4 0 9
ARTIGO/ARTICLE
Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( 5 ) : 4 0 9 -4 1 2 , set-out, 2 0 0 4
Pr evalence of Epstein-Bar r vir us antibodies in healthy childr en and
adolescents in Vitór ia, State of Espír ito Santo, Br azil
Prevalência de anticorpos anti-vírus Epstein-Barr em crianças e adolescentes
saudáveis em Vitória, Estado do Espírito Santo, Brasil
Cecília M. Figueir a-Silva
1and Fausto E.L. Per eir a
2ABSTRACT
Th e p re va le n c e a n d a ge d i stri b u ti o n o f Ep ste i n - Ba rr vi ru s i n f e c ti o n va ri e s i n d i f f e re n t p o p u la ti o n s a n d th e re i s li ttle i n f o rm a ti o n a b o u t th e e p i d e m i o lo gy o f th i s i n f e c ti o n i n Bra zi l. We stu d i e d th e p re va le n c e o f EBV a n ti b o d i e s i n a sa m p le o f 2 8 3 c h i ld re n a n d a d o le sc e n ts b e twe e n 1 a n d 2 1 ye a rs o ld . Th e sa m p le wa s ta k e n f ro m two n e i gh b o rh o o d s i n Vi tó ri a ( c a p i ta l c i ty o f Esp i ri to Sa n to , Bra zi l) . Th e Sã o Pe d ro ( SP) n e i gh b o rh o o d re p re se n te d a n a re a wi th lo we r so c i o e c o n o m i c sta tu s a n d th e Pra i a s ( P) n e i gh b o rh o o d re p re se n te d a n a re a wi th h i gh e r SES. An ti - VCA ( Vi ru s Ca p si d An ti ge n ) a n ti b o d i e s we re d e te c te d b y ELISA a n d a n ti - EBNA ( Ep ste i n - Ba rr Nu c le a r An ti ge n ) a n ti b o d i e s we re d e te c te d b y a n a n ti - c o m p le m e n t i m m u n o f lu o re sc e n c e m e th o d , b o th u si n g c o m m e rc i a l k i ts. Th e re su lts sh o we d a n o ve ra ll p re va le n c e ra te s o f a n ti - VCA a n d a n ti - EBNA o f 7 1 % a n d 5 4 % re sp e c ti ve ly. Th e p re va le n c e f o r b o th a n ti - EBV a n ti b o d i e s wa s h i gh e r a n d p ro b a b ly th e i n f e c ti o n o c c u rre d e a rli e r i n th e SP n e i gh b o rh o o d . Am o n g th e va ri o u s so c i o e c o n o m i c f a c to rs stu d i e d o n ly lo w f a m i ly i n c o m e a n d m a te rn a l e d u c a ti o n le ve l we re si gn i f i c a n tly c o rre la te d wi th a h i gh e r f re q u e n c y o f p o si ti ve se ro lo gy f o r a n ti -VCA. Th e se re su lts d e m o n stra te th a t th e re i s a h i gh p re va le n c e o f EBV a n ti b o d i e s i n c h i ld re n a n d a d o le sc e n ts li vi n g i n Vi tó ri a , th a t o c c u rs m o re f re q u e n tly a t a yo u n ge r a ge i n c h i ld re n f ro m f a m i li e s wi th lo w so c i o e c o n o m i c sta tu s. In a d d i ti o n , th e re su lts d e m o n stra te a n i n te rm e d i a te a ge d i stri b u ti o n p a tte rn b e twe e n th o se re p o rte d i n d e ve lo p e d a n d u n d e rd e ve lo p e d c o u n tri e s.
Ke y-words: Ep ste i n - Ba rr vi ru s. In f e c ti o u s m o n o n u c le o si s. EBV a n ti b o d i e s.
RESUMO
O ví ru s Ep ste i n - Ba rr te m va ri a ç õ e s ge o grá f i c a s n a p re va lê n c i a e n a i d a d e d a so ro c o n ve rsã o , e p o u c o s e stu d o s a b o rd a m e ste s a sp e c to s n o Bra si l. O o b je ti vo d e ste tra b a lh o f o i e stu d a r a p re va lê n c i a d e a n ti c o rp o s a n ti - EBV e m u m a a m o stra d e 2 8 3 c ri a n ç a s e a d o le sc e n te s d e 1 a 2 1 a n o s d e i d a d e , re si d e n te s n o s b a i rro s Sã o Pe d ro ( SP) e Pra i a s ( P) n o m u n i c í p i o d e Vi tó ri a , ES. A p e sq u i sa d e a n ti c o rp o s a n ti - VCA f o i f e i ta p o r ELISA e a d e a n ti - EBNA p o r u m m é to d o d e i m u n o f lu o re sc ê n c i a a n ti c o m p le m e n to , a m b o s u ti li za n d o k i ts c o m e rc i a i s. Os re su lta d o s m o stra ra m 7 1 % d e p o si ti vi d a d e p a ra o a n ti - VCA e 5 4 % p a ra o a n ti - EBNA. A f re q ü ê n c i a d o a n ti - VCA f o i si gn i f i c a ti va m e n te m a i o r e a i d a d e d a so ro c o n ve rsã o m e n o r n a a m o stra d o b a i rro Sã o Pe d ro . Ma i o r f re q ü ê n c i a d e so ro lo gi a p o si ti va p a ra o a n ti - VCA f o i e n c o n tra d a e n tre o s gru p o s d e b a i x a re n d a e m e n o r e sc o la ri d a d e m a te rn a . Esse s re su lta d o s d e m o n stra m q u e a p re va lê n c i a d e a n ti c o rp o s a n ti - EBV é a lta n a p o p u la ç ã o d e Vi tó ri a , se n d o m a i s f re q ü e n te e p re c o c e n a s c ri a n ç a s e a d o le sc e n te s d e f a m í li a s d e b a i x a re n d a e m e n o r e sc o la ri d a d e , c o m c u rva d e d i stri b u i ç ã o e tá ri a i n te rm e d i á ri a e n tre a o b se rva d a e m p a í se s d e se n vo lvi d o s e su b d e se n vo lvi d o s.
Pal avr as-chave s: Ví ru s Ep ste i n - Ba rr. Mo n o n u c le o se i n f e c c i o sa . An ti c o rp o s a n ti - ví ru s Ep ste i n - Ba rr.
1 . De par tme nto de Pe diatr ia do Ce ntr o B io mé dic o da Unive r sidade Fe de r al do Espír ito Santo , Vitó r ia, ES. 2 . Núc le o de Do e nç as Infe c c io sas do Ce ntr o B io mé dic o da Unive r sidade Fe de r al do Espír ito Santo , Vitó r ia, ES.
Addr e ss to: Pr o f. Fausto E. L. Pe r e ir a. Av. Mar e c hal Campo s 1 4 6 8 , Mar uípe , 2 9 0 4 0 - 0 9 1 Vitó r ia, ES. B r azil Fax: 5 5 2 7 3 3 3 5 7 2 0 6
e - mail fe lp@ ndi. ufe s. b r
4 1 0
Figue ir a - Silva CM a nd Pe r e ir a FEL
Altho ugh Epstein-B ar r vir us ( EB V) infec tio n is ub iquito us in all human po pulatio ns, pr imar y EB V infe c tio n var ie s in
r e latio n to po ve r ty and c r o wde d living c o nditio ns. In Afr ic a,
S o u th e a s t As i a a n d La ti n Am e r i c a th e s e r o c o n ve r s i o n
o c c ur s e a r ly in c h ildh o o d a n d in fe c tio us m o n o n uc le o s is
i s le s s fr e q ue n t4 1 2 1 5 1 8 1 9 2 7. I n de ve lo pe d c o un tr ie s th e
s e r o c o n ve r s i o n o c c u r s i n a d o l e s c e n c e a n d i n fe c ti o u s
mo no nuc le o sis is mo r e fr e que nt1 1 1 6 1 9 2 0 2 4 2 6. Ho we ve r e ve n in
de ve lo pe d c o untr ie s pr imar y infe c tio n o c c ur s e ar lie r and
m o n o n u c l e o s i s i s l e s s fr e q u e n t a m o n g c h i l d r e n fr o m impo ve r ishe d familie s in c r o wde d living c o nditio ns2 4.
In B r azil the r e ar e fe w r e po r ts o n the pr e vale nc e o f EB V
infe c tio n and antib o die s in sample s o f he althy pe o ple : thr e e
studie s in the c ity o f São Paulo6 7 8 and o ne amo ng indige no us
native s fr o m the Amazo n r e gio n5 8.
EB V infec tion is c losely assoc iated with B urkitt’s lymphoma, Ho dgk in’s dise ase , naso phar ynge al c ar c ino m a and B c e ll
lymphoma in immunosuppressed patients1 0. Assoc iation of EB V
infec tion with B urkitt’s lymphoma and Hodgkin’s disease in
B razil has been reported in Rec ife2 2, Salvador2 3 and São Paulo9.
B u r k i tt’s l ym p h o m a a n d Ho dgk i n ’s di s e a s e we r e , respec tively, 1 1 .1 % and 5 .7 % of all lymphomas diagnosed in
c hildren aged 1 to 1 5 years old at the Onc ology Division of
Children’s Hospital Nossa Senhora da Gloria in Vitória ( Bortolini
et al, 2 0 0 0 , unpublished data) . This high frequency of lymphomas that are frequently assoc iated with EBV infec tion in the state of
Espir ito Santo le ad us to inve stigate the fr e q ue nc y o f EB V
antibodies in c hildren living in Vitoria, the state c apital. The study
was c arried out by testing anti-VCA ( Virus Capsid Antigen) and anti-EB NA ( Epstein-B arr Nuc lear Antigens) antibodies in two
samples of c hildren from two distinc t soc ioec onomic c onditions.
PATIENTS AND METHODS
From February 1 , 2 0 0 1 to April 3 0 , 2 0 0 1 two random samples of c hildren and adolesc ents aged 1 to 2 1 years old were studied. The c hildren whose parents c onsented to partic ipate in the study were selec ted. One sample ( denominated São Pedro) of 1 4 5 c hildren and adolesc ents originated from the Unit for Health Promotion in the neighborhood of São Pedro where families o f lo w so c io e c o no m ic c o nditio ns live . The o the r sam ple
( deno minated Pr aias) , with 1 3 8 c hildr en and ado lesc ents, originated from nurseries and sc hools of the neighborhoods near the beac h, inc luding Jardim Camburi, Mata da Praia, Jardim da Penha, Praia do Canto and Santa Lúcia, where families with higher soc ioec onomic c onditions are resident. Vitória has 2 9 1 ,8 8 9 inhabitants ( 1 0 0 ,1 3 3 aged 1 to 2 0 years old)2 1. The loc ation of
the neighborhoods is indic ated in Figure 1 .
All c hildr e n o r ado le sc e nts we r e sub j e c te d to a c linic al e valuatio n, and no ne pr e se nte d signs o r sympto ms o f ac ute o r c hr o nic dise ase . Fo r e ac h o ne we c o lle c te d info r matio n r e gar ding so c io e c o no mic c o nditio ns.
Afte r c o nse nt was o b taine d, 5 ml o f b lo o d was c o lle c te d b y ve no punc tur e fr o m e ac h c hild and the se r a we r e sto r e d a t -2 0o C. All se r a we r e te ste d within six mo nths o f sto r age .
Anti-VCA IgG was detected by ELISA method using commercial
kits ( DiasorimTM, Italia) . Anti-EBNA antibodies were detected by an
anti-complement immunofluorescence method using infected and non-infected Raji cells as substrate. ( Kits from BiognostTM, Germany) .
For anti-EBNA antibodies the sera were diluted to 1 :8 0 and results
were considered positive for dilutions higher than 1 :5 . All tests were
performed in the same laboratory at the University Hospital. The
sensitivity and specificity of the tests used are higher than 8 7 .5 % The main cross reaction in ELISA tests for anti-VCA is with rheumatoid
factor, that is more frequent in elderly people17 25.
Statistic al analysis was per fo r med using the so ftwar e SPSS
Ve r sio n 8 .0 fo r Windo ws. Chi squar e o r Fisc he r ’s e xac t te sts we r e use d fo r c o m par iso n o f pr o po r tio ns and Stude nt’s t
te st fo r c o mpar iso n o f me ans. The r e sults we r e c o nside r e d
signific ant fo r p value s le ss than 0 .0 5 .
This researc h was approved by the Ethic s Committee of the
Biomedic al Center of the Federal University of Espirito Santo.
RESULTS
The data o n age , ge nde r and so c io e c o no mic var iab le s fo r
the two sample s studie d ar e sho wn in Tab le 1 . The r e sults o f
the se r o lo gy fo r anti-EB V antib o die s ar e in Tab le s 2 and 3 . Age distr ib utio n o f po sitive se r o lo gy fo r anti-VCA antige n is
in Figur e 2 . Th e c o m pa r is o n o f th e diffe r e n t va r ia b le s
de mo nstr ate s that the two sample s did no t diffe r in r e gar d to ge n d e r a n d a ge d i s tr i b u ti o n s , b u t s h o we d s i gn i fi c a n t
diffe r e nc e s in r e spe c t to inc o me , mate r nal e duc atio n, b o dy weight and height, and duratio n o f breastfeeding. The fac ilities
fo r tr e a te d wa te r a n d s a n ita r y s ys te m a n d th e s ta tus o f immunizatio n we r e similar in b o th sample s. The fr e que nc y
o f p o s i ti ve s e r o l o gy wa s s i gn i fi c a n tl y h i gh e r a n d th e
s e r o c o n ve r s io n o c c ur r e d e a r lie r in c h ildr e n with fa m ily inc o mes less than twenty minimum salar ies and with mater nal
e duc atio n le ve l o f e le me ntar y sc ho o l o r le ss ( Tab le 4 ) .
4 1 1 Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( 5 ) :4 0 9 -4 1 2 , set-out, 2 0 0 4
The sample size was suffic ie nt fo r this c r o ss-se c tio nal
study, if we ac c e pt an alpha e r r o r up to 5 % and a b e ta e r r o r
up to 8 0 % , using an estimated prevalenc e o f 7 0 % , as o bserved
in c hildr e n in São Paulo8. The two sample s we r e no t diffe r e nt
in age and ge nde r b ut diffe r e d in so c io e c o no mic par ame te r s
( in c o m e un de r 2 0 m in im um s a la r ie s , m a te r n a l le ve l o f
Ta ble 1- Ma in so cio eco no m ic a nd dem o gra phic va ria bles studied in two sa m ples o f children a nd a do lescents fro m two different neighbo rho o ds in Vito ria , ES.
São Pedro Praias
Variable ( n = 1 4 5 ) ( n = 1 3 8 ) P value
Age ( mean ± SD) 6 .3 5 ± 4 .5 9 7 .4 2 ± 4 .5 2 0 .0 5 0 *
Gender ( M / F ) 6 6 / 7 9 7 5 / 6 3 0 .1 3 8 * *
Family income in minimum salaries ( n/%)
< 1 0 1 4 5 7
> 1 0 0 ( 0 %) 1 3 1 ( 9 4 .9 %) 0 .0 0 0 * *
Maternal education level ( n/%)
illiterate 0 8 ( 5 .5 %) 0 ( 0 %)
elementary education 1 0 8 ( 7 4 .4 %) 0 ( 0 ) %
secondary education 2 9 ( 2 0 .0 %) 1 9 ( 1 3 .7 %)
university education 0 ( 0 %) 1 1 9 ( 8 6 .2 %) 0 .0 0 0 * *
Body weight ( mean ± SD of percentile value) 4 3 .5 6 ± 2 8 .9 1 5 8 .3 3 ± 2 4 .5 2 0 .0 0 0 *
Height ( mean ± SD of percentile value) 4 7 .8 2 ± 2 7 .7 2 5 8 .6 2 ± 2 7 .9 8 0 .0 0 0 *
* T test; * * χ2
test; SD = standard deviation
Ta ble 2 - Gender distributio n o f preva lence o f a ntibo dies a nti-EBV ( IgG a nti-VCA a nd IgG a nti-EBNA) in a sa m ple o f 283 children a nd a do lescents living in Vitó ria , E. Sa nto , Bra zil.
Anti-VCA Anti-EBNA
male female M + F male female M + F
Serology no
% no
% no
% no
% no
% no
%
Positive 9 5 6 7 .4 1 0 6 7 4 .6 2 0 1 7 1 .1 7 5 5 3 .1 7 8 5 4 .9 1 5 3 5 4 .1
Negative 4 6 3 2 .6 3 6 2 5 .3 8 2 2 8 .9 6 6 4 6 .8 6 4 4 5 .0 1 3 0 4 5 .9
Total 1 4 1 1 4 2 2 8 3 1 4 1 1 4 2 2 8 3
χ2
test: male VCA x female VCA, p = 0 .1 7 8 ; male EBNA x female EBNA, p = 0 .7 6 9 ; M+ F,VCA x M+ F
EBNA, p = 0 .0 0 0 .
e d u c a ti o n , l o we r s ta tu r e a n d we i g h t, d u r a ti o n o f
b r e astfe e ding) . Clinic al e valuatio n sho we d that all c hildr e n we r e asympto matic , with no signs o r sympto ms o f po ssib le
r e c e nt EB V infe c tio n.
DISCUSSION
The overall prevalenc e of anti-EB NA antibodies in Vitória
corresponds well to that which is reported worldwide: progressively
higher prevalence of positive serology with increasing age, reaching a peak in the second decade of life, and without sex bias. The
pattern o f age distributio n o f po sitive sero lo gy in Vito ria is
somewhere between the distributions observed in developed
countries of Europe, United States and Canada1 1 1 3 1 6 1 9 2 0 and those
observed in underdeveloped countries of the African Continent4.
The prevalenc e of anti-VCA antibodies was similar to that
observed in São Paulo8 and lower than that observed in the
indigeno us po pulatio n o f the Amazo n r egio n5. In additio n,
seroconversion occurred later in our sample than in both of these groups, in whom 9 0 % had positive serology by five years of age.
The fr e que nc y o f po sitive se r o lo gy fo r b o th anti-VCA and
anti-EB NA antib o die s was highe r in c hildr e n fr o m São Pe dr o
than in c hildr e n fr o m the Pr aias ne ighb o r ho o d, c o nfir ming
that the pr e vale nc e o f EB V infe c tio n is highe r and pr o b ab ly the pr im ar y infe c tio n o c c ur s e ar lie r in c hildr e n o f lo we r
so c io e c o no mic status. In fac t o ur r e sults de mo nstr ate that
the pr e vale nc e o f EB V antib o die s and the e ar lie r infe c tio n
c o r r e late s with lo w family inc o me and lo w le ve l o f mate r nal e duc atio n ( Tab le 4 ) . In additio n, in the ne ighb o r ho o d o f São
Pe dr o th e fr e q ue n c y o f po s itive s e r o lo gy wa s h igh e r in
c hildr e n that ar e c ar e d fo r in a nur se r y ( data no t sho wn) ,
suppo r ting the im po r tanc e o f c r o wding in fur the r ing the spr e ad o f EB V.
With regard to the anti-EB NA antibodies the results showed
that the r e we r e fe we r po sitive te sts fo r this assay than fo r
Ta ble 3 - Sero lo gy fo r IgG a nti-VCA a nd IgG a nti-EBNA to EBV in children fro m Pra ia s a nd Sã o Pedro neighbo rho o ds, in Vito ria , ES, Bra zil.
Anti-VCA* Anti-EBNA* *
Praias São Pedro Praias São Pedro
Serology no % no % no % no %
Positive 88 6 3 .7 1 1 3 7 7 .9 75 5 4 .3 78 5 3 .7
Negative 50 3 6 .2 32 2 2 .0 63 4 5 .6 67 4 6 .2
Total 1 3 8 1 4 5 1 3 8 1 4 5
*χ2 Test: p = 0 .0 0 9 * * χ2 Test: p = 0 .9 2 5
Ta ble 4 - Distributio n o f a nti-VCA a ntibo dies a cco rding fa m ily inco m e a nd m a terna l level o f educa tio n in children fro m Vito ria , ES, Bra zil.
Anti-VCA + Anti-VCA - p*
Family income* *
< 2 0 minimum salaries 1 2 7 4
> 2 0 minimum salaries 74 41 0 .0 4 0
Maternal level of education
elementary education 93 23
above elementary education 1 0 8 59 0 .0 0 4
*χ2 Test * * Minimum salary is approximately US$ 8 6 .0 0 .
4 1 2
anti-VCA antibodies. However all anti-EBNA positive children had anti-VCA antibodies, whereas some anti-VCA positive cases were
negative for anti-EBNA. We have not reached a good explanation
for these results. Previous studies on EBV prevalence have not
measured anti-EBNA antibodies. Andiman et al1, observed that
anti-EBNA antibodies appeared as late as six months after infection. Yadav et al2 7 also repo rted a lo wer frequenc y o f anti-EB NA
antibodies among infected children in Malasia. It is accepted that
EBNA are less immunogenic and that the anti-EBNA antibodies
appear later after infection than anti-VCA. In fact Sumaya & Ench2 3
in a follow-up of children with clinical manifestations of infectious
mononucleosis demonstrated that anti-EBNA antibodies appeared
later and with lower titers than the anti-VCA antibodies. Thus, it is possible that the seroconversion to EBNA occurs slowly in younger
children. To further support this theory, a study in adults ( blood
bank donors) in Cuba reported similar frequencies of anti-VCA
and anti-EBNA antibodies1 6.
Our r e sults de mo nstr ate that the r e is a high pr e vale nc e
o f EB V antibo dies in c hildren and ado lesc ents living in Vitó ria, that o c c ur s mo r e fr equently at a yo unger age in c hildr en fr o m
familie s with lo w so c io e c o no mic status, with an inte r me diate
age distr ib utio n patte r n b e twe e n tho se r e po r te d in de ve lo pe d
and unde r de ve lo pe d c o untr ie s.
ACKNOWLEDGMENTS
We thank Latha Nagonna for help in editing. This researc h was supported by Hospital Universitário Cassiano Antonio Moraes.
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2 0 . Pe r e ir a MS, B lak e JM, Mac r ae AD. EB vir us antib o dy at diffe r e nt age s. B r itish Me dic al J o ur nal 4 : 5 2 6 - 5 2 7 , 1 9 6 9 .
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