WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTÉ INFORMAL CONSULTATION ON EPIDEMIOLOGY AND CONTROL OF YELLOW FEVER IN TROPICAL AFRICA, OCCQE/WHO Bobo Dioulasso, 20-23 March 197I MASS VACCINATION CAMPAIGNS AGAINST YELLOW FEVER Technical considerations f o r a future p o l i c y by P. Brès, M.D. V i r u s Diseases Recent epidemics have shovm that the threat of outbreaks o f yellow fever i s becoming greater due to i n c r e a s i n g penetration i n t o f o r e s t areas and r a p i d i t y i n t r a n s p o r t a t i o n . Our knowledge of the s u r v i v a l of the yellow fever v i r u s i n t r o p i c a l f o r e s t s of A f r i c a , i t s transmission from animal to animal and from animal t o man, i s l a r g e l y i n s u f f i c i e n t , but from present evidence i t appears c l e a r l y that v a c c i n a t i o n i s the best way to protect a population at r i s k i n the endemicity zone. Mass v a c c i n a t i o n campaigns i n French-speaking zones i n I94O-I96O have proved t h e i r e f f i c a c y . However problems a r i s e from the extent of the endemic zone i n which approximately two hundred m i l l i o n people l i v e with d i f f i c u l t communications i n many places and costs too great f o r l o c a l budgets. Another problem i s the b i r t h rate of populations which are renewed by 50 per cent i n f i f t e e n years. I t would be unwise not to maintain r e g u l a r l y immunity i n t h i s renewed f r a c t i o n which was the one mainly a f f e c t e d during epidemics i n Senegal (1) and Upper V o l t a (2). For t h i s reason e x t e r n a l assistance should be d i r e c t e d t o give countries i n the endemic zone the means to follow-up by themselves the Immunization programmes and t o produce the necessary vaccine. This report w i l l t r y to analyze some of the t e c h n i c a l parameters Involved i n the Implementation of a n t i - y e l l o w fever mass Immtinization i n t r o p i c a l A f r i c a . At f i r s t view they appear d i f f e r e n t i n the attack phase and the maintenance phase. 1. Attack phase ENGLISH ONLY INDEXED
This phase i s c h a r a c t e r i z e d by the importance o f the means which are necessary and which are roughly comparable to those of the smallpox and measles v a c c i n a t i o n campaigns. They w i l l be reviewed i n the f o l l o w i n g order: teams, vaccine and strategy. 1.1 V a c c i n a t i n g teams
Vaccinations may be performed e i t h e r by subcutaneous or intracutaneous methods using Jet-injectors. The number of teams operating i n a country must be determined according t o the s i z e of the population and t o the surface of the country, that i s to the density of the population. I t w i l l be r e l a t i v e l y lower i n densely populated countries and r e l a t i v e l y higher f o r widely scattered populations. For use i n the estimates (table 1) we have compared the number o f teams i n d i f f e r e n t c o u n t r i e s , whenever known (column 2 ) , t o the population and t h i s gave an average o f one team per 664 000 - o r approximately 700 000 Inhabitants. VIR/71.5 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 articles. Ce document ne constitue pas une publication. Il ne doit faire l'objet d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation de l'Organisation Mondiale de la Santé. Les opinions exprimées dans les articles signés n'engagent que leurs auteurs.
page 2
The a c t i v i t y o f a team w i t h one J e t - i n j e c t o r may v a r y c o n s i d e r a b l y when i t o p e r a t e s i n urban a r e a s , where i t i s e a s i e r t o a s s e m b l e p e o p l e t h a n i n r u r a l a r e a s where i t i s more difficult. From d i f f e r e n t c o m p l e t e d progjramraes, an average speed f o r a team can be e s t i m a t e d 25 000 v a c c i n a t i o n s p e r month o f 20 w o r k i n g days i n c l u d i n g time f o r t r a n s p o r t a t i o n . From t h e s e two mean v a l u e s i t a p p e a r s t h a t the time n e c e s s a r y f o r one team t o v a c c i n a t e 700 000 p e r s o n s w i l l be 700 000 : 25 000 = 28 months. On the same b a s i s , a h y p o t h e t i c number of v a c c i n a t i n g teams has been c a l c u l a t e d f o r each c o u n t r y i n the endemic zone o f y e l l o w f e v e r and the l e n g t h o f the v a c c i n a t i n g campaign has been o b t a i n e d from i t ( t a b l e 1). The l e n g t h ol' the campaigns v a r i e s from c o u n t r y t o c o u n t r y , between 14 «uid 30 months, around a mean v a l u e o f 28. In f a c t . In many c o u n t r i e s i n the t r o p i c s communications a r e v e r y d i f f i c u l t d u r i n g the r a i n y s e a s o n and we can e s t i m a t e t h a t the p e r i o d o f a c t i v i t y o f the teams would be l i m i t e d t o n i n e months p e r y e a r . T h i s p r o l o n g s the programme t o a p e r i o d o f t h r e e y e a r s . The p o s s i b l e number o f v a c c i n a t i o n s p e r month f o r each c o u n t r y i s g i v e n i n t a b l e (column 4 ) . The c o u n t r i e s have been grouped r e g i o n a l l y as shown on the map ( f l g . l ) . a l l t h e 300 teams be w o r k i n g siisTiltaneously t h e y would p e r f o r m a t o t a l o f 7 500 000 v a c c i n a t i o n s p e r month. 1.2 Vaccine supplies zone 1 Should
=
The maximum need o f v a c c i n e f o r the a t t a c k phase, i f a l l i n h a b i t a n t s i n the endemic were t o be v a c c i n a t e d , would be 7 500 000 p e r month f o r about 28 months. The v a c c i n e f o r mass v a c c i n a t i o n i s u t i l i z e d i n the c o n d i t i o n s d e s c r i b e d by i . e . w i t h a f u r t h e r 1:10 d i l u t i o n , the b a t c h b e i n g o f a s u f f i c i e n t p o t e n c y . For o f mass v a c c i n a t i o n , the v a c c i n e i s f i l l e d I n ampoules o f 200, 100 o r 50 d o s e s . improvements a r e s t i l l n e c e s s a r y t o have a b e t t e r a d a p t a t i o n o f the p r e s e n t a t i o n t o i t s use w i t h J e t - i n j e c t o r s i n f i e l d c o n d i t i o n s . The s o u r c e s where such a v a c c i n e i s a v a i l a b l e were t h e f o l l o w i n g i n
Penna (3), t h e purpose Some o f the v a c c i n e
I97O: per
I n s t i t u t e Oswaldo C r u z , R i o de J a n e i r o , B r a z i l - t h r e e t o f i v e m i l l i o n doses y e a r a t 0.02 US$ p e r dose p l u s f r e i g h t c h a r g e s (30 p e r 100)
I n s t i t u t e C a r l o s F i n l a y , B o g o t a , Colombia - I . 5 t o 2 m i l l i o n doses p e r y e a r a t 0.02 US$ p e r dose p l u s f r e i g h t c h a r g e s (30 p e r 100) I n s t i t u t P a s t e u r , Dakar, S e n e g a l p l u s f r e i g h t charges (30 per - 10 100) m i l l i o n doses p e r y e a r a t 0.04 US$ p e r dose
The Yaba L a b o r a t o r y , Lagos, N i g e r i a has t o be modernized t o r e a c h the 10 m i l l i o n dose l e v e l o f p r o d u c t i o n . WHO has o f f e r e d a c o n s u l t a n t and a s e n i o r l a b o r a t o r y t e c h n i c i a n t o f a c i l i t a t e t h i s m o d e r n i z a t i o n f o r w h i c h new equipment i s n e c e s s a r y . Other The first little s u p p l i e s o f v a c c i n e a r e a l s o a v a i l a b l e from p r i v a t e Industry. Institutes
amount o f v a c c i n e w h i c h i s a t p r e s e n t a v a i l a b l e e v e r y y e a r i n the t h r e e and 17 m i l l i o n doses and c o u l d p r o b a b l y be m i l l i o n doses. T h i s would r e a c h 30 000
mentioned, i s between l 4 . 5 more t h a n 20 doses
increased to a
m i l l i o n doses w i t h the amount doses which a r e theoretically
produced 1 500 000
by t h e Yaba L a b o r a t o r y i n 1972.
A t p r e s e n t the a v a i l a b l e amount i s a p p r o x i m a t e l y
p e r month i n c o n t r a s t t o the 7 500
necessary.
page 3 1.3 Strategy
L a u n c h i n g s i m u l t a n e o u s l y s u c h a campaign w i t h JOO teams i n 30 c o u n t r i e s i s o b v i o u s l y not f e a s i b l e , but t h e p r e v i o u s e s t i m a t e s g i v e the o r d e r o f magnitude o f the problem. V a c c i n a t i o n o f a l l the I n h a b i t a n t s o f the endemic zone would n o t I n c o n c e i v a b l e w i t h the e x p e r i e n c e o f s m a l l p o x e r a d i c a t i o n , but the r e a l r i s k f o r y e l l o w f e v e r would not J u s t i f y i t and a l i m i t e d progreunme appears more r e a s o n a b l e . As o n l y 1 500 000 doses o f v a c c i n e are a v a i l a b l e a t p r e s e n t I n s t e a d o f 7 500 000, o n l y 1/5 o f the t o t a l p o p u l a t i o n c o u l d be v a c c i n a t e d . T h i s r a t i o c o u l d i n c r e a s e i f more v a c c i n e became a v a i l a b l e and/or i f l e s s t h a n 30 c o u n t r i e s were t o participate. The v a c c i n a t i o n programme can be l i m i t e d by e s t a b l i s h i n g e x c l u s i o n s and p r i o r i t i e s . The d i f f i c u l t y l i e s i n the c h o i c e o f v a l i d c r i t e r i a (see below) n o t t o a l t e r the e p i d e m i o l o g i c a l v a l u e o f the l i m i t e d programme. No s o l u t i o n can be u n i v e r s a l but the e p i d e m i o l o g i c a l s i t u a t i o n must be s t u d i e d i n each c o u n t r y . E x c l u s i o n o f c h i l d r e n u n d e r s i x months o f age i s a d m i t t e d t o a v o i d n e u r o m e n i n g e a l p o s s i b l e c o m p l i c a t i o n s . The p o p u l a t i o n s n o r t h o f t h e boundary zone i n M a l i , N i g e r , Chad and Sudan have not been i n c l u d e d i n T a b l e 1 and have been assumed t o r e p r e s e n t h a l f o f the p o p u l a t i o n o f the whole c o u n t r i e s . The e x c l u s i o n o f p r e v i o u s l y v a c c i n a t e d p e r s o n s would i m p l y t h a t r e c o r d s o f v a c c i n a t i o n s have been r i g o r o u s l y e s t a b l i s h e d and t h a t t i m e would be a v a i l a b l e f o r e x a m i n i n g each i n d i v i d u a l c a s e i n the v a c c i n a t i o n campaign, w h i c h would be v e r y difficult. One may wonder what would be the e p i d e m i o l o g i c a l v a l u e o f l i m i t i n g the v a c c i n a t i o n t o age groups u n d e r 16 y e a r s o f age, most o f w h i c h are a t t e n d i n g s c h o o l s . T h i s r e p r e s e n t s a p p r o x i m a t e l y 50 per c e n t o f the p o p u l a t i o n as i t a p p e a r s i n the f o l l o w i n g d a t a from I v o r y C o a s t :
Ages: Percentages:
0-14 46.1
15-24 15.6
25-34 15.8
35-44 10.6
45-54 6.4
5 5 + 5-5
A n o t h e r argument c o u l d be t h a t i n r u r a l a r e a s e l d e r p e o p l e p o s s e s s s e v e r a l group B a n t i g e n s , but t h e i r p r o t e c t i v e r o l e i s n o t y e t known. The l i m i t e d programme c o u l d be based on g e o g r a p h i c a l p r i o r i t i e s d e r i v e d from e p i d e m i o l o g i c a l mainly: h i s t o r i c a l knowledge o f p e r i o d i c a l r e c u r r e n c e o f y e l l o w f e v e r , e i t h e r u r b a n o r J u n g l e t y p e , w h i c h may be i n d i c a t i v e o f an e n z o o t i c f o c u s o r a p e r i o d i c f i e l d o f e x p a n s i o n i n c o n n e x i o n w i t h an e n z o o t i c f o c u s . Such r e c u r r e n c e s appear i n the map ( f i g . 2 ) . The v a l i d i t y o f t h i s c r i t e r i a depends c ï i the r e l i a b i l i t y i n the n o t i f i c a t i o n of cases; important c i t i e s or populated areas;
data,
-
d e v e l o p i n g a r e a s , w i t h work i n t h e f o r e s t ; m a j o r a t i o n o f the r i s k by a h i g h d e n s i t y o f v e c t o r m o s q u i t o e s . The locally
a v a i l a b l e e p i d e m i o l o g i c a l d a t a might be i n s u f f i c i e n t and would J u s t i f y f u r t h e r r e s e a r c h . These c r i t e r i a c o u l d l e a d t o a mapping o f " s e n s i t i v e a r e a s " i n each country. As a c o r o l l a r y t o a l i m i t e d v a c c i n a t i o n programme, i t i s n e c e s s a r y t o m a i n t a i n i n each c o u n t r y a system o f s u r v e i l l a n c e on the p a t t e r n w h i c h has been proposed by WHO and d e s c r i b e d on s e v e r a l o c c a s i o n s .
page 4 2. Maintenance phase
The necessity of maintenance comes from the renewal of the population which reaches 46,1 per cent i n 14 years (see above). In f a c t , outbreaks i n Senegal or i n Upper V o l t a have shown that ten years or even l e s s were enough to r e c o n s t i t u t e a receptive f r a c t i o n of population f o r an outbreak. In large A f r i c a n c i t i e s , the moving population a c t s as a d i l u t i n g f a c t o r f o r the protected f r a c t i o n which may r a p i d l y decrease below a dangerous level. Furthermore, i n r u r a l areas, a f r a g i l e e q u i l i b r i u m e x i s t s , between n a t u r a l I n f e c t i o n and n a t u r a l p r o t e c t i o n . I f i t i s changed by v a c c i n a t i o n , one must not allow l a t e r on the b u i l d i n g of a v i r g i n bulk of c h i l d r e n exposed to an explosive propagation of the v i r u s . I t has been shown that c i r c u l a t i n g antibodies f o l l o w i n g v a c c i n a t i o n may be detected at l e a s t 1? years a f t e r v a c c i n a t i o n (4) and i t i s believed, though not demonstrated, that p r o t e c t i o n might be l i f e long. So, r e v a c c i n a t i o n does not seem imperative, except i n an epidemic focus i n order to r e i n f o r c e the previous coverage. The maintenance phase w i l l have to deal only with c h i l d r e n and i t can be envisaged i n two d i f f e r e n t ways, the choice of which w i l l depend l a r g e l y on the organization of p u b l i c h e a l t h s e r v i c e s i n each country. In urban areas, c h i l d r e n may be vaccinated i n schools or i n Maternal and C h i l d Health d i s p e n s a r i e s . A l t e r n a t i v e l y , mobile teams may be used. Vaccination i n f i x e d centres w i l l cost almost only the vaccine p r i c e . In r u r a l areas, mobile teams w i l l be a necessity. Advantage w i l l be taken of the p o s s i b i l i t y to vaccinate simultaneously against other diseases: measles, smallpox and BCG (5) (6) and t h i s w i l l lower the expenses. Conclusion An attempt has been made to work out the extent of a mass v a c c i n a t i o n campaign, covering the endemic yellow fever area i n A f r i c a . Though t h e o r e t i c a l , t h i s gives an idea of the s i z e of the problem. In p r a c t i c e , l i m i t e d v a c c i n a t i o n programmes should be implemented i n areas which are at r i s k of epidemic, as determined by epidemiological c r i t e r i a which have been examined. The attack phase would have to be followed by a maintenance phase, the l o g i s t i c s of which are d i f f e r e n t .
page 3
REFERENCES
1. 2.
P. Brès, et a l (1966)
Méd. trop. 26, 21 Document OCCGE,
P. K. Campaore et a l . Rapp. f i n a l lOè Conf. techn. OCCGE. Bobo Dioulasso, 1, 219-231 H. A. Penna l n Yellow Fever Vaccination. E. C. Rosenzweig et a l (1963)
3. 4. 5. 6.
Wld H l t h Org. Monograph Series No.30. 1956
Amer. J . trop. Med. & Hyg., 12, 230-235
H. M. Meyer et a l (1969)
B u l l . Wld Hlth Org. 30. 783-794
Y. Robin. Organisation Commune Contre l e s Grandes Endémies, Rapport de l a Xe Conference, 1970
Table 1.
NUMBER OF VACCINATING TEAMS AND LENGTH OF CAMPAIGNS (a) Vaccinating teams (b) Population ' hypothetic (In thousands) No vaccinations ^ per month ( i n thousands) length of campaign ( i n months)
West A f r i c a OCCGE Dahomey Ivory Coast Mali Niger Senegal Togo Upper V o l t a Total Others Gambia Ghana Guinea Liberia Nigeria Portuguese Guinea S i e r r e Leone Total s n t r a l West A f r i c a OCEAC Cameroon C e n t r a l A f r . Rep. Chad Congo, Peopled Rep. of Gabon Total Others E q u a t o r i a l Guinea Total East A f r i c a Ethiopia Somalia Sudan Total 23 900 2 745, 7 385 34 030 346 5 562 1 488 1 730* 870 480 10 130 8 3 1 62 350 376 790 130 650 529 2 47? 2 4 2 1 3 1 5 571 100 393* 903* 685 772 175 7 12 10 14 11 4 4 6 4 3 5 3 7 100 150 100 75 125 75 175 26 27 24 25 29 23 29
9
21 599
3
1 12
20 10
5 2 90 1 4
-
25 300 125 50 2 250 25 100
14 28 30 22 28 21 25
79 300
30 10 12 8 8
8 2 3 2
1
200 50 75 50 25
28 30 23 17 19
-
1
25
14
346 34 4 11 850 100 275 28 27 27
Figures given i n United Nations Demographic Yearbook 1968 As estimated f o r the Twenty-third World Health Assembly, May 1970 * Figure given represents the population considered as l i v i n g i n the endemic zone unknown
Table page 2 Population ( i n thousands) Vaccinating No v a c c i n a t i o n s t e a m s p e r month hypothetic ( i n thous«mds) length of campaign ( I n months)
Central Africa E a s t A f r i c a n Community Kenya Tanzania Uganda Total Others Angola Burundi Congo, Dem. Rwanda 5 362 3 406 16 730 3 405 Total Orand T o t a l 28 903 205 240 10 209 12 590 8 1^3 30 932
15 18 12
375 450 300
27 28 27
8 5 24
Rep. o f
200 125 600 125
27 27 28 27
155
300
7 500
F i g u r e s g i v e n i n U n i t e d N a t i o n s Demographic Yearbook I968 '^^^ As e s t i m a t e d f o r t h e T w e n t y - t h i r d W o r l d H e a l t h Assembly, May Unknown 1970
Fig.l
YELLOW-FEVER ENDEMIC AREA, AFRICAN CONTINENT 1970