W O R L D H E A L T H O R G A N I Z A T I O N
^ ORGANISATION M O N D I A L E D E L A S A N T É , ;
GUIDE FOR THE CONTROL OF EMERGENCIES CAUSED BY YELLOW FEVER IN AFRICA
VIR/YF/83.13 ENGLISH ONLY
INDtX5?G
Dakar, 30 May t o 3 June 1983
D r a f t agenda i t e m 7.
0
POST-VACCINATION FOLLOW-UP ^ ' ' * P by
T. P. Monath
C e n t e r s f o r D i s e a s e C o n t r o l F o r t C o l l i n s , C o l o r a d o , 80522 USA
Two a s p e c t s d e s e r v e c o n s i d e r a t i o n w i t h r e g a r d t o f o l l o w - u p o f mass y e l l o w f e v e r 17D v a c c i n a t i o n c a m p a i g n s : ( 1 ) d e m o n s t r a t i o n o f v a c c i n e p o t e n c y a t t h e t i m e o f
a d m i n i s t r a t i o n and ( 1 1 ) s u r v e i l l a n c e f o r a d v e r s e r e a c t i o n s . 1. V a c c i n e P o t e n c y .
P r e v i o u s f i e l d t r i a l s have c l e a r l y d e m o n s t r a t e d t h a t 17D v a c c i n e g i v e n by
j e t - i n j e c t i o n o r s y r i n g e and n e e d l e r e s u l t s i n a c c e p t a b l e s e r o c o n v e r s i o n r a t e s ( 9 0 - 9 5 % ) i n A f r i c a n p o p u l a t i o n s ( 1 ) . S e v e r a l f a c t o r s may a f f e c t s e r o c o n v e r s i o n t o t h e v a c c i n e , i n c l u d i n g ( 1 ) n u t r i t i o n a l s t a t e , ( 1 1 ) s i m u l t a n e o u s a d m i n i s t r a t i o n o f o t h e r v a c c i n e s , and ( i i i ) p r e e x i s t i n g h e t e r o l o g o u s f l a v i v i r a l i m m u n i t y . C h i l d r e n w i t h k w a s h i o r k o r show marked i m p a i r m e n t i n a n t i b o d y p r o d u c t i o n a f t e r 17D v a c c i n a t i o n ( 2 ) . P e r s o n s g i v e n 17D and c h o l e r a v a c c i n e s s i m u l t a n e o u s l y o r 1 t o 3 weeks a p a r t showed r e d u c e d a n t i b o d y r e s p o n s e s t o b o t h v a c c i n e s ( 3 , 4) b u t o t h e r v a c c i n e c o m b i n a t i o n s c a n be u s e d w i t h o u t i n t e r f e r e n c e , i n c l u d i n g YF and BCG; YF and s m a l l p o x ; and YF and m e a s l e s ( 1 , 5 ) . V a r i o u s s t u d i e s have shown a r e d u c t i o n i n v a c c i n e s e r o c o n v e r s i o n i n A f r i c a n p o p u l a t i o n g r o u p s w i t h p r e v a c c i n a t i o n h e t e r o l o g o u s f l a v l v i r a l a n t i b o d i e s ( 6 ) . I n t h e s e s t u d i e s , 17D v a c c i n e p r o d u c e d i n mouse b r a i n was g i v e n by s c a r i f i c a t i o n , a method w h i c h may n o t be a s e f f e c t i v e a s s u b c u t a n e o u s i n o c u l a t i o n . I n p e r s o n s g i v e n 17D c h i c k embryo v a c c i n e by t h e s u b c u t a n e o u s r o u t e , p r e e x i s t i n g h e t e r o l o g o u s i i m n u n i t y d i d n o t a p p e a r t o i n t e r f e r e w i t h r a t e o f s e r o c o n v e r s i o n o r r e d u c e n e u t r a l i z i n g a n t i b o d y t i t e r ( 7 ) .
The 17D v a c c i n e s c u r r e n t l y p r o d u c e d a r e q u i t e t h e r m o l a b i l e ( 8 ) and must be s t o r e d and t r a n s p o r t e d u n d e r " c o l d - c h a i n " c o n d i t i o n s . R e s e a r c h o n s t a b l i z e r s h a s been r e p o r t e d ( 9 ) b u t n o t a s y e t i m p l e m e n t e d . B e c a u s e o f t h e c o l d - c h a i n r e s t r i c t i o n , and t h e
p o s s i b i l i t y t h a t p r o p e r r e f r i g e r a t i o n may be i n t e r r r u p t e d d u r i n g emergency c o n t r o l e f f o r t s , i t i s s t r o n g l y recommended ( 1 ) t h a t s e r o c o n v e r s i o n r a t e s be documented i n one o r more a p p r o p r i a t e g r o u p s o f vaccinées, and ( 2 ) t h a t r e p r e s e n t a t i v e a m p o u l e s o f v a c c i n e u s e d i n t h e f i e l d be r e t u r n e d t o a n a p p r o p r i a t e l a b o r a t o r y ( u s u a l l y t h e m a n u f a c t u r e r ) f o r p o t e n c y t e s t i n g .
An example o f a s t u d y o f t h i s s o r t I s f o u n d i n r e f e r e n c e 10. One o r more v i l l a g e s , p r e f e r a b l y a t t h e l i m i t s o f t h e c o l d - c h a i n s h o u l d be s e l e c t e d f o r s t u d y . B l o o d s a m p l e s s h o u l d be o b t a i n e d i m m e d i a t e l y p r i o r t o v a c c i n a t i o n and r e p e a t s a m p l e s a t l e a s t 10 d a y s l a t e r . C a r e i s needed t o p o s i t i v e l y i d e n t i f y e a c h i n d i v i d u a l i n v o l v e d i n t h e s t u d y and t o make c e r t a i n t h a t he/she r e c e i v e s t h e v a c c i n e . I f p o s s i b l e , v i l l a g e s s h o u l d be s e l e c t e d w h i c h a r e o u t s i d e o f a r e a s o f a c t i v e w i l d YF v i r u s t r a n s m i s s i o n . A sample s i z e o f 50 i s recommended; t h i s s h o u l d d i s t i n g u i s h between an u n a c c e p t a b l e ( 7 5 % ) a n d
a c c e p t a b l e ( 9 0 % ) s e r o c o n v e r s i o n r a t e ( 9 5 % c o n f i d e n c e l i m i t s ) .
B l o o d samples s h o u l d be t e s t e d f o r n e u t r a l i z a t i o n n e u t r a l i z i n g a n t i b o d y a t a r e f e r e n c e l a b o r a t o r y .
The issue of this document d o e s not constitute formal publication. It should not be reviewed, a b s t r a c t e d or quoted without the agreement of the World Health Organization. Authors alone are responsible for views e x p r e s s e d in signed articles.
C e document ne constitue p a s une publication.
Il ne doit faire l'objet d ' a u c u n compte rendu ou r é s u m é ni d'aucune citation s a n s l'autorisation de l'Organisation Mondiale de la S a n t é . Les opinions e x p r i m é e s dans les articles s i g n é s n'engagent que leurs auteurs.
VIR/yF/83.1b
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2. A d v e r s e R e a c t i o n s
2.1. G e n e r a l C o n s i d e r a t i o n s . S e r i o u s i d v e r s e r e a c t i o n s t o 17D v a c c i n e a r e s a i d t o be e x t r e m e l y r a r e , a l t h o u g h r e c e n t o b s e r v a t i o n s ( b e l o w ) must now be c o n s i d e r e d . No a b n o r m a l i t i e s i n l i v e r f u n c t i o n t e s t s a r e a s s o c i a t e d w i t h 17D v a c c i n a t i o n ( 1 1 ) ]
A l l e r g i c r e a c t i o n s , I n c l u d i n g s l t l n e r y t h e m a m u l t i f o r m e r . i B h , u r t i c a r i a , a n g i o n e u r o t i c edema and asthma a r e d e s c r i b e d , but a r e c o n s i d e r e d t o o c c u r a t a v e r y l o w r a t e
( a p p r o x i m a t e l y 1:1,000,000) and a r e s e e n p r e d o m i n a n t l y I n p e r s o n s w i t h a n a l l e r g i c h i s t o r y ( e s p e c i a l l y t o e g g s ) ( 1 2 - 1 5 ) . N e u r o l o g i c a l a c c i d e n t s a r e e x t r e m e l y uncommon ( 1 6 , 1 7 ) , V a c c i n a t i o n 'fas r e p o r t e d t o e x a c e r b a t e o r p r o v o k e t h e o n s e t o f m u l t i p l e s c l e r o s i s i n one s t u d y ( 1 8 ) , but t h e s e d a t a a r e open t o o t h e r i n t e r p r e t a t i o n s .
P r e g n a n t Women and Young I n f a n t s . On t h e o r e t i c a l g r o u n d s , t h e s e p e r s o n s a r e u s u a l l y e x c l u d e d from r o u t i n e p r o p h y l a c t i c v a c c i n a t i o n . However, d u r i n g YF e p i d e m i c s , t h e r i s k o f a c q u i r i n g YF i s g e n e r a l l y c o n s i d e r e d a g r e a t e r h a z a r d t h a n t h e t h e o r e t i c a l v a c c i n e r i s k , and t h e s e i n d i v i d u a l s have been Immunized. M o r e o v e r , i t I s u s u a l l y n o t p o s s i b l e t o d i s t i n g u i s h women i n e a r l y p r e g n a n c y d u r i n g mass c a m p a i g n s .
No a d v e r s e e f f e c t s o f 17D v a c c i n e on t h e f e t u s have been r e p o r t e d , but I t s h o u l d be e m p h a s i z e d t h a t c a r e f u l l a r g e - s c a l e f o l l o w - u p s t u d i e s have not been done. Such s t u d i e s c o u l d be a c c o m p l i s h e d i n t h e s e t t i n g of f u t u r e mass v a c c i n a t i o n c a m p a i g n s , b u t would r e q u i r e a s p e c i a l commitment. Because o f t h e I m p o r t a n c e o f t h i s q u e s t i o n and t h e f a c t t h a t i t i s r e p e a t e d l y r a i s e d , such a commitment I s j u s t i f i e d .
S i m i l a r f o l l o w - u p o f i n f a n t s l e s s t h a n 6 months a l s o i s w a r r a n t e d t o e x c l u d e o c c u r r e n c e o f n e u r o l o g i c a l a c c i d e n t s i n t h i s age g r o u p .
R e p o r t s o f S e r i o u s and F a t a l A d v e r s e R e a c t i o n s . Two s e p a r a t e b u t a p p a r e n t l y s i m i l a r e p i s o d e s have been r e p o r t e d ( b u t a r e u n p u b l i s h e d ) .
o f s e v e r e
lÙl'i.
^^^"^ ^ ' " " " ^ ^ ^ ^ ^"«"«^ 28 S e p t e m b e r , 39 c a s e s ( i e t - ï n l e c M o n ?7n . '"'"^^ r e p o r t e d . These o c c u r r e d d u r i n g a ma^s c a m p a i g n v a c c i n a t i o n s T^ r ! P ^ ^ o r m e d . On t h i s b a s i s , t h e i n c i d e n c e was 5.3/100,000 v a c c i ^^rèente^s :îl" b u
/ ''''' ^ " " " ^ ' ^ " ' d i f f e r e n t c l i n i c a l p L t u r e \ \ V ^" ^'^^^'^^ «^^«le c h i l d had a d i s t i n c t v a c c i n a t i o i " L t o r i e f ^ I n f e c t i o n a t t h e i n o c u l a t i o n s i t e ) . P r e v i o u sto t h e 1 : : : n f z : t i : i ^ L ^ l " a : e ^ r ; r ^ h r : : a c ^ ^ r " ^ = ' ~
The c l i n i c a l f e a t u r e s were o u i t-o i i n 4 f « ~ .
o a t i e n t s o r e s e n t e d I n fl u n i f o r m : a f t e r v a c c i n a t i o n I n t h e m o r n i n g , p a t i e n t s p r e s e n t e d i n t h e a f t e r n o o n o r evenlni? u ^ ^ h f ^ , , . . , . J 4 r , 1
( i n o c u l a t i o n s i t e ) i n f l a m m a t i o n (edema, hea ^a ^ n r u r l r t l f' l .
, ^ h o o r i 7 o H T n Q O W ^ T - O J ! neac, p a i n , p r u r i t i s ) . No l y m p h a d e n o p a t h y was
i r f n l L e d
hv c!rH1n '1 i n f l a m m a t i o n e x t e n d e d d l s t a l l y and p r o x l m a l i y . and was f o l l o w e d by c a r d i o v a s c u l a r c o l l a p s e u n r e s p o n s i v e t o c o r t i c o s t e r o i d s A s l n a l e a u t o p s y was P e r f o r m e d . T i s s u e s a t t h e s i t e o f i n f l a m m a t i o n l h : : : r c o Î g e s t î o : ' h e m o r r h a g e , and i s c h e m i c n e c r o s i s o f t h e d e r m i s w i t h I n f i l t r a t i o n o f n e u t r o p h i l s and e o s i n o p h i l s ; d e a t h was due t o c o n g e s t i v e h e a r t f a i l u r e and p u l m o n a r y edema. No m e n t i o n was made o f t h e p r e s e n c e o r a b s e n c e o f v a s c u l i t i s .H e m a t o l o g i c a l e x a m i n a t i o n s r e v e a l e d a m i l d e o s i n o p h i l i a I n 4 p a t i e n t s . T h r e e p a t i e n t s were d i a b e t i c ( 2 d i e d ) . S e r a f r o m 2 o f 6 p a t i e n t s c o n t a i n e d p r e c i p i t a t i n g s u b s t a n c e s i n p r e s e n c e o f 17D v a c c i n e ; 3 o f 6 had an a b n o r m a l serum e l e c t r o p h o r e s i s . F o u r o f 6 s e r a c o n t a i n e d CF a n t i b o d i e s t o n o r m a l c h i c k e n embryo e x t r a c t a t l o w t i t e r s ( 1 : 8 - 1 6 ) .
Two l o t s o f v a c c i n e used i n t h e c a m p a i g n were s t u d i e d a t D a k a r and f o u n d t o c o n t a i n a c c e p t a b l e l e v e l s o f p r o t e i n ( 0 . 2 mg/0.5 m l ) . The e x a c t v a c c i n e l o t s g i v e n t o r e a c t o r s were n o t t e s t e d .
D u r i n g t h e c a m p a i g n , 5 dose v a c c i n e ampoules were pooled t o p r e p a r e 50 and ICQ d o s e s f o r use i n t h e j e t - i n j e c t o r s . I t i s p o s s i b l e that the pooled v a c c i n e c o u l d have been c o n t a m i n a t e d a t t h i s s t a g e . However, I t i s d i f f i c u l t t o i m p l i c a t e b a c t e r i a l
c o n t a m i n a t i o n or a t o x i n i n t h e c l i n i c a l p i c t u r e .
VIR/YF/83.15 page 3 A number of r e v i e w e r s c o n c l u d e d t h a t t h e p i c t u r e most c l o s e l y r e s e m b l e d an a l l e r g i c r e a c t i o n o f t h e a r t h u s t y p e ( i . e Type I I I h y p e r s e n s i t i v i t y r e a c t i o n s i n i t i a t e d by a n t i g e n - a n t i b o d y c o m p l e x e s ) , and t h a t h y p e r s e n s i t i v i t y t o egg p r o t e i n may have been r e s p o n s i b l e . T h i s s o r t of r e a c t i o n i s d i s t i n c t f r o m t h e i m m e d i a t e (Type I )
h y p e r s e n s i t i v i t y r e a c t i o n s u s u a l l y a s s o c i a t e d w i t h YF 17D v a c c i n e i n a t o p i c i n d i v i d u a l s . 2.3.2 Ghana, 1982 (20)
On O c t o b e r 2 6 t h , an u n d e t e r m i n e d number o f s t a f f a t WACRI, New T a f o were v a c c i n a t e d w i t h 17D v a c c i n e ( D a k a r l o t 7 8 5 ) . S i x i n d i v i d u a l s d e v e l o p e d f u l m i n a n t r e a c t i o n s between
2 and 6 h o u r s a f t e r v a c c i n a t i o n ; t h e r e were 2 d e a t h s ( 3 3 . 3 % ) . A l l c a s e s were a d u l t m a l e s 29 t o 51 y e a r s o f age. V a c c i n e was g i v e n f r o m a 50 dose v i a l ; a c c o r d i n g t o the
i n f o r m a t i o n r e c e i v e d ( 2 0 ) , i t was d e l i v e r e d " i n t r a m u s c u l a r l y " . R e a c t i o n s were u n i f o r m : , s w e l l i n g , t e n d e r n e s s and b l i s t e r s a t t h e i n o c u l a t i o n s i t e , f e v e r and h e a d a c h e . D e a t h (2 c a s e s ) f o l l o w e d s e v e r a l h o u r s a f t e r o n s e t o f t h e l o c a l r e a c t i o n .
H i s t o p a t h o l o g i c e x a m i n a t i o n o f t i s s u e s f r o m t h e 2 f a t a l c a s e s was n o t p a r t i c u l a r l y r e v e a l i n g . T h e r e was m i l d - m o d e r a t e i n f l a m m a t i o n ( m i x e d p o l y s and m o n o n u c l e a r c e l l s ) o f t h e s u b c u t a n e o u s t i s s u e t a k e n f r o m t h e s i t e o f i n o c u l a t i o n i n one c a s e . T h e r e was a l s o a q u a n t i t y o f u n i d e n t i f i e d c r y s t a l l i n e m a t e r i a l w h i c h p o l a r i z e d l i g h t and was i n the deep t i s s u e of t h e i n o c u l a t i o n s i t e .
S e r a f r o m A p a t i e n t s were t e s t e d f o r a n t i b o d i e s ; 2 o f t h e 4 had a n t i b o d y p a t t e r n s s u g g e s t i n g t h a t t h e y may have r e c e i v e d YF i m m u n i z a t i o n a t some t i m e b e f o r e the
v a c c i n a t i o n p r o d u c i n g t h e r e a c t i o n .
The c l i n i c a l f e a t u r e s i n t h e s e c a s e s r e s e m b l e t h o s e i n t h e 1974 I v o r y C o a s t e p i s o d e . The o c c u r r e n c e o f a l a r g e number o f a d v e r s e r e a c t i o n s i n a s i n g l e g r o u p o f i n d i v i d u a l s a t one l o c a t i o n , s u g g e s t s an a l l e r g i c r e a c t i o n t o a v a c c i n e c o n t a m i n a n t r a t h e r t h a n egg h y p e r s e n s i t i v i t y . The l o t o f v a c c i n e u s e d i s c u r r e n t l y u n d e r
e x a m i n a t i o n a t D a k a r .
I t w i l l be u s e f u l f o r p a r t i c i p a n t s a t t h i s m e e t i n g t o d i s c u s s t h e s e u n t o w a r d e v e n t s and t o f o r m u l a t e recommendations f o r f u r t h e r s t u d y .
VIR/YF/83. 15 page 4
R e f e r e n c e s
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