What is the PCR (Polymerase Chain Reaction) positivity rate in herpes meningitis?

PCR Positivity Rate in Herpes Meningitis

The PCR positivity rate for herpes simplex virus in meningitis is high, with reported sensitivities of 96-98% and specificities of 95-99% in adults with herpes simplex encephalitis, though the rate may be lower in pure meningitis cases. 1

Diagnostic Accuracy of PCR in Herpes Meningitis

HSV-1 and HSV-2 PCR Positivity

• CSF PCR is the gold standard for confirmation of viral meningitis, including herpes meningitis 1
• In adults with herpes simplex encephalitis, PCR has reported sensitivities of 96-98% and specificities of 95-99% 1
• For herpes simplex encephalitis in neonates and infants, sensitivity is more variable at 75-100% 1
• In a study specifically examining HSV-2 meningitis, real-time PCR detected HSV-2 DNA in 80% of patients with clinical HSV-2 meningitis compared to 72% with nested PCR 2
• The sensitivity of real-time HSV-2 PCR was found to be 87% in primary meningitis and 70% in recurrent meningitis 2

Factors Affecting PCR Positivity

• False-negative results may occur if hemoglobin or other inhibitors are present in CSF 1
• The presence of fewer than 10 WBCs/mm³ in CSF has been associated with a higher likelihood of a negative CSF PCR result 1
• An initially negative CSF PCR result for herpes simplex virus may become positive if the test is repeated 1-3 days after initiation of treatment 1
• Timing of CSF collection affects PCR positivity - samples taken within the first week of symptom onset have higher positivity rates 3
• PCR positivity decreases after initiation of acyclovir therapy, with most positive results occurring no later than day 8 after starting treatment 3

Viral Load and Disease Characteristics

• HSV-2 viral load is significantly higher in primary meningitis than in recurrent meningitis 2
• Viral load correlates with the degree of inflammation in the CSF 2
• In recurrent lymphocytic meningitis, HSV-2 can be detected repeatedly from CSF in multiple disease episodes 4

Other Herpes Viruses and PCR Detection

• PCR can detect varicella zoster virus (VZV) DNA, although a negative test result does not exclude the diagnosis of varicella encephalitis 1
• VZV IgM antibodies may be present in CSF even when VZV PCR is negative 1
• PCR is valuable for detection of cytomegalovirus (CMV) with high sensitivity and specificity for CNS involvement 1
• Epstein-Barr virus (EBV) can be detected by PCR, but positive results should be correlated with clinical findings as latently infected mononuclear cells can cause false-positive results 1

Clinical Implications

• Although a positive PCR may not lead to specific antiviral treatment in all cases, identifying the viral pathogen allows for accurate diagnosis, discontinuation of unnecessary antibiotics, reduced investigations, and shorter hospital stays 1, 5
• In undiagnosed cases with clinical features of herpes simplex encephalitis, consider repeating PCR 3-7 days later on a second CSF specimen if initial results are negative 1
• No cause is found in 30-50% of patients with presumed viral meningitis despite PCR testing 1

Regional Variations

• The spectrum of herpes viral meningitis may differ by geographic region and population characteristics 6
• In some African populations, EBV is more frequently detected in CSF of patients with viral meningitis than HSV, particularly in HIV-positive individuals 6