Vaccine 20 (2002) 1425–1428

Varicella seroprevalence in a random sample of the Turkish population

G. Kanra a,∗ , S. Tezcan b , S. Badur c , Turkish National Study Team1
a Pediatric Infectious Disease Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey
b Department of Public Health, Faculty of Medicine, Hacettepe University, Ankara, Turkey
c Department of Microbiology, Faculty of Medicine, Istanbul University, Istanbul, Turkey

Received 9 January 2001; received in revised form 20 September 2001; accepted 29 October 2001

Abstract
Chicken pox highly contagious and common throughout the world, is an infectious disease caused by varicella zoster virus (VZV).
This study was conducted to determine the seroprevalence of VZV in a population under age 30 and to identify the relationship of
VZV seroprevalence and several characteristics of the study subjects in nine provinces of Turkey. The sampling method of 30 clusters
recommended for field studies was used for selecting subjects of a pre-determined number in the rural and urban areas in each province.
For this, a total of 60 groups, 30 clusters in the rural and 30 in the urban areas were determined. It was planned that a total of 4800 subjects,
including 600 subjects from five big provinces (Istanbul, Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from the remaining smaller
provinces (Samsun, Erzurum, Trabzon, Edirne), be included in the study. ELISA method was used to examine the blood samples for VZV
seropositivity. Positive VZV seroprevalence was detected in 77.8% of 4387 subjects under age 30 in nine provinces of Turkey. There was
no difference in seroprevalence rate between rural and urban areas. Seroprevalence was found to be 79.0% in urban areas and 76.3% in rural
areas. Seroprevalence increased with age. Seroprevalence was 20% at the age of 1 year, subsequently increased to 40% at the age of 4 years,
60% at the age 6 years, 80% at the age of 8 years, 85% at the age of 10 years, and then remained at 85–90% in subjects over the age of 10
years. In order to develop vaccination protocols and take appropriate preventive health care measures against diseases in different countries,
it is very important to know the seroprevalence of any disease for an individual country. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Varicella; Seroprevalance; Vaccine

1. Introduction
Chicken pox is an infectious disease caused by varicella
zoster virus (VZV). Ninety percent of all cases in the USA
occur in children under the age of 15 years. The incidence
of disease is similar in both sexes and different races. Virus
from an infected person contaminates a healthy individual
via contact with fluids from skin lesions or droplets through
respiratory system [1,2].
In general, life-long immunity develops following infec-
tion to chicken pox. This immunity depends on the antibody
production as a result of cellular immunologic response.
Cellular immunity may weaken with advancing age and the
virus may be reactivated. Consequently, this reactivation

∗ Corresponding author. Tel.: +90-312-3114963; fax: +90-312-3108241.

1 Alp H: Associate Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Atatürk University, Erzurum, Turkey. Bulut A: Professor
of Public Health, Department of Pediatrics, Faculty of Medicine, Istanbul University, Istanbul, Turkey. Cin S: Professor of Pediatrics, Department
of Pediatrics, Faculty of Medicine, Ankara University, Ankara, Turkey. Çan G: Associate Professor of Pediatrics, Department of Pediatrics, Faculty
of Medicine, Karadeniz Technical University, Trabzon, Turkey. Dündar C: Pediatrician, Department of Pediatrics, Faculty of Medicine, 19 Mayis
University, Samsun, Turkey. Egemen A: Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey. Eskiocak
M: Pediatrician, Department of Pediatrics, Faculty of Medicine, Trakya University, Ankara, Turkey. Evliyaoglu N: Associate Professor of Pediatrics,
Department of Pediatrics, Faculty of Medicine, Çukurova University, Adana Turkey. Güraksin A: Associate Professor of Pediatrics, Department of
Pediatrics, Faculty of Medicine, Atatürk University, Erzurum, Turkey. Mocan H: Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine,
Karadeniz Technical University, Trabzon, Turkey. Öztürk F: Associate Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, 19 Mayis
University, Samsun, Turkey. Saka G: Pediatrician, Department of Pediatrics, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Sidal M: Professor
of Pediatrics, Department of Pediatrics, Faculty of Medicine, Istanbul University, Istanbul, Turkey. Ulukol B: Associate Professor of Pediatrics, Department
of Pediatrics, Faculty of Medicine, Ankara University, Ankara, Turkey. Tanyer G: Professor of Pediatrics, Ankara Hospital, Ministry of Health, Ankara,
Turkey. Tas MA: Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Yazicioglu M: Pediatrician,
Department of Pediatrics, Faculty of Medicine, Trakya University, Edirne, Turkey. Dagbasi N: Glaxo-SmithKline Beecham, Istanbul, Turkey. Velicangil
Ö: Glaxo-SmithKline Beecham, Istanbul, Turkey.

0264-410X/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S 0 2 6 4 - 4 1 0 X ( 0 1 ) 0 0 4 5 9 - 5
1426 G. Kanra et al. / Vaccine 20 (2002) 1425–1428
leads to pain and vesicles on the dermatome of sensory
nerves, presenting as herpes zoster infection. [1,2].
Chicken pox is not a notifiable disease in Turkey. More-
over, because Turkey has not conducted a community-based
study on this disease, the exact incidence is not known.
Therefore, we conducted a study to determine the seropreva-
lence of VZV in the population under age 30 and to identify
the relationship between VZV seroprevalence and several
characteristics of the study subjects in nine provinces of
Turkey. The subjects and locations provide a representative
sample of geographic, demographic and socio-economical
characteristics of Turkey.
2. Materials and methods
The present study of seroprevalence of VZV was
conducted in nine provinces of Turkey. The sampling
method of 30 clusters was used for selecting subjects of
a pre-determined number in the rural and urban areas in
each province. This is a practical method recommended by
World Health Organisation for field studies [3–5]. For this,
a total of 60 clusters in the rural (30 clusters) and urban (30
cluster) areas were determined and the related lists were
sent to the principal investigator in each city.
The provinces included were Istanbul, Ankara, Izmir,
Adana, Diyarbakir, Samsun, Trabzon, Erzurum and Edirne.
Because one-third of Turkish population live in these areas,
we believe that the seroprevalence of study subjects would
be highly representative of the entire country. In addition
to providing a representative cross sample, these provinces
also draw intense migration from neighbouring cities and
communities farther away.
In each province, sample sizes were determined from pub-
lished data on varicella seroprevalance and sample size for-
mula for cluster sample size for each group of subjects under
age 30 for seroprevalence estimates within 95% confidence
rate [6].
Therefore, it was planned that a total of 4800 subjects,
including 600 subjects from five big provinces (Istanbul,
Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from
the remaining smaller provinces (Samsun, Erzurum, Trab-
zon, Edirne), be included in the study. These number were
distributed among 0–30 years of age population of each
province proportional to the actual size. The age groups were
separated in to 5-year groups. The number and distribution
of population in each province was obtained from the State
Institute of Statistics. When the investigators reached the
cluster (villages in rural area and streets in urban area) the
door number to start was chosen randomly. Then until the
predetermined number in each age group is reached houses
were visited.
In order to provide a standard practice, investigators in
each centre were appropriately trained on such issues as the
selecting subjects, obtaining informed consent, applying the
questionnaire, taking blood sample, and collecting, storing
and transporting sera for the serum. Additionally, the au-
thorised ethics committee in each centre approved this sero-
prevalence study, and the entire study was pre-approved by
the ethics committee of the Ministry of Health. Each poten-
tial subject who was interviewed and who agreed to partic-
ipate read and signed a written informed consent form.
A questionnaire about several characteristics of subjects
was used to obtain data on VZV epidemiology (for their
parents or guardians supplied those under age 18, informa-
tion). Following the interviews, appropriate blood samples
were taken from subjects for seroprevalence analyses.
Serum analyses were performed at the Microbiology Lab-
oratory of Istanbul University Faculty of Medicine.
Serum samples were obtained from the blood sam-
ples and transported to the related laboratory in accor-
dance with the principles of cold chain. For each serum
sample, a quantitative investigation for anti-varicella
virus-IgG (anti-VZV-IgG) antibodies was performed using
Dade-Behring micro-ELISA kits (Dade Behring Marburgh,
Germany). The sensitivity and specificity of the ELISA
method is approved especially for the field studies [7,8].
All serum samples including controls and references were
diluted by 1/10 and added to two separate cupules, one con-
taining viral antigen and the other containing control antigen.
Following an incubation period of 60 min at 37 ◦ C, cupules
were irrigated three times so that the unbounded materials
were removed, then peroxidase-labelled anti-human conju-
gate (100 ␮l) was added to the cupules. Following incubation
period of of 60 min at 37 ◦ C cupules were irrigated again,
and the chromogen substrate was added to the cupules. The
reaction occurring in ELISA plates stored at room tempera-
ture for 30 min was terminated by adding 100 ␮l of stopper
buffer solution to each cupule. Subsequently, absorbency
value for each cupule was detected by reading at 450 nm.
By considering the absorbency values for cupules covered
with or without antigen and using ␣-method, anti-VZV-IgG
level was quantitatively determined for each serum
sample.
As this was a descriptive study only percentages were
calculated and no further statistical analysis was made.
3. Results
This seroprevalence study included a total of 4461 sub-
jects representative of the population under age 30 in nine
provinces of Turkey (Table 1).
In Ankara, Izmir and Erzurum, more subjects than tar-
geted sample size were questioned and subjected to blood
analysis. The size of participation was also larger than ex-
pected, representing the population in related provinces.
Generally, seroprevalences could not be determined in 5.1%
of sampled subjects and 6.7% of interviewed subjects. The
main reason for this was that blood sampling could not be
performed in children under 1 year of age due to the diffi-
culty of obtaining blood sample.
 G. Kanra et al. / Vaccine 20 (2002) 1425–1428 1427

Table 1
Distribution of subjects selected for sampling, interviewed and underwent blood sampling in nine provinces (Turkey 1998)
Provinces Number of Positive Number of interviewed subjects Number of subjects
sampled subjects seroprevalence undergoing blood analysis
Number Percentagea Number Percentageb

Istanbul 600 79.8 563 93.8 554 98.4

Ankara 600 78.2 636 106.0 606 95.3
Izmir 600 73.2 627 104.5 612 97.6
Adana 600 80.9 570 95.0 543 95.3
Diyarbakir 600 83.6 540 90.0 468 86.7
Samsun 450 75.8 430 95.6 312 72.6
Erzurum 450 76.9 387 86.0 568 99.8
Trabzon 450 78.2 387 86.0 371 95.9
Edirne 450 69.7 379 84.2 353 93.1
Total 4800 77.8 4701 97.9 4387 93.3
a Percentages calculated for the number of sampled subjects in each city.
b Percentages calculated for the number of interviewed subjects in each city.

The distribution of subjects in nine provinces is presented
in Table 2 by several characteristics. The percentage of sub-
jects under the 1 year of age was low due to the reasons
mentioned above. Of subjects included in the study, 47.3%
were male and 51.5% female. By family size, 64.3% had
five or less family members and 34.6% had six or more fam-
ily members. Of subjects, 65.3% were living in urban areas,
6.3% in suburban areas, and 28.4% in rural areas.
Positive VZV seroprevalence was detected in 77.8% of
4387 subjects under age 30 in nine provinces of Turkey.
Table 2
Several characteristics of subjects participating in VZV seroprevalence
study in nine provinces, Turkey (1998)
Characteristic Number
Table 3 shows the distribution of VZV seroprevalences by
several subject characteristics. Although the average rate was
around 75–80%, seroprevalence rates by provinces ranged
from a low of 69.7% (Edirne) to a high of 83.6% (Di-
yarbakir). There was no difference in seroprevalence rate
between rural and urban areas. Seroprevalence was found to
be 79.0% in urban areas and 76.3% in rural areas.
Seroprevalence increased with age. Seroprevalence was
20% at the age of 1 year, subsequently increased to 40% at
the age of 4 years, 60% at 6 years of age, 80% at the age of
8 years, 85% at the age of 10 years, and then remained at
85–90% in subjects over the age of 10 years.
Percentage

Age Table 3
0 57 1.3 Positive VZV seroprevalence for population under age 30 by several
1–3 495 11.3 socio-demographic characteristics in nine cities of Turkey (1998)
4–6 503 11.5 Characteristic Number Positive
7–9 513 11.7 seroprevalence (%)
10–14 864 19.7
Age (n = 4335)
15–19 746 17.0
0 57 19.3
20–24 611 13.9
1–3 495 32.5
25–29 546 12.5
4–6 503 59.4
Unknown 52 1.1
7–9 513 81.1
Total 4387 100
10–14 864 88.1
Sex 15–19 746 90.2
Male 2076 47.3 20–24 611 91.2
Female 2259 51.5 25–29 546 91.9
Unknown 52 1.2
Sex (n = 4335)
Total 4387 100
Male 2076 76.0
Family size
Female 2259 79.7
Five and less 2819 64.3
Six and more 1518 34.6 Family size (n = 4387)
Unknown 50 1.1 Five and less 2819 78.1
Total 4387 100 Six and more 1518 80.6
Location Location
Urban area 2863 65.3 Urban area 2863 79.0
Suburb 279 6.3 Suburb 279 74.8
Rural area 1245 28.4 Rural area 1245 76.3
Total 4387 100 Total 4387 77.8
1428 G. Kanra et al. / Vaccine 20 (2002) 1425–1428
4. Discussion
Varicella is an important health care problem because it
is common throughout the world, is highly contagious and
carries a high secondary attack rate [1].
In order to develop vaccination protocols and take appro-
priate preventive health care measures against diseases in
different countries, it is very important to know the sero-
prevalence of any disease for an individual country. This
study which was conducted using the 30 cluster sampling
method in nine provinces of Turkey, including both rural
and urban areas, providing a representative data for Turkey.
The ratio of realized population to targeted population was
93.3%. In general, this figure was sufficient except for the
age group under 1 year of age. The main reason for this was
that blood sampling was not performed in children under
the age one due to the difficulty of obtaining blood sample.
When comparing various seropositivity studies, methods
of antibody detection should be similar. We used ELISA
method, currently the most accurate method, which is sen-
sitive, specific and especially recommended for field studies
[7,8].
The results of our study can be considered comparable
with those in the literature [9–12]. Varicella seropositivity
was 32.5% at the end of age 3, 59.4% at the end of age 6 and
81.1% at the end of age 9, and it was concluded that most of
the cases occurred before age 10. When seropositivity was
evaluated by age, seropositivity showed a linear increase
from age 2 to age 10. At this point, it reaches a plateau
showing only moderate increases with age. Seropositivity
was already 88.1% at the end of age 14 and then increased
to 92% at the age 30.
Several studies in the literature have reported that vari-
cella is most frequently seen between ages 4 and 10 [11,12].
However, several studies have reported that seropositivity
ranges between 80 and 100% in adults [12,13]. It has been
reported that the age at which people are infected for the
first time is higher, and that this disease is more important
for adults and adolescents in Asian countries [7].
In our study, there was no difference in seropositivity
between sexes. Seropositivity rates were equivalent in ru-
ral and urban areas and among the nine provinces studied.
Studies performed in other countries also support that there
is no significant seropositivity difference between sex and
race. [11,12]. However, seropositivity has been reported to
be lower in adults living in rural areas than those living in
urban areas [14].
The results of our study showed that varicella is a dis-
ease affecting the general population, causing infection re-
gardless of sex and socio-economical class, and is highly
common during the pre-school and primary school period.
These results are similar to those of studies conducted in
other countries. Based on the results of our study, it will
be useful for Turkey to establish a childhood vaccination
program.
Acknowledgements
This study was supported by Glaxo-SmithKline.
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