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  • 8/2/2019 Cytomegalovirus Transmission in Special-Care Centers

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    1993;91;79PediatricsWu

    Chen-Yang Shen, Whi-Wen Chang, Shu-Fen Chang, Eng-Shang Huang and Cheng-WenChildren

    Cytomegalovirus Transmission in Special-Care Centers for Mentally Retarded

    http://pediatrics.aappublications.org/content/91/1/79

    the World Wide Web at:The online version of this article, along with updated information and services, is located on

    ISSN: 0031-4005. Online ISSN: 1098-4275.

    PrintIllinois, 60007. Copyright 1993 by the American Academy of Pediatrics. All rights reserved.by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarkedPEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,

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    PED IA TR ICS V o l. 91 N o. 1 Janu ary 1 993 79

    Cy tom ega lov iru s T ran sm iss ion in Spec ia l-C are C en te rs fo r M enta llyR etarded C h ild ren

    C hen-Y ang Sh en , P hD ; W hi-W en C hang ; S hu -F en C h ang , M S ; E ng -Shan g H uang , P hD ; andC heng -W en W u, M D , PhD

    ABSTRACT . Th is s tudy aim ed to determ ine wheth ersp ec ia l-ca re cen ters for m en ta lly re ta rded ch ild ren a reh igh -r isk se tt in gs for cy tom ega lov iru s (CM V ) tran sm is-s io n . S erum and u r ine sp ec im en s ob ta in ed from 31 1 m en -ta lly re ta rded ch ild ren aged 3 to 12 in th ree cen ters w erecom pared for CM V serop ositiv ity and CM V v iru r ia w ithsp ec im en s from 360 norm a l ch ild ren o f th e sam e ages. Ase ro pos itiv ity ra te o f73 .5% and a v iru r ia ra te o f 8 .7%w ere fo und am on g the ch ildren a tten d in g sp ecia l-carecen ters . T hese rates w ere signif ican tly h igh er than th e59 .2% seropos itiv ity and 1 .7% viru ria fou nd am ong nor-m al ch ild ren . B y lo g ist ic regression analysis , it w asshow n that th e preva len ce of CM V virur ia in th e c las s/cen ter w a s on e o f th e m ost im p or tan t de term in an ts foracqu iring CM V infec tion . T he da ta su ggest th at acqu isi-tion o f CM V from playm ates or c la s sm ates occurs fre -quen tly in sp ecia l-care cen ters and tha t hor izon ta l tran s-m ission of v iru s is th e m ost p lau sib le exp lanation for th eh ig her preva len ce o f CM V in fec tio n am on g m enta lly re-tard ed ch ild ren . Ped ia tr ics 1993;91 :79-82 ; cy tomega lo v i -rus , men ta lly r eta rd ed ch ild ren , ch ild ca re cen te rs .

    ABBREV IA TION S. CM V , cytom ega lov irus ; PC R , p olym e rasech ain re act ion .

    Cytom eg a lov irus (CM V ), a m em ber o f the hum anherpesv irus group , rem ain s the m os t comm on causeo f co ngen ita l v ira l in fectio n . A cqu isitio n o f CM Vinfectio n appea rs to requ ire c lose o r in tim a te con tac tw ith ind iv idu als exc re tin g CM V in the ir s aliv a, u r ine ,o r o th er sec re tions . Inc rea sing ep idem io lo g ic and v i-ro log ic ev iden ce ind ica te s tha t day -care cen te rs a reh ig h -risk se ttings fo r CM V transm issio n . In m anystud ie s , CM V infec tion h as been d em onstra ted to bem o re comm on am ong young ch ild ren in g roup carethan in h om e care .2 In add ition , v irus sam ple s re -cove red from ind iv idu al ch ild ren in the sam e day-care cen ter m ay show id en tical pa tte rn s a fte r re str ic-tion enzym e d ig es tion .4 F ew er da ta are ava ilab leconce rn ing the risk o f acq u irin g CM V in fec tion incen te rs fo r the m en ta lly hand icapp ed . In on e stu dy ,no sig n ifican t co rre latio n w as fo und b etw een thep reva len ce o f CM V urina ry shedd ing in ch ild ren andthe typ e of cen te r (reg u la r d ay -ca re cen te r vs d ev el-opm en ta lly de lay ed cen te r) .5 Furthe r stud ie s are re -From the Ins titu te of B iom edical Sc iences , A cad em ia S in ica , T a iw an,epub-lic of C hina ; and Dep artm ent of M ic ro bio lo gy an d Immunolog y, U nive rsityof N o rth C aro lina, C hapel H ill.R eceived for publicatio n Feb 24 , 1992; acc ep ted Ju l 9, 199 2.R eprin t reque s ts to (C .-Y .S .) Ins titu te of B iom edical Sc ien ce s, A cadem iaS in ic a, T aip ei, 11529, T a iw an.PED IA TR IC S (IS SN 0(131 4005 ). C opy righ t 993 by th e Am eric an A cad-cm v of Pedia tric s.

    qu ired to de term in e w heth e r th e lack of d iffe ren ce inv ira l shedd ing rep re sen ts a g en e ra l ep id em io lo g ictrend or m erely g eo grap h ic v ariab ility in v irus trans -mission .

    The purpo se of th is study w as to determ ine th epreva len ces o f CM V seropo sitiv ity an d CM V viru riain ch ild ren in cen te rs fo r th e m en ta lly reta rded an d tocom pare these p rev alen ces w ith tho se in a reg u la rday -care cen te r an d a prelim ina ry scho o l, in o rde r toeva lua te the im po rtance o f in tracen te r tran sm iss ionof CM V in sp ec ia l-ca re cen te rs fo r m en ta lly re ta rdedch i ld ren .

    MATER IALS AND M ETHODSTh ree h und red eleven m entally re tard ed ch ild ren from three

    sp ecial-c are c en ters for th e m entally re tard ed an d 360 no rm al ch il-d ren from one regu lar day-c are cen ter and one pre lim ina ry schoo lw ere enro lled fo r th is s tudy . A ll the cen te rs an d the schoo l w ere inm etro po lita n T aip ei, T aiw an , an d a ll the ch ild ren w ere be tw een th eag es of 3 an d 12 . B ased on th e B ine t-S im on in te llig enc e scale ,ch ild ren in th e retarded g rou p w e re class ifie d in th e cate go ries ofm ild or m ode rate /seve re m enta l reta rd ation . N inety -fo ur (30% ) ofth e m enta lly reta rded ch ild ren bo ard ed at scho ol and th e o th ersliv ed a t hom e. B ased o n m ed ica l re cords, no en ro l led ch ild renw e re k now n to hav e a d iagn osis of cong en ita l CM V .

    A fte r re ceiv in g in form ed consen t, w e in terv iew ed th e p aren tsof each s tud y su bje ct to co llec t in form ation o n dem og rap hic an dlifesty le ch ara cter istics, hy g ien ic pract ices , fe ed in g m eth ods , andth e pre sen ce o f y oung child ren in th e h om e. U rine spec im ens w e reco lle cte d from eve ry ch ild . Se rum sp ec im ens w e re co lle cted f romall no rm al ch ild ren and w e re ran dom ly co lle cte d from a to tal o f170 retarded ch ildren from th e three cente rs. U rine sp ec im en sw ere co llec ted 1 m on th ea rlie r th an se rum spec im ens . A n ti-CM VIg G an tibo dy w as de tec ted us ing a comm ercia l en zym e- link edim muno sorben t assay (CMV SIA , S igm a , S t L ouis, M O ). Sam p lesw ith absorb anc e greater th an th e m anufa ctu rers re com m end edcu tof f w ere con sid ered p osi tiv e for an ti-CM V Ig G an tibo dy . C y-tom eg alo v irus v iru ria w as iden tified by th e pre sen ce o f the CM V -specific im m ediate -ea rly gene sequence am plified by the poly-m erase ch ain rea ctio n (PCR ). T he p rim ers an d PCR p ro toco lem ployed fo r CM V detection h ave b een d esc rib ed prev ious ly7 7an d the spe cific ity an d sens itiv ity of th e PCR p ro toco l fo r CM VDNA detect ion w e re eva lua ted in ou r la bo rato ry . T he pair o f prim -ers used cou ld d ete ct al l the v ira l iso la tes te ste d so far , w ith asen sitiv ity of 1 infected ce ll ou t of 1 000 000; th is assay gave co n-siste n tly negative resu lts w h en it w as per form ed on DNA o f re-la ted hum an he rpe s v iru ses . In ad dit ion , w e as ses sed th e sens itiv -ity an d spe cific ity o f the p rim ers b y com pa ring the resu lts o f v ira liso la t ion and PCR . Fo r th is com par iso n , 1 9 ur ine sam ple s fromin fan ts w ith co ngenita l CMV in fect ion or susp ected CM V -in du cedhepatitis w ere su b jecte d to v iru s iso la tion andCR using the pa iro f pr im e rs. C ytom ega lov irus w as iso late d from 15 of 19 sp ec i-m ens , w h ile 16 o f 1 9 w e re PCR positive . In th is ca se , the PCR tes tp icked u p all the p osi tive sam ples th at had b een id en tifie d byv irus iso lation . S pec im ens f rom ch ild ren k now n to b e n onshed-d ers o f CM V , and w ho w ere seronega tive for CM V , w ere used asn ega tive con tro ls fo r the as say .

    S in ce ea ch ch ild had been in the sam e cen ter or cla ss fo r at lea stI y ear , the preva len ce of CMV viruria in a cla ss or c en ter w a s u sed

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    80 C YT O M E G AL O V IR U S T R AN SM ISS IO N

    to def ine the expo sure to CMV that each study subject m ight haveexperienced. B ased on prev ious finding s indicating that the rate o fCMV excre tion ranges from 1% to 2 .4% among children o f sim ilarage in the same area of Taiwan,8 the environmental CMV expo surew as def ined as high if the prevalence w as g reater than I in 15children; moderate if the prevalence w as betw een 0 and I in 15 ;and low if no one in the class or center shed CMV in urine.U nivariate analy sis and multiple lo gis tic regress ion analysis w eredone to determ ine the risk factors for CMV seropositiv ity . In thisstudy , w e res tric ted our goal to making inferences about the e ffe cto f the setting in which retarded children had been exposed toCMV . The cons ideration o f bio lo g ic plausibility w as the most im -po rtant criterion fo r inc lusion o f variable s in the log is tic mode l.There fore, except for the fac tor o f different se ttings for CMV ex-posure (measured as the prevalence o f CMV v iruria in a c lass o rcenter), al l know n risk factors for acquiring CMV infection w ereincluded in the lo gis tic model. Known risk facto rs included age,so cio economic status (indicated by fam ily income and schoo ly ears o f childrens father), and the presence o f siblings at home. Abackward elimination strategy was employ ed to sele ct the optimalmode l.9 In addition, univ ariate analy sis fo r CMV viruria w as doneto de term ine risk factors for urinary CMV shedding .

    R E S U L T SA n t i-C M V IgG a n t ib od y w a s fo u n d in 59 .2% (213 /

    360) o f n o r m a l ch ild r en a n din 73 .5% (125 /170 ) ofmentally re tarded children. The prevalences o f anti-CM V IgG a n t ib o d y in th e t h r ee sp ec ia l-ca r e cen t er sw er e 78 .8% (52 /6 6 ) , 77 .8% (21 /27), and 67 .5% (52/77); n o sign if ica n t d iffer en ce w a s fou n d am on g cen -ters (P = .27 ) . The influence o f s ix known or sus-p ec t ed va r ia b le s on se r op osit ive st a t u s is sh ow n inthe Table. B y univariate analys is , four fac tors ap-p ea r ed t o b e sig n ifica n t in in cr ea sin g th e r isk o f b e in gC M V ser o p o sit ive : o ld e r a g e, b e in g m en t a lly r e -t a r d ed , b o a r d in g a t s ch o o l, a n d b ein g in a cen t e r /class w here CMV viruria w as more prevalent. B ylo g istic reg ression analys is , w ith contro l for otherknow n risk fac tors, children in an environmentw h er e C M V v ir u r ia w a s m or e p r eva len t h a d a n in -

    creased risk o f being CMV seropositiv e (risk ratio1 .7 ; confidence interval, 1 .1 to 2 .7 ), though age (riskratio = 2 .1 ; confidence interval, 1 .6 to 2 .9 ) also re -mained a statistically significant risk fac tor.

    T h e r e la t ion s b e tw een d iffer en t se t t in gs fo rre tarded/normal children and the age-spec ific prey-alences o f seropositiv ity or v iruria are illustrated inthe Figure. The seroprevalence increased w ith age inboth groups. 1 -low ever, the rate of increase w ashigher in the retarded children in special-care centersthan in no rmal children. The prevalence o f v iruriaamong normal children decreased w ith age , but theprevalence of v iruria among mentally re tarded chil-dren in spec ial-care centers remained at a lev el o f 8%or higher in different age groups .

    U rinary shedding o f CMV w as found in 8 .7% o fmentally retarded children, w hich was significantlyhigher than the 1 .7% shedding rate in no rmal chil-dren (P < . 01 ) . D ifferences betw een indiv idual spe-c ial-care centers w ere no tignificant (P = .32 ). A sexpected, childrens shedding status w as strongly as-soc iated w ith the ir env ironment, and the risk of be-ing a CMV shedder w as much higher for children ina center/c lass w here CMV viruria w as highly prey-alent (P < .01). Cytomegalov irus v iruria w as moreprevalent among children boarding at schoo l than athome (7 .5% vs 4 .5%). How ever, the difference wasnot statis tically significant (P = .2 2 ) . In our results , noassoc iation was found betw een CMV viruria and age(P = .77 ) or soc ioeconomic status (P = .8 2). U nexpect-edly , the presence of siblings at home did no t appearto carry risk fo r urinary shedding of CMVP = . 47 ) .

    D I SCU S S IONOur results demonstrate that the prevalence of

    CM V vir u r ia a n d of se r o p osit iv it y am on g ch ild r en

    T A B L E . Risk Fac tors A ssessed in Re lation to A nti-Cy tomegalov irus IgG A ntibody S tatus*Risk Factor N o. S eropos itiv e/

    N o. Tes ted (%)P Value

    . .Unovarsate . -MultsvarsateAge, y

    3- 5 85/1 66 (5 1 .2 )

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    .- A g e

    w9 - 1 2

    ART IC LES 81

    CcDeID0

    10 0

    8O

    60#{149}

    40

    20

    03- 5 6 - 8

    F ig 1. A ge-speci f i c p r evalen ce of an t ibody to cy tom egalov i r us andcytom ega lovirus v iruria in child ren aged 3 to 12 in diffe ren t set-t ings: 0 , sero preva len ce o f n orm al ch ild ren in reg u la r scho ol; A ,se rop rev alence of m entally reta rded ch ild ren in spe cial-ca re cen -ter ; #{149},viru ria in n orm al ch ild ren in regu lar schoo l; A , v iru ria inre tard ed ch ild ren in spec ial-care cen ter .

    a tten d in g specia l-ca re cen ters fo r the m en ta lly re -t ar ded w er e sign i f i can t l y h igher t han those of gr oupsof p re scho o l ch ild ren and schoo lch ild ren of sim ila rages. O u r re su lts also show tha t th e p reva lence o fCM V v i r u r ia in the cen t er /class w as one of the m ostim portan t de term in an ts fo r acqu ir ing CM V in fec -tion . S ince a lm ost all m en ta lly re ta rd ed ch ild ren w erein an env ironm en t in w hich CM V viru ria w as h ig h lyp r evalen t (nam ely , m or e t han I in 15 ch i l d r en in ac la ss/cen ter shed CM V in urine ), w e sugg es t tha tspec ia l-ca re cen te rs fo r the se ch ild ren are h igh -r iskse ttings fo r CM V transm ission . A lth ough deve lop -m en tal delay and low I Q ar e sequelae of congen i talCM V in f ect i on ,10 t he gr eater possib i l i t y of beingCM V ser oposi t i v e obser ved am ong r etar ded ch i l d r enin sp ec ia l-ca re cen te rs cann o t be d irectly a ttribu ted tothe con gen ita l ab norm a lity th at ch a rac ter izes thesech ild ren . In our re su lts , the inc rea se in ra te s o f serop -ositiv ity w ith ag e is su re ly based o n th e inc rea sedlike liho od o f expo su re to CM V over tim e. H ow eve r ,t h er e w as alm ost no d i f fer ence in the p r evalence ofCM V in f ect i on in the youngest age gr oup betw eenno rm a l an d re ta rd ed ch ild ren . T he h igh er se ro p rev -alence obser ved in t he m en tal l y r et ar ded ch i l d r enw as re la ted to th e speed of CM V transm ission am ongthem . T he ratio o f se ro p rev alence am ong ch ild ren incen ters fo r th e m en ta lly reta rded vs se rop reva lencein the regu la r day -care cen te r o r the p re lim ina ryschoo l in creased w ith age , from 1 .0 (51 .9% /5 1 .1% ) int h e 3- th r ough 5-year age gr oup t o 1.1 (68.3% /62.1% )in the 6 - th ro ugh 8 -y ea r g roup an d 1 .3 (84 .3% /6 6 .7% )in the 9 - th roug h 12-yea r g rou p . O n th e o th er h an d ,t h e r elat i onsh ip betw een age and shedd ing st at u sm anife sted its elf d iffe ren tly in d iffe ren t se ttings .

    W hereas the p rev alence o f v iru r ia rem a ined a lm ostt h e sam e am ong m en tal l y r etar ded ch i l d r en in d i f -fer en t age gr oups, the p r evalence of v i r u r ia in nor m alprescho o l ch ild ren or schoo lch ild ren w as age -depen-den t, as exp ected , and th e shedd in g ra te d ecreasedw ith inc rea sin g ag e. Th ese observa tion s sug gest tha tacqu isition o f CM V from playm ate s o r cla ssm ate so ccu rred freq uen tly in sp ec ia l-ca re cen te rs , an d in -tracen te r transm issio n of v irus is the m ost p lausib leexp lan a tio n o f the h igh er p reva lence o f CM V infec -tio n am ong m en tally re ta rd ed ch ild ren receiv ing spe -c ia l ca re.

    Our conclu sion , based on t he ser ologic data, i sfu r the r streng thened by our f ind in g tha t ch ild ren ina CM V -p reva len t env ironm en t w ere ve ry lik ely tosh ed CM V . N o ev idence fo r an inc rea sed risk o f v ira lsh edd in g w as fo und in ch ild ren w ith sib lin gs a th om e , sugg esting tha t CM V viru ria w as le ss lik ely tobe caused by hor i zon tal t r ansm ission w i th in the f am -ily in ou r stud y . F urthe r stud ies , d em onstra ting tha tv i r al i solates f r om ind iv idual ch i l d r en w i t h in eachcen ter exh ib i t i d en t i cal r est r i ct i on endonuclease d i -g es tion p a tte rns, w ou ld b e v ery use fu l to co nfirm ou rhypo thesis .

    R ecen tly , D NA am p lifica tion b y PC R has b eensh ow n to be a re liab le p ro cedu re fo r d etec ting CM Vinfectio n . P o lym erase cha in reactio n h as b een u sedf or det ect i ng CM V in f ect i on in pat ien ts w i t h congen -ita l CM V in fec tion , o rgan transp lan ts , o r acqu iredim m unode ficiency syn drom e .7 1 2 4 H ow eve r, in no r-m al ind iv iduals such as ch i l d r en in t he age r angestu d ied (3 th roug h 12), v ery little v irus m ay b e shedin u rine , an d PCR m igh t b e le ss sensitive . G iv en tha t,w e cannot t otal l y r u le ou t the possib i l i t y t hat thesh ed d ing rate s o bse rved in th is stu dy m igh t be low erthan th e ac tua l rate s , and the shedd in g s tatu s o f ch il-d ren m igh t, the refo re, b e m iscla ssif ied . H ow eve r,su ch nond iffe ren tia l m iscla ssif icatio n o f ex posu resta tu s w ou ld b ias th e risk ratio tow ard the nu ll.1 5T her efor e, t he st r ength of the obser ved r elat i onsh ipbetw een ser oposi t i v i t y and env i r onm ent al exposu r eto CM V in th e cu rren t cen te r/c la ss cou ld be a con-se rva tive estim a te .

    I n th i s study , w e used the p r evalence of CM V vim -na obser ved at st udy en r ol lm en t t o r ep r esen t a gen -er al ep idem iologic t r end and to ser ve as an ind icat orof the env i r onm en t t hat a ch i l d m igh t have exper i -enced . A ltho ugh h ig h p reva lence o f CM V viru riaw as cons is ten tly fo und in th e d iffe ren t spec ia l-ca recen te rs , and alth ough know n risk fac to rs fo r CM Vacqu is ition had b een consid e red in da ta an a lysis , th isc ro ss-sec tio na l desig n , theo retica lly , cann o t d istin -gu ish w he the r con tac t w ith a CM V shedd er in thec la ss p receded the d eve lopm en t o f se ro pos itiv ity . It isalso unclear w hether som e of these ch i l d r en acqu i r edCM V p r ior t o en t r y i n t o t h e cen t er s, si n ce CM V se-r ologies and v i r al cu l tu r es w er e not ob t ained at t hetim e of en try in to the cen te rs . S e ria l co llectio n o fsp ec im ens and te sting is requ ired to p rov id e fu rthe rcon firm a tion of o ur find ing .

    T he r i sk of being CM V ser oposi t i v e i s appar en t l yh igher in b r east - fed ch i l d r en t han in bot t l e- fed ch i l -d r en , as dem onst r at ed by ou r analysi s of the subsetof nor m al ch i l d r en in ou r study (67% ser oposi t i v i t y

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    82 CY TOM EGALOV IRU S TRANSM ISS IO N

    fo r b reast-fed vs 42% for bo ttle-fed ). U nexp ec ted ly ,w e cou ld a ttrib u te little se ro pos itiv ity to b reast-feed -ing in th e subset o f re ta rd ed ch ild ren (5 2% for b reast-fed v s 5 6% for b o ttle -fed ) . Th is fin d ing m igh t resu ltfrom the fac t tha t ou r sero lo g ic da ta o rig ina ted fromthe tim e po in ts s ev era l yea rs a fte r feed in g du rin gin fan cy . Ev en so , it is no t lik ely th at re ta rd ed ch ild renw ere m ore like ly to be breas t-fed , re su ltin g in the irobserved h ig he r p reva lence o f CM V serop ositiv ity . Inad d ition , based o n our fin d ing , the p e rcen tage o fch ild ren w ith a h isto ry o f b reast-feed ing is alm ost th esam e in norm a l ch ild ren and in reta rded ch ild ren(47% vs 43% ).

    SUMMARYOur find ings hav e id en tified an in crea sed r isk of

    CM V tran sm ission in sp ec ia l-care cen ters for m en -ta lly reta rded ch ild ren , an d w e hav e a lso cha rac te r-ized assoc ia ted risk facto rs fo r CM V seropo sitiv ity .W e su ggest tha t CM V sero prev alence is sig n if ican tlya sso cia ted w ith g rea ter p rev alence o f v iru r ia in thecen te rs and th at ch ild - to -ch ild transm issio n o ccursm o re o ften in cen te rs ca rin g fo r m en ta lly re ta rd -ed ch ild ren than in regu lar day -ca re cen te rs andschoo ls .

    ACKNOWLEDGMENT STh is s tudy was suppo rted by gran ts D OH 8O -19 and DOH81 -1 3

    from th e D epa rtm ent o f H ealth , T aiw an , R epublic of C hina.W e th an k S how -L in Y ang , G in-M e i L in , an d M aio-F en Chao for

    exc ellen t te chn ica l a ssis tan ce. Th e a ssistan ce of D r C a thy F le tch erin rev ie win g the m anusc rip t is g ratefu lly ackn ow led ged .

    REFERENCES1. S tagno S , Pass R F , Dw orsky M E , A lford C A . C ongenita l an d pe rinata l

    cy tom ega lovirus infec tion . S u mi ti P er i; ta to l. 1983;7 :31-422 . Pass R F, H utto C , R eyno lds DW , P olh ill R B . Increased frequency of

    cytom eg alov irus infection in children in g ro up day ca re .ed ia tr ic s .1 9 8 4 ; 7 4 : 1 2 1 - 1 2 6

    3. Hutto C , R icks R , G a rvie M , Pass R E Epidem iolo gy of cytom eg alov irusin fectio ns in yo ung child ren : d ay ca re vs hom e care .ed ia tr In fec t D in I.1985;4 :149-152

    4 . A d ler SP . T he m olecu la r ep id em io logy of cy tom eg alo v irus tran sm iss ionam ong children a ttend ing a d ay ca re center. In fe ct D in . 3985;152:760-76 8

    5. Jo nes LA , Duk e-Duncan PM , Yeag er A S . C ytom eg alov iral in fectio ns ininfant-todd ler cente rs: c enters for the dev elopm en tally de lay ed v ersusreg ular d ay ca re . I Ir tfe ct D in . 1985;153:953-955

    6. H sia K , Spector DH , L aw rie J, Spe cto r SA . En zym atic am p lific ation o fhum an cytom eg alov iru s sequence s by polym era se chain reactio n . J Cl i n tMic ro ln io l . I 989 ;27:1 802-1 809

    7 . D emm ler G J, B uffo ne G J, Sch im bo r SM , M ay RA . D ete ction of cy tom e-ga lovirus in u rine from new borns by using p olym erase chain reac tionD NA am plifica tio n. I In fe ct D in . 1 98 8; 1 5 6: 11 77 -1 18 4

    8. Shen C Y , C h ang SF , C hang WW , C hao M F, H uang ES , W uW . Cy t ome -ga lovirus S hed ding in Sch ool C h ildren in T a iw an: A nnua l R eport (inC hine se ). Ta ipe i, T aiw an : D ept o f H ealth , T aiw an , R epub lic of C h ina;1990

    9. K leinb aum DC , K upp er LL , M o rg ens tern H .pidem io log ic R esearch:P r inc ip le and Q tva tz tita tio o M eth ods . N ew Y ork , NY : V an N ostrand R e in-hold C o; 1 982 :447-45 6

    10. M e lish M E , H anshaw JB . C ong enital cy tom ega lovirus in fectio n : d eve l-opm enta l prog ress of infants dete cted by rou tine screenin g .JDC .1 9 7 3 ; 1 2 6 : 1 9 0

    11. Saig al S . L uynk 0, L a rk e B , C hern esky M A . The outcom e in ch ildrenw ith co ngenital cy tom ega loviru s infec tion : a lon gitud inal fo llow -u pstudy . A /DC . 1982;136:896-901

    12. Sp ector SA , H sia K , D en aro F , Spector D H . U se o f m o lecular probe s tod ete ct h um an cytom eg alov iru s and hum an immunode ficiency . Cli ,:Cbtenn . 1989;3 5:15 81-l 587

    13. G erna C , Z ip eto D , Pa rea M , et a l. M on itoring of h um an cytom eg alov -irus infec tions and gan cic lovir tre atm ent in heart transplan t re cip ien tsby de term in ation o f v irem ia , an tigen em ia , an d DNA em ia. In fec t D in .1991;164:488-498

    14. O live DM , M ufti SA , S im sek M , Fayez H , N ak ib WA . D irec t de tec tion o fhum an cytom ega lov iru s in urine specim ens from rena l tran sp lan t pa -tien ts fo llow ing polynie ra se cha in reac tion am plifica tion . J M ed V iro l .1 9 8 9 ; 2 9 : 2 3 2 - 2 3 7

    15. B arron B A . The e ffe cts o f m isc lassific atio n on the es tim a tion of rela tiver isk . Biome tr ic s . 1977;33:414-418

    JOHN LOCKE ON A CASE O F CONGEN ITAL HAND ANOM ALY (1678)

    A lth ough Jo hn L ocke (1632-1 704) is u sua lly reco gn ized as on e o f B ritain s fo re-m ost ph ilo sop he rs , he is far le ss kn ow n as an as tu te and know ledgeab le ph ysic ian .Am ong the m ed ica l no tes in the ten vo lum es of h is jou rn als , k ep t be tw een 1675 and1695 , is th e fo llow in g report o f a 3 -yea r-o ld g ir l w ith a con gen ita l h an d anom a ly1 :

    Sat . A ug . 6 1 16781 I saw a litt le g ir le o f 3 ye ars o ld , w ho h ad the rig h t han d very ex traord in ary . Th epa lm e of th e hand w as ins tead o f co ncave , co nvex an d p ro tube ran t. Th e thum b , l ittle fin ger and ringfinge rs of the na tural siz e , th e fore fin ger tw ic e as b ig as ord ina ry , bu t th e s tran ge st an d m os t irre gu larof a ll w as the m iddle fing er w hich w as b ig ger than any m ans ord ina ry th um b, and m uch long er thanany m an s f ing er. It h ad also a gre at na ile p rop ort ion ab le up on it b en t som eth ing backw ard s andtow a rds th e l ittle finge r, v ery w h ite , bu t h ad noe m otion . It w as th e m os t l ike in sh ap e an d b ign esse an dlen g th to a gre at beane cod of an yth ing I know . T he ch ild w as borne thu s. O n ly sin ce i ts b irth th is fin geris g rown in proportio n as th e res t o f th e b ody h ath donne .

    REFERENCE1 . D ew hu rst K . Job ::: L ock e: P hy sic ian an d Ph ilo sop he r. London: T he W ellc om e M edic al L ibrary ; 19 63 :14 0-1 41

    N oted by T .E .C ., Jr ., M D

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    1993;91;79Pediatrics

    WuChen-Yang Shen, Whi-Wen Chang, Shu-Fen Chang, Eng-Shang Huang and Cheng-Wen

    ChildrenCytomegalovirus Transmission in Special-Care Centers for Mentally Retarded

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