Differences Between IgG and IgM in Diagnosing Herpes Simplex Infections
IgM is a poor indicator of recent herpes simplex infection while IgG indicates past exposure and ongoing latent infection, making nucleic acid amplification tests (NAATs) the preferred diagnostic method for active herpes lesions. 1, 2
Diagnostic Value of IgG vs IgM
- IgG antibodies develop within several weeks after HSV infection and persist indefinitely, indicating past exposure and ongoing latent infection 3
- Although theoretically useful for detecting recent infection, HSV-specific IgM is unreliable as approximately one-third of patients with recurrent genital herpes caused by HSV-2 have IgM responses 1
- IgM antibodies to HSV-2 glycoprotein G-2 (gpG-2) are typically found in primary HSV-2 infections but not in recurrent HSV-2 infections, making them potentially useful only for retrospective diagnosis of initial infections 4
- Commercial type-specific HSV-1 or HSV-2 antibody assays can be false negative in 12-30% of patients with recurrent HSV DNA-positive genital lesions 5
Preferred Diagnostic Methods for Active Infections
- NAATs such as PCR are the first-line diagnostic tests for HSV detection in patients with active genital lesions due to their superior sensitivity (11-71% higher than viral culture) 2, 1
- PCR allows simultaneous detection and typing of HSV-1 and HSV-2 in a single reaction, is faster (approximately two hours), and requires less strict sample transportation conditions 1, 2
- Viral culture is the second choice if NAAT is unavailable, but has lower sensitivity, especially for ulcerative or crusting lesions 2, 6
- Direct sampling from vesicular lesions or the base of ulcers provides the best diagnostic yield 2
Appropriate Use of Serological Testing
- Type-specific serology should be used for:
- Widespread screening for HSV antibodies is discouraged 2, 3
- Serological tests alone cannot determine the etiology of a presenting genital lesion with certainty 1
Clinical Significance of HSV Type Determination
- HSV typing is essential for counseling and prognosis 2
- Up to 50% of first-episode genital herpes cases are caused by HSV-1 2
- Recurrences and subclinical viral shedding are less frequent with genital HSV-1 than HSV-2 2
- The same medication dosages are recommended for both HSV-1 and HSV-2 genital infections 2
Limitations of Serological Testing
- Type-specific HSV-1 and HSV-2 IgM ELISAs do not reliably detect HSV-1 and HSV-2-specific IgM antibodies 7
- Commercial HSV-2 serologic tests using enzyme immunoassay (EIA) have significant specificity limitations, especially at lower index values 3
- For low positive results, confirmation with a second test using a different glycoprotein G antigen is recommended 3
- A negative result within 12 weeks of potential exposure may represent the "window period" and should be repeated after 12 weeks if recent acquisition is suspected 3