Can IgM (Immunoglobulin M) for scrub typhus come back falsely positive in Hepatitis A virus (HAV) infection?

IgM for Scrub Typhus Can Produce False Positive Results in HAV Infection

Yes, IgM antibody tests for scrub typhus can produce false positive results in patients with Hepatitis A virus (HAV) infection. This cross-reactivity is an important diagnostic consideration when evaluating patients with febrile illnesses.

Understanding Cross-Reactivity in Serological Testing

• Serological tests for scrub typhus, particularly IgM-based assays, can produce false positive results in patients with other infections including HAV 1
• False-positive reactions have been documented in patients with various infections including malaria, tuberculosis, and typhoid fever using IgM-based tests for scrub typhus 1
• Similar to other serological tests, cross-reactivity can occur due to antigenic similarities or non-specific immune activation during acute infections 2

Diagnostic Challenges with Scrub Typhus Testing

• Clinical diagnosis of scrub typhus is difficult because symptoms closely resemble other febrile illnesses including viral hepatitis 2
• The sensitivity and specificity of scrub typhus IgM tests vary significantly depending on the testing methodology:
  • IgM ELISA tests show sensitivity of approximately 86.5% 2
  • Rapid immunochromatographic tests for scrub typhus IgM demonstrate variable sensitivity (23.8-39.1%) with better specificity (86.2-99.5%) 3

HAV Diagnostic Considerations

• HAV infection is confirmed by detecting HAV IgM antibody, which typically becomes detectable 5-10 days before symptom onset 4
• HAV IgM antibody usually remains detectable for up to 6 months after infection but can occasionally persist for up to 1 year 4
• False-positive HAV IgM results can occur due to low positive predictive value of assays in populations with low prevalence of acute hepatitis A 4

Diagnostic Approach for Suspected Co-infections or Cross-Reactivity

• When evaluating patients with suspected HAV infection and positive scrub typhus IgM:
  • Confirm HAV infection with specific HAV IgM testing 4
  • Consider the epidemiological context and clinical presentation 2
  • Use more specific confirmatory tests for scrub typhus when available, such as microimmunofluorescence assays (M-IFA) which have superior performance 2

Recommendations for Clinical Practice

• In areas where both HAV and scrub typhus are endemic, consider the possibility of cross-reactivity when interpreting positive IgM results 1
• When diagnostic uncertainty exists, use multiple testing methods or paired serum samples to improve diagnostic accuracy 2
• The InBios Scrub Typhus Detect IgM ELISA has been shown to have improved diagnostic accuracy compared to older tests, with sensitivity of 93% and specificity of 91% at appropriate cutoff values 5
• Always interpret serological results in the context of the patient's clinical presentation and epidemiological factors 2

Pitfalls and Caveats

• Relying solely on a single IgM test for either scrub typhus or HAV may lead to misdiagnosis 2
• False-positive IgM results can occur with various viral infections including acute infectious mononucleosis, cytomegalovirus, and parvovirus 4
• Low-titer positive results should be interpreted with caution as they have higher false-positive rates 5
• Consider the timing of sample collection, as IgM antibodies may not be detectable early in the course of infection 3