At what age should pneumococcal (Streptococcus pneumoniae) titers be checked in individuals with recurrent infections?

Pneumococcal Titer Testing in Recurrent Infections

Pneumococcal titers should be checked in children aged 2 years and older who have recurrent serious bacterial infections (defined as two or more serious bacterial infections such as bacteremia, meningitis, or pneumonia within a 1-year period). 1

Indications for Pneumococcal Titer Testing

• Pneumococcal titer testing is indicated primarily for patients with recurrent respiratory infections to identify those with selective antibody deficiency despite normal immunoglobulin levels 2
• Testing is particularly important in children with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy) who are at highest risk for pneumococcal infection 3
• Children with congenital or acquired immunodeficiency diseases, including HIV infection, who have recurrent serious bacterial infections should be evaluated for pneumococcal antibody response 3
• Patients with suspected immunodeficiency who have normal total IgG levels but continue to experience recurrent infections should be tested for specific pneumococcal antibody response 4

Age Considerations for Testing

• Pneumococcal antibody testing should begin at age 2 years or older, as younger children have naturally poor responses to polysaccharide antigens 5
• Children under 2 years of age generally cannot mount adequate responses to pneumococcal polysaccharide antigens, making titer testing less useful before this age 4, 5
• The ability to develop antibodies against different pneumococcal polysaccharides develops gradually in the first years of life 4
• Vaccination status should be assessed during the adolescent immunization visit at 11-12 years of age for those with risk factors 3

Testing Protocol

• Baseline (pre-immunization) pneumococcal antibody titers should be measured before vaccination 4
• Post-immunization titers should be obtained 4-6 weeks after pneumococcal vaccination 6, 4
• An adequate response is generally defined as:
  • Post-immunization antibody titer of ≥1.3 μg/ml or greater, OR
  • At least a four-fold increase from baseline titer 5, 7
• Testing should include multiple serotypes, as response varies by serotype and age 5

Interpretation of Results

• Patients who fail to develop protective antibody levels against any serotype tested (approximately 6.4% of children with recurrent infections) may have a specific antibody deficiency 4
• IgG2 subclass deficiency may be associated with poor pneumococcal antibody response, but normal IgG2 levels do not guarantee adequate response 6, 2
• Age significantly influences the intensity of response to pneumococcal polysaccharides, with adults showing much stronger responses than children 5
• Some patients may have transient responses, particularly those with undetectable IgG2 at the time of immunization 6

Management Based on Titer Results

• Patients who fail to respond adequately to pneumococcal vaccination may benefit from IgG replacement therapy 4
• For non-responders, re-vaccination may be attempted, though some patients will still fail to develop adequate protection 2
• Patients with functional or anatomic asplenia should receive antimicrobial prophylaxis (oral penicillin G or V) regardless of antibody response 3
• Intramuscular or intravenous immunoglobulin administration may be useful for preventing pneumococcal infection in children with immunodeficiency who have recurrent, serious bacterial infections 3

Common Pitfalls to Avoid

• Not testing pneumococcal titers in patients with recurrent infections who have normal total immunoglobulin levels 2, 4
• Failing to recognize that a normal IgG2 level does not exclude a specific anti-pneumococcal antibody deficiency 2
• Not considering age when interpreting pneumococcal antibody responses, as younger children naturally have lower responses 5
• Withholding vaccination in patients with uncertain vaccination history 3