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Recommendations for
potential confirmatory strategies for the detection of type-specific
antibodies to HSV type 2 vary with respect to the commercial assays
employed and the patient populations analyzed.
Evaluation of
confirmatory strategies for detection of type-specific antibodies against
herpes simplex virus type 2.
Eing BR, Lippelt L, Lorentzen EU,
Hafezi W, Schlumberger W, Steinhagen K, Kuhn JE.
Journal of Clinical
Microbiology
2002;40:407-413.
Summary:
Question
What is the optimal combination of commercial glycoprotein G-2-based
herpes simplex virus type 2 type-specific antibody assays with regard to
diagnostic performance and cost efficiency?
Design
This study describes a blinded determination of the diagnostic
performance, in a high HSV 2-risk population, of three commercial
type-specific ELISA assays and a commercial immunoblot assay for the
detection of type-specific antibodies to HSV-2 compared to a "gold
standard" based on the majority agreement of the commercial tests.
Based on the results of the commercial serological assays, potential
confirmatory strategies were evaluated.
Participants
The cases were 194 HIV-negative female prostitutes seen for routine
examinations and the controls were 56 non-selected hospitalized patients
without HSV type-common antibodies.
Description of Tests and Diagnostic
Standard
Serum samples were tested using three glycoprotein G-2-based HSV-2
type-specific antibody ELISA assays: 1) anti-HSV-2 immunoglobulin G ELISA
(Euroimmune, Gross-Groenau, Germany), 2) HSV-2-specific IgG ELISA (Gull
Laboratories, Bad Homburg, Germany), and 3) HSV-2 IgG ELISA (Radim,
Sulzbach, Germany), and using a gG-2-based HSV-2-specific immunoblot,
anti-HSV-1/HSV-2 gG Western blot (Euroimmune). The immunoblot consisted of
HSV-1 Western blot strips with an additional gG-2 band blotted onto the
bottom of the strips to detect HSV-2. All serum samples were also tested
for the HSV type-common IgG and IgM antibodies with the Enzygost HSV/IgG
and IgM ELISA (Dade Behring, Marburg, Germany). All tests were carried out
according to the manufacturers' instructions. Sera were considered true
HSV negatives if they were negative for HSV type common IgG antibodies and
showed no reactivity with HSV antigens by the immunoblot. The diagnostic
standard for an HSV-2 antibody positive sample was defined as three or
four positive results in the four-test panel. For samples with two
positive results, the immunoblot result determined the HSV-2 serostatus.
Main Outcome Measures
The sensitivity, specificity, positive predictive value (PPV), and
negative predictive value (NPV) of each assay for the detection, in a
high-risk population, of HSV-2 specific antibodies, as defined by the
majority results of the four-test panel described above, were determined.
The sensitivity, specificity, PPV, NPV, and additional cost per sample of
6 combinations of the same four tests used as confirmation strategies for
the detection of HSV-2 specific antibodies were also determined.
Main Results
Of the 194 sera from female prostitutes, 191 were positive for HSV
type-common antibodies, 90 were HSV-2 positive by the immunoblot, and 108
were reactive in at least one of the three ELISA tests. One hundred
thirty-five of 194 sera gave concordant results in all four HSV-2-specific
assays. The performance of each test is shown in the table. The Euroimmune
ELISA test had the highest sensitivity and the immunoblot had the highest
specificity. The performance of six confirmatory strategies, each
employing an ELISA for screening, was evaluated. The combination of
retesting all sera with positive or equivocal results from a first ELISA
test (Euroimmune) using a second ELISA test (Gull) and confirming
discrepant results with the immunoblot gave the highest overall
sensitivity (100%) and specificity (97.1%), and the lowest additional cost
per sample (79%) for the samples tested.
| Performance
of commercial HSV type-specific assays. |
| Test |
Sensitivity% |
Specificity% |
PPV% |
NPV% |
| Euroimmune |
100 |
89.2 |
89.2 |
100 |
| Gull |
94.4 |
96.1 |
95.5 |
95.2 |
| Radim |
61.2 |
95.1 |
91.2 |
74.6 |
| Immunoblot |
98.9 |
100 |
100 |
99.0 |
Authors' Conclusions
Commercially available gG-2-based assays and
confirmatory strategies based on them exhibit favorable diagnostic
performances for the identification of HSV-2 antibody positive sera.
Recommendations for confirmatory strategies may vary significantly with
respect to the assays employed and the prevalence of HSV-2 in the samples
analyzed.
Source of funding: None given.
For correspondence: Joachim Kuhn,
Institute of Medical Microbiology, Von-Stauffenberg-Strasse 36,
D-48151Muenster, Germany. E-mail address: kuehnj@uni-muenster.de.
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