What is the clinical significance of varicella (chickenpox) IgG (Immunoglobulin G) and IgM (Immunoglobulin M) antibodies in diagnosing and managing varicella infection?

Clinical Significance of Varicella IgG and IgM Antibodies

Varicella IgG testing is the preferred method for determining immunity to chickenpox, while IgM indicates recent or active infection; IgG should be used for screening purposes and IgM for diagnosing acute infection. 1

Interpretation of Varicella Antibody Tests

Varicella IgG

• Positive IgG: Indicates immunity to varicella due to previous infection or vaccination 1
• Negative IgG: Indicates susceptibility to varicella infection 1
• IgG antibodies typically persist for life following natural infection 2
• Commercial ELISA tests are preferred for screening due to higher specificity, particularly for healthcare personnel 1
• Latex agglutination (LA) tests are more sensitive but may produce false-positive results 2, 1

Varicella IgM

• Positive IgM: Indicates recent or active varicella infection 3
• IgM antibodies typically appear 3-5 days after onset of infection, peak during the second week, and disappear within approximately two months 3
• IgM response is robust in primary varicella infection (chickenpox) 3, 4
• IgM can also be detected in herpes zoster (shingles) in 84% of cases, though the response is generally less pronounced than in primary infection 5

Clinical Applications

1. Immunity Screening

• Healthcare Workers: All healthcare personnel should be screened for varicella immunity using IgG testing 2, 1
• Immunocompromised Patients: Patients with inflammatory bowel disease or other immunocompromising conditions should be screened by history or IgG testing 2
• Pre-Vaccination: Serologic screening before vaccination is cost-effective in healthcare settings 1

2. Diagnosis of Acute Infection

• Serology is not useful for diagnosis of active chickenpox or shingles lesions - direct detection methods from lesion samples are preferred 2
• For suspected recent infection without visible lesions, IgM testing can be helpful 3
• Both IgG and IgM antibodies appear early in primary infection, with most patients developing both within 7 days of symptom onset 4

3. Management of Exposure in Susceptible Individuals

• For unimmunized, seronegative high-risk patients (immunosuppressed, pregnant) exposed to varicella:
  • Varicella zoster immune globulin (VZIG) should be administered within 10 days of exposure 2
  • After VZIG, patients should be observed for 28 days 2

Important Considerations and Pitfalls

1. False Positives with LA Testing: Using only a single concentration of serum with LA testing can lead to false positives, leaving individuals vulnerable to infection 2

2. Vaccine-Induced Immunity: Commercial assays may not detect vaccine-induced immunity despite protection 1

   • Available tests are not optimized to detect antibody to the vaccine virus 2
   • 99% of adults develop antibodies after the second dose of vaccine, but seroconversion does not always result in full protection 2

3. Cross-Reactivity: Avoid testing samples that may contain passively acquired VZV IgG (e.g., after blood transfusion) 2

4. Post-Vaccination Testing: Routine testing after vaccination is not recommended due to limitations in commercial assays 1

5. Self-Reported History: Self-reported history without healthcare provider verification may be unreliable; serological testing is preferred when history is uncertain 1

Algorithm for Varicella Immunity Assessment

1. For Immunity Screening:

   • Test for varicella IgG using commercial ELISA
   • If positive: Consider immune
   • If negative: Recommend vaccination (2 doses, 4 weeks apart) for healthy individuals

2. For Suspected Acute Infection:

   • If lesions are present: Direct detection methods from lesion samples (PCR, culture)
   • If no lesions but recent exposure/symptoms: Test for both IgG and IgM
     • IgM positive + IgG negative or low: Primary infection
     • IgM positive + high IgG: Possible reactivation (herpes zoster) or reinfection
     • IgM negative + IgG positive: Past infection, likely not acute

3. For Post-Exposure Management:

   • Check IgG status
   • If negative and high-risk: Administer VZIG within 10 days
   • If negative and not high-risk: Consider vaccination within 3-5 days of exposure