The data from this large, multisite clinical trial demonstrate the excellent performance of the HSVQx
for detection of both HSV-1 and HSV-2 from anogenital lesions. The assay provides a potential mechanism for increased availability of highly sensitive detection of HSV in persons with lesions. Like well-characterized laboratory-developed research PCR assays (16
), the system detected HSV from far more patients than the FDA-approved commercially available culture-based assay used for comparison in the study. Further, when the results were compared to those of PCR testing performed in a respected research laboratory, the results of the two assays were comparable. Indeed, the DNA-based assays had the capacity to detect dual HSV-1 and HSV-2 infections, which cannot be accomplished using the culture-based system. Although the impact of not having an HSV-1 culture result was negligible in this study (only 2/504 [<0.4%] participants had dual infections [data not shown]), it is useful to have any assay that provides results accurately and quickly for those populations in which dual infections might be more common. In addition to increased sensitivity, the HSVQx
assay provides a convenient method for collecting specimens in transport medium, which can be stocked at room temperature and easily transported to laboratories for testing. As a commercially available assay, the BD Qx
assay for HSV detection also has the potential advantage of being added to a laboratory platform already in wide use for detection of gonococcal and chlamydial infections.
Our analyses were rigorous, employing multiple methods. Confirmation of the sensitivity and specificity estimates derived by comparison with the patient infected standard was obtained using latent-class analysis. In fact, the latent-class analysis-estimated sensitivity was even higher than the estimate obtained in comparison with the patient infected standard. This is likely due to the fact that the latent-class analysis does not assume that culture-negative results represent uninfected individuals. The improved limit of detection of the HSVQx assay ( and ), and thus the ability to correctly identify infections with fewer organisms in the specimen, results in improved clinical sensitivity over culture.
This study is not without limitations. The study was limited to evaluation of lesions occurring in the anogenital region, and thus, further study will be needed to evaluate the utility of the test for detection of HSV from oral lesions and from other locations. The study design did not allow assessment of asymptomatic genital shedding, an important cause of HSV transmission that can be detected by PCR from about 10% of specimens in persons with genital HSV-2 infections.
Highly sensitive and specific tools for HSV diagnosis and typing are needed. Serological testing has proven helpful in some settings but is not currently recommended for routine screening (5
). Antibody responses may take months to develop following infection, delaying diagnosis and potentially resulting in either spread of infection to others by persons unaware that they have HSV or troublesome anxiety in persons awaiting test results. Finally, in persons with HSV infections, a positive serological test does not identify the location of infection, a fact that may hamper adoption of measures to reduce transmission to others.
HSV is the most common cause of genital lesions, irrespective of appearance, worldwide. Globally, it is the most common cause of genital ulceration and many lesions that are not “classical.” In contrast, the most common cause of a “typical” chancre in multiple studies is still HSV (13
). Conversely, about 20 to 25% of lesions identified as HSV by experts are not actually attributable to HSV and are due to other causes. As a result, with the wide availability of more sensitive tests, there is now an opportunity to operationalize the recommendation that all genital lesions that are not known to be a recurring problem with a known diagnosis (i.e., HSV or other dermatological process) should be tested for HSV.
The changing epidemiology of genital herpes also warrants increased testing with emphasis on determining, not only the presence or absence of infection, but, when herpes is diagnosed, the type of virus present. The proportion of genital HSV caused by HSV-1 is increasing, and in some studies, the proportion of genital herpes caused by HSV-1 equals or exceeds the proportion caused by HSV-2. While the presentations of initial genital herpes due to HSV-1 and HSV-2 are clinically indistinguishable (3
), compared to genital HSV-1 infection, genital HSV-2 infection recurs more often and is associated with higher rates of asymptomatic genital shedding, differences that may impact management decisions. While there are data to encourage the provision of chronic suppressive antiviral therapy to persons with HSV-2 infection, there are not similar recommendations for HSV-1. Addition of the HSVQx
to the laboratory diagnostic menu will positively impact our ability to identify, and therefore manage, this highly prevalent infection.