760 150

W O R L D H E A L T H O R G A N i Z A T l O N

ORGANISATION MONDIALE DE LA SANTÉ .

F X P F R T C G M T T T F E CN Y F L L O W F F V E R V A C C I N E

WHC/YFV/IO'^

18 Mprch 1957

Gencv;. 8-13 : . p r i l 1957 ORIGINAL: SPANISH

P r o v i s i o n a l ngenda Item 8

THE OCCURRENCE OF ENCEPHALITIS AND OTHER COMPLICATIONS IN CONNEXION WITH VACCINATION AGAINST YELLOW FEVER

EXEERIENCE IN YE!iEZUELA by

IV R. I . D I R Z

E Q U I P M E N T

The minimum equipment c o n s i s t s o f : p. J e e p ; a p o r t a b l e aluminium t a b l e ;

two gl^.sa vacuum flp.sks; an i c e c r u s h e r ; n p o r t a b l e p e t r o l stove of the Colemp.n t y p e ; e. p e t r o l Inmp; a h e r m e t i c a l l y c l o s i n g c o n t a i n e r ; 150-200 s h o r t , X-u-go- c a l i b r e n e e d l e s , usup.lly measuring 5/8 x 21; two s p e c i a l s y r i n g e s graduated i n 1/2 mis, o f 20 ml c a p n c i t v , which Is s u f f i c i e n t f o r ko persons; c o t t o n wool;

raerthlolrte sclut-'on; rubber stamps f o r the d i t e nnd s e r l n l number; v a c c i n a t i o n c e r t i f i c a t e s of the type shown i n Annex I , which are Issued immediately a f t e r v a c c i n a t i o n from a c o u n t e r f o i l book c o n t R i n l n g 100 c e r t i f i c a t e s , the c o u n t e r f o i l s b e i n g r e t a i n e d f o r the r e c o r d s o f the l i v i s l o n ; ampoules o f p h y s i o l o g i c a l s a l i n e prepared i n t h e country or of B r i t i s h or American o r i g i n , h o l d i n g 250 or 500 m l . R e c e n t l y we hnve been f i t t i n g the Jeeps w i t h s m a l l r e f r i g e r a t o r s o f somewhat more thp.n 1 c u b i c f o o t c a p a c i t y under the f r o n t compartment where t h e d r i v e r s i t s . These are o f Americen o r i g i n and work w i t h p e t r o l vapour, which i s c i r c u l a t e d by pump s u c t i o n . The temperature f a l l s t o about 5°C and the purpose I s , p r i m a r i l y , t o s t o r e t h e v a c c i n e I f the vacuum f l a s k s Irreak or t h e supply o f Ice i s exhausted, I n a d d i t i o n t o p r o t e c t i n g the s y r i n g e s h o l d i n g s o l u t i o n from l i g h t and heat d u r i n g w a i t i n g p e r i o d s . R e c e n t l y we have a l s o been u s i n g p o r t a b l e , b a t t e r y - o p e r a t e d megaphones. These l o u d - s p e a k e r s , which are p o w e r f u l and weigh o n l y about 2 k g , can be c a r r i e d on f o o t or horseback.

WHO/YFV/IO page 2

PERSONNEL

I n g e n e r a l , v a c c i n a t i o n i s d i r e c t e d or c a r r i e d out by medical o f f i c e r s o f t h e

D i v i s i o n or o f the H e a l t h U n i t s , a l l o f vhom are on f u l l time employment, i n c o n j u n c t i o n w i t h n u r s i n g and s e c r e t a r i a l s t a f f . Tn the almost I n a c c e s s i b l e a r e a s , v a c c i n a t i o n i s c a r r i e d out, vhen there l a no p h y s i c i a n , by a male p u b l i c h e a l t h nurse w i t h s u i t a b l e t r a i n i n g ; the minimum v a c c i n a t i o n u n i t c o n s i e t s o f the nurse and the d r i v e r , t h e l a t t e r b e i n g a l s o employed f o r advance propaganda and t h e d i s t r i b u t i o n o f c e r t i f i c a t e s . When t r a n s p o r t i s by f o o t or on horseback the personnel i s reduced to the p h y s i c i a n o r

nurse a l o n e .

PROCEDURE

I t i s a r o u t i n e requirement t h a t the v a c c i n e be kept e x c l u s i v e l y i n crushed i c e and t h a t i t must be d i s c a r d e d when the i c e Is exhausted and the v a c c i n e exposed t o heat. This v e r y r a r e l y o c c u r s , s i n c e there i s always an a d d i t i o n a l vacuum f l a s k w i t h s u f f i c i e n t Ice a v a i l a b l e .

The p r e p a r a t i o n and a d m i n i s t r a t i o n o f the v a c c i n e a r e i n accordance w i t h t h e

i n s t r u c t i o n s o f the l a b o r a t o r y o f o r i g i n and w i t h the number o f doses i n each ampoule.

The s t o c k s o l u t i o n s are kept In vacuum f l a s k s c o n t a i n i n g I c e , away from the l i g h t and v e r y r a r e l y f o r more than two h o u r s . I n s t r u c t i o n s are g i v e n t o d i s c a r d them a f t e r three hours. The s o l u t i o n s f o r v a c c i n a t i o n are prepared d i r e c t l y In the s y r i n g e and are used immediately. When the number o f persons f a l l s o f f , as happens a t the end o f the v a c c i n a t i o n s e s s i o n , the personnel have orders t o d i s c a r d the s o l u t i o n every 20 minutes and prepare a new one, although the s y r i n g e should always be kept i n the r e f r i g e r a t o r .

I t i s r o u t i n e p r a c t i c e , before proceeding w i t h a v a c c i n a t i o n campaign, t o o b t a i n a census o r estimate o f the p o p u l a t i o n , above a l l In r u r a l a r e a s , and a census o f t h e r e f r i g e r a t o r s i n the area. Advance propaganda Is c a r r i e d out u s i n g loud-speakers from the h e a l t h e d u c a t i o n cinema and megaphones, and the p o p u l a t i o n Is asked t o a t t e n d a t p l a c e s which they can reach w i t h o u t much d i f f i c u l t y . The v a c c i n a t o r opens t h e most s u i t a b l e type o f ampoule a f t e r having assembled the p o p u l a t i o n . I n Venezuela

WHO/YFV/IO page 5

v a c c i n a t i o n has been d i r e c t e d more towards the r u r a l a r e a s , those most exposed b e i n g v a c c i n a t e d i n p r e f e r e n c e , l e a v i n g p r o t e c t i o n o f the c i t i e s t o the Aedes c o n t r o l campaign

I t Is only i n the l a s t two years t h a t , owing t o a c e r t a i n r e s i s t a n c e o f Aëdes t o DDT and D i e l d r i n , mass v a c c i n a t i o n has been c a r r i e d out i n c e r t a i n c i t i e s c l o s e t o f o r e s t a r e a s , thus p r o t e c t i n g the i n h a b i t a n t s should t h e r e be a spread of the d i s e a s e i n t o the c i t y , or should they make e x c u r s i o n s i n t o the f o r e s t .

COMPLICATIONS

I n Venezuela, 2 Oko 596 v a c c i n a t i o n s were car:--led out up t o 1 January 1957• We have r e c e i v e d v a c c i n e s from both European and American s o u r c e s , based on v i r u s 17D.

We have no experience w i t h v a c c i n e f o r s c a r i f i c a t i o n or w i t h v a c c i n e of any other k i n d . I n the a t t a c h e d sheets we g i v e a s e r i e s of q u e s t i o n s , based on t e c h n i c a l recommendations d i r e c t e d t o m e d i c a l o f f i c e r s i n charge of h e a l t h u n i t s and t o r u r a l m e d i c a l o f f i c e r s ,

concerning p o s t - v a c c i n a l r e a c t i o n s observed by them d u r i n g the most r e c e n t v a c c i n a t i o n s i n the area under t h e i r j u r i s d i c t i o n . By the end of March i t may be p o s s i b l e t o

c o l l e c t more e x t e n s i v e data which w i l l be submitted d u r i n g d i s c u s s i o n of t h i s paper.

We would s t a t e t h a t i n Venezuela t h e r e has been no e n c e p h a l i t i s due t o y e l l o w f e v e r v a c c i n a t i o n , apart from one d o u b t f u l case observed by Drs Roche and P i f a n o .

T h i s case wcs v a c c i n a t e d on 50 October 195^ and, from the f o l l o w i n g 15 November, showed symptoms of f e v e r and headache a l t h o u g h , i n the o p i n i o n of Dr P i f a n o , P r o f e s s o r of T r o p i c a l M e d i c i n e , the c l i n i c a l p i c t u r e of e n c e p h a l i t i s was not p r e s e n t .

We have r e c e i v e d o n l y some t e n complaints r e g a r d i n g subcutaneous abscesses, and we have never had cases of tetanus among the c o m p l i c a t i o n s .

I n Venezuela there are ^7 h e a l t h u n i t s and i+65 r u r a l m e d i c a l o f f i c e r s , d l s t r i b u t e v * over 11 h e a l t h c e n t r e s and 594 r u r a l m e d i c a l p o s t s . These are r e s p o n s i b l e f o r the o b s e r v a t i o n of r e a c t i o n s f o l l o w i n g v a c c i n a t i o n , when t h i s i s not done by the p h y s i c i a n s o f the Y e l l o w Fever and Plague D i v i s i o n . A l t h o u g h these m e d i c a l o f f i c e r s were a l l on the a l e r t and, t o a c e r t a i n e x t e n t , opposed t o the v a c c i n e , the o n l y immediate r e a c t i o n s d u r i n g the f i r s t t h r e e days, r e p o r t e d by them were f e v e r , a r t i c u l a r p a i n s , headache, or merely malaise l a s t i n g f o r a v e r y s h o r t t i m e ; these r e a c t i o n s o c c u r r e d i n o n l y 10 per c e n t , of the persons v a c c i n a t e d . I t may be asked whether such complaints do not r e p r e s e n t the probable p r o p o r t i o n of s l i g h t cases of i l l n e s s e x p e r i e n c e d by the p o p u l a t i o n i n the normal course o f e v e n t s , and -tre not connected w i t h the v a c c i n e .

w n i

A t the end o f 1954 we noted, on u s i n g American v a c c i n e which was s o l d t o us by the N a t i o n a l Drug Company, a marked Increase In the immediate f e b r i l e r e a c t i o n s . We c a r r i e d out t e s t s i n v a r i o u s towns w i t h about 10 000 i n h a b i t a n t s , immunizing them w i t h batches of v a c c i n e from d i f f e r e n t sources. We found t h a t i n those towns where t h e American v a c c i n e a l r e a d y mentioned was used, about 20 per c e n t , of the persons

v a c c i n a t e d showed immediate f e b r i l e r e a c t i o n s of s h o r t d u r a t i o n , whereas In n e i g h b o u r - i n g towns where v a c c i n e coming from B r a z i l and Colombia was used, such f e b r i l e

r e a c t i o n s o c c u r r e d i n l e s s than 10 per c e n t , of those v a c c i n a t e d . I n o t h e r towns, groups of persons were s i m u l t a n e o u s l y v a c c i n a t e d w i t h d i f f e r e n t batches of v a c c i n e , and o n l y those upon whom the American v a c c i n e was used showed an i n c r e a s e i n r e a c t i o n s a p p r o x i m a t e l y i n the same p r o p o r t i o n .

I t should be noted t h a t the v a c c i n e prepared i n previous years by the U n i t e d S t a t e s P u b l i c H e a l t h S e r v i c e , i n Montana, behaved Just as w e l l as the B r a z i l i a n and Colombian v a c c i n e .

I n the f o l l o w i n g t a b l e we g i v e a summary of the l a b o r a t o r i e s w h i c h have sent us v a c c i n e , showing the number of v a c c i n a t i o n s c a r r i e d out, the percentage of immediate r e a c t i o n s : f e v e r , a r t i c u l a r p a i n s , headache, e t c . , i n the f i r s t t h r e e days, and t h e percentage of l a t e r e a c t i o n s : e n c e p h a l i t i s .

Source

Number of v a c c i n a t i o n s

^ of r e a c t i o n s

Source

Number of v a c c i n a t i o n s

immediate f e v e r , a r t i c u l a r p a i n s , headache, e t c .

l a t e e n c e p h a l i t i s

I n s t i t u t o Oswaldo Cruz

R i o de J a n e i r o , B r a z i l

807

-

I n s t i t u t o C a r l o s F i n l a y

Bogota, Colombia

760 150

-

The N a t i o n a l Drug Company

S w i f t w a t e r , Pa, USA 559

259

-

Rocky Mountain L a b o r a t o r y

US P u b l i c H e a l t h S e r v i c e loi^

255

-

I n s t i t u t voor Tropische Hygiene en Geographische P a t h o l o g i e ,

Amsterdam, Netherlands

9

ACCINATION C S R T I I ΠC A T E AM) GJUNTERFOIL

SERIES Q No. 087797

aged years

YELLOW FEVER AND PIAGUE DIVISION

SERIES Q SAS No. 087797 S

aged years r e s i d i n g i n r e s i d i n g i n

has been vaccinated against yellow fever on a t

has been vaccinated aginst yellow fever en a t

BATCH BATCH

SIOJATUHE OF MEDICAL OFFICER SIGNATURE OP MEDICAL OFFICER

page 6

APPENDIX I I

YELLOW FEVER AND PLAGUE DIVISION

POST-VACCINAL REACTIONS

The r e a c t i o n s which occur a f t e r y e l l o w f e v e r v a c c i n r . t i o n may be c l a s s i f i e d a s e a r l y , l^i-te and a l l e r g i c .

The e a r l y r e a c t i o n s may be: l o c a l o r g e n e r a l , w i t h o u t a f f e c t i n g t h e c e n t r a l nervous system.

The l a t e r e a c t i o n s may be: r e a c t i o n s which a f f e c t t h e c e n t r a l nervous s y s t e m or a r e v i s c e r o t r o p i c ( h e p a t i t i s ) ,

1, L o c a l r e a c t i o n s . These appear on the f i r s t day of t h e i n o c u l a t i o n and l a s t f o r

one t o t h r e e d a y s , They may t a k e the f o l l o w i n g forms :

(a) s e n s i t i v i t y , erythema, s w e l l i n g i n the neighbourhood of t h e p o i n t o f i n o c u l a t i o n , w i t h l o c a l p a i n ;

(b) s l i ^ t r i s e i n temperature (37° t o 38°C), o c c a s i o n a l l y w i t h s h i v e r i n g - (c) headache w i t h o r w i t h o u t photophobia, s t i f f n e s s and p a i n i n the l i m b s , 2, G e n e r a l r e a c t i o n s w i t h o u t involvement of t h e c e n t r a l nervous system. These appear between t h e f o u r t h and e i g h t h day a f t e r v a c c i n a t i o n , b e i n g more f r e q u e n t on the s i x t h and seventh days, and l a s t i n g from a few hours up t o f o u r days. T h i s r e a c t i o n a l syndrome may be c h a r a c t e r i z e d by:

(a) moderate f e v e r ;

(b) i n f l u e n z a l symptoms and g e n e r a l m a l a i s e ;

(c) headache, p a i n behind t h e eyes, s t i f f n e s s and a r t i c u l a r p a i n s ; (d) a s t h e n i a and a n o r e x i a -

(e) abdominal disorders^, nausea and v o m i t i n g ; ( f ) a l b u m i n u r i a which d i s a p p e a r s on t h e t e n t l i d a y ,

5, B e a c t l o n s w h i c h a f f e c t t h e c e n t r a l nervous system. These appear 12 t c 15 days a f t e r v a c c i n a t i o n , w i t h c h a r a c t e r i s t i c m e n i n g o - e n c e p h a l i t i c symptoms, and nay o r m y not be preceded by g e n e r a l r e a c t i o n s on t h e f i f t h and s i x t h d a y s ,

A , ^fenlngeal r e a c t i o n s . On t h e f i f t e e n t h day when e v e r y t h i n g appears t o have r e t u r n e d t o normal i n t h e case o f e a r l y r e a c t i o n s , f e b r i l e r e l a p s e w i t h a

WHO/YFV/IO page 7 Appendix 2

temperature of 39°C, p a r t i c u l a r l y intense f r o n t a l headache, K e r n i g s i g n , p a i n f u l r i g i d i t y of the neck and v e r t e b r a l column. Wlien lumbvn,r puncture shows an

increase i n pressure and albumin content as w e l l as a count of from one to

s e v e r a l hundred c e l l s per cubic m i l l i m e t r e , t h i s confirm the meningeal r e a c t i o n . These acute symptoms which l a s t from f i v e t o s i x days disappear l e a v i n g only a more or l e s s g e n e r a l d e b i l i t y .

B. E n c e p h a l i t i c r e a c t i o n s . when the ri;".c^i.or. i s meningeal i t i s accompanied or followed by symptoms of e n c e p h a l i t i s which may take the f o l l o w i n g forms:

(a) motor form. Temporary motor p a r a l y s i s , a t t a c k s of convulsions, i n v o l u n t a r y movements;

(b) sensory form, h y p e r e s t h e s i a , e i t h e r g e n e r a l i z e d or l i m i t e d to c e r t a i n r e g i o n s . Hypoesthesia f o l l o w i n g the area of d i s t r i b u t i o n of c e r t a i n

nerves, sensation of c o l d i n the e x t r e m i t i e s and n e u r a l g i a , i n p a r t i c u l a r f a c i a l or s c i a t i c .

(c) :--<sychic and mental form. M e n t a l confusion, l o s s of the idea o f time, place and i d e n t i t y , amnesia and insomnia;

(a) • l.-";" -r,'- form. l e t h a r g i c symptoms with an i r r e s i s t i b l e d e s i r e t o sleep.

Hepatic r e a c t i o n s

(a) h e p a t i t i s . -his occurs two t o seven months a f t e r immunization;

(b) i c t e r i c syndrome. 'vo t o three months a f t e r v a c c i n a t i o n . A l l e r g i c r e a c t i o n s

(a) u r t i c a r i a and vague malaise a few hours a f t e r the i n o c u l a t i o n , l a s t i n g from a few hours up t o two days;

(b) symptoms of seriim sickness which appear on the t h i r t e e n t h day. In some cases symptoms o f erythema multiforme, a t t a c k s of asthma, e t c . , have been d e s c r i b e d and on one occasion, Quincke's edema, with intense u r t i c a r i a , gastro- i n t e s t i n a l symptoms and severe dyspnea i n s u b j e c t s with a h i s t o r y of a l l e r g y .

WHO/YFV/IO page 8 Appendix 2

The f o l l o w i n g h e a d i n g s a r e s u g g e s t e d f o r t h e t a b u l a t i o n o f d a t a s

Age, Day o f a p p e a r a n c e

C l i n i c a l No. o f y e a r s o r o f symptoms a f t e r C l i n i c a l

•-.•ases months Sex d a t e o f v a c c i n a t i o n p i c t u r e

End o f t h e r e a c t i o n