Overview
Definition:
Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders characterized by a defect in the innate or adaptive immune system, leading to increased susceptibility to infections
Vaccine guidance is crucial as certain vaccines, particularly live attenuated ones, pose a risk in specific PID types.
Epidemiology:
Estimated incidence of PIDs is around 1 in 2000 live births, with significant variation depending on the specific defect
Severe forms are diagnosed in infancy, while milder forms may present in childhood or adulthood
Accurate diagnosis and appropriate management, including vaccine strategies, are vital for improved outcomes.
Clinical Significance:
Mishandling of vaccines in patients with PIDs can lead to severe adverse events, including disseminated infection or vaccine failure
Conversely, timely and appropriate vaccination is essential for providing some level of protection against preventable diseases, even in immunocompromised individuals
Understanding defect-specific guidance is paramount for pediatricians and immunologists.
Vaccine Guidance By Defect
Severe Combined Immunodeficiency Scid:
Live attenuated vaccines (MMR, Varicella, Rotavirus, BCG) are contraindicated due to severe risk of disseminated infection
Inactivated vaccines can be administered but may elicit a suboptimal response
Hematopoietic stem cell transplantation is often required.
Agammaglobulinemia X Linked Bruton S Tyrosine Kinase Deficiency:
Live attenuated vaccines are contraindicated
Inactivated vaccines can be given, but antibody responses will be poor without immunoglobulin replacement therapy
Regular IVIG or SCIG is essential.
Common Variable Immunodeficiency Cvid:
Live attenuated vaccines are generally avoided or used with caution, especially if there is significant B-cell dysfunction or asplenia
Inactivated vaccines can be given, but response may be impaired
Intravenous or subcutaneous immunoglobulin replacement is standard therapy.
Selective Iga Deficiency:
Live attenuated vaccines are generally safe
However, caution is advised with oral polio vaccine (OPV) if associated with anti-IgA antibodies
Inactivated vaccines are safe and effective.
Deficiency Of Phagocytes Neutropenia Chronic Granulomatous Disease:
Live attenuated vaccines are generally safe, but caution is advised with Rotavirus vaccine in severe neutropenia
Inactivated vaccines are safe and effective
Management of recurrent infections is key.
Deficiency Of Complement Components:
Live attenuated vaccines are generally safe
However, individuals with deficiencies in the terminal complement components (C5-C9) are at increased risk of Neisseria meningitidis infections, so vaccination against meningococcus is crucial
Inactivated vaccines are safe.
Deficiency Of Innate Immunity Toll Like Receptor Defects:
Vaccine response can be variable depending on the specific defect
Generally, live attenuated vaccines are safe, but inactivated vaccines are preferred for maximum safety
Careful monitoring is advised.
Autoinflammatory Syndromes:
Live attenuated vaccines are generally safe
However, caution may be warranted with Rotavirus vaccine in patients on long-term immunosuppressive therapy
Inactivated vaccines are safe and recommended.
General Vaccination Principles In Pid
Live Attenuated Vaccines:
Contraindicated in severe T-cell defects (e.g., SCID), B-cell defects with significant B-cell dysfunction (e.g., XLA, some CVID), and certain other severe PIDs where risk of disseminated infection outweighs benefit
Use with caution in specific conditions.
Inactivated Vaccines:
Generally safe and recommended for all PID patients to provide protection against preventable infections
However, immune response may be suboptimal, necessitating higher doses, booster doses, or careful monitoring of antibody titers.
Vaccine Scheduling:
Follow standard immunization schedules as much as possible, but tailor based on the specific PID defect
Consult with an immunologist for personalized recommendations
Consider delaying live vaccines until immune function is better understood or improved.
Monitoring Antibody Response:
For inactivated vaccines, serial measurement of antibody titers may be necessary to confirm adequate immune response and determine the need for booster doses
This is particularly important for vaccines like pneumococcal and meningococcal conjugate vaccines.
Prophylaxis And Treatment:
Vaccination should be considered an adjunct to, not a replacement for, prophylactic antibiotics, immunoglobulin replacement, and other supportive therapies
Prompt treatment of infections is crucial regardless of vaccination status.
Diagnostic Approach To Vaccine Adverse Events
History Taking:
Detailed history of vaccine administration (type, dose, date)
Onset and nature of symptoms
Timeline of events
Prior history of infections or immune dysfunction.
Physical Examination:
Thorough physical examination to assess for signs of disseminated infection, rash, fever, or organ involvement
Assess hydration and vital signs.
Investigations:
Complete blood count with differential
Immunoglobulin levels (IgG, IgA, IgM)
Lymphocyte subsets (CD3, CD4, CD8, CD19, CD20, CD56)
Functional immune assays (e.g., T-cell proliferation, B-cell differentiation)
Viral PCR or culture for suspected disseminated vaccine-related infection.
Differential Diagnosis:
Other infectious causes unrelated to vaccine
Underlying PID exacerbation
Other immune-mediated reactions
Concurrent illness.
Management Of Vaccine Adverse Events
Immediate Management:
Discontinue further live attenuated vaccinations
Supportive care including hydration and fever control
Prompt empirical antibiotic therapy if bacterial co-infection is suspected
Antiviral therapy if viral dissemination is confirmed.
Specific Management:
For disseminated live vaccine infections (e.g., Varicella in SCID), specific antiviral therapy is indicated
For suspected immune dysregulation, consult with an immunologist for potential immunomodulatory agents
If the patient is on immunoglobulin replacement, ensure adequate levels.
Reporting Adverse Events:
All suspected vaccine adverse events, especially in immunocompromised individuals, should be reported to national pharmacovigilance centers and immunodeficiency registries
This aids in post-marketing surveillance and understanding vaccine safety.
Key Points
Exam Focus:
Know which live vaccines are contraindicated in which specific PIDs (e.g., SCID, XLA, CGD)
Understand the rationale behind these contraindications (risk of dissemination)
Recognize that inactivated vaccines are generally safe but may have suboptimal responses.
Clinical Pearls:
Always consider the possibility of an underlying PID in infants and children with recurrent severe infections
Discuss vaccine plans with a pediatric immunologist for immunocompromised patients
Promptly investigate any concerning reaction following vaccination in a potentially immunocompromised child.
Common Mistakes:
Administering live attenuated vaccines to patients with known severe T-cell or B-cell defects
Failing to consider PID in a child with recurrent infections and significant vaccine reactions
Not monitoring antibody responses to inactivated vaccines in immunocompromised individuals.