Performance of commercial enzyme-linked immunosorbent assays (ELISA) for diagnosis of HSV-1 and HSV-2 infection in a clinical setting

Thesis (Master's)--University of Washington, 2016-06

Background FDA-approved ELISA assays for determining type-specific herpes simplex virus (HSV) serostatus are widely used in clinics. We compared the performance of such assays with the University of Washington western blot (UW WB) in patients who sought confirmation of their HSV serostatus. Methods We reviewed charts of all persons evaluated at the Westover Heights Clinic (WHC) in Portland, Oregon, from July 2010 through September 2015, who had a HSV ELISA, followed by UW WB. Results Of 864 persons, 47% were women. The median age was 36 years (range 18-73 years). By UW WB, 286 (33%) persons were HSV-1 seropositive only, 104 (12%) were HSV-2 seropositive only, 134 (16%) were both HSV-1 and HSV-2 seropositive, 235 (27%) were HSV seronegative, and 105 (12%) were indeterminate. Using the UW WB as reference, the ELISA was 70.2% sensitive and 91.6% specific for HSV-1, and 91.9% sensitive and 57.4% specific for HSV-2. Among 284 persons who were HSV-1 seropositive by ELISA according to manufacturer’s cutoff index value ≥1.1, 255 were confirmed by the UW WB (positive predictive value, PPV=92%). Of the 412 persons that were HSV-1 seronegative by the ELISA, 304 were seronegative by UW WB (negative predictive value, NPV= 70.0%). Among 456 persons with HSV-2 ELISA seropositivity, 193 tested HSV-2 positive by the UW WB (PPV=50.7%). Of the 283 persons HSV-2 seronegative by ELISA, 17 were found UW WB positive (NPV= 93.7%). Among 261 persons with an ELISA HSV-2 index value 1.1 - 2.9, 39.8% confirmed by UW WB, compared with 78.6% of the 70 persons with an ELISA index value >3 (p<0.0001)). The risk of false positive HSV-2 results was not found to differ between persons with or without HSV-1 antibody (50.5% vs 47.5%, p=0.57). Conclusions FDA approved ELISAs have poor PPV for HSV-2 and poor NPV for HSV-1 in clinical practice. More accurate commercially available type-specific HSV antibody diagnostic tests are needed.