Is IgG avidity testing useful in non‑pregnant patients?

IgG Avidity Testing in Non-Pregnant Patients

IgG avidity testing has limited utility in non-pregnant patients and should not be used as a standalone diagnostic tool, as low avidity can persist for years after primary infection and cannot reliably differentiate acute from chronic toxoplasmosis outside the pregnancy context. 1

Primary Limitation of Avidity Testing

The fundamental problem with IgG avidity testing is that it cannot differentiate between acute and chronic infection when used alone, because low IgG avidity can persist for years after primary infection 1. This limitation applies to all patient populations, but is particularly problematic in non-pregnant patients where the clinical urgency differs significantly from pregnancy scenarios.

Clinical Context Matters

In Pregnancy vs. Non-Pregnancy

• In pregnant women, avidity testing serves a specific time-sensitive purpose: high avidity (>35%) can definitively exclude recent infection (<3 months) and provide reassurance, avoiding unnecessary interventions 2
• In non-pregnant patients, this time-sensitive decision-making is rarely necessary, as the consequences of acute versus chronic infection differ fundamentally 1
• The pregnancy-specific panels used by reference laboratories include avidity testing as part of comprehensive evaluation, not as a standalone test 1

When Avidity Testing May Have Some Role

Symptomatic Non-Pregnant Patients

In symptomatic patients (e.g., those with chorioretinitis or lymphadenopathy), avidity testing showed some utility but with significant limitations:

• High avidity reliably indicates chronic infection with 100% positive predictive value across commercial assays 3
• However, low avidity does NOT reliably diagnose acute infection, with negative predictive values ranging from 95.3% to 99.2% 3
• In one study of symptomatic patients, the avidity method was considered helpful for ocular toxoplasmosis, but borderline results were common (38 of 104 specimens) 4

Immunocompromised Patients

• In immunocompromised patients (HIV, transplant recipients, those on immunosuppressive drugs), screening for chronic infection to assess reactivation risk is more important than timing acute infection 5
• Avidity testing adds little value in this population, as the primary concern is detecting any seropositivity that indicates risk of reactivation 5

Practical Algorithm for Non-Pregnant Patients

For routine non-pregnant patients:

1. Initial screening: IgG and IgM testing only 1

   • If IgG negative, IgM negative: No infection
   • If IgG positive, IgM negative: Chronic infection (no avidity needed)
   • If IgG positive, IgM positive: Proceed to step 2

2. For IgG+/IgM+ results:

   • Send to reference laboratory for comprehensive panel, not just avidity 1
   • Reference panels include multiple tests (IgA, IgE, differential agglutination) that commercial labs don't offer 1
   • Avidity alone is insufficient 1, 5

3. If avidity is performed:

   • High avidity: Confirms chronic infection 3, 2
   • Low or borderline avidity: Repeat testing in 4 weeks required 2, as this cannot confirm acute infection 1, 3

Key Pitfalls to Avoid

• Never rely on avidity testing alone in any patient population 1, 5
• Do not assume low avidity equals acute infection - some individuals maintain low avidity indefinitely 1, 2
• Avoid commercial laboratory avidity results without reference lab confirmation when clinical decisions depend on timing of infection 1
• Remember that maturation of avidity is unpredictable - in documented cases, avidity failed to become high even after 6-11 months of follow-up 6

Bottom Line for Clinical Practice

In non-pregnant patients, standard IgG and IgM testing is usually sufficient. 1 If timing of infection is truly critical for clinical management (rare outside pregnancy), send samples to a toxoplasmosis reference laboratory for comprehensive evaluation rather than relying on avidity testing alone 1. The cost-effectiveness and clinical utility of avidity testing is primarily established for pregnancy screening, not general populations 3.