Literature review > Issue_1 > Review Ribes et al. 

With the growing availability of commercial test kits that can accurately differentiate between antibodies to herpes simplex virus (HSV) -1 and those to HSV-2, HSV serology is becoming, in recent years, an important testing option for diagnosing herpes infections and a reliable instrument to obtain epidemiological data. These tests depend upon the detection of antibodies to glycoprotein G (gG-1 in HSV-1 infection and gG-2 in HSV-2 infection).

Historically, HSV-1 infection has been acquired in early childhood, and this is still true in developing countries. Presently, in industrialized countries, the majority of adolescents are still susceptible to the infection and HSV-1 now accounts for a substantial percentage of genital herpes, mainly in young people; hence, type-specific serology tests can be important diagnostic tools in clinical practice.

In the USA, diagnostic kits must pass rigorous tests by the US Food and Drug Administration (FDA) before being marketed. Even though the tests are approved by the regulatory authority, it is always important to have data on their performances in the field. The two tests for HSV-1 compared in the paper by Ribes et al., Meridian and MRL, are, at the moment, the only FDA-approved assays. Unfortunately, one of them is no longer commercially available: Meridian withdrew type specific HSV-1 and -2 early in 2001. Also in 2001, MRL, the manufacturer of the other test, changed its name to Focus Technologies and the EIA kit is now marketed under the brand name HerpeSelect® ELISA. The immunoblot used in the study is now commercialised under the brand name HerpeSelect® Immunoblot, which is a single nitrocellulose strip where glycoproteins gG-1, gG-2, and a type common protein mixture are applied in bands, resembling a simplified Western blot. The type specific glycoproteins are the same as those used in the ELISA test.

The sensitivity and specificity of HerpeSelect® Immunoblot compared with the University of Washington Western blot for HSV-1 were 99-100% and 93-95%, respectively [1]. Even if the same antigen is used for the immunoblot and ELISA for HSV-1, the former test allows better performances: in the same institution, ELISA compared to Western blot showed 91-96% sensitivity and 92-95% specificity [1].

The results reported by Ribes et al. show a good sensitivity (98.2%) and a relatively low specificity (93.8%) for the MRL test, now HerpeSelect®. These figures are indeed only slightly better than those reported by R Ashley [1] at the University of Washington. This discrepancy can depend on different populations examined or, more likely, on the fact that the confirmatory tests used were different.

The authors report that the false positive results were usually just above the equivocal range and suggest that a more conservative cut-off for the positive range might be indicated for this assay. Unfortunately, they do not report the number of true positive specimens in the same range of values that could appear false negative with higher cut-offs, making it difficult to evaluate whether the sensitivity can be improved by adopting this solution. Equivocal test results may be due to low titer antibody response, sometimes during seroconversion, or technical artifacts; hence, a confirmatory test should be performed, at least on specimens in the equivocal range or just above, even if it can substantially increase the costs.

Overall, even if it is disappointing that more than 3% of the individuals tested had false results, this study confirms the adequacy of HerpeSelect® for patient testing, but also emphasizes the need for more accurate assays. Since serological diagnosis can be important in several conditions worldwide, is highly desirable to see published in peer-reviewed journals rigorous studies comparing performances of assays for HSV-1 available in countries other than the USA

References:

1. Ashley RL. Performance and use of HSV type-specific serology test kits. Herpes.
2002;9:38-45.

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