children out of step with immunization

8/12/2019 Children Out of Step With Immunization

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1975;55;877PediatricsCarol F. Phillips

Children Out of Step With Immunization

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C h ild re n O u t o f S te p W ith Im m u n iz a tio n

P E D I A T R I C S F O R T H E C LIN IC IA N 8

C ar ol F P hillip s M D

F rom th e D epar tm ent of Pedia tric s, U niversity o f V erm on t Co lleg e of M ed icine, Bu rlin gto n

O n e of th e m ost im po rta n t ad va n ce s in m o de rnm edic in e is th e ab ility to p reven t d isea se bya pp rop ria te im m u n iz a tion . B y m e an s o f im m un o-p rop hy lax is m an y fo rm e rly d re a de d d ise a se s suc ha s po lio m y elitis , d ip h th eria , an d m e a sles arebeco m ing m ed ica l rar itie s . In fac t, v acc ina tiona ga in st sm a llpo x ha s be e n so su c ce ssfu l tha t it isn o lon ge r co nsid ered necessa ry in the U nitedS ta tes . S ch ed u le s fo r rou tine im m u nizatio ns o fin fan ts are p ub lishe d by the A m e rica n A c ad e m yo f P ed ia tric s a n d a re fa m ilia r to a ll w ho d e live rm ed ic al c are to ch ild re n . T h is sc he du le in clu de sD P T (d iph the ria-te ta nu s a nd pe rtu ss is ) a ndtriv alen t o ra l p o lio v ac cine a t a ge 2 , 4 , an d 6m o nths and a bo oste r o f D P T and po lio a t 18m onth s and p re scho o l. S ub sequen tly tetan us andd iph th eria boo ste rs are g iv en ev ery ten years .M easle s , m um ps, and rube lla a re recom m ended at1 y ea r o f ag e. T he re is n o d iffic u lty in fo llo w ingth is ro u tin e if th e c h ild is see n fo r w e ll-c h ild ca rea t o r n ea r th e re co m m e nd ed sc he du le . T hed ile m m a fo r a ll d oc to rs is th e c h ild w ho re c eiv e ssp o ra d ic cris is ca re o r no c are a t a ll. T h is is th ec h ild w h o is o u t o f s te p w ith im m un iz atio n .R e ce n t s tud ies ha ve p ro v id e d va lua b le in fo rm a -tio n on w ay s tha t the p re sen t im m un iza tionsc he du le s c an b e m od ffied a nd co nso lida te d tom ee t th e ind iv idua l need s o f th ese ch ild ren .

T E T A N U ST e ta nus is an o rga n ism w id e sp rea d in th e so il.

T he e ffec tiv en ess o f te ta nus tox o id w a s w e llp rov en du ring W orld W a r II w h e re ex ten s iveim m un iza tio n o f A m eric a n so ld ie rs v irtua lly elim -m ate d the d ise ase in o u r tro op s. T h e v a cc inebe ca m e so pop u lar tha t, du ring the 1 95 0s a nd1 96 0s , su m m e r c am p s req u ire d y ea rly b oo s ters a so ne o f the re qu ire m e n ts fo r ac c ep ta nc e. E ve ryla cera tio n or in ju ry seen in a ho sp ita l em ergencyroom w as also trea ted w ith a te tanus bo oste r,o cc as io na lly w itho u t de term in ing if a b as ic serie sof tetanu s tox o id had ev e r been g iven . In pa tien tsw ho ha d re c eiv ed freq ue n t bo os te r sho ts , a n

inc rea sin g inc idence o f loca l reac tion s (sw ellin g ,re dne s s , itch ing , an d p ain ) and system ic (u rtica r iala nd a n g io ne u ro tic e de m a) rea c tio ns w e re se e n .S tud ie s show ed th at the se pa tien ts possessede x tre m e ly h ig h le v els o f te tan us an tib od y .

It is ge n era lly ac c ep te d tha t a se rum le ve l o f0 .01 an tito x in un its pe r m il lilite r is su ffic ie n t top ro te c t ag ain s t te tan us . G o ld3 sh ow ed in 1 93 8tha t o ne sh o t o f tetanu s to xo id p rodu ces noim m un ity b u t se rves a s a p rim er. A secondin je c tion , g iv en up to tw o ye ars la te r, w illp rod uc e p ro tec tiv e le v els o f an tib od y w ith in 5 to14 da ys . P ee b les e t a l.4 s tud ie d the a n tibo dy le ve lp rod uc ed by va ry in g n um be rs o f in je c tion s o fte tanus toxo id a n d the le ng th o f p ro te c tionp rov ide d b y th e se im m un iza tio ns . T he ir s tud ycon sisted m ain ly o f pa tien ts hav ing a w ell-docu -m e nte d h isto ry o f fo u r o r m o re te tan us to xo idin jec tions (usu ally th ree be fo re the age o f 7m o n ths and a bo oste r 12 m o nths la te r) . In th esepa tien ts th ey sh ow ed th at te tanus an tibo dy w ase x tre m e ly lo ng -las tin g a nd tha t the se p atien tsw ere p ro ba b ly p ro te cted fo r 3 0 y ea rs . W ith a9 9 .9% co nfide nc e, th ey w o u ld b e p ro tec te d fo r12 .3 ye a rs . H is s tu dy g rou p in clud ed te n ch ild re nw h o h ad re c eiv ed o n ly th re e te tan us to xo idim m uniza tions in ea rly in fancy and no boo ste rs .T hese p a tien ts had ad eq ua te an tib ody leve ls bu tha d th e s te e pe st ra te o f fa ll-o ff o f an tibo dy .A na lys is show s they w ere p robab ly p ro tec ted fo rabo u t n ine o r ten yea rs . T hese s tud ie s sh owc lea rly th at (1 ) te tan us is a go od im m u niz in gagen t w h ich produ ces stab le an tib ody prov id inglon g-term p ro tec tion ; (2 ) in te rru p tion of theim m u n iz a t io n sc he du le doe s no t a ffe ct theresu lting im m un ity ( the re is no need to re sta r t

(R ece ived A u gus t 21 ; rev ision accep ted fo r p ub licationN ovem ber 1 1 , 1974 .)A D D R E S S F O R R E P R IN T S : D ep artm en t o f P ed ia tric s ,U niversity o f V erm on t C ollege of M edic ine , B urling to n ,V erm ont 05 401 .

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8 8 IM M U N IZ A T IO N

im m un iza tio ns ; c oun t a ll D P T o r D T sho ts w h end eterm in ing the n um be r o f te ta nu s im m un iza -tion s th e c h ild h as re ce iv ed ); (3 ) afte r a b as icse rie s o f tw o or th re e in jec tio ns p lus a bo os te r,d ip h th eria te tan us bo os te r e ve ry te n y ea rs is ave ry sa fe , co nse rv a tiv e reco m men da tion ;5 a nd (4 )if th e pa tie n t h as h ad fou r do ses o f tox o id an d th eim m un iza tio n h isto ry is w ell doc u m e n te d , the re isn o n ee d to g ive a te tan us b oo s ter a t th e tim e o fin ju ry if th e las t te ta nu s to xo id w as g iv en w ith infiv e ye ars .

DI P HT HE RI AS eve ra l o u tb reak s o f d iph the ria hav e o ccurred

in th e U n ite d S tate s in the pa st fe w y e ars . E p id e -m io lo g ica l in vestiga tion o f o ne of these ou tb reaks6sho w e d no s ta tis tic a l d iffere nc e in th e risk o fac qu irin g d ip h th eria in fec tio n (d efin e d as a th ro atcu ltu re po sit ive fo r d ip h th eria ) in those w ithco m p le te , p art ia l , o r n o p rev io us d iph the riaim m u nizatio n . H ow ev er , th e risk o f c lin ica l d iph -the ria w a s 30 tim e s g rea te r fo r tho se w ith nod ip th en a im m u niza tions an d 11 .5 tim e s g re ate r inthose w ith p artia l im m un izatio ns w h en co m paredw ith th ose w h o w e re fu lly im m u n iz e d . D iph -the ria im m un iz at ion p re ve n ts c lin ic al d ise a se bu tha s n o e ffe ct on th e c arrie r sta te . T he re fo re , h ighpe rcen tages o f im m un e c itiz en s in a com m un ityw ill n o t se rv e to p ro tec t the u n im m un ize d o r top re ve n t ep ide m ics . T he o n ly p ro tec tio n ag ain s td iph the ria is ad eq ua te im m un iza tion o f a ll inch -viduals .

D iph the ria toxo id is a go od im m un iz ing ag en tw h ic h p ro du ce s lo ng -las tin g an tib od y co m p ara b lew ith th a t p rod uc ed b y te ta nu s to xo id . S ch eib el etal.7 s tu d ied 19 1 c h ild ren fo r p ers is te nc e o f d lip h -th e na a nd te ta nus an tib od y . T h ese c h ild renre ce iv ed tw o im m un iza tio ns in ea rly in fan c y an da boo s te r on e ye ar la te r. A t 1 3 to 1 4 y ea rs o f a ge8 8% sti ll h ad p ro te ct ive le ve ls o f a n tib od y a ga in std iph the ria an d 96 % ag ains t te ta nu s .

A d u lt an d pe d ia tric d ip h th eria te tan us p re pa -ra tio ns d iffer on ly in the a m ou n t o f d iph the riato xo id p rese n t . S inc e th ere is go od e v ide nc e tha tth e inc id en ce o f a dv erse rea ct ion s to d iph the riato xo id inc rea ses w ith a ge ,8 th e ad u lt p re p ara tio nis ca refu lly co n tro lled to con ta in n o m o re than 2 ifu n its o f d iph the ria to xo id .9 T he p ed ia tric p rep a-ra tion c on ta in s a va ry in g a m ou n t u p to 25 if un its .P a tie n ts ov er the ag e o f 5 ye ars sh ou ld rec eivea du lt D T . A fte r th e b as ic se rie s p lu s a bo os te r, a bo oste r eve ry ten years is adequa te fo rm a in ten an c e o f im m un ity to b o th te ta nu s a ndd iph the ria . if a p atien t re ce iv es a bo os te r do se o fon ly te ta nu s toxo id a t th e t im e of a n in ju ry , it w illb e d iffic u lt to m a in ta in a de qu ate d ip h th eria a n ti-b o d y sin ce d iph th eria tox o id is n o t ava ilab le

co m m e rcia lly ex c ep t in c om bina tion w ith te tan -us . T h e re fo re D T b oo s ters sho u ld be g ive n inem e rge nc y roo m s w h en te tan us b oo s ters a rede em ed ne ce ssary .

P E R T U S S I SP e rtu ss is is a p ro lo ng ed an d de b ilita tin g d ise a se

at an y ag e b u t m o st o f th e m orta lity oc c u is inin fan ts un de r th e a ge o f 1 ye ar. T he re is go ode v id e nc e tha t a d eq ua te p e rtu ss is im m u n iz a tionc an d ec re ase th e in c ide nc e o f d ise ase . {1 76 } F orim m u n iz a tio ns to p ro tec t the g rou p at h igh es trisk i.e. in fan ts ), they m us t be s ta r ted early .

T he c u rre n tly re c om m e nd ed im m u niz a tionschedu le ca lls fo r a b as ic se rie s o f th ree pe rtu ssisim m u n iz a tio ns a t 2 , 4 , an d 6 m on ths o f a ge a ndtw o b ooste rs . T he basic se rie s is spaced a t tw o-m on th in te rva ls b ec a use it is m o st c on ve n ien t tog iv e po lio v a cc ine a t the sam e tim e , a nd triv ale n to ra l p o lio va c cin e is b es t g ive n at in te rv als o feig h t w eeks o r lo nge r . W ilk ins et haverec en tly sh ow n tha t if the in terv al b e tw e e npe rtu ss is sho ts is 60 da ys o r lon ge r the an tibo dypro duc e d b y tw o im m u niza tio ns is equ al to th atpro duc e d b y th ree m o n th ly in je c tion s a nd isp ro te c tive . A s p re v iou sly m e n tione d , S c he ibe l etal.7 ha v e sh ow n tha t tw o do se s o f d iph the ria-te ta nu s in in fan c y p lus a bo os te r on e ye a r la te rg ive s a d eq ua te long -la s ting p ro te ction ag ains td ip h th eria a n d te ta nu s. T he se d ata su gg es t tha t aba s ic se rie s o f tw o D P T in jec tion s spaced a t lea st6 0 da y s ap art p lu s a b oo ster on e ye a r la te r w ou ldbe a s effe c tive as the cu rren tly re c om m e nd edseries .

N eu ro lo g ic c o m p lic atio ns ha ve b e en re p o rte da fte r p ertu ssis im m u n iz a tion . T h e inc id en ce o fthe se reac tio ns in S w eden is 1 in 3 ,600 .12 C o m p a -ra b le in c ide nc e fig u re s in the U n ite d S ta te s a red iffic u lt to find . T h ere is no e v id e nc e tha t thea dv e rse rea c tion s to p e rtu ss is im m u n iz a tionin cre a se w ith ag e . H o w ev er, the m orta lity o f thed isease is m a in ly in in fan ts . T he re fo re , th e risk o fim m un iza tio n w ou ld se em to be u n ju s tif ie d ino lde r c h ild ren . T he e xa ct a ge at w h ich pe rtu ss isi m m u n i z a ti o n sh ou ld be d iscon tinued is unc lea r.T h e cu rren t rec om m en da tio ns sta te tha t p ertu ss isim m un iza tio n is no t usua lly g ive n a fter ag e 6 .

C O M B IN IN G D P T W IT H V IR A L V A C C IN E SW ith the inc rea sed n um be r o f va cc in es re co m -

m e nd ed fo r rou tine u se , it is de s irab le to be a b leto g iv e sev era l im m un iz ation s at th e sam e tim e .H a rdy et al . 3 h av e sho w n th a t D P T an d ora l p o liova cc in e m a y be sa fe ly g iv e n tog eth e r. In o lde run im m un iz ed c h ild ren it w o u ld b e a dva n tag eo usto g ive D T , p o lio , an d m e a s les s im u ltan eo us ly .

T w o re ce n t s tud ie s ha ve sh ow n th at D P T d o es



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PEDIATRICS F O R THE C LIN IC IAN 8 7 9

not interfere with the immune response tomeasles vaccine. M arshall 4 et al . studied 50Guatemalan children. One haif of the group wasgiven measles Schwartz strain) vaccine alone andthe other one half received DPT and measlesvaccine. The rate of seroconversion for measleswas similar in both groups. In a larger field trialdone in N igeria, Landrigan et a l . 5 studied fourgroups of 125 children each. One group receivedmeasles Schwartz) and smallpox vaccines; thesecond was given yellow fever vaccine only; thethird group received DPT and polio; and group 4received measles, smallpox, yellow fever, D PT ,and polio. A nalysis of the data is not yet completebut measles antibody developed in 92 of thechildren in group 1 and 95 in group 4. There-fore, D PT or DT ), polio, and measles can begiven simultaneously with safety and efficacy.

POL I OThe basic series of Sabin polio immunizations

recommended by the American A cademy ofPediatrics is three doses of trivalent vaccine givenapproximately eight weeks apart and a boosterone year later for a total of four doses. The US.Public H ealth Service recommends a total ofthree doses of vaccine-the first dose at 6 to 12weeks, a second 8 weeks later, and a booster in 8to 12 months. H ardy et al . 3 compared these tworecommended schedules in a large group ofinfants. A fter the booster dose, satisfactory levelsof immunity were achieved in both groups.Therefore, a child can be adequately immunizedwith a schedule of two trivalent oral polio immu-nizations eight weeks apart and a booster oneyear later.

The need for an additional booster dose of poliovaccine at ages 4 to 6 years has not been welldocumented. Occasionally, a child w ill fail todevelop antibody after vaccine has been given.Interference caused by preexisting, asymptomaticenterovirus infection has been suggested as apossible explanation. The rationale for the pre-school booster dose is to immunize children whomay have failed to respond to a previous immuni-zation.

A recent serum survey6 of Syracuse childrenaged 4 to 6 years, most w ith documented historyof immunization against polio, showed that anti-body was not detected to type I polio in 45 andto type I I I in 37 . The serum in this study wasscreened for neutralizing antibody at a dilution of1:8. The authors concluded that these childrenwere apparently susceptible to polio and prob-ably need to be reimmunized.To further study this problem L innemann

aL 7 studied 296 first-grade children and 319

seventh-graders. They confirmed the immuniza-tion history in 82 . W hen serum of these childrenwere screened at a dilution of 1:8, their findingswere in agreement with the Syracuse study.W hen the sera were tested at a dilution of 1:2, anextremely high percentage of children hadneutralizing antibody. The level of antibodyneeded to protect against infection has neverreally been determined. However, it is mostprobable that any detectable level of neutralizingantibody is sufficient to protect the individualfrom disease. This study also showed no differencein antibody titer between those who receivedthree, four, or five doses of vaccine. There was nosignif icant difference in the proportion of chil-dren with low antibody titer when compared bysocioeconomic group. The percentage of childrendemonstrating antibody was similar in the twoage groups, demonstrating that polio antibody islong-lasting.

Large numbers of children were immunized inthe 1950s with inactivated Salk vaccine. A seriesof three monthly injections plus a booster oneyear later was considered adequate immuniza-tion. Serum antibody was produced but no local,gastrointestinal tract immunity was achieved.M any of these children have subsequentlyreceived a complete series of oral polio vaccine.M cCollough et al . 8 studied 200 school-aged chil-dren who had received a complete series of Salkvaccine. They showed that a single dose oftrivalent vaccine provided an adequate boosterresponse in these children.

C O M IN T IO N S O F L IV EV IR L V C CIN ES

Until recently, it has been felt that live viralvaccines could not be given together because theywould interfere with each other and one couldnot be sure that the patient would developimmunity to all-or indeed to any-of the viruses.Oral polio vaccine containing all three types ofpolio virus is now well accepted. W e also knownow that we can safely and effectively combinelive viral vaccines-either in one shot as withmeasles-mumps-rubella vaccine or by differentroutes such as oral polio plus smallpox, measles,and mumps. Stokes et a l . 9 immunized 715 chil-dren aged 7 months to 7 years w ith a vaccinecontaining attenuated measles, mumps and rubel-la virus, combined into a 1-mi injection. Thesechildren had no detectable antibody to any ofthese three viruses. T hey found that reactions,mostly fever, were similar to those seen in chil-dren receiving measles immunization alone. Anti-body to measles developed in 96 of the children,mumps antibody in 95 , and rubella antibody in



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8 8 IMMUN IZAT ION

94 . Other studies have conf i rmed the ef f i cacyand safety of this combination.

The indi v idual vaccines which w e commonlyuse can also be adm inistered simul taneously .Karchmer e t a l. {176 }studied 235 chi l dren aged 9months to 3 years. These chi l dren had receivedtw o doses of oral pol i o prev iously . To one groupthey administered a dose of tr i valent oral pol io, asmal lpox vaccination, and separate injecti ons ofSchw artz strain measles and Jery l L ynn strainmumps subcutaneously . The other chi l drenreceived only one vaccine. The i ncidence ofsubsequent f ever in chi l dren receiv ing al l fourimmunizations was sim i lar to that seen w i thmeasles vaccination alone. The rate of serocon-version was sim i lar w hether the vaccines w eregiven singly or in combination.

There are no publ i shed studies on the ef f i cacyof combi ning in a single sy ringe several indiv i dualvaccines i.e., a measles and a mumps vaccine)made by di f f erent manufacturers. The advantageto the chi ld of receiv ing less shots i s obv ious.H ow ever, unexpected problems have resul tedf rom combining vaccines. I n the late 1950 s aquadruple vaccine contai ning diphtheri a-pertus-sis-tetanus and k i l l ed pol i o v i rus w as marketed.Tests of the potency of several l ots of thi s vaccinewere conducted by the M assachusetts D epart-ment of H eal th. These tests show ed that theanti genici ty of the pertussi s component of thevaccine was unexpectedly low i f the vaccine w asnot used very promptly af ter manufacture.

Immunizations agai nst mumps, measles, andrubel l a are given only once, antibody ti ters arenot usual l y done, and no boosters are given.Therefore, unti l studies have been done to proveef f i cacy, combi ning i ndiv idual vaccines f romdi f f erent manuf acturers into one shot can not berecommended.

Testing for tubercul in reacti v i ty i s consideredimportant in routine w el l -chi ld care. I n addi tion,it i s recommended that chi l dren w ho are know nto be tubercul i n reactors should receive tubercu-losis therapy prior to receiv ing measles vaccine.M any l i ve v i ral vaccines interf ere w i th tubercul intesti ng, 3 usual l y w hen the testi ng i s attemptedseveral days to several w eeks af ter the vaccine isgiven. B erkov i ch and Starr 4 studied the ef f ect ofl i ve poi io type I vaccine on routine tubercul intesting. They found that the f i rst decrease intubercul in sensi t i v i ty occurred four to six weeksaf ter i ngestion of the vaccine and persisted for aslong as two months. Thi s ef f ect was seen in onl yabout one thi rd of the chi l dren tested. I n theremaining tw o thi rds no change occurred.

S U M M A R YFrom the many studies ci ted several poi nts can

be seen.1) D iphtheria and tetanus are good immunizingagents w hich produce long-term immuni ty . 2) Aseries of two diphtheri a-tetanus plus a booster oneyear later i s adequate for basic immunization. 3)Tw o injections of pertussis at least 60 days apartproduce levels of agglutinin that are equal to theamount produced by three injecti ons. 4) Pro-longed time betw een the inj ections of the basicseries of diphtheria-tetanus does not interf erew i th the f inal immuni ty . There is no need to restart a DPT ser ies. 5) A f ter the basic seriesand booster a D T every ten years i s adequate topreserve immuni ty . 6) A series of tw o tr i valentoral pol io doses eight weeks apart and a boosterone year later i s adequate for basic immunizati on.7) L ive v i ral vaccines can be given together, and,i f desi red, oral pol io, smal lpox, measles, andmumps can be given simul taneously .

For a chi ld over the age of 1 year w ho has hadno immunizations, the fol l ow ing schedule couldbe uti l i zed. Fi rst v i si t: D PT or D T ), tr i valentpol i o, tine test; tw o months later: DPT r D T ),tr i valent pol io, measles; and one year later: D T ,tri valent pol io. I f desi red, mumps and rubel l a canalso be given at the time of the second v isi t. W i thcurrent inf ormation avai l able, i t i s now possiblef or us as physicians to adequately immunize inthree v isi ts the chi l d w ho is out of step w i thimmunization.

R E F E R E N C E S1. A meri can A cademy of Pediatri cs: Report of the

Commi ttee on Inf ecti ous D iseases. Evanston, I l l i -nois: A A P 1 9 7 4 p 3

2. Edsal l , C., E l l i ott, M . W ., Peebles, T . C ., L ev ine, L ., andEldred, M . C.: Excessi ve use of tetanus toxoid boost-ers. J A MA 2 0 2 :1 7 1967.

3. Gold, H .: A cti ve Immuni zati on againt tetanus by meansof tetanus toxoid alum -precipi tated ref i ned. J. Lab.Clin . M ed., 23:903, 1938.

4. Peebles, T . C., L ev ine, L ., E ldred, M . C., and Edsal l , C .:Tetanus toxoid emergency boosters. N . EngI . J.M ed., 280:575, 1969.5. Communi cable D isease Center , U .S Publ i c H eal thServ i ce: Recommendati on of the Publ i c H eal thServ i ce A dv i sory Comm i ttee on Immuni zati onPracti ces: D iphther ia and tetanus toxoids andpertussi s vaccine. M orbidi ty and M ortal i ty W eek l yRep., 20:396, 1971

6. M i l ler, L . W ., O lder, J. J., Drake, J., and Z immerman, S.:Diphtheria immuni zation: Ef f ect upon carri ers andthe control of outbreak s. A . J. D is. Chi l d., 123:197,1972

7. Scheibel , I ., B entzon, M . W ., Chri stensen, P. E., andB ieri ng, A .: D urati on of immuni ty to diphtheri a and



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te tan us a fter ac tive im m u nizatio n . A c ta P ath o l.M ic ro b io l. S can d ., 67 :380 , 196 6 .

8 . P ap penhe im er, A . M ., E dsa ll, G ., L aw rence , H . S ., andB an ton , H . J. : A study of reac tion s fo llow ing ad m in-is tra tion of c ru de and pu rified d iph th eria tox o id inan adu lt p opu la tion . A m . J. H yg ., 52 :35 3, 1950 .

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1975;55;877PediatricsCarol F. Phillips

Children Out of Step With Immunization

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