg/day

    • 6-mercaptopurine >1.5mg/kg/day

    • Sulfasalazine is not immunosuppresive.

  • Biological agents (e.g. infliximab, rituximab, abatacept, tocilizumab, eculizumab, etc.)—at any dose within the last 6 months.

Recommendations

The European League Against Rheumatism (EULAR) guidance on immunization of children on immunosuppressive treatment broadly recommends:

  • Inactivated routine vaccines:

    • Administer as per local schedule

    • If child’s immunization not up-to-date, ‘catch-up’ immunizations should ideally be given before commencing immunosuppressants

  • Live vaccines:

    • If possible, check varicella-zoster IgG status prior to treatment initiation, and administer the varicella vaccine to seronegative patients 3–4 weeks prior to starting treatment

    • Booster doses for varicella vaccine and MMR can be considered in patients on low-dose steroids or methotrexate <15mg/m2/week

    • In addition, the Infectious Diseases Society of America (IDSA) guidelines suggest to consider 1° varicella vaccine for chronic inflammatory disease with long-term, low-level immunosuppression

  • Additional vaccines:

    • Influenza and pneumococcal vaccines

  • Siblings should receive MMR, as per usual schedule, and varicella vaccine if non-immune and >1 year old.

Patients on rituximab

  • Inactivated routine vaccines:

    • Safe, but response to inactivated vaccines impaired

    • Aim to administer >4 weeks prior to commencing treatment (or if already on rituximab >4 weeks prior to the next dose).

  • Live vaccines:

    • Avoid all live vaccines for 6 months after treatment.

  • Additional vaccines:

    • Give inactivated influenza vaccine in autumn, regardless of the timing of rituximab or the lymphocyte count

    • Patients who have not already had pneumococcal immunization should ideally commence immunization 3 months before commencing the first course of rituximab with two doses of glycoconjugate pneumococcal vaccine (PCV10 or PCV13)

    • There is no evidence that a dose of pneumococcal plain polysaccharide vaccine confers additional benefit in these patients

    • Administer tetanus immunoglobulin to any patient receiving rituximab within the last 6 months with a contaminated wound

    • Once IgG concentration in the normal range, check specific antibodies (e.g. tetanus, Hib, serotype-specific pneumococcal antibodies, measles); if low, re-immunize and check levels.

Patients on eculizumab

Specifically at increased risk of meningococcal disease, given the central role of C5 (bound by eculizumab) in the complement cascade:

  • Additional meningococcal immunization.

Chemotherapy for malignancy

  • Inactivated routine vaccines:

    • Safe but should not be administered during induction or consolidation therapy.

  • Live vaccines:

    • Avoid in patients actively receiving treatment, and for 6 months following cessation of treatment.

  • Additional vaccines:

    • Pneumococcal vaccine

    • Inactivated influenza vaccination should be offered from the age of 6 months, during maintenance chemotherapy, and if autumn occurs in the first 6 months following completion of chemotherapy

    • At 6 months following completion of chemotherapy, administer a booster dose of all routine vaccines (or alternatively check serology, and administer a booster dose of the relevant vaccine if antibodies are below correlate of protection).

Haematopoietic stem cell transplantation

Conditioning therapy before transplantation removes the humoral immune memory from previous infections and immunizations, and makes these children severely immunocompromised.

  • Inactivated routine vaccines:

    • Prior to HSCT, vaccination, as per local schedule, should be completed if not immunosuppressed and >4 weeks prior to HSCT.

  • Live vaccines:

    • MMR and varicella vaccination in children >12 months of age who are not immunosuppressed and >4 weeks prior to HSCT

    • Avoid BCG, unless absolutely necessary; seek expert advice.

  • Additional vaccines:

    • Annual inactivated influenza vaccine from first autumn after commencement of re-immunization.

  • Passive immunization:

    • Passive immunization for contact with chickenpox/shingles or measles is required until 12 months after HLA-identical sibling donor allogeneic HSCT, syngeneic HSCT, or autologous HSCT, and 18 months after all other allogeneic HSCT. This is required, regardless of pre-chemotherapy antibody status.

Re-immunization

  • Re-immunization (i.e. repeating all immunizations received during 1° vaccination course) should begin 12 months after HLA-identical allogeneic HSCT, syngeneic HSCT, or autologous HSCT, and 18 months after all other allogeneic HSCT.

  • This should be delayed if

    • Immunosuppressive drugs used within 6 months (12 months for live vaccines)

    • IVIG has been used within 3 months

    • Evidence of chronic GVHD.

Solid organ transplant

  • Inactivated routine vaccines:

    • Childhood/adolescent immunizations (including HPV) should be given, whenever possible, prior to solid organ transplantation.

  • Live vaccines:

    • MMR and varicella vaccine should be given at least 4 weeks prior to transplant (if not immunosuppressed)

    • Avoid live vaccines after solid organ transplantation.

  • Additional vaccines:

    • Pneumococcal and influenza immunizations

    • Hepatitis B vaccine to be given prior to transplantation.

Hyposplenia/asplenia/functional asplenia

Specific increased risk of pneumococcal disease, with case reports of overwhelming meningococcal infection.

  • Live and inactivated routine vaccinations:

    • Administer, as per local routine schedule.

  • Additional vaccines:

    • Give pneumococcal and influenza vaccines

    • Meningococcal vaccines.

If undergoing splenectomy, give all vaccines 2 weeks before surgery, if possible.

Nephrotic syndrome

  • Inactivated routine vaccines:

    • Administer, as per local routine schedule.

  • Live vaccines:

    • Give MMR and varicella vaccines during remission when off steroids for 3 months or off other immunosuppressants for 6 months.

  • Additional vaccines:

    • Pneumococcal/influenza immunization.

If on rituximab, immunize.

Renal failure/chronic renal disease/dialysis

  • Live and inactivated routine vaccinations:

    • Administer, as per local routine schedule.

  • Additional vaccines:

    • Pneumococcal/influenza immunization

    • Hepatitis B vaccine (increased risk due to dialysis).

Chronic liver disease

  • Live and inactivated routine vaccinations:

    • Administer, as per local routine schedule.

  • Additional vaccines:

    • Pneumococcal/influenza immunization

    • Combined hepatitis A and hepatitis B vaccination to avoid further liver insult.

Cyanotic heart disease/heart failure

  • Live and inactivated routine vaccinations:

    • Administer, as per local routine schedule.

  • Additional vaccines:

    • Influenza and pneumococcal immunization

    • If on aspirin, consider varicella vaccination from 12 months of age to decrease the risk of Reye’s syndrome

    • RSV prophylaxis.

Cystic fibrosis/bronchiectatic conditions/home ventilation

  • Live and inactivated routine vaccinations:

    • Administer, as per local routine schedule.

  • Additional vaccines:

    • Influenza and pneumococcal immunization

    • RSV prophylaxis.

Premature infants

  • Inactivated routine vaccinations:

    • Administer, as per local routine schedule, at the normal chronological age (even if on steroid therapy for chronic lung disease)

    • Particular attention to timely routine booster doses.

  • Live vaccines:

    • Administer, as per local routine schedule, at the normal chronological age

    • Rotavirus vaccination should be given, even if the patient still in the NICU.

  • Additional vaccines:

    • Consider influenza immunization from 6 months of age where additional risk factors exist, e.g. chronic lung disease

    • For influenza, in preterm infants <6 months, a cocooning strategy of immunizing family members may be considered

    • RSV prophylaxis, as appropriate, for first RSV season.

Monitoring post-immunization

  • Infants born ≤28 weeks’ gestation in hospital at the time of first immunization should be monitored for 48–72 hours after their first vaccine. If apnoea/bradycardia/desaturation occurs, then the child should be admitted and monitored for their second immunization.

  • No requirement for monitoring if the baby was discharged from the neonatal unit by 60 days of age.

Further reading

Heijstek MW, Ott de Bruin LM, Bijl M, et al. EULAR recommendation for vaccination in paediatric patients with rheumatic diseases. Ann Rheum Dis 2011;70:1704–12.Find this resource:

Menson EN1, Mellado MJ, Bamford A, et al.; Paediatric European Network for Treatment of AIDS (PENTA) Vaccines Group, PENTA Steering Committee and Children's HIV Association (CHIVA). Guidance on vaccination of HIV-infected children in Europe. HIV Med 2012;13:333–6.Find this resource:

Public Health England. Immunisation against infectious disease: the ‘Green Book’. 2013. Available at: Immunization of the immunocompromised child <https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book>.

Rubin LG, Levin MJ, Ljungman P, et al.; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:309–18.Find this resource: