WORLD H E A L T H ORGANIZATION ORGANISATION MONDIALE DE LA S A N T B ^
^,VIR/RC/74.45 (Arbo) IGLISH ONLY INDtXEO
MEEl'ING OF DIRECTORS OF WHO REFERENCE CENTRESipR ARBOVIRUSES, CHLAMYDIAE AND RICKETTSIAE \ Geneva, 1-5 A p r i l 197^
THE APPARENT BARRIER TO THE EXTENSION OF YELLOW FEVER TO EAST AFRICA AND ASIA. by Wilbur G. Downs and Robert E. Shope Yale U n i v e r s i t y School o f Medicine, New Haven, Connecticut, USA 1. 1.1 DESCRIPTION OF THE BARRIER Yellow fever i s not known to have occurred on the eastern coast of A f r i c a of the
or i n A s i a , i n s p i t e of s u s c e p t i b l e huinan beings and a high prevalence urban vector mosquito, Aedes a e ^ p t i , i n much of the area.
1.2
There i s no f a c t u a l evidence to support an assumption that yellow fever
v i r u s has ever been introduced and therefore that a presumption of a b a r r i e r is valid.
1.3
The existence of a b a r r i e r i s predicated on the assumption that yellow Favoring t h i s , Aedes aegypti which probably
fever v i r u s has been introduced.
o r i g i n a t e d i n A f r i c a (Edwards, 1932) may have been introduced by ships embarking from East A f r i c a and Madagascar a t the end of the nineteenth century 1956). (Smith,
Dengue fever, caused by a v i r u s which i s transmitted a l s o by A. aegypti, In modem times the repeated
was recorded i n A s i a i n 1853 (Carey, D.E., 1 9 7 1 ) .
i n t r o d u c t i o n of Aedes aegypti by ship i s l e s s l i k e l y because of improved s a n i t a t i o n where water i s l e s s frequently stored i n open wooden c o n t a i n e r s . Airplanes,
however, o f f e r frequent and e x c e l l e n t opportunity f o r transport o f Aedes a e g y p t i . which could i n turn carry yellow fever v i r u s .
l.A
Transport of yellow fever on ships t o the New World Involved shipboard
cycles
of man and Aedes aegypti w i t h e i t h e r or both capable of i n i t i a t i n g an urban c y c l e i n r e c e p t i v e areas. Where f o r e s t cycles or conditions f o r f o r e s t c y c l e s d i d not a f t e r seasonal epidemics. Today yellow fever may
e x i s t , yellow fever disappeared
be introduced i n t o a receptive area e i t h e r by I n f e c t e d mosquitoes or by v l r e m i c man. The issue of this document does not constitute formal publication. It should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed article*. Ce document ne constitue pas une publication. Il ne dolt faire l'objet d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation da l'Organisation Mondiale de la Santé. Les opinions exprimées dans les articles signés n'engagent que leurs auteurs.
V I R / i ^ ' j / r * .4'.)
{:\rï:o)
2.
HYPOTHESES TO EXPLAIN BARRIER
2.1
Hypothesis:
dengue v i r u s I n t e r f e r e s w i t h y e l l o w f e v e r v i r u s t r a n s m i s s i o n E p i d e m i c s o f dengue f e v e r o f t e n a l t e r n a t e w i t h y e l l o w fever first.
i n Aedes a e g y p t i . and
i n c a s e s where o v e r l a p o c c u r s , y e l l o w f e v e r t r a n s m i s s i o n may t e r m i n a t e
Dengue v i r u s i n f e c t i o n o f Aedes a e g y p t i may i n t e r f e r e w i t h t r a n s m i s s i o n o f y e l l o w fever v i r u s . That t h i s i s so under l a b o r a t o r y c o n d i t i o n s was r e p o r t e d by r e s u l t s have been r e p r o d u c e d by Hayes (197A). Sabin Itis situa-
(1952) whose e x p e r i m e n t a l
d o u b t f u l t h a t t h i s mechanism would be e f f e c t i v e e x c e p t i n dengue e p i d e m i c t i o n s whero a h i g h p e r c e n t a g e o f Aedes a e g y p t i were i n f e c t e d .
I f the mechanism
c o n t r i b u t e s t o t h e b a r r i e r e f f e c t , t h e n i n t e r r u p t i o n o f dengue t r a n s m i s s i o n by use o f a dengue v a c c i n e might remove the b a r r i e r .
2.2
Hypothesis:
immunity t o h e t e r o l o g o u s
group B a r b o v i r u s e s d i m i n i s h e s
yellow
fever viremia. die.
Dengue immune i n d i v i d u a l s a r e s u s c e p t i b l e t o y e l l o w f e v e r and may i n f e c t i o n o f monkeys w i t h W e s s e l s b r o n (Henderson, ejt a l . , 1967)
Experimental
o r Kyasanur F o r e s t d i s e a s e bility spread
( T h e i l e r and A n d e r s o n , 197A) v i r u s e s d i m i n i s h e d s u s c e p t i W e s s e l s b r o n v i r u s c o u l d s e r v e as a b a r r i e r t o the T h e i l e r and Anderson viremia
to yellow fever v i r u s .
o f f o r e s t y e l l o w f e v e r t o monkeys i n E a s t A f r i c a .
(1974) have shown t h a t r h e s u s monkeys immune t o dengue have a d i m i n i s h e d
when c h a l l e n g e d 6 t o 9 months l a t e r w i t h F r e n c h v i s c e r o t r o p i c y e l l o w f e v e r v i r u s o f A f r i c a n o r i g i n and w i t h JSS y e l l o w f e v e r v i r u s of South American o r i g i n . bodies Asia. in to Anti-
t o m u l t i p l e dengue t y p e s a r e p r e v a l e n t i n y e l l o w f e v e r r e c e p t i v e a r e a s o f Were y e l l o w f e v e r t o be i n t r o d u c e d , human d i s e a s e m i g h t be e x p e c t e d t o o c c u r c o n t a c t s , b u t many o f those i n f e c t e d would n o t d e v e l o p s u f f i c i e n t While experimental viremia
primary
i n f e c t mosquitoes.
e v i d e n c e f a v o r s t h i s h y p o t h e s i s , i t does i n New World popula-
n o t e x p l a i n why y e l l o w f e v e r e p i d e m i c s h i s t o r i c a l l y o c c u r r e d
t i o n s t h a t must c e r t a i n l y have had a h i g h degree o f dengue immunity.
•.•iR/ri;j/7''."'
^^r•( . )
2.3
Hypothesis:
Aedes a e g y p t i o f A s i a and t h e e a s t e r n c o a s t o f A f r i c a have fever
l o w e r y e l l o w f e v e r v i r u s v e c t o r competency than A. a e g y p t i from y e l l o w epidemic areas.
D i n g e r , £t a l . (1929) showed t h a t Aedes a e g y p t i from J a v a
c o u l d t r a n s m i t F r e n c h v i s c e r o t r o p i c y e l l o w f e v e r t o r h e s u s monkeys and the same group demonstrated t h a t t r a n s m i s s i o n c o u l d o c c u r w i t h m o s q u i t o e s i n f e c t e d 147 days p r e v i o u s l y . Aedes a l b o p l c t u s , by c o n t r a s t , were poor v e c t o r s . Philip fever
(1956) demonstrated the a b i l i t y o f A s i a n Aedes a e g y p t i t o t r a n s m i t y e l l o w v i r u s and G i l l e t t & Ross (1955) a l s o made s i m i l a r o b s e r v a t i o n s .
These demon-
s t r a t i o n s were n o t q u a n t i t a t i v e . I . e . t h e y were n o t c o r r e l a t e d w i t h the amount of i n f e c t i n g v i r u s i n the m o s q u i t o , t h e i n f e c t i v e t h r e s h o l d , t h e p e r c e n t a g e of m o s q u i t o e s i n f e c t e d and t h e p e r c e n t a g e o f those i n f e c t e d c a p a b l e o f t r a n s m i t t i n g by b i t e . and These a r e i m p o r t a n t parameters. Data a v a i l a b l e from s t u d i e s o f Anderson
A i t k e n (1974) a r e n o t s u f f i c i e n t t o a l l o w c o n c l u s i o n s , b u t i n d i c a t e t h a t a t i s a poor v e c t o r o f F r e n c h v i s -
l e a s t one s t r a i n of Aedes a e g y p t i from T h a i l a n d c e r o t r o p i c v i r u s under l a b o r a t o r y c o n d i t i o n s .
2.4
Hypothesis:
Yellow
f e v e r v i r u s has been i n t r o d u c e d
t o the O r i e n t b u t human populations i s possible
d i s e a s e was n o t r e c o g n i z e d
and t h e w i l d p r i m a t e and f o r e s t m o s q u i t o of a f o r e s t c y c l e .
were not r e c e p t i v e t o e s t a b l i s h m e n t although not l i k e l y .
This hypothesis occur i n ^\sia.
E p i d e m i c s o f f e v e r and j a u n d i c e
None have
been shown to be y e l l o w f e v e r a l t h o u g h
c e r t a i n l y n o t a l l have been s t u d i e d adequ-
a t e l y and we a r e aware t h a t i n N i g e r i a , a y e l l o w f e v e r e p i d e m i c proceeded f o r 2 months w i t h an e s t i m a t e d 100,000 c a s e s b e f o r e r e c o g n i t i o n (Carey, et a l . , 1972).
Few s t u d i e s o f s u s c e p t i b i l i t y t o y e l l o w f e v e r v i r u s o f A s i a n p r i m a t e s and f o r e s t mosquitoes have been done. but The young Macacus cynomologus was s u s c e p t i b l e
the a d u l t Macacus cynomologus and Macacus n e m e s t r i n u s were much l e s s so
( S c h i i f f n e r , e t a l . , 1930).
3.
SHOULD MEASURES TO PREVENT INTRODUCTION OF YELLOW FEVER TO ASIA BE CONTINUED?
3.1
Probably
the b e s t e v i d e n c e t h a t a t r u e b a r r i e r e x i s t s i s t h e c o n t i n u e d
absence o f y e l l o w f e v e r i n s p i t e of i n c r e a s i n g o p p o r t u n i t i e s f o r i n t r o d u c t i o n , i n c r e a s e d human p o p u l a t i o n and i n c r e a s e d numbers o f Aedes a e g y p t i . t h i s presumed b a r r i e r , WHO c o n t i n u e s implement: I n s p i t e of
t o have a r e s p o n s i b i l i t y t o recoimend and
a. s u r v e i l l a n c e f o r and r e p o r t i n g o f y e l l o w f e v e r on a w o r l d - w i d e basis. b. q u a r a n t i n e of c e r t a i n t r a v e l l e r s .
c. a i r p o r t and s e a p o r t s a n i t a t i o n . d. v a c c i n e s t o c k p i l i n g , q u a l i t y c o n t r o l , and r e s e a r c h on s t a b i l i t y ,
c o n t a m i n a n t s , and d e l i v e r y methods. e. c o n t i n g e n c y plans f o r large scale epidemics.
A.
RESEARCH NEEDS
A.l
Because the b a r r i e r ( i f i t e x i s t s i n f a c t ) m i g h t be b r o k e n by changes i n and s p e c i f i c a l l y by a change i n v e c t o r competency o f
human o r w i l d l i f e e c o l o g y
A s i a n Aedes a e g y p t i o r e v e n t u a l l y t h e e l i m i n a t i o n o f dengue v i r u s from A s i a by v a c c i n a t i o n , research 1. i n y e l l o w f e v e r e p i d e m i o l o g y i s needed. These needs i n c l u d e :
S t u d i e s o f v e c t o r competency o f Aedes a e g y p t i from A s i a and the e a s t c o a s t of A f r i c a .
2.
S t u d i e s i n Aedes a e g y p t i o f i n t e r f e r e n c e by dengue v i r u s w i t h v p i 1 n\.j^ f r - r - ^ r transmission.
3.
D e t a i l e J e p i d e m i o l o g i c a l s t u d i e s of yellow
fever v i r u s i n East fever-free
A f r i c a i n b o t h e n z o o t i c f o r e s t a r e a s and y e l l o w c o a s t a l zones. A.
S t u d i e s o f s u s c e p t i b i l i t y o f A s i a n p r i m a t e s and v e c t o r of p o t e n t i a l f o r e s t v e c t o r s .
competency
5.
New and improved b i o l o g i c a l c o n t r o l methods f o r m o s q u i t o e s .
VIR/RC/7''t.4^: ( A f i H ) ) page b
5.
CONTINGENCY PLANS FOR EPIDEMICS
5.1
Epidemics
o f y e l l o w f e v e r have o c c u r r e d d u r i n g t h e p a s t 5 y e a r s i n b o t h F o r t u n a t e l y , n a t i o n a l govemments have been a b l e Should
South America and A f r i c a .
t o o b t a i n v a c c i n e and have sought and r e c e i v e d e x p e r t c o n s u l t a t i o n . a y e l l o w f e v e r epidemic
a c h i e v e pandemic p r o p o r t i o n s w h i c h i s c o n c e i v a b l e i n The e x i s t i n g surveil-
A s i a , w o r l d v a c c i n e s u p p l i e s m i g h t not be s u f f i c i e n t .
l a n c e , r e f e r e n c e c e n t r e , v a c c i n e s t o c k p i l i n g , and e x p e r t c o n s u l t a n t team schemes s h o u l d be m a i n t a i n e d and s t r e n g t h e n e d . I n a d d i t i o n r e s e a r c h on p o s -
s i b l e methods t o produce 17-D y e l l o w f e v e r v a c c i n e r a p i d l y i n l a r g e q u a n t i t y s h o u l d be s u p p o r t e d . P r o d u c t i o n o f v a c c i n e i n b r a i n s o f baby mice has been
proposed and may be f e a s i b l e .