Should Varicella (varicella-zoster virus) Immunoglobulin G (IgG) levels be checked before administering the varicella vaccine to an individual with an uncertain history of varicella infection or vaccination?

Should Varicella IgG Levels Be Checked Before Varicella Vaccination?

For most adults with uncertain or negative varicella history, serologic testing for VZV IgG before vaccination is cost-effective and recommended, particularly in healthcare settings and for immunocompromised patients, though it is not mandatory for routine immunocompetent adults. 1

Primary Guideline Recommendations

For Immunocompromised Patients (IBD, HIV, Transplant)

• At diagnosis of IBD, unvaccinated adults and children should be screened by history of chickenpox (or shingles) for susceptibility to primary infection. 1
• If the history is uncertain or negative, or the patient grew up in a tropical or subtropical climate, they should be tested for varicella zoster virus IgG. 1
• HIV-infected persons who are susceptible to VZV (those who have not been vaccinated, have no history of varicella or herpes zoster, or are seronegative for VZV) should receive postexposure prophylaxis with VariZIG as soon as possible after exposure. 1
• It is important to avoid testing a sample which may contain VZV IgG obtained passively, for example by blood transfusion. 1

For Healthcare Personnel

• In health-care institutions, serologic screening before vaccination of personnel who have a negative or uncertain history of varicella and who are unvaccinated is likely to be cost effective. 1
• Birth before 1980 is not considered evidence of immunity for healthcare personnel because of the possibility of nosocomial transmission to high-risk patients. 1
• Institutions may elect to test all healthcare personnel regardless of disease history because a small proportion of persons with a positive history of disease might be susceptible. 1

For General Adult Population

• Prevaccination screening for varicella is cost-effective when there is a seroprevalence of >30% in the patient population. 1
• The majority of adults (88-91%) have been exposed to VZV even without recalled chickenpox, making serologic testing particularly valuable in identifying the truly susceptible minority. 2

Evidence Supporting the Predictive Value of History

Positive History

• A positive varicella history accurately predicts immunity with a positive predictive value of 98.5%. 3
• Among adolescents with a positive chickenpox history, 90.8% had VZV-IgG suggesting prior infection. 4
• All 142 persons with a history of varicella were VZV IgG seropositive in one study. 5

Negative or Uncertain History

• The negative predictive value of a negative history of varicella is only 23%, meaning most people with negative history are actually immune. 3
• Among pregnant women with a negative history of varicella, 71% had positive antibody test results and were actually immune. 6
• Among those with uncertain history, 84-90% had VZV-IgG suggesting prior infection. 4, 6
• Combining negative and uncertain histories, 74-84% would receive vaccine unnecessarily without serologic testing. 4

Practical Algorithm for Clinical Decision-Making

Step 1: Assess Patient Category

• Immunocompromised patients (IBD, HIV, transplant, immunosuppressive therapy): Always test if history is uncertain or negative 1
• Healthcare personnel: Test all with negative or uncertain history 1
• Pregnant women exposed to varicella: Expeditious antibody testing is mandatory 6
• General immunocompetent adults: Testing is cost-effective but not mandatory 1

Step 2: Interpret History

• Definite positive history of chickenpox or shingles: Consider immune, no testing needed (except healthcare workers where institutions may test all personnel) 1, 7
• Negative or uncertain history: Proceed to serologic testing in high-risk groups 1
• Grew up in tropical/subtropical climate: Test regardless of history due to lower childhood exposure rates 1

Step 3: Act on Results

• Seronegative: Administer 2 doses of varicella vaccine, 4 weeks apart (or 1 month or more apart per some guidelines) 1, 8
• Seropositive: No vaccination needed; patient is immune 1
• For immunocompetent patients where testing is not performed: Vaccinate with 2-dose series; no harm occurs if already immune 8

Important Clinical Caveats

When Testing Is Most Critical

• Testing is essential before starting immunosuppressive therapy to allow time for vaccination completion at least 3 weeks before immunomodulators are started. 1
• Subsequent immunization should only be administered 3-6 months following cessation of all immunosuppressive therapy. 1

When Testing May Be Skipped

• For immunocompetent adults aged 50+ being considered for zoster vaccination: No screening for varicella history is necessary, as the majority have been exposed and zoster vaccines are safe in VZV-seronegative individuals. 2, 8
• High seroprevalence (88-91%) in adults means most without recalled chickenpox were actually exposed through subclinical or forgotten childhood infection. 2

Common Pitfalls to Avoid

• Don't assume absence of recalled chickenpox means VZV-seronegative status - most adults have been exposed even without clinical disease. 2
• Don't confuse varicella (chickenpox) vaccination with herpes zoster (shingles) vaccination - these are different vaccines for different purposes. 2
• Don't delay urgent immunosuppressive therapy to complete varicella vaccination series - balance disease control needs with infection prevention. 1
• Don't test samples that may contain passively acquired antibodies (e.g., recent blood transfusion), as this will give false-positive results. 1

Cost-Effectiveness Considerations

• In young adults, serologically testing those with a negative history and vaccinating those without protective antibodies is the most cost-effective approach. 3
• Testing prevents vaccine wastage in the 74-84% of people with negative/uncertain history who are actually immune. 4
• However, a small but important proportion (9%) of those with positive chickenpox history would remain susceptible even without testing. 4