Acta Derm Venereol 91
Acta Derm Venereol 2011: 91: 333–336
© 2011 The Authors. doi: 10.2340/00015555-1033
Journal Compilation © 2011 Acta Dermato-Venereologica. ISSN 0001-5555
This paper reports survey-based data on the diagnosis
and management of genital herpes simplex virus (HSV)
infection in 14 countries of the Eastern European Net-
work for Sexual and Reproductive Health (EE SRH).
Only 43% of the countries could provide the number of
genital HSV cases recorded at national level. Eighty-six
percent of countries employed syndromic management
in cases of genital ulcer disease. Most countries perfor-
med type-specific and/or non-type-specific enzyme im-
munoassays to detect HSV antibodies. Non-type-specific
serology for diagnostic purposes should be actively dis-
couraged. Direct detection methods for HSV, such as
PCR, antigen detection and culture, are available in
the region, but their usage was extremely low. Their use
in Eastern European countries should be actively pro-
moted. The availability of laboratory services must be
improved, and countries in the region should implement
consensus recommendations for the laboratory diagno-
sis of genital HSV infections in order to improve clinical
practice. Key words: genital herpes infection; diagnosis;
(Accepted September 29, 2010.)
Acta Derm Venereol 2011; 91: 333–336.
Marius Domeika, Department of Medical Sciences, Uppsala
University, Dag Hammarskjölds väg 17, SE-75185 Uppsala,
Sweden. E-mail: email@example.com
Although healthcare in Eastern European countries
has undergone substantial changes during the past
two decades, issues related to the diagnosis and ma-
nagement of sexually transmitted infections (STIs)
remain largely neglected by local health authorities.
We have previously reported the establishment of the
international collaboration group, the Eastern European
Network of Sexual and Reproductive Health (EE SRH)
(1), a project supported by the Swedish International
Development Cooperation Agency (SIDA). The EE
SRH currently includes representatives from 15 parti-
cipating countries. The main objective of this network
is to facilitate improvement in reproductive healthcare
in Eastern Europe, firstly via the improvement, harmo-
nization and assurance of quality of diagnostic testing
and management of STIs and other reproductive tract
Genital herpes simplex virus (HSV) infection is one
of the most prevalent life-long incurable STIs. Data on
the laboratory methods used by both public and private
section services in the region have not been available
The aim of this study was to collect data regarding
the availability of diagnostic services and diagnostic
tests used, as well as the relative importance of genital
HSV infection in 14 EE SRH countries, in order better
to understand the diagnostic needs of Eastern Europe.
In May 2009 a questionnaire was sent to country representatives
of the EE SRH. The questionnaire enquired about the diagnosis
of genital HSV infection in each country, including: (i) the
availability and number of samples tested and morbidity due
to genital HSV infection in the country; (ii) the occurrence of
genital ulcer disease (GUD) in clinics providing services for
STIs; (iii) the aetiology of GUD in patients attending clinics;
(iv) the main diagnostic tests used for genital HSV infection and
their manufacturers; (v) the use of syndromic management for
GUD; (vi) the availability and use of laboratory confirmatory
testing; and (vii) the populations tested (mandatory). Where
further clarification was needed, telephone interviews and
personal interviews during the annual meeting of the EE SRH
were held subsequently.
Survey of Diagnostic Services for Genital Herpes in Fourteen Countries
in Eastern Europe
Marius DoMEIkA1, karen BABAyAN2, Rashad ISMAIloV3, Iryna SHIMANSkAyA4, krasimira CHUDoMIRoVA5, Tatjana
BRIlENE6, oleg kVlIVIDzE7, Judith DEAk8, Gulsum ASkARoVA9, Galina MAMAJEVA10, Vesta kUCINSkIENE11, Natalia
FRIGo12, Alevtina SAVICHEVA13, Tatiana kRASNoSElSkICH14, Gennadiy MAVRoV15, olim kASyMoV16, olga IzVEkoVA17,
Magnus UNEMo18 and Ronald CAMpBEll BAllARD19
1Department of Medical Sciences, Uppsala University, Uppsala, and Eastern European Committee of Swedish Health Care Community, Stockholm, Sweden,
2Medical-Scientific Centre of Dermatology and STI, Yerevan, Armenia, 3Skin and Venereal Disease Dispensary, Baku, Azerbaijan, 4Department of Dermato-
venereology, Belarus Medical Academy of Postgraduate Studies, Minsk, Belarus, 5Department of Dermato-Venereology, Plovdiv Medical University, Plovdiv,
Bulgaria, 6Biomedical Centre, University of Tartu, Tartu, Estonia, 7Department of Medicine, Tbilisi State University, Tbilisi, Georgia, 8University of Szeged,
Szeged, Hungary, 9Research Institute of Skin and Venereal Disease Dispensary, Alma-Ata, Kazakhstan, 10Republican Skin and Venereal Disease Dispensary,
Bishkek, Kyrgyzstan, 11Skin and Venereal Diseases Department of Kaunas University of Medicine, Kaunas, Lithuania, 12Microbiology Laboratory, Central
Institute for Skin and Venereal Diseases, Moscow, Russia, 13DO Ott Institute of Obstetrics and Gynecology, RAMS, and 14Department of Dermatology and
Venereology, Pavlov State Medical University, St. Petersburg, Russia, 15Institute of Dermatology and Venereology, Academy of Medicine, Ukraine, 16Department
of Skin and Venereal Diseases, Institute of Postgraduate Medical Education, Dushanbe, Tajikistan, 17Institute of Dermato-Venereology, Tashkent, Uzbekistan,
18Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro,
Sweden, and 19Division of STD Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, USA
M. Domeika et al.
Representatives from 14 of the 15 EE SRH Network
countries completed the questionnaire. only six
countries (43%) recorded the number of new cases
of genital HSV infection each year. Among those re-
porting, the incidence per 100,000 inhabitants ranged
from 3.1 (Georgia) to 81.1 (kyrgyzstan) (Fig. 1). How-
ever, the rates of infection do not distinguish between
primary and recurrent genital herpes.
Estimates of the proportion of genital ulcerations that
are either syphilis or genital HSV infection are shown
in Table I.
Syndromic management principles in GUD were
reported by all countries, except Estonia and Russia.
However, all countries, with the exception of Armenia,
used some laboratory testing in order to establish a de-
finitive diagnosis in at least some clinics (Table II).
only lithuania had a few laboratories performing iso-
lation and typing of HSV (distinguishing HSV-1 and
HSV-2) for routine diagnosis. Anti-viral susceptibility
testing was not undertaken in any country.
Antigen detection using direct immunofluorescence
(DIF) was used in 33% of participating countries survey-
ed, but only in a minority of clinics, i.e. approximately
3.5% in Belarus, 5% in Tajikistan, 8% in kyrgyzstan,
10% in Ukraine and 50% performing testing for HSV
in Estonia. Antigen detection of HSV by enzyme-linked
immunosorbent assay (ElISA) was used only in Estonia
and was available at all laboratories performing any test
polymerase chain reaction (pCR) was available for
detection of HSV in 2/3 of countries, i.e. in laboratories
in Georgia (unknown), Belarus (3.5%), kyrgyzstan
(7%), Estonia (20%), kazakhstan (30%), Hungary
(50%), lithuania (unknown), Russia (unknown) and
Herpes simplex virus serological testing
ELISA testing for detection of non-type specific HSV anti-
bodies was available in 2/3 of countries, namely Belarus,
Estonia, Georgia, Hungary, kyrgyzstan, lithuania,
Russia, Tajikistan and Ukraine. Most countries applied
serological tests aimed at detection of either IgM and/
or IgG antibodies. In Bulgaria, a complement-fixation
test was occasionally used.
Type-specific serological testing was available in 86%
of countries, excluding Armenia and Hungary.
Populations mandatorily tested for genital herpes
of 14 counties surveyed, seven (50%) had initiated
mandatory testing for genital herpes in specific patient
groups. The groups targeted varied from country to
country. For example, Georgia targeted HIV-positive
individuals; Hungary targeted pregnant women (in early
first semester and late trimester); Kazakhstan targeted
pregnant women at the first antenatal visit, and women
who had had spontaneous abortions; kyrgyzstan and
Tajikistan targeted pregnant women during the first,
second and trimesters of pregnancy; Ukraine targeted
men who have sex with men, and HIV-positive patients;
and Uzbekistan targeted pregnant women during the first
semester of pregnancy. For testing purposes, depending
on the test availability, either type-non-specific or type-
specific serological tests or PCR were employed.
participating countries in the European Union (EU) and
Georgia used a broad selection of diagnostic systems
produced in the West. However, in-house, non-commer-
cial reagents were often used, particularly for the direct
No. of new cases registered in 2008 per 100,000
Fig. 1. Number of newly registered genital herpes simplex virus (HSV)
infection cases per 100,000 inhabitants in Eastern European Network for
Sexual and Reproductive Health (EE SRH) countries that reported having
data on HSV morbidity in 2008.
Table I. Approximate percentage of patients attending dermato-
venereology clinics in Eastern Europe with genital ulcer disease
(GUD), and percentage of patients with GUD with a confirmed
diagnosis of syphilis and herpes simplex virus (HSV) infection
Country GUD (%)Syphilis (%) Genital HSV (%)
Acta Derm Venereol 91
Diagnostic services for genital herpes in Eastern Europe
detection of HSV. Non-EU countries mainly used tests
(both for the detection of virus and antibodies) manu-
factured in Russia. Additionally, Ukraine and Belarus
also used locally manufactured HSV test systems. In a
small number of cases laboratories in non-EU countries
used ElISA kits produced in the West.
This study was designed to investigate the availability
of diagnostic services and diagnostic tests used, as well
as the relative importance of genital HSV infection in
14 of the EE SRH countries, of which four are part of
The results clearly showed that genital HSV infection
is a presumed major cause of GUD and that, in the vast
majority of cases, a definitive diagnosis is not establis-
hed using laboratory testing, even if facilities exist. It
should be remembered that both Treponema pallidum
and HSV might coexist in the same lesion (2). Because
of the diversity of the signs and symptoms of genital
HSV infections, a laboratory confirmed diagnosis should
be made whenever possible (3). The reported inci-
dence figures varied considerably between the different
countries surveyed. However, these exact figures must
be interpreted with caution. Accordingly, completely re-
liable incidence figures and figures of relative percentage
of HSV and syphilis in GUD may not be available due
to the inadequacy of the diagnostic services available
(use of inappropriate diagnostic tests and reagents),
uneven access to the point-of-care sites (where tests for
HSV are performed), and suboptimal systems for case
reporting and epidemiological surveillance.
Viral isolation, HSV DNA detection by pCR and HSV
antigen detection by enzyme immunoassay or DIF, all
could be used for direct virus detection. However, pCR
techniques have higher sensitivity and are less dependent
on transport time and some other variables (4). Viral
isolation was available only for routine diagnostics in
one of the 14 EE SRH countries surveyed, while direct
detection of viral DNA was available in a further nine
countries. In Tajikistan viral detection is achieved solely
using DIF, while in Bulgaria, Azerbaijan and Armenia
no direct detection of HSV in lesions was available.
Clearly, there is a need to reinforce the regional capa-
city for the direct detection of HSV, preferably using
validated pCR techniques. Furthermore, HSV typing to
distinguish HSV-1 and HSV-2 has important prognostic
consequences, since the recurrence rate is significantly
lower in HSV-1 compared with HSV-2 genital infection,
and typing also needs to be encouraged in the region.
Although type-specific HSV serology may be a useful
tool for the diagnosis and management of genital HSV
infection in selected cases, generally it is not of high
diagnostic value. Serology is necessary for staging of
genital herpes as either primary or recurrent disease
(in combination with culture or pCR). In addition,
type-specific serology can identify discordant couples,
which might reduce transmission risk and the risk of
congenital disease (5). Unfortunately, nine (64%) of the
14 countries surveyed indicated that they used HSV anti-
body tests that cannot differentiate between infections
caused by HSV-1 and HSV-2. These tests are of little
diagnostic value for genital HSV infection, especially
in impoverished communities, where oral-labial HSV-1
infections are commonly acquired during childhood.
In general, many of the surveyed countries had mo-
dern diagnostic tools necessary to provide a definitive
diagnosis of this infection. However, for several diffe-
rent reasons these tests were not widely used: firstly, the
number of testing and/or point-of-care sites providing
such testing varied and in the majority of the countries
Table II. Availability of laboratory tests used for the laboratory diagnosis of genital herpes simplex virus (HSV) infection in 14 Eastern
European Network for Sexual and Reproductive Health (EE SRH) countries
Detection of antibody
specific Abs CFT DIF-AgEIA-Ag
+: approach or assay available; DIF–Ag: detection of virus antigen using direct immunofluorescence test; EIA-Ag: detection of virus antigen using enzyme
immunoassay; NAATs: nucleic acid amplification tests; ELISA HSV 1/2 Abs: enzyme-linked immunosorbent assay for detection of antibodies to both HSV
type 1 and type 2; ELISA type specific Abs: ELISA for detection of HSV-type-specific antibodies; CFT: complement fixation test.
Acta Derm Venereol 91
336 Download full-text
M. Domeika et al.
was limited, which made access to those services un-
even between the countries and even within the same
country; secondly, health services lacked resources to
cover costs for such testing, so it was up to the physician
to motivate the patient to pay for this relatively expen-
sive diagnostic testing; and thirdly, it was also up to the
physician to identify the need for testing, knowing that
this virus infection is incurable and rarely treated even
if properly diagnosed.
Although bacterial STIs remain a significant public
health problem and are a main focus in many East Euro-
pean countries, the relative importance of HSV in GUD
has increased globally (6–8). It is unlikely that Eastern
Europe is any different, bearing in mind the recent
reduction in cases of primary and secondary syphilis
(9). Furthermore, the differentiation between genital
HSV infection and other infectious or non-infectious
aetiologies of genital ulceration is difficult, and labo-
ratory confirmation of the infection should always be
sought. Diagnosis based only on clinical symptoms has
been shown to have a low sensitivity, even in carefully
monitored populations. False-positive clinical diagnoses
also occur frequently (10).
The recent important advances in the laboratory diag-
nosis of genital HSV infection, the decrease in cost of
acyclovir and the emerging importance of genital herpes
as a cofactor in transmission of HIV (11) indicate that
more attention should be paid to HSV as a cause of
genital ulceration. There is clearly a need to improve
access to high-quality diagnostics for HSV infection in
many Eastern European countries.
In order to improve the present situation, consensus
guidelines aimed at optimizing the laboratory diagnosis
of HSV infections in the region have been developed
(12) and, it is hoped, will soon be adopted and imple-
mented in the EE SRH countries.
The present study was supported by a grant from the East Europe
Committee of the Swedish Health Care Community, SIDA.
The authors declare no conflicts of interest.
Domeika M, Savicheva A, Sokolovskiy E, Ballard R, 1.
Unemo M; Eastern European Network for Sexual and
Reproductive Health (EE SRH Network). Quality enhan-
cements and quality assurance of laboratory diagnosis of
sexually transmitted infections in Eastern Europe. Int J STD
AIDS 2009; 20: 365–367.
Chapel TA, Jeffries CD, Brown WJ. Simultaneous infection 2.
with Treponema pallidum and herpes simplex virus. Cutis
1979; 24: 191–192.
Corey l, Holmes kk. Genital herpes simplex virus infec-3.
tions: current concepts in diagnosis, therapy, and preven-
tion. Ann Intern Med 1983; 98: 973–983.
Corey l, Wald A. Genital herpes. In: Holmes kk, Sparling 4.
pF, Stamm WE, piot p, Wasserheit JN, Corey l, et al., edi-
tors. Sexually transmitted diseases, 4th edition. New york:
McGraw-Hill; 2008, p. 399–438.
Brown zA, Selke S, zeh J, kopelman J, Maslow A, Ashley 5.
Rl, et al. The acquisition of herpes simplex virus during
pregnancy. N Engl J Med 1997; 337: 509–515.
Bruisten SM, Cairo I, Fennema H, pijl A, Buimer M, 6.
peerbooms pG, et al. Diagnosing genital ulcer disease in a
clinic for sexually transmitted diseases in Amsterdam, The
Netherlands. J Clin Microbiol 2001; 39: 601–605.
Moodley p, Sturm pD, Vanmali T, Wilkinson D, Connolly 7.
C, Sturm AW. Association between HIV-1 infection, the
etiology of genital ulcer disease, and response to syndromic
management. Sex Transm Dis 2003; 30: 241–245.
Risbud A, Chan-Tack k, Gadkari D, Gangakhedkar RR, 8.
Shepherd ME, Bollinger R, et al. The aetiology of genital
ulcer disease by multiplex polymerase chain reaction and
relationship to HIV infection among patients attending
sexually transmitted disease clinics in pune, India. Sex
Transm Dis 1999; 26: 55–62.
World Health Organization (WHO). Regional office of 9.
Europe. Syphilis. Total. Incidence rate per 100,000 popula-
tion, for 1998–2008. Sexually transmitted infections (STI).
CISID. Available from: http://data.euro.who.int/cisid/.
langenberg AG, Corey l, Ashley Rl, leong Wp, Straus SE. 10.
A prospective study of new infections with herpes simplex
virus type 1 and type 2. Chiron HSV Vaccine Study Group.
N Engl J Med 1999; 341: 1432–1438.
Wald A, Link K. Risk of human immunodeficiency virus in- 11.
fection in herpes simplex virus type 2-seropositive persons:
a meta-analysis. J Infect Dis 2002; 185: 45–52.
Domeika M, Bashmakova M, Savicheva A, kolomiec N, 12.
Sokolovskiy E, Hallén A, et al. Guidelines for the laboratory
diagnosis of genital herpes in Eastern European Countries.
Euro Surveill 2010; 15. pii: 19703.
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