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Eriskinde Epstein-Barr virus enfeksiyonunun seroprevalansi ve risk faktorleri/Seroprevalence and risk factors for Epstein-Barr virus infection in adults.

This study has not been presented previously as an abstract in any congress or symposium.


Amac: Insan herpes virus 4 olarak da bilinen Epstein-Barr virus, infeksiyoz mononukleoz hastaliginin etkenidir. EBV infeksiyonlari cok sayida malignitelerle de iliskilendirilmektedir. Bu calismanin amaci, eriskinde EBV seroprevalansini ve risk faktorlerini belirlemektir.

Gerec-Yontem: Bu calisma, Istanbul'da Haydarpasa Numune Egitim ve Arastirma Hastanesi'nde Agustos 2012 ve Ekim 2012 tarihleri arasinda yapildi. 500 olguda ELISA yontemiyle EBV VCA IgG testi yapildi. Yas, cinsiyet, meslek, egitim durumu, gelir duzeyi, yasanilan yer, yasanilan ev ve kronik hastalik durumlari irdelendi. Risk gruplari arasindaki farklilik istatistiksel olarak arastirildi.

Bulgular : Calismaya katilan 500 olguda ortalama yas 47.7 [+ or -] 19.1 (15-87 yas arasi) idi ve 292 olgu erkekti. Ortalama EBV seropozitifligi %96.4 idi. %90.8 olguda, 15 yasina gelene kadar sezopozitiflik olusmaktaydi.Yas, cinsiyet, meslek, egitim durumu, gelir duzeyi, yasanilan yer, yasanilan ev ve kronik hastalik durumlari acisindan istatistiksel olarak anlamli farklilik saptanmadi.

Sonuc: EBV seropozitifligi oldukca yuksekti ve 15 yasina kadar olgularin %96'si seropozitif hale gelmekte idi. EBV seroprevalansi ve risk faktorleri arasinda anlamli bir baglanti saptanmadi.

Anahtar kelimeler: Epstein-Barr virus enfeksiyonlari, seroprevalans, risk faktorleri


Introduction: Epstein-Barr virus (EBV), also known as human herpesvirus 4, is the causative agent of infectious mononucleosis. Infection with EBV is associated with multiple malignancies. The aim of this study was to determine the seroprevalence and risk factors for seropositivity.

Materials and Methods: This study was conducted in Haydarpasa Numune Training and Research Hospital in Istanbul between August 2012 and October 2012. EBV VCA IgG antibody was measured using commercial ELISA in 500 cases. Age, gender, occupation, education level, family income, the area and type of residence, and chronic illness of the participants were also evaluated. Differences between risk groups were statistically analylzed.

Results: The participants' mean age was 47.7 [+ or -] 19.1 years (15-87 years) and 292 of the 500 participants were male. Mean EBV seropositivity was 96.4%, and 90.8 % of the cases become seropositive for EBV by 15 years of age. No significant associations with age, gender, occupation, education level, family income, area and type of residence, and chronic illness were detected.

Conclusions: EBV seropositivity rates were very high and about 91% of the cases become seropositive for EBV by 15 years of age. There was no significant relationship between risk factors and seroprevalence of EBV.

Key Words: Epstein-Barr virus infections, seroprevalence, risk factors


Epstein-Barr Virus (EBV) is a latent virus from the family Herpesviridae which is transmitted via the oropharyngeal secretions, blood, and contaminated belongings of infected individuals. EBV is the causative agent of infectious mononucleosis, which is a generally self-limiting condition characterized by fever, sore throat, and lymphadenopathy. However, the virus is known to be associated with Burkitt lymphoma, lymphoproliferative diseases, nasopharyngeal carcinoma, Hodgkin's lymphoma, primary central nervous system lymphoma in AIDS patients, and autoimmune diseases such as multiple sclerosis ([1]).

The serologic profile of EBV infection is determined using specific antibodies against the major antigens of the virus including EBV nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) ([2]). VCA IgM is found in the serum for 4-8 weeks during the active phase of the disease. In contrast, EBV VCA IgG appears early in acute infection and remains positive for the lifetime of the patient. Therefore EBV VCA IgG is commonly used in epidemiologic studies ([3]). EBV seropositivity rates in adults in Turkey have been reported as 80-99.4% ([3,4]).

Due to the oncogenic potential of EBV and its known role as an etiologic factor for many idiopathic diseases, determining EBV seropositivity is important for identifying individuals at risk ([5]). The present study was conducted with individuals over the age of 15 living in Istanbul, which receives immigrants from many regions of Turkey. The aim was to determine EBV seroprevalence and identify any significant differences in seroprevalence based on age, sex, occupation, education level, economic status, chronic diseases, and place and type of residence.

Materials and Methods

This study was performed between August and October 2012 in Haydarpasa Numune Training and Research Hospital. A total of 500 individuals aged 15 years and over who presented to the Haydarpasa Numune Hospital Infectious Diseases Polyclinic and Blood Bank were included. Previously prepared standard questionnaires were filled in during face-to-face interviews. The study participants were asked about their age, sex, occupation, education level, economic status, chronic diseases, area and type of residence, and underlying diseases. Individuals with history of blood transfusion or surgery and immunosuppressed individuals were excluded. Ethics committee approval was obtained from the Haydarpasa Numune Training and Research Hospital Ethical Council (decision number HNEAH.KA.EK-2012/50). A venous blood sample of about 5 cc was obtained from the participants and the serum samples were preserved at -20[degrees]C until analysis. Micro-ELISA was used to measure EBV VCA IgG antibody levels (NovoTec NovaLisa EBV VCA IgG ELISA (Dietzenbach, Germany) as per the manufacturer's instructions. The formula n=[t.sup.2]pq/[d.sup.2] was used to calculate the sample size required to determine the EBV VCA IgG seroprevalence in the adult Turkish population. Statistical analyses were done using the NCSS (Number Cruncher Statistical System) 2007 Statistical Software (Utah, USA) package. Data were analysed using descriptive statistics (mean, standard deviation) and categorical data were compared using chi-square and Fisher's exact test. The results were evaluated at a significance level of p<0.05.


The mean age of the 500 study participants was 47.7[+ or -]19.1 (15-87) years and 292 (58.4%) were males. EBV VCA IgG positivity was found in 479 (96.4%) of the participants. No statistically significant differences emerged in the age and gender distribution of EBV VCA IgG-positive participants (p>0.05, p=0.748) (Tables 1 and 2). There was no statistically significant difference in the gender distribution of the participants according to age groups (p>0.05) (Table 3).

Analysis of seropositivity rates in terms of participants' occupation, education level, and income levels revealed no statistically significant differences (p>0.05 for all) (Tables 4-6). There were no statistical differences in seropositivity according to the participants' place of and type of residence (p>0.05) (Table 7). The presence of a chronic disease was also not significantly associated with EBV VCA IgG positivity (p>0.05) (Table 8).


EBV is present in the saliva of asymptomatic seropositive individuals and is easily transmitted between people. It is known that socioeconomic level, hygiene habits, and crowded living conditions influence EBV seroprevalence, and higher seropositivity rates are seen in developing countries ([6]). In our study, the overall EBV seroprevalence was 96.4%. Our findings are consistent with those of other seroprevalence studies conducted in our country ([3,7]). Customary Turkish behaviors showing love and respect, such as hand kissing, hugging and kissing the cheeks in greeting, are believed to facilitate the transmission of EBV through saliva and may cause this high seroprevalence.

It is known that having an EBV infection at an early age has harmful effects. Burkitt lymphoma is more common among infants who have primary EBV infection at very early ages and the accompanying high EBV viremia ([8]). Many studies have shown that EBV seroprevalence increases with age ([7,9-11]). In our study, presence of EBV IgG antibodies was analysed in individuals aged 15 years and over. The EBV IgG positivity rate was 90.77% in the 15-25 years group and 97.78% in participants over 75 years old, with no statistically significant differences between age groups. This lack of significant age-related differences in seropositivity may be due to the participants having encountered a large number of viruses before the age of 15.

We also analyzed sex differences in EBV seropositivity and found that seropositivity rates were higher in males than in females. However, the difference was not statistically significant. In a study conducted with students of Edinburg University, Higgins et al. ([12]) determined seropositivity rates of 68.1% in males and 78.5% in females, which was a statistically significantly difference. In another study of children between 6-19 years of age, EBV seroprevalence was found to be higher in girls than in boys (68.9%, 64.2%) ([13]). A study by Ozkan et al. ([3]) demonstrated that women had similar rates to men.

In the present study, we investigated the relationship between EBV seropositivity and education level. The participants were classified as illiterate, literate without formal education, primary school graduate, secondary school graduate, high school graduate, and university graduate/postgraduate. No statistically significant association was found between educational level and seroprevalence. This result is consistent with that reported by Ozkan et al. ([3]). In contrast, Balfour et al. ([9]) analyzed the relationship between family education level and seropositivity and found that seropositivity was 72% for those who did not attend high school, 63% for high school graduates, and 56% for those with education beyond high school. Another study showed that EBV seropositivity in individuals with education below high school, at the high school level, and beyond high school was 83.5%, 69.5%, and 59%, respectively ([13]). As suggested by these studies, higher education level has been linked to better hygiene habits and consequently a lower risk of virus transmission. High levels of transmission in childhood indicated the importance of family education. Contamination with EBV is known to be affected by socioeconomic status ([3]). A study analyzing the correlation between income level and EBV seropositivity reported rates of 81% in the low-income group, 75% in the mid-level income group, and 54% in the high-income group ([13]). In a seroprevalence study including 283 individuals in Brazil, it was reported that EBV seropositivity increases with decreasing socioeconomic level of the families ([14]). However, the findings of our study indicate that EBV seropositivity does not change significantly according to income level.

A limitation of our research is that our analysis only included adults, and did not include children. Therefore, we were unable to identify differences in seroprevalence among children, among whom EBV exposure is the highest and general manifests with subclinic infection, and we could not determine the risk factors that affect seropositivity in this age group.

In conclusion, this study based on the adult population of Istanbul has shown that EBV seropositivity reaches 90% by the age of 15. Due to the high seropositivity rate, there were no significant differences between groups with regard to risk factors. Because EBV infection early in life increases its oncogenicity, it is vitally important to prevent transmission to the very young. The lack of an effective vaccine against EBV increases the importance of protective measures. Identifying and eliminating the risk factors for virus transmission will lead to a reduction in EBV seroprevalence.

Ethics Committee: This study was approved by a Local Ethics Committee

Informe Consent: A consent form was filled out by all participants

Contributor 1- Concepts, Design, Definition of intellectual content, Literature search, data analysis

Manuscript preparation, Statistical analysis

Contribitor 2- Concepts, Design, Definition of intellectual content, Manuscript preparation

Contribitor 3- Concepts, Data analysis, Definition of intellectual content, Literature search, Manuscript preparation, Manuscript editing,design

Contribitor 4. Concepts, Data analysis, Definition of intellectual content , Manuscript preparation

Contribitor 5. Concepts, Data analysis, Definition of intellectual content , Manuscript preparation

Contribitor 6. Concepts, Data analysis, Definition of intellectual content , Manuscript preparation

Contribitor 7. Concept. Data analysis. Definition of intellectual content. Manuscript preparation


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(2.) Sirekbasan S, Celik DG, Abdelkareem A, Yuksel P, Aslan M, Saribas S, Kocazeybek B. Epstein-barr virusu infeksiyonu tanisinda EBV IgM/IgG ve monospot testlerinin irdelenmesi. Klimik Derg. 2012;25:107-10.

3. Ozkan A, Kilic SS, Kalkan A, Ozden M, Demirdag K, Ozdarenli A. Seropositivity of Epstein- Barr virus in Eastern Anatolian region of Turkey. Asian Pac J Allegy Immunol. 2003;21(1):49-53.

4. Gecgel SK, Ersoy A, Sevinir BB, Sinirtas M, Goral G. Epstein-Barr virus enfeksiyonlarinin tanisinda PCR sonuclarinin degerlendirilmesi. Mikrobiyol Bul. 2012;46(4):594-606.

(5.) Fidan I, Yuksel S, Imir T. Degisik yas gruplarina Epstein-Barr virus antikorlarinin arastirilmasi. Infeksiyon Derg. 2005;19:453-6.

(6.) Takeuchi K, Tanaka-Taya K, Kazuyama Y, Ito YM, Hashimoto S, Fukayama M, Mori S. Prevalence of Epstein-Barr virus in Japan: trends and future prediction. Pathol Int. 2006;56(3):112-6.

(7.) Yetkin G, Ay S, Tekerekoglu MS, Abut Iseri L. Inonu Universitesi Tip Fakultesi Hastanesi'ne basvuran 1-18 yas grubu cocuklarda Epstein-Barr virus (EBV) seroprevelansi. Flora. 2008;13(2):79-82.

(8.) Piriou E, Asito AS, Sumba PO, Fiore N, Meddeldrop JM, Moormann AM, Ploutz-Synder R, Rochford R. Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma. J Infect Dis. 2012 ;205(6):906-13.

(9.) Balfour HH Jr, Sifakis F, Sliman JA, Knight JA, Schmeling DO, Thomas W. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acqusition. 2013;208(8):1286-93.

(10.) Suntornlohanakul R, Wanlapakorn N, Vongpunsawad S, Thongmee T, Chansaenroj J, Poovorawan Y. Seroprevalence of Anti-EBV IgG among various age groups from Khon Kaen province, Thailand. Asian Pac J Cancer Prev. 2015;16(17):7583-7.

(11.) Ozsoy M, Yilmaz N, Gokalp N. Klinik yakinmalari olan ve olmayan bireylerde Epstein-Barr virus gostergelerinin serolojik olarak arastirilmasi. Mikrobiyol Bult. 2001;35:465-72.

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Jale Altintas (1), Serpil Erol (1), Derya Ozturk Engin (1), Seyfi Ozyurek (1), Seniha Senbayrak (1), Asuman Inan (1), Zeynel Abidin Demir (1)

Haydarpasa Numune Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey

Sorumlu yazar: Derya Ozturk Engin, Haydarpasa Numune Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey Mobile phone: +90 50575126 55

Table 1. EBV VCA IgG positivity distribution by age group

              EBV VCA IgG (+)  EBV VCA IgG (-)
              n = 479          n = 21           P value
Age (years)   n    %           n     %

 15-25 years   59   90.77      6     9.23       0.052
 26-35 years  104   98.11      2     1.89       0.327
 36-45 years   78   92.86      6     7.14       0.201
 46-55 years   62  100         0     0.00       0.169
 56-65 years   69   97.18      2     2.82       0.957
 66-75 years   63   94.03      4     5.97       0.595
>75            44   97.78      1     2.22       0.804

Table 2. EBV VCA IgG positivity distribution by sex

        EBV VCA IgG (+)  EBV VCA IgG (-)
        n = 479          n = 21           P

Sex     n    %           n      %
Female  198  95.19       10     4.81
Male    278  96.19       11     3.81      0.748

Table 3. EBV VCA IgG positivity distribution by age and sex

                      EBV VCA IgG (+)  EBV VCA IgG (-)
                      n = 479          n = 21          P value
                      n      %         n     %

              Female  27     90        3     10
 15-25 years  Male    32     91.40     3      8.60     0.843
              Female  33     97.10     1      2.90
 26-35 years  Male    68     95.80     3      4.20     0.748
              Female  25     89.30     3     10.70
 36-45 years  Male    51     91.10     5      8.90     0.793
              Female  23    100        0      0.00
 46-55 years  Male    37     97.40     1      2.60     0.433
              Female  23     95.80     1      4.20
 56-65 years  Male    44     95.70     2      4.30     0.972
              Female  37     97.40     1      2.60
 66-75 years  Male    25     86.20     4     13.80     0.085
              Female  29     93.50     2      6.50
>75           Male    14    100        0      0.00     0.331

Table 4. EBV VCA IgG positivity distribution by occupation

                   EBV VCA IgG (+)   EBV VCA IgG (-)
                   n = 479           n = 21           P value

Occupation         n      %          n     %
Unemployed         89      92.71     7     7.29       0.131
Homemaker         126      95.45     6     4.55       0.927
Worker             45      93.75     3     6.25       0.633
Civil servant of   34     100        0     0.00       0.432
Retired            82      97.62     2     2.38       0.592
Doctor/Nurse       23     100        0     0.00       0.643
Self-employed/     80      96.39     3     3.61       0.833
freelance worker

Table 5. EBV VCA IgG positivity distribution by education level

                      EBV VCA IgG (+)  EBV VCA IgG (-)
                      n = 479          n = 21         P value

Education level       n       %        n     %
Illiterate             63      94.03   4     5.97     0.595
Literate without       25     100      0     0.00     0.597
formal education
Elementary school     139      96.53   5     3.47     0.880
Middle school          71      94.67   4     5.33     0.762
High school            97      96.04   4     3.96     0.968
University/Graduate    84      95.45   4     4.55     0.788

Table 6. EBV VCA IgG positivity distribution by monthly income level

               EBV VCA IgG (+)  EBV VCA IgG (-)
               n = 479          n = 21          P value
               n       %        n      %

 <500 TL       116     96.67     4     3.33     0.859
  500-1000 TL  220     94.42    13     5.58     0.164
 1000-2000 TL  104     97.20     3     2.80     0.654
>2000 TL        39     97.50     1     2.50     0.925

Table 7. EBV VCA IgG positivity distribution by area of type of

                      EBV VCA IgG (+)   EBV VCA IgG (-)
                      n = 479           n = 21           P
                      N       %         n      %

Area of    Rural       29     96.67     1      3.33      0.841
           Suburban    20     95.24     1      4.76      0.862
           Urban      430     95.77    19      4.23      0.795
Type of    Separate   112     94.12     7      5.88      0.366
residence  house
           Apartment  361     96.52    13      3.48      0.436
           Other        6     85.71     1     14.29      0.673

Table 8. EBV VCA IgG positivity distribution according to chronic

                  EBV VCA IgG (+)   EBV VCA IgG (-)
                  n = 479           n = 21         P value
                  n      %          n     %

DM                68      97.14     2     2.86     0.834
CKD               37      94.87     2     5.13     0.717
CHF               37      92.50     3     7.50     0.458
COPD              26      92.86     2     7.14     0.734
Hypo-             10     100.00     0     0.00     0.513
Liver disease     16      94.12     1     5.88     0.693
Malignancy        13     100        0     0.00     0.973
HT                50      98.04     1     1.96     0.677
Other              6     100        0     0.00     0.614

DM: Diabetes mellitus, CKD: Chronic kidney disease, CHF: Chronic heart
failure, COPD: Chronic obstructive pulmonary disease, HT: Hypertension
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Title Annotation:2017-0010-arastirma
Author:Altintas, Jale; Erol, Serpil; Engin, Derya Ozturk; Ozyurek, Seyfi; Senbayrak, Seniha; Inan, Asuman;
Publication:Mediterranean Journal of Infection, Microbes and Antimicrobials
Article Type:Report
Date:Jan 1, 2017
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