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Type-specific
serologic testing for HSV should be performed with glycoprotein
G-based tests.
Inaccuracy of certain commercial
enzyme immunoassays in diagnosing genital infections with herpes simplex
virus types 1 or 2.
Morrow RA, Friedrich D.
American Journal of
Clinical Pathology 2003;120:839-844.
Summary:
Question
What are the sensitivities and specificities of three commercial tests
based on crude antigen and one using glycoprotein G compared to Western
blot for the detection of type-specific antibodies to HSV-1 and HSV-2 in
serum samples?
Design
Results of four commercial assays based on HSV-1 and HSV-2 crude antigens
or glycoprotein G were compared to Western blot for the detection of
type-specific antibodies to HSV-1 and HSV-2 in convalescent serum samples
from patients with culture-documented first symptomatic or recurrent
episodes of genital herpes lesions and from asymptomatic patients.
Participants
Single serum samples obtained from three groups of patients presenting to
the Virology Research or the University of Washington Family Medicine
clinics were tested. 1) Convalescent samples were drawn 28 to 90 days
after the onset of symptoms from patients having primary infection with
HSV-1 (n = 17) or HSV-2 (n = 49). Persons with primary infection were
seronegative within the first 2 weeks of symptom onset and later developed
antibody to the infecting virus type as determined by Western blot
analysis. Twenty of the 49 patients with first episodes of HSV-2 genital
lesions had antibody to HSV-1 in acute serum samples. 2) Samples were
obtained within 6 months after a culture-documented recurrence from 30 and
49 patients with HSV-1 or HSV-2 genital infections, respectively. Western
blot analyses showed that none of the patients with HSV-1 had HSV-2
antibody, while 31 of the 49 HSV-2 antibody-positive patients also had
HSV-1 antibodies. 3) Serum samples from 23 asymptomatic patients, who were
HSV-2 antibody positive by Western blot and HSV-2 virus positive by PCR or
culture of anogenital secretions, were tested.
Description of Tests and Diagnostic
Standard
Two ELISA assays, one for HSV-1 and one for HSV-2, from each of four
manufacturers including DiaSorin (Stillwater, MN), Zeus Scientific
(Raritan, NJ), Wampole Laboratories (Cranbury, NJ), and Focus Technologies
(Cypress, CA) were performed according to the manufacturers' instructions.
Results of the DiaSorin assay were interpreted by two methods: 1)
calculation of the predominant antibody according to the manufacturer's
formula, and 2) use of cutoff ELISA values for HSV-1 and HSV-2 without
regard for the test result of the other type. Samples with equivocal
results were excluded from analyses.
Main Outcome Measures
The sensitivity and specificity of each HSV type-specific serologic assay
weredetermined for both HSV-1 and HSV-2 antibody detection as compared to
the results of Western blot analyses. To determine overall concordance
with Western blot results, both the HSV-1 and HSV-2 test results had to be
in accord with the respective Western blot result to be counted as
concordant.
Main Results
The proportion of samples with correct diagnoses of HSV-1 and HSV-2
infections by each ELISA assay compared to culture results in 66 patients
with newly acquired genital HSV and in 79 patients with recurrent
infections are shown in table 1. The sensitivity, specificity, and
concordance of each of the HSV type-specific ELISA assays for the
detection of HSV-1 and HSV-2 antibodies in 168 serum samples from all the
patient groups compared to Western blot results are shown in table 2.
Authors' Conclusions
The Zeus and Wampole tests were insensitive
for detecting early HSV infection. The non-glycoprotein G-based tests were
generally more sensitive for detecting antibody after a recurrent HSV-2
episode than for diagnosing first episodes. The specificities for the
Zeus, Wampole, and DiaSorin tests were low compared to the Western blot.
Overall, the non-glycoprotein G-based tests had inadequate specificity for
an accurate diagnosis of either HSV-1 or HSV-2 in many of the patient
sample groups. The Focus ELISA consistently performed more accurately.
Source of funding: In part by NIH
Herpes Program, National Institutes of Health
For correspondence:
Dr. Rhoda Morrow, Virology, Room G815, 8G-3, Children's Hospital and
Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA 98105
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