WORLD HEALTH ORGANIZATION EXPERT CCM^ITTEE ON YELLO!^ FEVER VACCINE Geneva, 6-13 A p r i l 1957 P r o v i s i o n a l agenda item 8 <*
ORG.\ N:SATI ;.-.\ MONDIALE DE LA SANTÉ VfflO/YFV/ll " 19 March 1957 I'll l . l ,
12
i w . j /
S
OIÎIGINAL: ENGLISH
STATISTICAL ANALYSIS OF INCIDENCE OF ENCEPHALITIS SUBSEQUENT TO 17D VAGCETATION
by K. Ueraura S t a t i s t i c a l Studies S e c t i o n VJHO
Stuart,
quoting the report by Lepine on 17D v a c c i n a t i o n at the I n s t i t u t
Pasteur, P a r i s , s t a t e s that "during 1952-53 there had occurred among 1800 c h i l d r e n l e s s than one year o f age at the time o f v a c c i n a t i o n , f i v e cases o f meningoencephalitis... . I n these cases the period between v a c c i n a t i o n and the onset o f
symptoms v a r i e d from 10 t o 19 days, the d u r a t i o n o f i l l n e s s from 48 hours t o 5 days." I t i s the purpose o f t h i s working note t o examine whether such an
occurrence o f e n c e p h a l i t i s cases among 1800 i n f a n t s cannot be rej^arded merely as a normal occurrence. Figures f o r the occurrence of cases from acute I n f e c t i o u s e n c e p h a l i t i s i n the g e n e r a l p o p u l a t i o n i n France are not a v a i l a b l e t o provide us w i t h an idea of what the normal incidence should have been among 1800 c h i l d r e n i f v a c c i n a t i o n i s presumed t o produce no f u r t h e r i n c i d e n c e . But > : e know that i n France deaths under one year 2 of age due t o acute i n f e c t i o u s e n c e p h a l i t i s dizring 1952-1953 numbered 161, i . e . , about 80 per annum. I n order t o estimate the number o f cases which could have
produced 80 deaths, ve apply the r a t i o o f cases (278) t o deaths (239) of acute 2 i n f e c t i o u s e n c e p h a l i t i s (both a t a l l ages) r e g i s t e r e d i n England and 'dales during the same p e r i o d . . The number of cases per annum i n France i s thus estiiuated a t :
80-1
-«
S t u a r t , G, (1956) Reactions f o l l o w i n g v a c c i n a t i o n a g a i n s t y e l l o w f e v e r . (Vforld H e a l t h Organization'. Monograph S e r i e s , No, 30, Yellow f e v e r v a c c i n a t i o n , p .l7o
2 Epidem. v i t a l S t a t i s t . Rep.. 1957, 10, 2
WHO/YFV/11 page 2
The estimated p o p u l a t i o n of France under one year of age as at 31 December 1952 being 791 200, the annual incidence r a t e i s : ^^79l"'^200°°° " ^-^'^ population
The number of cases expected to a r i s e during a period of 19 days among 1800 i n f a n t s i s therefore :
The p r o b a b i l i t y t h a t f i v e or more cases occur among 1800 i n f a n t s i n 19 days i s t h e n worked out by means of the f o l l o w i n g f o r m u l a , where x denotes the number of c a s e s : e - ° - ^ ^ ' ^ X 0.0111^ xl The numerical values of P(x) f o r x - 5 or more computed by means
P(x) where e « 2,71828.
of t h i s formula are shown i n the t a b l e below:
X
P(x) 0 . 000 000 000 001 389 0. 000 000 000 000 003 0. 000 000 000 000 000 0. 000 000 000 001 392
5 6 7 or more Total
I t i s seen t h a t the p r o b a b i l i t y f o r f i v e cases or more a r i s i n g from a group o f 1800 -12 i n f a n t s during a p e r i o d of 19 days i s 1,39 x 10 , an exceedingly low f i g u r e which
i n d i c a t e s t h a t i t i s extremely u n l i k e l y t h a t the observed f i v e cases occurred by pure chance. I n the above d i s c u s s i o n we have ignored the p o s s i b l e d i f f e r e n c e i n e p i d e m i o l o g i c a l c o n d i t i o n s between France and England and Wales, p o s s i b l e v a r i a t i o n i n age s p e c i f i c case f a t a l i t y r a t e s , the p o s s i b i l i t y of u n d e r - r e p o r t i n g of cases or deaths, as w e l l as the p o s s i b i l i t y of seasonal or l o c a l v a r i a t i o n i n the incidence r a t e . No data are
WHO/ïFV/11 page 3
a v a i l a b l e i n t h i s connexion except f o r the seasonal v a r i a t i o n i n France which seems to be f a i r l y s m a l l . Nevertheless, i t would be i n t e r e s t i n g t o consider a
h y p o t h e t i c a l incidence r a t e 10 times as high as the rate used above t o a l l o w f o r unknown p o s s i b i l i t i e s . I n t h a t case the p r o b a b i l i t y P(x) would be: „ ,..x
-0.111
Even according t o t h i s formula the p r o b a b i l i t y o f f i v e oases or more would be 1.28 X 10 , s t i l l a very s m a l l q u a n t i t y .
As a c o n c l u s i o n we may s t a t e t h a t the occurrence o f f i v e e n c e p h a l i t i s cases among the 1800 c h i l d r e n vaccinated w i t h 17D vaccine cannot be considered as due t o chance o n l y , unless extremely high l o c a l i n f e c t i o n e x i s t e d at the time of the t r i a l .