R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 8 ( 2 ) :1 0 5 - 1 0 8 a b r - ju n , 1 9 9 5 .
PREV A LEN CE O F CYTO M EG A LO V IRUS IN FEC TIO N IN
D IFFEREN T PA TIEN T G RO UPS O F A URBA N
U N IV ERSITY IN BRA ZIL
Jo s é H erm ô g en es R o cco S uassu n a, Leila Lo p es Leite an d
Lu cia H elen a C av alh eiro V illela
T his s t u d y s o u g h t f o r e t n d e n c e o f p r e v i o u s C M V in f e c t i o n i n p a t i e n t s o f a g e n e r a l h o s p i t a l s e r v i n g t h e l o w i n c o m e p o p u l a t i o n o f R i o d e fa n e i r ' o . A n e n z y m e i m m u n o a s s a y w a s u s e d t o d e t e c t an t i- C M V a n t i b o d i e s i n 7 1 3 t y p i c a l h o s p i t a l p a t i e n t s c l a s s i f i e d in t o e i g h t d i f f e r e n t g r o u p s . P o s i t i v e t e st s w e r e f o u n d i n 8 7 % o f p r e g n a n t w o m e n , 8 5 % o f n e w b o r n s , 6 1 % o f p e d i a t r i c p a t i e n t s , 7 7 % o f a d o l e s c e n t p a t i e n t s , 8 1 % o f a d u l t p a t i e n t s , 8 7 % o f d i a l y s e d t r a n s p l a n t c a n d i d a t e s , 8 9 % o f k i d n e y d o n o r s , a n d 9 2 % o f p a t i e n t s a f t e r t r a n s p l a n t a t i o n . D e p e n d i n g o f t h e s u b g r o u p s t u d i e d t h e s e r e s u lt s c a r r y d i f f e r e n t m e a n i n g s a n d n e c e s s i t a t e d i f f e r e n t c l i n i c a l a p p r o a c h e s . T h e r is k o f c o n g e n i t a l d i s e a s e is p r o b a b l y l o w i n v ie w o f t h e r e d u c e d n u m b e r o f p r e g n a n t w o m e n s t ill s u s c e p t i b l e t o p r i m a r y i n f e c t i o n . T h e n u m b e r o f p r i m a r y i n f e c t i o n s w ill a l s o b e lo w in t r a n s p l a n t r e c ip ie n t s . H o w e v e r , t h o s e s t ill s u s c e p t i b le w ill a l m o s t c e r t a i n l y a c q u i r e t h e i n f e c t i o n f r o m , t h e i r d o n o r . P r o p h y l a c t i c C M V m a t c h i n g in k i d n e y t r a n s p l a n t a t i o n is n o t a r e a l is t i c a p p r o a c h d u e t o t h e l o w p r o b a b i l i t y o f f i n d i n g p a i r s o f s e r o n e g a t i v e d o n o r s a n d r e c ip ie n t s .
K e y - w o r d s : C y t o m e g a l o v i r u s . C o n g e n i t a l i n f e c t i o n . I m m u n o s u p p r e s s i o n . T r a n s p l a n t a t i o n .
Most adult individuals display serological ev id ence o f p ast cyto m egalo v irus (CMV) infectio n but the great majority o f these episo d es are no t clinically d etected due to their benig n nature. A fter the initial o r primary infection, cytomegalovirus usually persists in the host in a latent, no n-rep licating state. In ind ustrialized co untries ev id ence o f past infectio n is fo und in 40 to 85% o f the adult population3. These figures may vary und er geo graphic and so cio eco no m ic influences so that co ntact w ith CMV usually happens at an earlier ag e and may affect a greater proportion o f the po pulatio n in d ev elo ping co untries12.
Primary cyto megalovirus infectio n can be asso ciated w ith sig nificant mo rbid ity and mortality in certain groups o f individuals. A mong these are includ ed tho se w ith an immature immune system such as fetuses,
tho se w ith im m uno d eficiency as a
Se ç ão d e N e fro lo g ia e T ran sp lan te R e n al an d Lab o rató rio d e Im u n o lo g ia C lín ic a. H o sp ital U n iv ersitário Ped ro Ern e sto . U n iv ersid ad e d o Estad o d o R io d e Jan e iro , Rio d e Jan e iro , RJ, Brasil
A d d r e s s t o : D r. Jo s é H . R. Su assu na. R. P ro fe sso r M an u el Fe rre ira 88/ 304, G áv ea, 2 2 4 5 1 - 0 3 0 R io d e Jan e iro , RJ, Brasil. R e c e b id o p ara p u b lic aç ão e m 18/ 10/ 94.
co nsequence o f d isease such as A IDS patients,
and tho se w ith m ed ically ind uced
im m uno sup p ressio n such as transp lant
recip ients and cancer patients undergoing therapy9.
This study w as designed to investigate the p rev alence o f CMV exp o sure in patients seen at a tertiary hospital serving the low inco me urban po pulatio n o f Rio d e Janeiro . Our purp o se w as no t to d eterm ine the prevalence o f CMV infectio n in the general po pulatio n. We sought instead to identify rates o f exp o sure to CMV fo r typical ■ in-hospital patients such as tho se und ergo ing m ed ical p ro ced ures o r treatments that p o se a risk o f cytomegalovirus transmission o r reactivation.
MATERIAL A ND M ETHO DS
We surveyed all the tests fo r CMV serology from SUS (Sistema Unificado de Saúde - Unified Health System) patients submitted to the clinical immunology labo rato ry o f Hospital Universitário Ped ro Ernesto betw een May 1990 and May 1991- A co m m ercial enzym e immunoassay (A bbo t CMV Total A B EIA Kit,
USA ) that d etects all classes o f
immunoglobulins against cytomegalovirus w as used throughout the study period. Patients
S u a s s u n a JH R , L e it e LL, V ille la LH C . P r e v a le n c e o f c y t o m e g a lo v ir u s in fe c t io n in d i ff e r e n t p a t i e n t g r o u p s o f a u r b a n u n iv e r s it y h o s p it a l in B r a z il. R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 8 :1 0 5 1 0 8 , a b r -ju n , 1 9 9 5 .
w ith acute illness, alread y und er
im m uno sup ressiv e therap y (exc ep t renal transplant recip ients), tho se w ith ma!;pnant d iseases und ergoing treatment, and those w ith confirmed o r susp ected A IDS w ere excluded.
We evaluated 713 patients, and classified them into eight different groups according to the so urce o f the sp ecim en: 1) pregnant w o men, 2) new bo rns, 3) pediatric patients betw een 1 and 11 years old, 4) ad o lescent patients betw een 11 and 18 years o f age, 5) adult patients, 6) renal transplant candidates o n dialysis, 7) live kid ney donors, and 8) renal transplant patients w ith more than 6 months after surgery.
So m e o f the samples w ere submitted to the labo rato ry due to a clinical suspicio n o f CMV infectio n. It is po ssible that this proced ure biased the study through the inclusio n o f patients w ith active infection. This selectio n bias w as partially dealt w ith by only recording the first serum sample for each individual patient. Presumably these samples w ere taken at a tim e w hen sero co nv ersio n had no t hap p ened yet and, therefo re, represent the prev alence fo r that particular group.
The prev alence rates betw een groups o f interest w ere co m pared using the chi-square test. Sig nificance w as set at p < 0.05.
RESULTS
We w ere able to co llect samples from 54 pregnant patients and their offspring (o ne tw in pregnancy). We also co llected 40 additional samples fro m new bo rns transferred to o ur ho sp ital and that had routine determination o f CMV serology. Results fo r the group o f paired mothers and new bo rns sho w ed an almost exact co rresp o nd ence (87.0% vs. 83.6% ) excep t fo r tw o new bo rns w ith abso rbance reading in the undetermined zo ne (Table 1). The 40 o ther new bo rns also sho w ed similar prevalence rates (87.5% ). A ll these results are no t significantly different from each o ther (p > 0.05).
T a b l e 1 - P r e g n a n t m o t h e r s a n d n e i o b o r n s w i t h p o s i t i v e c y t o m e g a l o v i r u s s e r o l o g y .______________________________________ Patient groups N2. tested Na. po sitive %* Pregnant w o m en 54 47 87,0 Offsp ring ** 55 46 83.6 Transfered new bo rns 40 35 87.5 A il new bo rns 95 81 85.2 * p > 0.05 fo r all groups
** o ne tw in pregnancy.
Table 2 show s the results fo r three groups stratified by age. Prevalence rates increased acco rd ing to the age strata the p atient belo nged to. They sho w a trend fo r acquisition o f infection early in life. The rates ho w ev er are significantly d ifferent o nly fo r p ed iatric patients in relation to the adult group (p <
0.001).
T a b l e 2 - H o s p i t a l p a t i e n t s w it h p o s i t i v e c y t o m e g a l o v i r u s s e r o l o g y .
Patient groups Na tested N- po sitiv e % Pediatric patients 118 72 61,0
A d olescent patients 39 30 76,9 A dult patients 121 98 81,0' * p < 0.05 - adult vs ped iatric patients.
Results fo r transplant patients and donors are d epicted o n Table 3- All three groups sho w higher prevalence rates than the group o f general adult in-patients. How ever, w hen compared to those adult patients, the rates are significantly different only fo r patients w hich have undergone transplantation (p < 0.05).
T a b l e 3 - T r a n s p l a n t p a t i e n t s a n d d o n o r s iv it h e v i d e n c e o f p r e v i o u s c y t o m e g a l o v i r u s i n f e c t i o n .
Patient groups No. tested No. positiv e %* Kidney d onors 75 67 89,3 Renal transplant cand idates 146 127 87,0 Renal transplant recip ients 65 60 92,3 .
’ p > 0.05 fo r all groups.
DISCUSSION
Cyto megalic inclusio n d isease o f the new bo rn is alm o st alw ays the result o f transplacental transmission during primary infectio n o f the mother8. Children o f mothers w ith reactivated CMV infection may acquire the virus but these episo des do no t usually result in significant d isease8. Therefo re, kno w led ge abo ut the rates o f pregnant w o m en still susceptible to primary infections in a given population are informative o f the risk o f CMV d isease to their offspring. The lesser these rates are, the lo w er is the risk o f CMV inclusio n disease developing in the new bo rn5.
Our study, as w ell as previous studies in São Paulo and Rio de Janeiro 4 7, have d o cum ented high rates o f p o sitiv e CMV serology in new bo rns suggesting that this w as due to passive transfer o f maternal IgG antibodies. Since w e tested samples from pairs o f p regnant w o m en and their new bo rn
children, the co nco rd ant results is in
agreement w ith this proposition.
S u a s s u n a JH R , L e it e LL, V ille la LH C . P r e v a le n c e o f c y t o m e g a lo v ir u s in fe c t io n in d i ff e r e n t p a t i e n t g r o u p s o f a u r b a n u n iv e r s it y h o s p it a l in B r a z il. R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 8 :1 0 5 1 0 8 , a b r j u n , 1 9 9 5
-For m etho d o lo gical reaso ns, w e w ere no t able to ascertain the exact age o f the patients. Our results therefo re must be taken w ith certain caution. Particularly in children’s group (less than 11 years o f age) the rates o f patients w ith po sitive serology is exp ected to change dramatically early in life. Nevertheless, the data do es serve to demo nstrate that the individuals in the ho sp ital po pulatio n under study did acquire the infectio n early in life, displaying a high p rev alence o f p ast-co ntact w ith CMV. This pattern is characteristic o f lo w inco m e
p o p u latio n s in d e v e lo p in g co untries712.
Our figures fo r adult patients and fo r organ donors are som ew hat lo w er than in another study o f CMV sero lo gy d o ne o n first time blo o d d o no rs in the city o f Rio de Janeiro . That report fo und a 97% prev alence rate o f anti- CMV antibo d ies14. This d iscrep ancy may
p erhap s b e ascribed to the different
m etho d o lo g ies used in the tw o stud ies. How ever, 31% o f tho se same blo o d donors also had sero lo gical evid ence o f co ntact w ith the hepatitis B virus14, suggesting that they w ere so m eho w selected to includ e high risk individuals.
The situation fo r organ (and blo o d ) donors and their recipients is, in relatio n to the risk o f d ev elo p ing clinically significant d isease, diametrically o p p o site to that o f pregnant m o thers and their o ffspring. The viral multiplication o f active infectio n is no t a prerequisite to viral transmission. Latently infected transfused o r transplanted cells can co nv ey the virus sho uld a no n-infected susceptible individual receive them3. These infectio ns can evo lve w ith a very severe clinical co urse, particularly in patients w ith immuno logical d eficiency o r immaturity3. In immunossupressed patients, the num ber o f individuals at risk o f develop ing aggressive primary infectio ns is lo w er in populations w ith a high prev alence o f seropositives. However, in tho se that are still suscep tible, the risk o f d ev elo p ing the d isease rises w ith the prev alence o f p ast-co ntact w ith CMV in the d o no r po pulation.
We and o ther w o rkers in Brazil have previously fo und lo w er rates o f positive CMV sero lo gy in pro spective kidney recipients6 11. This w as p ro bably due to the less sensitive assays used at that time. The current results sho w that only 13% transplant candidates are still suscep tible to primary CMV infection. As
exp ected , kidney dono rs also had a very high prevalence o f po sitive CMV sero lo gy. As a co nsequence, the few susceptible seronegative transplant recipients w ill have a 9 in 10 chance o f being exp o sed to CMV carryed w ithin the graft. Pro bably fo r this reaso n, po st-renal
transp lant p atients sho w ed hig her
serop revalence rates than o ther groups o f individuals.
One last p o int that d eserv es co m m ent is the recent pro po sitio n o f allocating kidneys o f CMV sero negative dono rs to CMV seronegative recipients (CMV matching) in ord er to prevent the o ccurrence o f the more severe primary infectio ns13. O ur results suggest that this app ro ach may no t be practical to implement. From the data presented , o ne can infer that the pro bability o f matching CMV seronegative kidney dono rs and recipients is und er 1.4%. Since, this w ill b e d o ne in add ition to the more
im po rtant im m uno lo gical co m p atibility
matching, this pro ced ure w ill almost certainly severely reduce the chances o f transplantation fo r CMV sero neg ativ e recip ients. O ther strategies such as im munizatio n1 o r drug prophylaxis2 w ill p ro bably b e more practical and effectiv e fo r preventing CMV d isease in seronegative kid ney recipients10.
In co nclusion, the po pulatio n in the general hospital studied sho w ed high rates o f previous co ntact w ith CMV. These figures carry d ifferent meanings and necessitate different clinical appro aches d ep end ing o f the subgroup o f patients the hospital physician is caring for.
RESUMO
E v i d ê n c i a d e i n f e c ç ã o p a s s a d a p o r c it o m e g a l o v í r u s f o i p e s q u i s a d a e m p a c i e n t e s d e u m h o s p i t a l q u e s e r v e à p o p u l a ç ã o d e b a i x a r e n d a n a c i d a d e d o R i o d e f a n e i r o . R e a l i z o u - s e , c o m u m i m u n o e n s a i o e n z i m ã t i c o , a p e s q u i s a d e a n t i c o i p o s an t i- C M V e m 7 1 3 p a c i e n t e s h o s p i t a l a r e s , d i v i d i d o s e m o i t o g r u p o s . A s t a x a s o b s e r v a d a s f o r a m 8 7 % p a r a g r á v i d a s , 8 5 % p a r a r e c é m - n a t o s , 6 1 % p a r a p a c i e n t e s p e d i á t r i c o s , 77% p a r a a d o l e s c e n t e s e 8 1 % p a r a a d u lt o s , 8 7 % p a r a p a c i e n t e s e m d i á l i s e , 8 9 % p a r a d o a d o r e s d e r im e 9 2 % p a r a p a c i e n t e s a p ó s o t r a n s p l a n t e r e n a l . E s t e s r e s u l t a d o s t ê m d i f e r e n t e s s i g n i f i c a d o s e i m p l i c a m e m d i f e r e n t e s a b o r d a g e n s c l í n i c a s d e p e n d e n d o d o s u b g r u p o e s t u d a d o . O r is c o d e i n f e c ç ã o c o n g ê n i t a p r o v a v e l m e n t e é b a i x o d e v i d o a o r e d u z i d o n ú m e r o d e m u l h e r e s g r á v i d a s a i n d a s u s c e p t ív e is a i n f e c ç õ e s p r i m á r i a s . P e l o m e s m o m o t iv o , o n ú m e r o d e i n f e c ç õ e s p r i m á r i a s d e v e r á s e r
S u a s s u n a JH R , L e it e LL, V ille la LH C . P r e v a le n c e o f c y t o m e g a lo v ir u s in fe c t io n in d iff e r e n t p a t i e n t g r o u p s o f a u r b a n u n iv e r s it y h o s p it a l in B r a z il. R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 8 :1 0 5 1 0 8 , a b r -j u n , 1 9 9 5 .
b a i x o n o s t r a n s p l a n t a d o s r e n a i s . E n t r e t a n t o , o s s o r o n e g a t i v o s q u a s e c e r t a m e n t e a d q u i r i r ã o a i n f e c ç ã o d e s e u d o a d o r e a c o m p a t i b i l i z a ç ã o d e d o a d o r e s e r e c e p t o r e s s o r o n e g a t i v o s n ã o d e v e r á s e r u m a a b o r d a g e m r e a l i s t i c a d e v i d o à b a i x a p r o b a b i l i d a d e d e e n c o n t r a r e s t e t ip o d e p a r .
P a l a v r a s - c h a v e s : C i t o m e g a l o v i r u s . I n f e c ç ã o c o n g ê n i t a . I m u n o s u p r e s s ã o . T r an s p la n t e .
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