NATIONS UNlES NATIONS ORGANISATION MONDIALE DE LA SANTE t ORLD HEALTH RGANIZATION REGIONAL OFFICE F O THE ~ M ~ D I T E R R A N ~ORIENTALE E M E R N ' MEDITERRANEAN REGIONAL COENITTEE FOR THE EASTERN MFDTTEMEhW Fifth Session Sub-Connittee A of the Regional Connittee for the Eastern deditarranenn, 3t,its nectiqg $n Alexandria last year adopted a r e s o l u t i o n ' requesting the G r g m i z n t i o v t o c o l l e c t experincntnl data on the question of i m u n i t y after vnccination in connection witht1t (a) t h e t i n e taken f o r s a t i s f a c t o r y imnunity t o develop nfter primnry vaccination 3 (b) the t i n e tnken f o r satisfactory i m u n i t y after the rovpccination, a f t e r one year, t w o . y e a r s , t h r e e years and thereaszer, as t h i s has a v e r y i m p o r t a n t bearing on spread. of smallpox f r m one country t o another..I t 1 In rosponse to t h i s request, t h e Regional Director, n f t e r i n v e s t i g a t i n g t h e subject subnits.Cbd results of his investigations! The q u a s t i o n o f i m u n i t y ' a f t c r vaccination a n d revaccination Was previously raised by one of the WH0,Menber S t a t e s d u r i n g t h e f i r s t session of t h e C k i t t e e on I n t e r n a t i o n a l Qaa'rantine in 1953. The Committee, finding t h c t the elucidation of these technical p o i n t s could only be sought from cxpcrts on immunization against s n a l l p o x , recor~ncndcdth2t they be referred t o appropriate experts f o r their observati,ons* This was endorsed later by the Seventh World Health AssenbJy. The Direct or-General, in accordance w i t h the r e q u e s t s of t h e Seventh World Health Assembly and of the Committee on , International Quarantine, consulted a number of experts, including experts in s m l l p o x , virologists, epidemiologists nnvd hygienists, as t o t h e i r views oh t h e sub j o c t . Considerable difference of o p i n i ~ ncane t o l i g h t , due, in part, t o the absence of s u f f i c i e n t f a c t u a l infornation and, in p a r t , t o t h e different meanings attributed to the word fwunitv. However, a comprwise could be made between t h e d i f f e , ~ e n tviewst . t h e word innunity in t h e e b o v ~connection being interpreted 2s meaning resistance to tho dlsease~ The r e s u l t s of these consultations were then subnitted t o the aecmd s u s s i o n of tho C m i t t e e on International Quarantine ( ~ctober-~ovembe~ 1954) The Comittce, a f t e r studying then expressed i t s opinion in its second r e p o r t to the Eighth World Health dsseubly, notine; "....- experts could ~ i v eno ~ x a c t _ i n f o r n a t i o n which could apply t o a l l individual Conseauentls, the rules i n Aa~endip4 of t h e Remlntions ( ~ n t o m t i o n a l cases. Certificate of Vaccination a ~ a i n s t~nallrrox) though t h e v n u lack a fim s c i e n t i f i c basis, a r o nevertheless ndniniatrativcls e x ~ e d i e n tin order t~ avoid d e l a y t o ~ e r s m son an international vovaae" The opinions of experts on the s u b j e c t may be summarized in the following: 1. As regards the'first question concerning the tihe taken f o r s a t i s f a c t o r y ~ i m n l t yt o develop a f t e r prihary vaccination, it is generally accepted t h a t by the time the vaccinal vesicle is formed the vaccinated person is resistant t o smallpox. This takes 5 7 days in the' primary - reaction* ~ o w k v e r ,this statement must be q u a l i f i e d if the perscai has been exposed t o s m a l l p a . As a general-rule, persons who develop &,vesicle.as t h e r e s u l t of .primary vaccination may be considered to have s a t i s f a c t o r y resistance about, six days (5-7 days) a f t e r vaccination, but there will be the occasional person who may develop smallpox up t o twelve days after vaccination as a rmult of exposure before or on the, day of.vaccinetion. The present period of e i g h t days after vaccination for the International Certificaks to become v a l i d se,ems t o be a r e a s o n a b l e compromise- 2. As f o r the development of satisfactory immunity after revacaination, t h i s depends in t h e firgt p l a c e on the time, elapsed since the previous vaccipation and the loss of resistance to smallpox after this vaccination. T h i s loss of resistance can b e assessed mainly in two wayst by the cutaneous r e a c t i o n t o revaccination, and by epidemi 01o g i c a l pnd c linioal obaervati an. (a) It is generally accepted that there is a r e l a t i o n s h i p between t h e cutaneous.seaction of an individual to revaccirmation and h i s resistance t o smallpox. A primary r e a c t i o n indicates tMt l i t t l e or no resistance was present a t the time of vaccinatim1 the accelprated reaction indicates partial resistance ; the allergic (immediate) repction or t h e absence of any reaction may indicate s u b s t a n t i a l resistance t o the disease prwided that it is .certain that the vaccine used was fully active and p o p e r l s amlied The results of experiments on these lines have shown that t w o years after successful vaccination~aboutone in twenty vaccinated pcrsons haye little o r no resistmce t o rmaccjnation; about me-third have p a r t i a l resistance, and &out two-thirds have s u b s t a n t i a l resistance* Five years after .successful vaccination about one in twolve have l i t t l e or no resistance t o pe- vgccination b u t only n b q t one-thir4 s t i l l have substantial resistance, the remainder having p a r t i a l resistance. (b) Epidernio10,gical and clinical absemations have also shown that t h e r e is a wide v a r i a t i o n in t h e degree and duration of resistance t o smallpox following vqccieati,on r The variation depends in part on t h e r,eaponse of the individual as shown abwe in t h e r e s u l t s o f ~ m a c c i n a t i o n , and i n p a r t on t h e demee and i n t e n s i t y of exposure t o i n f e c t i o n and & the characteristics of t h e infect in^ variola virus. Therefore, individual exceptions m , t o t h o general r u l e must be anticipated. With t h a t p r w i s o it day be said t h a t cpidemi 01ogical and clinical observations suggest that t h e r e s i s t a n c e t o smallpox of successfully vaccinated persons may have decreased within a p e r i o d of between t w o and f i v e years t b such an extent that an appreciable number of them w i l l be susceptible t o i n f e b t i o n , although o degree of resistance may p e r s i s t as shown b y attenuatton o f the disease. There is reasonable agreement between the t w o methods of assessment. Since cmwrmisc is always necessary in t h e application of' observed facts t o cdmini s tra€iivo r c g u l a ti ons, it would appear that the present pcrtod of v a l i d i t y of t h e vaccination c e r t i f i c a t e of t h r e e years is reasonable. The development of s a t i s f a c t o r y , immunity after revaccination presents no problem in the cass of persons who have n o t been exposed t o smallpox. It is only i n t h c case of those who have been exposed t o smallpox,t h a t the problem i s more difficult Experience has shown t h a t m a c c i n a t i o n of a susceptible person before exposure w i l l prevent the disease and that an the first or second day after exposure t o smallpox may, but by no means always does, p r o t e c t against revaccination the disease, though it usually p r d u c e s some m o d i f i c a t i o n of it. on thc t h i r d and fourth day after exposure may produce some m o d i f i c a t i o n but. will . n o t usually prevent t h e disease in a susceptible person. Rev*ccinatFon It f o l l o w s from what is mentioned above that .a person who is successfully revaccinated before a p e r i o d of three years since the previous vac.cinati on has expired, mny reas onably be conaiaered t o s a t l s f a c t o r i l y protected against smallpox for a f u r t h e r three-year p e r i o d fron t h e day of revaccination^ be If, on the o t h e r hana, revaccination at 1engthening.periods.nYter thls time has expired, an increasing i a performed p r o p o r t i o n of persons must be assuned t o be susceptible t o infection gt t h e f i n e ~f revaccination, and therefore cannot be c o n s i d e r e d satlsfaotorily protected immediately on revacclnntion. Since , . t h e average #incubstdon .,period of smllpox is twelve , days L., there l w j J l be q , p e r i o d ,dpring which it is uncertain whether such an exgoewd p e p o n has ,,been.spcc~~ssruLly protected o r no&,by rovacpi,nntlon. klearly a compromise is necessary f o r thcs smll b u t important group of those viho'have been ebposed 'to smllpox. The number of dzys a f t e r revaccination accepted' as giving a reasonable nargin af s a f e f j f o r this group wbuld appear t o be an adninistrativq and n o t 'h technicdl decision. 16 should, liowever, be stressed tHat since p r o t c c t i & by ~ a c c i n a t i ~ ' d e p e n * dins - p a r t on t h e ~rasponse of t h e individual and in part rm .the $qgree of exposure ~a,yariola,both f a c t o r s being very y n r i a b l e , , w h t e v e r decision taken a b s o l u t e sccuriky cannot be assured. It is n o t e ~ o r f hthat ~ the Eighth World Health Assembly, by its resolution 012 I International Quamntine r e f e r r e d t o t h e Committee on International Quarantine f o r further consideration, t h e question of the progressive loas o f inmwlity f o l l o w i n g vaccination and t h e tine and degree of development of imnunity f o l l o w i n e revsocination. The ~ e $ i o n a iD i r e c t o r w i l l f o l l o w u p this matter and i-nfdm t h e Regional Camitteemofany f u r t h e r d e v e l o p q a f s .
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