SUPPLEMENT ARTICLE

Serological Testing for Herpes Simplex Virus

(HSV)1 and HSV-2 Infection
Anna Wald and Rhoda Ashley-Morrow
Departments of Medicine, Epidemiology, and Laboratory Medicine, University of Washington, Seattle

Serological tests for herpes simplex virus (HSV) that can accurately distinguish between HSV-1 and HSV-2
are now commercially available. These tests detect antibodies to HSV glycoproteins G-1 and G-2, which evoke
a type-specific antibody response. Focus Technologies produces the HerpeSelect-1 and HerpeSelect-2 enzymelinked immunosorbent assay tests and the HSV-1 and HSV-2 HerpeSelect1/2 Immunoblot. Diagnology has
marketed POCkit-HSV-2, a point-of-care test for HSV-2 that allows blood from a finger stick to be tested in
a clinic. These tests can be used to confirm a genital herpes diagnosis, establish diagnosis of HSV infection
in patients with atypical complaints, identify asymptomatic carriers, and identify persons at risk for acquiring
HSV. Potential settings for use of these tests include sexually transmitted disease clinics, prenatal clinics, and
clinics that care for patients with human immunodeficiency virus. Patient interest in HSV serological tests
appears high.
Most people with herpes simplex virus (HSV)2 infection have unrecognized disease [1]. Despite the relatively mild course of their infection, these persons still
pose a risk of transmission to their sexual partners [2].
Pregnant women with unrecognized genital HSV infections pose a risk of transmission to their neonates
[3]. Even persons with clinical complaints relating to
HSV-2 infection often remain undiagnosed, because
their presentations are atypical and the confirmatory
laboratory tests that are in wide use have high rates of
false-negative results. The development of diagnostic
tools for genital herpes has lagged behind the development of diagnostic tools for other infections that are
characterized by a large proportion of asymptomatic
individuals, such as syphilis, chlamydia, and HIV. Molecular tests for Chlamydia trachomatis and sensitive
and specific antibody tests for HIV rapidly proceeded

Grant support: NIH Herpes Program project grant AI-30731.

Reprints or correspondence: Dr. Anna Wald, University of Washington
Virology Research Clinic, 1001 Broadway, Ste. 320, Seattle, WA (annawald@u
.washington.edu).
Clinical Infectious Diseases 2002; 35(Suppl 2):S17382
 2002 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2002/3508S2-0005$15.00

from research laboratory use in clinical trials to commercial availability and application in clinical or public
health practice. In contrast, despite the development in
research laboratories of HSV typespecific serological
tests over a decade ago [4, 5], the adaptation of these
tests to a marketable format has been slow and their
clinical use limited. However, during the past 3 years
the Food and Drug Administration (FDA) has approved HSV typespecific serologies, and these are now
available commercially. Other tests are in development.
The next challenge will be to apply these tests to appropriate populations for clinical and public health
benefit. The present article reviews the basis for development of type-specific serologies for HSV-1 and
HSV-2, discusses the clinical interpretation of test results, and summarizes settings in which the use of such
tests may be of benefit.

SEROLOGICAL DIAGNOSIS OF HSV-1

AND HSV-2
Antibody tests based on glycoprotein G. HSV-1 and
HSV-2 share the majority of their immunogenic sequences. This cross-reactivity results in antibodies that
react with almost equal efficiency to both HSV subtypes
HSV-1 and HSV-2 Serologies CID 2002:35 (Suppl 2) S173

regardless of whether an HSV-1 or HSV-2 infection has triggered the response [6, 7]. One structural protein, glycoprotein
G (gG-1 in HSV-1 and gG-2 in HSV-2), appears to elicit a
predominantly type-specific response. The immunodominant
human epitopes on HSV-1 are widely distributed through the
protein [8]. The most reactive epitopes on HSV-2 glycoprotein
G appear to reside within the homologous portions of the
protein [911] but, in tests with human sera, bind antibodies
only from patients with HSV-2 infections.
Several research or reference laboratories have developed
tests based on recognition of antibodies to gG-1 or gG-2. Western blot is one alternative that, when performed correctly, is
accurate for both HSV-1 and HSV-2 antibody detection [4, 12,
13]. Other formats depend on gG-1 and gG-2 that have been
affinity-purified from infected cell protein mixtures by use of
monoclonal antibodies [14, 15] or lectins such as Helix pomatia
[16]. Recombinant gG-1 and gG-2 constructs have been developed for these tests as well [17].
Commercial type-specific HSV tests. Tests based on glycoprotein G are now on the market in kit form from Focus
Technologies (formerly MRL Diagnostics) and from Diagnology (table 1). These kits have been approved by the FDA for
herpes serological diagnosis in adults and, in the case of the
Focus tests, for detection of HSV antibodies in pregnant women
as well. Focus tests include a pair of enzyme-linked immunosorbent assay (ELISA) kits called HerpeSelect-1 ELISA and
HerpeSelect-2 ELISA that detect antibodies to gG-1 and gG-2,
respectively. The tests are in standard 96-well plate format and
contain bacculovirus recombinant gG-1 (HSV-1) or gG-2
(HSV-2). Although 8-well strips can be snapped off for lowvolume testing, these tests are basically intended for highthroughput testing and can be run on an automated platform.
The second test is called the HerpeSelect1/2 Immunoblot and
consists of a single paper strip to which gG-1, gG-2, a typecommon antigen, and a control protein (for confirming that
serum has been added) have been applied. A single strip is used
for simultaneous testing for HSV-1 and HSV-2 antibodies (figure 1). This test is more expensive than ELISA but is well suited
to low-volume laboratory settings. Testing by HerpeSelect
ELISA or immunoblot can be ordered from Focus Technologies
reference laboratory, or the kits can be purchased by other
laboratories. Additional information about these tests can be
found at http://www.focusanswers.com or 800-445-0185.
The Diagnology test (POCkit-HSV-2) uses lectin-purified
gG-2 and a lateral flow membrane format that allows capillary
blood from a finger stick to be tested in the clinic setting (figure
2). This point-of-care format is designed for direct patient testing of blood but can also be used on single sera in the laboratory. Diagnology is seeking FDA clearance of a Clinical Laboratory Improvement Amendmentswaived format for the test
that will allow wider use in clinics and offices that do not have
S174 CID 2002:35 (Suppl 2) Wald and Ashley-Morrow

Table 1. Herpes simplex virus (HSV)2 antibody tests based

on glycoprotein G, which is recommended for type-specific
HSV antibody testing.

Test name

Company

HerpeSelect2 ELISA

Focus

Sensitivity,
%

Specificity,
%

96100

97100

HerpeSelect immunoblot

Focus

97100

98

POCkit-HSV-2

Diagnology

93100

9497

Cobas-HSV-2

Roche

93

98

Captia Select-HSV-2

Trinity

9092

9199

NOTE.

ELISA, enzyme-linked immunosorbent assay.

trained personnel. Because POCkit-HSV-2 detects only HSV-2

antibodies, patients with genital HSV-1 infection will not be
identified by this method. Additional information about
POCkit-HSV-2 can be found at http://www.diagnology.com or
877-776-2548.
The HSV gG-1 and gG-2 ELISAs developed by Gull Laboratories have been the most widely studied commercial tests
[13, 1820]. The tests obtained FDA approval in 1999 and were
marketed, briefly, as Premier HSV-1 ELISA IgG and Premier
HSV-2 ELISA IgG after the purchase of Gull by Meridian Biosciences. Meridian recently withdrew these tests from the market, and they are no longer available.
Quidel Corporation has developed a point-of-care membrane
test for antibodies to HSV-1 and HSV-2 (QuickVue-HSV). This
test is not yet on the market.
Two other gG-2based tests have been produced by Trinity
Biotech (Captia Select EIA, marketed by Wampole Laboratories) and Roche (Cobas Core HSV-2 IgG EIA) but have not
undergone FDA review. These tests do not detect HSV-1 antibodies, a potential disadvantage in light of increasing genital
HSV-1 incidence [21, 22].
Performance of commercial glycoprotein Gbased tests.
The Focus ELISA tests have been tested against Western blot
in unselected sera with 100% sensitivity and specificities of 98%
(HSV-1) and 96% (HSV-2) [23]. We tested the Focus ELISAs
against Western blot in sera from 252 clients from the Seattle
King County Sexually Transmitted Disease (STD) Clinic. This
group had an HSV-1 seroprevalence of 57% and HSV-2 seroprevalence of 33% by Western blot. Sensitivity and specificity
of HerpeSelect-1 ELISA were each 89% in this group. Sensitivity
and specificity of HerpeSelect-2 ELISA were 96% and 97%,
respectively (R.A., unpublished observations). A group of sera
from 241 prenatal patients (HSV-1 prevalence 73%; HSV-2
prevalence 24%) was also tested. Sensitivity and specificity of
HerpeSelect-1 ELISA were 96% and 95%. Sensitivity and specificity of HerpeSelect-2 ELISA were 100% and 96%, respectively.
Preliminary data suggest that HSV-1 and HSV-2 antibodies can

Figure 1. Immunoblots are scored as reactive if a glycoprotein G-1 (gG-1) and/or gG-2 band and the herpes simplex virus (HSV) common
antigen band are observed. The antihuman serum band must be observed for the test to be valid.

be detected a median of 23 weeks after the onset of first

episodes of genital herpes (R.A., unpublished observations).
The Focus immunoblot also was tested in STD and prenatal
populations and had sensitivity and specificity of 99%100%
and 93%96%, respectively, for HSV-1 and sensitivity and specificity of 97%100% and 94%98%, respectively, for HSV-2.
All 3 Focus tests performed well in comparison tests performed
at the Central Public Health Laboratory (CPHL) in London
using their monoclonal antibody blocking assay as a gold standard [24].
The POCkit-HSV-2 test has been tested against the CPHL
monoclonal antibody blocking ELISA and against the University of Washington Western blot. Sensitivity ranged from 93%
to 96% and specificity from 95% to 98% [13, 25, 26]. We also
found that a median of only 2 weeks from onset was required
to demonstrate HSV-2 seroconversion by POCkit-HSV-2 [27].
Caution is advised in interpreting the POCkit-HSV-2 test, because the reading of a positive result can be subjective. In 1
study that used banked sera, 5%10% of tests were read differently by 1 of 3 readers [28]. The test dot should have a
definitive color change to deep pink or red to be called positive
(figure 2).
The HSV-2 typespecific serology tests that are commercially
available but not FDA approved have limited performance data
against accepted standard tests. Cobas has a sensitivity of 93%
and specificity of 98% when culture is used as a marker of
infection and pediatric sera (presumed negative) for specificity
calculations [18]. The Captia Select HSV-2 EIA has been somewhat less sensitive (90%92%) with 91%98% specificity [29,
30].
Commercial tests that are not based on glycoprotein G.
Serological assays based on antigen preparations from whole
virus or from crude infected-cell protein mixtures detect predominantly type-common antibodies. Although the most serious problem with these tests is their inability to detect HSV2 antibodies in HSV-1seropositive patients, the tests also

mistakenly type antibodies in patients with only HSV-1 or only

HSV-2 infection [19, 31]. HSV-1 and HSV-2 share most of
their antigenic sequences; therefore, most herpes antibodies are
type-common. A number of companies offer tests that are
based on relative reactivity of serum antibodies to crude preparations of HSV-1 versus HSV-2 antigens. These tests are either
described as type-specific in marketing literature or provide
kit instructions for determining HSV-1 versus HSV-2 antibodies. However, the accuracy of crude antigenbased tests for
HSV-2 antibody detection is low compared with glycoprotein
Gbased tests, and their use is not recommended (table 2).

CLINICAL USE OF TYPE-SPECIFIC HSV

SEROLOGIES
A major reason for the lack of commercial development of
glycoprotein Gbased HSV testing has been the perception on
the part of health care providers that in an asymptomatic patient the diagnosis of HSV-2 infection is undesirable, because
it may have adverse psychosocial sequelae and unclear benefits
[3235]. This view has been formed on the basis of substantial
literature that shows persistent psychosocial distress in some
people who are diagnosed with clinically evident genital herpes
[3638]. There is a general reluctance to inflict on an otherwise
healthy person a diagnosis of a condition that might otherwise
be asymptomatic if the diagnosis may result in significant distress. In addition, counseling regarding genital herpes generally
cannot be accomplished within the short period typically allotted for patient visits. Finally, numerous studies have documented the discomfort of health care providers with obtaining
detailed sexual history and providing safer sex counseling
[3941]. However, there are several settings in which typespecific serologies for the diagnosis of HSV-1 and HSV-2 infection are potentially useful and in which the acceptance of
these tests by the patients is high (table 3). These settings and
HSV-1 and HSV-2 Serologies CID 2002:35 (Suppl 2) S175

Figure 2. Diagnologys point-of-care herpes simplex virus (HSV)2 serology. This test kit is about the size of a credit card and can be performed
in !10 min in the office, using capillary blood from a finger stick. The test membrane contains a dot with lectin-purified glycoprotein G-2 (gG-2)
on the right and an antihuman antibody reagent on the left. (Left) A positive test result with definitive red color change of both the gG2containing dot and the human serum control dots (arrow). (Right) A negative test result with only the control dot showing a red color change.
If neither dot turns color, the test is invalid and must be repeated with an additional capillary blood or serum sample.

the interpretation of the type-specific HSV antibody tests are

reviewed below.
Interpretation of antibody to HSV-2. What is the clinical
interpretation of a positive HSV-2 antibody test in a patient
with atypical or no genital symptoms? Prospective studies have
shown that virtually all patients with HSV-2 antibody have
genital herpes [42, 43]. We provided a standardized counseling
session regarding clinical manifestations of genital herpes to 42
women and 11 men without a history of genital herpes who
had positive antibody tests for HSV-2 [44]. The patients were
randomly selected when they presented for primary care [45].
During the follow-up, 33 recognized typical herpes recurrences
and 13 reported localized genital soreness or itching; HSV was
isolated or detected by PCR in the genital tracts of 44 of 53 of
these patients. Thus, all but one had either clinical evidence of
a genital herpes recurrence or had documented viral shedding
in the genital tract. Overall, the frequency of recurrences was
lower and the duration shorter compared with patients who
had a clinical history of genital herpes. Such mildly symptomatic or asymptomatic persons may not need antiviral therapy
but require education and counseling to prevent transmission
of HSV-2 to their sex partners and, potentially, to neonates.
S176 CID 2002:35 (Suppl 2) Wald and Ashley-Morrow

Although oral HSV-2 infection has been reported in 20%

of patients with primary genital HSV-2, HSV-2 recurs rarely in
the mouth, and oral HSV-2 infection in the absence of genital
infection is unusual [46, 47]. Thus, antibody to HSV-2 indicates
genital herpes in almost all patients. These persons should be
counseled similarly to patients with clinical diagnosis of genital
herpes.
Interpretation of antibody to HSV-1. What is an appro-

Table 2. Tests based on crude antigen, which is not recommended for type-specific testing.

Test name

Company

Correct
diagnosis,
%

Immunosimplicity HSV-1 and -2 IgG

Diamedix

61

Herpes 1 or 2 IgG Clin-ELISA

Diasorin

69

Herpes 1-IgG or Herpes 2-IgG

Sigma

62

HSV-1 or HSV-2 IgG ELISA

Wampole

85

HSV-1 or HSV-2 ELISA

Zeus

79

NOTE. ELISA, enzyme-linked immunosorbent assay; HSV, herpes

simplex virus.

Anonymous
questionnaire

Questionnaire

Fairley et al. [79]

Vonau et al. [76]

NOTE.

Attitudes to HSV-2
serotesting

Free HSV-2 testing

Exposure/intervention

Desire to test for HSV-2

self and partner

Acceptance of testing

Outcomes and
measures

STD Clinic, Seattle, WA; n p

HSV-2 serological testing; Acceptance of testing
1477 for free testing and n p
free vs. $15/test
3099 for $15/test

Randomly chosen women at

Knowledge of genital
Acceptance of HSV-2
1st prenatal visit in a central
herpes and attitudes to
testing
London hospital (n p 100)
HSV-2 testing

Consecutive STD clinic patients in Leeds, UK (n p

200)

Randomly chosen primary

care patients, Seattle, WA

Study population
type and setting

OR, odds ratio; STD, sexually transmitted disease.

Whittington et al. [20] Cross-sectional

Cross-sectional

Study design

Acceptance of herpes simplex virus (HSV)2 type-specific serology testing.

Oliver et al. [45]

Reference

Table 3.

18% accepted testing at $15 vs. 52% when free. For

all groups, free testing was associated with increased uptake (P ! .01). In multivariate analysis, acceptance higher with free testing (OR, 7.5), increasing age, and white vs. black (OR, 3.3)

80% would consider testing, 76% would encourage

partner to test

92% of patients wanted to know whether they have

HSV-2; 91% wanted partners tested; median score 9/
10 for desire to test; 65% expected routine testing

62% agreed to participate (59% of women and 70% of

men, P p .01); reasons for refusal included not
wanting to participate in research (22%), not wanting
to have blood drawn (15%), lack of time (11%),
knew that s/he did not have HSV (10%), and others

Reported findings

priate interpretation of a positive HSV-1 test in a person who

lacks a history of oral or genital herpes? Serological surveys
have indicated that the prevalence of HSV-1 infection rises
steadily throughout childhood and adolescence [48]. Most of
these infections probably represent oral HSV-1 acquisition.
However, in sexually active adults, the incidence of genital HSV1 is high [21, 22, 49, 50], and seroconversion to HSV-1 can be
consistent with genital as well as with oral herpes. In a study
of 19 people who seroconverted to HSV-1 during a prospective
study of a candidate herpes vaccine, 6 developed genital disease,
6 had oral disease, and 7 acquired HSV-1 antibodies without
localizing signs or symptoms [51]. Thus, in a patient who seroconverts to HSV-1 but does not have symptoms that localize
the infection in the mouth or genital area, it is not possible to
ascertain the site of the infection.
The inability of type-specific serology alone to indicate the
site of HSV-1 infection has been used by some clinicians to
suggest that serologies for antibody to HSV-1 are not helpful
[52]. An alternative interpretation, however, is that a positive
HSV-1 antibody test indicates that this person is no longer at
risk for HSV-1 infection. Discussion can then take place to
review transmission risk from oral or genital sites and to review
symptoms of recurrent genital herpes.
Distinguishing between HSV-1 and HSV-2 infections. Although careful studies have shown that the severity of genital
herpes episodes is similar in HSV-1 and HSV-2 infections, the
predilection for recurrences is much lower for HSV-1 than for
HSV-2. Among patients with documented newly acquired HSV1 infection, the median time to first recurrence was 310 days,
compared with the median time to first recurrence of 49 days
among patients with newly acquired HSV-2 infection [53]. This
means that 50% of patients with genital HSV-1 will not have
even 1 recurrence in the initial year after infection, compared
with patients with HSV-2 infection, who will have, on average,
45 recurrences.
The other reason to identify the infecting type is to alert the
patient to the risk of acquiring HSV-2 infection in addition to
HSV-1. Acquisition of HSV-2 in a person with genital HSV-1
infection has been documented, and a subsequent pattern of
recurrences is consistent with HSV-2 infectionthat is, frequent recurrences [5456]. This is especially important when
both partners have a history of genital herpes but the type is
unknown, because these couples are often told that safer sex
is not a necessary precaution from the standpoint of genital
herpes.
Of interest, acquisition of HSV-1 in a HSV-2 seropositive
patient is very rarely observed, which suggests that HSV-2 offers
more protection against HSV-1 than vice versa [5]. When both
partners have HSV-1 or both partners have HSV-2 infection,
the risk and the clinical sequelae of infection with another strain
of HSV-2 (or HSV-1) appears to be insignificant [57].
S178 CID 2002:35 (Suppl 2) Wald and Ashley-Morrow

Confirmation of clinical diagnosis. Clinical diagnosis of

genital herpes is often far from certain, even if the presentation
appears typical. Many experts recommend that laboratory confirmation be obtained even if the presentation is consistent with
genital herpes. A prospective study of 155 patients monitored
in a clinical research setting who acquired HSV-2 infection
showed that the sensitivity of clinical diagnosis was 39% and
the positive predictive value was 81% [51]. Thus, for every 4
correct clinical diagnoses of genital herpes, 1 patient received
the diagnosis of genital herpes in error. This suggests that, even
among highly trained personnel, genital herpes lesions are often
misdiagnosed and that a significant portion of genital herpes
diagnoses that are based on clinical examination alone is
incorrect.
Although an argument can be made that viral culture is most
appropriate in a patient presenting with genital lesions, it is
important to remember that viral cultures are not always positive even in primary genital herpes and are usually negative
in recurrent genital herpes [58, 59]. The high rate of falsenegative viral culture results further complicates the delivery
of a diagnosis of genital herpes to the patient. Undoubtedly,
many patients are convinced that the clinical diagnosis of genital herpes is erroneous when the opinion of the clinician is
followed by a negative result of the confirmatory laboratory
test. This scenario can be avoided with appropriate use of serological tests, although care must be taken to ensure that the
antibody status is ascertained in an appropriate time frame to
allow for the development of antibodies. This situation is analogous to the diagnosis of HIV infection, where a lag is observed
after primary infection before serological tests become reactive.
Atypical presentations of genital herpes. Another setting
in which serological tests are appropriate is that of patients who
present with atypical genital lesions. Studies have shown that
these lesions often represent undiagnosed genital herpes [60],
usually HSV-2, and because of the mild and infrequent nature
of the recurrences in many infected persons, isolation of HSV
may be difficult. One approach is to ask the patient to come
to the clinic early at the next appearance of these lesions, to
obtain fresh material for viral isolation. An alternative is to
obtain blood for serological testing for HSV-1 and HSV-2 antibodies. In our experience, the latter approach is usually more
direct and more economical.
Partner with genital herpes. Discordance in HSV infection
in a sexual partnership can be established only by type-specific
testing of the susceptible person, if the type of infection is
known in the potential source partner, or by testing of both
partners if it is not. At least a quarter of couples that are
discordant for genital herpes by clinical history will be concordant by serological tests [61]. This can occur either because
the infection was transmitted subclinically earlier in the rela-

tionship or because of unrecognized HSV acquisition in a prior

relationship.
Accurate knowledge of infection status can guide patient
education and counseling if the partnership is discordant and
often brings enormous relief if a stable, long-term partnership
is found to be herpes-concordant. Because condoms have been
found to be effective in reducing the transmission of HSV-2
from men to women, discordant couples can receive counseling
on consistent condom use [62]. Antiviral therapy is currently
under investigation for reducing the risk of transmission in
such partnerships.
HSV serologies during pregnancy. Type-specific serologies
are also useful to identify persons who may be at especially
high risk for adverse sequelae from HSV acquisition. Perhaps
the most obvious example is that of a pregnant woman who
does not have HSV-2 infection herself but who has a partner
with HSV-2 infection, a scenario that applies to an estimated
10% of couples [63]. Studies have consistently shown that acquisition of genital HSV-2 or HSV-1 toward the end of pregnancy carries a 30%50% risk of neonatal herpes [64, 65]. Most
of those events occur when a woman unknowingly acquires
genital herpes and does not have clinical disease at the time of
delivery. Thus, targeted behavioral intervention to the susceptible women must rely on the identification of women who are
susceptible to acquiring the infection in pregnancy [66].
There are 2 potential schemes for identifying the susceptible
women. One is to serologically test those pregnant women
without a history of HSV-2 infection, identify those who are
susceptible, and, subsequently, test the partners. If the couple
is discordant for HSV-1 or HSV-2, appropriate counseling can
be provided for the couple to avoid unprotected sexual intercourse and oral-genital contact toward the end of pregnancy.
An alternative strategy, if a woman is susceptible and the partner
is not able or willing to come in for serological testing, can rely
on provision of counseling to the woman without knowledge
of partner status. This may have some advantages in terms of
implementation of a testing program, despite the inability to
precisely tailor the counseling message to the womans individual situation. Adherence to the counseling messages may be
lower if the risk is less well defined. There is urgent need to
test these potential strategies for intervention among HSV-susceptible pregnant women.
A woman who tests positive for HSV-2 antibodies during
pregnancy can be reassured that her risk of transmission of
infection to the neonate is small, but a careful examination is
warranted at term [67]. If no symptoms or lesions consistent
with genital herpes are present, the woman can deliver vaginally.
If there is evidence of HSV reactivation at term in the genital
area, an abdominal delivery is recommended. There have been
small trials of suppressive acyclovir toward the end of pregnancy
for the prevention of recurrences at term [6871]. Although

these data are promising, some experts caution against widespread use of acyclovir, because there is remaining concern
about the potential hematologic and renal toxicity of the drug
in the fetus.
Women are routinely tested for a variety of infections during
pregnancy; thus, it is likely that the routine use of HSV serological tests would be well accepted as has been the experience
with HIV antibody tests [7275]. One study in a London prenatal care clinic showed that 80% of women would consider
HSV antibody tests if they were available [76].
HSV serologies in STD clinics. Another setting in which
serological testing is likely to be useful is that of STD clinics.
Serological surveys in STD clinics have shown that the rates of
HSV-2 infection range from 25% to 80%, depending on the
sex and race of the population [77, 78]. As among the general
population, most patients with HSV-2 antibody who are seen
in STD clinics do not have a history of genital herpes [60]. It
is important to note that a significant proportion of patients25% in the Seattle STD clinicpresenting for care in
STD clinics request STD screen and do not have a specific
clinical complaint (M. Golden, personal communication).
These patients are usually evaluated for inflammation of the
genital tract, and serological tests for syphilis and HIV are
performed. However, the current standard of care is not to
perform HSV serology, thus avoiding diagnosing an infection
that is certainly more frequent in the United States than either
unsuspected syphilis or HIV infection.
Patients express considerable interest in obtaining serological
testing for HSV-2. For example, in a British STD clinic, 190%
of patients wanted to know their HSV-2 antibody status, and
a similar proportion were also interested in having their partners tested [79]. Of interest, 65% thought that type-specific
serological testing for HSV was included among the standard
tests offered.
The acceptance of HSV-2 testing depends partly on the cost
of the test. In the Seattle STD clinic, 52% of patients accepted
serological testing when it was offered free as part of a research
project, compared with 18% of patients who agreed when there
was a $15 charge for the test [20]. Other statistically significant
correlates of acceptance of HSV serological tests included older
age and white race. The largest difference in acceptance of the
free versus paid test was among blacks: 42% consented when
the test was free, compared with 4% when the test required
payment. Among whites, the rate of acceptance was 55% when
the test was free, compared with 24% when the test had a fee.
These data suggest that economic situation explains much of
the differential acceptance of the test among patients seeking
STD care. Programmatic budgetary issues have been raised as
barriers to the availability of HSV serological tests in STD clinic
settings. Although fiscal constraints may truly interfere with
offering this test without charge, as with other traditional tests
HSV-1 and HSV-2 Serologies CID 2002:35 (Suppl 2) S179

in STD clinics, there should be no such barriers to making

these tests available at a small charge. Along with the availability
of type-specific HSV serology, patients in STD clinics should
be explicitly told when their evaluation does not include a test
for HSV, because many patients are under the impression that
a comprehensive evaluation is routinely performed [79].
HSV serologies in HIV infection. Numerous studies indicating the interaction between HIV and HSV-2 have been
reviewed elsewhere [80]. In brief, several studies have shown
that HSV-2 infection facilitates HIV acquisition, and some studies have suggested that HSV-2 infection may also predispose
to HIV transmission [81]. Natural history studies of HSV-2
infection in HIV-infected persons have shown that the HSV
shedding rate among such persons is significantly higher than
among immunocompetent men and that much of the shedding
among men who have sex with men occurs from the perianal
area and is unrecognized by the patients [82, 83]. This suggests
that this population is at higher risk for further transmission
of HSV-2 to the sexual partner. Recent recommendations from
the Centers for Disease Control and Prevention regarding
screening of HIV-infected persons for STDs does not recommend serological testing for HSV infection [84]. However, it
seems that testing for HSV-2, in combination with education
and counseling, and judicious use of antiviral agents in persons
with both HIV and HSV infection is a reasonable approach to
limiting further spread of both infections.
In summary, the commercial availability of type-specific antibody tests for HSV-1 and HSV-2 will increase the diagnosis
of this infection. The difficulty of ascertaining that the appropriate test is performed is considerable, because neither physicians nor patients have been taught to request brand-name
tests. However, only glycoprotein Gbased tests have acceptable
accuracy, although other tests remain on the market. Several
populations appear to be appropriate for serological testing for
HSV, including pregnant women, STD clinic patients, and persons with HIV infection. The barriers to serological testing for
HSV include fiscal constraints in some settings and, at least as
important, reluctance on the part of clinicians to offer the test
that patients are increasingly likely to request.

5.

6.
7.

8.

9.

10.

11.

12.

13.
14.

15.

16.

17.

18.

19.

20.

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