Immunization of persons with chronic diseases: Canadian Immunization Guide

# Introduction
Chronic diseases may increase a person's risk of infection, or increase a person's risk of more severe disease should infection occur. There is also an increased risk of nosocomial exposure to vaccine-preventable diseases due the increased likelihood of prolonged hospitalization and frequent outpatient visits associated with chronic disease. Therefore, it is important that people with chronic diseases who are immunocompetent be immunized with both live and non-live (e.g., inactivated or recombinant) vaccines, according to routine immunization schedules. Vaccines may be less immunogenic in this population and additional vaccines, additional doses, or higher dosages of vaccines may be required to provide adequate protection.
Ideally, vaccination is best accomplished early in the disease when the response is likely to be similar to other persons of a similar age with no chronic medical condition. If a disease progresses and immunosuppressive therapy is required, vaccine requirements and recommendations may change.
In general, individuals with chronic disease are at higher risk of invasive pneumococcal disease, influenza and influenza-related complications, and should be immunized using the recommended vaccine and schedule.
COVID-19 vaccine is currently recommended for all individuals 6 months of age and older, including those with chronic conditions. This vaccine has not yet been added to Table 1, or to the text for chronic conditions other than autoimmune disease, pending recommendations for post-pandemic use.
For information about vaccination of people with immunodeficiencies, who are immunosuppressed or have HIV infection, refer to  in Part 3.

# Chronic diseases

## Asplenia or hyposplenia
Asplenic or hyposplenic people have absent or defective splenic function. This condition can occur as a result of congenital absence of the spleen, surgical removal of the spleen, or medical conditions that result in poor or absent splenic function, such as sickle cell disease or thalassemia major, among others. All people, regardless of age, who have absent or defective splenic function, are at increased risk of fulminant bacteremia, which is associated with a high mortality rate. Risk is highest in the first 2 years following splenectomy but remains elevated for life.
Careful attention should be paid to immunization status when elective surgical splenectomy is planned so that all of the necessary vaccines are administered at least 2 weeks before surgery. In the case of an emergency splenectomy, vaccines are best given 2 weeks after the splenectomy for optimal vaccine responses. If a person is discharged earlier and there is a concern that she or he might not return, vaccines should be given before discharge.
Persons with asplenia or hyposplenia should receive all routine vaccinations, including annual influenza vaccine. In addition, particular attention should be paid to ensuring that all asplenic or hyposplenic individuals receive *Haemophilus influenzae- type b (Hib) regardless of age or previous immunization history, quadrivalent conjugate meningococcal vaccine, serogroup B meningococcal vaccine and both pneumococcal conjugate and polysaccharide vaccines, as these individuals are highly susceptible to infection with encapsulated bacteria. Hepatitis B vaccines are indicated for those who require repeat transfusions, such as individuals with sickle cell anemia or thalassemia.

## Autoimmune conditions
Autoimmune conditions (referred to in former versions of the CIG as inflammatory diseases) encompass a broad category of related diseases in which an individual's immune system attacks his or her own cells. The spectrum of autoimmune conditions is diverse. The relative degree of autoimmunity in individuals with autoimmune conditions is variable depending on the underlying condition, the severity and progression of disease, and the use of medications that impact immune function. Common autoimmune conditions include systemic inflammatory diseases such as systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis and juvenile arthritis; as well as organ-specific inflammatory conditions such as Crohn's disease and ulcerative colitis, Graves' disease, Hashimoto's thyroiditis, multiple sclerosis, myasthenia gravis, Goodpasture's syndrome, pemphigus vulgaris, psoriasis, idiopathic thrombocytopenic purpura and, autoimmune hemolytic anemia.
Infections are among the most common causes of morbidity, hospitalization and death in individuals with an autoimmune condition. An increased risk of infection and infection-related complications is thought to be due to both an altered immune response associated with the autoimmune condition itself and to the immunosuppressive nature of the treatments required to control the underlying inflammatory condition.
Individuals with autoimmune disease not being treated with immunosuppressive drugs are not considered significantly immunocompromised and can receive routine immunization, including live vaccines. Rheumatic disease modifying agents, such as hydroxychloroquine, sulfasalazine, or auranofin are not generally identified as immunosuppressive, nor are topically-administered non-absorbable formulations of steroids. For children receiving chronic salicylate therapy for autoimmune conditions, inactivated influenza vaccine (IIV) rather than live attenuated influenza vaccine (LAIV) should be used (refer to ).
Individuals with autoimmune conditions should receive, in addition to routine immunization, influenza vaccine annually. Vaccination status should be assessed promptly and routine immunizations updated if needed. Any indicated live vaccines should be given as early as possible, as immunosuppression may be required in the future and live vaccines may then be contraindicated. If immunosuppressive therapy is anticipated in the near future, pneumococcal conjugate and polysaccharide vaccines should be given. Because of immunodeficiencies associated with autoimmune inflammatory disease, some experts recommend giving these vaccines at diagnosis.
COVID-19 infection has been associated with the development of an intense inflammatory response, as well as autoimmune phenomena, in some people, though whether these occur more often in people with autoimmune conditions is unclear. There has been a theoretical concern that inflammation elicited by mRNA vaccines for COVID-19 could exacerbate existing autoimmune diseases, despite the fact that applications of mRNA technology for COVID-19 vaccines have been optimized to reduce this risk through modifications to the RNA and lipid constructs. Participants with autoimmune conditions who were not immunosuppressed were not excluded from clinical trials for mRNA COVID-19 vaccines, but they constituted a very small proportion of trial participants and represented a very narrow spectrum of autoimmune conditions. Data from observational studies in individuals with autoimmune conditions indicate that the frequency and severity of adverse events in this population is comparable to that of individuals without autoimmune conditions and to what was reported in clinical trials. The onset of new autoimmune disease or disease exacerbation following vaccination with mRNA COVID-19 vaccines has been rare or comparable to the background incidence of these events in the general population. NACI recommends that a complete vaccine series with an mRNA COVID-19 vaccine should be offered to individuals in the authorized age group with an autoimmune condition.
For individuals with dermatologic disorders, care should be taken not to administer vaccine into affected areas, as this procedure may exacerbate the condition. Bacille Calmette-Guerin (BCG) vaccine is contraindicated if there is extensive skin disease at or near the site of injection. Live replicating smallpox vaccine is contraindicated in a non-outbreak situation.
For individuals with chronic inflammatory diseases who are being treated with immunosuppressive therapies including biologic response modifiers, refer to  in  in Part 3.

## Cancer
People with cancer have a higher risk of contracting infectious diseases and a higher risk of developing complications because many cancers and their treatments affect the immune system. Therefore, it is important that children and adults with cancer receive protection from vaccine preventable diseases whenever possible.
Generally, cancer alone, if it is not hematologic, is not sufficient to cause immunosuppression to the extent that an individual cannot receive live vaccines. If chemotherapy is not required, all routine vaccines should be given. Influenza vaccine should be given annually. Other vaccines may be indicated, depending on which organs or systems are affected by the tumour. If chemotherapy is to be given, any immunizations required, as well as annual influenza vaccine, should be completed before beginning chemotherapy whenever possible.
For hematologic cancers or for people on immunosuppressive therapies, refer to  in  in Part 3.

## Cochlear implants
People who have received a cochlear implant are at increased risk for bacterial meningitis and for otitis media. In addition to all age appropriate vaccinations, people with cochlear implants and those who are receiving cochlear implants should receive annual influenza vaccine, pneumococcal conjugate and polysaccharide vaccines if age less than 18 years, or pneumococcal polysaccharide vaccine if 18 years of age or older, and Hib vaccine if 5 years of age or older regardless of Hib vaccination history.

## Endocrine and metabolic diseases
People with diabetes mellitus have defects in phagocytic and neutrophil function. In addition, they often have complications of diabetes such as cardiovascular, neurovascular, renal and other end-organ dysfunction and are at greater risk of complications from infection. Persons with other metabolic disorders, such as thyroid disorders, or morbid obesity (Body Mass Index of 40 or higher) are at high risk of influenza-related complications.
Routine immunization, including annual influenza vaccine, is recommended for persons with endocrine and metabolic disorders. In addition to routine immunization, people with diabetes should receive pneumococcal conjugate and polysaccharide vaccines if age less than 18 years or pneumococcal polysaccharide vaccine if 18 years of age or older. There is no evidence that vaccination interferes with glycemic control.
There is an association between yellow fever vaccine-associated viscerotropic disease and a history of thymus disease. Yellow fever vaccine is contraindicated in persons with a history of thymus disease associated with abnormal thymus function (e.g., thymoma, thymectomy or myasthenia gravis). If travelling to a yellow fever endemic or epidemic area, expert advice should be sought concerning the risks of exposure to yellow fever, the ability to adhere to mosquito protection measures, and the risk of vaccine-associated disease.

## Heart disease
In individuals with chronic heart disease, viral and bacterial infections may precipitate cardiac decompensation and lead to hospitalization. There is evidence that giving influenza vaccine to those with coronary artery disease has some protective effect on subsequent cardiac events.
People with cardiac disease should receive routine immunization, including annual influenza vaccine, as they are at high risk of influenza-related complications. Individuals with chronic heart disease should also receive pneumococcal conjugate vaccine and polysaccharide vaccine if less than 18 years or pneumococcal polysaccharide vaccine if 18 years of age or older.
Young children with certain chronic cardiac conditions are at high risk of respiratory syncytial virus (RSV) associated hospitalization. The monoclonal antibody preparation, palivizumab, is recommended to protect against severe infection in infants less than 12 months of age with haemodynamically significant congenital heart disease at the onset of the RSV season. 
Live replicating smallpox vaccine is contraindicated in a non-outbreak situation for specific cardiac conditions (Table 2).

## Hematologic disorders (non-malignant)
Non-malignant hematologic disorders include different types of chronic anemia and hemoglobinopathy, as well as bleeding disorders. For further discussion on vaccines recommended for people with anemia due to sickle cell disease or other hemoglobinopathies associated with splenic dysfunction, refer to .
Some hematologic disorders require frequent or chronic administration of blood products. Recent administration of blood products may interfere with the antibody response to live vaccines, and receipt of plasma or immunoglobulin may result in false positive antibody tests. Refer to  in Part 1 for additional information.

### Anemia and hemoglobinopathy
People with anemia may be at increased risk of complications from vaccine- preventable diseases. In addition to routine immunization, people with chronic anemia or hemoglobinopathy should receive influenza vaccine annually. If there is a need for repeated blood transfusions, hepatitis B vaccine is required. If there is splenic dysfunction, refer to .

### Bleeding disorders
People with bleeding disorders such as hemophilia may differ from the healthy population with respect to the potentially increased risk of infection as a result of exposure to blood products and the risk of hematoma formation from parenteral injections. In addition to routine immunization, people with hemophilia and other clotting factor disorders receiving repeated transfusions of blood or blood products should receive hepatitis B vaccines unless already infected or immune. Pre-immunization serologic testing for hepatitis B should be performed if they have already had repeated exposure to blood products. In addition, those receiving repeated infusions of plasma-derived clotting factors should receive hepatitis A vaccine.
Before beginning immunization of any child, vaccine providers should ensure that there are no symptoms or signs compatible with an undiagnosed bleeding disorder. If such indicators are present, a diagnosis should be established before commencing immunization. For example, in any child who has a history of an intramuscular (IM) hematoma following an IM injection, an undiagnosed bleeding disorder, such as hemophilia, should be considered. If a disorder is present, it should be optimally managed prior to immunization to minimize the risk of bleeding. Hemophiliacs may receive clotting factor concentrates to optimize their clotting factor level before they receive a parenteral vaccine or a passive immunizing agent.
Generally there is no evidence of increased risk of bleeding in those with bleeding disorders following IM versus subcutaneous injections. There is evidence to suggest that IM administration is safe when given with a small gauge needle (23 gauge or smaller) and when firm pressure is applied to the injection site for  2 minutes. There is also evidence that immunization by the subcutaneous route for vaccine intended for intramuscular administration may be associated with more local reactogenicity and a diminished immune response, compared to the IM route.
Individuals receiving long-term anticoagulation may also be safely immunized through either the IM or subcutaneous route as recommended for a specific vaccine, using the same precautions as for bleeding disorders, without discontinuation of their anticoagulation therapy.

## Kidney disease and patients on dialysis
Bacterial and viral infections are a major cause of morbidity and mortality in people with renal disease or who are undergoing chronic dialysis (hemodialysis or peritoneal dialysis). People with chronic kidney insufficiency and dialysis may have mild defects in T cell function, while in individuals with nephrotic syndrome, urinary loss of antibody may occur. Also, because these persons are also in frequent contact with the health care system, they are at greater risk of hospital-acquired infection from vaccine preventable diseases.
People with chronic renal disease or those who are undergoing dialysis should receive all routine vaccinations, including annual influenza vaccine. In addition to routine immunization, hepatitis B and pneumococcal vaccines (conjugate and polysaccharide vaccines if age less than 18 years, polysaccharide vaccine if 18 years of age or older) are recommended. Those with nephrotic syndrome should receive both the conjugate and the polysaccharide vaccines even if age 18 years or older. Since individuals with impaired renal function may experience a less than optimal response to immunization, higher vaccine doses and re-immunization may be required. Monitoring vaccine titers may be helpful.
For information about kidney transplant candidates and recipients, refer to  in  in Part 3.

## Liver disease
Chronic liver disease can impact innate and adaptive immune mechanisms. Splenic dysfunction may also occur if the liver disease is severe. Hepatic encephalopathy or chronic alcohol consumption may lead to aspiration pneumonia. Alcoholism is also a risk factor for invasive pneumococcal disease. Newly acquired hepatitis A or hepatitis B in persons who already have chronic liver disease from another cause could lead to more severe disease and rapid hepatic decompensation. Those with ascites have an altered immunoglobulin production and distribution.
People with chronic liver disease should receive all routine immunizations, including annual influenza vaccine, conjugate and polysaccharide pneumococcal vaccine if age less than 18 years or polysaccharide pneumococcal vaccine if age 18 years or older, as well as hepatitis A vaccine and hepatitis B vaccine if not already infected or immune. Vaccination should be completed early in the course of liver disease, as the immune response to vaccine is suboptimal in advanced liver disease. Since individuals with chronic liver disease may experience a less than optimal response to immunization, higher vaccine doses and re-immunization may be required.

## Lung disease
Individuals with chronic lung diseases such as bronchopulmonary dysplasia, cystic fibrosis, asthma or chronic obstructive pulmonary diseases (COPD) are at increased risk of complications of influenza and pneumococcal infection. Those with cystic fibrosis are also at increased risk of complications from varicella infection, which may cause a transient worsening of lung function. Young children with chronic lung disease of prematurity who require ongoing oxygen therapy are at high risk of respiratory syncytial virus (RSV) associated hospitalization. Many individuals with more severe chronic lung disease have bacterial colonization due to poor mucociliary clearance and bronchiectasis, pneumatoceles, or defects in pulmonary macrophage function.
People with chronic lung disorders should receive influenza vaccine annually in addition to other routine immunization. Live attenuated influenza vaccine (LAIV) is contraindicated for persons with current severe asthma (currently on oral or high dose inhaled glucocorticosteroids or active wheezing, or those with medically attended wheezing in the 7 days prior to immunization). In these situations, inactivated influenza vaccine (IIV) should be used. Pneumococcal vaccines are also recommended, including for those with asthma requiring medical care in the preceding 12 months. Conjugate and polysaccharide vaccines should be given if age less than 18 years, and pneumococcal polysaccharide vaccine if 18 years of age or older. The monoclonal antibody preparation, palivizumab, is recommended to protect against severe infection in children less than 24 months of age with chronic lung disease of prematurity who require ongoing oxygen therapy in the six months preceding or during the RSV season.

## Neurologic disorders
Persons with neurological disorders are at increased risk of hospitalization with influenza. Some studies suggest that influenza vaccine may decrease the risk of stroke.
In addition to all routine immunizations, people with neurological or neurodevelopmental conditions should receive annual influenza vaccine (with the exception of anyone who developed Guillain-Barre Syndrome  within 6 weeks after a previous dose of influenza vaccine unless another cause was found). Some neurological conditions also predispose to pneumococcal infections. Pneumococcal vaccines are recommended for those with chronic cerebrospinal fluid (CSF) leak or difficulty handling respiratory secretions. Those less than 18 years of age should receive both pneumococcal conjugate and polysaccharide vaccines and those aged 18 years or older should receive polysaccharide vaccine.
Neurological conditions are generally not a contraindication to immunization. Some neurologic conditions, such as autism spectrum disorders, are diagnosed in childhood over the time period that routine vaccines are administered, causing concern that immunization may have caused the condition. Others that are present at birth or that begin during infancy, such as cerebral palsy, spina bifida, seizure disorders, neuromuscular diseases and inborn errors of metabolism, may have symptom onset before the receipt of the vaccines routinely recommended in infancy. There is no evidence that immunization causes or aggravates these conditions and these conditions are not reasons to delay or avoid vaccinations. On the contrary, patients with chronic neurological conditions benefit from optimal vaccination.
Certain neurologic disorders (e.g., multiple sclerosis), may be treated with immunosuppressive therapies. In this situation, recommendations for immunocompromised persons should be applied. For information, refer to  in Part 3.

## Salicylate therapy in children
Individuals less than 18 years of age receiving low doses of salicylate therapy (e.g., acetylsalicylic acid ) require special consideration regarding live influenza and varicella vaccines because of an association between wild-type influenza or varicella infection, salicylate therapy and Reye's syndrome. Reye's syndrome, which causes damage to the brain and liver, is a rare complication that most commonly occurs in children taking ASA at the time of wild-type infection with these viruses.
Children and adolescents receiving chronic salicylate therapy are at high risk of influenza-related complications and should receive inactivated influenza vaccine annually (IIV). LAIV should not be administered to children currently receiving ASA.
Health care providers should weigh the theoretical risks associated with varicella vaccine against the known risks associated with wild-type varicella infection. Because adverse events have not been reported with the use of salicylates after varicella immunization, people with conditions requiring chronic salicylate therapy should be considered for immunization, with close subsequent monitoring.

# Co-morbidities
Guidance on immunization for those with more than one chronic condition is an emerging area of inquiry; evidence to support guidance on immunization of people with co-morbidities is lacking. There is some evidence that co-morbidities may have additive risk for complications from vaccine preventable diseases, such as influenza. As a general principle, when considering immunization of people with co-morbidities, all conditions and medications should be considered in relation to the indications, precautions and contraindications for each vaccine.

# 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.
There are no contraindications to family members receiving routine live vaccines.
Please note that the information in the text and tables is complementary and both should be used.
Consider optimizing control of bleeding disorders prior to receipt of parenteral injections. For people with sickle cell disease, refer to  section.
Including asthma requiring medical care on the preceding 12 months.
People known to have developed GBS within 6 weeks of previously receiving a vaccine should not receive repeat doses of that vaccine unless an alternative cause for the GBS was identified.
May be considered in persons with chronic illnesses for whom there is an increased risk of serious consequences from travellers' diarrhea. Vaccine benefits have not been studied in these specific groups. Vaccine is of limited benefit and is not routinely recommended, except for high-risk travellers who are 2 years of age and older.
Given as combined vaccine (diphtheria, tetanus, pertussis;  polio, Hib, hepatitis B depending on age and previous vaccine history).
Routine use: Follow routine immunization schedules with age-appropriate booster doses.
May be given as combined vaccine.
If age  5 yr, one dose regardless of previous Hib vaccine history to be given at least 1 yr after last dose if any dose(s) given before age 5 yr.
Vaccine recommended for conditions requiring repeated transfusions such as sickle cell disease or thalassemia major.
Higher dosage recommended; post-immunization serology recommended with re-immunization if hepatitis B surface antibody titre (anti-HBs) less than 10 IU/L; periodic monitoring of anti-HBs titre recommended. Initially annual monitoring of antibody levels may be considered. Optimal timing and frequency should be based on the severity of the clinical condition and the ongoing risk of acquisition of HB infection.
Vaccinate early in course of hepatic disease; for people with advanced liver disease, assess seroconversion and consider re-immunization with increased antigen content vaccine if anti-HBs less than 10 IU/L.
The recombinant zoster vaccine (not the live zoster vaccine) may be considered for immunocompromised adults 50 years of age and older based on a case-by-case assessment. 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. Refer to  and -vaccine.html) in Part 4.
Children (6 months to 17 years): Given the burden of influenza B disease, either IIV4 or LAIV should be used, including for those with non-immune compromising chronic health conditions. IIV4 should be used for children for whom LAIV4 is contraindicated. If IIV4 is not available and LAIV is not available or contraindicated, IIV3 should be used. Adults: Any available influenza vaccine should be used. IIV should be used for adults 18  59 years for whom LAIV is contraindicated or not recommended.
Annual influenza vaccine is recommended for everyone 6 months of age or older. "Recommended" here refers to groups for whom it is particularly recommended because of the high risk of complications from influenza.
Periodic re-immunization with quadrivalent conjugate meningococcal vaccine also recommended.
Either serogroup B meningococcal vaccine can be used; 4CMenB vaccine (for those 2 months of age and older) or MenB-fHBP (for those 10 years of age and older). The timing of booster doses has not yet been determined. Refer to  in Part 4.
For those with chronic CSF leak or chronic neurologic conditions that may impair clearance of oral secretions, cochlear implant or for whom an implant is planned.
Abbreviations:
IIV: inactivated influenza vaccine
IIV3: trivalent inactivated influenza vaccine
IIV4: quadrivalent inactivated influenza vaccine
LAIV: live attenuated influenza vaccine
RZV: recombinant zoster vaccine
Please note that the information in the text and tables is complementary and both should be used.
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years if no immune suppression and not on chronic salicylate therapy, in which case IIV4 should be used.
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years:
LAIV may be used for children age 2-17 years and adults age 18-59 years
LAIV may be used for children age 2-17 years:
Consider optimizing control of bleeding disorders prior to receipt of parenteral injections. For people with sickle cell disease, refer to  section.
Including asthma requiring medical care on the preceding 12 months.
People known to have developed GBS within 6 weeks of previously receiving a vaccine should not receive repeat doses of that vaccine unless an alternative cause for the GBS was identified.
When RZV is contraindicated, unavailable or inaccessible, LZV may be considered.
LAIV or IIV can be used in children above age 2 years with chronic conditions. A quadrivalent vaccine is preferred. IIV is recommended for adults with chronic conditions.
Annual influenza vaccine is recommended for everyone 6 months of age or older. "Recommended" here refers to groups for whom it is particularly recommended because of the high risk of complications from influenza.
Contraindicated for persons with current severe asthma (currently on oral or high dose inhaled glucocorticosteroids or active wheezing, those with medically attended wheezing in the 7 days prior to immunization), children and adolescents 217 years of age currently receiving aspirin or aspirin-containing therapy, and those with immune compromising conditions, excluding those with stable HIV infection on highly active antiretroviral therapy (HAART) and with adequate immune function  use IIV.
Contraindicated in uncorrected congenital malformation of gastrointestinal tract such as Meckel's diverticulum that could predispose to intussusception.
Diffuse vaccinia virus infection can occur in persons with acute atopic dermatitis or other widespread exfoliative skin disorders. Smallpox vaccine is contraindicated in people with known underlying heart disease or who have three or more known major cardiac risk factors (i.e., hypertension, diabetes, hypercholesterolemia, heart disease at age 50 years in a first-degree relative, and smoking). Persons with inflammatory eye disease may be at increased risk for inadvertent inoculation as a result of touching or rubbing the eye. Deferring vaccination is prudent for persons with inflammatory eye diseases requiring steroid treatment until the condition resolves and therapy is complete.
If typhoid vaccine is indicated, use the non-live vaccine.
 Susceptible people with cystic fibrosis are a priority for varicella immunization.
There is an association between yellow fever vaccine-associated viscerotropic disease and a history of thymus disease. Yellow fever vaccine is contraindicated in persons with a history of thymus disease associated with abnormal thymus function (e.g., thymoma thymectomy or myasthenia gravis).
Abbreviations:
BCG: Bacille Calmette-Guerin vaccine
IIV: inactivated influenza vaccine
LAIV: live attenuated influenza vaccine
LZV: live zoster vaccine
MMRV: Measles, Mumps, Rubella, Varicella
RZV: recombinant zoster vaccine

# Chapter revision methodology
The Part 3 Working Group conducted a literature review on recommendations for yellow fever vaccination related to thymus function. The section on  has been updated to clarify that yellow fever vaccine is contraindicated in persons with a history of thymus disease associated with abnormal thymus function (e.g., thymoma, thymectomy, myesthenia gravis). Previously, it was stated that YF vaccine was "not generally recommended" in this population.
The duration of injection site compression following immunization of individuals with  and individuals receiving long-term anticoagulation was brought forward as guidance requiring further assessment. The previous recommendation was to apply pressure at the injection site for 5-10 minutes. A literature review was conducted for evidence to inform recommendations on the duration of pressure application following immunization in the identified groups. An independent and systematic search of Ovid MEDLINE, Embase, Scopus, and PubMed for studies or reports published between 1946 and 2020 using keywords which include "immunization", "vaccin\*", "anticoagulant", "bleeding disorder or blood-clotting disorder", "pressure", and "intramuscular injection" yielded 99 publications addressing the application of pressure to the injection site following immunization of individuals with bleeding disorders or individuals receiving anticoagulants. The search was limited to publications in English and human studies. Although primary evidence related to the topic was scarce, the majority of the publications provided recommendations that were based on expert opinion or findings from a primary research study by Evans et al. The study reported that following the use of a 23-gauge needle and 1 to 2 minutes of pressure applied to the injection site in children with hemophilia receiving the hepatitis B vaccine, only six of 153 IM injections (4%) resulted in bruising, and none of the children required treatment with clotting factor concentrates. Findings from the literature review and the proposed recommendation were circulated among WG members who agreed on the recommendation to apply firm pressure to the injection site for  2 minutes in the specified groups.
Publications pertaining to vaccination of persons with selected specific conditions were searched using the search strategy (vaccine OR vaccination OR immunization), AND (splenectomy OR asplenia OR hyposplenia OR "chronic inflammatory disease" OR rheumatic OR IBD OR, "renal disease" OR "kidney disease" OR nephrotic OR ESRD OR diabetes) This additional literature review conducted to identify changes in evidence or vaccine recommendations for persons with the aforementioned conditions did not lead to any new findings that would warrant further revisions to the corresponding sections.
The section on 'Asplenia or hyposplenia' was revised to state that there are other conditions of concern in addition to sickle cell disease or thalassemia major that are associated with splenic dysfunction.
The two tables in the chapter outlining recommendations for use of non-live and live attenuated vaccines for persons with chronic diseases were updated. These tables' contents reflect some of the information in the main text of the chapter and include extra details, and are intended to be used as a complementary resource with the text. The contents of the text and tables were extracted from the corresponding vaccine-specific chapters in  of the CIG and from NACI statements.