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human herpes virus 4 ( hhv-4 ) , also called epstein - barr virus ( ebv ) , as a member of herpesviridae , is one of the most common viruses in humans .
it is commonly associated with non - specific clinical signs and is usually presented by painful sore throat , swollen glands , chills , fever and chronic fatigue syndrome .
the primary ebv infection in africa , southeast asia and latin america occurs in early childhood , while in developed countries the first peak of infection seems to be before the first five years of life while the second peak is during adolescence ( 3 ) . according to epidemiological studies the average age of ebv primary infection is increasing ( 4 ) , e.g. in us , it ranges from 50% for 5 year olds to 90% for 25 years old ( 5 ) . in brazil
the pattern of positive ebv igg ab showed a higher prevalence with increasing age , reaching a peak in the second decade of life ( 3 ) . in spain ,
the distribution of primary infection has shown two peaks , one at the age of two to four years and another at the age of 14 - 18 years ( 6 ) .
a recent study of 94 children in the republic of china demonstrated that 78.6% had ebv - vca igg by the end of the first year of life and 80.7% were seropositive by the age of three ( 7 , 8) . a similar study in chile revealed that 50% of children from low and medium socioeconomic level had been primarily infected by the age of two in comparison with 5.9% of high socioeconomic children of the same age ( 9 ) . in malaysian children
the presence of ebv - igm antibody , occurred at four to six months and by eight years many children became infected with ebv ( 10 ) .   since the clinical picture of ebv primary infection could be challenging , and because this infection usually causes no symptoms and can be indistinguishable from other mild , brief infections of children such as streptococcal throat infection , it is important to use the best clinical means for diagnosis ( 6 , 10 ) . the routine diagnosis of ebv primary infection is based on several serological tests such as indirect fluorescent antibody ( ifa ) , rapid monospot tests ( for heterophile antibodies ) and enzyme immune assay ( eia ) for detection of early antigens ( ea ) , the viral capsid antigens ( vca ) or the ebv nuclear antigen ( ebna ) ( 11 - 13 ) .
to the best of our knowledge , there is no study on the incidence of ebv primary infection in iran .
the aim of this study was to determine the incidence of ebv primary infection , among iranian suspected patients who had referred to namazi hospital of fars province ( south of iran ) by the elisa method .
the studied population consisted of 346 suspected patients who had referred to the professor alborzi clinical microbiology research center , namazi hospital , shiraz , southern iran , during march 2007 to march 2011 .
the major clinical manifestations of these patients included painful sore throat , swollen glands , chills , fever and tiredness .
there were 211 males ( 61% ) and 135 females ( 39% ) with an age range of 0 to 20 years ( 6.31  4.66 : 10.97 years ) .
the study population was distributed to four age groups , as follow : group i ( 0 - 5 years , n = 192 ) , group ii ( 6 - 10 years , n = 96 ) , group iii ( 11 - 15 years , n = 38 ) , and group iv ( 16 - 20 years , n = 20 ) . a 5 ml blood sample was collected from each individual ; sera was separated and stored at -20c for further examination .
the igm antibodies against ebv vca were evaluated by a standard commercially available elisa kit ( euroimmun , lubeck , germany ) .
descriptive analysis and chi - square tests were used to explain the results and compare between the incidence of ebv infection in different age and sex groups .
the data were analyzed by the spss software ( spss for windows , version 16 , spss inc . , chicago , il , usa ) .
the studied population consisted of 346 suspected patients who had referred to the professor alborzi clinical microbiology research center , namazi hospital , shiraz , southern iran , during march 2007 to march 2011 .
the major clinical manifestations of these patients included painful sore throat , swollen glands , chills , fever and tiredness .
there were 211 males ( 61% ) and 135 females ( 39% ) with an age range of 0 to 20 years ( 6.31  4.66 : 10.97 years ) .
the study population was distributed to four age groups , as follow : group i ( 0 - 5 years , n = 192 ) , group ii ( 6 - 10 years , n = 96 ) , group iii ( 11 - 15 years , n = 38 ) , and group iv ( 16 - 20 years , n = 20 ) .
a 5 ml blood sample was collected from each individual ; sera was separated and stored at -20c for further examination .
the igm antibodies against ebv vca were evaluated by a standard commercially available elisa kit ( euroimmun , lubeck , germany ) .
descriptive analysis and chi - square tests were used to explain the results and compare between the incidence of ebv infection in different age and sex groups .
the data were analyzed by the spss software ( spss for windows , version 16 , spss inc . , chicago , il , usa ) .
out of 346 patients , 104 ( 30.00% ) were positive for ebv vca - igm , from whom 62.5% and 37.5% were males and females , respectively .
there was no significance difference in the incidence of ebv primary infection between males and females ( p > 0.05 ) ( figure 1 ) .
our results showed that 61.5% of ebv vca - igm positive patients belonged to age group i , 30% to age group ii , 5.8% to age group iii and finally 1.9% to age group iv .
statistical analysis revealed that there were no significant differences between age group i ( 64/192 ) and ii ( 32/96 ) , ii ( 32/96 ) and iii ( 6/38 ) , iii ( 6/38 ) and iv ( 2/20 ) ( p > 0.05 ) .
however , the incidence of ebv primary infection was significantly different between age groups i and iii ( p < 0.05 ) and also between age groups i and iv ( p < 0.05 ) ( figure 2 ) .
symptomatic acute ebv primary infection is clinically associated with infectious mononucleosis ( i m ) accompanied by fever , tonsillopharyngitis , hepatosplenomegaly , lymphadenopathy , and the increase of mononuclear blood cell number ( 1 , 14 , 15 ) .
fever , pharyngitis and lymphadenopathy are the classic triad of i m ( 2 , 14 ) . in the present study ,
the most common symptoms of our cases included fever , temperature reaching 40c , sore throat with and without exudates and painful cervical lymphadenopathy .
since the monospot test has an approximate sensitivity and specificity of 85% and 94% for diagnosis of ebv infection , and it may be negative in about 50% of cases under age of 12 ( 1 , 3 ) , definitive diagnosis for ebv infection is based on vca - igm and vca - igg antibodies detection ( 8 , 14 , 16 , 17 ) .
the presence of vca - igm in more than 80% of acute sera is the best indication for confirming ebv primary infection within four to eight weeks since infection , while after this period such indication disappears .
its shortened presence in very young children is related to the lower titer achieved ( 14 , 17 - 19 ) . in an earlier study in the united kingdom ,
92% of ebv infected patients were anti vca - igm positive ( 14 , 16 ) .
our study showed that 30% of 346 cases with typical symptomatic ebv infection were vca - igm positive .  
different population - based studies have reported various prevalence rates of ebv infection in children , from 20% to 80% at age two to three years in different regions . in industrialized and developed countries with high standards of living ,
it was shown that in malaysian children , primary infection indicated by emergence of ebv igm antibody , occurred at four to six months of age , while all children were seropositive by age of eight ( 10 ) . in another study in japan ,
anti vca - igm positive rate in infants with acute primary infection was 25% yet 80% in those four years of age and over ( 23 ) . in this study ,
the highest incidence of ebv primary infection belonged to the age group i ( 0 - 5 years ) with a rate of 61.5% .
this percentage decreased with age and reached 1.9 % by the age 16 - 20 years .
previous studies declared that there is no difference in ebv seroprevalence between different genders in children ( 24 - 26 ) . in the present study ,
there was also no significance difference in ebv primary infection incidence between males and females . to sum up
, we can conclude that accurate and on time diagnosis of ebv primary infection in both children and adolescents will help prevent unnecessary hospitalization , medication , and incorrect medical decisions .
moreover , in most cases , the best means to differentiate ebv primary infection from other infections and malignancies is by detection of igm specific antibodies against viral capsid antigen ( vca - igm ) in the sera . among different serological assays ,
background : many children become infected with epstein - barr virus ( ebv ) during their childhood . since the clinical profile of ebv primary infection is challenging , it is important to use the best diagnostic clinical means . 
 detection of igm against viral capsid antigen ( vca ) by elisa has been shown to be a reliable method.objectives:this study was conducted to demonstrate the incidence of ebv primary infection , among suspected patients referred to namazi hospital , shiraz , iran.patients and methods : the sample included 346 patients with an age range of 0 to 20 years ( 6.31  4.66 : 10.97 years ) . 
 a volume of 5 ml of blood was collected from each case . 
 the patients were divided to four age groups . 
 the sera were tested for the presence of vca - igm by commercially available anti - ebv - vca elisa kit.results:the results indicated that 104 ( 30.0% ) of the patients were ebv vca igm positive , with no significant difference in the incidence of ebv primary infection between males and females . however , the incidence of infection was significantly different between age group i ( 0 - 5 years ) and iii ( 11 - 15 years ) , and also between age group i ( 0 - 5 years ) and iv ( 16 - 20 years ) ( p < 0.05).conclusions : considering the results , accurate and on time diagnosis of ebv primary infection in both children and adolescents will help prevent unnecessary hospitalization , medication and incorrect medical decisions . 
 in addition , this will decrease further treatment costs and related medical procedures .