21 referensi rubella

7/25/2019 21 referensi rubella

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{149}N618 . .00 onfh 5 {149}7o ,,hs l0 -l3m onths 3-IS yeasASE OF IN FA NTS A ND C HIL DR EN

FI G 1. Incidence of rubella virus isola tion cor-

re lated w ith age in infants and children w ith con-

genita l rubella (data accum ulated from studies by

N ew Y ork U nivers ity R ubella Research G roup).

1. Rubella virus infection acquired in

utero generally persists throughout preg-

nancy and is presen t atbirth. V irus has

been recovered from fetal tissues obta ined

by therapeutic abortions perform ed w eeks

and m onths after m aternal rubella infec-

tion. A t birth , v irus has been cultured from

pharyngeal secre tions , urine , cerebrospinal

flu id, and m any other tissues.

2. Infants w ith congenita l rubella infec-

tion m ay con tinue to shed virus for m onths

after birth. Recent s tudies by our group

indicate that virus-shedding decreases

w ith advancing age. Prelim inary data are

sum m arized in Figure 1. Positive cultures

were detected in 63 of 119 infants during

the first m onth of life ; in 31 of 68 infants ,

5 to 7 m onths of age; in 7 of 84 infants,

10 to 13 m onths old , and in none of 20

children, 3 to 15 years old.

33 5

D IA G N O S IS A N D M A N A G E M E N T : C O N G E N IT A L R U B E L L A

Louis Z . C ooper, M .D., n Sau l K rugm an , M .D .

D epartmen t of Pediatrics Ne w York U niversity School of M edic ine N ew York N Y

I N T R O D U C TO RY N O T E :A discuss ion of som e com m on problem of ped ia tr ics

regu la rly appears as the las t ar ticle preceding the E xperience and R eason

sec tion E ach of these shor t papers is in tended to present current practice in

regard to diagnosis or therapy or both The E ditor w ill w elcom e sugges tions

for desirable topics

T lIE epidem ic of rubella in the UnitedStates in 1964 was one of the m ost

extensive in m edical h istory. It w as in-

evitable that m any susceptible pregnant

w om en w ould be infected. The precise toll

in neonata l death and disability is un-

known. It has been estim ated that 10,000

to 20,000 infants m ay have been born withcongenita l m alform ations.

The tcra togenic effect of rubella infec-

tion acquired in early pregnancy has been

w ell docum ented since G reggs original re-

port in 1941. The turning point in our

knowledge of the pathogenesis of congeni-

ta l rubella occurred in 1962. In that year

rubella virus w as successfully cultivated in

tissue cultu re by W eller and Ncva2and by

Parkm an, B uescher, and A rtenstc in.3 This

s ignificant contribution provided m any in-

vestigators w ith the techniques needed for

the study of the natural his tory of rubella

infection. These studies w ere the subject of

a sem inar at the International Childrens

C enter in Paris in 1964 and a sym posium

a t a join t m ee ting of the A m erican Pedi-

a tric Socie ty and the Society for Pedia tric

R esearch in Philadelphia in 1965.

S U M M A R Y O F R E C E N T A D V A N C E S

N ew observations by m any investigators

have added to our know ledge of the

pathogenesis, c linical aspects, and cpidem -

iological aspects of congenita l rubella in-

fection. These recent advances m ay be

sum m arized as follow s:

A ided by P ublic H ealth S ervice G rant A I-04335 from the N ational Institute of A llergy and Infectious

I)iseases an d a grant from the N ational F oundation-M arch of D im es.

AD D RESS: (L .Z .C. or S .K .) as above, 550 First A venue, N ew Y ork , N.Y . 10016.

P E D I AT R I C S V O L . 37, N o. 2 , F E R U RY 1966

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336 CON GEN ITA L RU BEL L A

T LE I

M A N I F EST A T I O N S O F C O N G E N I T A L H D B E L L A

o m m o n U nc omm on o r Rare

H istory of maternal rubel la Jaundice

L ow birth weight Dermatoglyphi e abnor-

Cataracts malityM c r o p ht h a l mi a Gl a u c o m a

Retinopathy Cl oudy cornea e a f n e s s My o c a r d i a l d a ma g e

Congeni tal heart di sease HepatitisThrombocytopenic p u r p u r a Generalized adenopathyHepatomegaly H emolytic anemia

Splenomegaly H ypoplasti e anemia

B one l esi ons (m etaphyseal Cerebrospinal f l uid pleo-

r a r e f a c t i o n c y t o s i s

La r g e a n t e r i or f o n t a n e l l e S past ic q uad ri par eses

Psychomotor retardation

3. Infants w ith congenital rubel la have

serum rubel la neutral izing antibody ti ters

comparable to those observed in their

mothers. The predominant antibody appears

to be 1gM (19S up to 7 months of age; bythe end of the f irst year, IgG (75) antibody

may be 67 D etectable levels of

neutral izing antibody appear to persist for

many years.8

4. The cl inical aspects of the rubel la

syndrome have been expanded to include

manifestations w hich were not recognized

as rubel la-associated defects prior to the

epidemic of 1964. The various common and

uncommon clinical manifestations of con-

genital rubel la are l isted in Table 1.

5. V irus isolation and neutralizing anti-

body studies have revealed that congenital

rubel la infection can occur in infants w ho

appear to be normal during the early

months of l i fe. A n adequate fol low-up of

infants w ith subcl inical infection is not

avai lable as yet. I t is w ell know n, how ever,

that the recognition of certain defects, suchas deafness, may be delayed.

6. Infants w ith congenital rubel la have

been show n to be contagious. W e are aw are

of 22 instances of rubel la in nurses, doctors,

medical students, and family members w ho

w ere intimately exposed to virus-shedding

infants.

D I G N O S IS O F C O N G E N IT L R U E L L

A diagnosis of congenital rubel la should

be suspected under the fol low ing circum-

stances : 1 maternal history of possible

rubel la or exposure to rubel la in early preg-nancy, and/or (2) the presence of one or

more of the various manifestations of the

rubel la syndrome, as l isted in Table 1.

Final conf irmation of a diagnosis of con-

genital rubel la with or w ithout cl inical

manifestations requires the support of a

virus laboratory. The fol low ing findings, ob-

served singly or in combination, are indic-

ative of a congenital infection: (1 isola-tion of rubel la virus from pharynx, urine,

cerebrospinal f luid or any tissue obtained on

biopsy; (2) the presence and persistence of

rubel la neutral izing antibody in the serum

of an infant over 5 to 6 months of age;

and (3) the identif ication of rubel la neutral-

izing antibody in the 1gM (195) f raction

of serum during early infancy.

M N G E M E N T O F IN F N T S W IT H

C O N G E N IT L R U E L L

The unique problems presented by in-

fants with congenital rubel la have high-

l ighted the need to provide guidel ines for

physicians w ho arc concerned w ith their

care. The fol low ing recommendations repre-sent our opinion based on information

avai lable at the present time.

sol t ion

The primary aim of isolation procedures

for these contagious infants is to prevent

the spread of infection to susceptible

w omen in the early stages of pregnancy.

Recent studies have indicated that intimate

contact is general ly required for the trans-

mission of rubel la. Rubel la virus is very

labi le and easi ly destroyed. The risk of

contracting rubel la via the air-borne route

is probably inconsequential . Consequently,

potential ly susceptible pregnant women

should avoid physical contact with these in-

fants.

I SO L A T I O N I N T H E H O SPI T A L Infants w ith

congenital rubel la should be admitted to a



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ARTICLES 337

separate room. In most hospi tals a private

room may be designated as the isolation

uni t. Per sonnel assigned to this uni t should

be selected on the basis of their immune

status and child-bearing potential . I f virus

laboratory faci l i ties are avai lable, i t w ould

be w ise to screen the staff members for

presence of serum rubel la neutral izing

antibody. Ideal ly, only immune persons

should be assigned to the rubel la unit. A

survey conducted prior to the1964 epi-

dcmic indicated that approximately 85

of w omen attending prenatal clinics w ere

immune to rubel la.10

ISO L AT IO N IN TH E H O M E: N o special pre-

cautions are necessary for the immediate

family. Potential ly susceptible female visi-

tors who may be pregnant should avoidphysical contact w ith the infant during the

period of contagion.

D uration of Iso lation

I f laboratory faci l i ties arc avai lable for

identif ication of rubel la virus, infants

should be considered contagious unti l nega-

tive throat sw ab and urine cul tures have

been obtained. A s indicated in Figure 1,

evidence of virus-shedding may disappear

by one month in some infants; on the other

hand, i t may be present in a small number

of infants at one year. If laboratory faci l i -

ties are not avai lable, one can only spec-

ulate about the probabil i ty that an infant

is contagious. The data presented in Figure

1 may be used as a guide.

M anagem ent in the N eonatal P eriod

Special attention should be devoted to

the skin, eyes, heart, and abdomen during

the dai ly examination.

SKIN: Thrombocytopcnic purpura is a

common manifestation of severe congenital

rubel la. In some cases, the purpura, w hich

appears during the first 24 hours af ter

birth, may be extensive and persistent for

weeks. In others, the petcchiac may be

scanty and transient. If the new born infant

is not examined dai ly, the latter lesions

may not be seen. A lthough w e are not

aw are of any control led study, w e do not

bel ieve administration of corticosteroids has

al tered the course of the thrombocytopenic

purpura. Spontaneous hemorrhage has been

rare in spi te of the severi ty of the throm-

hocytopenia.

E Y E S : Corneal clouding, if present, may

be transient and easi ly overlooked. If i t per-

sists, this important f inding may indicate

infanti le glaucoma. Ophthalmoscopic cx-

amination is required for detection of the

smaller cataracts as well as for visual ization

of rubel la retinopathy patchy black pig-mentation quite variable in size and loca-

tion). The small rubel la cataract is a cen-

tral lcnticular opaci ty easi ly visual ized with

the + 8 lens held 6 to 8 in. f rom the in-

fant s eye.

HEART: A uscultation for the presence ofa cardiac murmur should be repeated dai ly.

M urmurs are usual ly detected by the end

of the f irst w eek. H ow ever, there may be

a delay of several w eeks.

A B D O M E N : H epatomegaly and spleno-

megaly may be minimal at birth; progres-

sive enlargement occasional ly occurs during

the neonatal period.

Fo llow -up Evaluation

The f requency of pediatric fol low -up cx-

aminations must be based on the cl inical

condition of the infant w ith congenital

rubel la. Since any organ system may be in-

volved by this infection, consul tation f rom

other special i sts is w arranted w hen ab-

normali tics arc f irst suspected. The con-

sul tant can be most ef fective if he has an

opportuni ty to fol low the course of the

disease f rom the beginning. Therapy of

specif ic abnormali ties does not require var-

iation from establ ished pediatric practice.

A s indicated previously, isolation precau-

tions may be indicated.

A ll chi ldren w ith congenital rubel la

should be given audiometric testing. W hen

hearing loss is suspected, even small in-

fants should be evaluated. H owever, this

evaluation may reasonably be deferred un-

ti l age 4 to 5 years in chi ldren w ith appar-

ently normal hearing. Rubella-associated

deafness is usual ly not complete. There-



4/6

CONGENITA L RU BELLA

fore it is quite desirable that hearing aids

be prescribed w hen indicated. A uditory

training should be started during infancy.

There is probably little to be gained

from surgery for the correction of unilateralcataract. W e have found differing opinions

among authorities concerning the optimal

age and type of surgical technique in the

case of bilateral cataracts. Operation before

the age of six months does not appear to

offer any advantage. In contrast surgery by

an ophthalmologist experienced in the man

agement of infantile glaucoma can prevent

blindness if performed early in the course

of this disease.

N o specific therapy is available for treat

ment of the rubella carrier. Since this ap

pears to be a self limiting condition the

possible benefit from any proposed treat

ment program must be carefully measured

against its potential hazard.

S U M M A RY

Studies on the natural history and course

of congenital rubella are currently in prog

ress in various pediatric centers in the

United States. Long term observation of

many infants w ith this disease should clarify

many of the problems difficult to cope with

today. W hen additional information be

comes available a more definitive report on

diagnosis and treatment may be indicated.

The final solution of the rubella problem is

dependent upon the development of a safe

and effective vaccine.

R E F E R E N C E S

1 Gregg N . M. : Congenital cataract follow ing

German measles in the mother. Trans.

Ophthal. S oc . A us t. 3 :3 5 1 94 1.2 W eller T. H. and N eva F. A . : Propagation in

tissue culture of cytopathic agents from pa

tients w ith rubella like illness. Proc . S oc.

Exp. B iol. N ied. 111:215 1962.

3. Parkman P. D . B uescher E. L. and A rten

stein M . S. : Recovery of rubella virus from

army recruits. Proc. S oc. Exp. Biol. M ed.

1 1 1 : 2 2 5 1 9 6 2

4. Seminar on the epidemio logy and prevention

of measles and rubella. A rch. Ges. V irus

forsch. 16:377 1965.

5 Rubella Symposium. A mer. J. D is. Child. 1 10 :

345 1965.

6 . A fford C . A . Jr. : S tudies on antibody in

congenital rubella infections. A mer. J. Dis .Child. 110:455 1955.

7. Bellanti J. A . A rte ns te in M . S . O ls on L . C .B ue sc he r E. L. L uhrs C . E . an d M ilste ad

K. L. : Congenital rubella. Amer. J. D is.

Child. 110:464 1965.

8 P lo tk in S . A . D u dg e on J. A . and Ram sayA . M . : Laboratory studies on rubella and

rubella syndrome. Brit. Med. J. 2 : 1 29 61963.

9. G reen R. H . B alsam o M . R. G ilesJ. P.K rug man S . and M irick G. S .: Studies of

the natural history and prevention of rubella.

Amer. J. D is . C hi ld . 1 10 :3 48 1 96 5.10 . Sever J. L. Schiff G. M . and H ue bne r R .J.:

Frequency of rubella antibody among preg

nant w omen and other animal populations.

O bs te t. G yne c. 2 3:1 53 1 9 64 .



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1966;37;335PediatricsLouis Z. Cooper and Saul Krugman

DIAGNOSIS AND MANAGEMENT: CONGENITAL RUBELLA

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DIAGNOSIS AND MANAGEMENT: CONGENITAL RUBELLA

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