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Vaccination in Immunocompromised and Febrile Patients

M3 India Newsdesk Mar 16, 2023

Immunocompromised or febrile patients provide special challenges for the administering physician when it comes to vaccination. By offering various vaccination strategies, this article will assist medical professionals in the treatment of such patients.

Vaccination is a process of inoculating the vaccine/ antigen into the human body and is also called active immunisation. It is one of the greatest inventions of mankind.

Vaccination among patients who are immunocompromised or febrile is challenging for the patients and the treating physician. Immunocompromised patients are in greater need of vaccination as they are more susceptible to infections. At the same time, immunogenicity and the efficacy of vaccines are lower and the risk of adverse effects with live vaccines is higher. A low-grade fever is not a contraindication of vaccines but parents are very much concerned about vaccination in their febrile child.

Vaccination in immunocompromised patients

Immunocompromised patients have weak or impaired immune systems. Various immunocompromised states which require special attention for planning vaccination are:

1. Primary immunodeficiency (congenital)

  • B- lymphocyte defects
  • T- lymphocyte defects
  • Phagocytic function disorders
  • Complement deficiency

2. Acquired immunodeficiency

  • HIV infection
  • Chronic diseases and immunosuppression
  • Transplant or cancer patients
  • Immunosuppressive therapy – Steroids, Chemotherapy, Radiotherapy
  • Asplenic patients
  • Autoimmune disease patients.

Issues faced by clinicians in vaccinating an immunocompromised individual

  • Increased susceptibility to infections
  • Increased severity of the disease
  • Poor immune response to the vaccine
  • Safety of vaccination is also an issue
  • The efficacy of the vaccine is sometimes doubtful

Classification of immunosuppression

This is based on the CD4 count. If the CD4 count is >25% the immunity is conserved and hence vaccination with live vaccines based on a risk-benefit ratio can be given

  • Conserved- No immunosuppression
  • CD4+T lymphocytes>25%
  • Moderate immunosuppression
  • CD4+ T lymphocyte 15-24%
  • Severe immunosuppression (Impaired, absent)
  • CD4+T lymphocyte <15%

Vaccination of patients with immunodeficiency

Vaccination of patients who are HIV positive

In case of progressive decline in CD4 T lymphocyte count, there is an increased risk of complications from infections, impaired effectiveness of vaccines, there may be a risk of serious adverse events from live vaccines. With a significantly low CD4 count, there may be a loss of prior immunity because of a lack of cell-mediated immunity.

Vaccination of patients with cancer

The effect of cancer chemotherapy is evident in all the haematological cell lines. Lymphocytes seem to have a slower recovery to safe values than neutrophils, monocytes or platelets and never seem to return to pre-treatment values anytime after the cessation of therapy. This is particularly true for CD4 + T lymphocytes which display a very slow return to normality and are found to be persistently reduced even after one year of cessation of therapy in 20 to 50% of the patients with malignancy.

Humoral immunity is also affected. At the end of chemotherapy, several patients have abnormally low levels of IgG, IgM and IgA serum concentrations. A good recovery in immunoglobin values is shown by nearly all patients within six months after completion of therapy but IgG subclass abnormalities or low serum concentrations of specific antibodies versus diphtheria pertussis and tetanus can persist for more than one year in a substantial proportion of children.

Different approaches suggested for vaccination in these patients

  1. Administering another complete vaccination schedule.
  2. Immunisation all of them with a booster dose without taking possible residual immunity into consideration.
  3. Evaluating first the serum level of antibodies against vaccine antigens and giving a booster dose to children with no protective levels.
  4. Continuing the regular vaccination schedule.

At present, an interval of at least six months is considered if necessary for the immune system to recover sufficiently to be able to produce an adequate immune response to vaccinations.

The general principle is avoiding all the live vaccines in all patients undergoing chemotherapy or radiotherapy and in children who have completed the treatment less than six months earlier. The administration of inactivated virus, subunit, recombinant, polysaccharide, or toxoid vaccines is also not recommended within three to six months of therapy because of the possibility of weak or absent response. Passive immunisation can be considered in order to provide protection in the case of exposure to particular pathogens for example HBV and measles.

  1. Among the routine vaccines BCG vaccine is usually given at birth; hence revaccination is usually not required in most children. However, it can be administered at least six months after completion of the standard dose chemotherapy in unimmunised children.
  2. OPV is absolutely contraindicated due to the increased risk of vaccine-associated paralytic poliomyelitis. Inactivated polio vaccine(IPV) can be used safely alone or in combination with other vaccines after an appropriate interval.
  3. Diphtheria, tetanus and pertussis or acellular pertussis vaccine can be given three to six months after the end of chemotherapy. Measles, mumps and rubella(MMR) can be administered to children with cancer at least after six months after completion of treatment. Passive immunisation with specific immunoglobulin is most effective if given within 72 hours of the contact.
  4. Children with cancer should be fully vaccinated with hepatitis B vaccines with demonstratable protective titres. One of the suggested schedules is to start the vaccination at diagnosis in previously unimmunised children in a high dose, which is double the routine dose and repeated after 1,2 and 12 months.
  5. Annual vaccination against influenza is recommended in all immunocompromised children because of the high risk of adverse outcomes from influenza infection.
  6. Hib, pneumococcal and meningococcal vaccinations can also be started three to six months from the end of chemotherapy in order to obtain an adequate immune response.
  7. Children, less than two years should receive the regular schedule of conjugated polysaccharide pneumococcal vaccine. Yellow fever and oral typhoid vaccines are absolutely contraindicated in patients with cancer.

Vaccination of solid organ transplant recipients

  1. IAP recommends the completion of all immunisations prior to transplant in accelerated schedules if needed.
  2. In solid organ transplant recipients in patients where immunisations have not been completed prior to transplant, vaccinations with inactivated vaccines can recommence six months post-transplant when immune suppression has been lowered.
  3. Boosters or inactivated vaccines should be given as per the schedule when the antibody levels wane, starting six months post-transplant.
  4. Annual inactivated influenza vaccination is recommended. All live vaccines are contraindicated in post-transplant.

Vaccination of patients with anatomical or functional asplenia

The risk of mortality from septicemia increases by about 50 times in post-splenectomy cases and is about 350 times in sickle cell disease and thalassemia.

Risk is higher in younger children than older children and adults and it is a high risk for serious infections with encapsulated organisms. All live and inactivated vaccines are indicated and pneumococcal, Hib influenza and meningococcal vaccines are a must.

Vaccination of patients receiving steroids

The immune status and the response to the vaccine would depend on the dose and duration of steroids.

There will be an absence of immune suppression if the dose is 20mg per day(Prednisone) or less than 2mg/kg in children and the duration of administration is less than 2 weeks. In these situations, killed vaccines are safe but less efficacious but all live vaccines are safe and efficacious during inhalation and topical therapy.

Outside of these conditions, no live vaccines(until 1 month after discontinuation of corticosteroid) should be given and the individual vaccine responses should be assessed after vaccination.

Vaccination in a febrile patient

  1. As a parent fever in a child is always a worrisome problem. Parents of febrile children are always anxious.
  2. However, CDC/IAP recommendations are we can give all routine vaccination to patients with mild fever and viral illness with cough, cold and diarrhoea.
  3. But as fever is also a side effect of most of the vaccines post-vaccination in a febrile child it is difficult to determine whether fever is due to illness or due to vaccine, so vaccination should be avoided in patients with high-grade fever.


Active immunisation is the best method to induce protection against various infections, even in immunocompromised children. However certain precautions need to be followed while administering live vaccines to these children. Besides, administrations of the inactivated killed vaccines may also have to be delayed for variable durations to achieve protective antibody levels. Administration of higher antigen content or more doses, assessment of the antibody response and frequent booster vaccines are other approaches which need further evaluation.


Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Shaukat Panjawani is a Consultant Paediatrician and Neonatologist at Olive Multispecialty Hospital, Vapi.

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