IDSA GUIDELINES

2013 IDSA Clinical Practice Guideline for

Vaccination of the Immunocompromised Host
Lorry G. Rubin,1 Myron J. Levin,2 Per Ljungman,3,4 E. Graham Davies,5 Robin Avery,6 Marcie Tomblyn,7 Athos Bousvaros,8
Shireesha Dhanireddy,9 Lillian Sung,10 Harry Keyserling,11 and Insoo Kang12
1
Division of Pediatric Infectious Diseases, Steven and Alexandra Cohen Children’s Medical Center of New York of the North Shore-LIJ Health System,
New Hyde Park; 2Section of Pediatric Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, Aurora; 3Department of Hematology,
Karolinska University Hospital; 4Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; 5Department of
Immunology, Great Ormond Street Hospital & Institute of Child Health, London, United Kingdom; 6Division of Infectious Diseases, Johns Hopkins
University School of Medicine, Baltimore, Maryland; 7Department of Blood and Marrow Transplant, H. Lee Moffitt Cancer Center and Research Institute,

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University of South Florida, Tampa; 8Department of Gastroenterology and Nutrition, Children’s Hospital Boston, Massachusetts; 9Department of Allergy
and Infectious Diseases, University of Washington, Seattle; 10Division of Hematology-Oncology, Hospital for Sick Children, Toronto, Ontario, Canada;
11
Division of Pediatric Infectious Diseases, Emory University of School of Medicine, Atlanta, Georgia 12Section of Rheumatology, Department of Internal
Medicine, Yale University School of Medicine, New Haven, Connecticut

An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompro-

mised adults and children. These guidelines are intended for use by primary care and subspecialty providers
who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investiga-
tion are highlighted.
Keywords. vaccination; immunization; immunocompromised patients; immunosuppression; asplenic patients;
immunodeficiency patients

EXECUTIVE SUMMARY Recommended immunization schedules for normal

adults and children as well as certain adults and chil-
These guidelines were created to provide primary care dren at high risk for vaccine-preventable infections
and specialty clinicians with evidence-based guidelines are updated and published annually by the Centers for
for active immunization of patients with altered immu- Disease Control and Prevention (CDC) and partner or-
nocompetence and their household contacts in order ganizations. Some recommendations have not been ad-
to safely prevent vaccine-preventable infections. They dressed by the Advisory Committee on Immunization
do not represent the only approach to vaccination. Practices (ACIP) to the CDC or they deviate from rec-
ommendations. The goal of presenting these guidelines
Received 4 October 2013; accepted 5 October 2013; electronically published is to decrease morbidity and mortality from vaccine-
4 December 2013. preventable infections in immunocompromised pa-
It is important to realize that guidelines cannot always account for individual var-
iation among patients. The guidelines are not intended to supplant physician judg- tients. Summarized below are the recommendations
ment with respect to particular patients or special clinical situations. The Infectious made by the panel. Supporting tables that provide addi-
Diseases Society of America considers adherence to these guidelines to be volun-
tary, with the ultimate determination regarding their application to be made by the
tional information are available in the electronic
physician in the light of each patient’s individual circumstances. version. The panel followed a process used in the devel-
An asterisk ( ) indicates recommendation for a course of action that deviates
from recommendations of the Advisory Committee on Immunization Practices,
opment of other Infectious Diseases Society of America
Centers for Disease Control and Prevention. guidelines, which included a systematic weighting of
Correspondence: Lorry G. Rubin (lrubin4@nshs.edu). the quality of the evidence and the grade of the recom-
Clinical Infectious Diseases 2014;58(3):e44–100
© The Author 2013. Published by Oxford University Press on behalf of the Infectious
mendation (Table 1). The key clinical questions and
Diseases Society of America. All rights reserved. For Permissions, please e-mail: recommendations are summarized in this executive
journals.permissions@oup.com. summary. A detailed description of the methods,
DOI: 10.1093/cid/cit684

e44 • CID 2014:58 (1 February) • Rubin et al

Table 1. Classification System for Assessing Strength of Recommendations and Quality of the Supporting Evidence

Strength of Clarity of Balance Between

Recommendation and Desirable and Undesirable Methodological Quality of
Quality of Evidence Effects Supporting Evidence (Examples) Implications
Strong recommendation, Desirable effects clearly Consistent evidence from well- Recommendation can apply to most
high-quality evidence outweigh undesirable effects, performed patients in most circumstances.
or vice versa RCTs or exceptionally strong Further research is unlikely to
evidence from unbiased change our confidence in the
observational studies estimate of effect.
Strong recommendation, Desirable effects clearly Evidence from RCTs with Recommendation can apply to most
moderate-quality outweigh undesirable effects, important limitations patients in most circumstances.
evidence or vice versa (inconsistent results, Further research (if performed) is
methodological flaws, indirect, or likely to have an important impact on
imprecise) or exceptionally our confidence in the estimate of
strong evidence from unbiased effect and may change the
observational studies estimate.
Strong recommendation, Desirable effects clearly Evidence for at least 1 critical Recommendation may change when
low-quality evidence outweigh undesirable effects, outcome from observational higher-quality evidence becomes
or vice versa studies, RCTs with serious flaws available. Further research (if
or indirect evidence performed) is likely to have an

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important impact on our confidence
in the estimate of effect and is likely
to change the estimate.
Strong recommendation, Desirable effects clearly Evidence for at least 1 critical Recommendation may change when
very low-quality outweigh undesirable effects, outcome from unsystematic higher-quality evidence becomes
evidence (very rarely or vice versa clinical observations or very available; any estimate of effect for
applicable) indirect evidence at least 1 critical outcome is very
uncertain.
Weak recommendation, Desirable effects closely Consistent evidence from well- The best action may differ depending
high-quality evidence balanced with undesirable performed on circumstances, patients, or
effects RCTs or exceptionally strong societal values. Further research is
evidence from unbiased unlikely to change our confidence in
observational studies the estimate of effect.
Weak recommendation, Desirable effects closely Evidence from RCTs with Alternative approaches likely to be
moderate-quality balanced with undesirable important limitations better for some patients under
evidence effects (inconsistent results, some circumstances. Further
methodological flaws, indirect, or research (if performed) is likely to
imprecise) or exceptionally have an important impact on our
strong evidence from unbiased confidence in the estimate of effect
observational studies and may change the estimate.
Weak recommendation, Uncertainty in the estimates of Evidence for at least 1 critical Other alternatives may be equally
low-quality evidence desirable effects, harms, and outcome from observational reasonable. Further research is very
burden; desirable effects, studies, RCTs with serious flaws likely to have an important impact on
harms, and burden may be or indirect evidence our confidence in the estimate of
closely balanced effect and is likely to change the
estimate.
Weak recommendation, Major uncertainty in the estimates Evidence for at least 1 critical Other alternatives may be equally
very low-quality of desirable effects, harms, and outcome from unsystematic reasonable. Any estimate of effect,
evidence burden; desirable effects may clinical observations or very for at least 1 critical outcome, is very
or may not be balanced with indirect evidence uncertain.
undesirable effects

Abbreviation: RCT, randomized controlled trial.

background, and evidence summaries that support each recom- 1. Specialists who care for immunocompromised patients
mendation can be found in the full text of the guidelines. share responsibility with the primary care provider for en-
suring that appropriate vaccinations are administered to im-
RECOMMENDATIONS FOR RESPONSIBILITY munocompromised patients (strong, low).
FOR VACCINATION 2. Specialists who care for immunocompromised patients
share responsibility with the primary care provider for rec-
I. Who Is Responsible for Vaccinating Immunocompromised ommending appropriate vaccinations for members of im-
Patients and Members of Their Household? munocompromised patients’ household (strong, very low).

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e45

RECOMMENDATIONS FOR TIMING OF vaccines for travel: yellow fever vaccine (strong, moderate)
VACCINATION and oral typhoid vaccine (strong, low).
9. Oral polio vaccine (OPV) should not be administered to
II. When Should Vaccines Be Administered to Immunocompe- individuals who live in a household with immunocompro-
tent Patients in Whom Initiation of Immunosuppressive Medi- mised patients (strong, moderate).
cations Is Planned? 10. Highly immunocompromised patients should avoid han-
3. Vaccines should be administered prior to planned immu- dling diapers of infants who have been vaccinated with rotavi-
nosuppression if feasible (strong, moderate). rus vaccine for 4 weeks after vaccination (strong, very low).
4. Live vaccines should be administered ≥4 weeks prior to im- 11. Immunocompromised patients should avoid contact
munosuppression (strong, low) and should be avoided within with persons who develop skin lesions after receipt VAR or
2 weeks of initiation of immunosuppression (strong, low). ZOS until the lesions clear (strong, low).
5. Inactivated vaccines should be administered ≥2 weeks
prior to immunosuppression (strong, moderate). VACCINES FOR INTERNATIONAL TRAVEL

RECOMMENDATIONS FOR VACCINES FOR IV. Which Vaccines Can Be Administered to Immunocompro-
HOUSEHOLD MEMBERS OF mised Persons Contemplating International Travel?
IMMUNOCOMPROMISED PATIENTS

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12. Clinicians may administer inactivated vaccines indicated
III. Which Vaccines Can Be Safely Administered to Individuals for travel based on the CDC annual schedule for immuno-
Who Live in a Household With Immunocompromised Pa- competent adults and children (strong, low).
tients? What Precautions Should Immunocompromised Pa- 13. Yellow fever vaccine generally should not be administered
tients Observe After Vaccination of Household Members? to immunocompromised persons (strong, moderate). If travel
to an endemic area cannot be avoided, vaccination can be
6. Immunocompetent individuals who live in a household
considered in the following minimally immunocompromised
with immunocompromised patients can safely receive inacti-
human immunodeficiency virus (HIV)–infected individuals:
vated vaccines based on the CDC–ACIP’s annually updated
(a) asymptomatic HIV-infected adults with CD4 T-cell
recommended vaccination schedules for children and adults
lymphocyte count ≥200 cells/mm3 (weak, low)
(hereafter, CDC annual schedule; strong, high) or for travel
(b) asymptomatic HIV-infected children aged 9 months–5
(strong, moderate).
years with CD4 T-cell lymphocyte percentages of ≥15
7. Individuals who live in a household with immunocom-
(weak, very low).
promised patients age ≥6 months should receive influenza
14. With certain exceptions (eg, yellow fever vaccine and
vaccine annually (strong, high). They should receive either:
MMR vaccine in certain HIV-infected patients [see recom-
(a) Inactivated influenza vaccine (IIV; strong, high) or
mendation 13 and “Recommendations for vaccination of HIV-
(b) Live attenuated influenza vaccine (LAIV) provided they
infected adults, adolescents, and children” section] and in certain
are healthy, not pregnant, and aged 2–49 years (strong,
HSCT patients [see “Recommendations for vaccination of he-
low). Exceptions include individuals who live in a
matopoietic stem cell transplant patients”]), live vaccines should
household with an immunocompromised patient who
not be given to immunocompromised persons (strong, low).
was a hematopoietic stem cell transplant (HSCT) recip-
ient within 2 months after transplant or with graft vs
host disease (GVHD) or is a patient with severe com- RECOMMENDATIONS FOR VARICELLA AND
bined immune deficiency (SCID). In these exceptions, ZOSTER VACCINES IN IMMUNOCOMPROMISED
LAIV should not be administered (weak, very low) or, PATIENTS
if administered, contact between the immunocompro-
VAR
mised patient and household member should be
V. Should Immunocompromised Patients or Those Scheduled
avoided for 7 days (weak, very low).
to Receive Immune Suppressive Therapy Receive VAR?
8. Healthy immunocompetent individuals who live in a
household with immunocompromised patients should 15. VAR should be given to immunocompetent patients
receive the following live vaccines based on the CDC annual without evidence of varicella immunity (ie, age-appropriate
schedule: combined measles, mumps, and rubella (MMR) varicella vaccination, serologic evidence of immunity,
vaccines (strong, moderate); rotavirus vaccine in infants clinician-diagnosed or -verified history of varicella or zoster,
aged 2–7 months (strong, low); varicella vaccine (VAR; or laboratory-proven varicella or zoster; strong, moderate) if
strong, moderate); and zoster vaccine (ZOS; strong, moder- it can be administered ≥4 weeks before initiating immuno-
ate). Also, these individuals can safely receive the following suppressive therapy (strong, low).

e46 • CID 2014:58 (1 February) • Rubin et al

 16. A 2-dose schedule of VAR, separated by >4 weeks for pa- RECOMMENDATIONS FOR VACCINATION OF
tients aged ≥13 years and by ≥3 months for patients aged PATIENTS WITH PRIMARY
1–12 years, is recommended if there is sufficient time prior IMMUNODEFICIENCY DISORDERS
to initiating immunosuppressive therapy (strong, low).
17. VAR should not be administered to highly immunocom- VIII. Which Vaccines Should Be Administered to Patients
promised patients. However, certain categories of patients (eg, With Primary (Congenital) Complement Deficiencies?
patients with HIV infection without severe immunosuppres- 26. Patients with primary complement deficiencies should
sion or with a primary immune deficiency disorder without receive all routine vaccines based on the CDC annual sched-
defective T-cell–mediated immunity, such as primary com- ule; none are contraindicated (strong, low).
plement component deficiency disorder or chronic granulo- 27. Patients with primary complement deficiencies and who are
matous disease [CGD]) should receive VAR, adhering to a 2- (a) aged 2–5 years should receive 1 dose of 13-valent pneu-
dose schedule separated by a 3-month interval (strong, mod- mococcal conjugate vaccine (PCV13) if they have re-
erate). ceived 3 doses of PCV (either 7-valent PCV [PCV7] or
18. VAR can be considered for patients without evidence of PCV13) before age 24 months and 2 doses of PCV13 (8
varicella immunity (defined in recommendation 16) who are weeks apart) if they have received an incomplete sched-
receiving long-term, low-level immunosuppression (weak, very ule of ≤2 doses of PCV7 (PCV7 or PCV13) before age
low).

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24 months (strong, low).
19. VAR should be administered to eligible immunocom- (b) aged 6–18 years with a classic pathway (C1, C2, C3, C4),
promised patients as the single antigen product, not VAR alternate pathway, or severe mannan-binding lectin
combined with MMR vaccine (strong, low). (MBL) deficiency who have not received PCV13 should
VI. Should Immunocompromised Patients or Those Who Will receive a single dose of PCV13 (strong, very low).
Undergo Immunosuppression Receive Herpes Zoster Vaccine? (c) aged ≥19 years with a classic pathway (C1, C2, C3, C4), al-
ternate pathway, or severe MBL deficiency who are PCV13
20. ZOS should be given to patients aged ≥60 years if it can
naive should receive a single dose of PCV13 (strong, very
be administered ≥4 weeks before beginning highly immuno-
low). For those who received pneumococcal polysaccharide
suppressive therapy (strong, low).
vaccine-23 (PPSV23), PCV13 should be administered ≥1
21. ZOS should be considered for varicella-positive patients
year after the last PPSV23 dose (weak, low)
(ie, persons with a history of varicella or zoster infection or
28. Patients aged ≥2 years with an early classic pathway, al-
who are varicella–zoster virus [VZV] seropositive with no
ternate pathway, or severe MBL deficiency should receive
previous doses of VAR) aged 50–59 years if it can be admin-
PPSV23 ≥8 weeks after PCV13, and a second dose of
istered ≥4 weeks before beginning immunosuppressive
PPSV23 should be given 5 years later (strong, low).
therapy (weak, low).
29. Patients with primary complement deficiencies should
22. ZOS should be administered to patients aged ≥60 years
receive conjugate meningococcal vaccine. A 4-dose series of
who are receiving therapy considered to induce a low level of
bivalent meningococcal conjugate vaccine and Haemophilus
immunosuppression (strong, low).
influenzae type b conjugate vaccine (HibMenCY; MenHi-
23. ZOS should not be administered to highly immunocom-
brix, GlaxoSmithKline) should be administered at age 2, 4, 6,
promised patients (strong, very low).
and 12–15 months for children aged 6 weeks–18 months
(strong, low) or a 2-dose primary series of meningococcal
RECOMMENDATIONS FOR INFLUENZA VACCINE conjugate vaccine, quadrivalent (MCV4) should be adminis-
IN THE IMMUNOCOMPROMISED HOST tered to patients with primary complement component defi-
ciency at age 9 months–55 years (MCV4-D [Menactra,
VII. Should Immunocompromised Persons Receive Influenza Sanofi Pasteur] for those aged 9–23 months; MCV4-D or
Vaccine? MCV4-CRM [Menveo, Novartis; CRM, diphtheria CRM197
24. Annual vaccination with IIV is recommended for immu- protein] for those aged 2–54 years; strong, low). For persons
nocompromised patients aged ≥6 months (strong, moderate) aged >55 years, MPSV4 (meningococcal polysaccharide
except for patients who are very unlikely to respond (although vaccine, quadrivalent) should be administered if they have
unlikely to be harmed by IIV), such as those receiving inten- not received MCV4 and MCV4 should be administered if
sive chemotherapy (strong, low) or those who have received they have received MCV4 (strong, low). For patients aged
anti–B-cell antibodies within 6 months (strong, moderate). 9–23 months, the doses should be administered 3 months
25. LAIV should not be administered to immunocompro- apart; for patients aged ≥2 years, the doses should be admin-
mised persons (weak, very low). istered 2 months apart. MCV4-D should be administered ≥4

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e47

 weeks after a dose of PCV13 because of a reduced antibody cytokine generation/response or cellular activation/inflam-
response to some pneumococcal serotypes when MCV4-D mation generation (strong, low).
and PCV7 are administered simultaneously (strong, low). 40. Live bacterial vaccines should not be administered to pa-
30. Patients with a primary complement component defi- tients with defects of the interferon-gamma/interleukin-12
ciency should be revaccinated with MCV4 (or MPSV4 for (IFN-γ/IL-12) pathways (strong, moderate).
those aged >55 years who have not received MCV4) every 5 41. Live viral vaccines should not be administered to patients
years (strong, low). with defects of IFN (alpha or gamma) production (strong, low).

IX. Which Vaccines Should Be Administered to Patients XI. Which Vaccines Should Be Administered to Patients
With Phagocytic Cell Deficiencies (eg, CGD, Leukocyte Adhe- With Minor Antibody Deficiencies?
sion Deficiency, Chediak–Higashi Syndrome)?

31. Patients with phagocytic cell deficiencies should receive 42. Patients with immunoglobulin (Ig)A deficiency or spe-
all inactivated vaccines based on the CDC annual schedule cific polysaccharide antibody deficiency (SPAD) should
(strong, low). Children aged 2–5 years should receive PCV13 receive all routine vaccinations based on the CDC annual
as in recommendation 27a (weak, very low). schedule, provided that other components of their immune
32. Patients aged ≥6 years with phagocytic cell deficiencies systems are normal (strong, low).
43. Children with SPAD or ataxia–telangiectasia should

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other than CGD (unless patient with CGD is receiving im-
munosuppressive medication) should receive PCV13 as in receive PCV13 as described in recommendations 27a–c (weak
recommendations 27b and 27c (weak, very low). to strong, very low to low). Those aged ≥2 years should receive
33. Patients aged ≥2 years with phagocytic cell deficiencies PPSV23 ≥8 weeks after indicated doses of PCV13, and a
other than CGD (unless patient with CGD is receiving im- second dose should be given 5 years later (strong, low).
munosuppressive medication) should receive PPSV23 ≥8 44. Monitoring of vaccine responses can be useful for assessing
weeks after receipt of PCV13, and a second dose of PPSV23 the degree of immunodeficiency of patients with minor anti-
should be given 5 years later (weak, low). body deficiencies and level of protection (weak, moderate).
34. Live bacterial vaccines, such as bacillus Calmette–Guérin 45. OPV should not be administered to IgA-deficient pa-
(BCG) or oral typhoid vaccine, should not be administered tients (strong, low).
to patients with a phagocytic cell defect (strong, moderate).
XII. Which Vaccines Should Be Administered to Patients
35. Live viral vaccines should be administered to patients
With Major Antibody Deficiencies Who are Receiving Immu-
with CGD and to those with congenital or cyclical neutrope-
noglobulin Therapy?
nia (weak, low).
36. Live viral vaccines should not be administered to pa- 46. Inactivated vaccines other than IIV are not routinely ad-
tients with leukocyte adhesion deficiency, defects of cytotox- ministered to patients with major antibody deficiencies
ic granule release such as Chediak–Higashi syndrome, during immunoglobulin therapy (strong, low).
question XIII, recommendations 50-or any other undefined (a) For patients with suspected major antibody deficien-
phagocytic cell defect (strong, low). cies, all inactivated vaccines can be administered as part
X. Which Vaccines Should Be Administered to Patients of immune response assessment prior to immunoglob-
With Innate Immune Defects that Result in Defects of Cytokine ulin therapy (strong, low).
Generation/Response or Cellular Activation (eg, Defects of the 47. IIV can be administered to patients with major antibody de-
Interferon-gamma/Interleukin-12 Axis)? ficiencies and some residual antibody production (weak, low).
48. Live OPV should not be administered to patients with
37. Patients with innate immune defects that result in major antibody deficiencies (strong, moderate).
defects of cytokine generation/response or cellular activation 49. Live vaccines (other than OPV) should not be adminis-
should receive all inactivated vaccines based on the CDC tered to patients with major antibody deficiencies (weak, low).
annual schedule (strong, very low).
38. For patients with innate immune defects that result in XIII. Which Vaccines Should Be Administered to Patients
defects of cytokine generation/response or cellular activa- With Combined Immunodeficiencies?
tion, PCV13 should be administered as in recommendations
27a–c (weak to strong, very low to low). 50. For patients with suspected combined immunodeficien-
39. The advice of a specialist should be sought regarding in- cies, all inactivated vaccines can be administered as part
dividual conditions concerning use of live vaccines in pa- immune response assessment prior to commencement of
tients with innate immune defects that result in defects of immunoglobulin therapy (strong, low).

e48 • CID 2014:58 (1 February) • Rubin et al

 (a) For patients with combined immunodeficiencies who are 57. HIV-infected children who are aged >59 months and
receiving immunoglobulin therapy, inactivated vaccines have not received Hib vaccine should receive 1 dose of Hib
should not be routinely administered (strong, low). vaccine (strong, low). Hib vaccine is not recommended for
51. For patients with combined immunodeficiencies and re- HIV-infected adults (weak, low).
sidual antibody production potential, IIV can be adminis- 58. HIV-infected children aged 11–18 years should receive a
tered (weak, very low). 2-dose primary series of MCV4 2 months apart (strong,
52. Children with partial DiGeorge syndrome ( pDGS) moderate). A single booster dose (third dose) should be
should undergo immune system assessment with evaluation given at age 16 years if the primary series was given at age 11
of lymphocyte subsets and mitogen responsiveness in order or 12 years and at age 16–18 years if the primary series was
to determine whether they should be given live viral vac- given at age 13–15 years (strong, low). If MCV4 is adminis-
cines. Those with ≥500 CD3 T cells/mm3, ≥200 CD8 T tered to HIV-infected children aged 2–10 years because of
cells/mm3, and normal mitogen response should receive risk factors for meningococcal disease, a 2-dose primary
MMR vaccine and VAR (weak, low). series of MCV4 should be administered with a 2-month in-
53. Patients with SCID, DGS with a CD3 T-cell lymphocyte terval between doses, and a booster dose should be given 5
count <500 cells/mm3, other combined immunodeficiencies years later (strong, very low).
with similar CD3 T-cell lymphocyte counts, Wiskott–Aldrich 59. HIV-infected patients should receive the HepB vaccine

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syndrome, or X-linked lymphoproliferative disease and familial series (strong, moderate), with consideration of high-dose
disorders that predispose them to hemophagocytic lymphohis- HepB vaccine (40 µg/dose) for adults (weak, moderate) and
tiocytosis should avoid all live vaccines (strong, moderate). adolescents (weak, low). One to 2 months after completion,
patients should be tested for anti-HBs (antibodies to HepB
RECOMMENDATIONS FOR VACCINATION OF surface antigen; strong, low). If a postvaccination anti-HB
HIV-INFECTED ADULTS, ADOLESCENTS, AND concentration of ≥10 mIU/mL is not attained, a second
CHILDREN 3-dose series of HepB vaccine (strong, low; alternative: 1
dose of HepB vaccine after which anti-HBs is tested ), using
XIV. Which Inactivated Vaccines Should Be Administered to standard dose (strong, moderate) or high dose (40 µg ;
HIV-Infected Patients? weak, low) for children and high dose for adolescents and
adults (strong, low), should be administered.
54. HIV-infected patients should be vaccinated according to
60. HepB vaccine containing 20 µg of HepB surface antigen
the CDC annual schedule for the following inactivated vac-
(HBsAg) combined with HepA vaccine (HepA–HepB;
cines: IIV (strong, high); PCV13 in patients aged <2 years
Twinrix), 3-dose series, can be used for primary vaccination of
(strong, moderate); H. influenzae type b conjugate (Hib)
HIV-infected patients aged ≥12 years (strong, moderate).
vaccine (strong, high); diphtheria toxoid, tetanus toxoid,
61. Internationally adopted HIV-infected children who have
acellular pertussis (DTaP) vaccine (strong, moderate);
received doses of OPV should receive a total of 4 doses of a
tetanus toxoid, reduced diphtheria toxoid, and reduced acel-
combination of OPV and IPV vaccine (strong, low).
lular pertussis (Tdap) vaccine (strong, very low); tetanus
62. HPV4 vaccine is recommended over bivalent human
toxoid, reduced diphtheria toxoid (Td) vaccine (strong, low);
papillomavirus (HPV2) vaccine because HPV4 vaccine pre-
hepatitis B (HepB) vaccine (strong, moderate); hepatitis A
vents genital warts (strong, low), although there are no data
(HepA) vaccine (strong, moderate); inactivated poliovirus
on differences between the vaccines for preventing cervical
(IPV) vaccine (strong, moderate); and quadrivalent human
dysplasia in HIV-infected women.
papillomavirus (HPV4) vaccine in females and males aged
11–26 years (strong, very low) with additions noted below.
55. PCV13 should be administered to HIV-infected patients XV. Should Live Vaccines Be Administered to HIV-Infected
aged ≥2 years as in recommendations 27a–c (strong, low to Patients?
moderate).
56. PPSV23 should be administered to HIV-infected chil- 63. HIV-exposed or -infected infants should receive rotavi-
dren aged ≥2 years of age who have received indicated doses rus vaccine according to the schedule for uninfected infants
of PCV (strong, moderate), HIV-infected adults with CD4 (strong, low).
T-lymphocyte counts of ≥200 cells/mm3 (strong, moderate), 64. HIV-infected patients should not receive LAIV (weak,
and HIV-infected adults with CD4 T-lymphocyte counts of very low).
<200 cells/mm3 (weak, low). PPSV23 should be given ≥8 65. MMR vaccine should be administered to clinically stable
weeks after indicated dose(s) of PCV13, and a second dose HIV-infected children aged 1–13 years without severe im-
of PPSV23 should be given 5 years later (strong, low). munosuppression (strong, moderate) and HIV-infected

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e49

 patients aged ≥14 years without measles immunity and with RECOMMENDATIONS FOR VACCINATION OF
a CD4 T-cell lymphocyte count ≥200/mm3 (weak, very HEMATOPOIETIC STEM CELL TRANSPLANT
low). PATIENTS
66. HIV-infected children with a CD4 T-cell percentage <15
(strong, moderate) or patients aged ≥14 years with a CD4 T- XVII. Should HSCT Donors and Patients Be Vaccinated Before
cell lymphocyte count <200 cells/mm3 should not receive Transplantation?
MMR vaccine (strong, moderate). 74. The HSCT donor should be current with routinely recom-
67. HIV-infected patients should not receive quadrivalent mended vaccines based on age, vaccination history, and expo-
MMR-varicella (MMRV) vaccine (strong, very low). sure history according to the CDC annual schedule (strong,
68. Varicella-nonimmune, clinically stable HIV-infected high). However, administration of MMR, MMRV, VAR, and
patients aged 1–8 years with ≥15% CD4 T-lymphocyte per- ZOS vaccines should be avoided within 4 weeks of stem cell
centage (strong, high), aged 9–13 years with ≥15% CD4 harvest (weak, very low). Vaccination of the donor for the
T-lymphocyte percentage (strong, very low), and aged ≥14 benefit of the recipient is not recommended (weak, moderate).
years with CD4 T-lymphocyte counts ≥200 cells/mm3 75. Prior to HSCT, candidates should receive vaccines indicat-
should receive VAR (strong, very low). The 2 doses should ed for immunocompetent persons based on age, vaccination
be separated by ≥3 months (strong, moderate). history, and exposure history according to the CDC annual

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schedule if they are not already immunosuppressed (strong,
RECOMMENDATIONS FOR VACCINATION IN very low to moderate) and when the interval to start of the
PATIENTS WITH CANCER conditioning regimen is ≥4 weeks for live vaccines (strong,
low) and ≥2 weeks for inactivated vaccines (strong, moderate).
XVI. What Vaccines Should Be Given to Patients With Cancer?
76. Nonimmune HSCT candidates aged ≥12 months should
69. Patients aged ≥6 months with hematological malignan- receive VAR (as a 2-dose regimen if there is sufficient time)
cies (strong, moderate) or solid tumor malignancies (strong, if they are not immunosuppressed and when the interval to
low) except those receiving anti–B-cell antibodies (strong, start the conditioning regimen is ≥4 weeks (strong, low).
moderate) or intensive chemotherapy, such as for induction
XVIII. Which Vaccines Should Be Administered to Adults
or consolidation chemotherapy for acute leukemia (weak,
and Children After HSCT?
low), should receive IIV annually.
70. PCV13 should be administered to newly diagnosed adults 77. One dose of IIV should be administered annually (strong,
with hematological (strong, very low) or solid malignancies moderate) to persons aged ≥6 months starting 6 months after
(strong, very low) and children with malignancies (strong, very HSCT (strong, moderate) and starting 4 months after if there
low) as described in recommendations 27a-c. PPSV23 should is a community outbreak of influenza as defined by the local
be administered to adults and children aged ≥2 years (strong, health department (strong, very low). For children aged 6
low) at least 8 weeks after the indicated dose(s) of PCV13. months–8 years who are receiving influenza vaccine for the
71. Inactivated vaccines (other than IIV) recommended for first time, 2 doses should be administered (strong, low).
immunocompetent children in the CDC annual schedule 78. Three doses of PCV13 should be administered to adults and
can be considered for children who are receiving mainte- children starting at age 3–6 months after HSCT (strong, low). At
nance chemotherapy (weak, low). However, vaccines admin- 12 months after HSCT, 1 dose of PPSV23 should be given pro-
istered during cancer chemotherapy should not be vided the patient does not have chronic GVHD (strong, low).
considered valid doses (strong, low) unless there is docu- For patients with chronic GVHD, a fourth dose of PCV13 can
mentation of a protective antibody level (strong, moderate). be given at 12 months after HSCT (weak, very low).
72. Live viral vaccines should not be administered during 79. Three doses of Hib vaccine should be administered 6–12
chemotherapy (strong, very low to moderate). months after HSCT (strong, moderate).
73. Three months after cancer chemotherapy, patients 80. Two doses of MCV4 should be administered 6–12 months
should be vaccinated with inactivated vaccines (strong, very after HSCT to persons aged 11–18 years, with a booster dose
low to moderate) and the live vaccines for varicella (weak, given at age 16–18 years for those who received the initial
very low); measles, mumps, and rubella (strong, low); and post-HSCT dose of vaccine at age 11–15 years (strong, low).
measles, mumps, and rubella– varicella (weak, very low) ac- 81. Three doses of tetanus/diphtheria–containing vaccine should
cording to the CDC annual schedule that is routinely indi- be administered 6 months after HSCT (strong, low). For children
cated for immunocompetent persons. In regimens that aged <7 years, 3 doses of DTaP should be administered (strong,
included anti–B-cell antibodies, vaccinations should be low). For patients aged ≥7 years, administration of 3 doses of
delayed at least 6 months (strong, moderate). DTaP should be considered (weak, very low). Alternatively, a

e50 • CID 2014:58 (1 February) • Rubin et al

 dose of Tdap vaccine should be administered followed by either aged <6 years and have end-stage kidney, heart, or lung
2 doses of diphtheria toxoid combined with tetanus toxoid disease; or are aged 6–18 years and have end-stage kidney
(DT) (weak, moderate) or 2 doses of Td vaccine (weak, low). disease should receive PCV13 as in recommendations 27a-c
82. Three doses of HepB vaccine should be administered 6– (strong, very low).
12 months after HSCT (strong, moderate). If a postvaccina- 91. Adults and children aged ≥2 years who are SOT candi-
tion anti-HBs concentration of ≥10 mIU/mL is not attained, dates or have end-stage kidney disease should receive PPSV23
a second 3-dose series of HepB vaccine (strong, low; alterna- if they have not received a dose within 5 years and have not re-
tive: 1 dose of HepB vaccine after which anti-HBs is tested ), ceived 2 lifetime doses (strong, moderate). Patients with end-
using standard dose (strong, moderate) or high dose (40 µg ; stage kidney disease should receive 2 lifetime doses 5 years
weak, low) for children and high dose for adolescents and apart (strong, low). Adults and children aged ≥2 years with
adults (strong, low), should be administered. end-stage heart or lung disease as well as adults with chronic
83. Three doses of IPV vaccine should be administered 6–12 liver disease, including cirrhosis, should receive a dose of
months after HSCT (strong, moderate). PPSV23 if they have never received a dose (strong, low). When
84. Consider administration of 3 doses of HPV vaccine 6–12 both PCV13 and PPSV23 are indicated, PCV13 should be
months after HSCT for female patients aged 11–26 years and completed 8 weeks prior to PPSV23 (strong, moderate).
HPV4 vaccine for males aged 11–26 years (weak, very low). 92. Anti-HBs–negative SOT candidates should receive the

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85. Do not administer live vaccines to HSCT patients with HepB vaccine series (strong, moderate) and, if on hemodial-
active GVHD or ongoing immunosuppression (strong, low). ysis and aged ≥20 years, they should receive the high-dose
86. A 2-dose series of MMR vaccine should be administered (40 µg) HepB vaccine series (strong, moderate). If a postvac-
to measles-seronegative adolescents and adults (strong, low) cination anti-HBs concentration of ≥10 mIU/mL is not at-
and to measles-seronegative children (strong, moderate) 24 tained, a second 3-dose series of HepB vaccine (strong, low;
months after HSCT in patients with neither chronic GVHD alternative: 1 dose of HepB vaccine after which anti-HBs is
nor ongoing immunosuppression and 8–11 months (or tested ) should be administered, using standard dose
earlier if there is a measles outbreak) after the last dose of (strong, moderate) or high dose for children (weak, low)
immune globulin intravenous (IGIV). and high dose for adolescents and adults (strong, low).
87. A 2-dose series of VAR should be administered 24 HepA-unvaccinated, -undervaccinated, or -seronegative
months after HSCT to varicella-seronegative patients with SOT candidates ( particularly liver transplant candidates)
neither GVHD nor ongoing immunosuppression and 8–11 aged 12–23 months (strong, moderate) and ≥2 years (strong,
months after the last dose of IGIV (strong, low). moderate) should receive a HepA vaccine series.
93. Combined HepA–HepB vaccine can be used for SOT
candidates aged ≥12 years of age in whom both vaccines
RECOMMENDATIONS FOR VACCINATION OF are indicated (strong, moderate).
SOLID ORGAN TRANSPLANT RECIPIENTS 94. The HPV vaccine series should be administered to SOT
candidates aged 11–26 years (strong, low-moderate).
XIX. For Adult and Child Solid Organ Transplant Candidates
95. SOT candidates aged 6–11 months can receive MMR
and Living Donors, Which Vaccines Should Be Administered
vaccine if they are not receiving immunosuppression and if
During Pretransplant Evaluation?
transplantation is not anticipated within 4 weeks (weak, very
88. Living donors should be current with vaccines based on low). If transplantation is delayed (and the child is not re-
age, vaccination history, and exposure history according to ceiving immunosuppression), the MMR vaccine should be
the CDC annual schedule (strong, high); MMR, MMRV, repeated at 12 months (strong, moderate).
VAR, and ZOS vaccine administration should be avoided 96. The VAR should be administered to SOT candidates
within 4 weeks of organ donation (weak, very low). Vaccina- without evidence of varicella immunity (as defined in rec-
tion of donors solely for the recipient’s benefit is generally ommendation 16) if they are not receiving immunosuppres-
not recommended (weak, low). sion and if transplantation is not anticipated within 4 weeks
89. Adults and children with chronic or end-stage kidney, liver, (strong, moderate). The VAR can be administered to varicel-
heart, or lung disease, including solid organ transplant (SOT) la-naive SOT candidates aged 6–11 months who are not im-
candidates, should receive all age-, exposure history-, and munosuppressed provided the timing is ≥4 weeks prior to
immune status-appropriate vaccines based on the CDC annual transplant (weak, very low). Optimally, 2 doses should be
schedule for immunocompetent persons (strong, moderate). administered ≥3 months apart (strong, low).
90. Adult SOT candidates; adults with end-stage kidney 97. SOT candidates aged ≥60 years (strong, moderate) and
disease; and pediatric patients who are SOT candidates; are varicella-positive candidates (as defined in recommendation

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e51

 22) aged 50–59 years (weak, low) who are not severely im- (strong, low-moderate) or about to be treated (strong, mod-
munocompromised should receive ZOS if transplantation is erate) with immunosuppressive agents as for immunocom-
not anticipated within 4 weeks. petent persons based on the CDC annual schedule.
106. PCV13 should be administered to adults and children with
XX. Which Vaccines Should Be Administered to SOT Recip-
a chronic inflammatory illness that is being treated with immu-
ients?
nosuppression as described in the standard schedule for children
98. Vaccination should be withheld from SOT recipients and in recommendations 27a–c (strong, very low-moderate).
during intensified immunosuppression, including the first 107. PPSV23 should be administered to patients aged ≥2
2-month posttransplant period, because of the likelihood of years with chronic inflammatory illnesses with planned initia-
inadequate response (strong, low). However, IIV can be ad- tion of immunosuppression (strong, low), low-level immuno-
ministered ≥1 month after transplant during a community suppression (strong, low), and high-level immunosuppression
influenza outbreak (weak, very low). (strong, very low). Patients should receive PPSV23 ≥8 weeks
99. Standard age-appropriate inactivated vaccine series after PCV13, and a second dose of PPSV23 should be given 5
should be administered 2 to 6 months after SOT based on years later (strong, low).
the CDC annual schedule (strong, low to moderate), includ- 108. VAR should be administered to patients with chronic
ing IIV (strong, moderate). inflammatory diseases without evidence of varicella immu-
100. PCV13 should be administered 2 to 6 months after

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nity (defined in recommendation 15; strong, moderate) ≥4
SOT if not administered before SOT, with the timing based weeks prior to initiation of immunosuppression (strong,
on the patient’s degree of immunosuppression, as described low) if treatment initiation can be safely delayed.
in recommendations 27a–c (strong, very low to moderate). 109. VAR should be considered for patients without evi-
101. For SOT patients aged ≥2 years, 1 dose of PPSV23 dence of varicella immunity (defined in recommendation
should be administered 2 to 6 months after SOT, with the 15) being treated for chronic inflammatory diseases with
timing based on the patient’s degree of immunosuppression, long-term, low-level immunosuppression (weak, very low).
and ≥8 weeks after indicated doses of PCV13, if not given 110. ZOS should be administered to patients with chronic in-
within 5 years and if the patient has received no more than 1 flammatory disorders who are aged ≥60 years prior to initia-
previous lifetime dose (strong, moderate). tion of immunosuppression (strong, low) or being treated with
102. HepB vaccine should be considered for chronic HepB- low-dose immunosuppression (strong, very low) and those
infected recipients 2 to 6 months after liver transplant in an who are aged 50–59 years and varicella positive prior to initia-
attempt to eliminate the lifelong requirement for HepB tion of immunosuppression (weak, low) or being treated with
immune globulin (HBIG; weak, low). low-dose immunosuppression (weak, very low).
103. MMR vaccine and VAR should generally not be admin- 111. Other live vaccines should not be administered to pa-
istered to SOT recipients because of insufficient safety and tients with chronic inflammatory diseases on maintenance
effectiveness data (strong, low), except for varicella in chil- immunosuppression: LAIV (weak, very low), MMR vaccine
dren without evidence of immunity (as defined in recom- in patients receiving low-level (weak, very low) and high-
mendation 15) who are renal or liver transplant recipients, level immunosuppression (weak, very low); and MMRV
are receiving minimal or no immunosuppression, and have vaccine in patients receiving low-level (weak, very low) and
no recent graft rejection (weak, moderate). high-level immunosuppression (strong, very low).
104. Vaccination should not be withheld because of concern 112. Other recommended vaccines, including IIV and HepB
about transplant organ rejection (strong, moderate). vaccine, should not be withheld because of concerns about
exacerbation of chronic immune-mediated or inflammatory
illness (strong, moderate).
RECOMMENDATIONS FOR VACCINATION OF
PATIENTS WITH CHRONIC INFLAMMATORY
DISEASES ON IMMUNOSUPPRESSIVE RECOMMENDATIONS FOR VACCINATION OF
MEDICATIONS PATIENTS WITH ASPLENIA OR SICKLE CELL
DISEASES
XXI. Which Vaccines Should Be Administered to Patients With
Chronic Inflammatory Diseases Maintained on Immunosup- XXII. Which Vaccines Should Be Administered to Asplenic Pa-
pressive Therapies? tients and Those With Sickle Cell Diseases?
105. Inactivated vaccines, including IIV, should be adminis- 113. Asplenic patients and those with sickle cell diseases
tered to patients with chronic inflammatory illness treated should receive vaccines including PCV13 for children aged <2

e52 • CID 2014:58 (1 February) • Rubin et al

 years, as recommended routinely for immunocompetent 121. Patients aged ≥24 months with a cochlear implant,
persons based on the CDC annual schedule. No vaccine is con- profound deafness and scheduled to receive a cochlear
traindicated (strong, moderate) except LAIV (weak, very low). implant, or persistent communications between the CSF and
114. PCV13 should be administered to asplenic patients and oropharynx or nasopharynx should receive PPSV23, prefera-
patients with sickle cell diseases aged ≥2 years based on the bly ≥8 weeks after receipt of PCV13 (strong, moderate).
CDC annual schedule for children and in recommendations 122. PCV13 and PPSV23 should be administered ≥2 weeks
27a–c (strong, very low-moderate). prior to cochlear implant surgery, if feasible (strong, low).
115. PPSV23 should be administered to asplenic patients and
patients with a sickle cell disease aged ≥2 years (strong, low) INTRODUCTION
with an interval of ≥8 weeks after PCV13, and a second dose
of PPSV23 should be administered 5 years later (strong, low). Vaccination of immunocompromised patients is important
116. For PPSV23-naive patients aged ≥2 years for whom a sple- because impaired host defenses predispose patients to an in-
nectomy is planned, PPSV23 should be administered ≥2 weeks creased risk or severity of vaccine-preventable infection. These
prior to surgery (and following indicated dose(s) of PCV13; patients may also have greater exposure to pathogens due to fre-
strong, moderate) or ≥2 weeks following surgery (weak, low). quent contact with medical environments [1]; however, vacci-
117. One dose of Hib vaccine should be administered to un- nation rates are frequently low [2–4]. Undervaccination of

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vaccinated persons aged ≥5 years who are asplenic or have a immunocompromised patients may occur because clinicians
sickle cell disease (weak, low). have insufficient or inaccurate information concerning the
118. Meningococcal vaccine should be administered to pa- safety, efficacy, and contraindication to vaccination of such pa-
tients aged ≥2 months who are asplenic or have a sickle cell tients. Specialty clinicians may lack the infrastructure needed to
disease (strong, low), as in recommendation 29. However, administer vaccines to their at-risk patient populations.
MCV4-D should not be administered in patients aged <2 Data on safety, immunogenicity, and efficacy/effectiveness of
years because of a reduced antibody response to some pneu- vaccines for immunocompromised populations are limited. Pre-
mococcal serotypes when both MCV4 and PCV are adminis- licensure studies often exclude immunocompromised persons,
tered simultaneously (strong, low). Revaccination with MCV4 and postlicensure studies examine small numbers of immuno-
(or MPSV4 for those aged >55 years who have not received compromised patients. These small numbers are problematic
MCV4) is recommended every 5 years (strong, low). when assessing adverse effects [5]. Furthermore, immune defects
vary among and within categories of patients with immune defi-
ciencies (eg, degree of immune deficiency, nutritional status, im-
munosuppressive regimen), which may limit the generalizability
RECOMMENDATIONS FOR VACCINATION OF of study findings.
PATIENTS WITH ANATOMIC BARRIER DEFECTS The objective of this guideline is to provide primary care and
AT RISK FOR INFECTIONS WITH VACCINE- specialty clinicians with evidence-based recommendations for
PREVENTABLE PATHOGENS active vaccination of immunocompromised patients and
members of their household in order to safely prevent vaccine-
XXIII. Which Vaccinations Should Be Given to Individuals
preventable infections, with the ultimate goal of decreasing asso-
With Cochlear Implants or Congenital Dysplasias of the Inner
ciated morbidity and mortality. Recommended vaccination
Ear or Persistent Cerebrospinal Fluid Communication With the
schedules for immunocompetent adults and children as well as
Oropharynx or Nasopharynx?
certain groups at high risk for vaccine-preventable infections are
119. Adults and children with profound deafness scheduled updated and published annually by the Centers for Disease
to receive a cochlear implant, congenital dysplasias of the Control and Prevention (CDC), the American Academy of
inner ear, or persistent cerebrospinal fluid (CSF) communi- Pediatrics (AAP), and the American Association of Family Phy-
cation with the oropharynx or nasopharynx should receive sicians [5]. Additional information on vaccination of immuno-
all vaccines recommended routinely for immunocompetent compromised patients is also available, for example, guidelines
persons based on the CDC annual schedule. No vaccine is for use of specific vaccines and guidelines for particular popula-
contraindicated (strong, moderate). tions [6–14], but comprehensive guidelines are not.
120. Patients with a cochlear implant, profound deafness and
scheduled to receive a cochlear implant, or persistent commu- SCOPE OF GUIDELINE
nications between the CSF and oropharynx or nasopharynx
should receive PCV13 as described in the standard schedule for This guideline addresses children and adults with primary
children and recommendations 27a–c (strong, low-moderate). (congenital) immune deficiencies; patients with secondary

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e53

immune deficiencies due to HIV infection, cancers associated [CGD], leukocyte adhesion deficiency, Chediak–Higashi syn-
with immune deficiency, cancer chemotherapy, stem cell or drome)?
solid organ transplant (SOT), sickle cell diseases, and surgical 10. Which vaccines should be administered to patients with
asplenia; and patients with chronic inflammatory diseases innate immune defects that result in defects of cytokine genera-
treated with systemic corticosteroid therapy, immunomodula- tion/response or cellular activation (eg, defects of the interfer-
tor medications, and/or biologic agents. Vaccination of immu- on-gamma/interleukin-12 [IFN-γ/IL-12] axis)?
nocompetent patients who have an anatomic host defense 11. Which vaccines should be administered to patients with
abnormality (eg, cerebrospinal fluid [CSF] leak) associated with minor antibody deficiencies?
vaccine-preventable infections and of individuals living in a 12. Which vaccines should be administered to patients with
household with immunocompromised patients is also ad- major antibody deficiencies who are receiving immunoglobulin
dressed. Vaccination of neonates (including premature neo- therapy?
nates), the elderly, burn patients, and pregnant women is 13. Which vaccines should be administered to patients with
beyond the scope of this guideline. combined immunodeficiencies?
This guideline addresses vaccines routinely recommended 14. Which inactivated vaccines should be administered to
on the basis of patient age, social or occupational history, in- human immunodeficiency virus (HIV)-infected patients?
creased risk of infection related to underlying disease or treat- 15. Should live vaccines be administered to HIV-infected

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ment of disease, and travel. Vaccines for bioterrorism are not patients?
addressed. Immunobiological agents administered for active 16. Which vaccines should be given to patients with cancer?
vaccination are addressed; immune globulin preparations and 17. Should hematopoietic stem cell transplant (HSCT)
monoclonal antibodies used for passive vaccination are not. donors and patients be vaccinated before transplantation?
This guideline focuses on vaccines available in the United 18. Which vaccines should be administered to adults and
States, which are often relevant to other areas. Informed children after HSCT?
consent prior to vaccination, including provision of a CDC 19. For adult and child SOT candidates and living donors,
vaccine information statement, documentation of the vaccina- which vaccines should be administered during pretransplant
tion, communication about vaccination to the patient ( parent) evaluation?
or to clinicians involved in the patient’s care, and discussion of 20. Which vaccines should be administered to SOT recipients?
vaccination registries, is beyond the scope of this document. 21. Which vaccines should be administered to patients with
The following 23 clinical questions are answered: chronic inflammatory diseases maintained on immunosuppres-
sive therapies?
22. Which vaccines should be administered to asplenic pa-
1. Who is responsible for vaccinating immunocompromised tients and those with sickle cell diseases?
patients and members of their household? 23. Which vaccines should be given to individuals with
2. When should vaccines be administered to immunocom- cochlear implants or congenital dysplasias of the inner ear or
petent patients in whom initiation of immunosuppressive med- persistent CSF communication with the oropharynx or naso-
ications is planned? pharynx?
3. Which vaccines can be safely administered to individuals
living in a household with immunocompromised patients, and
METHODOLOGY
what precautions should immunocompromised patients
observe after vaccination of household members? Practice Guidelines
4. Which vaccines can be administered to immunocompro- “Practice guidelines are systematically developed statements to
mised patients contemplating international travel? assist practitioners and patients in making decisions about appro-
5. Should immunocompromised patients or those scheduled to priate healthcare for specific clinical circumstances” [6]. Attributes
receive immunosuppressive therapy receive varicella vaccine (VAR)? of good guidelines include validity, reliability, reproducibility,
6. Should immunocompromised patients or those who will clinical applicability, clinical flexibility, clarity, multidisciplin-
undergo immunosuppression receive zoster vaccine (ZOS)? ary process, review of evidence, and documentation [6].
7. Should immunocompromised patients receive influenza
vaccine? Panel Composition
8. Which vaccines should be administered to patients with The Infectious Diseases Society of America (IDSA) Standards
primary (congenital) complement deficiencies? and Practice Guidelines Committee (SPGC) collaborated with
9. Which vaccines should be administered to patients with partner organizations and convened a panel of 12 experts in vac-
phagocytic cell deficiencies (eg, chronic granulomatous disease cination of immunocompromised patients with a goal of devising

e54 • CID 2014:58 (1 February) • Rubin et al

recommendations for clinical practice. The panel represented RESULTS
diverse geographic areas, pediatric and adult practitioners, and a
wide breadth of specialties (gastroenterology, immunology, infec- The results are organized into general sections (vaccine safety,
tious diseases, hematology and oncology, rheumatology, and vaccine efficacy, timing of vaccination, vaccination of individu-
stem cell and solid organ transplantation) and organizations als living in a household with immunocompromised patients,
(CDC; American College of Rheumatology; North American vaccine administration, travel vaccines, varicella and zoster
Society for Pediatric Gastroenterology, Hepatology, and Nutri- vaccination of immunocompromised patients, influenza vacci-
tion; AAP; Pediatric Infectious Diseases Society; and European nation of immunocompromised patients) and sections on vac-
Group for Blood and Marrow Transplantation). cines for specific immunocompromising conditions ( primary
immune deficiency, HIV infection, oncology, HSCT, SOT, pa-
tients with chronic inflammatory diseases on immunosuppres-
Process Overview and Consensus Development Based on sive medications, asplenia, and patients with CSF leaks or
Evidence cochlear implants). Each section on immunocompromising
Panel subgroups reviewed the initial literature search, selected conditions addresses both inactivated and live vaccines. Recom-
references, evaluated evidence, drafted recommendations, and mendations for vaccination of patients with immunocomprom-
summarized the evidence for each section. Published guidelines ising conditions are provided in Tables 2–7. Recommendations

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[7, 8, 15] formed the basis for recommendations on vaccination not addressed by the CDC ACIP or the AAP Committee on In-
of patients with HIV or HSCT, with modifications based on fectious Diseases or that deviate from their recommendations
newer references and discussion among panel members. The are marked with an asterisk.
evidence evaluation process was based on the IDSA Handbook
General Principles
on Clinical Practice Guideline Development, which involves a
Definitions of High- and Low-Level Immunosuppression
systematic weighting of the quality of evidence and the grade of
The degree of immune impairment in patients with primary or
recommendation using the Grading of Recommendations As-
secondary immunodeficiency is variable. For this guideline,
sessment, Development and Evaluation (GRADE) system
certain generalizations have been made. Patients with high-
(Table 1) [9].
level immunosuppression include those:
Drafts were circulated among panel members for commen-
tary and discussed on 14 occasions by teleconference or in- • with combined primary immunodeficiency disorder (eg,
person meeting. Feedback from 3 external peer reviews and severe combined immunodeficiency),
endorsing organizations was obtained and used to modify the • receiving cancer chemotherapy,
document. The guideline was reviewed and endorsed by AAP; • within 2 months after solid organ transplantation,
American Society of Hematology; American Society of Pediat- • with HIV infection with a CD4 T-lymphocyte count <200
ric Hematology/Oncology; European Group for Blood and cells/mm3 for adults and adolescents and percentage <15 for
Marrow Transplantation; North American Society for Pediatric infants and children,
Gastroenterology, Hepatology, and Nutrition; and Pediatric In- • receiving daily corticosteroid therapy with a dose ≥20 mg
fectious Diseases Society. The guideline was reviewed and ap- (or >2 mg/kg/day for patients who weigh <10 kg) of prednisone
proved by the IDSA SPGC and board of directors. or equivalent for ≥14 days, and
• receiving certain biologic immune modulators, that is, a
tumor necrosis factor-alpha (TNF-α) blocker or rituximab [14].
Literature Review and Analysis After HSCT, duration of high-level immunosuppression is
The expert panel reviewed and analyzed literature published highly variable and depends on type of transplant (longer for
from January 1 1966 plus some more recent publications. Com- allogeneic than for autologous), type of donor and stem cell
puterized English-language literature searches of the National source, and posttransplant complications such as graft vs host
Library of Medicine PubMed database were performed using disease (GVHD) and their treatments.
the terms “vaccination,” “vaccine,” “immunization,” and names
of specific vaccines for each patient population or disorder Patients with low-level immunosuppression include:
under consideration. Selected references in selected publica- • asymptomatic HIV-infected patients with CD4 T-lympho-
tions were also reviewed. The literature was limited for many cyte counts of 200–499 cells/mm3 for adults and adolescents
vaccines and patient populations and primarily comprised case and percentage 15–24 for infants and children,
series evaluating vaccine immunogenicity and safety in particu- • those receiving a lower daily dose of systemic corticoste-
lar populations of immunocompromised patients. There were roid than for high-level immunosuppression for ≥14 days or
few comparative or efficacy trials described in the literature. receiving alternate-day corticosteroid therapy, and

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e55

Table 2. Vaccination of Persons With HIV Infection

Low-Level or No Immunosuppressiona High-Level Immunosuppressionb

Strength, Strength,
Vaccine Recommendation Evidence Quality Recommendation Evidence Quality
Haemophilus influenzae b conjugate U: age <5 y Strong, high U: age <5 y Strong, high
R: age 5–18 yc Strong, low R: age 5–18 yc Strong, low
Hepatitis A U Strong, moderate U: age 1 y Strong, moderate
Hepatitis Bd R Strong, moderate R Strong, moderate
Diphtheria toxoid, tetanus toxoid, acellular U Strong, moderate U Strong, moderate
pertussis
Tetanus toxoid, reduced diphtheria toxoid, U Strong, very low U Strong, very low
and reduced acellular pertussis
Tetanus toxoid, reduced diphtheria toxoid U Strong, low U Strong, low
Human papillomavirus (HPV4)e U: 11–26 y Strong, very low U: 11–26 y Strong, very low
Influenza-inactivated (inactivated influenza U Strong, high U Strong, high
vaccine)
Influenza-live attenuated (live attenuated Xf Weak, very low X Weak, very low

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influenza vaccine)
Measles, mumps, and rubella–live U: age 12 mo–13 y Strong, moderate X: age 12 mo–13 y Strong, moderate
U: age ≥14 y Weak, very low X: age ≥14 y Strong, moderate
Measles, mumps, and rubella–varicella–live X Strong, very low X Strong, very low
Meningococcal conjugateg U: age 11–18 y Strong, moderate U: age 11–18 y Strong, moderate
Pneumococcal conjugate (PCV13) U: age <5 y Strong, moderate U: age <5 y Strong, moderate
R: age 5 yh Strong, moderate R: age 5 y Strong, moderate
R: age 6–18 yh Strong, low R: age 6–18 y Strong, low
R: age ≥19 yi Strong, low R: age ≥19 yi Strong, very low
Pneumococcal polysaccharide (PPSV23)j R: age ≥2 y Strong, moderate R: age 2–18 y Strong, moderate
R: adult (CD4 T lymphocytes Weak, low
<200 cells/mm3)
Polio–inactivated (inactivated poliovirus U Strong, moderate U Strong, moderate
vaccine)
Rotavirus–live U Strong, low U Weak, very low
Varicella–live U: age 1–8 y Strong, high X Strong, moderate
U: age ≥9 y Strong, very low
Zoster–live X Strong, low X Strong, moderate

Abbreviations: R, recommended—administer if not previously administered or not current; such patients may be at increased risk for this vaccine-preventable
infection; U, usual—administer if patient not current with recommendations for dose(s) of vaccine for immunocompetent persons in risk and age categories; X,
contraindicated.
a
Asymptomatic human immunodeficiency virus (HIV) infection with CD4 T-cell lymphocyte counts of 200–499 cells/mm3 for adults and adolescents and
percentages of 15–24 for infants and children.
b
CD4 T-cell lymphocyte count <200 cells/mm3 for adults and adolescents and percentage <15 for infants and children.
c
One dose.
d
High-dose hepatitis B vaccine (40 µg) should be considered for adults (weak, moderate) and adolescents (weak, low) with HIV infection. The latter
recommendation deviates from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention.
e
Quadrivalent human papillomavirus vaccine (HPV4) is preferred over HPV2 vaccine because of its activity against genital warts. This recommendation deviates
from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention.
f
Live attenuated influenza vaccine may be considered in otherwise healthy HIV-infected patients aged 5–17 years on combination antiretroviral therapy regimen for
≥16 weeks with CD4 T-lymphocyte percentage ≥15 and HIV plasma RNA <60 000 copies.
g
For HIV-infected patients, meningococcal conjugate vaccine, quadrivalent is administered as a 2-dose primary series separated by ≥2 months. A booster dose
(third dose) should be administered at age 16 years if the initial series was given at 11–12 years and at age 16–18 years if the initial series was given at age 13–15
years.
h
For patients not fully vaccinated with PCV13 by previous administration.
i
For patients aged ≥19 years with HIV who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the last PPSV23 dose (weak,
low).
j
PPSV23 should be administered 8 weeks or longer after indicated dose(s) of PCV13. A second dose of PPSV23 should be administered 5 years after the initial
dose.

e56 • CID 2014:58 (1 February) • Rubin et al

Table 3. Vaccination of Patients With Cancer

Starting ≥3 mo Postchemotherapy and ≥6 mo Post

Anti–B-Cell Antibodies for Inactivated Vaccines;
Prior to or During Chemotherapy See Each Live Vaccine for Interval

Strength, Strength,
Vaccine Recommendation Evidence Quality Recommendation Evidence Quality
Haemophilus influenzae b conjugate Ua Weak, low U Strong, moderate
Hepatitis A Ua Weak, low U Strong, very low
Hepatitis B Ua Weak, low U Strong, moderate
R: adults Strong, very low
Diphtheria toxoid, tetanus toxoid, Ua Weak, low U: age 0–18 y Strong, moderate
acellular pertussis; tetanus toxoid, R: adults with acute lymphoblastic Weak, very low
reduced diphtheria toxoid, and leukemia or lymphoma
reduced acellular pertussis
Human papillomavirus U: 11–26 ya Weak, very low U Strong, very low
Influenza-inactivated (inactivated Ua Strong, low-moderatea Ub Strong, moderate
influenza vaccine)

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Influenza-live attenuated (live X Weak, very low U Strong, low
attenuated influenza vaccine)
Measles, mumps, and rubella–live Xc Strong, moderate Starting at 3 mo: U Strong, low
Measles, mumps, and rubella– Xc Strong, moderate Starting at 3 mo: U Weak, very low
varicella–live
Meningococcal conjugate Ua Weak, low U Strong, low
Pneumococcal conjugate-13 (PCV13) R: <6 y Strong, low U Strong, low
R: age ≥6 yd Strong, very low
Pneumococcal polysaccharide R: age ≥2 y Strong, low U Strong, low
(PPSV23)
Polio–inactivated (inactivated Ua Weak, low U Strong, low
poliovirus vaccine)
Rotavirus–live X Strong, very low Not applicable
Varicella–live Xc Strong, moderate Starting at 3 mo: Ue Weak, very low
Zoster–live Xc Strong, very low Starting at 3 mo: Ue Weak, very low

Abbreviations: R, recommended—administer if not previously administered or not current; such patients may be at increased risk for this vaccine-preventable
infection; U, usual—administer if patient not current with recommendations for dose(s) of vaccine for immunocompetent persons in risk and age categories; X,
contraindicated.
a
Administer inactivated influenza vaccine (IIV) annually to patients with hematological malignancies (strong, moderate) or solid tumor malignancies (strong, low)
except those receiving anti–B-cell antibodies such as rituximab or alemtuzumab or intensive chemotherapy such as for induction or consolidation chemotherapy for
acute leukemia (weak, low). Administration of inactivated vaccines other than IIV, which are routinely recommended for healthy children in the annually updated
CDC recommendations, can be considered for children with malignancies who are receiving maintenance chemotherapy (weak, low). However, vaccines
administered while receiving cancer chemotherapy should not be considered valid doses (strong, low). Administration of indicated inactivated vaccines 2 or more
weeks prior to chemotherapy is preferred.
b
IIV can be administered ≤3 months after chemotherapy, but response rate may be low.
c
These live vaccines should not be administered unless the vaccine is otherwise indicated based on the annually updated Centers for Disease Control and
Prevention recommendations AND the patient is not immunosuppressed AND there will be an interval of ≥4 weeks prior to initiation of chemotherapy.
d
For patients aged ≥19 years with human immunodeficiency virus who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the
last PPSV23 dose (weak, low).
e
Although measles, mumps, and rubella vaccine has been given safely 3 months after completion of chemotherapy, data on the safety, immunogenicity, and
efficacy of varicella or zoster vaccine after completion of chemotherapy are not available.

• those receiving methotrexate (MTX) ≤0.4 mg/kg/week, oligosaccharide, inactivated whole or partially purified
azathioprine ≤3 mg/kg/day, or 6-mercaptopurine ≤1.5 mg/kg/ viruses, and proteins in virus-like particles). Limited evi-
day [10]. dence indicates that inactivated vaccines generally have the
same safety profile in immunocompromised patients as in
Safety of Vaccination of Immunocompromised Persons immunocompetent individuals [11]. However, the magni-
Vaccines are categorized as live or inactivated (ie, nonlive tude, breadth, and persistence of the immune response to
vaccines include toxoids and other purified proteins, puri- vaccination may be reduced or absent in immunocompro-
fied polysaccharide, protein–polysaccharide conjugate or mised persons.

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e57

Table 4. Vaccinations Prior to or After Allogeneic or Autologous Hematopoietic Stem Cell Transplant

Pre-HSCT Post-HSCT

Strength, Evidence Recommendation; Earliest Time Strength, Evidence

Vaccine Recommendation Quality Posttransplant; Number of Doses Quality
Haemophilus influenzae b U Strong, moderate R; 3 mo; 3 doses Strong, moderate
conjugate
Hepatitis A U Strong, very low R; 6 mo; 2 doses Weak, low
Hepatitis B U Strong, low R; 6 mo; 3 doses Strong, moderate
DTaP, DT, Td, Tdap U Strong, low R; age <7 y: DTaP; 6 mo; 3 doses Strong, low
R; age ≥7 y: DTaP ; 6 mo; 3 doses Weak, very low
OR DTaP: weak,
1 dose Tdap, then 2 doses DT or moderate
Td; 6 mo DT, Td: weak, low
Human papillomavirus U: 11–26 y Strong, very low U; 6 mo; 3 doses Weak, very low
Influenza-inactivated (inactivated U Strong, low R; 4 mo Strong, moderate
influenza vaccine)
Influenza-live attenuated (live X Weak, very low X Weak, very low
attenuated influenza vaccine)

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Measles, mumps, and rubella–live Ua Strong, very low Xb Strong, low
a
Measles, mumps, and rubella– U Weak, very low X Strong, very low
varicella–live
Meningococcal conjugate U Strong, very low R; age 11–18 y; 6 mo; 2 doses Strong, low
Pneumococcal conjugate (PCV13) Rc Strong, low R; 3 mo; 3 doses Strong, low
Pneumococcal polysaccharide Rc Strong, very low R; ≥12 mo post if no GVHD Strong, low
(PPSV23)
Polio-inactivated (inactivated U Strong, very low R; 3 mo; 3 doses Strong, moderate
poliovirus vaccine)
Rotavirus–live X Weak, very low X Weak, very low
Varicella–live Ua Strong, low Xd Strong, low
Zoster–live Ra,e: age 50–59 y Weak, very low X Strong, low
Ua: age ≥60 y Strong, low X Strong, low

Abbreviations: DT, diphtheria toxoid, tetanus toxoid, DTaP, diphtheria toxoid, tetanus toxoid, acellular pertussis; GVHD, graft-vs-host disease; HSCT, hematopoietic
stem cell transplant; R, recommended—administer if not previously administered or current; such patients may be at increased risk for this vaccine-preventable
infection; Td, tetanus toxoid, reduced diphtheria toxoid; Tdap, Tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis; U, usual—administer if
patient not current with recommendations for dose(s) of vaccine for immunocompetent persons in risk and age categories; X, contraindicated.
a
These live vaccines should not be administered unless the vaccine is otherwise indicated based on the annually updated Centers for Disease Control and
Prevention recommendations AND the patient is not immunosuppressed AND there will be an interval of ≥4 weeks prior to transplant.
b
Administer to adolescents and adults (strong, low) and to children (strong, moderate) if measles seronegative, the timing is ≥24 months after transplant, no GVHD
is present, and the patient is not receiving immunosuppressive medication. Two doses should be administered.
c
If not previously administered.
d
Administer if varicella seronegative, the timing is ≥24 months after transplant, no GVHD is present, and the patient is not receiving immunosuppressive
medication. Two doses should be administered (strong, low).
e
Consider if the patient is not severely immunosuppressed AND the patient is varicella immune as defined by documentation of age-appropriate varicella
vaccination, serologic evidence of immunity, documentation of varicella or zoster infection, or birth in the United States before 1980 [45] AND there will be an
interval of ≥4 weeks prior to transplant.

Indicates recommendation for a course of action that deviates from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease
Control and Prevention.

Live vaccines are generally contraindicated in immunodefi- because paralytic poliomyelitis has occurred after vaccination.
cient patients because attenuation is relative. However, there In contrast, VAR is generally considered contraindicated for
are important evidence-based exceptions, such as administra- children with inflammatory bowel disease (IBD) who are re-
tion of VAR or MMR vaccine to HIV-infected children with ceiving 6-mercaptopurine. Also, live, attenuated, cold-adapted
mild to moderate immune deficiency (Tables 2–7) [7]. It is im- intranasal influenza vaccine is not administered to immuno-
portant to distinguish between contraindications based on clin- compromised patients based on insufficient clinical data to
ical evidence and contraindications based on theoretical support these judgments. The decision to administer or with-
considerations. Oral polio vaccine (OPV) is contraindicated for hold a vaccine should be based on balancing the burden of the
patients with severe combined immune deficiency (SCID) vaccine-preventable disease and risk of developing severe or

e58 • CID 2014:58 (1 February) • Rubin et al

Table 5. Vaccinations Prior to or After Solid Organ Transplant

Pretransplant Starting 2–6 mo Posttransplant

Strength, Strength,
Vaccine Recommendation Evidence Quality Recommendation Evidence Quality
Haemophilus influenzae b U Strong, moderate U Strong, moderate
conjugate
Hepatitis A U: age 12–23 mo Strong, moderate R, if not completed pretransplant Strong, moderate
R: ≥2 y Strong, moderate
Hepatitis B U: age 1–18 y Strong, moderate R, if not completed pretransplanta Strong, moderate
R: ≥18 y Strong, moderate
Diphtheria toxoid, tetanus toxoid, U Strong, moderate U, if not completed pretransplant Strong, moderate
acellular pertussis; tetanus
toxoid, reduced diphtheria
toxoid, and reduced acellular
pertussis
Human papillomavirus U: females 11–26 y Strong, moderate U: females 11–26 y Strong, moderate
U: males 11–26 y Strong, low U: males 11–26 y Strong, low
Influenza-inactivated (inactivated U Strong, moderate Ub Strong, moderate

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influenza vaccine)
Influenza-live attenuated (live X Weak, low X Weak, low
attenuated influenza vaccine)
Measles, mumps, and rubella–live Rc: 6–11 mo Weak, very low X Strong, low
Ud: age ≥12 mo Strong, moderate
Measles, mumps, and rubella– Ud Strong, moderate X Strong, low
varicella–live
Meningococcal conjugate U Strong, moderate U Strong, moderate
Pneumococcal conjugate (PCV13) U: age ≤5 y Strong, moderate U: Age 2–5 y Strong, moderate
R: age ≥6 ye Strong, very low R: age ≥6 y if not administered Strong, very low
pretransplante
Pneumococcal polysaccharide R: age ≥2 y Strong, moderate R: age ≥2 y, if not administered Strong, moderate
(PPSV23) pretransplant
Polio-inactivated (inactivated U Strong, moderate U Strong, moderate
poliovirus vaccine)
Rotavirus–live Uc Strong, moderate X Strong, low
Varicella–live Rf: 6–11 mo Weak, very low Xg Strong, low
Ud Strong, low
Zoster–live Rh: age 50–59 y Weak, low X Strong, low
Ui: age ≥60 y Strong, moderate

Abbreviations: R, recommended—administer if not previously administered or not current; such patients may be at increased risk for this vaccine-preventable
infection; U, usual—administer if patient not current with annually updated Centers for Disease Control and Prevention recommendations for immunocompetent
persons in risk and age categories; X, contraindicated.
a
Consider hepatitis B vaccine for hepatitis B-infected liver transplant patients (weak, low).
b
Inactivated influenza vaccine may be administered to solid organ transplant recipients despite intensive immunosuppression (eg, during the immediate
posttransplant period), particularly in an outbreak situation (weak, low).
c
Administer only if patient is not immunosuppressed and the timing is ≥4 weeks prior to transplant.
d
Administer only if patient is nonimmune, not severely immunosuppressed, and the timing is ≥4 weeks prior to transplant.
e
For patients aged ≥19 years who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the last PPSV23 dose (weak, low).
f
Administer only if patient is not immunosuppressed and the timing is ≥4 weeks prior to transplant. This recommendation deviates from recommendations of the
Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention.
g
Selected seronegative patients with renal or liver transplant have been safely vaccinated. This recommendation deviates from recommendations of the Advisory
Committee on Immunization Practices, Centers for Disease Control and Prevention.
h
Administer only if patient is not severely immunosuppressed, the timing is ≥4 weeks prior to transplant, and the patient is varicella immune as defined by
documentation of age-appropriate varicella vaccination, serologic evidence of immunity, documentation of varicella or zoster infection, or birth in the United States
before 1980 [45, 375]. This recommendation deviates from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control
and Prevention.
i
Administer only if patient is not severely immunosuppressed and the timing is ≥4 weeks prior to transplant.

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e59

e60
•
Table 6. Vaccination of Persons With Chronic Inflammatory Diseases on Immunosuppressive Medications
CID 2014:58 (1 February)

Planned Immunosuppression Low-level Immunosuppressiona High-level Immunosuppressiona

Strength, Evidence Strength, Evidence Strength, Evidence

Vaccine Recommendation Quality Recommendation Quality Recommendation Quality
Haemophilus influenzae b U Strong, moderate U Strong, low U Strong, low
conjugate
Hepatitis A U Strong, moderate U Strong, low U Strong, low
Hepatitis B U Strong, moderate U Strong, low U Strong, low
•
Rubin et al

Diphtheria toxoid, tetanus toxoid, U Strong, moderate U Strong, low U Strong, low
acellular pertussis; tetanus
toxoid, reduced diphtheria
toxoid; tetanus toxoid, reduced
diphtheria toxoid, and reduced
acellular pertussis
Human papillomavirus U: 11–26 y Strong, moderate U: 11–26 y Strong, low U: 11–26 y Strong, very low
Influenza-inactivated (inactivated U Strong, moderate U Strong, moderate U Strong, moderate
influenza vaccine)
Influenza-live attenuated (live X Weak, very low X Weak, very low X Weak, very low
attenuated influenza vaccine)
Measles, mumps, and rubella–live Ub Strong, moderate X Weak, very low X Weak, very low
Measles, mumps, and rubella– Ub Strong, low X Weak, very low X Strong, very low
varicella–live
Meningococcal conjugate U Strong, moderate U Strong, moderate U Strong, low
Pneumococcal conjugate (PCV13) Rc Strong, moderate U: <6 y Strong, low U: <6 y Strong, low
R: ≥6 yc strong, very low R: ≥6 yc strong, very low
Pneumococcal polysaccharide R: age ≥2 y Strong, low R: age ≥2 y Strong, low R: age ≥2 y Strong, very low
(PPSV23)
Polio-inactivated (inactivated U Strong, moderate U Strong, moderate U Strong, low
poliovirus vaccine)
Rotavirus–live U Strong, moderate X Weak, very low X Weak, very low
Varicella–live Ub Strong, moderate Xd Weak, very low X Strong, moderate
Zoster–live R: age 50–59 ye Weak, low R: age 50–59 ye Weak, very low X Weak, very low
U: age ≥60 y strong, low U: age ≥60 y Strong, very low

Abbreviations: R, recommended—administer if not previously administered or not current; such patients may be at increased risk for this vaccine-preventable infection; U, usual—administer if patient not current with
recommendations for dose(s) of vaccine for immunocompetent persons in risk and age categories; X, contraindicated.
a
Low-level immunosuppression includes treatment with prednisone <2 mg/kg with a maximum of ≤20 mg/day; methotrexate ≤0.4 mg/kg/week; azathioprine ≤3 mg/kg/day; or 6-mercaptopurine ≤1.5 mg/kg/day.
High-level immunosuppression regimens include treatment with doses higher than those listed for low-dose immunosuppression and biologic agents such as tumor necrosis factor antagonists or rituximab.
b
Administer only if patient is nonimmune, not severely immunosuppressed, and the timing is ≥4 weeks prior to initiation of immunosuppressive medications.
c
For patients aged ≥19 years who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the last PPSV23 dose (weak, low).
d
Administration of varicella vaccine can be considered for nonvaricella-immune patients treated for chronic inflammatory disease who are receiving long-term low-dose immunosuppression (weak, very low). This
recommendation deviates from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention.
e
This recommendation deviates from recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention [10].

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Table 7. Vaccination of Persons With Asplenia or a Sickle Cell Disease, Cochlear Implants, or Cerebrospinal Fluid Leak

Asplenia or a Sickle Cell Disease Cochlear Implantsa or Cerebrospinal Fluid Leak

Strength, Evidence Strength, Evidence

Vaccine Recommendation Quality Recommendation Quality
Haemophilus influenzae b U: age <5 y Strong, moderate U Strong, moderate
conjugate R: age ≥5 y weak, low
Hepatitis A U Strong, moderate U Strong, moderate
Hepatitis B U Strong, moderate U Strong, moderate
Diphtheria toxoid, tetanus toxoid, U Strong, moderate U Strong, moderate
acellular pertussis; tetanus
toxoid, reduced diphtheria
toxoid; tetanus toxoid, reduced
diphtheria toxoid, and reduced
acellular pertussis
Human papillomavirus U Strong, moderate U Strong, moderate
Influenza-inactivated (inactivated U Strong, moderate U Strong, moderate
influenza vaccine)
Influenza-live attenuated (live X Weak, very low U Strong, moderate

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attenuated influenza vaccine)
Measles, mumps, and rubella–live U Strong, moderate U Strong, moderate
Measles, mumps, and rubella– U Strong, moderate U Strong, moderate
varicella–live
Meningococcal conjugate R: age 2–55 yb Strong, low U Strong, moderate
Meningococcal polysaccharide R: age >55 yb Strong, low U Strong, moderate
Pneumococcal conjugate (PCV13) U: age <6 yc Strong, moderate U: age <6 yc Strong, moderate
R: age ≥6 yd Strong, very low R: age ≥6 yd strong, low
Pneumococcal polysaccharide R: age ≥2 ye Strong, low R: age ≥2 ye Strong, moderate
(PPSV23)
Polio-inactivated (inactivated U Strong, moderate U Strong, moderate
poliovirus vaccine)
Rotavirus–live U Strong, moderate U Strong, moderate
Varicella–live U Strong, moderate U Strong, moderate
Zoster–live U Strong, moderate U Strong, moderate
Abbreviations: R, recommended—administer if not previously administered or not current; such patients may be at increased risk for this vaccine-preventable
infection; U, usual—administer if patient not current with recommendations for dose(s) of vaccine for immunocompetent persons in risk and age categories; X,
contraindicated.
a
Includes patients with profound hearing loss who are scheduled to receive a cochlear implant or have inner ear–cerebrospinal fluid communication.
b
A 2-dose primary series should be administered with an additional dose every 5 years.
c
Two doses of PCV13 for children aged 2–5 years who have not received doses of PCV or received <3 doses of PCV7.
d
If PCV13 has not been administered. For patients aged ≥19 years who have received PPSV23, PCV13 should be administered after an interval of ≥1 year after the
last PPSV23 dose (weak, low).
e
Administer 8 or more weeks after indicated dose(s) of PCV13 with a single revaccination with PPSV23 5 years after the initial dose (strong, moderate).

life-threatening infection with the wild-type pathogen and the clinical evidence indicates that vaccines are not important trig-
risks of adverse effects from vaccination. gers of disease flares in such patients and should not be withheld
Concerns have been expressed that antigenic stimulation of for that reason (see “Recommendations for Vaccination of Pa-
vaccination could trigger a flare or onset of chronic inflamma- tients with Chronic Inflammatory Diseases of Immunosuppres-
tory disease. The Institute of Medicine recently assessed the sive Medications” section).
relationships between vaccines (MMR, acellular pertussis- For SOT patients, concerns have been raised that vaccination
containing, DT, tetanus toxoid, influenza, HepB, HepA, and might trigger rejection. However, the preponderance of clinical
HPV vaccines) and adverse effects [5]. Evidence was inade- evidence, most relating to trivalent inactivated influenza
quate to establish or refute a causal relationship between each vaccine (IIV), indicates that vaccines are not important triggers
vaccine and onset or exacerbation of multiple sclerosis, systemic of rejection episodes and should not be withheld for that
lupus erythematosus (SLE), vasculitis, rheumatoid arthritis (RA), reason (see “Recommendations for Vaccination of Solid Organ
or juvenile idiopathic arthritis. Overall, the preponderance of Transplant Recipients” section).

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e61

Vaccine Efficacy and Effectiveness recommend revisions to the IDSA SPGC, board, and other col-
There are few data on vaccine efficacy or effectiveness in immu- laborating organizations for review and approval.
nocompromised patients. In children with sickle cell disease,
there was a 93% reduction in the rate of invasive pneumococcal RECOMMENDATIONS FOR RESPONSIBILITY
disease caused by vaccine serotypes after routine administration FOR VACCINATIONS
of 7-valent pneumococcal conjugate vaccine (PCV7) [12];
however, herd-type immunity may have contributed to vaccine I. Who Is Responsible for Vaccinating Immunocompromised
effectiveness. Other examples are the demonstrated efficacy of Patients and Members of Their Household?
IIV in HIV-infected adults [13] and cardiac transplant patients,
and the efficacy of VAR against severe varicella in renal and Recommendations
liver transplant recipients [16–18], children with leukemia [19], 1. Specialists who care for immunocompromised patients
and children with HIV [20]. share responsibility with the primary care provider for en-
The estimate of effectiveness of most vaccines in immuno- suring that appropriate vaccinations are administered to im-
compromised patients is based on a surrogate marker, typically munocompromised patients (strong, low).
serum antibodies against the pathogen. However, there are lim- 2. Specialists who care for immunocompromised patients
itations to the use of antibody measurements for determination share responsibility with the primary care provider for rec-

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of the adequacy of preexisting immunity or a response to vacci- ommending appropriate vaccinations for members of im-
nation. For many pathogens, a serum antibody concentration munocompromised patients’ households (strong, very low).
that correlates with protection (eg, a protective concentration
Evidence Summary
of antibodies to ≥1 proteins of Bordetella pertussis) has yet to
In many cases, immunocompromised patients visit specialists
be established [21, 22]. Asplenic patients may require a higher
more frequently than they do their primary care clinician, pro-
antibody concentration than immunocompetent persons in
viding opportunities for vaccination. For example, vaccination
order to protect against invasive infection with Streptococcus
rates were higher among pregnant women offered influenza
pneumoniae and Haemophilus influenzae type b [23, 24]. The
vaccine by their obstetrician or other specialty provider com-
correlation of antibody concentration with protection may be
pared with those not offered vaccine (70.8% vs 14.4%) [29].
imperfect because such assays do not measure antibody func-
Therefore, specialists are in a pivotal position to ensure vaccina-
tional activity [25]. Assays of functional antibodies [26] or anti-
tion by administering vaccines or providing specific advice to
body avidity [27] may be more predictive of protection. For
patients and primary care providers. Specialists should educate
prevention of zoster, cell-mediated immunity (CMI) is more
patients and members of their household on the importance of
closely associated with protection than are serum antibody con-
vaccination of household members for the protection of the im-
centrations [28].
munocompromised patient.

Guideline and Conflict of Interest

All panel members complied with the IDSA’s policy on conflict RECOMMENDATIONS FOR TIMING OF
of interest, which requires disclosure of any financial or other VACCINATION
interest that might be construed as constituting an actual, po-
II. When Should Vaccines Be Administered to Immunocompe-
tential, or apparent conflict. They were provided IDSA’s con-
tent Patients in Whom Initiation of Immunosuppressive Medi-
flict-of-interest disclosure statement and asked to identify ties
cations is Planned?
to companies that develop products that might be affected by
promulgation of the guideline. Information was requested re- Recommendations
garding employment, consultancies, stock ownership, honoraria, 3. Vaccines should be administered prior to planned immu-
research funding, expert testimony, and membership on com- nosuppression if feasible (strong, moderate).
pany advisory committees. The panel decided on a case-by-case 4. Live vaccines should be administered ≥4 weeks prior to
basis whether conflict should limit member participation. Poten- immunosuppression (strong, low) and should be avoided within
tial conflicts are listed in the Acknowledgments section. 2 weeks of initiation of immunosuppression (strong, low).
5. Inactivated vaccines should be administered ≥2 weeks
Revision Dates prior to immunosuppression (strong, moderate).
At annual intervals, the panel chair, SPGC liaison advisor, and
SPGC chair will determine the need for guideline revisions Evidence Summary
by reviewing the current literature. If necessary, the entire Certain immunocompromised patients have a window of op-
panel will be reconvened. When appropriate, the panel will portunity before initiation of immunosuppressive medications

e62 • CID 2014:58 (1 February) • Rubin et al

Table 8. Safety of Administration of Live Vaccines to Contacts of Immunocompromised Persons

Recommendation for Administering

Vaccines (When Indicated) to Healthy
Transmissibility from Vaccinated Immunocompetent Contacts of
Live Vaccine Shedding of Agent? (site) Immunocompetent Person? Immunocompromised Patients
Influenza, live, Yes (nasal secretions) Rare (from 1 vaccinated toddler) Administer (strong, low); vaccinated
attenuated nasal persons to avoid close contact with
persons with hematopoietic stem cell
transplant or severe combined
immune deficiency for 7 d (weak, very
low)
Measles, mumps, Measles: no No, except mother-to-infant Administer (strong, moderate)
and rubella Mumps: no transmission of rubella vaccine
Rubella: yes (nasopharynx, in low virus via breast milk
titer; breast milk)
Polio, oral Yes (stool) Yes, with rare cases of vaccine- Do not administer (strong, high)
associated paralytic poliomyelitis
Rotavirus, oral Yes (stool) Yes, but no reported cases of Administer (strong, low)
symptomatic infection in contacts

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Typhoid, oral No No Administer (strong, low)
Varicella Yes (skin lesions) Rare, limited to vaccinees with skin Administer (strong, moderate); if skin
lesions lesions develop, avoid close contact
with immunocompromised persons
Yellow fever No, except possibly shed in Yes (at least 3 cases of encephalitis in Administer (strong, moderate) except to
breast milk infants exposed to the vaccine via women who are nursing
nursing)
Zoster Yes (rarely recovered from Not reported Administer to those aged ≥60 y (strong,
injection site vesicles) moderate); if skin lesions develop,
avoid close contact with
immunocompromised persons

during which indicated vaccines can be administered while the healthcare personnel at a long-term care facility for elderly pa-
patient is immunocompetent (or more immunocompetent tients reduced mortality more than vaccination of the patients
than following initiation of immunosuppression). However, in- [30, 31]. All members of the immunocompromised patient’s
dicated treatment of underlying disease should not be delayed household as well as all healthcare contacts should be vaccinat-
to achieve vaccination goals. Response to vaccination and safety ed. Requiring annual influenza vaccination of healthcare per-
of live vaccines is higher prior to initiation of immunosuppres- sonnel can increase vaccination rates [32]. However, data
sion. After administration of live viral vaccines, the period of supporting the effectiveness of vaccinating adults to protect
viral replication and development of immunologic response is young infants from pertussis are limited [33]. Household
generally <3 weeks, so vaccination ≥4 weeks prior to immuno- members should be up-to-date with all routinely recommended
suppression (2 weeks prior for inactivated vaccines) is likely to vaccinations including annual influenza vaccine [34].
be safe [16]. Development of a robust immune response may III. Which Vaccines Can Be Safely Administered to House-
take longer than these time intervals, however, particularly if the hold Members of Immunocompromised Patients, and What
vaccination is for primary vaccination rather than as a booster. Precautions Should Immunocompromised Patients Observe
After Vaccination of Household Members?

RECOMMENDATIONS FOR VACCINATION OF

HOUSEHOLD MEMBERS OF Recommendations (Table 8)
IMMUNOCOMPROMISED PATIENTS 6. Immunocompetent individuals who live in a household with
immunocompromised patients can safely receive inactivated vac-
Reduction of exposure to vaccine-preventable infections is im- cines based on the CDC–ACIP’s annually updated recommend-
portant for risk reduction. This can be accomplished by educat- ed vaccination schedules for children and adults (hereafter, CDC
ing immunocompromised patients and members of their annual schedule; strong, high) or for travel (strong, moderate).
household on infection control practices and by vaccinating 7. Individuals who live in a household with immunocom-
household members and healthcare contacts to provide a promised patients age ≥6 months should receive influenza
“circle of protection.” For example, influenza vaccination of vaccine annually (strong, high). They should receive either:

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e63

 (a) Inactivated influenza vaccine (IIV; strong, high) or administration to household members. Although data are
(b) Live attenuated influenza vaccine (LAIV) provided they limited, it is considered safe to administer LAIV to individuals
are healthy, not pregnant, and aged 2–49 years (strong, who live with immunocompromised persons except for HSCT
low). Exceptions include individuals who live in a recipients in protected environments with positive air pressure
household with an immunocompromised patient who and hepa-filtered air [41]. HSCT patients within 2 months after
was a hematopoietic stem cell transplant (HSCT) recip- transplant or with GVHD and patients with a primary SCID
ient within 2 months after transplant or with graft vs are likely to be severely immunocompromised; therefore, in the
host disease (GVHD) or is a patient with severe com- opinion of the panel, household members should not receive
bined immune deficiency (SCID). In these exceptions, LAIV.
LAIV should not be administered (weak, very low) or, The only report of transmission of MMR viruses from im-
if administered, contact between the immunocompro- munocompetent vaccinees involved transmission to nursing
mised patient and household member should be neonates of rubella vaccine virus via breast milk [42]. Yellow
avoided for 7 days (weak, very low). fever encephalitis developed in at least 3 nursing infants follow-
8. Healthy immunocompetent individuals who live in a ing yellow fever vaccination of their mothers [43].
household with immunocompromised patients should Transmission of varicella virus from immunocompetent
receive the following live vaccines based on the CDC annual persons has been limited to vaccinees who developed a rash,

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schedule: combined measles, mumps, and rubella (MMR) and the risk appears to be low [44, 45]. Therefore, susceptible
vaccine (strong, moderate); rotavirus vaccine in infants aged household members should receive VAR to protect immuno-
2–7 months (strong, low); varicella vaccine (VAR; strong, compromised persons from potential exposure to wild-type
moderate); and zoster vaccine (ZOS; strong, moderate). disease. Household members aged ≥60 years who qualify for
Also, these individuals can safely receive the following vac- zoster vaccination should be vaccinated. Individuals with a
cines for travel: yellow fever vaccine (strong, moderate) and VAR- or ZOS-associated rash may be contagious and should
oral typhoid vaccine (strong, low). avoid close contact with immunocompromised persons until
9. OPV should not be administered to individuals who live the lesions have resolved [45–47].
in a household with immunocompromised patients (strong, Children receiving rotavirus vaccines may shed live virus in
moderate). stool for 2–4 weeks and transmit vaccine virus, but sympto-
10. Highly immunocompromised patients should avoid matic disease is rare [48, 49]. In a study of 110 pairs of infant
handling diapers of infants who have been vaccinated with twins in which 1 twin was given a 2-dose monovalent rotavi-
rotavirus vaccine for 4 weeks after vaccination (strong, very rus vaccine (RV1; Rotarix, GlaxoSmithKline) series and the
low). other placebo, the transmission rate was 18.8% (95% confi-
11. Immunocompromised patients should avoid contact dence interval [CI], 10.9%–29.0%), but none of the affected
with persons who develop skin lesions after receipt VAR or infants became symptomatic [50]. The risk of transmission
ZOS until the lesions clear (strong, low). and the theoretical risk of developing rotavirus disease as a
result of the contact are lower than the risk of an unimmu-
Evidence Summary nized infant developing rotavirus diarrhea with wild-type
When transmission of live vaccine from a vaccine recipient virus with resultant rotavirus disease in the immunocompro-
occurs, illness from an attenuated vaccine strain is likely to be mised contact.
less severe than from wild-type virus or bacteria. Studies of Healthcare personnel should receive influenza vaccine annu-
vaccine virus shedding after vaccination with LAIV have dem- ally and receive HepB, VAR, MMR, and Tdap vaccines or
onstrated that 80% of healthy recipients aged 8–36 months provide documentation of immunity to minimize exposure of
shed vaccine virus strains for a mean duration of 7.6 days [35– immunocompromised persons in healthcare facilities. Manda-
40]. Among 345 patients aged 5–49 years, 30% had detectable tory annual influenza vaccination, recommended by multiple
virus in nasal secretions after receiving LAIV. Duration and professional organizations, has been implemented in certain
amount of shedding correlated inversely with age, and maximal healthcare facilities, resulting in very high influenza vaccine
shedding occurred within 2 days of vaccination [36, 41]. LAIV coverage [36, 51–53].
virus was transmitted in a day-care center to 1 healthy toddler OPV, which is administered internationally, but not in the
who remained asymptomatic. Based on this single case, the es- United States, is associated with a risk of transmission to
timated frequency of transmission is 0.6%–2.9% among tod- household members, with a small risk of vaccine-associated
dlers attending a day-care center [40]. Transmission of LAI paralytic poliomyelitis (VAPP) in those household members.
virus to an immunocompromised person has not been demon- The risk is higher in immunocompromised individuals living
strated despite nonrestrictive recommendations for LAIV with a vaccinee [54, 55].

e64 • CID 2014:58 (1 February) • Rubin et al

Vaccine Administration Information for International Travel” (both at http://wwwnc.
Most vaccine doses and routes are the same for immunocom- cdc.gov/travel).
promised and immunocompetent persons. An exception is Immunocompromised persons should avoid travelling to
HepB vaccine for adult hemodialysis patients whose regimen is areas where yellow fever is endemic [62]. Data are very limited
3 or 4 40-µg doses vs 3 10- or 20-µg doses for immunocompe- on yellow fever vaccine in immunocompromised persons. In-
tent adults receiving Recombivax (Merck) or Engerix (GlaxoS- vestigators recently studied the effect of yellow fever vaccine in
mithKline), respectively [56], or for certain HIV-infected 70 patients with rheumatic diseases including RA, SLE, and
patients not responding to standard regimens [57, 58] (see HIV spondyloarthropathies who were treated with immunosuppres-
section). Certain immunocompromised patients may have sive drugs [63]. Mild adverse effects (eg, rash, myalgia, elevated
thrombocytopenia that may be a relative contraindication to an hepatic transaminases) occurred in 22.5% of vaccinees, suggest-
intramuscular injection. Clinical experience suggests that intra- ing a reasonably safety profile. However, sample size was inade-
muscular injections are safe if the platelet count is ≥30 000– quate for detecting rare serious complications, and cases of
50 000 cells/mm3, a ≤23-gauge needle is used, and constant yellow fever vaccine–associated viscerotropic disease have been
pressure is maintained at the injection site for 2 minutes [59]. reported in this population [62]. Yellow fever vaccine has been
Inactivated poliovirus (IPV) vaccine and pneumococcal poly- safely administered to a limited number of post-HSCT patients
saccharide vaccine-23 (PPSV23) may be administered subcuta- [64–66] and to more than 200 HIV-infected adults, the majori-

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neously. An intradermal IIV is licensed. Multiple indicated ty of whom had CD4 T-cell lymphocyte counts >200 cells/mm3
vaccines can be administered simultaneously, with the same [62, 67, 68]. An increase in relapse of multiple sclerosis was
recommendations as for immunocompetent persons. noted in 7 yellow fever vaccine recipients [69].

VACCINES FOR INTERNATIONAL TRAVEL RECOMMENDATIONS FOR VAR AND ZOS IN

IMMUNOCOMPROMISED PATIENTS
IV. Which Vaccines Can Be Administered to Immunocompro-
mised Persons Contemplating International Travel? VAR
V. Should Immunocompromised Patients or Those Scheduled
Recommendations to Receive Immunosuppressive Therapy Receive VAR?
12. Clinicians may administer inactivated vaccines indicated
for travel based on the CDC annual schedule for immuno-
competent adults and children (strong, low). Recommendations
13. Yellow fever vaccine generally should not be adminis- 15. VAR should be given to immunocompetent patients
tered to immunocompromised persons (strong, moderate). without evidence of varicella immunity (ie, age-appropriate
If travel to an endemic area cannot be avoided, vaccination varicella vaccination, serologic evidence of immunity, clini-
can be considered in the following minimally immunocom- cian-diagnosed or -verified history of varicella or zoster, or
promised human immunodeficiency virus (HIV)–infected laboratory-proven varicella or zoster; strong, moderate) if it
individuals: can be administered ≥4 weeks before initiating immunosup-
(a) asymptomatic HIV-infected adults with CD4 T-cell pressive therapy (strong, low).
lymphocyte count ≥200 cells/mm3 (weak, low) 16. A 2-dose schedule of VAR, separated by >4 weeks for pa-
(b) asymptomatic HIV-infected children aged 9 months–5 tients aged ≥13 years and by ≥3 months for patients aged 1–
years with CD4 T-cell lymphocyte percentages of ≥15 12 years, is recommended if there is sufficient time prior to
(weak, very low). initiating immunosuppressive therapy (strong, low).
14. With certain exceptions (eg, yellow fever vaccine and 17. VAR should not be administered to highly immunocom-
MMR vaccine in certain HIV-infected patients [see recom- promised patients. However, certain categories of patients
mendation 13 and HIV section] and in certain HSCT pa- (eg, patients with HIV infection without severe immunosup-
tients [see HSCT section]), live vaccines should not be given pression or with a primary immune deficiency disorder
to immunocompromised persons (strong, low). without defective T-cell–mediated immunity, such as
primary complement component deficiency disorder or
Evidence Summary chronic granulomatous disease [CGD]) should receive VAR,
The immunocompromised person’s vaccination status should adhering to a 2-dose schedule separated by a 3-month inter-
be assessed and vaccinations updated as needed before travel val (strong, moderate).
[60, 61]. Helpful information can be found at the CDC Travel- 18. VAR can be considered for patients without evidence of
ers’ Health website and in the “Yellow Book—CDC varicella immunity (defined in recommendation 16) who are

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e65

 receiving long-term, low-level immunosuppression (weak, immunity, (2) risk of exposure to varicella has diminished, (3)
very low). antiviral agents are available for treatment, (4) chemotherapy
19. VAR should be administered to eligible immunocom- regimens change frequently and often are more immunosup-
promised patients as the single antigen product, not VAR pressive than those under which varicella vaccination was
combined with MMR vaccine (strong, low). studied, and (5) protection will likely be superior if vaccination
occurs after significant immune recovery.
Evidence Summary The CDC ACIP recommends that patients on chemotherapy
Varicella severity and mortality are increased in children and or radiation for hematopoietic malignancies receive live virus
adults for many conditions associated with immune compro- vaccines when in remission and off therapy for ≥3 months
mise and immunosuppressive therapy [70, 71]. VAR, which with evidence of substantial CMI recovery [11, 45].
contains live-attenuated VZV (Oka strain), is not licensed for HSCT. Safety and immunogenicity were satisfactory when
use in immunocompromised patients because of its potential to VAR was administered to a small number of HSCT recipients
cause severe disease in patients who lack sufficient T-cell– (allogeneic and autologous) at 12–24 months posttransplanta-
mediated immune responses [72–74]. tion when they were not immunosuppressed and met criteria
Varicella vaccination with sufficient time prior to immuno- similar to those for other immunocompromised children [85].
suppression is useful in patients without evidence of varicella More than 30 additional allogeneic HSCT recipients safely re-

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immunity (defined in recommendation 16). Immune response ceived 2 doses of VAR 24 months after transplant when they
is nearly optimal in 2 to 3 weeks, and replicating VZV should were off therapy, had no GVHD, had a normal phytohemag-
be cleared after 3 weeks. Vaccine-related rash, which has oc- glutinin or mitogen response, and had a CD4 T-cell lympho-
curred up to 42 days after vaccination, is uncommon after 21 cyte count ≥200 cells/mm3 [86]. At least 85% developed
days in immunocompetent vaccinees [46, 75]. Vaccine virus specific antibody, generally in association with VZV-specific
given in the week before starting therapy for malignancy was CMI. Similarly, VAR was safely administered ≥2 years after
associated with 1 death and has resulted in reactivation of VZV HSCT to 46 children who were off immunosuppression, had a
that subsequently became resistant to antiviral drugs [73, 76, CD4 T-cell lymphocyte count ≥200 cells/mm3, and had re-
77]. A 2-dose schedule that is separated by ≥28 days for those sponded to ≥1 other vaccine [87]. VAR is commonly safely ad-
aged ≥13 years and by ≥3 months for children aged 12 ministered ≥24 months after successful HSCT. The clinical
months–12 years is desirable for maximal protection. Most efficacy of VAR in this situation has not been established. The
VAR studies of immunocompromised children used a single presence or absence of anti-varicella antibody is not likely an
dose; therefore, the potential for protection is likely greater accurate predictor of protection, since VZV-specific CMI is es-
than what has been reported to date. Some immunocompro- sential for recovery from VZV infections. Patients receiving
mised patients had lower immune response to VAR than that VAR must not be receiving prophylactic anti-herpes viral
observed in immunocompetent persons [78, 79]. therapy or immune globulin therapy because these treatments
Malignancy. Leukemic children on maintenance chemother- interfere with vaccine effect.
apy were vaccinated within a specific window for timing of che- Renal transplant. Varicella vaccination after renal transplan-
motherapy and lymphocyte concentration threshold. Two tation, within carefully controlled limits of maintenance immu-
doses induced either VZV-specific humoral immunity or CMI, nosuppression and immunologic specifications, was well
or both, in >90% of vaccinees [19, 80, 81] and resulted in >85% tolerated. At 6–12 months after vaccination, 75%–85% had
efficacy after household exposure. VAR was safely administered VZV antibody. Mild varicella occurred 2–4 years after vaccina-
to >50 Japanese children with nonlymphoma tumors with clin- tion in 3 of 34 patients [17].
ical and immunological outcomes similar to those for acute leu- Liver transplant. VAR was administered after liver transplanta-
kemia [82, 83]. The results of >10 other small vaccination tion to 15 varicella-naive children and to 7 previously vaccinated
studies in approximately 150 children with solid tumors closely children who had lost their VZV antibody. These patients were
replicated the Japanese experience. ≥6 months posttransplantation, were on limited dosages of im-
Varicella vaccination in children with leukemia was often munosuppressive medications, and had not been treated for re-
complicated, however, by systemic reactions (eg, fever and dis- jection episodes during the prior month. No safety issues were
seminated rash in 40%) that affected the chemotherapy sched- identified. Immune responses were good, and 10 varicella expo-
ule and required treatment with acyclovir [73, 82, 84]. Severe sures occurred without subsequent varicella [16, 18].
reactions have occurred in children with other malignancies HIV infection. Approximately 100 children aged <8 years
[82]. Additional arguments against the use of VAR in children with HIV safely received VAR without alterations in their CD4
with malignancies include the following: (1) children who re- T-cell lymphocyte percentage or count or in their plasma viral
ceived VAR prior to immunosuppression may retain protective load [79, 88]. They had a baseline CD4 T-cell lymphocyte

e66 • CID 2014:58 (1 February) • Rubin et al

percentage ≥15 and most were on combination antiretroviral VI. Should Immunocompromised Patients or Those Who
therapy (cART). Two doses administered 3 months apart re- Will Undergo Immunosuppression Receive ZOS?
sulted in good immune responses similar to those in HIV-
infected children convalescing from natural varicella, which Recommendations
appeared not to pose risk for repeat infection. Effectiveness of 20. ZOS should be given to patients aged ≥60 years if it can
VAR in HIV-infected children is suggested by several long- be administered ≥4 weeks before beginning highly immuno-
term follow-up studies with effectiveness in preventing varicella suppressive therapy (strong, low).
(82%) and zoster (100%) [20, 89]. Optimal timing for vaccina- 21. ZOS should be considered for varicella-positive patients
tion is after ≥3 months of successful cART [79]. (ie, persons with a history of varicella or zoster infection or
Other immunosuppressive conditions. Patients with cellular who are varicella–zoster virus [VZV] seropositive with no
immune deficiencies, patients receiving immunosuppressive previous doses of VAR) aged 50–59 years if it can be admin-
drugs similar in type and dose to those used for the conditions istered ≥4 weeks before beginning immunosuppressive
mentioned above, and patients receiving high-dose steroid therapy (weak, low).
therapy should not receive VAR [90, 91]. VAR was safe and im- 22. ZOS should be administered to patients aged ≥60 years
munogenic in 25 pediatric patients with rheumatic diseases who are receiving therapy considered to induce a low level of
who were receiving MTX, and no disease flares were associated immunosuppression (strong, low).

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with vaccination [92, 93]. Six pediatric patients with IBD on im- 23. ZOS should not be administered to highly immunocom-
munosuppressive therapy who received VAR tolerated it and promised patients (strong, very low).
had good immune responses; however, 5 of them received their
initial dose of VAR prior to immunosuppression [92]. There Evidence Summary
are no data on VAR in patients receiving biological immuno- Persons with varicella immunity that was induced by VAR are
suppressants, patients receiving drugs that deplete B cells or at lower risk for HZ than those with a history of varicella
antagonize costimulatory molecules, or varicella-naive immu- disease and should not receive ZOS. In some clinical situations,
nocompromised adults. Since adults are less responsive to VZV immunosuppression that results in increased risk for zoster can
antigens and more susceptible to varicella complications than be delayed for a significant period of time (eg, prior to organ
children, there is additional uncertainty about vaccination transplantation, chemotherapy, use of biological modifiers);
timing for adults who have been severely immunosuppressed. however, urgent treatments should not be delayed. ACIP sug-
Most advisory groups indicate that adult vaccination should be gests administering ZOS ≥2 weeks prior to immunosuppres-
guided by recommendations for children; however, VAR sion [10]; the panel suggests 4 weeks for all live vaccines. A
should be administered only when an immunocompromised strong VZV-specific response to ZOS occurs within 2 weeks in
adult has substantially recovered from immunosuppression. immunocompetent persons [96].
MMRV vaccine has not been evaluated in immuno- ZOS should be considered in varicella-positive patients (ie,
compromised patients and should not be administered to persons with a history of varicella or zoster infection or are
persons with primary or secondary immunodeficiency because VZV seropositive with no previous doses of VAR) who will
it contains ≥7-fold more VZV than monovalent VAR. When undergo immunosuppressive therapy and are aged 50–59 years.
administered as a first dose to immunocompetent children Some vaccine-boosted immunity may persist during immuno-
aged <4 years, it is significantly more likely to cause fever and suppression and attenuate, if not prevent, subsequent HZ.
febrile seizures than MMR vaccine and VAR administered sepa- ZOS will likely be well tolerated in patients receiving low-
rately [94, 95]. dose immunosuppressive therapies defined by the ACIP as “not
sufficiently immunosuppressive to cause concerns for vaccine
Herpes Zoster Vaccine safety” [10], such as low-dose prednisone (<2 mg/kg; maximum
The incidence and severity of herpes zoster (HZ) increase with ≤20 mg/day), MTX (≤0.4 mg/kg/week), azathioprine (≤3 mg/
age and also with degree of immune compromise. ZOS is not li- kg/day), and 6-mercaptopurine (≤1.5 mg/kg/day). ZOS was
censed for use in highly immunocompromised patients for the well tolerated in a cohort of 62 adults with hematological malig-
same reasons as those against administration of VAR to these nancies, including 31 with stem cell transplant (autologous, 26;
patients. Two differences that may be relevant are that ZOS allogeneic, 5), except for 1 patient who experienced trigeminal
contains 14-fold more (at expiry) live VZV than does VAR and zoster 3 weeks after vaccination [97]. Vaccine efficacy in these
most immunocompromised patients at risk for HZ (except al- patient populations is unknown.
logeneic HSCT patients) had previously developed primary Absence of safety and efficacy data precludes ZOS in patients
VZV immunity and should have residual VZV-specific on biological immunosuppressants. However, clinical features of
immune memory, even with immunosuppression. HZ that developed in >100 patients receiving TNF-α modulators

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e67

for RA resulted in acceptable severity, suggesting that such pa- malignancies, among whom no safety issues were identified [38,
tients could tolerate the less-pathogenic VZV in ZOS [98, 99]. 39, 106, 107]. LAIV and IIV were compared in 243 pediatric pa-
Risk of zoster is higher for patients receiving anti–TNF-α anti- tients with HIV infection aged 5–17 years on a stable cART
bodies than for those receiving TNF-α-antagonists [98]. Data on regimen [39]. Safety and immunogenicity of both vaccines were
zoster vaccination of varicella-immune immunocompromised similar to those reported in immunocompetent children.
patients aged <50 years are limited. Preliminary results of zoster
vaccination in 286 HIV-infected adults on stable antiretroviral RECOMMENDATIONS FOR VACCINATION OF
therapy showed safety and immunogenicity. PATIENTS WITH PRIMARY
IMMUNODEFICIENCY DISORDERS
RECOMMENDATIONS FOR INFLUENZA
VACCINE IN THE IMMUNOCOMPROMISED Primary immunodeficiency disorders are a heterogeneous
HOST group that includes genetic congenital disorders that affect the
functioning of either the innate or adaptive immune systems
VII. Should Immunocompromised Patients Receive Influenza [108]. Defects of the adaptive immune system are divided into
Vaccine? defects in antibody production alone or defects in T cells that
result in combined (cell- and antibody-mediated) immunodefi-

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Recommendations ciency. Depending on the type of disorder, the impaired
24. Annual vaccination with IIV is recommended for immu- immune response may result in vaccine failure or, with live vac-
nocompromised patients aged ≥6 months (strong, moderate) cines, vaccine-associated disease. However, vaccination can be
except for patients who are very unlikely to respond (although safe and effective in many situations. Vaccination of asplenic
unlikely to be harmed by IIV), such as those receiving inten- patients is addressed in question XXII.
sive chemotherapy (strong, low) or those who have received VIII. Which Vaccines Should Be Administered to Patients
anti–B-cell antibodies within 6 months (strong, moderate). With Primary (Congenital) Complement Deficiencies?
25. LAIV should not be administered to immunocompro-
mised persons (weak, very low). Recommendations
26. Patients with primary complement deficiencies should
Evidence Summary receive all routine vaccines based on the CDC annual sched-
IIV can be safely administered to and is indicated annually for ule; none are contraindicated (strong, low).
all immunocompromised patients aged ≥6 months including 27. Patients with primary complement deficiencies and who
patients receiving immunosuppressive therapy for chronic in- are:
flammatory disease, oncology patients receiving chemotherapy, (a) aged 2–5 years should receive 1 dose of pneumococcal
immunosuppressed transplant patients, HIV patients, and conjugate vaccine (PCV)13 if they have received 3
primary immunodeficiency patients (eg, common variable doses of PCV (either 7-valent PCV [PCV7] or PCV13)
immune deficiency [CVID]) [100–104]. Patients aged <9 years before age 24 months and 2 doses of PCV13 (8 weeks
who have never received influenza vaccine or received only 1 apart) if they have received an incomplete schedule of
dose in the previous season should be vaccinated with 2 doses ≤2 doses of PCV7 (PCV7 or PCV13) before age 24
given 1 month apart [41]. Relatively small observational studies months (strong, low).
support the immunogenicity of IIV in all these groups except (b) aged 6–18 years with a classic pathway (C1, C2, C3, C4),
primary immunodeficiency patients. Data summarized else- alternate pathway, or severe mannan-binding lectin
where in this guideline emphasize the safety of IIV in immuno- (MBL) deficiency who have not received PCV13 should
compromised populations. Immune response to IIV is good in receive a single dose of PCV13 (strong, very low).
most children with IBD or rheumatologic inflammatory illness- (c) aged ≥19 years with a classic pathway (C1, C2, C3, C4),
es, except those receiving anti–TNF-α antibodies. Immune re- alternate pathway, or severe MBL deficiency who are
sponse is often poor in cancer chemotherapy patients; in adults PCV13 naive should receive a single dose of PCV13
receiving azathioprine, infliximab, or rituximab; and in SOT re- (strong, very low). For those who have received
cipients receiving mycophenolate. A single study of antibody- PPSV23, PCV13 should be administered ≥1 year after
deficient patients on immunoglobulin therapy showed poor the last PPSV23 dose (weak, low).
immunogenicity but no safety issues [105]. 28. Patients aged ≥2 years with an early classic pathway, al-
LAIV is contraindicated in immunocompromised patients ternate pathway, or severe MBL deficiency should receive
because the risks are unknown in most populations. It has been PPSV23 ≥8 weeks after PCV13, and a second dose of
studied in HIV-infected patients and 28 children with PPSV23 should be given 5 years later (strong, low).

e68 • CID 2014:58 (1 February) • Rubin et al

 29. Patients with primary complement deficiencies should (strong, low). Children aged 2–5 years should receive PCV13
receive conjugate meningococcal vaccine. A 4-dose series of as in recommendation 27a (weak, very low).
bivalent meningococcal conjugate vaccine and Haemophilus 32. Patients aged ≥6 years with phagocytic cell deficiencies
influenzae type b conjugate vaccine (HibMenCY; MenHi- other than CGD (unless patient with CGD is receiving im-
brix, GlaxoSmithKline) should be administered at age 2, 4, 6, munosuppressive medication) should receive PCV13 as in
and 12–15 months for children aged 6 weeks–18 months recommendations 27b and 27c (weak, very low).
(strong, low) or a 2-dose primary series of meningococcal 33. Patients aged ≥2 years with phagocytic cell deficiencies
conjugate vaccine, quadrivalent (MCV4) should be adminis- other than CGD (unless patient with CGD is receiving im-
tered to patients with primary complement component defi- munosuppressive medication) should receive PPSV23 ≥8
ciency at age 9 months–55 years (MCV4-D [Menactra, weeks after receipt of PCV13, and a second dose of PPSV23
Sanofi Pasteur] for those aged 9–23 months; MCV4-D or should be given 5 years later (weak, low).
MCV4-CRM [Menveo, Novartis] for those aged 2–54 years; 34. Live bacterial vaccines, such as bacillus Calmette–Guérin
strong, low). For persons aged >55 years, MPSV4 should be (BCG) or oral typhoid vaccine, should not be administered
administered if they have not received MCV4 and MCV4 to patients with a phagocytic cell defect (strong, moderate).
should be administered if they have received MCV4 (strong, 35. Live viral vaccines should be administered to patients
low). For patients aged 9–23 months, the doses should be with CGD and to those with congenital or cyclical neutrope-

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administered 3 months apart; for patients aged ≥2 years, the nia (weak, low).
doses should be administered 2 months apart. MCV4-D 36. Live viral vaccines should not be administered to pa-
should be administered ≥4 weeks after a dose of PCV13 tients with leukocyte adhesion deficiency, defects of cytotox-
because of a reduced antibody response to some pneumo- ic granule release such as Chediak–Higashi syndrome (see
coccal serotypes when MCV4-D and PCV7 are administered section on combined immunodeficiencies), or any other un-
simultaneously (strong, low). defined phagocytic cell defect (strong, low).
30. Patients with a primary complement component defi-
ciency should be revaccinated with MCV4 (or MPSV4 for Evidence Summary
those aged >55 years who have not received MCV4) every 5 For inactivated vaccines, but not for live viral vaccines except in
years (strong, low) [109]. CGD patients, patients with phagocytic cell defects should have
normal immune responses and the same adverse effects as immu-
Evidence Summary nocompetent individuals. Patients with CGD are not at increased
Immunogenicity of MPSV4 has been demonstrated in patients risk for infections with pneumococcus [127, 128], and there is
with complement deficiencies [110–116]. Revaccination is limited data on the risk of invasive pneumococcal infection in pa-
needed to maintain levels of antibody to both MPSV4 [113, tients with other phagocytic cell defects [127, 128]. There are no
115] and MCV4 [117–119]. Occasional reports of poor or aber- data on which to base a recommendation for live, oral rotavirus
rant antibody responses in patients with early classic comple- vaccine in CGD patients with IBD. Staphylococcus aureus is a
ment component deficiency [120–123] support the potential major pathogen in individuals with phagocytic defects. Because
(not established) importance of monitoring antibody responses influenza infection may predispose to respiratory infection with
in this subset. CDC’s ACIP recommends routine use of PCV13 this organism [129], annual influenza vaccination is important.
for immunocompromised persons [109, 124]. MCV4-D can in- Live vaccines, especially viruses, should be avoided in pa-
terfere with the response to some serotypes of PCV7 when both tients with leukocyte adhesion deficiency or cytotoxic granule-
are administered simultaneously [481]. release defects (eg, Chediak–Higashi syndrome) because the
Since influenza may predispose to invasive bacterial respira- defective cytotoxicity of T and natural killer (NK) cells results
tory infection [125, 126], annual influenza vaccination is im- in abnormal immune response [130, 131]. Since some defects
portant in this group. Influenza vaccine has not been studied in that affect neutrophil function may also affect lymphocyte
patients with complement deficiencies, but safety is likely function and potentially depress response to live vaccines, indi-
similar to that in immunocompetent persons. viduals with phagocytic defects undefined at a molecular level
IX. Which Vaccines Should Be Administered to Patients should not receive live vaccines. Dissemination of BCG can
With Phagocytic Cell Deficiencies (eg, CGD, Leukocyte Adhe- occur in CGD patients [132–135]. There are no reported cases
sion Deficiency, Chediak–Higashi Syndrome)? of vaccine-associated disease caused by live oral typhoid
vaccine in CGD patients. However, nontyphoidal salmonella
Recommendations infection is the most common cause of bacteremia [127], con-
31. Patients with phagocytic cell deficiencies should receive firming poor control of this group of organisms. Therefore, live
all inactivated vaccines based on the CDC annual schedule oral typhoid vaccine should be avoided in CGD patients.

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e69

 X. Which Vaccines Should Be Administered to Patients (weak to strong, very low to low). Those aged ≥2 years
With Innate Immune Defects Resulting in Defects of Cytokine should receive PPSV23 ≥8 weeks after indicated doses of
Generation/Response or Cellular Activation (eg, Defects of the PCV13, and a second dose should be given 5 years later
Interferon-gamma/Interleukin-12 Axis)? (strong, low).
44. Monitoring of vaccine responses can be useful for assess-
Recommendations ing the degree of immunodeficiency of patients with minor
37. Patients with innate immune defects that result in antibody deficiencies and level of protection (weak, moder-
defects of cytokine generation/response or cellular activation ate).
should receive all inactivated vaccines based on the CDC 45. OPV should not be administered to IgA-deficient pa-
annual schedule (strong, very low). tients (strong, low).
38. For patients with innate immune defects that result in
Evidence Summary
defects of cytokine generation/response or cellular activa-
Patients with minor antibody deficiencies are likely to be able
tion, PCV13 should be administered as in recommendations
to mount at least partial antibody responses to vaccines, which
27a–c (weak to strong, very low to low).
may aid in the assessment of the degree of immunodeficiency.
39. The advice of a specialist should be sought regarding in-
In some instances, apparently minor antibody deficiencies are
dividual conditions concerning use of live vaccines in pa-
associated with a CMI defect (eg, DiGeorge syndrome [143,

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tients with innate immune defects that result in defects of
144]), which is an important consideration before giving live
cytokine generation/response or cellular activation/inflam-
vaccines. In SPAD [145], protein–polysaccharide conjugate
mation generation (strong, low).
vaccines will, to some extent, overcome the defect and produce
40. Live bacterial vaccines should not be administered to pa-
some antibody response [146].
tients with defects of the interferon-gamma/interleukin-12
In ataxia–telangiectasia, response to PPSV23 is, for the most
(IFN-γ/IL-12) pathways (strong, moderate).
part, poor. In small studies, PCV7 was immunogenic in most
41. Live viral vaccines should not be administered to pa-
patients, although not comparable to immunocompetent con-
tients with defects of IFN (alpha or gamma) production
trols [147–149]. OPV should not be administered to IgA-defi-
(strong, low).
cient patients [150–152].
Evidence Summary XII. Which Vaccines Should Be Administered to Patients
There is a group of heterogeneous defects of innate immunity With Major Antibody Deficiencies Receiving Immunoglobulin
in which cytokine generation or response and resultant cellular Therapy?
activation and inflammation are abnormal. In some cases,
functioning of the adaptive immune response may also be af-
Recommendations
fected. Inactivated vaccines often induce adequate immune re-
46. Inactivated vaccines other than IIV are not routinely ad-
sponses without serious adverse events in patients with defects
ministered to patients with major antibody deficiencies
of cytokine generation/response or cellular activation (eg,
during immunoglobulin therapy (strong, low).
defects of the IFN-γ/IL-12 axis). However, given the increasing
(a) For patients with suspected major antibody deficien-
variety of newly recognized disorders, an immunologist should
cies, all inactivated vaccines can be administered as part
be consulted. Many have increased susceptibility to mycobacte-
of immune response assessment prior to immunoglob-
rial infections including disseminated BCG [136–140]. Many
ulin therapy (strong, low).
molecular defects can result in defects of antiviral immunity
47. IIV can be administered to patients with major antibody
[141, 142], contraindicating the use of live viral vaccines.
deficiencies and some residual antibody production (weak,
XI. Which Vaccines Should Be Administered to Patients
low).
With Minor Antibody Deficiencies?
48. Live OPV should not be administered to patients with
major antibody deficiencies (strong, moderate).
Recommendations 49. Live vaccines (other than OPV) should not be adminis-
42. Patients with immunoglobulin (Ig)A deficiency or spe- tered to patients with major antibody deficiencies (weak,
cific polysaccharide antibody deficiency (SPAD) should low).
receive all routine vaccinations based on the CDC annual
schedule, provided that other components of their immune Evidence Summary
systems are normal (strong, low). Most patients with major antibody deficiency disorders will be
43. Children with SPAD or ataxia–telangiectasia should on immunoglobulin replacement therapy in order to receive
receive PCV13 as described in recommendations 27a–c continual passive immunity. Vaccination with live or

e70 • CID 2014:58 (1 February) • Rubin et al

inactivated vaccines is rarely undertaken in patients receiving with similar CD3 T-cell lymphocyte counts, Wiskott–
immunoglobulin for complete agammaglobulinemia. These pa- Aldrich syndrome, or X-linked lymphoproliferative disease
tients will not have antibody response, although a T-cell re- and familial disorders that predispose them to hemophago-
sponse that aids recovery from some viral infections is possible. cytic lymphohistiocytosis should avoid all live vaccines
IIV can be useful in patients with an incomplete deficiency (strong, moderate).
of antibody production who are receiving immunoglobulin re-
placement therapy. In these patients, it is possible that the im- Evidence Summary
munoglobulin does not contain antibodies against circulating Vaccines are often administered before diagnosis of combined
strains of influenza, and T-cell–mediated responses are likely to immune deficiency. Inactivated vaccines do not cause signifi-
contribute to protection from severe disease. Some patients cant adverse effects, whereas live vaccines (eg, rotavirus) may
with CVID responded to polysaccharide and protein vaccine produce chronic infection in patients with combined immune
antigens; the magnitude of response may have correlated with deficiency [161–163]. Immunity in DGS patients varies from
clinical severity of the immunodeficiency [153–155]. Adults normal to complete athymia. With a CD3 T-cell lymphocyte
with major humoral immunodeficiencies, mainly on immuno- count >500 cells/mm3 and normal mitogen response, MMR
globulin therapy, had very poor responses to IIV, particularly and VZV vaccines are safe and produce high seroconversion
those with CVID, but had some response to the A (H1N1) rates [164–166]; however, antibody levels may fall significantly
after 1 year [167] (a finding of unclear clinical significance).

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component [105].
VAPP is a recognized complication of major antibody defi- There are no published data on live virus vaccination in other
ciency syndromes [156–158], but the absence of chronic OPV partial T-cell defects. Extrapolation from HIV-infected persons
secretors among 2 sizeable cohorts of antibody-deficient pa- suggests that a CD4 T-cell lymphocyte count ≥200 cells/mm3
tients suggests that the condition is rare [159, 160]. There is no (adults) or percentage ≥15 (children) is a reasonable criterion
published evidence of harm from inactivated vaccines unique but is of uncertain validity.
to this patient population. T-cell–deficient children receiving live viral vaccines have de-
Live virus vaccines should be avoided since the risk is veloped VAPP [168], disseminated measles infection including
unknown and they are unlikely to lead to protection because of pneumonitis [169–171], and chronic rotavirus infection [161–
preexisting neutralizing antibody from administered immuno- 163, 172] after receiving the relevant vaccines. In disorders that
globulin. predispose to hemophagocytic lymphohistiocytosis (eg, perfor-
XIII. Which Vaccines Should Be Administered to Patients in deficiency), immune response to viruses is abnormal because
With Combined Immunodeficiencies? of defective cytotoxicity of T and NK cells. Therefore, live vac-
cines should be avoided [173]. Disseminated BCG may be the
Recommendations presenting feature of SCID or it may develop during stem cell
50. For patients with suspected combined immunodeficien- transplantation [174].
cies, all inactivated vaccines can be administered as part
immune response assessment prior to commencement of RECOMMENDATIONS FOR VACCINATION OF
immunoglobulin therapy (strong, low). HIV-INFECTED ADULTS, ADOLESCENTS, AND
(a) For patients with combined immunodeficiencies who CHILDREN
are receiving immunoglobulin therapy, inactivated vac-
cines should not be routinely administered (strong, XIV. Which Inactivated Vaccines Should Be Administered to
low). HIV-Infected Patients?
51. For patients with combined immunodeficiencies and re-
sidual antibody production potential, IIV can be adminis- Recommendations (Table 2)
tered (weak, very low). 54. HIV-infected patients should be vaccinated according to
52. Children with partial DiGeorge syndrome ( pDGS) the CDC annual schedule for the following inactivated vac-
should undergo immune system assessment with evaluation cines: IIV (strong, high); PCV13 in patients aged <2 years
of lymphocyte subsets and mitogen responsiveness in order (strong, moderate); H. influenzae type b conjugate (Hib)
to determine whether they should be given live viral vac- vaccine (strong, high); diphtheria toxoid, tetanus toxoid,
cines. Those with ≥500 CD3 T cells/mm3, ≥200 CD8 T acellular pertussis (DTaP) vaccine (strong, moderate);
cells/mm3, and normal mitogen response should receive tetanus toxoid, reduced diphtheria toxoid, and reduced acel-
MMR vaccine and VAR (weak, low). lular pertussis (Tdap) vaccine (strong, very low); tetanus
53. Patients with SCID, DGS with a CD3 T-cell lymphocyte toxoid, reduced diphtheria toxoid (Td) vaccine (strong, low);
count <500 cells/mm3, other combined immunodeficiencies hepatitis B (HepB) vaccine (strong, moderate); hepatitis A

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e71

 (HepA) vaccine (strong, moderate); inactivated poliovirus prevents genital warts (strong, low), although there are no
(IPV) vaccine (strong, moderate); and quadrivalent human data on differences between the vaccines for preventing cer-
papillomavirus (HPV4) vaccine in females and males aged vical dysplasia in HIV-infected women.
11–26 years (strong, very low) with additions noted below.
55. PCV13 should be administered to HIV-infected patients Evidence Summary
aged ≥2 years as in recommendations 27a–c (Table 2; Administration of inactivated vaccines to HIV-infected persons
strong, low to moderate). appears safe as no increases in adverse effects or HIV-specific
56. PPSV23 should be administered to HIV-infected chil- adverse effects have been recognized. However, data are not suffi-
dren aged ≥2 years who have received indicated doses of cient to comment on rare adverse effects. Concern about acceler-
PCV (strong, moderate), HIV-infected adults with CD4 T- ating progression of the HIV infection is unfounded. A transient
lymphocyte counts of ≥200 cells/mm3 (strong, moderate), increase in plasma HIV viral load may occur after vaccination in
and HIV-infected adults with CD4 T-lymphocyte counts of children not receiving cART but this resolves in 2 to 6 weeks
<200 cells/mm3 (weak, low). PPSV23 should be given ≥8 [102, 175, 176]. Patients receiving cART do not experience signifi-
weeks after indicated dose(s) of PCV13, and a second dose cant changes in viral load or T-cell concentrations after adminis-
of PPSV23 should be given 5 years later (strong, low). tration of either live or inactivated vaccines [79, 177–181]. In
57. HIV-infected children who are aged >59 months and general, live vaccines are contraindicated in HIV-infected persons
with low CD4 T-cell lymphocyte counts or percentages.

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have not received Hib vaccine should receive 1 dose of Hib
vaccine (strong, low). Hib vaccine is not recommended for Vaccination guidelines for HIV-infected adolescents and
HIV-infected adults (weak, low). adults have been published by the CDC, National Institutes of
58. HIV-infected children aged 11–18 years should receive a Health (NIH), and HIV Medical Association (HIVMA) of
2-dose primary series of MCV4 2 months apart (strong, IDSA [8]; guidelines for HIV-infected children have been pub-
moderate). A single booster dose (third dose) should be lished by CDC, NIH, HIVMA of IDSA, Pediatric Infectious
given at age 16 years if the primary series was given at age 11 Diseases Society, and AAP [7].
or 12 years and at age 16–18 years if the primary series was HIV-infected children often have lower antibody and CMI
given at age 13–15 years (strong, low). If MCV4 is adminis- responses to vaccines than immunocompetent persons, al-
tered to HIV-infected children aged 2–10 years because of though these responses may still be protective [79, 88, 177–180,
risk factors for meningococcal disease, a 2-dose primary 182]. The vaccine-induced responses correlate with the adequa-
series of MCV4 should be administered with a 2-month in- cy of the CD4+ T-cell pool and plasma HIV load at the time of
terval between doses, and a booster dose should be given 5 vaccination, each of which is an independent predictor of the
years later (strong, very low). magnitude of the immune response [79, 177, 178, 180, 183]. In
59. HIV-infected patients should receive the HepB vaccine some, but not all, studies, the CD4+ T-cell lymphocyte percent-
series (strong, moderate), with consideration of high-dose age at the time of vaccination in children on a stable cART
HepB vaccine (40 µg/dose) for adults (weak, moderate) and regimen is a better predictor of response than is the nadir per-
adolescents (weak, low). One to 2 months after completion, centage count prior to starting cART [79, 177–179]. Antibody
patients should be tested for anti-HBs (antibodies to HepB levels from prior vaccination may increase after cART even in
surface antigen; strong, low). If a postvaccination anti-HB the absence of a vaccine boost. Responses to vaccines are signif-
concentration of ≥10 mIU/mL is not attained, a second 3- icantly better in patients who have been on cART ≥3 months,
dose series of HepB vaccine (strong, low; alternative: 1 dose specifically after improvement in the CD4+ T-cell lymphocyte
of HepB vaccine after which anti-HBs is tested ), using stan- percentage (optimally ≥15) and reduction in plasma HIV viral
dard dose (strong, moderate) or high dose (40 µg ; weak, load (optimally to <1000 copies/mL), suggesting that vaccina-
low) for children and high dose for adolescents and adults tions should be delayed until cART has been undertaken [184].
(strong, low), should be administered.
60. HepB vaccine containing 20 µg of HepB surface antigen Influenza Vaccination With IIV
(HBsAg) combined with HepA vaccine (HepA–HepB; Antibody responses to IIV are blunted in patients who have un-
Twinrix), 3-dose series, can be used for primary vaccination of treated HIV [185–187] and are improved in patients who do
HIV-infected patients aged ≥12 years (strong, moderate). not have progressive HIV disease and/or are receiving cART
61. Internationally adopted HIV-infected children who have [188]. Efficacy of IIV in HIV-infected adults was established in
received doses of OPV should receive a total of 4 doses of a 5 controlled trials; efficacy and clinical effectiveness ranged
combination of OPV and IPV vaccine (strong, low). from 27% to 78% [13, 189]. In HIV-infected adults, IIV was not
62. HPV4 vaccine is recommended over bivalent human associated with increased or unusual adverse effects, although
papillomavirus (HPV2) vaccine because HPV4 vaccine rare adverse effects may not have been detected [41]. In contrast

e72 • CID 2014:58 (1 February) • Rubin et al

with previous reports [190, 191], subsequent prospective trials given to immunocompetent adults without concern for hypores-
found no significant long-term difference in HIV RNA levels ponsiveness if the recipient has received MPSV [213, 214]. If
between influenza-vaccinated and unvaccinated HIV-positive MCV4 is administered to HIV-infected children aged ≥2 years, a
patients [192, 193]. The monovalent 2009 pandemic A (H1N1) 2-dose primary series of MCV4 should have a 2-month interval
vaccine was immunogenic in HIV-infected children but less between doses [215, 216]. A single dose of MCV4 was safely ad-
immunogenic in HIV-infected adults than in HIV-uninfected ministered to 320 HIV-infected children aged >11 years on
adults [194]. No safety issues were identified [181, 195], al- cART with a CD4 T-cell lymphocyte percentage ≥15 [215] and
though the presence of the adjuvant “Adjuvant System 03” to children aged 2–11 years with a CD4 T-cell lymphocyte per-
(ASO3) was associated with a small increase in plasma HIV centage ≥25. Antibody against ≥1 serotype showed a 4-fold
RNA in 1 study [176]. increase to 1 or more antigens in 88% of vaccinees and in 50%–
70% of individual serotypes. Although antibody levels were sig-
Pneumococcal Vaccination nificantly lower than in HIV-uninfected children, protective
PCV is safe and efficacious [196–199] in HIV-infected children titers were present in 55%–90% (depending on serotype) after
and is more immunogenic than PPSV23 [200–202]. However, vaccination. Antibody levels fell approximately 50% in the 6
the antibody produces decays more rapidly than in uninfected months after vaccination. A 2-dose regimen of MCV4 was ad-
children, has lower functional activity, and the anamnestic re- ministered to 59 HIV-infected children aged 2–10 years with a

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sponse is blunted [203]. Two doses of PCV7 were safely admin- good safety profile and generally good immunogenicity that
istered to HIV-infected children aged <18 years on cART, varied with serogroup [216]. Response after a single MCV4 dose
followed by 1 dose of PPSV23 [178]. The antibody response was high to serogroup A (92%) and W-135 (98%); responses im-
was excellent and persistence was similar to that observed in proved after a second dose for serogroup C (from 43% to 80%; P
uninfected children. Although PCV13 has not been studied in < .0001) and serogroup Y (from 76% to 84%; P = .38).
HIV-infected children, PCV13 has replaced PCV7 in the vacci-
nation schedule [124, 204]. A randomized, controlled trial of Diphtheria, Tetanus, Pertussis Vaccination
PCV7 in HIV-infected adults in Malawi, the majority of whom Children with HIV often have low to undetectable levels of anti-
were not on antiretroviral therapy, showed that the vaccine was body against pertussis, diphtheria, and tetanus [179, 217–221]
safe and had an efficacy of 75% in preventing recurrent invasive after receiving 3 or 4 doses of Diphtheria toxoid, whole cell per-
pneumococcal infection [205]. CDC’s ACIP recommends tussis, tetanus toxoid vaccine (DPT) or diphtheria toxoid, tetanus
routine use of a single dose of PCV13 for immunocompro- toxoid, acellular pertussis (DTaP) vaccine. Booster vaccination of
mised adults [109]. HIV-infected children with DTaP is safe and does not signifi-
PPSV23 efficacy has been studied primarily in adults/adoles- cantly affect the CD4 T-lymphocyte cell count or HIV RNA
cents with CD4 T-lymphocyte counts ≥200 cells/mm3. Most levels [179, 221]. Although the booster dose of DTaP vaccine sig-
studies have shown that PPSV23 reduces pneumococcal bacter- nificantly increases anti-pertussis [179] and anti-tetanus [218]
emia and decreases mortality in HIV-infected adults [206– antibody levels, they remain significantly lower than those
208]. However, 1 study performed in Uganda found an increase induced in uninfected children after a primary series or a booster
in pneumococcal disease in vaccine recipients [209]. Although dose at 4 to 6 years. The efficacy of primary or booster DTaP vac-
efficacy is uncertain for individuals with CD4 counts <200 cination in HIV-infected children is unknown. Tdap vaccination
cells/mm3, PPSV23 should be offered to such patients with has not been studied in HIV-infected children or adults.
consideration of revaccination once antiretroviral therapy has
resulted in a CD4 count ≥200 cells/mm3. Hepatitis B Vaccination
HepB infection is commonly acquired by infants born to
Haemophilus influenzae Type b Vaccination mothers dually infected with HepB virus (HBV) and HIV. The
HIV-infected children not on cART are less likely to respond to efficacy of infant prophylaxis against HBV, HepB, and HepB
Hib vaccine, and their antibody responses often fall below immune globulin (HBIG) within 12 hours of birth in the pres-
levels associated with long-term protection (≥0.15 µg/mL) ence of HIV infection is unknown. However, prophylaxis is
within 1 year [210]. Nevertheless, Hib vaccination was highly likely to minimize, but not entirely prevent, mother-to-child
effective over a 2-year period in HIV-infected children in South transmission [222]. Children born to HIV-infected mothers
Africa [182, 211] and Malawi [212]. should receive their first dose of HepB vaccine before hospital
discharge [223].
Meningococcal Vaccination HepB vaccine is indicated and can be safely given to HIV-
As in immunocompetent persons, MCV4 is preferred over infected patients, but immunogenicity is lower than in HIV-
MPSV4 for HIV patients aged 9 months–54 years and can be negative adults. Only 18%–72% of HIV-positive persons

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e73

develop protective concentrations of antibodies to HepB others suggest a single dose of vaccine followed by anti-HBs
surface antigen (HBsAg), which are generally lower in magni- testing 2 weeks later. Current guidelines from the CDC, NIH,
tude and wane more quickly than in adults without HIV infec- and the HIV Medicine Association of the IDSA for the preven-
tion [56, 224–226]. Low CD4 count and ongoing HIV viremia tion and treatment of opportunistic infections in HIV-infected
are associated with poor vaccine responses [57, 225–228]. In adolescents and adults recommend giving the complete series
patients not receiving cART, only 30%–50% develop a protec- in patients with a positive isolated HBV core antibody and a
tive antibody response (anti-HBs concentration of ≥10 mIU/ negative test for HBV DNA [8].
mL in immunocompetent persons) [229]. However, protective
levels are reached in 60%–70% of vaccinees receiving cART, Hepatitis A Vaccination
with responsiveness proportional to the percentage of CD4+ T HepA is immunogenic in HIV-infected patients, and no safety
lymphocytes and the extent of virus suppression [230–234]. issues were identified in more than 300 vaccinees [177, 243,
The frequent failure of the primary vaccine series is the ratio- 244]. Almost 100% of HIV-infected children on cART with a
nale for testing for anti-HBs after the third dose of vaccine. CD4 T-cell lymphocyte percentage ≥20–25 seroconverted
When antibody was absent after the standard primary series, a [245]. Younger HIV-infected children have antibody responses
subsequent single booster dose significantly increased the similar to those of uninfected vaccinees, but responses are 10-
number of vaccinees with protective antibody levels in 2 studies to 50-fold lower in older children with a longer duration of
HIV infection. HIV-infected persons should be vaccinated

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[230, 235] but led to only a small increase in another study
[229]. Repeating a 3-dose series induced protective antibody against HepA prior to a decline in CD4 counts to improve the
levels in >75% of patients who failed an initial series [236]. likelihood of an adequate response. Although responses are
However, this response also declined quickly after boosting, better in patients who respond to cART, vaccination should not
even when vaccines containing a higher content of HBsAg were be delayed in at-risk patients. Seroreversion occurs in 10% of
used [230, 233, 236]. Doubling the HepB vaccine dosage from HIV-infected vaccinees within 2 years, but a third dose of
20 µg to 40 µg significantly increased seroconversion rates [57, HepA vaccine is safe and generates high antibody titers that are
58]. In the pre-cART era, the dose of HBsAg was successfully similar in magnitude to those achieved with 2 doses in unin-
doubled for HIV-infected children [237]. All strategies are fected persons. Eighty-five percent of HIV-infected adults
more successful in patients who are on cART. In HIV-infected maintained seropositive antibodies 6 to 10 years after 2 doses of
patients aged 12–20 years who received primary vaccination vaccine [246].
with a 3-dose series of high-dose HepB vaccine (40 µg of
Polio Vaccination
HBsAg; given as Engerix-B, as is done for dialysis patients) or a
Anti-polio antibody concentrations after IPV vaccination are
combined HepA–HepB vaccine (Twinrix), the response rate
lower in HIV-infected children who are not receiving cART
(73%–75% seroresponse) was superior to that with standard
than in uninfected children [247]. Also, booster responses in
HepB vaccine containing 20 µg of HBsAg (Engerix-B; 60%
untreated HIV-infected adults are significantly blunted [248].
seroresponse) [233, 238]. A similar outcome occurred with a 3-
dose series of high-dose HepB vaccine among 267 adult HIV- HPV Vaccination
infected patients with CD4 T-lymphocyte counts >200 cells/ HPV4 vaccine was safe and immunogenic when administered
mm3, the majority of whom were receiving antiretroviral to 126 HIV-infected children aged 7–11 years with CD4 T-lym-
therapy [58]. Seroreversion is also common. Approximately phocyte percentages ≥15 [180]. However, there are no data re-
30% of HIV-infected children who were vaccinated while re- garding safety and efficacy of either vaccine in HIV-positive
ceiving cART did not have seroprotective antibody levels 3 adolescents. HPV4 vaccine was safe and immunogenic in 109
years after vaccination, but 82% had an anamnestic response to HIV-infected adult males [249]. For HIV-infected patients,
a single additional dose of HepB vaccine [239]. The importance HPV4 vaccine is preferred over HPV2 vaccine because of the
of persistent anti-HBs is unclear. There is no evidence in HIV- protection afforded by HPV4 vaccine against genital warts,
uninfected children that loss of antibody after successful vacci- which are more prevalent and more subject to relapse in HIV-
nation results in subsequent clinically significant infection or infected patients than in HIV-uninfected persons [250].
chronic infection [240]. XV. Should Live Vaccines Be Administered to HIV-Infected
For HIV-infected patients who are negative for HBsAg and Patients?
anti-HBs but are anti-HBc (antibodies to HepB core antigen)
positive, there is a possibility of recrudescence of past, occult Recommendation (Table 2)
HBV infection and vaccination recommendations vary. Some 63. HIV-exposed or -infected infants should receive rotavi-
data suggest that these patients are not HBV immune and rus vaccine according to the schedule for uninfected infants
should receive a complete vaccine series [241, 242], while (strong, low).

e74 • CID 2014:58 (1 February) • Rubin et al

 64. HIV-infected patients should not receive LAIV (weak, [258, 259]. MMR vaccine was safely administered to HIV-in-
very low). fected children with ≥15% CD4 T lymphocytes in >1200 pa-
65. MMR vaccine should be administered to clinically stable tients [260, 261]. However, some severe complications occurred
HIV-infected children aged 1–13 years without severe im- in children with lower CD4 T-cell lymphocyte percentages or
munosuppression (strong, moderate) and HIV-infected pa- counts [262]. Titers of MMR antibodies increased after cART
tients aged ≥14 years without measles immunity and with a in previously vaccinated patients, but ≥50% remained seroneg-
CD4 T-cell lymphocyte count ≥200/mm3 (weak, very low). ative. Administration of an additional dose of MMR vaccine to
66. HIV-infected children with a CD4 T-cell percentage <15 children on cART who had ≥15% CD4 T lymphocytes induced
(strong, moderate) or patients aged ≥14 years with a CD4 T- detectable measles antibody in 75%–90% [218, 257, 260],
cell lymphocyte count <200 cells/mm3 should not receive rubella antibody in >90%, and mumps antibody in >60% [260].
MMR vaccine (strong, moderate). No significant adverse effects have been associated with vaccine
67. HIV-infected patients should not receive quadrivalent administration in adults with CD4 counts >200 cells/mm3
MMR-varicella (MMRV) vaccine (strong, very low). [263].
68. Varicella-nonimmune, clinically stable HIV-infected
patients aged 1–8 years with ≥15% CD4 T-lymphocyte per- Varicella Vaccination
centage (strong, high), aged 9–13 years with ≥15% CD4 ACIP recommends varicella vaccination for HIV-positive chil-

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T-lymphocyte percentage (strong, very low), and aged ≥14 dren with mild to moderate immune suppression based on
years with CD4 T-lymphocyte counts ≥200 cells/mm3 safety data [45, 79, 256]. No data exist regarding vaccine safety
should receive VAR (strong, very low). The 2 doses should or efficacy in HIV-infected adults (see Varicella section).
be separated by ≥3 months (strong, moderate).

Evidence Summary Zoster Vaccination

Rotavirus Vaccination Preliminary data on zoster vaccination in HIV-infected adults
HIV infection is neither a contraindication nor a precaution for on stable antiretroviral therapy showed safety in 286 patients
the 2 licensed live-attenuated rotavirus vaccines for HIV-infect- and immunogenicity (see Zoster vaccine section).
ed or HIV-exposed infants [251]. To date, rotavirus vaccine
trials in resource-poor countries, which invariably involved RECOMMENDATIONS FOR VACCINATION IN
administration to HIV-infected infants, have not uncovered PATIENTS WITH CANCER
unusual or severe adverse events. Monovalent live rotavirus
vaccine (RV1; Rotarix; GlaxoSmithKline) was safe and immu- XVI. Which Vaccines Should Be Given to Patients With
nogenic in 178 HIV-infected infants including 13 with CD4 Cancer?
T-lymphocyte percentages <25 [252, 253]. Pentavalent live rota-
virus vaccine (RV5; RotaTeq; Merck) has been associated with Recommendations (Table 3)
persistent, severe diarrhea in infants with SCID [162]. There 69. Patients aged ≥6 months with hematological malignan-
are no data on the efficacy of rotavirus vaccines in HIV-infected cies (strong, moderate) or solid tumor malignancies (strong,
children. low) except those receiving anti–B-cell antibodies (strong,
moderate) or intensive chemotherapy, such as for induction
LAI Vaccination or consolidation chemotherapy for acute leukemia (weak,
LAIV is not licensed for administration to immunocompro- low), should receive IIV annually.
mised patients and is not recommended by the CDC for immu- 70. PCV13 should be administered to newly diagnosed
nocompromised patients. LAIV was safely administered to 188 adults with hematological (strong, very low) or solid malig-
HIV-infected children and adults who fulfilled certain clinical nancies (strong, very low) and children with malignancies
and immunologic criteria [38, 39, 106]. The immune response (strong, very low) as described in recommendations 27a-c.
to LAIV in HIV-infected patients was comparable to that in PPSV23 should be administered to adults and children aged
uninfected individuals [38, 39, 106]. ≥2 years (strong, low) at least 8 weeks after the indicated
dose(s) of PCV13.
MMR Vaccination 71. Inactivated vaccines (other than IIV) recommended for
The prevalence and titer of measles antibody is low in measles- immunocompetent children in the CDC annual schedule
vaccinated HIV-infected children, even if they are receiving can be considered for children who are receiving mainte-
cART [218, 254–257]. Rubella antibody titers are also reduced nance chemotherapy (weak, low). However, vaccines admin-
in HIV-infected children with significant immune suppression istered during cancer chemotherapy should not be

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e75

 considered valid doses (strong, low) unless there is docu- myeloma, the immune response to 1 dose of vaccine was only
mentation of a protective antibody level (strong, moderate). 19% [278]. Similar results have been seen in patients with lym-
72. Live viral vaccines should not be administered during phoma [279–281], although a more recent study showed a
chemotherapy (strong, very low to moderate). higher seroprotection [282]. A 2-dose schedule is a possible
73. Three months after cancer chemotherapy, patients strategy but was not more immunogenic in some studies [308]
should be vaccinated with inactivated vaccines (strong, very and has not been recommended by ACIP. Adults with lympho-
low to moderate) and the live vaccines for varicella (weak, ma who received a 2-dose schedule showed responses of ap-
very low); measles, mumps, and rubella (strong, low); and proximately 30% after 1 dose and approximately 45% after 2
measles, mumps, and rubella–varicella (weak, very low) ac- doses of vaccine [337]. Two doses of pandemic 2009 A (H1N1)
cording to the CDC annual schedule that is routinely indi- vaccine in patients with chronic myeloid leukemia and B-cell
cated for immunocompetent persons. In regimens that malignancies resulted in a higher seroconversion than 1 dose;
included anti–B-cell antibodies, vaccinations should be however, seroconversion was still lower than after a single dose
delayed at least 6 months (strong, moderate). in immunocompetent controls [328]. No patient who received
maintenance rituximab responded to vaccination. Similarly,
Evidence Summary none of 67 lymphoma patients responded to adjuvanted 2009
Therapy for cancer has become increasingly intensive and has A (H1N1) vaccine within the first 6 months after rituximab

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included immunosuppressive monoclonal antibodies. Since therapy [284]. The response to IIV was impaired in lymphoma
many vaccination studies were conducted during an era in which patients who completed a rituximab-containing regimen ≥6
weaker immunosuppressive therapies were used, the results of months earlier [285].
such studies might not accurately represent the current risks and Patients receiving intensive chemotherapy are likely to be
benefits of vaccinations in oncology patients today. less responsive to influenza vaccination; however, the seasonal
Inactivated vaccines in children. Children with cancer can nature of influenza may warrant timely administration of IIV to
safely receive inactivated vaccines. In general, the vaccines induce immunity. The effectiveness is likely to be low in those
should not be administered during induction or consolidation at highest risk for severe disease. Most influenza virus infections
therapy because of poor response rates during these periods in acute leukemia patients undergoing chemotherapy were no-
[264]. While vaccines administered during less-intensive socomially acquired; therefore, influenza vaccination of family
phases of chemotherapy are less immunogenic compared with members and hospital staff should be strongly encouraged or
those administered off chemotherapy [265], they are not required [286].
harmful and appear to provide seroprotection for some patho- Data on IIV efficacy in adult patients with solid tumors are
gens for some patients [266–269]. Many children have protec- limited. In lung cancer patients, the vaccination response was
tive serum antibodies against certain vaccine-preventable similar to that seen in immunocompetent controls [287]. Simi-
diseases ≥6 months after cessation of chemotherapy [270]. The larly, the humoral response was adequate in a group of women
routine childhood vaccination schedule should be reinitiated 3 with breast cancer [288, 289]. In a study of patients with
months after completion of chemotherapy, when cellular and various solid tumors, the response to vaccination was better
humoral immunity has recovered [271–274]. Routine revacci- than in patients with lymphoma [290]. Breast cancer patients
nation with a single dose of each vaccine antigen can be consid- with ongoing chemotherapy had poorer responses [291]. Influ-
ered [270, 275], but it is uncertain if this is necessary. Another enza vaccination was cost effective in working-age patients with
management plan that can be considered for patients who have cancer [292].
received intense chemotherapy is serologic testing for vaccine- Pneumococcal vaccine. Antibody responses to PPSV23 are
preventable diseases with a recognized serologic correlate of often impaired in patients with hematological malignancies, in-
protection (eg, diphtheria toxoid, Hib, HepA, HepB, IPV, cluding patients with multiple myeloma [278] or treated Hodgkin
rubella, influenza, measles, tetanus toxoid, varicella vaccines) lymphoma [293, 294]. In contrast, a good response can be ob-
and vaccination of those with inadequate serum antibody con- tained before antitumor therapy is initiated [295, 296]. Antibody
centrations. responses can be elicited in splenectomized patients with non-
Influenza vaccine. Influenza vaccination with IIV is recom- Hodgkin and Hodgkin lymphomas [297]. Repeated vaccinations
mended for immunocompromised patients [41, 276]. Patients with PPSV23, before and after splenectomy, induced repeated an-
with colorectal cancer who received influenza vaccine had tibody responses and were not associated with serious adverse
fewer chemotherapy interruptions and higher 1-year survival effects during administration of approximately 600 doses to 380
rates [277]. Study results in patients with hematological malig- patients [298, 299]. A single dose of a PCV7 gave suboptimal re-
nancies have been variable and are probably related to the type sponses in patients who had been treated for Hodgkin lymphoma
of malignancy and treatment received. In patients with multiple [300] or chronic lymphocytic leukemia [301]. Priming with

e76 • CID 2014:58 (1 February) • Rubin et al

PCV7 improved the response to the PPSV23 in patients with pre- Recommendations (Table 4)
viously treated Hodgkin lymphoma, including splenectomized 74. The HSCT donor should be current with routinely rec-
patients [302, 303]. No data regarding the safety or immunogenic- ommended vaccines based on age, vaccination history, and
ity of PCV13 in these patients are available [124, 204], but CDC’s exposure history according to the CDC annual schedule
ACIP recommends routine use of PCV13 for immunocompro- (strong, high). However, administration of MMR, MMRV,
mised persons [109, 124]. Patients with mixed solid tumors were VAR, and ZOS vaccines should be avoided within 4 weeks of
reported to respond well to vaccination with PPSV23 [290]. stem cell harvest (weak, very low). Vaccination of the donor
Diphtheria–tetanus–pertussis vaccine. Hammarström et al for the benefit of the recipient is not recommended (weak,
showed that 41% of acute leukemia patients were not seropro- moderate).
tected against tetanus [304]. In contrast, Nordoy et al reported 75. Prior to HSCT, candidates should receive vaccines indi-
that treatment of low-grade non-Hodgkin lymphoma patients cated for immunocompetent persons based on age, vaccina-
with radio immunotherapy did not influence immunity to tion history, and exposure history according to the CDC
tetanus [280]. Responses to DT vaccinations in adult patients annual schedule if they are not already immunosuppressed
with hematological malignancies have not been systematically (strong, very low to moderate) and when the interval to start
studied. Six or more months after completing chemotherapy of the conditioning regimen is ≥4 weeks for live vaccines
for leukemia, all of 59 children had protective antibody titers (strong, low) and 2 weeks for inactivated vaccines (strong,

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against tetanus and all responded to a single dose of booster moderate).
vaccination [270]. 76. Nonimmune HSCT candidates aged ≥12 months should
HepB vaccine. Patients with hematological malignancies, receive VAR (as a 2-dose regimen if there is sufficient time)
particularly B-cell lymphomas treated with anti-CD20 mono- if they are not immunosuppressed and when the interval to
clonal antibody therapy, are prone to reactivation of HepB in- start the conditioning regimen is ≥4 weeks (strong, low).
fection during therapy [305]. The response rate to HepB
vaccination is poor in patients who were receiving therapy for Evidence Summary
hematological malignancies [306, 307]. Although there are no Donor immunity can be transferred to the HSCT recipient
data, it may be reasonable to vaccinate unvaccinated patients [311–318], and vaccination of the donor has been shown to
with HepB vaccine either prior to or after discontinuation of improve posttransplant immunity [315, 319–321]. However,
therapy against their malignancy. there are logistical problems to vaccinating donors and ethical
Preliminary data suggest that immune responses for patients considerations if a vaccine is administered solely for the benefit
who received monoclonal antibodies for lymphoma are poor of the HSCT recipient. Only vaccines that are indicated and rec-
for at least the first 6 months after completion of treatment ommended based on the donor’s age, vaccination history, and
[308]. A recent study suggests that responses to recall antigens exposure history should be administered. It is not known if vac-
are better than primary responses against antigens not previ- cination of donors with MMR, MMRV, VAR, or ZOS vaccines
ously encountered [309]. Patients who received autologous within 4 weeks of stem cell harvesting causes safety issues for
HSCT and thereafter rituximab responded well to vaccination the HSCT recipient.
with Hib and tetanus vaccines but not to PPSV23 given 6 and 9 In most HSCT patients, antigen-specific antibody titers pro-
months after the last rituximab infusion [310]. gressively decrease with time after HSCT, and patients may
Contraindication to live viral vaccines. Live viral vaccines are become susceptible to infections such as tetanus [314, 322], po-
contraindicated during chemotherapy because of the risk of liovirus [323–325], and measles [326, 327]. The clinical rele-
disseminated disease. Administration after 3–6 months appears vance of decreased antibodies to vaccine-preventable diseases
to be safe [266, 269]. Although VAR has been administered to among recipients is difficult to assess because, with the excep-
children with acute lymphoblastic leukemia receiving mainte- tion of infections caused by pneumococci and influenza, a
nance chemotherapy, it is generally not administered during limited number of cases of vaccine-preventable diseases have
these therapies [81, 83]. been reported among HSCT recipients [328]. In general, post-
HSCT patients should be viewed as “never vaccinated” patients
regardless of the pre-HSCT vaccination history of the patient or
RECOMMENDATIONS FOR VACCINATION OF the donor.
HEMATOPOIETIC STEM CELL TRANSPLANT The guidelines for vaccination of HSCT candidates and re-
PATIENTS cipients have been adapted from the Guidelines for Preventing
Infectious Complications among Hematopoietic Cell Trans-
XVII. Should HSCT Donors and Patients Be Vaccinated Before plant Recipients: A Global Perspective that was prepared in col-
Transplantation? laboration with several international organizations [15]. Based

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e77

on available data, there are no differences in recommendations 82. Three doses of HepB vaccine should be administered
for autologous and allogeneic HSCT patients. 6–12 months after HSCT (strong, moderate). If a postvaccina-
It has been shown that existing recipient immunity frequent- tion anti-HBs concentration of ≥10 mIU/mL is not attained,
ly is retained for several months after HSCT [316, 326]. Patients a second 3-dose series of HepB vaccine (strong, low; alterna-
respond poorly to vaccination early after HSCT. By vaccinating tive: 1 dose of HepB vaccine after which anti-HBs is tested ),
the seronegative patient before HSCT, it is likely that some pro- using standard dose (strong, moderate) or high dose (40 µg ;
tection will persist. No data exist regarding the interval needed weak, low) for children and high dose for adolescents and
between varicella vaccination and start of conditioning; adults (strong, low), should be administered.
however, a 4-week interval is likely to be safe. In patients with 83. Three doses of IPV vaccine should be administered 6–12
cancer who are undergoing chemotherapy and in children with months after HSCT (strong, moderate).
acute leukemia that is in remission, a rash has been noted up to 84. Consider administration of 3 doses of HPV vaccine 6–12
60 days after vaccination [329, 330]. The strategy of pretrans- months after HSCT for female patients aged 11–26 years
plant vaccination of seronegative patients has not been tested in and HPV4 vaccine for males aged 11–26 years (weak, very
a clinical study. However, this strategy is likely to be safe low).
because children with acute leukemia who received VAR subse- 85. Do not administer live vaccines to HSCT patients with
quently underwent allogeneic HSCT without developing clini- active GVHD or ongoing immunosuppression (strong, low).

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cal manifestations of varicella [331]. 86. A 2-dose series of MMR vaccine should be administered
XVIII. Which Vaccines Should Be Administered to Adults to measles-seronegative adolescents and adults (strong, low)
and Children After HSCT? and to measles-seronegative children (strong, moderate) 24
months after HSCT in patients with neither chronic GVHD
Recommendations (Table 4) nor ongoing immunosuppression and 8–11 months (or
77. One dose of IIV should be administered annually earlier if there is a measles outbreak) after the last dose of
(strong, moderate) to persons aged ≥6 months starting 6 immune globulin intravenous (IGIV).
months after HSCT (strong, moderate) and starting 4 87. A 2-dose series of VAR should be administered 24
months after if there is a community outbreak of influenza months after HSCT to varicella-seronegative patients with
as defined by the local health department (strong, very low). neither GVHD nor ongoing immunosuppression and 8–11
For children aged 6 months–8 years who are receiving influ- months after the last dose of IGIV (strong, low).
enza vaccine for the first time, 2 doses should be adminis-
tered (strong, low). Evidence Summary
78. Three doses of PCV13 should be administered to adults Influenza vaccine. Influenza, which is often a severe illness after
and children starting at age 3–6 months after HSCT (strong, HSCT, is associated with mortality of 10%–15% in individuals
low). At 12 months after HSCT, 1 dose of PPSV23 should be not treated with antiviral medication [332]. Patients infected
given provided the patient does not have chronic GVHD with the 2009 pandemic influenza A (H1N1) virus were at in-
(strong, low). For patients with chronic GVHD, a fourth creased risk for pneumonia and for mechanical ventilation and
dose of PCV13 can be given at 12 months after HSCT (weak, had significant mortality despite oseltamivir therapy [333, 334].
very low). Fatal influenza illness can occur several years after HSCT [332].
79. Three doses of Hib vaccine should be administered 6–12 Lifelong annual vaccination with IIV is therefore recommended
months after HSCT (strong, moderate). for all HSCT recipients. The time when vaccination should be
80. Two doses of MCV4 should be administered 6–12 initiated after HSCT depends, in part, on anticipation of influ-
months after HSCT to persons aged 11–18 years, with a enza in the patient’s community but is more likely to be effec-
booster dose given at age 16–18 years for those who received tive when the time interval after HSCT is longer, preferably ≥6
the initial post-HSCT dose of vaccine at age 11–15 years months [335–337]. Even in cases where there is no serological
(strong, low). response, T-cell responses that prevent serious disease may be
81. Three doses of tetanus/diphtheria–containing vaccine elicited [338, 339]. During community outbreaks, HSCT recipi-
should be administered 6 months after HSCT (strong, low). ents should be vaccinated against influenza immediately if it is
For children aged <7 years, 3 doses of DTaP should be ad- >4 months after HSCT. Children aged <9 years who are receiv-
ministered (strong, low). For patients aged ≥7 years, admin- ing influenza vaccine for the first time require 2 doses adminis-
istration of 3 doses of DTaP should be considered (weak, tered ≥4 weeks apart. For IIV, data regarding the effectiveness
very low). Alternatively, a dose of Tdap vaccine should be of a second dose in older children and adults are conflicting.
administered followed by either 2 doses of DT vaccine However, studies showed improved response rates to vaccines
(weak, moderate) or 2 doses of Td vaccine (weak, low). against 2009 pandemic A (H1N1) [335, 337, 340]. LAIV should

e78 • CID 2014:58 (1 February) • Rubin et al

not be used because the safety and efficacy of this vaccine in booster). Ideally, posttransplant patients are viewed as “never
HSCT patients are unknown and an IIV alternative exists. vaccinated” and, consequently, they should receive full doses of
Pneumococcal vaccine. HSCT recipients are at a significantly toxoids, DT, and DTaP. However, DTaP is indicated only for
higher risk for invasive pneumococcal infection than the children aged <7 years. Tdap is less likely than DTaP vaccine to
general population [341–344]. However, PPSV23 is usually in- cause local side effects in immunocompetent adults. Prelimi-
effective when given during the first year after transplantation, nary data in autologous HSCT recipients [361, 362] show that
particularly in patients with chronic GVHD [345–349]. In 3 the response to pertussis (and tetanus) antigens in Tdap is
prospective trials, PCV7 given after HSCT was more immuno- poor, irrespective of the timing of vaccination post-HSCT
genic than historical controls given PPSV23 [350–352]. In a [361], suggesting that this vaccine should be used as a booster
comparative trial of PCV7 and PPSV23 in adult HSCT recipi- rather than as part of the primary series. A 3-dose series of a
ents, PCV7 given to donors and recipients was more immuno- vaccine with high tetanus and pertussis content, that is, DTaP,
genic than PPSV23 given to donors and recipients [353]. In 1 may be more immunogenic in HSCT recipients and thus
of these trials there were similar and substantial antibody re- should be considered for the initial vaccination regardless of
sponses to vaccination with a 3-dose PCV7 series whether patient age.
started at 3 months (early) or 9 months (late) posttransplant HepB vaccine. There are limited data regarding the efficacy
[350]. Thus, early vaccination may be preferred. However, early of HepB vaccination in HSCT recipients. In a study of autolo-

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vaccination may result in a shorter duration of protective con- gous HSCT recipients, 69% seroconverted after a vaccine series
centrations of antibody, and a fourth booster dose may be indi- [363]. Similarly, in a study of allogeneic HSCT recipients, 64%
cated if vaccination is given early after HSCT [350]. It is likely seroconverted; this rate was lower than that in age-matched
beneficial to administer PPSV23 for the fourth dose of vaccine controls [364]. Thus, a determination of postvaccine anti-HBs
starting 12 months after HSCT to provide immunity to addi- concentration is indicated in order to determine if additional
tional serotypes [350, 354]. However, a fourth dose of PCV13 doses of vaccine are needed.
might be preferable in patients with chronic GVHD who are MMR vaccine. Most HSCT patients become seronegative to
unlikely to respond to PPSV23 [346, 349, 355]. CDC’s ACIP measles during an extended follow-up [326, 327]. There have
recommends routine use of PCV13 for immunocompromised been reports of severe and fatal measles in HSCT recipients
persons [109, 124]. [365, 366]. Administration of MMR vaccine can be considered
Hib conjugate vaccine. Vaccination with Hib can elicit pro- 2 years after transplantation in allogeneic HSCT patients
tective immune responses after allogeneic HSCT [347, 348, without chronic GVHD or ongoing immunosuppression. In
356]. The timing after HSCT is important since the immune re- Brazil, 34 patients who were not receiving immunosuppressive
sponse to Hib vaccine early after HSCT, that is, <6 months, re- drugs were safely vaccinated 1–2 years after HSCT [367]. Since
sulted in poor responses in children who received transplants adults who experience natural measles infection prior to trans-
[357]. plantation usually retain immunity for several years after
Diphtheria–tetanus–pertussis vaccine. There are 2 categories HSCT, it is recommended that a measles serology be per-
of diphtheria and tetanus vaccines: those containing a “full” formed, with vaccination of only seronegative patients. The re-
dose of diphtheria toxoid in combination with tetanus toxoid sponses to measles vaccine varied, with a higher response rate
(DT) and those containing a reduced quantity of diphtheria observed in adults than in children [367–370]. In order to
toxoid (Td). In the United States, DT vaccine is not approved achieve protective and long-lasting immunity, a second dose is
for persons aged >6 years due to adverse effects. However, ex- recommended for children who have undergone HSCT.
perience with adult HSCT recipients indicates a lower risk for Rubella vaccination is indicated in women with the potential to
adverse effects than in previously vaccinated immunocompe- become pregnant. The presence of measles antibodies from
tent adults [358], suggesting that the adverse effect profile of IGIV or other blood products may interfere with the response
DT vaccine may be acceptable in this population. It has not yet to measles vaccine and possibly certain other live vaccines, for
been determined whether the immune response to Td is equiv- example, varicella. Therefore, it is appropriate to delay adminis-
alent to the response to DT vaccine. tration of these vaccines for 8 months (after an IGIV dose of
HSCT recipients may be vulnerable to complications from 400 mg/kg body mass) or 11 months (after an IGIV dose of 2
pertussis, although there are very limited published data [359, gm/kg body mass). However, if risk of exposure to measles is
360]. For immunocompetent individuals, acellular pertussis high, MMR vaccine can be given sooner, but the dose should
vaccine that is administered as DTaP is recommended in young be repeated after the interval noted above [223].
children, and a single booster dose of a vaccine containing Varicella vaccine. VAR can be considered for seronegative
Tdap is recommended in children starting at age 10 years and HSCT recipients who meet the criteria for live virus vaccination
for adolescents and adults (to replace a dose of adult Td delineated above for measles vaccine. One center required a

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e79

CD4 T-lymphocyte count ≥200 cell/mm3 and documentation 92. Adults and children aged ≥2 years who are SOT candi-
of a response to ≥1 other vaccine as prerequisites for VAR ad- dates or have end-stage kidney disease should receive
ministration [85, 87, 371]. ZOS should not be administered as PPSV23 if they have not received a dose within 5 years and
there are no data on safety or effectiveness. have not received 2 lifetime doses (strong, moderate). Pa-
Other vaccines. There are no data regarding vaccination of tients with end-stage kidney disease should receive 2 lifetime
HSCT recipients with HPV vaccines. The use of BCG vaccine is doses 5 years apart (strong, low). Adults and children aged
contraindicated because it is a live bacterial vaccine with a po- ≥2 years with end-stage heart or lung disease as well as
tential risk of serious adverse effects. The same is true for live adults with chronic liver disease, including cirrhosis, should
rotavirus vaccines that are licensed by the US Food and Drug receive a dose of PPSV23 if they have never received a dose
Administration only for young infants. (strong, low). When both PCV13 and PPSV23 are indicated,
Patients with chronic GVHD can mount responses to PCV13 should be completed 8 weeks prior to PPSV23
protein-based vaccines. The risk for exacerbation of GVHD is (strong, moderate).
low based on experience in several hundred patients [325, 348, Anti-HBs–negative SOT candidates should receive the HepB
350, 358]. However, vaccination with polysaccharide-based vac- vaccine series (strong, moderate) and, if on hemodialysis
cines is often ineffective, and PCV13 is preferred over PPSV23 and aged ≥20 years, they should receive the high-dose (40
in patients with GVHD [349, 355]. Although there are no data, µg) HepB vaccine series (strong, moderate). If a postvaccina-

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it might be reasonable to delay vaccination of patients treated tion anti-HBs concentration of ≥10 mIU/mL is not attained,
with high doses of corticosteroids or recent therapy with im- a second 3-dose series of HepB vaccine (strong, low; alterna-
munosuppressive monoclonal antibodies such as rituximab or tive: 1 dose of HepB vaccine after which anti-HBs is tested )
alemtuzumab because the antibody response may be low. Live should be administered, using standard dose (strong, moder-
vaccines are not recommended because their safety is not ate) or high dose for children (weak, low) and high dose for
assured given the immunosuppression of GVHD and its adolescents and adults (strong, low). HepA-unvaccinated,
therapy. -undervaccinated, or -seronegative SOT candidates ( particu-
larly liver transplant candidates) aged 12–23 months
RECOMMENDATIONS FOR VACCINATION OF (strong, moderate) and ≥2 years (strong, moderate) should
SOLID ORGAN TRANSPLANT RECIPIENTS receive a HepA vaccine series.
93. Combined HepA–HepB vaccine can be used for SOT
XIX. For Adult and Child Solid Organ Transplant Candidates candidates aged ≥12 years of age in whom both vaccines
and Living Donors, Which Vaccines Should Be Administered are indicated (strong, moderate).
During Pretransplant Evaluation? 94. The HPV vaccine series should be administered to SOT
candidates aged 11–26 years (strong, low-moderate).
Recommendations (Table 5) 95. SOT candidates aged 6–11 months can receive MMR
88. Living donors should be current with vaccines based on vaccine if they are not receiving immunosuppression and if
age, vaccination history, and exposure history according to transplantation is not anticipated within 4 weeks (weak, very
the CDC annual schedule (strong, high); MMR, MMRV, low). If transplantation is delayed (and the child is not re-
VAR, and ZOS vaccine administration should be avoided ceiving immunosuppression), the MMR vaccine should be
within 4 weeks of organ donation (weak, very low). Vaccina- repeated at 12 months (strong, moderate).
tion of donors solely for the recipient’s benefit is generally 96. The VAR should be administered to SOT candidates
not recommended (weak, low). without evidence of varicella immunity (as defined in rec-
89. Adults and children with chronic or end-stage kidney, ommendation 16) if they are not receiving immunosuppres-
liver, heart, or lung disease, including solid organ transplant sion and if transplantation is not anticipated within 4 weeks
(SOT) candidates, should receive all age-, exposure history-, (strong, moderate). The VAR can be administered to varicel-
and immune status-appropriate vaccines based on the CDC la-naive SOT candidates aged 6–11 months who are not im-
annual schedule for immunocompetent persons (strong, munosuppressed provided the timing is ≥4 weeks prior to
moderate). transplant (weak, very low). Optimally, 2 doses should be
91. Adult SOT candidates; adults with end-stage kidney administered ≥3 months apart (strong, low).
disease; and pediatric patients who are SOT candidates; are 97. SOT candidates aged ≥60 years (strong, moderate) and
aged <6 years and have end-stage kidney, heart, or lung varicella-positive candidates (as defined in recommendation
disease; or are aged 6–18 years and have end-stage kidney 22) aged 50–59 years (weak, low) who are not severely im-
disease should receive PCV13 as in recommendations 27a-c munocompromised should receive ZOS if transplantation is
(strong, very low). not anticipated within 4 weeks.

e80 • CID 2014:58 (1 February) • Rubin et al

Evidence Summary enhanced-potency vaccine, accelerated schedules (if transplant
SOT candidates should receive indicated vaccinations prior to is imminent), and adjuvants [394, 395]. Seroconversion was
transplantation, preferably early in their disease [372–374]. Live better after repeated high-dose (80 μg) vaccine administration
vaccines are generally not administered just prior to or post- in nonresponders in 1 study [396]. Despite a report of immuni-
transplant. Vaccination guidelines for SOT candidates and re- ty transfer from vaccinated living liver donors [397], HepB vac-
cipients have been published [373, 374], including information cination of these donors is not recommended.
on travel-related vaccines [375] and the 2009 pandemic influen- Vaccination of SOT candidates with HepA vaccine is impor-
za A (H1N1) vaccine [376]. tant because this vaccine can cause fulminant hepatitis in pa-
A standard vaccine series should be given to pediatric SOT tients with underlying liver disease, particularly HepC. Patients
candidates with the aim of completing the primary series and with chronic liver disease respond to HepA vaccine, although at
booster doses prior to transplantation [1, 377]. Vaccinated chil- lower rates than do immunocompetent individuals [398, 399].
dren with chronic renal failure had serum antibodies against Vaccination before liver disease becomes advanced is likely to
measles, mumps, rubella, varicella, HepB, H. influenzae type b, be more effective [400]. Combined HepA–HepB vaccine is
and S. pneumoniae in 1 study [378]. In another study [379], useful in pretransplant vaccination.
early MMR vaccination led to protective titers in 88% of infants Transplant patients are at higher risk for HPV-related genital
with chronic renal failure. Practices for monitoring specific an- warts, cervical cancer, and other anogenital malignancies. Data

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tibody titers vary [380]. It may be reasonable to monitor titers are awaited on efficacy of pretransplant vaccination in preven-
to some vaccine-preventable pathogens (eg, HepB) [381, 382]. tion of posttransplant HPV infection.
However, except for annual monitoring of anti-HBs titers in Live vaccines. The risk of posttransplant disease from pre-
hemodialysis patients and kidney recipients, there is no consen- transplant administration of live vaccines such as VAR, MMR,
sus on the interpretation of results or the implications for re- or ZOS vaccines has not been completely defined. A waiting
vaccination. period of 4 weeks was chosen based, in part, on the outer range
Because influenza can be severe in patients with end-stage of risk for developing skin lesions postvaccination for most pa-
organ disease, annual vaccination with IIV is recommended for tients. Many patients receive posttransplant chemoprophylaxis
all transplantation candidates or recipients aged ≥6 months for herpes simplex and cytomegalovirus infections that is active
[373, 376, 383]. against VZV, which helps prevent infection but also reduces
Patients awaiting transplant are at increased risk for invasive vaccine efficacy. Most transplant centers will not administer
pneumococcal disease. CDC’s ACIP recommends routine use of live vaccines to candidates scheduled for transplant within 3 to
PCV13 for immunocompromised persons, including those who 4 weeks; however, more data are needed to determine the
have had a SOT [109, 124]. Protective titers can be attained after optimal timing of vaccination.
pneumococcal polysaccharide vaccination in most patients [384, Rotavirus vaccines should be administered to pretransplant
385], although these titers can wane within 2 years [386]. Because infants starting at age 2 months (6 weeks is acceptable) with
most adults have protective titers to Hib, pretransplant Hib vacci- completion of the series by age 8 months. Although viral shed-
nation of adults is unnecessary. In addition, adult patients who ding can occur for ≥15 days after administration, it is unknown
require splenectomy should receive MCV4. whether adverse consequences will result if transplantation
Fewer than 50% of patients with chronic kidney disease have occurs shortly after vaccination (Table 5).
protective titers against tetanus [387]. Five years after Td VAR should be considered in SOT candidates because of
booster vaccination of a cohort of hemodialysis patients, 71% disease severity after transplantation [71]. Fewer than 5% of
had protective antibody levels to tetanus, but only 32% had adult renal transplant candidates were varicella-seronegative
protective titers to diphtheria [387]. Tdap vaccination has not [401]. Children with nephrotic syndrome in remission who
been studied in this population. were not significantly immunosuppressed were safely vaccinat-
HepB can be transmitted via HBsAg-positive or HBsAg-nega- ed [82], but long-term efficacy remains unknown. VAR was
tive/anti-HBc–positive donors [388, 389], blood transfusions, safely administered to uremic children, including those await-
and, rarely, nosocomial outbreaks. HepB vaccination is less effec- ing transplantation [17, 402–404], and to 11 adults awaiting
tive in patients on hemodialysis than in patients at an earlier stage renal transplantation [401]. Almost all pediatric vaccinees sero-
of renal disease [390, 391]. Hemodialysis guidelines [56] recom- converted after 2 doses, and VZV antibody persisted in 75%–
mend high-dose vaccine (ie, 40 µg), testing anti-HBs levels 1 to 2 100% for ≥2 years after transplantation. The incidence of
months after the last dose of the vaccine series and also annually, varicella in vaccinees was reduced by approximately 75% after
as well as revaccination if anti-HBs levels are <10 mIU/mL. transplantation compared with the incidence in unvaccinated
HepB vaccination is also less effective in patients with end- renal transplant recipients; the severity of illness was generally
stage liver disease [372, 392, 393]. Vaccination strategies include milder in vaccinees who developed varicella. VAR was safe and

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e81

effective in 704 pediatric renal transplant candidates [17, 402], 103. MMR vaccine and VAR should generally not be admin-
with 42% retaining VZV antibodies >10 years posttransplant istered to SOT recipients because of insufficient safety and
[402]. Vaccinated patients had a lower risk for varicella post- effectiveness data (strong, low), except for varicella in chil-
transplant, less severe disease, and less HZ than unvaccinated dren without evidence of immunity (as defined in recom-
patients [402]. Pediatric liver transplantation candidates had a mendation 15) who are renal or liver transplant recipients,
seroconversion rate of 95% in 1 study [16], but only 3 of 11 se- are receiving minimal or no immunosuppression, and have
roconverted in another study [405]. Varicella vaccination of 29 no recent graft rejection (weak, moderate).
children with chronic liver disease who were not receiving im- 104. Vaccination should not be withheld because of concern
munosuppressive medication resulted in seroconversion, al- about transplant organ rejection (strong, moderate).
though antibody levels were lower than in immunocompetent
children [406]. Some authors recommend monitoring varicella Evidence Summary
titers and administering a third dose pretransplant if titers The optimal time to begin vaccination after transplant is not
wane [407], However, commercially available assays exhibit defined, but many centers wait ≥2 months to avoid high doses
poor sensitivity for detection of VAR-induced antibodies. of antirejection medications that would impede seroconversion.
ZOS should be administered to pretransplant candidates The degree of immunosuppression varies by patient, and some
who meet ACIP-defined criteria (aged ≥60 years and not se- patients may not mount adequate vaccine responses at 2

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verely immunosuppressed) or are aged 50–59 years, are varicel- months posttransplant. An exception may be administration of
la-positive (defined in recommendation 22), and not severely IIV 1 month after SOT during a community outbreak of influ-
immunocompromised if transplantation is not expected within enza based on expert opinion [376].
4 weeks [10]. This recommendation is based on posttransplant Influenza can cause severe illness in SOT patients [276, 383].
morbidity of zoster rather than evidence of ZOS efficacy in this Seroconversion has varied by vaccine and among transplant
setting. types [103, 104, 408–419]. Efficacy and effectiveness have varied
XX. Which Vaccines Should Be Administered to SOT Recip- by epidemic strain and between influenza A and B virus types
ients? and influenza A subtypes [103, 104], as well as by immunosup-
pressive regimen (eg, mycophenolate mofetil) or recent rejec-
Recommendations tion [409, 416, 419, 420]. Some studies have noted increased
98. Vaccination should be withheld from SOT recipients responses with repeat doses of influenza vaccine [410]. Effec-
during intensified immunosuppression, including the first tiveness of influenza vaccine was demonstrated against influen-
2-month posttransplant period, because of the likelihood of za-like illness in 29% and 33% of heart recipients who received
inadequate response (strong, low). However, IIV can be ad- 1 of 2 influenza vaccines compared with 63% of control unvac-
ministered ≥1 month after transplant during a community cinated heart transplant recipients [413]. In 2 studies, cellular
influenza outbreak (weak, very low). immune responses to influenza vaccine were impaired [415,
99. Standard age-appropriate inactivated vaccine series 421]. In a recent study of 51 730 adult renal transplant recipi-
should be administered 2 to 6 months after SOT based on ents, influenza vaccination in the first posttransplant year was
the CDC annual schedule (strong, low to moderate), includ- associated with lower risks of allograft loss and death [422]. A
ing IIV (strong, moderate; Table 5). recent randomized controlled trial of high-dose intradermal
100. PCV13 should be administered 2 to 6 months after (15 µg) vs standard-dose intramuscular influenza vaccine in
SOT if not administered before SOT, with the timing based organ transplant recipients found no significant differences in
on the patient’s degree of immunosuppression, as described response, suggesting that the intradermal vaccine may be an ac-
in recommendations 27a–c (strong, very low to moderate; ceptable alternative [423].
Table 5). ACIP recommends PCV13 for adults and children with a SOT
101. For SOT patients aged ≥2 years, 1 dose of PPSV23 and PPSV23 for adults and children aged ≥2 years with a SOT
should be administered 2 to 6 months after SOT, with the [109, 124]. Pneumococcal vaccination with PPSV23 is associated
timing based on the patient’s degree of immunosuppression, with seroconversion rates as high as 94% in some, but not all,
and ≥8 weeks after indicated doses of PCV13, if not given studies [411, 424–427]. In adult renal transplant patients, anti-
within 5 years and if the patient has received no more than 1 body levels and persistence after PCV7 were not superior com-
previous lifetime dose (strong, moderate). pared with the levels and persistence in those receiving PPSV23
102. HepB vaccine should be considered for chronic HepB- [427, 428]. Adult liver recipients did not have an enhanced re-
infected recipients 2 to 6 months after liver transplant in an sponse to PPSV23 after a prior dose of PCV7 (“prime-boost”
attempt to eliminate the lifelong requirement for HepB strategy), and the authors concluded that 1 PPSV23 dose remains
immune globulin (HBIG; weak, low). the standard for posttransplant recipients [429].

e82 • CID 2014:58 (1 February) • Rubin et al

 Two doses of PCV7 raised serotype-specific antibody after incidence or seasonality of rejection [444, 407]. Kimball et al
the first dose of PCV7 in pediatric SOT recipients, although at found that influenza vaccination did not lead to anti-HLA allo-
lower titers than in controls; antibody levels did not rise further antibodies nor increased frequency of rejection in heart recipi-
after the second PCV7 dose or when a subsequent dose of ents [443]. A recent study involving 17 kidney and lung
PPSV23 was administered [430]. Barton et al studied the ad- transplant recipients demonstrated augmentation of cellular al-
ministration of 3 doses of PCV7 followed by PPSV23 in pediat- loimmunity after influenza vaccination. However, the clinical
ric SOT recipients [431]. Mean concentrations increased 2-fold implications are unclear [445]. A study of >50 000 adult renal
in all organ groups after 2 doses of PCV7; however, heart and transplant recipients showed no deleterious effect with vaccina-
lung recipients appeared to benefit from the third PCV7 dose. tion. Importantly, influenza vaccination during the first year
PPSV23 resulted in significantly higher antibody titers to some after transplantation was associated with decreased risks of al-
PCV7 serotypes [431]. Booster vaccination with Td produced lograft loss and death [422].
good responses in pediatric renal transplant recipients [432].
HepB vaccination in pediatric liver recipients showed a 70%
seroconversion rate, with another 50% of nonresponders con- RECOMMENDATIONS FOR VACCINATION OF
verting after additional booster and double doses [433]. Re- PATIENTS WITH CHRONIC INFLAMMATORY
sponses were superior in children receiving monotherapy DISEASES ON IMMUNOSUPPRESSIVE
MEDICATIONS

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rather than combination therapy for immunosuppression
[433]. To eliminate the requirement for long-term therapy with
costly HBIG after liver transplantation for HepB, some centers Patients with chronic inflammatory diseases (including
have vaccinated these recipients. However, seroconversions oc- immune-mediated and autoimmune diseases) are often treated
curred in a small proportion of patients using standard or high- with immunosuppressive drugs, as single agents or in combina-
dose HepB vaccine [434, 435]. Some anti-HBs–positive liver tion, for long periods of time. Initiation of immunosuppression
recipients transplanted for diseases other than HepB infection should not be delayed to facilitate vaccination if immediate
lost their protective titers posttransplant [394]. treatment is needed.
Some liver recipients who were seropositive for HepA pre- XXI. Which Vaccines Should Be Administered to Patients
transplant became seronegative posttransplant [436]. Vaccina- With Chronic Inflammatory Diseases Maintained on Immuno-
tion with a 2-dose HepA vaccine series was well tolerated in 37 suppressive Therapies?
liver transplant recipients, but only 26% of the recipients were
seropositive at 7 months postvaccination [399]. In another Recommendation (Table 6)
study, satisfactory seroconversion rates in renal and liver recipi- 105. Inactivated vaccines, including IIV, should be adminis-
ents were followed by a rapid decline in HepA antibody titers tered to patients with chronic inflammatory illness treated
[437]. (strong, low-moderate) or about to be treated (strong, mod-
There are no published data on the immunogenicity of HPV erate) with immunosuppressive agents as for immunocom-
vaccine in SOT recipients. SOT recipients have significant mor- petent persons based on the CDC annual schedule.
bidity from HPV warts [438]; therefore, HPV4 vaccine is pre- 106. PCV13 should be administered to adults and children
ferred over HPV2 vaccine in this population. with a chronic inflammatory illness that is being treated with
Varicella-related safety after transplant was shown in a small immunosuppression as described in the standard schedule
series of pediatric liver, renal, and intestine transplant recipi- for children and in recommendations 27a–c (strong, very
ents [16–18, 439]. In contrast, significant disease was reported low-moderate; Table 6).
after inadvertent administration of VAR to transplant recipients 107. PPSV23 should be administered to patients aged ≥2
[74, 440]. In a recent report of vaccination of 36 pediatric liver years with chronic inflammatory illnesses with planned initia-
recipients with VAR in which the vaccine was administered a tion of immunosuppression (strong, low), low-level immuno-
median of 3.0 years posttransplant, vaccination was found to be suppression (strong, low), and high-level immunosuppression
safe and seroprotective [441]. No data exist on the safety of ro- (strong, very low). Patients should receive PPSV23 ≥8 weeks
tavirus vaccine posttransplant. after PCV13, and a second dose of PPSV23 should be given
Case reports and small series have raised the question of 5 years later (strong, low).
whether vaccines trigger allograft rejection [417]; virtually all 108. VAR should be administered to patients with chronic
larger studies found no excess rejection or clinically significant inflammatory diseases without evidence of varicella immu-
allograft dysfunction after vaccinations [408, 409, 411–413, 418, nity (defined in recommendation 15; strong, moderate) ≥4
442–444, 407]. One study of 3601 heart transplant recipients at weeks prior to initiation of immunosuppression (strong,
multiple centers found no vaccine-related differences in the low) if treatment initiation can be safely delayed.

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e83

 109. VAR should be considered for patients without evi- inactivated H1N1 influenza vaccine was reduced in patients
dence of varicella immunity (defined in recommendation with rheumatic diseases on various immunosuppressive regi-
15) being treated for chronic inflammatory diseases with mens compared with immunogenicity in immunocompetent
long-term, low-level immunosuppression (weak, very low). controls. Patients receiving tocilizumab, an anti–interleukin-6
110. ZOS should be administered to patients with chronic in- receptor antibody, for treatment of RA or juvenile idiopathic
flammatory disorders who are aged ≥60 years prior to initia- arthritis had antibody responses to IIV that were similar to
tion of immunosuppression (strong, low) or being treated those of the comparator groups [454, 455]. Patients tolerated
with low-dose immunosuppression (strong, very low) and IIV without serious adverse effects or disease flare [456–458].
those who are aged 50–59 years and varicella positive prior to There are few studies of inactivated vaccines other than IIV
initiation of immunosuppression (weak, low) or being in chronic inflammatory disease populations treated with im-
treated with low-dose immunosuppression (weak, very low). munosuppression. In adults, responses to PPSV23 were similar
111. Other live vaccines should not be administered to pa- among patients with RA treated with TNF-α blockers and im-
tients with chronic inflammatory diseases on maintenance munocompetent controls [459]. However, patients with RA
immunosuppression: LAIV (weak, very low), MMR vaccine and psoriatic arthritis treated with MTX had reduced responses
in patients receiving low-level (weak, very low) and high- regardless of anti–TNF-α treatment [459–461], and patients re-
level immunosuppression (weak, very low); and MMRV ceiving rituximab had reduced responses [462]. RA patients

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vaccine in patients receiving low-level (weak, very low) and treated with rituximab and MTX had decreased antibody re-
high-level immunosuppression (strong, very low). sponse to PPSV23 compared with RA patients on MTX alone;
112. Other recommended vaccines, including IIV and HepB however, both groups had similar responses to tetanus toxoid
vaccine, should not be withheld because of concerns about [462]. Antibody response to PPSV23 in 190 adults with RA was
exacerbation of chronic immune-mediated or inflammatory not adversely affected by treatment with tocilizumab [463]. An-
illness (strong, moderate). tibody response to some PCV7 serotypes was decreased in 31
pediatric patients with juvenile rheumatic diseases on anti–
Evidence Summary TNF-α therapy compared with the response in immunocompe-
Findings from 2 prospective trials of IIV in children with IBD tent controls [464]. CDC’s ACIP recommends routine use of
[446, 447] suggest that IIV is safe and effective, although immu- PCV13 for immunocompromised persons including those re-
nogenicity may be decreased in patients treated with TNF-α ceiving immunosuppressive medications [109, 124]. Immune
antibodies. In both studies, children receiving 6-mercaptopu- responses to MCV4 were good irrespective of degree of immu-
rine or azathioprine had seroprotection rates comparable to nosuppression in 234 children and young adults with juvenile
those of immunocompetent controls and nonimmunosup- idiopathic arthritis in a multicenter open-label study [465].
pressed IBD patients for all 3 strains in the vaccine. Children HepB vaccine was safe and induced an immune response in
treated with TNF-α antibodies, however, had normal seropro- most of 44 RA patients in a prospective study [466].
tection rates to both type A vaccine strains but lower seropro- Protection against varicella is important because of the po-
tection and seroconversion rates to the type B vaccine strain. tential severity of varicella infection. Unfortunately, published
Vaccination was not associated with disease exacerbation. In 1 data on varicella vaccination in this population are limited [93]
study, the overall coverage with inactivated vaccines, including (see Varicella section).
IIV, in patients with IBD was low, indicating the need for more Although no studies have been published on zoster vaccina-
outreach and education for patients and medical providers [4]. tion in patients receiving immunosuppression, ACIP has con-
Uncontrolled studies of patients with rheumatic inflammato- cluded that vaccination is safe in adults receiving ≤20 mg per
ry chronic illnesses receiving disease-modifying drugs suggest- day of prednisone or other low-level immunosuppression [10].
ed an adequate immune response to IIV. In children with An expert panel of the American College of Rheumatology en-
rheumatologic conditions receiving disease-modifying anti- dorsed these recommendations [467] and stated “until more re-
rheumatic drugs, seroprotection rates to influenza vaccine search becomes available it may be advisable to avoid zoster in
ranged from 80% to 98% [448]. In adults with RA or SLE, IIV patients actively receiving TNFα inhibitors.” Zoster vaccination
was safe and induced protective antibody concentrations in could be considered prior to initiation of immunosuppression
most patients. However, immunogenicity was reduced in pa- for patients aged 13–49 years with a chronic immune-mediated
tients receiving azathioprine, infliximab, or rituximab in some or inflammatory disorder who have a history of varicella or
studies [100, 101, 449–452]. In addition, antibody response to who are seropositive despite no previous varicella vaccination;
vaccine was reduced in patients with RA who received rituxi- however, safety and effectiveness data are lacking. MMR revac-
mab compared to the response in immunocompetent persons cination of patients with juvenile idiopathic arthritis resulted in
or RA patients receiving MTX [453]. Immunogenicity to a good immune response to all 3 viruses without serious

e84 • CID 2014:58 (1 February) • Rubin et al

adverse effects despite continued therapy with MTX or recent MCV4-D should not be administered in patients aged <2
therapy with etanercept or anakinra [468, 469]. However, data years because of a reduced antibody response to some pneu-
are lacking on the safety of primary MMR vaccination and vac- mococcal serotypes when both MCV4 and PCV are adminis-
cination with other live vaccines in this population. tered simultaneously (strong, low). Revaccination with MCV4
Exacerbations of autoimmune disease temporally related to (or MPSV4 for those aged >55 years who have not received
influenza vaccination have been reported, yet prospective con- MCV4) is recommended every 5 years (strong, low).
trolled trials do not support a cause-and-effect relationship (see
“Safety of Vaccination of Immunocompromised Patients”). Evidence Summary
Specifically, influenza vaccination did not increase disease ac- The rate of invasive pneumococcal disease caused by vaccine se-
tivity in patients with SLE or RA [100, 101, 451, 453, 470–472]. rotypes in children aged <5 years with sickle cell diseases fell by
HepB vaccination had no effect on disease activity in patients 93% after implementation of vaccination with PCV7 [12];
with SLE or RA [466, 473]. Similarly, pneumococcal vaccina- however, some of this reduction may have been due to herd-type
tion was not associated with worsening of clinical disease activ- immunity. In children aged >2 years with sickle cell disease who
ity or laboratory measures of disease activity in patients with were given 2 doses of PCV7 followed by a single dose of
RA or SLE [474]. MMR vaccination did not affect disease activ- PPSV23, antibody levels to all serotypes in PCV7 were greater
ity in patients with juvenile idiopathic arthritis [469]. An in- than in children given PPSV23 alone [475]. CDC’s ACIP recom-
mends routine use of PCV13 for asplenic patients [109, 124].

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crease in disease relapses was observed in 7 patients with
multiple sclerosis vaccinated with yellow fever vaccine [69]. The optimal timing of PPSV23 vaccination is ≥2 weeks prior
to splenectomy. If vaccination cannot be completed by this time,
it should be performed ≥2 weeks following splenectomy because
RECOMMENDATIONS FOR VACCINATION OF this timing results in higher antibody concentrations or opsono-
PATIENTS WITH ASPLENIA OR SICKLE CELL phagocytic titers compared with vaccination at a shorter interval
DISEASES before or after surgery [476–478]. There are no similar data on
the effect of timing of Hib, MCV4, or MPSV4 vaccination on se-
XXII. Which Vaccines Should Be Administered to Asplenic Pa-
rologic responses in patients undergoing splenectomy.
tients and Those With Sickle Cell Diseases?
A study in children aged <5 years with sickle cell disease vacci-
Recommendations (Table 7) nated with Hib vaccine demonstrated a safety and immunoge-
113. Asplenic patients and those with sickle cell diseases nicity profile that was similar to that of controls [479]. In a study
should receive vaccines including PCV13 for children aged <2 of 23 patients aged 9–23 years who were splenectomized for
years, as recommended routinely for immunocompetent Hodgkin disease, antibody response was less than in the control
persons based on the CDC annual schedule. No vaccine is con- group, but most patients responded to vaccination [480].
traindicated (strong, moderate) except LAIV (weak, very low). A lower antibody response to certain PCV13 serotypes was
114. PCV13 should be administered to asplenic patients and observed when infants were simultaneously vaccinated with
patients with sickle cell diseases aged ≥2 years based on the PCV13 and MCV4-D. Therefore, MCV4-D should be adminis-
CDC annual schedule for children and in recommendations tered ≥4 weeks after PCV13 [481, 482]. This was not observed
27a–c (strong, very low-moderate). when infants were simultaneously vaccinated with PCV7 and
115. PPSV23 should be administered to asplenic patients and Hib-MenCY [117].
patients with a sickle cell disease aged ≥2 years (strong, low)
with an interval of ≥8 weeks after PCV13, and a second dose RECOMMENDATIONS FOR VACCINATION OF
of PPSV23 should be administered 5 years later (strong, low). PATIENTS WITH ANATOMIC BARRIER DEFECTS
116. For PPSV23-naive patients aged ≥2 years for whom a AT RISK FOR INFECTIONS WITH VACCINE-
splenectomy is planned, PPSV23 should be administered ≥2 PREVENTABLE PATHOGENS
weeks prior to surgery (and following indicated dose(s) of
PCV13; strong, moderate) or ≥2 weeks following surgery XXIII. Which Vaccinations Should Be Given to Individuals
(weak, low). With Cochlear Implants or Congenital Dysplasias of the Inner
117. One dose of Hib vaccine should be administered to un- Ear or Persistent CSF Communication With the Oropharynx
vaccinated persons aged ≥5 years who are asplenic or have a or Nasopharynx?
sickle cell disease (weak, low).
118. Meningococcal vaccine should be administered to pa- Recommendations (Table 7)
tients aged ≥2 months who are asplenic or have a sickle cell 119. Adults and children with profound deafness scheduled
disease (strong, low), as in recommendation 29. However, to receive a cochlear implant, congenital dysplasias of the

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e85

 inner ear, or persistent cerebrospinal fluid (CSF) communi- epidemiology of vaccine-preventable infections, mediators
cation with the oropharynx or nasopharynx should receive of vaccine protection and adverse effects of vaccines, and
all vaccines recommended routinely for immunocompetent effects of vaccines that contain new adjuvants on vaccine
persons based on the CDC annual schedule. No vaccine is protection and adverse effects of vaccines.
contraindicated (strong, moderate; Table 7). b) Establishment of a registry of immunocompromised
120. Patients with a cochlear implant, profound deafness and vaccine recipients, particularly those receiving live vaccines,
scheduled to receive a cochlear implant, or persistent commu- to provide additional safety data.
nications between the CSF and oropharynx or nasopharynx c) Uptake of IIV and other vaccines offered by subspecialists
should receive PCV13 as described in the standard schedule for compared with primary care providers and other strategies to
children and recommendations 27a–c (strong, low-moderate). increase vaccine uptake in immunocompromised patients.
121. Patients aged ≥24 months with a cochlear implant, d) Transmission of LAIV and rotavirus vaccine to immuno-
profound deafness and scheduled to receive a cochlear compromised patients.
implant, or persistent communications between the CSF and e) Efficacy and safety of zoster vaccination in:
oropharynx or nasopharynx should receive PPSV23, prefera-
1. Patients aged ≥60 years and <60 years with planned
bly ≥8 weeks after receipt of PCV13 (strong, moderate).
immunosuppression that increases the risk for zoster,
122. PCV13 and PPSV23 should be administered ≥2 weeks
2. Patients receiving low-level immunosuppression,

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prior to cochlear implant surgery, if feasible (strong, low).
3. Patients with HIV infection,
Evidence Summary 4. Patients with chronic inflammatory disorders who are
The AAP policy statement includes recommendations for receiving severe immunosuppression (eg, tocilizumab
pneumococcal, Hib, and influenza vaccinations for children anti–IL-6 receptor antibody) or cyclophosphamide,
with cochlear implants [483]. CDC guidelines stress the impor- 5. Immunocompromised populations whose varicella
tance of vaccination against S. pneumoniae for these patients. immunity was induced by varicella rather than infection
CDC’s ACIP recommends routine use of PCV13 for adults and from wild-type virus, and
children with a cochlear implant [109, 124]. PCV13 has re- 6. Efficacy of pretransplant zoster vaccination in order
placed PCV7, and no data are available regarding immunoge- to prevent posttransplant zoster in SOT candidates.
nicity and safety of PCV13 in these patients. A second dose of HIV
PPSV23 can be considered for patients with a cochlear implant, f ) Optimal time to initiate vaccination after starting cART
profound deafness who are scheduled to receive a cochlear for HIV infection.
implant, or persistent CSF communication with the orophar- g) HepB vaccination of HIV-infected persons who are anti-
ynx or nasopharynx 5 years after the initial dose, although this HBs negative but anti-HBc positive (eg, no vaccination or 3-
is not recommended by the ACIP or AAP. The immunogenici- dose series or single dose followed by anti-HBs testing 2
ty of PCV7 compared with PPSV23 was evaluated in a prospec- weeks later).
tive study of 174 patients with cochlear implants [484]. For h) Indications for and effect of revaccination of patients vac-
children aged 2–5 years, PCV7 was more immunogenic than cinated prior to initiating cART.
PPSV23. A review of invasive pneumococcal disease in children
aged 24–59 months at high risk of pneumococcal disease re- Malignancy
vealed 31 cases. Four (13%) were caused by serotypes covered i) Safety, immunogenicity, and efficacy of vaccines in patients
in PPSV23 but not in PCV13, indicating the importance of with malignancy treated with contemporary regimens (eg, im-
PPSV23 in this patient population; however, 44% were caused munogenicity and safety of acellular pertussis vaccines with
by serotypes not covered by either vaccine [124]. low [ap] or high [aP] antigen content); safety, immunogenici-
ty, and effectiveness of IIV including vaccines with adjuvants
during intensive chemotherapy and initial months afterward;
FUTURE DIRECTIONS AND GAPS IN need for a routine booster dose after completing chemothera-
KNOWLEDGE IN VACCINATION OF py; optimal timing of inactivated and live vaccines after com-
IMMUNOCOMPROMISED PATIENTS pleting chemotherapy; and duration of impaired response to
vaccines after regimens that include anti–B-cell antibodies).
Listed below are areas that warrant future investigation.
General HSCT/SOT

a) Understanding the basic aspects of vaccines in various j) Safety and immunogenicity of single and multiple doses
categories of immunocompromised patients, including the of DTaP or Tdap following HSCT.

e86 • CID 2014:58 (1 February) • Rubin et al

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Acknowledgments. The Expert Panel expresses its gratitude to external the National Institutes of Health, and the HIV Medicine Association
reviewers Drs Mary Healy, Gregory Poland, and Jane Seward. The panel also of the Infectious Diseases Society of America. MMWR Recomm Rep
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Abbreviations
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in patients with juvenile idiopathic arthritis: a randomized trial.
cART, combination antiretroviral therapy
JAMA 2013; 309:2449–56.
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body responses in postsplenectomy trauma patients receiving the 23- HPV4, quadrivalent human papillomavirus vaccine

Vaccination of Immunocompromised Host • CID 2014:58 (1 February) • e99

 HSCT, hematopoietic stem cell transplant pDGS, partial DiGeorge syndrome
HZ, herpes zoster PPSV, pneumococcal polysaccharide vaccine
IBD, inflammatory bowel disease RA, rheumatoid arthritis
BIDSA, Infectious Diseases Society of America SCID, severe combined immune deficiency
IFN-γ/IL-12, interferon-gamma/interleukin-12 SLE, systemic lupus erythematosus
IGIV, immune globulin intravenous SOT, solid organ transplant
IIV, inactivated influenza vaccine SPAD, specific polysaccharide antibody deficiency
IPV, inactivated poliovirus vaccine SPGC, Standards and Practice Guidelines Committee
LAIV, live attenuated influenza vaccine Td, tetanus toxoid, reduced diphtheria toxoid vaccine
MBL, mannan-binding lectin Tdap, tetanus toxoid, reduced diphtheria toxoid, and reduced
MCV4, meningococcal conjugate vaccine, quadrivalent acellular pertussis vaccine
MMR, measles, mumps, and rubella vaccine TNF, tumor necrosis factor
MMRV, MMR-varicella vaccine TT, tetanus toxoid
MTX, methotrexate VAPP, vaccine-associated paralytic poliomyelitis
NK, natural killer VAR, varicella vaccine
OPV, oral polio vaccine VZV, varicella-zoster virus

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PCV, pneumococcal conjugate vaccine ZOS, zoster vaccine

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