Immunization of immunocompromised persons: Canadian Immunization Guide
Introduction and general principles
Individuals may be immunocompromised as a result of a congenital condition, an illness or medications that suppress immune function. In general, immunocompromised persons are more susceptible to vaccine-preventable infections and may have severe infections.  The safety and effectiveness of vaccines in immunocompromised persons are determined by the type of immunodeficiency and degree of immunosuppression. Each immunocompromised person is different and presents unique considerations regarding immunization. The relative degree of immunodeficiency is variable depending on the underlying condition, the progression of disease and use of immunosuppressive agents.  Immunodeficiency can also vary over time in many people and the decision to recommend for or against a particular vaccine will depend upon a case-by-case analysis of the risks and benefits. There is potential for serious illness and death if immunocompromised people are under-immunized and every effort should be made to ensure adequate protection through immunization; however, inappropriate use of live vaccines can cause serious adverse events in some immunocompromised people as a result of uncontrolled replication of the vaccine virus or bacterium.
Primary care providers and specialists caring for immunocompromised patients share responsibility for ensuring appropriate vaccination of immunocompromised patients and their households. When in doubt, primary care providers should consult a specialist with experience in managing patients with the specific immunocompromising condition of concern.
The following recommendations reflect general best practices and are subject to individual considerations and new evidence as it arises.

# Inactivated vaccines
Inactivated vaccines may generally be administered to immunocompromised people if indicated because the antigens in the vaccine cannot replicate and there is no increase in the risk of vaccine-associated adverse events; however, the magnitude and duration of vaccine-induced immunity are often reduced. For complex cases, referral to a physician with expertise in immunization and/or immunodeficiency is advised.

# Live attenuated vaccines
In general, people who are severely immunocompromised or in whom immune status is uncertain should not receive live vaccines because of the risk of disease caused by the vaccine strains. In less severely immunocompromised people, the benefits of vaccination with routinely recommended live vaccines may outweigh risks. Before giving an immunocompromised person a live vaccine, a physician with expertise in immunodeficiency should be consulted.

# Immunoglobulins
For temporary passive protection against some infections, immunoglobulin therapy (nonspecific or pathogen specific) may be indicated for pre or post exposure. The monoclonal antibody preparation, Palivizumab (SynagisTM) is an antibody directed specifically against respiratory syncytial virus (RSV) that may be considered to reduce complications of RSV infection in children less than 24 months of age who are severely immunocompromised.

# Serologic testing and re-immunization
Immune response to vaccines may be inadequate in immunocompromised people and vaccinees may remain susceptible despite vaccination. If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered. For infants less than 18 months of age, a positive serologic test may detect maternal antibody and not reflect an active immune response in the infant. Seroconversion or an increase in titre, or a repeat test after 18 months of age showing persistent antibody, indicate an active response. Results of serologic testing may also be confounded by passive antibody in those receiving immunoglobulin therapy.
Please note that the information in the text and tables is complementary and both should be used. Refer to  in Part 4 for additional information, especially concerning vaccine doses, schedules and boosters.

# General principles
Several general principles apply to the immunization of immunocompromised individuals:
- Maximize benefit while minimizing harm.
- Susceptibility to infection and ability to respond to a vaccine vary according to degree of immune suppression.
- Immunize at the time when maximum immune response can be anticipated.
	+ Immunize prior to any planned immunosuppression, if possible.
	+ Delay immunization if the immunodeficiency is transient (if this can be done safely because exposure is unlikely).
	+ Stop or reduce immunosuppression to permit better vaccine response, if appropriate.
- Consider the immunization environment broadly.
	+ Vaccinate family members and other close contacts when appropriate.
	+ Strongly encourage up-to-date vaccinations, including annual influenza vaccination, for all healthcare workers providing care to immunocompromised people.
- Avoid live vaccines unless:
	+ immunosuppression is mild and data are available to support their use.
	+ the risk of natural infection is greater than the risk of immunization.
- Monitor serologic response, if appropriate test and correlate of protection is available, and boost if antibody level is inadequate.
	+ The magnitude and duration of vaccine-induced immunity are often reduced in immunocompromised individuals.

# Family or medical history
Primary or secondary immunodeficiencies may be undiagnosed in young children presenting for routine immunizations, which include live vaccines. This is particularly important to consider in infants receiving live vaccines before 12 months of age.
A significant primary immunodeficiency in which live vaccines would be contraindicated usually declares itself in the first few months of life. The only live vaccine routinely given to children less than 12 months of age is rotavirus, which can be given as early as 6 weeks of age. Chronic rotavirus infection from the vaccine strain has occurred in infants with unrecognized severe combined immunodeficiency. BCG vaccine is given at birth in some populations and measles vaccine may be given at 6-12 months of age in an outbreak or after exposure.
Clues pointing to the presence of significant immunodeficiency may be found in the medical or family history. Infants with a history of failure to thrive, recurrent or prolonged oral candidiasis despite treatment, or recurrent serious infections such as pneumonia or sepsis may have an immunodeficiency. A family history of primary immunodeficiency may be known or may be suspected on the basis of a family history of early infant deaths. However, the family history can be negative. Routine newborn screening for severe combined immunodeficiency is now performed in some regions of Canada. Maternal human immunodeficiency virus (HIV) infection puts the infant at risk of immunodeficiency in the first year of life if HIV has been transmitted to the infant. Routine prenatal blood work in Canada includes HIV testing. If an infant shows clinical clues suggesting immunodeficiency, the mother's prenatal HIV screening result should be obtained.  If a mother was not screened in pregnancy, the possibility of perinatal HIV infection from undiagnosed maternal infection should be considered.
Primary immunodeficiency
There are currently more than 300 distinct genetic defects of immunity. These are grouped under general headings below.

# Predominantly antibody (B cell) deficiencies
B cell defects (defects of humoral immunity) include X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID), selective immunoglobulin A (IgA) deficiency, specific polysaccharide antibody deficiency (SPAD), and immunoglobulin G (IgG) subclass deficiency.
Individuals with defects in antibody production are highly susceptible to encapsulated bacteria such as *Streptococcus pneumoniae, Haemophilus influenzae- and *Neisseria meningitidis.*
- Most patients with severe defects of antibody production, such as XLA or CVID are not able to mount a significant humoral response.  While administration of inactivated vaccines is not harmful, it may be futile.  As a general rule, people with severe antibody defects can be protected from many of the vaccine preventable infections with the use of replacement immunoglobulin (Ig) therapy or pathogen-specific Ig preparations; however, the level of antibody to specific pathogens in these products may be variable.
- For those with less severe antibody deficiency and expected ability to mount some antibody response, especially selective IgA deficiency or IgG subclass deficiency, vaccination is recommended to increase the level of protection. Receipt of replacement Ig is not a contraindication for use of inactivated vaccines; however, Ig can interfere with the immune response to some live attenuated viral vaccines such as measles and varicella vaccine.
- Repeat doses of Ig should not be given to individuals with known selective IgA deficiency unless the benefit outweighs the risk, because of the very rare risk of an anaphylactic reaction to traces of IgA in the product. If indicated, an Ig product with the least amount of IgA should be used and given with caution under close observation.

## Inactivated vaccines
In general, inactivated vaccines should be administered according to routine immunization schedules to people with less severe primary B cell defects who have some capacity for B or T cell responses. Hepatitis B vaccine should be given at double the routine dose and using a 3- or 4-dose schedule. Human papillomavirus (HPV) vaccine should be given following routine age indications but using a 3-dose schedule regardless of age.
In addition to routine vaccines, individuals with primary B cell defects should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of *Haemophilus influenzae- type b (Hib) vaccine after age 5 years regardless of prior Hib vaccination history. Quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered if 2 months of age or older. For infants 6 months of age or older, inactivated influenza vaccine should be given annually, even if receiving Ig, as Ig may not have antibody to the current influenza strains.  However, humoral response may be reduced.

## Live attenuated vaccines
Patients with severe B cell defects (XLA, CVID), and others receiving regular immunoglobulin replacement therapy, should not receive measles-mumps-rubella (MMR), measles-mumps-rubella-varicella (MMRV) or varicella vaccines as Ig will interfere with the efficacy of these vaccines.
Individuals with partial B cell defects and known intact T cell immunity and some ability to produce antibody who are not receiving Ig should receive MMR and univalent varicella vaccines as appropriate for age. MMRV has not been evaluated in immunodeficiency. All other live vaccines such as rotavirus, live attenuated influenza, live herpes zoster vaccine, Bacille Calmette-Guerin (BCG), oral polio, smallpox, oral typhoid and yellow fever vaccines are contraindicated. If travel to an area where yellow fever is being transmitted cannot be avoided, consideration of vaccination in consultation with a specialist is advised.
People with selective IgA deficiency who have no concomitant defects in T cell function can receive most live vaccines. Live mucosal vaccines (rotavirus, live attenuated influenza vaccine (LAIV), oral typhoid) are likely safe and may be used although there may be lack of mucosal response. Some experts prefer to use inactivated vaccines if available (e.g., inactivated influenza vaccine, parenteral inactivated typhoid vaccine). However, given that there are limited data on the use of live mucosal vaccines, consultation with an immunologist is advised and immunization with these vaccines should be individually assessed.
The diagnosis of IgG subclass deficiency should be based on documented failure to produce adequate amounts of specific antibody and not on quantitative Ig levels.  Individuals with documented IgG subclass deficiency with intact T cell function who are not receiving regular Ig replacement therapy can receive routine live vaccines although response may be suboptimal. All live vaccines may be given to individuals with isolated SPAD.

# Combined T and B cell immunodeficiencies (with or without associated /syndromic features) and Immune dysregulation
Individuals with T cell or combined deficiency are particularly susceptible to infections with virtually all viruses and many bacteria. T cell defects may be severe (e.g., severe combined immunodeficiency, complete DiGeorge syndrome) or partial (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia telangiectasia, hyper IgM syndrome, hyper IgE syndrome, X-linked lymphoproliferative disease, familial predisposition to hemophagocytic lymphohistiocytosis). Those with severe defects will not respond to any vaccines. Those with partial defects may have some response.

## Inactivated vaccines
For those with severe combined immunodeficiency, administration of inactivated vaccines is not harmful, but will not provide protection.
Inactivated vaccines should be given to those with partial immunodeficiency although response may be suboptimal. Hepatitis B vaccine should be given at double the routine dose and using a routine 3- or 4-dose schedule.  HPV vaccine should be given following routine age indications but using a 3-dose schedule regardless of age.
In addition to routine vaccines, individuals with partial T cell or combined defects should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history. Quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered if 2 months of age or older. Inactivated influenza vaccine should be given annually, as Ig may not protect. However, humoral response may be reduced.

## Live attenuated vaccines
All live attenuated vaccines are contraindicated for individuals with severe T cell defects. Exposure to natural infection or inadvertent live attenuated vaccine administration can usually be managed with rapid administration of Ig or pathogen-specific Ig with or without appropriate antiviral treatment. Live vaccines are also generally contraindicated for those with Wiskott-Aldrich syndrome, ataxia telangiectasia, X-linked lymphoproliferative disease, or familial predisposition to hemophagocytic lymphohistiocytosis.
Live attenuated vaccines may be considered for those with partial T cell defects after assessment of immune competence. Those with partial DiGeorge syndrome, or other combined defects, and a total CD4  lymphocyte count of > 500 x 106/L and normal mitogen response should receive MMR and univalent varicella vaccines as MMRV has not been evaluated in this population. MMRV and other live vaccines are contraindicated.

# Phagocytic and neutrophil disorders
People with phagocytic and neutrophil disorders (e.g., congenital neutropenia, cyclic neutropenia, leukocyte adhesion and migration defects, chronic granulomatous disease (CGD), myeloperoxidase deficiency and Chediak-Higashi syndrome) are at increased risk for bacterial infections.

## Inactivated vaccines
All routine inactivated vaccines and others required because of travel or exposure should be given. Pneumococcal conjugate vaccine (regardless of age) and pneumococcal polysaccharide vaccine if 2 years of age or older are indicated for all conditions other than CGD. CGD does not increase the risk of invasive pneumococcal disease, so conjugate vaccine should be used according to routine schedules and polysaccharide vaccine is not indicated. Inactivated influenza vaccine should be given annually. Influenza vaccine is especially important in patients with CGD due to increased morbidity and mortality with staphylococcal lung infections that are associated with influenza.

## Live attenuated vaccines
Live bacterial vaccines (BCG, oral typhoid) are contraindicated in all phagocytic or neutrophil defects. Live attenuated viral vaccines (rotavirus, MMR, varicella, MMRV, herpes zoster) should be given according to routine schedules to persons with neutropenia or CGD, and live attenuated influenza vaccine (LAIV) or yellow fever vaccine may be given if indicated. All live attenuated viral vaccines are contraindicated with leukocyte adhesion defect (LAD), Chediak-Higashi syndrome and other defects in cytotoxic granule release, and in any other undefined phagocytic cell defect. 

# Complement deficiency
Individuals with complement, properdin, factor D or B or mannan-binding lectin deficiency are particularly susceptible to infections with *N. meningitidis- but also susceptible to other encapsulated bacteria such as *S. pneumoniae- and *Haemophilus influenzae*. In general, response to vaccines is expected to be normal and there are no contraindications.

## Inactivated vaccines
Inactivated vaccines should be administered according to routine immunization schedules.  
In addition to routine vaccines, quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered if 2 months of age or older. Pneumococcal conjugate vaccine should be given regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history. Influenza vaccine (inactivated or live attenuated, as appropriate for age) should be given annually.

## Live attenuated vaccines
Individuals with complement deficiency should receive all routine live attenuated vaccines and any other live vaccines that are indicated (e.g., for travel or after exposure).

# Defects of innate immunity
Innate immune defects of cytokine generation or cellular activation, such as defects of the interferon-gamma/interleukin-12 axis, increase susceptibility to mycobacterial disease. Toll-like receptor signaling pathway deficiencies (i.e. IRAK4 and MyD88 deficiency) increase susceptibility to pneumococcal and other pyogenic bacterial infections. Some innate defects may result in increased susceptibility to viral infections.

## Inactivated vaccines
All routine inactivated vaccines should be given. Persons with IRAK4 and MyD88 deficiency or other defects causing increased risk for pyogenic bacterial infections should receive conjugate pneumococcal vaccine regardless of age and polysaccharide pneumococcal vaccine at age  2 years. Other inactivated vaccines should be used as indicated for travel or exposure.

## Live attenuated vaccines
A specialist should be consulted before giving live vaccines to persons with innate immune defects of cytokine generation or response or cellular activation defects. Persons with interferon gamma/interleukin-12 axis defects have a greater susceptibility to intracellular bacteria (i.e. salmonella or mycobacteria).  For those patients, live bacterial vaccines (BCG, oral typhoid) are contraindicated.  Live viral vaccines are contraindicated in patients with defects in alpha/beta or gamma interferon production.  All live vaccines are contraindicated in nuclear factor kappa B pathway defects.
- Use 5 dose schedule for post exposure prophylaxis
- Post-immunization serology recommended
Abbreviations:
 anti-HBs = antibody to hepatitis B surface antigen 
 Ig =  immunoglobulin
Most patients with severe B cell deficiency (e.g., X-linked agammaglobulinemia, common variable immunodeficiency) and patients with severe T cell defects (e.g., severe combined immunodeficiency, complete DiGeorge syndrome) are unable to respond to any vaccine. Inactivated vaccines are safe but not effective. They should be given only if some antibody production is expected. Those with less severe defects should receive inactivated vaccines as indicated here. 
Given as combined vaccine (diphtheria, tetanus, pertussis;  polio, Hib depending on age and previous vaccine history). 
Routine use: Follow routine immunization schedules with age-appropriate booster doses.
May be given as combined vaccine.
Regardless of prior history of Hib vaccination and at least 1 year after any previous dose
Initially annual monitoring of antibody levels may be considered.  Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. 
Recombinant inactivated zoster vaccine may be considered in immunocompromised adults  50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks. 
For CGD, give pneumococcal conjugate vaccine according to the routine schedule; pneumococcal polysaccharide vaccine is not indicated.
Persons with IRAK4 and MyD88 deficiency or other innate defects causing increased risk for pyogenic bacterial infections should receive polysaccharide pneumococcal vaccine at age  2 years.
Abbreviation: Ig = immunoglobulin
Major B cell deficiency:  X-linked agammaglobulinemia, common variable immunodeficiency and other major antibody defects: all live vaccines contraindicated. Those with partial B cell defects and known intact T cell function who are not receiving regular Ig therapy may receive MMR and varicella vaccines. Other live vaccines are contraindicated.
Severe combined immunodeficiency, complete DiGeorge syndrome and others with severe T cell deficiency: all live vaccines contraindicated. Those with partial defects (see text) may receive MMR and varicella vaccine.   
All live vaccines contraindicated with leukocyte adhesion defect, Chediak-Higashi syndrome and other defects in cytotoxic granule release, and any other undefined phagocyte defect
A specialist should be consulted before giving live vaccines to persons with defects of cytokine generation / response or cellular activation defects. Live bacterial vaccines are contraindicated in defects of interferon gamma/interleukin-12 pathways. Live viral vaccines are contraindicated in patients with defects of alpha or gamma interferon production. All live vaccines are contraindicated in nuclear factor kappa B pathway defects.
Consult with immunologist in cases of IgA deficiency; some experts may prefer inactivated vaccine for persons with IgA deficiency
Routine use: follow routine immunization schedules with age-appropriate booster doses
Regular immunoglobulin replacement therapy will affect the efficacy of the vaccine. Refer to   for the recommended intervals between Ig and subsequent immunization.
If travel to an area where yellow fever is being transmitted cannot be avoided, consider use of the vaccine in consultation with a specialist.
Acquired (secondary) immunodeficiency
Acquired immunodeficiency states result from medical conditions that directly or indirectly cause immunosuppression (e.g., malignant hematologic disorders or solid tumours, hematopoietic stem cell transplantation, HIV-infection). Acquired immunodeficiency may also occur due to immunosuppressive therapies (e.g., long-term steroid treatment, cancer chemotherapy, other cytotoxic therapy, biological response modifiers, calcineurin inhibitors, radiation therapy) used to treat these conditions as well as to treat solid organ transplant recipients and a range of chronic inflammatory conditions (e.g., inflammatory bowel disease, arthritis, psoriasis, systemic lupus erythematosus).

# Acquired complement deficiency
People who are receiving the terminal complement inhibitor eculizumab (SolirisTM, Alexion Pharmaceuticals Inc.) for paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome or other conditions are at high risk of invasive meningococcal infections. In addition to all age-appropriate routine vaccines, quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered. They must be vaccinated at least 2 weeks prior to receiving the first dose of eculizumab, if possible, and every 3-5 years thereafter if they continue to use the drug.
Hemolysis can be precipitated by the combination of meningococcal B vaccines and eculizumab if the underlying hemolytic condition is not yet under control. For patients already receiving eculizumab, meningococcal B vaccine should be given after the underlying hemolytic condition is under control and less than one week after a dose of eculizumab. For more information, refer to the .

# Malignant hematologic disorders
(e.g., leukemia, lymphomas, blood dyscrasias or other malignant neoplasms affecting the bone marrow or lymphatic systems)

## Inactivated vaccines
In general, inactivated vaccines should be administered to people with malignant hematologic disorders according to routine immunization schedules, although response may be sub-optimal. Immunization should be given at least 2 weeks prior to the start of immunosuppressive therapy or when immunosuppressive therapy is at the lowest level unless the risk of imminent exposure to the pathogen is high. Hepatitis B vaccine should be given at double the routine dose and using a 3 or 4 dose schedule. HPV vaccine should be given following routine age indications but using a 3 dose schedule regardless of age. Doses of any vaccine received while on immunosuppressive therapy should be repeated once no longer immune suppressed, unless an adequate antibody response can be demonstrated. 
Individuals with malignant hematologic neoplasms should also receive conjugate pneumococcal vaccine (regardless of age), pneumococcal polysaccharide vaccine if age 2 years or more, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history, because of increased susceptibility to these infections. For infants 6 months of age or older, annual immunization with inactivated influenza vaccine is also recommended.

## Live attenuated vaccines
Live attenuated vaccines are contraindicated in individuals with severe immunodeficiency due to blood dyscrasias, lymphomas, leukemias of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems and in people undergoing immunosuppressive chemotherapy or radiotherapy treatment for these conditions.
In general, if the cancer is in remission and chemotherapy and/or radiotherapy have been completed for at least 3 months, and T cell function is normal, the person is no longer considered immunocompromised and live vaccines may be given. Live vaccines should be deferred for at least 6 months after therapy with anti B-cell antibody.

# Non-hematologic malignant solid tumours

## Inactivated vaccines
Inactivated vaccines should be administered to people with malignant solid tumours according to routine immunization schedules. Immunization should be given at least 2 weeks prior to the start of immunosuppressive therapy or when immunosuppressive therapy is at the lowest level unless the risk of imminent exposure to the pathogen is high. Hepatitis B vaccine should be given at double the routine dose and using a 3- or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule regardless of age. Doses of any vaccine received while on immunosuppressive therapy should be repeated once no longer immune suppressed unless an adequate antibody response can be demonstrated.
In addition, pneumococcal conjugate vaccine (regardless of age) and polysaccharide vaccine (if age 2 years or more) should be given because of increased susceptibility to invasive pneumococcal disease. For infants 6 months of age or older, annual immunization with inactivated influenza vaccine is also recommended.

## Live attenuated vaccines
Live vaccines are contraindicated in people undergoing immunosuppressive treatment for any malignant solid tumour.  
In general, if chemotherapy has been completed for at least 3 months and the cancer is in remission, the person is no longer considered immunocompromised.

# Hematopoietic stem cell transplantation (HSCT): autologous or allogeneic
HSCT is the transplantation of hematopoietic stem cells following bone marrow ablation or non-ablative conditioning (chemotherapy and/or radiotherapy to deplete the hematopoietic system prior to transplant). HSCT recipients receive either their own cells (autologous HSCT) or cells from a donor (allogeneic HSCT). Stem cells are sourced from bone marrow, peripheral blood, or umbilical cord blood.
Virtually all HSCT recipients experience a prolonged period of immune suppression following transplantation. Antibody titres to vaccine-preventable diseases decrease after allogeneic or autologous HSCT. Duration of immune suppression varies, depending on type of transplant (allogeneic or autologous), stem cell source, stem cell manipulation and post-transplant complications. Allogeneic HSCT recipients experience profound immune suppression in the post-transplant period, with recovery of the immune system approximately 1-2 years after HSCT. However, this recovery is delayed in the presence of immunosuppressive medication and chronic graft-versus-host disease (cGVHD). Recovery usually occurs earlier after autologous HSCT but still requires several months. 
In general, T cells capable of responding to new antigens are generated at 6 to 12 months after transplant, earlier in young children and later in adults. Although reconstitution occurs earlier after autologous HSCT than after allogeneic HSCT, the approaches to vaccination are the same. Efficacy data for vaccines in HSCT recipients are limited.
Vaccination in accordance with transplant centre-specific immunization guidelines is generally part of routine post-transplant care provided by the transplant centres.

# Pre-HSCT immunization
If time permits, careful consideration must be given to the pre-transplant immunization status of the HSCT candidate. All routine inactivated vaccines should be given as appropriate for age. In addition, conjugate pneumococcal vaccine (regardless of age) and polysaccharide pneumococcal vaccine (if age 2 years or more) should be given if not previously received. If the transplant is planned during the influenza season, inactivated influenza vaccine should be given. Inactivated vaccines should be given at least 2 weeks prior to onset of the pre-transplant conditioning regimen. Live vaccines should not be given within 4 weeks of the start of conditioning. BCG should not be given at any time to those with a condition that will likely eventually require HSCT. BCG may persist in the body for at least a few years, and perhaps indefinitely, so there is a theoretical risk of reactivation post-transplant.
Donor vaccination may improve responses of the HSCT recipient to some vaccines; however, due to logistical and ethical issues it is often not feasible. When the HSCT donor is related to the recipient, consideration should be given to immunizing the donor before stem cell collection. As a minimum, the donor should have received all routine age-appropriate vaccines including routine boosters, COVID-19 vaccines, and influenza vaccine if stem cell collection is to occur during the influenza season. Inactivated vaccines should be given at least 2 weeks prior to stem cell collection. Live parenteral vaccines are contraindicated within 4 weeks of stem cell collection. For autologous HSCT, inactivated vaccines should be given at least 2 weeks before and live parenteral vaccines at least 4 weeks before stem cell collection.
If indicated for age and by immune status, and if feasible, a primary series of a non-live COVID-19 vaccine should be completed at least 2 weeks prior to onset of the pre-transplant conditioning regimen for allogeneic HSCT and at least 2 weeks prior to stem cell collection for autologous HSCT.
Doses of COVID-19 vaccine may be given at an interval shorter than the recommended interval of 8 weeks, respecting the minimum authorized interval.
If the recipient or donor is eligible for a booster dose, consideration should be given to administering the booster at least 2 weeks prior to stem cell collection, if feasible.
At this time, it is not known if giving an extra dose of COVID-19 vaccine prior to conditioning or stem cell collection would improve response to COVID-19 vaccine post-HSCT.
If transplantation is urgent, it should not be delayed to facilitate donor or recipient vaccination.

# Post-HSCT immunization
HSCT recipients should be viewed as "never immunized" and require re-immunization after transplant because the ablation of hematopoietic cells in the bone marrow pre-transplant eliminates most or all immune memory. In addition, certain vaccine preventable diseases pose increased risk for HSCT recipients of all ages (e.g., pneumococcus, Hib, measles, varicella, and influenza). HSCT recipients respond poorly to polysaccharide vaccines, such as pneumococcal polysaccharide 23-valent vaccine. If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered.

## Inactivated vaccines
All routine inactivated vaccines should be given (or repeated) for HSCT recipients generally beginning 6 to 12 months post-transplant (pneumococcal conjugate vaccine may be given beginning at 3 to 6  months post-transplant, inactivated influenza vaccine may be given beginning at 4 to 6 months post-transplant). Pneumococcal conjugate vaccine and Hib vaccine should be given regardless of age. Those 2 years of age or older should receive pneumococcal polysaccharide vaccine at 12 to 18 months post-transplant (6 to 12 months after the last dose of pneumococcal conjugate vaccine) if no GVHD. Hepatitis B vaccine should be given at double the dose used in the routine 3-dose schedule. HPV vaccine should be given using a 3-dose schedule, regardless of age. For those with risk factors for invasive meningococcal disease (e.g., functional hyposplenia), quadrivalent conjugate meningococcal is recommended and meningococcal B vaccine should be considered.
The primary series (initial or repeat) of COVID-19 vaccine should be initiated 3 to 6 months after HSCT. In general, it is recommended that the immunization of immunocompromised persons occur at a time when the immune response can be maximized. However, delaying COVID-19 vaccination to maximize the immune response needs to be weighed against the risk of infection while waiting, taking into consideration risk of exposure and local transmission of SARS-CoV-2. Time of initiation should also take into account the immune status of the HSCT recipient, including B-lymphocyte counts, receipt of immunosuppressive therapy currently or within the past 3 months, rituximab therapy or other anti-B cell monoclonal antibody within the last 12 months, and active GVHD or moderate to severe cGVHD.
Individuals with recent or current immunosuppressive therapy or active cGVHD are expected to have lower seroconversion rates, but nevertheless, rates of 56%, 63% and 73% have been reported in HSCT recipients on immunosuppression. New cGVHD and worsening of cGVHD have occasionally been reported after receipt of a COVID-19 vaccine, but whether or not vaccination was causal is not known. Patients at risk for GVHD should be advised that a cGVHD flare may occur but relationship to the vaccine is unknown. Careful monitoring of patients with a history of cGVHD is warranted. If new onset or exacerbation of GVHD occurs after COVID-19 vaccination, the decision to give a further dose should be made on an individual basis, taking into consideration risk of exposure to SARS-CoV-2 and the severity of the GVHD.

## Live attenuated vaccines
MMR and univalent varicella vaccines may be considered 24 months or more post-transplant provided there is no evidence of chronic GVHD, immunosuppression has been discontinued for at least 3 months, the underlying disease for which the transplant was done (if immunosuppressive), is not active, and the person is considered immunocompetent by a transplant specialist. Yellow fever vaccine may be given if the above criteria are met and travel to an area with risk of yellow fever acquisition cannot be avoided. Other live vaccines are contraindicated. Note that some HSCT recipients may be receiving regular doses of immunoglobulin which will interfere with the response to live vaccines, in which case these vaccines (excluding yellow fever), should be deferred until 8-11 months after the last dose of immunoglobulin. Live herpes zoster vaccine is not recommended post HSCT.
- Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine unless receiving routine IG replacement therapy.
- Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine unless receiving routine IG replacement therapy.
- Double the routine dose;  3 or 4  dose schedule  recommended
- Post-immunization monitoring of anti-HBs titres recommended with booster dose  if titre less than 10 IU/L
- 3 doses of Pneu-C-13 vaccine at least 4 weeks apart
- If GVHD, give 4th dose of Pneu-C-13  and delay polysaccharide until GVHD   resolved
- Consider re-immunization after 1 year
- Give as needed for post-exposure management
- Use 5 dose schedule for post-exposure prophylaxis
- Beginning 6 to 12 months post-HSCT for pre-exposure prophylaxis
- Post-immunization serology recommended
- Serology recommended after  2nd  dose
- Serology recommended after 2nd dose
Abbreviations:
anti-HBs = antibody to hepatitis B surface antigen     
 Ig = immunoglobulin
For preferred type of COVID-19 vaccine, intervals between doses, and booster dose recommendations, refer to the  chapter.
Given as combined vaccine (diphtheria, tetanus, pertussis;  polio, Hib depending on age and previous vaccine history).
May be given as a combined vaccine.
Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection.
Recombinant inactivated zoster vaccine may be considered in immunocompromised adults  50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks.
Give when immunosuppression has been discontinued for at least 3 months, no chronic GVHD, no Ig in the past 8 to 11 months (except for yellow fever vaccine) and considered immunocompetent by a transplant specialist.

# Solid organ transplantation
Solid organ transplant recipients are at increased risk of severe illness with many vaccine preventable diseases, including invasive pneumococcal or Hib disease, influenza, varicella, and HPV-related diseases.

# Pre-solid organ transplantation
Pre-transplant immunization is routine at most transplant centres. Ideally, all non-immune solid organ transplantation candidates should be immunized prior to transplantation and as early in the course of disease as possible because vaccine response may be reduced in people with organ failure pre-transplant. In addition, vaccines are more immunogenic if given before transplantation because the immunosuppressive medications given after transplant to prevent and treat rejection of the transplanted organ may diminish the vaccine response. It is especially important that live vaccines are given pre-transplant if possible, as these will be contraindicated post-transplant. MMR and varicella vaccine may be given to infants 6-11 months of age if transplantation is expected to occur before age 12 months. If transplantation is delayed, repeat doses should be given starting at one year of age.
Inactivated vaccines should be given according to routine immunization schedules, with the exceptions that hepatitis B vaccine should be given at double the usual dose using a 3- or 4-dose schedule if on dialysis or immunocompromised. If immunocompromised, HPV vaccine should be given using a 3-dose schedule regardless of age. In general, routine age indications should be followed, however HPV vaccination may be considered prior to an imminent transplantation in a 7- or 8-year-old child, recognizing that there is no immunogenicity data for this age group. The risk of HPV-associated warts is high post-transplant; HPV 9- or 4-valent vaccine will provide additional protection over that of the 2-valent vaccine. In addition, transplant candidates should receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination history.
Inactivated influenza vaccine should be given annually. Hepatitis A vaccine is indicated for liver transplant candidates and others with risk factors for hepatitis A. Quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered if there are risk factors for meningococcal infection (e.g., hyposplenia, complement deficiency, or increased risk of exposure from travel or occupation).
Inactivated vaccines should be given at least 2 weeks before transplantation and live attenuated vaccines (MMR, MMRV, varicella, zoster, rotavirus, LAIV) should be given at least 4 weeks prior to transplantation. Live zoster vaccine should be used only if the inactivated zoster vaccine is contraindicated or unavailable. BCG may persist in the body for at least a few years, and perhaps indefinitely. It should not be given to any patient who is anticipated to likely need an organ transplant in the future, unless potential benefit outweighs the risk of reactivation post-transplant.
Antibody response should be determined by serology for those vaccines with an antibody correlate of immunity available. For infants less than 18 months of age, presence of passive maternal antibody must be considered.
Living donors should have received all age-appropriate vaccines. Live vaccines should not be given in the 4 weeks before organ procurement.

# Post-solid organ transplantation
Solid organ recipients generally receive lifelong immunosuppression, which varies substantially depending on the organ transplanted. Usually the degree of immune suppression is greatest in the first 3 to 6 months post-transplant, although this timeline varies if treatment for acute organ rejection is required. In the absence of this later scenario, immune suppression typically progresses to the maintenance phase between 6 months -1 year, but a significant degree of immune suppression persists indefinitely. A minority of transplant recipients who experience chronic rejection, persistent organ dysfunction, or chronic infections, remain profoundly immune suppressed.

## Inactivated vaccines
In general, vaccination with inactivated vaccines should not be re-initiated until maintenance immunosuppression is attained. Recommended inactivated vaccines that were not given pre-transplant and recommended booster doses should be given. Hepatitis B vaccine should be given at double the usual dose and using a 3-dose or 4-dose schedule. HPV vaccine should be given following routine age indications but using a 3-dose schedule, regardless of age.
If serologic testing is available and there is a clear antibody correlate of protection, measurement of post-immunization antibody titres to determine immune response and guide re-vaccination and post-exposure management should be considered.

## Live attenuated vaccines
Live vaccines are generally contraindicated after transplant.  However, univalent varicella vaccine has been given to selected pediatric renal and liver transplant recipients without recent graft rejection and receiving minimal or no immune suppression; consultation with an expert is advised regarding varicella vaccination of non-immune organ transplant recipients.
Most newly transplanted solid organ recipients receive vaccination in accordance with transplant centre-specific immunization guidelines as part of routine post-transplant care.
- Individuals 5 years of age and older: 1 dose recommended
- Individuals 5 years of age and older: 1 dose recommended
 - Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine
- Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine
- Post-immunization monitoring of anti-HBs titres recommended with booster dose  if titre less than 10 IU/L
- May be considered for pre-transplant administration prior to routinely recommended age, if reasonably close to minimum recommended age for vaccination
- Use 5 dose schedule for post-exposure prophylaxis
- Post-immunization serology recommended
- Post-immunization serology recommended
- Post-immunization serology recommended
- Consider post-immunization serology
Abbreviations:
anti-HBs = antibody to hepatitis B surface antigen     
 Ig = immunoglobulin
Whenever possible, vaccine series should be completed pre-transplantation. Vaccines given post-transplant may not be sufficiently immunogenic.
Inactivated vaccines should be given at least 2 weeks before transplantation and, in general, should not be given post-transplant until baseline immunosuppression levels are attained   
Given as combined vaccine (diphtheria, tetanus, pertussis;  polio, Hib depending on age and previous vaccine history). 
Routine use: follow routine immunization schedules with age-appropriate booster doses 
May be given as combined vaccine.
Regardless of prior history of Hib vaccination and at least 1 year after any previous dose
Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection. 
Recombinant inactivated zoster vaccine may be considered in immunocompromised adults  50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks
Pneu-C-13 vaccine followed by Pneu-P-23 vaccine is recommended. Antibody titres decline after 3 years; however, experience with re-immunization with Pneu-C-13 after solid organ transplant is limited.
Live attenuated vaccines should be given at least 4 weeks prior to transplantation
BCG may remain in the body for at least a few years, and perhaps indefinitely. Use only if benefit outweighs potential risk of reactivation post-transplant
MMR and univalent varicella vaccine may be given to infants as early as 6 months of age if transplantation is anticipated before 12 months of age. If transplantation is delayed, repeat doses should be given starting at one year of age. MMRV not recommended for age < 12 months at this time.

# Immunosuppressive therapy
Long-term immunosuppressive therapy is used for various disease conditions including cancer, organ transplantation, GVHD following HSCT, and chronic inflammatory conditions (e.g., inflammatory bowel disease, inflammatory arthritis, psoriasis, systemic lupus erythematosus). Therapies include cancer chemotherapy, radiation therapy, long term high-dose steroid treatment (prednisone equivalent of  2 mg/kg/day or 20 mg/day if weight > 10 kg, for  14 days), cytotoxic drugs, calcineurin inhibitors, chimeric antigen receptor (CAR) T cell therapy targeting lymphocytes, biological response modifiers and antibodies that target lymphocytes.
Most of these therapies have their greatest impact on cell-mediated immunity, although T cell-dependent antibody production can also be adversely affected. Monoclonal antibodies that deplete B cells profoundly affect antibody production; this effect can last for several months or years following completion of therapy. The nature of the person's underlying disease should also be considered.
CAR T cell cancer immunotherapy involves reprogramming a patients own T cells to identify and eliminate malignant cells. The patients T cells are obtained, modified in a laboratory, then infused back into the individual. Commercial CAR T cells from allogeneic donors are also available. CAR T cell therapy is used most frequently to treat hematologic malignancies, especially of B cell origin (e.g., CD19). This therapy eliminates malignant as well as normal cells expressing the target antigen, resulting in profound and prolonged loss of B lymphocytes and thus antibody production.
In general, if a patient is 3 months post-chemotherapy and the cancer is in remission, or if immunosuppression has been discontinued for at least 3 months (6 months or more for anti-B cell antibodies or CAR T cells targeting lymphocytes), the person is no longer considered immunocompromised.

# Prior to immunosuppressive therapy
Vaccination status should be reviewed for immunocompetent persons who might be anticipating initiation of immunosuppressive treatments or who have diseases that might lead to immunodeficiency. Ideally, all appropriate routine vaccines or boosters should be administered before the initiation of immunosuppressive therapy so that optimal immunogenicity is achieved. Although inactivated vaccines can be safely administered at any time before, during or after immunosuppression, inactivated vaccines should be administered at least 14 days before initiation of immunosuppressive therapy to optimize immunogenicity. Live vaccines should be administered at least 4 weeks before immunosuppressive therapy is started to reduce the risk of disease caused by the vaccine strain.
People undergoing immunosuppressive therapy are at higher risk of invasive pneumococcal disease and influenza-related complications; therefore, in addition to routine vaccines they should receive conjugate pneumococcal vaccine regardless of age and polysaccharide pneumococcal vaccine if aged 2 years or more, as well as annual immunization with inactivated influenza vaccine. Hib vaccine may be recommended in some circumstances, such as following organ transplants.

# During or after immunosuppressive therapy
If immunization cannot be completed prior to initiation of immunosuppressive therapy, generally a period of at least 3 months should elapse between therapy cessation and the administration of inactivated vaccines (if possible, to ensure maximum immunogenicity) or live vaccines (to reduce the risk of disease caused by the vaccine strain). However, this interval may vary with the type and intensity of treatment, underlying disease, or urgency of vaccination if vaccines are needed for post-exposure or outbreak management. For example, whereas immunization can occur as early as 4 weeks following discontinuation of long term high-dose systemic steroid therapy, a longer interval of 6 to 12 months or more may be required in case of therapy with rituximab (or other monoclonal anti-B cell antibody) and some other biological response modifiers. B cell enumeration is generally performed during rituximab therapy and should be reviewed prior to immunization.
Recipients of CAR T cell therapy directed against lymphocytes should be regarded as never immunized and managed as HSCT recipients are. The primary series (initial or repeat) of inactivated vaccines, including COVID-19 vaccines which should be initiated 3 to 6 months after CAR T cell therapy. Antibody response is unlikely while B cell aplasia persists, but cellular responses may occur.
Live vaccines may be given immediately on discontinuation of high dose steroid therapy if duration was less than 14 days. Corticosteroid therapy is not a contraindication to immunization with live vaccines when steroid therapy is short-term (i.e., less than 14 days); or low-to-moderate dose (prednisone equivalent of less than 2 mg/kg/day or less than 20 mg/day if weight > 10 kg); or physiologic replacement therapy; or administered topically, inhaled, or locally injected (e.g., joint injection). An exception is LAIV, which is contraindicated in individuals with severe asthma who are currently receiving high dose inhaled steroids.
For recipients of therapy with long term effects on the immune system, such as CAR T directed against lymphocytes, anti-B cell antibody, and some other biological response modifiers, live vaccines should not be given until adequate immune reconstitution has been confirmed by an expert.
The following principles apply if immunosuppressive therapy cannot be stopped.

## Inactivated vaccines
Inactivated vaccines (as indicated under Prior to immunosuppressive therapy, above) may be administered if needed during immunosuppression. If risk of exposure is low, inactivated vaccines may be temporarily delayed until the person is the least immunosuppressed.  Doses may need to be repeated when the person is no longer immunosuppressed unless antibody response can be demonstrated. Hepatitis B vaccine should be given at double the usual dose and using a 3- or 4-dose schedule.  HPV vaccine should be given following routine age indications but using a 3-dose schedule, regardless of age. Inactivated influenza vaccine should be given during influenza season except for those on induction chemotherapy for leukemia or receiving anti-B cell antibodies, who are unlikely to respond. If zoster vaccine is indicated, inactivated zoster vaccine should be considered.

## Live attenuated vaccines
Live vaccines are generally contraindicated.  Because immunosuppressive drugs have been reported to cause reactivation of latent tuberculosis infection and predisposition to other opportunistic infections, avoidance of live vaccines during high level immunosuppressive therapy is prudent.
The safety and efficacy of live vaccines during low dose intermittent or maintenance therapy with non-corticosteroid immunosuppressive drugs are generally unknown, with the exception of varicella and live herpes zoster (HZ) vaccines, which can be considered for those receiving low dose methotrexate ( 0.4 mg/kg/week); azathioprine ( 3 mg/kg/day), or 6-mercaptopurine ( 1.5 mg/kg/day). Inactivated herpes zoster vaccine should be used unless it is contraindicated or unavailable. If combination low dose immunosuppression is being used, an expert should be consulted. A careful risk benefit assessment should be done if other live attenuated vaccines are to be considered in patients on low dose immunosuppression.

# Infants exposed to immunosuppressive therapy in the womb
Special consideration should be given to immunizing infants who have been exposed to monoclonal antibodies in the womb.  Some monoclonal antibodies taken during pregnancy can, similar to maternal antibodies, pass through the placental barrier, potentially resulting in various forms of temporary immunosuppression in infants. For example, rituximab taken during pregnancy is associated with B-cell depletion in both mother and fetus, while infliximab can be detected in infants up to 6 months after birth.
- Due to the potential risk of disseminated disease, administration of BCG and oral polio vaccines is contraindicated in such infants who are less than 6 months of age.  A longer interval of 6-12 months should be observed following rituximab therapy. Oral polio vaccine is no longer used in Canada but continues to be used in some other countries.
- There are no data at this time regarding the potential risk associated with rotavirus (RV) vaccine in these infants.  Prior to RV immunization, laboratory tests may be useful in assessing humoral and cellular immune status. When considering immunization in the absence of laboratory test results, the decision to immunize should be based on an individual risk-benefit assessment. For example, in jurisdictions with ongoing RV immunization programs, indirect protection through herd immunity is likely to be high and withholding immunization may be considered until more information about the effects of monoclonal antibodies in the womb becomes available.  Alternatively, in jurisdictions that do not have RV immunization programs and where exposure to wild-type rotavirus may be high, immunization with RV vaccine may be prudent to reduce the risk of potential complications from RV infection.
- Immune responses to live vaccines that are administered at or after one year of age (e.g., MMR or MMRV vaccine) are not considered to be affected by exposure to monoclonal antibodies in the womb.
- Infants exposed to monoclonal antibodies in the womb should receive all inactivated vaccines according to routine schedule, keeping in mind that immune response during the first few months may be suboptimal, depending on the monoclonal used and the gestational period during which it was administered.
Monoclonal antibodies administered to the mother during breastfeeding are thought to have very little or no impact on the infant. Transfer of monoclonal antibodies through breast milk is limited, and the minimal quantities that are ingested are likely to be broken down in the infants gastrointestinal tract. Infants of breastfeeding women receiving monoclonal antibody treatment post-partum should therefore be immunized with both live and inactivated vaccines according to routine schedules, unless the infant was also exposed to monoclonal antibody in the womb.

# HIV infection
The degree of immune suppression varies widely among HIV-infected individuals, reflecting disease stage and response to antiretroviral therapy. Immune suppression is approximately predicted by a recent CD4 count and CD4 percentage.
Children who are immune suppressed at HIV diagnosis and have already received routine vaccines should have antibody titres measured where possible and, if indicated, should be revaccinated after immune recovery.    

## Inactivated vaccines
When possible, vaccines should be given early in the course of HIV infection although there is no contraindication to the use of inactivated vaccines at any time. If immune suppression is severe in an untreated or newly treated patient and likelihood of exposure to the vaccine-preventable disease is low, vaccination may be deferred pending immune recovery after effective antiretroviral therapy.
Inactivated vaccines should be administered to HIV-infected people according to routine immunization schedules, with the exceptions that hepatitis B vaccine should be given at double the routine dose and using a 3 or 4 dose schedule.  HPV vaccine should be given following routine age indications but using a 3 dose schedule regardless of age. There is a high risk of HPV-associated warts with HIV infection; HPV 9 or 4 valent vaccine will provide additional protection over that of the 2 valent vaccine. For those 6 months of age or older, annual immunization with inactivated influenza vaccine is recommended. HIV-infected people should also receive pneumococcal conjugate vaccine regardless of age, pneumococcal polysaccharide vaccine if 2 years of age or older, and one dose of Hib vaccine after age 5 years regardless of prior Hib vaccination. Quadrivalent conjugate meningococcal vaccine is recommended and meningococcal B vaccine should be considered.  Hepatitis A vaccine is recommended for those with risk factors for hepatitis A acquisition. If herpes zoster vaccine is indicated by age, inactivated zoster vaccine should be considered.

## Live attenuated vaccines
The risks and benefits of a live vaccine need to be carefully considered in consultation with an infectious disease specialist/immunologist.
In general, infants should receive rotavirus vaccine according to routine schedule, as risk from infection with wild strain outweighs theoretical risk from the vaccine. If the infant is known to have severe immunodeficiency, consultation with a specialist is recommended.
MMR, varicella, live herpes zoster vaccines may be considered early in the course of HIV-infection if immune function is normal. Although LAIV is generally contraindicated, studies have shown it to be safe and immunogenic and many experts would consider using it for HIV-infected children on antiretroviral therapy and with normal immune function (see below). MMRV and other live vaccines are contraindicated at this time because of lack of data on safety. If immune suppression is already advanced at diagnosis, live vaccines should be deferred pending potential immune recovery with treatment. Consensus thresholds based on immunologic categories have been determined for the use of MMR, univalent varicella, live zoster vaccines and LAIV as follows:
- Asymptomatic HIV-infected children 12 months of age and older without severe immunosuppression (i.e., CD4   15% and CD4 cell count  500  106/L for at least 6 months in children 1 through 5 years old and  15% and CD4 cell count  200  106/L for at least 6 months in those  6 through 13 years of age) may receive MMR and univalent varicella vaccines.
- Immunization with MMR may be considered for susceptible HIV-infected adolescents and adults with CD4 cell count  200  106/L. There are no published data on the use of varicella vaccine in susceptible HIV-infected adults. HIV-infected adults should be asked for a history of varicella disease or vaccination, and if negative for both, serology should be requested to determine susceptibility. Based on expert opinion, varicella immunization may be considered for susceptible HIV-infected adults with CD4 cell count 200  106/L.
- Inactivated zoster vaccine is preferred. Live zoster vaccine may be considered if not severely immunosuppressed and inactivated vaccine is contraindicated or unavailable. Live zoster vaccine is contraindicated in persons with CD4 cell count < 200  106/L.
- If MMR or varicella vaccines were given to individuals with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months.
- Live attenuated influenza vaccine may be considered in otherwise healthy HIV-infected patients aged 517 years on combination antiretroviral therapy regimen for 16 weeks with CD4 T-lymphocyte percentage 15 and HIV plasma RNA <60 000 copies.
- Individuals 5 years of age and older: 1 dose recommended 
- Pre-exposure prophylaxis for travel: consider Ig with hepatitis A vaccine
- Post-exposure prophylaxis: Ig recommended along with hepatitis A vaccine unless immune function is normal
- Post-immunization monitoring of anti-HBs titres recommended with booster dose  if titre less than 10 IU/L
 - Use 5 dose schedule for post-exposure prophylaxis
- Post-immunization serology recommended
 Contraindicated if CD4 < 200 x 106 cells/L
- Adolescents and adults: consider 2 doses 3-6 months apart if susceptible  and not significantly immunocompromised
- Contraindicated in advanced HIV/AIDS
- If given to an individual  with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months
- Consider post-immunization serology
 If the infant is known to have severe immunodeficiency, consult a specialist in pediatric HIV or immunology
- Adolescents and adults: consider 2 doses 3-6 months apart if susceptible and not significantly immunocompromised
- Contraindicated in advanced HIV/AIDS
- If given to child with perinatal HIV infection before antiretroviral therapy was begun and serological response is not demonstrated, doses should be repeated once on effective therapy for at least 6 months
- Consider post-immunization serology
- Vaccinate well in advance of travel to monitor potential adverse events
- Consider post-immunization serology
Abbreviations:
 HBV = Hepatitis B virus
HCV = Hepatitis C virus
anti-HBs = antibody to hepatitis B surface antigen
LAIV = Live attenuated influenza vaccine
Given as combined vaccine (diphtheria, tetanus, pertussis;  polio, Hib depending on age and previous vaccine history). 
Routine use: follow routine immunization schedules with age-appropriate booster doses
May be given as combined vaccine.
Regardless of prior history of Hib vaccination and at least 1 year after any previous dose
Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the immunocompromised state and the ongoing risk of acquisition of HB infection 
Recombinant inactivated zoster vaccine may be considered in immunocompromised adults  50 years of age on a case by case basis. Data on the use in immunocompromised individuals is limited, but based on the burden of zoster illness in this population and the general safety of inactivated vaccines, the benefits of vaccination are expected to outweigh the risks
2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58(3):e44-100.
Close contacts
Annual influenza vaccine and up-to-date routine immunizations are recommended for household members and other close contacts of people with chronic diseases, as well as for their health care workers. Non-immunized close contacts of immunocompromised people should be immunized against pertussis, Hib, rotavirus, pneumococcus, measles, mumps, rubella, varicella, zoster and influenza as appropriate for age. Non-immune household or close contacts of immunocompromised people should be given hepatitis B vaccine. In addition, non-immune close contacts of HSCT recipients and close contacts of solid organ transplant candidates and recipients should receive hepatitis A vaccine if other risks for hepatitis A infection are present.
Vaccine viruses in MMR vaccine are not transmitted to contacts. Transmission of varicella vaccine virus from people with post-varicella vaccine rash occurs but is rare. Susceptible close contacts of immunocompromised people should receive MMR, MMRV, varicella or herpes zoster vaccine as appropriate for age. If the varicella vaccine recipient develops a varicella-like rash, the rash should be covered and the vaccinee should avoid direct contact with the immunocompromised person for the duration of the rash.
Infants living in households with persons who have or are suspected to have immunosuppressive conditions or who are receiving immunosuppressive medications can receive rotavirus vaccine. Following administration of rotavirus vaccine, viral antigen shedding in the stool may be detected in some vaccinees and may persist for up to 4 weeks. Transmission to household contacts occurs but is uncommon and many experts believe that the benefit of protecting immunocompromised household contacts from naturally occurring rotavirus by immunizing infants outweighs the theoretical risk of transmitting vaccine virus. To minimize the risk of transmission of vaccine virus during the 4 weeks after immunization, careful hand washing should be performed after contact with the vaccinated infant, especially after handling feces (e.g., after changing a diaper), and before food preparation or direct contact with the immunocompromised person.
Annual influenza immunization with influenza vaccine is recommended for close contacts of immunocompromised persons. Because of the theoretical risk for transmission, recipients of live attenuated influenza vaccine should avoid close association with persons with severe immunocompromising conditions (e.g., hematopoietic stem cell transplant recipients requiring isolation in hospital) for at least 2 weeks following vaccination.
Oral polio vaccine should not be administered to household contacts of an immunocompromised person. If there are household contacts who have received live, oral polio vaccine in another country within the last 6 weeks, they should not have contact with immunocompromised persons. Oral polio vaccine is not available in Canada.
Smallpox vaccine is available in Canada only for selected personnel working with vaccinia virus in research laboratories, or if an exposure to smallpox were to occur. Generally, smallpox vaccine should not be administered to household or close contacts of an immunocompromised person in a non-emergency situation. If vaccination is required in an outbreak situation, precautions should be taken to prevent spread to the immunocompromised person and other household and close contacts.
Immunocompromised travellers
A growing number of Canadians with reduced immune competence are travelling to tropical and low-income countries. Although the degree and range of infectious disease risks can increase significantly when an immunocompromised individual travels to other countries, the principles outlined above apply.
Travellers may require additional vaccines, depending on their destinations. Some travel vaccines may be contraindicated in immunocompromised individuals.  
For additional information about immunization of immunocompromised travellers, refer to the Committee to Advise on Tropical Medicine and Travel statement on   in Part 4 and  in Part 3.