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Ninth Annual Meeting of the American Academy of Pediatrics
NINTH ANNUAL MEETING OF THE AMERICAN ACADEMY OF PEDIATRICS CINCINNATI, OHIO---NoVEMBER
16-18,
1939
Round Table Discussion on the Preventio~ of Contagious Diseases
Chairman: J.A. Toomey, M.D., Cleveland, Ohio Assistants : E.B. Shaw, M.D., San Francisco, Calif. G. W. Kutscher, Jr., M.D., Asheville, N. C. C. F. McKhann, M.D., Boston, Mass. J. S. Baird, M.D., Pittsburgh, Pa. H. T. Price, M.D., Pittsburgh, Pa. Secretaries : Ralph E. Pray, M.D., Fargo, N. D. A. S. Traisman, M.D., Chicago, Ill. Convalescent Mumps Serum G. W. Kutscher, Jr., M.D., Asheville, N. C. A l t h o u g h there is n o t h i n g new concerning the etiology, diagnosis, a n d treat. m e n t of p a r o t i t i s in t h e p a s t fifteen years, some progress h a s been m a d e in the p r o p h y l a x i s a g a i n s t t h e disease. The l a t t e r is i l l u s t r a t e d b y a n experience in a b o y s ' camp t h i s l a s t s u m m e r . One h u n d r e d a n d ~wenty-five boys a t t e n d e d t h i s camp, a n d fifty-two of t h e m had n e v e r h a d m u m p s . T h i r t e e n d a y s a f t e r the camp opened, m u m p s was dlscovered in a boy who h a d suffered a n e c k i n j u r y . The orthopedic surgeon had applied a r e s t r a i n i n g b a n d a g e w h i c h included t h e lower j a w as well as the neck. F e v e r developed w h i c h could not be explained on t h e b a s i s of injury. The dressi n g s were removed, a n d b i l a t e r a l p a r o t i t i s was discovered. T h i s boy h a d been visited in t h e i n f i r m a r y b y every fellow camper susceptible to m u m p s ; hence, all were exposed. The problem t h e n p r e s e n t e d i t s e l f : W h a t should be done for the r e m a i n i n g fifty-one s u s c e p t i b l e boys, some of w h o m were 300 miles f r o m home? Three of the camp directors who h a d h a d m u m p s in recent y e a r s (one had recovered only one m o n t h previously) offered t h e i r blood. F i f t e e n h u n d r e d cubic c e n t i m e t e r s were collected, and f r o m t h i s 500 c.c. of c o n v a l e s c e n t s e r u m was obtained. The serum was found sterile and W a s s e r m a n n negative, and the samples were pooled. On t h e f o u r t h d a y a f t e r the first case of m u m p s w a s discovered, t h e convalescent serum was administered. The ages of these boys were b e t w e e n 9 and 16 years. To those y o u n g e r and of l i g h t e r w e i g h t 8 c.c. of the s e r u m were a d m i n i s t e r e d i n t r a g l u t e a l l y ; to the older a n d h e a v i e r boys, 10 c.c. Those w i t h a h i s t o r y of a l l e r g y were g i v e n skin tests, w i t h o u t s h o w i n g a n y reaction. There were no delayed serum r e a c t i o n s or m a r k e d local t e n d e r n e s s at the site of t h e injections. There was no increase in t e m p e r a t u r e , s a v e in one i n s t a n c e , w h e n f o u r t e e n d a y s a f t e r exposure a n d t e n d a y s a f t e r r e c e i v i n g a dose of t h e serum, a n o t h e r case of m u m p s developed. A l t h o u g h t h e r e 'was f a i l u r e to protect here, there w a s also a h i s t o r y of a possible outside exposure. This boy developed a v e r y mild a t t a c k of t h e disease. The late A l f r e d Hess, in 1915, was the first to report upon t h e prophylactic use of c o n v a l e s c e n t whole blood in parotitis. The s e v e n t e e n children in his series 405
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w e r e 100 p e r c e n t p r o t e c t e d b y t h e u s e of f r o m 6 to 8 c.c. of blood. Reagan~ in 1925, w a s t h e first to r e p o r t on t h e u s e of c o n v a l e s c e n t s e r u m p r o p h y l a c t i c a l l y in d o s e s o f f r o m 2 to 4 c.c., w i t h p r a c t i c a l l y 100 p e r c e n t success. R e a g a n a d v i s e s t h e u s e of t h e s e r u m b e f o r e t h e s e v e n t h d a y f o l l o w i n g e x p o s u r e . T h e l i t e r a t u r e c o n t a i n s s e v e r a l a d d i t i o n a l r e f e r e n c e s to t h e u s e o f c o n v a l e s c e n t s e r u m a g a i n s t mumps. P o s s i b l y t h e dose of f r o m 8 to 10 c.e. of s e r u m g i v e n in t h i s s t u d y w a s l a r g e r t h a n n e c e s s a r y . H a l f of t h e dose m i g h t h a v e b e e n a d e q u a t e . 14owever~ s i n c e o n l y one o f t h e d o n o r s w a s a r e c e n t c o n v a l e s c e n t , i t w a s t h o u g h t w i s e to u s e t h e l a r g e r dose, e s p e c i a l l y s i n c e it w a s a v a i l a b l e . W i t h a r e c o g n i z e d i n f e e t l o n i n c i d e n c e of b e t w e e n 20 a n d 50 p e r c e n t f o l l o w i n g i n t i m a t e e x p o s u r e , i t is b e l i e v e d t h a t t h i s p r o c e d u r e p r o t e c t e d b e t w e e n f i f t e e n a n d t w e n t y - f i v e b o y s a g a i n s t t h e disease. T h e one f a i l u r e to p r o t e c t allows a p r o t e c t i o n i n c i d e n c e in t h i s s t u d y of 98.04 p e r cent. I n o t h e r w o r d s , f i f t y o u t o f f i f t y - o n e s u s c e p t i b l e a n d e x p o s e d b o y s w e r e p r o % e t e d a g a i n s t m u m p s . Since it is well k n o w n t h a t c o n v a l e s c e n t m e a s l e s s e r u m will o f t e n p r o l o n g t h e i n c u b a t i o n p e r i o d f o l l o w i n g e x p o s u r e to m e a s l e s , t h i s f a c t w a s k e p t i n m i n d i n t h i s s t u d y . B e c a u s e o f t h e f a c t t h a t no a d d i t i o n a l c a s e s d e v e l o p e d in t h e r e m a i n i n g five w e e k s o f c a m p f o l l o w i n g t h e a d m i n i s t r a t i o n of t h e s e r u m , i t is b e l i e v e d t h a t doses of f r o m 8 to 10 e.e. of c o n v a l e s c e n t s e r u m will a d e q u a t e l y p r o t e c t b o y s o f t h i s a g e a g a i n s t t h e disease. S u c h a course a l l o w e d u s to k e e p t h e c a m p open for the season.
DISCUSSION DR. J. W. BRUCE~ LOUISVILT,E.--In the differential diagnosis of mumps~ milking a l o n g S t e n s e n ' s d u c t p r o d u c e d a p u r u l e n t s e c r e t i o n in n o n e p i d e m i e p a r o t i t i s . DR. 3/I. Z E L I G S , CINCINNATI.--In a b o a r d i n g school where t h e r e were eighty-five boys, two cases of m u m p s developed. F i f t y boys g a v e histories of never h a v i n g h a d m u m p s . F r o m 5 to 10 c.e. of convalescent s e r u m were given to every one of t h e eighty-five boys~ a n d t h e r e were no other cases of m u m p s i n t h e i n s t i t u t i o n . C H A I R M A N T O O M E Y . - - I n a n o r p h a n a g e n u m b e r i n g 410 children~ two cases of m u m p s developed. A l t h o u g h p r o p h y l a x i s a n d p a s s i v e i m m u n i t y were n o t employed~ no other cases developed. DR. S. K A R E L I T Z , NEW u cubic c e n t i m e t e r s of s e r u m were adminis. tered to f o u r t e e n y o u n g s t e r s u n d e r 5 y e a r s of a g e who h a d developed m u m p s . O f t h e fourteen~ five were n o t modified b y t h e serum. O n l y local r e a c t i o n s were obtained. F r o m these f a c t s I a m u n a b l e to d r a w a n y definite conclusions. DR. S H A W . - - I t should be given.
seems p l a u s i b l e t h a t as t h e a g e of t h e child increases more s e r u m
DR. A. F. ABT~ CHICAG0.--The m a i n t h i n g is to increase t h e dose with increase in w e i g h t . DR. H. T R E M A I N E , B O I S E . - - F r o m o b s e r v a t i o n s it seems t h a t t h e y o u n g e r t h e patients, the better the results. DR. G. L. D R E N N A N , J-;kCKSONVILLE~ I s L - - M u m p s is a f a i r l y c o m m o n c a u s e of d e a f n e s s . I n a s t u d y o f 10,000 d e a f children above 2 y e a r s of age, f r o m 2 to 3 per cent of acquired deafness followed mumps. DR. S t t A W . - - I t is p r o b a b l y similar to t h a t w h i c h follows m e n i n g i t i s a n d proba b l y is due to d a m a g e in t h e cochlea a n d is s e c o n d a r y to t h e v e r y c o m m o n m e n i n g e a l involvement.
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DR. A. S. T R A I S M A N , CHIOAGo.--What is the frequency of recurrent epidemic parotitls ? DR. K U T S C t I E R . - - I do not have exact figures, but it is rare. DR. Y. V. G R E E N E B A U M , CINCn~NATL--I-Iave you ever seen p u r p u r a in m u m p s ? CHAIRMAN TOOMEY.--No. DR. T. P. S A L T I E L , C m c A o o . - - W h a t is the procedure to follow when a susceptible f a t h e r and mother have been exposed to a child with m u m p s ? DR. K U T S C I t E R . - - T h e supposition, of course, is t h a t the f a t h e r and m o t h e r h a v e not h a d m u m p s . I f t h e y h a v e n o t h a d m u m p s , t h e same procedure should be followed as in the case of children.
Poliomyelitis Joseph S. ]Baird, M.D., Pittsburgh, Pa. We had two or three cases of poliomyelitis late in July. New cases are still giving trouble even now in November. There were, in all, about forty cases in the city, and twenty-three cases from outside the city came in for care. All were children. The twenty-three cases occurred along the river, and at no time were there two children in one family who were stricken with the disease at the same time. No contacts were indicated between eases. ~ Nine deaths, all bulbar types, were reported. Dr. I~[enry T. Price at Children's ]:Iospital in Pittsburgh had ten patients on whom he used the respirator. Four made good recovery. The average number of respiratory days was 280. During the past month~ he reported five cases even though there has been frost. Recently there has been no work on the prevention of poliomyelitis that has been of any value. From work done at Detroit it may be concluded that convalescent serum does no good. The Public t t e a l t h m e n in M i c h i g a n h a v e verified this opinion. T h e y report t h a t n a s a l s p r a y used as p r e v e n t i o n h a s a c t u a l l y done d a m a g e a n d been of no benefit.
Dr. Albert Sabin, Cincinnati, Ohio The shortest comment on the present status of prophylaxis and specific therapy of poliomyelitis would be that there isn't any. When we inquire why there isn't any~ we find that as regards prophylaxis experimental studies both in monkeys and man established that available vaccines were either ineffective or dangerous, or both, that little or no protection can be expected from immune~ convalescent, or adult sera i and that, while certain nasal chemical sprays can protect monkeys against infection by the olfactory route, similar sprays in human beings have yielded no evidence of protection against the natural disease. Although it has been glibly stated in recent years that the virus invades the human nervous system by the olfactory pathway, there is no evidence derived from studies on human beings that such is actually the case. ]V[y own studies on more than 2,000 serial sections of olfactory bulbs from ten cases of human poliomyelitis failed to reveal the lesions which I have always been able to find in monkeys whose nervous systems were infected via the olfactory route. I mention this not as conclusive evidence against the olfactory portal of virus entry in man, but rather to indicate that there is as yet no good evidence for it. All this is brought up here because a n y hope t h a t m a y possibly be e n t e r t a i n e d f o r the prophy]actlc effects of the spraying or instillation of certain chemical substances into the nose is dependent upon the v i r u s i n v a d i n g the h u m a n n e r v o u s s y s t e m b y t h e o l f a c t o r y route.
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Specific i m m u n e s e r u m t h e r a p y a f t e r s i g n s a n d s y m p t o m s of t h e disease, e i t h e r p r e p a r a l y t i c or p a r a l y t i c , a r e a p p a r e n t h a s n e i t h e r t h e o r e t i c a l n o r p r a c t i c a l b a s i s a t t h e p r e s e n t t i m e . T h e o r e t i c a l l y , t h e r e is e v e r y r e a s o n to b e l i e v e t h a t m o s t of t h e cells t h a t a r e g o i n g to be a f f e c t e d b y t h e v i r u s a r e i n v a d e d s e v e r a l d a y s be. f o r e t h e a p p e a r a n c e of c l i n i c a l s i g n s a n d t h a t n o t e v e n l a r g e a m o u n t s of a n t i b o d y c a n i n f l u e n c e t h e effects of t h e i n t r a c e l l u I a r v i r u s or p r e v e n t i t f r o m s p r e a d i n g to o t h e r cells. T h e b e s t e v i d e n c e f o r t h i s as r e g a r d s p o l i o m y e l i t i s is f o u n d in m o n k e y s w h i c h develop s i g n i f i c a n t a m o u n t s o f n e u t r a l i z i n g a n t i b o d y as a r e s u l t o f v a c c i n a t i o n a n d y e t a r e f u l l y s u s c e p t i b l e to n a s a l i n s t i l l a t i o n o f t h e v i r u s . P r a c t i c a l l y , as is well k n o w n b y now, t h e r e s u l t s o f p r o p e r l y c o n t r o l l e d s t u d i e s in m a n s h o w e d no effect of c o n v a l e s c e n t s e r u m e i t h e r in t h e p r e p a r a l y t i c or paralytic stages. The suggestion that injections of vitamin C can prevent the d e v e l o p m e n t of p a r a l y s i s in m o n k e y s h a s n o t b e e n c o n f i r m e d in c a r e f u l l y cont r o l l e d e x p e r i m e n t s in w h i c h i t w a s f o u n d t h a t n e i t h e r l a r g e n o r s m a l l a m o u n t s o f t h e n a t u r a l or s y n t h e t i c v i t a m i n m o d i f i e d t h e c o u r s e of t h e e x p e r i m e n t a l d i s ease in any way. DISCUSSION C H A I R M A N T O O M E Y . - - D o e s s e r u m do a n y good? t h a t n o t e n o u g h s e r u m is used.
L e v i n s o n of Chicago t h i n k s
DR. M c E : H A N N . - - M o n k e y s a n d h u m a n b e i n g s are n o t the same. Therefore, the work done on m o n k e y s does not show w h a t can be done on h u m a n beings. I n Boston, t h e v i r u s h a s been i n j e c t e d i n t r a s p i n a l l y ( i n t r a c e r e b r a l l y ) a n d c o n v a l e s c e n t s e r u m (]50 c.c.) h a s been g i v e n with no benefit. C H A I R M A N T O O M E Y . - - I f one i n t r o d u c e s poliomyelitis virus in t h e e x p e r i m e n t a l a n i m a l b y w a y of the g a s t r o i n t e s t i n a l t r a c t a n d t h e n gives serum~ poliomyelitis does n o t result. DR. S H A W . - - S e r u m does some good. The real a r g u m e n t is, Can a n y a m o u n t of s e r u m g i v e n do a n y good? Should it be p o u r e d in, w i t h no set a m o u n t s given? No one h a s ever s t a n d a r d i z e d the a m o u n t s to be a d m i n i s t e r e d . R e m e m b e r t h a t m u c h of t h e s e r u m m a y have no potency, m a y n o t be h y p e r i m m u n e serum. I t h a s been m y experience t h a t p a t i e n t s who are given s e r u m do b e t t e r t h a n those who receive none. E x p e r i m e n t s on h u m a n b e i n g s cannot, of course, c o m p a r e with those on monkeys. P o l i o m y e l i t i s m a y n o t be j u s t a disease of t h e c e n t r a l nervous system. T h e r e is a s y s t e m i c phase. I f there is, we should c e r t a i n l y u s e serum. DR. M c K H A N N . - - I believe t h a t s e r u m m i g h t influence the p r e p a r a l y t i c , b u t I h a v e no a d e q u a t e b a c k g r o u n d f o r t h i s s t a t e m e n t . DR. I. A. ABT, CuIcAOO.--Belief in a t h e r a p e u t i c procedure dies h a r d . W h y not f a c e t h e f a c t s ? W e have no p r o p h y l a c t i c n o r c u r a t i v e t r e a t m e n t s . W e know nothi n g a b o u t it. DR. E. G. H O R T O N , Co~mMBUS.--The L o r d is m e r c i f u l in our cases of poliomyelitis. I h a v e lost f a i t h in m y a b i l i t y to do a n y t h i n g a b o u t it. E v e n severe cases have come t h r o u g h t h i s year. DR. H. B. S I L V E R , NEWAKK, N. g . - - D r . K r a m e r of B r o o k l y n s a y s t h a t n a s a l w a s h i n g s w i t h ephedrine do some good. T h i s t r e a t m e n t m a y be used some day. Diphtheri~, It. T. Price, M.D., P i t t s b u r g h , ' P a . W h a t s t a g e is d i p h t h e r i a in a n d w h a t is i t ? W i l l it be r e l e g a t e d to a h e a p of u n k n o w n s . ~ T h a t is a l w a y s a p o s s i b i l i t y , t h o u g h a r a r e one. T h e first t h i n g to
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do is to s t a m p o u t t h e focus. T h e l a c k of c o o p e r a t i o n of t h e m e d i c a l p r o f e s s i o n in p r o t e c t i n g c h i l d r e n m a y r e s u l t i n a s e v e r e e p i d e m i c . F i r s t t o x i n - a n t i t o x i n w a s used, a n d n o w t o x o i d , b u t t h e u s e of e i t h e r is a l w a y s f o l l o w e d b y a S e h i c k t e s t . R e m e m b e r t h a t s t r e p t o c o c c i c t h r o a t i n f e c t i o n s w e r e o f t e n c a l l e d l a r y n g e a l dipht h e r i a i n d a y s g o n e by. W e n o w realize m o r e w h a t d i p h t h e r i a is. I f we do diagnose i t p r o p e r l y , s e r u m s h o u l d g i v e r e s u l t s . DISCUSSION C H A I R M A N T O O M E Y . - - H o w m u c h of our p r e s e n t decrease in m o r b i d i t y is due to a n a t u r a l lull r a t h e r t h a n to p r o p h y l a c t i c m e a s u r e s ? W e a r e p r o b a b l y in a ~rough of t h e disease. D R . G. I:L F E L L M A N , MILWAUK~E.--We m a y h a v e a n experience similar to the one in "Vienna in 1933. T h e r e the s e r u m proved of no value. DR. K A R E L I T Z . - - R e f u g e e children c o m i n g into t h i s c o u n t r y now f r e q u e n t l y give a h i s t o r y o f h a v i n g h a d diphtheria. N o n e have been g i v e n p r o p h y l a x i s , a n d t h e y have a b o u t t h e s a m e n u m b e r of d i p h t h e r i a cases with no p r o p h y l a x i s as we do with it. D R . A. D. K A I S E R , ROCt{ESTEI{, N. u before or a f t e r the Schiek test.
or two i n o c u l a t i o n s should be given
DR. @ R E E N E B A U ] V L - - I t is good practice to give t h e combined d i p h t h e r i a a n d t e t a n u s toxoid i f the follow-up Schick test is positive. DR. 1 V [ c K H A N N . - - R e p e a t e d Schick t e s t s give p s e u d o r e a c t i o n s . W h e n one is goi n g to r e p e a t a Schick test, there should be a n i n t e r v a l of f r o m two to f o u r weeks. DR. I. A. A B T . - - 1 a m n o t sure t h a t t h i s is a lull in d i p h t h e r i a . I t m a y be perm a n e n t . W e m a y wake u p to find ourselves in a n epidemic o f r e f r a c t o r y cases. A u s t r i a did n o t i m m u n i z e at all. Despite this, there was no d i p h t h e r i a there f o r t e n years. T h e n a f t e r t h a t t h e r e was a terrific epidemic. DR. tI. B. M E T T E L , I~DIA~A>OLIS.--Whether the Schick test is n e g a t i v e or positive, we have only a skin reading. I t does not m e a n t h a t t h e child is protected 9t g a i n s t diphtheria. DR. F E L L M A N . - - H o w
m a n y are u s i n g combined d i p h t h e r i a a n d t e t a n u s toxoid?
DR. K U T S C H E R . - - I would not give s e r u m f o r p u n c t u r e w o u n d s if I h a d given t e t a n u s - d i p h t h e r i a c o m b i n a t i o n s before. DR. t t O R T O N . - - S o m e p r a c t i c i n g p h y s i c i a n s do n o t know d i p h t h e r i a . p r o t e s t a g a i n s t t h e single shot i m m u n i z a t i o n s .
I should
DR. I. A. A B T . - - I n t e t a n u s , m a k e every p u n c t u r e w o u n d a n open wound, clean it out, a n d incise it. T h e n you w o n ' t need passive i m m u n i t y a n d y o u c a n avoid t h e use of so m u c h serum. DR. Z E L I G S . - - D o y o u feel t h a t two h y p o d e r m i c s o f a l u m - p r e c i p i t a t e d toxoid would raise t h e t i t e r i f u s e d at t w o - m o n t h i n t e r v a l s i n s t e a d of three-week i n t e r v a l s ? DR. P R I C E . - - T h e m e t h o d is to use t h e second dose o f toxoid in three weeks. T h e n do a Schick test. I f positive, r e p e a t t h e toxoid. DR. S H A W . - - T h e c a p a c i t y of the p a t i e n t to p r o d u c e a n t i t o x i n f r o m shots is the all-determining factor.
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DR. M. L. C O O P E R , CINCINNATL--Merety t h e a d m i n i s t r a t i o n of a Schiek test gives elevated t i t e r in the blood. DR. M e K H A N N . - - I n m y experience several p a t i e n t s with n e g a t i v e Schiek t e s t s have developed d i p h t h e r i a . However, the Schiek t e s t indicates some resistance to diphtheria. DR. B A I R D . - - A recent P u b l i c H e a l t h c o n v e n t i o n s u m m a r y s t a t e d t h a t two doses o f a l u m toxoid g i v e n f r o m t h r e e to f o u r weeks a p a r t are more effective t h a n t h r e e doses of toxold plain. DR. G. F. P A T T E R S O N , CINC~NNArrI.--Of 123 children, o n e - f o u r t h were imm u n i z e d w i t h t o x i n - a n t i t o x i n . The o t h e r s were i m m u n i z e d with toxold. F o r t e n y e a r s t h e c h i l d r e n h a d Sehick t e s t s each year. T h e entire g r o u p h a s r e m a i n e d n e g a tive u n t i l t h i s y e a r when t h e r e were seven positives. D R . F . B. M I N E R , FLINT, M i c h . - - S k i n s e n s i t i v i t y s o m e t i m e s gives a f a l s e p o s i t i r e S e h i c k t e s t . Give t w o d o s e s of a l u m t o x o i d , one a t 9 m o n t h s of a g e a n d t h e second dose at 10 m o n t h s . R e p e a t t h e Schiek t e s t on e n t e r i n g school. DR. D R E N N A N . - - W h a t
dose of p r e c i p i t a t e d toxoid is u s e d ?
C H A I R M A N T O O M E Y . - - T h i s dose h a s b e e n v a r i a b l e . T h e doses r e c o m m e n d e d b y t h e C o m m i t t e e on I m m u n i z a t i o n a n d T h e r a p e u t i c P r o c e d u r e s f o r A c u t e I n f e c t i o u s D i s e a s e s o f t h e A m e r i c a n A c a d e m y of P e d i a t r i c s are as f o l l o w s : " T h r e e t y p e s o f m a t e r i a l a r e u s e d to i m m u n i z e a g a i n s t d i p h t h e r i a : (1) d i p h t h e r i a t o x o i d a n d (2) a l u m - p r e c l p i t a t e d t o x o i d f o r c h i l d r e n u n d e r 10 y e a r s of age, e a c h t o x o i d m a t e r i a l to be i n j e c t e d i n doses of 0.5 e.c., 1 e.e., a n d 1 e.e. a t two- to f o u r - w e e k i n t e r v a l s . V a r i a t i o n s of t h e s e doses o f t h e t o x o i d s h a v e b e e n u s e d i f r e a c t i o n s f o l l o w t h e i n i t i a l i n j e c t i o n . O n e - t e n t h c u b i c c e n t i m e t e r , 0.2 e.e. a n d 0.5 e.c. a r e g i v e n e v e r y t w o to f o u r w e e k s , a n d a n a d d i t i o n a l dose o f 1.0 c.e. m a y be g i v e n i f t h e r e a c t i o n s a r e n o t too severe. (3) A h o r s e a n d g o a t t o x i n - a n t l t o x l n f o r p e r s o n s o v e r :10 y e a r s of a g e i n j e c t e d s u b c u t a n e o u s l y i n doses o f 0.5 e.e. a n d 1 e.e. a t two- to f o u r - w e e k i n t e r v a l s . " DR. R. P. EOGERS~ GREENWIGIt, C o N N . - - W h a t is t h e relative reaction f o l l o w i n g a Schick t e s t a n d t h a t a f t e r a dose of toxoid in a child n e g a t i v e to t h e Sehick t e s t ? C H A I R M A N T O O M E Y . - - T h e r e have been no r e a c t i o n s in children n e g a t i v e to t h e Sehick test, b u t t h e r e will a l w a y s be some reaction, a l t h o u g h o f t e n slight, to a n i n j e c t i o n o f toxoid. DR. I. R. C O H N , TOLEDO.--Is p r e c i p i t a t e d toxoid p r e f e r r e d over fluid toxoid? H o w a b o u t t h e v a l u e of d i p h t h e r i a - t e t a n u s toxoid? CHAIRMAN TOOMEY.--I t h e m a t e r i a l of choice. DR. I. P . B R O N S T E I N , protect ?
believe t h a t p r e c i p i t a t e d toxoid m i x t u r e will become
CHICAGO.--I%r how l o n g a period will t e t a n u s toxoid
D R . S t I A W . - - T h l s h a s n o t b e e n d e t e r m i n e d as y e t . I n c a s e s of t e t a n u s , a n t i t o x i n g i v e s a p r o t e e t l o ~ f o r o n l y a s h o r t a n d v a r i a b l e p e r i o d of t i m e . Medicol e g a l c o n s i d e r a t i o n s l e a d t o t h e u s e o f m a n y d o s e s o f t e t a n u s a n t i t o x i n , b u t it is h a r d to p r o v e h o w m u c h i m m u n i t y o f a n y v a l u e is a c t u a l l y t h u s p r o v i d e d . A good m a n y c a s e s of t e t a n u s h a v e b e e n g i v e n t e t a n u s a n t i t o x i n as a p r o p h y l a c t i c . I t seems reasonably assured that the patient who has been given tetanus toxoid, and t h e n f o l l o w i n g i n j u r y h a s b e e n g i v e n a s e c o n d dose o f toxoid, h a s a b e t t e r prosp e c t o'f b e i n g c o m p l e t e l y p r o t e c t e d a g a i n s t t e t a n u s t h a n one w h o is g i v e n : o n l y tetanus antitoxin.
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DR. M. F. OSTERLIN, TR&VEI~SECITY, MIc:I.--How many shots of toxoid should be given to obtain a negative Schick test? I had a p a t i e n t to whom I gave the injections without obtaining a negative Schick test. C H A I R M A N T O O M E Y . - - V e r y frequently those persons who seem problems iu immunization are really nothing more than p a t i e n t s who have become sensitive to the products c o n t a i n e d i n the broth in which the b a c t e r i a grew, and it will be f o u n d . t h a t the m a j o r i t y of these p a t i e n t s who still show reaction a f t e r immunizatiou are sensitive to these products. Prevention of Measles Charles F. lYIcKhann, M.D., Boston, Mass. Deaths from measles are usually to cmnplications of the disease, especially pulmouary disorders caused b y the streptococcus or pneumococcus. ~Iany of these complications m i g h t be prevented b y adequate iso]atlon of measles patients. P a t i e n t s with measles should not be placed t o g e t h e r on group isolation, but should be on individual precautions in separate rooms, i f possible. Thus, patients w i t h measles will not carry the disease to one another, but they may by coughing or sneezing disseminate , either by direct contact or b y air-borne infections~ secondary organisms to their bed neighbors. Since deaths are more numerous at the younger ages~ precautions should be especially stringent in these groups. ~/Iasks of proper filtering design wl]l help to prevent the spread of dangerous organisms from the personnel to the p a t i e n t . Investigations as to the role of air-borne infection in the spread of measles and its complications have been carried on in the past three years. Definite s t a t e m e n t s as to ~he rMative proportion of direct personnelto-patient infection and of air-borne infection in the dissemination of measles and complicating organisms, as well as an appraisal of the value of ultraviolet light in prevention of transmission, cannot as yet be made. Sulfanilamide and sulfapyridine have been observed not to have any effect on the course of measles, but may be effective in the t r e a t m e n t of streptococcal or pneumococeal complications. Some authors have recommended the use of these drugs throughout the course of the febrile eruptive stage as a preventive of serious complications. Should such a procedure be proved relatively free from danger and effective, its wide adoption would f u r t h e r minimize the dangers of the disease and render the search for bio]oglc p r e v e n t i v e s less important. Specific t r e a t m e n t of measles is not as yet possible a f t e r the appearance of tile eruption. Large doses of sermn may be effective in m i t i g a t i n g the severity of the attack, i f given before the rash appears. An active immunization is urgently needed and is promised b y the work of Wenekebach and others who claim to have cultivated the v i r u s in chick embryos and to have observed t h a t a f t e r cultivation the virus becomes a t t e n u a t e d and an injection into susceptible persons produces a modified disease. When measles virus, either a t t e n u a t e d or of normal strength, becomes available, inoculation of p a t i e n t s with subsequent partial immunization of p a t i e n t s who have received full s t r e n g t h virus will be justified. P r e v e n t i o n or modification of the disease b y the use of human immune bodies in the form of convalescent serum, adult immune serum, or immune globulin (placental e x t r a c t ) remains the only reasonably dependable prophylactic procedure. Yet w i t h the diminution in complications following b e t t e r isolation of measles p a t i e n t s and with successful therapy available for some of the more severe complications, even the prevention or modification of measles by the use of serum need be used only in selected instances. Convalescent serum an~[ human immune globulin (placental extract) seem to be somewhat more effective than adult immune serum, while convalescent serum
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has the a d v a n t a g e over immune globulin of being more uniform in its potency and it seldom causes a local reaction at the point of injection. The dosage of any o f these agents is determined, in addition to potency, b y the time of administration, age and sex of the patient, and possibly b y the degree of exposure. Convalescent serum is usually effective in from 4- to 6-c.e. dosage; immune globulin from 2 to ~ c.c.; and adult immune serum, from 15 to 20 c.e. I m m u n i t y resu]tlng from the administration of these substances is passive in character and of short duration, seldom lasting more than two or three weeks. The time o f a d m i n i s t r a t i o n is a factor of great importance in determining w h e t h e r prevention or modification of the disease will be induced. E a r l y in the incubation period, the injection in the doses given above will usually p r e v e n t the disease, while later in the incubation period larger amounts are needed; and a f t e r the onset of symptoms, still larger amounts are required i f any effect is to be achieved. I n measles modified by the use of serum, the incubation period is often prolonged,. necessitating the lengthening of the quarantine period of children who receive the serum. S e v e r i t y of the disease is reduced o f t e n t i m e s so much t h a t the typical features of the disorder are not observed. Complications are usually avoided. W h e t h e r the extreme modification which is sometimes obtained results in active p e r m a n e n t immunity has not been definitely determined. However, in general, the a t t e n u a t e d disease is thought to give p e r m a n e n t immunity and is, therefore, the desirable result of serum administrations. I n certain types of patients, notably institutional cases, or acutely or chronically ill debilitated children, especially those between 6 months and 2 years of age, during which time the death rate in measles is high, protection through the use of serum should be obtained if possible. DISCUSSION DR. I. B. SILBE]~, CLEVP,LANI).--Reaction from imumne globulin has seemed to aggravate some cases. DR. K A R E L I T Z . - - T h e extraction of globulin from human blood seems a good prospect. Then standardized doses would be possible. Blood from the cord, third labor stage, and laked blood could provide the source. No two workers in measles are able to compare their results as far as doses, effect, etc., are concerned. I believe that schools are not good controls. DR. COI-IN.--Should sulfanilamide be given as treatment of measles.~ DR. M c K I I A N N . - - I feel that sulfanilamide should be given to those persons who have complications of this disease. ])R. GREENEBAU1VL--Is there any value in the use of immune globulin by mouth ? DR. McKHANN.
I do not believe so.
DR. K U T S C H E R . - - W h a t is the duration of immunity following serum to modify nmasles? DR. M c K H A N N . - - T h i s is merely a passive immune principle and such immunity may be lost within a few weeks. DR. COI-IN.--Is natural immunity present in some children? DR. M c K H A N N . - - T h e r e is a possibility that some children may be immun% but the number is so few that, for practical purposes, it may be ignored.
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Scarlet Fever John A. Toomey, M.D., Cleveland, Ohio There have been many complaints about the reactions which follow injections o f s c a r l e t f e v e r t o x i n d u r i n g t h e p r o c e s s of a c t i v e i m m u n i z a t i o n . T h a t r e a c t i o n s occur is o b v i o u s s i n c e m a n y p r o c e d u r e s h a v e b e e n r e c o m m e n d e d to a v o i d t h e m . T h e D i c k s n o w g r o w t h e i r o r g a n i s m s i n b r o t h - f r e e m e d i a , a n d a f t e r J a n . 1~ 1940, all i m m u n i z i n g t o x i n s will be of t h i s t y p e . P r i c e a n d h i s a s s o c i a t e s at C h i l d r e n ' s t t o s p i t a l in P i t t s b u r g h a r e a t t e m p t i n g to c o n c e n t r a t e a n d p u r i f y t h e s e t o x i n s . They claim good results with their product. I t m a y be s t a t e d in p a s s i n g t h a t t h e 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 is i n t e r e s t e d in a toxoid, t t o w e v e r , t h e o n l y t h i n g a p r a c t i c i n g p h y s i c i a n c a n n o w o b t a i n is t h e s t a n d a r d i z e d t o x i n of t h e S c a r l e t F e v e r C o m m i s s i o n . T h e r e is no d o u b t in m y m i n d t h a t we c a n i m m u n i z e p e r s o n s w h o h a v e p o s i t i v e s k i n t e s t s to t h e p o i n t w h e r e t h e i r t e s t s b e c o m e n e g a t i v e a n d t h a t t h i s i m m u n i z a tion p r o c e d u r e is of p r a c t i c a l v a l u e . I n t h e p a s t , 25 p e r c e n t o f t h e n u r s e s w h o c a m e on o u r w a r d s a n d w h o w e r e e x p o s e d to s c a r l e t f e v e r c o n t r a c t e d t h e disease. S i n c e 1926 we h a v e i m m u n i z e d n e a r l y 2,000 n u r s e s w h o h a d p o s i t i v e t e s t s a n d h a v e h a d o n l y e i g h t f a i l u r e s of i m m u n i z a t i o n . S o m e b e l i e v e t h a t s u c h p e r s o n s a r e r e n d e r e d n e g a t i v e to s k i n t e s t s , b u t are m a d e m o r e s u s c e p t i b l e to local inf e c t i o n s . T h i s h a s n o t b e e n our e x p e r i e n c e . N u r s e s w i t h u p p e r r e s p i r a t o r y i n f e c tions-throat, e t c . - - a t t h e C i t y H o s p i t a l h a v e b e e n d i r e c t l y a d m i t t e d to t h e C o n t a g i o u s t t o s p i t a ] f o r t h e p a s t t h r e e y e a r s , a n d t h e r e h a s b e e n no m a r k e d inc r e a s e in t h e n u m b e r of u p p e r r e s p i r a t o r y i n f e c t i o n s . The economic benefits received by the hospital and the patient more than compensate for the reactions suffered. M a n y o f t h e n u r s e s h a d b o t h local a n d g e n e r a l r e a c t i o n s , f a i r l y s e v e r e a t t i m e s w i t h a r t h r i t i s , a d e n i t i s , etc., a n d i m m u n i z a t i o n h a d to be s t o p p e d i n t w e n t y - f i v e i n s t a n c e s . O v e r 99 p e r c e n t of t h e s e p e r s o n s w h o h a d a n e g a t i v e D i c k t e s t a f t e r t h e y h a d b e e n a c t i v e l y i m m u n i z e d did n o t c o n t r a c t s c a r l e t f e v e r . On t h e o t h e r hand, many persons with negative Dick tests who have not been immunized have c o n t r a c t e d t h e d i s e a s e . I n s h o r t , a n e g a t i v e D i c k t e s t is n o t as i n d i c a t i v e as a p o s i t i v e one in a n u n i m m u n i z e d i n d i v i d u a l , b u t i t is still a p r a c t i c a l t e s t . S c a r l e t f e v e r a n t i t o x i n s were so b u l k y a n d c a u s e d so m a n y r e a c t i o n s (6,000 u n i t s in 20 c.c. of h o r s e s e r u m ) t h a t we d i s c o n t i n u e d t h e i r u s e f o r s e v e r a l y e a r s . A f e w y e a r s ago i t w a s d i s c o v e r e d t h a t s c a r l e t f e v e r a n t i t o x i n could be conc e n t r a t e d a n d t h a t m o s t of t h e f a c t o r s c a u s i n g t h e r e a c t i o n s we o b j e c t e d to could be d i g e s t e d o u t b y e n z y m e s a n d t h e r e m a i n i n g a l b u m i n d i a l y z e d , precipitated~ a n d filtered a w a y . T h e L e d e r l e L a b o r a t o r i e s c o n c e n t r a t e d t h e i r m a t e r i a l d o w n to a p p r o x i m a t e l y 3 c.c. W e t r i e d t h i s a n t i t o x i n i n o v e r 800 c a s e s ( L e d e r l e ) , i n j e c t i n g i t i n t r a m u s c u l a r l y , a n d we w e r e a s t o n i s h e d a t t h e r e s u l t s o b t a i n e d a f t e r i t s use. T h e t e m p e r a t u r e u s u a l l y d r o p p e d to n o r m a l w i t h i n t w e l v e h o u r s a f t e r inj e c t i o n ; t h e r e w a s a d e c r e a s e in t h e n u m b e r o f c o m p l i c a t i o n s ; t h e p a t i e n t s f e l t s u b j e c t i v e l y b e t t e r w i t h i n t h e s a m e p e r i o d of t i m e , a n d t h e r a s h o f t e n disap~ p e a r e d w i t h i n t w e n t y - f o u r h o u r s or w a s g r e a t l y modified. T h e n u m b e r of Serum r e a c t i o n s w a s n o t m o r e t h a n f r o m 8 to ]1 p e r c e n t , t h e a p p r o x i m a t e r e s rate we o b t a i n e d in p a t i e n t s w h o h a d b e e n g i v e n c o n c e n t r a t e d d i p h t h e r i a s e r a of h i g h potency. P a r k e , D a v i s & Co. also c o n c e n t r a t e d t h e i r a n t i t o x i n to a p p r o x i m a t e l y 3 c.c. W e also n s e d t h i s ' a n t i t o x i n in 800 c a s e s a n d c a n s t a t e t h a t t h e r e s u l t s w e r e e q u a l l y as good as t h o s e w i t h t h e L e d e r l e m a t e r i a l . W e n o w h a v e a t l e a s t t w o a n t i t o x i n s ( L e d e r ] e a n d P a r k e , D a v i s ) w h i c h we f e e l a r e m u c h b e t t e r t h a n conv a l e s c e n t s e r u m . T h e l a t t e r is e x p e n s i v e a n d n o t a l w a y s e a s y to o b t a i n . F u r t h e r -
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more, it m u s t be pooled material, a n d it c a n n o t be standardized. The dose of c o n v a l e s c e n t serum in v a r i o u s localities r a n g e s front 25 to 75 cents for 1 c.e. A t h e r a p e u t i c dose of 50 c.e. would cost f r o m $12.50 to $37.50. A t h e r a p e u t i c dose of commercial scarlet f e v e r a n t i t o x i n costs front $8.89 to $10.00. Commercial a n t i t o x i n s can be s t a n d a r d i z e d at a c e r t a i n s t r e n g t h , a n d t h i s s t a n d a r d i z a t i o n can be r e p e a t e d easily; hence their use seems m o s t practicable. DISCUSSION DR. K A R E L I T Z . Would horse antibody serum administered intravenously give the same r e s u l t s as 50 c.c. of h u m a n c o n v a l e s c e n t s e r u m ? I n other words, would it drop the t e m p e r a t u r e in e i g h t e e n hours? Since t h e r a s h a n d f e v e r of scarlet f e v e r m a y d i s a p p e a r in f r o m twelve to e i g h t e e n hours a f t e r f r o m 50 to 60 c.c. of c o n v a l e s c e n t serum is i n j e c t e d i n t r a v e n o u s l y , t h e u s u a l t i t e r of t h i s s e r u m is a b o u t 5 u n i t s per cubic centimeter. Can y o u o b t a i n equally good results w i t h such small a m o u n t s of horse serum a n t i t o x i n ? I g e t larger areas of b l a n c h i n g w i t h f r o m 1 to 2 u n i t s of h u m a n scarlet f e v e r a n t i b o d y t h a n w i t h 5 u n i t s of horse serum a n t i t o x i n . This m a y be explained b y the g r e a t e r diffusibility of the h u m a n serum. DR. D R E N N A N . - - H o w does the new scarlet fever antitoxin compare with h u m a n convalescent serum? C H A I R M A N T O O M E Y . - - W e feel it is much more efficient. Temperature comes down very rapidly. I t is less expensive; it is a product t h a t is easily standardized and easily kept, and the physician can secure it any time he wishes. DR. T R A I S M A N . - - H a v e you had any experience with intradermal immunization? Is it preferred over the regular method ? C H A I R M A N T O O M E Y . - - D r . Earl introduced the intradermal method. I t has been a theory t h a t the skin is a better organ of immunization t h a n other tissues, b u t this point has not been ascertained definitely. There is no clinical evidence along this line. DR. C O H N . - - D o immunized nurses have more sore throats t h a n usual? C H A I R M A N T O O M E Y . - - N o . All persons in the N u r s e s ' T r a i n i n g School, Cleveland City Hospital, with upper respiratory infections are admitted to the Contagious Hospital. We have had no relative increase in the number of patients admitted with sore throats. T h e P r e v e n t i o n of P e r t u s s i s b y t h e U s e of B a c t e r i a l Vaccines E d w a r d B. Shaw, M.D., S a n f r a n c i s c o , Calif. The control of p e r t u s s l s h a s a l w a y s p r e s e n t e d a n u r g e n t a n d difficult problem for t h e physician. The success of i m m u n o l o g i c m e t h o d s for t h e control of some other i n f e c t i o n s has, u n t i l t h e l a s t f e w years, s i m p l y emphasized t h e i n u t i l i t y of similar m e t h o d s i n w h o o p i n g cough. Saner, in r e v i v i n g a n d i m p r o v i n g the use of bacterial vaccine for t h e p r e v e n t i o n of t h i s disease, p r e s e n t e d a m e a s u r e whose value a n d l i m i t a t i o n s e n g a g e the i n t e r e s t of e v e r y p e d i a t r i c i a n . I t would be v e r y t i m e - c o n s u m i n g to outline t h e complete h i s t o r y of t h i s development. V a c c i n e s p r e p a r e d f r o m the B o r d e t - G e n g o u bacillus h a v e long b e e n used for a t t e m p t e d i m m u n i z a t i o n . One should especially credit t h e f u n d a m e n t a l w o r k of M a d s e n l a n d H u e n e k e n s , e' b u t t h i s use w a s p r e v i o u s l y r e s t r i c t e d m o s t l y to t h e i n t e r v a l b e t w e e n exposure a n d t h e onset of cough. S a n e r ' s especial c o n t r i b u t i o n was the d e v e l o p m e n t of a s t a n d a r d m e t h o d e m b r a c i n g t h e use of f r e s h l y isolated
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strains of especial antigenic properties, grown in such a manner as to preserve their autigenielty; the employment of tremendously large dosage; and performance of immunization prior to exposure. Since the introduction of these m~thods, numerous studies have been made to determine their precise value. Significant observations are based on methods which substantially follow those of Sauer. I t has been stated t h a t the complement fixation response3 is significant evidence of immunity but even if this is unquestioned, it does not provide a method for t e s t i n g immunity as simple and effective as the Schiek test. The only feasible method by which the effectiveness of immunity can be estimated {s the comparison of disease incidence in vaccinated groups and similarly constituted control groups. I t is almost impossible to constitute experimental groups of children so as to control adequately all of the p o t e n t i a l variables in such a study. The capacity for immunization varies w i t h respect to constitution, age, race, other infections i etc. Constant antigenicity of the vaccine has been f a i r l y well assured, but the pertussis bacillus is a notably poor antigen. Degree of exposure influences the likelihood of attack and is affected by such factors as duration and location of contact, the amount and i n t e n s i t y of coughing, and the stage of the disease of the patient. The complexities of this problem make it impossible to arrive quickly at an arithmetical expression for the likelihood of producing immunity. A number of groups have been honestly studied, w i t h the production of a wide range of coneluslons. Observers agree t h a t the injection of these vaccines is almost p e r f e c t l y safe and is accompanied by very little discomfort. I t is also agreed t h a t the production of an immune response adequate to protect against ordinary exposure is a useful objective which justifies such minor discomfort, risk, and expense as is involved. The effectiveness and duration of protection are open to considerable disagreement. I t is a mistake, as F a b e r says,4 to insist upon or expect a " s o l i d '~ immunity.
Hemophilus pertussis is a poor antigen, and even the i m m u n i t y induced by the disease is often inadequate to prote~t~ after a time, against intimate exposure. In order for vaccine to prove its value, it is necessary only to demonstrate t h a t it increases the resistance against attack; when this is agreed upon, modification of method and extension of application may be expected to improve results. I t is doubtless improper to accept any single series as conclusive, but a careful perusal of all of the published reports leads almost inescapably to the conviction t h a t the use of vaccine appreciably and beneficially affects the immune state of the individual. The figures of Sauerp who has probably the largest total experience, of I~endriek and Eldering,s Schermerhorn,~ lViiller,s and Singer-Brooks 9 all persuasively support the value of vaccines. Doull and his co-workers~o alone have presented a series with extremely adverse conclusions. They found the incidence of the disease not demonstrably affected and its severity to be questionably benefited. This result is in such contrast to other experiences as to raise the question of w h e t h e r technical differences (preparation of vaccine?) contribute to the discrepancy. An opinion need not be based entirely on comparison of vaccinated with unvaccinated patients. The experience of S a u e r ~ and of several others has demons t r a t e d poor protection in those given small doses, and augmented effect has been shown in one series using extremely large dosage.~s One can thus compare a series using small dosage w i t h one using large dosage. An experiment of SingerBrooks was also very convincing; using siblings for controls, she compared the incidence of pertussis in those actually exposed who had had no vaccine, who had been given Saner-type vaccine, or who had been given a bacterial .extract of altogether different antigenic nature. Tremendously b e t t e r results were apparent
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in the vaccine group as compared with the control group or those given the other antigen, the latter p a t i e n t s constituting an even b e t t e r control group than those to which nothing was done. An opinion of the value of vaccines need not rest solely on the comparison of huge groups. Whooping cough is extremely contagious and a history of a t t a c k is notably reliable. Experiences in small groups multiply over and over to add to the conviction of the average pediatrician t h a t vaccine is of value; this, at least, is my personal observation. A most convincing small-scale experiment was carried out b y the MacDonalds, who used their own four children as experimental subjects. Two children, one a twin, were immunized with Sauer vaccine; the other twin and another child were not immunized. A f t e r a lapse of tlve months, all four children were inoculated intranasally w i t h living pertussis bacillus. The two who were not immunized developed typical pertussis; the two who were given vaccine were resistant not only to inoculation, but to continued exposure in the household to the other two children. E v e n i f one is not justified in drawing extensive conclusions from this experiment, it seems to me to demonstrate convincingly t h a t vaccine is capable of producing immunity. E v e n i f we conclude t h a t vaccine increases resistance, however, we cannot quickly arrive at an estimate of the duration of this effect. I t is safe to say t h a t protection varies and is not prolonged. The probability is great (although c e r t a i n t y is lacking) that, i f immunity has once been effectively stimulated, it can be enhanced dependably later on b y reinjection of vaccine, perhaps by only a single dose. F a b e r proposes t h a t this be done annually; this is not conducive to childhood friendships. I t might be adequate to reinject vaccine only in the f a c t of known exposure when once a basic i m m u n i t y had been produced. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. ]1. 12. 13.
Madsen, T.: J. A. M. A. 101: ]87, 1933. Huenekens, E. J.: Am. J. Dis. Child. 14: 283, 1917. Daughtry-Denmark, L.: Am. J. Dis. Child. 52: 587, 1936. Faber, H. K.: J. I~ 13: 277, 1938. Sauer, L. W.: J. A. M. A. 112: 305, 1939. Kendrick, P., and Eldering, G.: Am. J. Pub. H e a l t h 26: 8, 1936. Schermerhorn, L. J.: J. PEDIAT. 13: 279, 1938. Miller, J. J.: J. PEDIAT. 13: 290, 1938. Singer-Brooks, C.: J. PEDIAT. 13: 292, 1938. Doull, J. A., a n d others: Am. J. Dis. Child. 58: 691, 1939. Sauer, L., and Hambrecht, L.: J. A. M. A. 91: 1861, 1928. Silverthorn, N., and Fraser, D. T.: Canad. 1Y[. J. 38: 556, 1938. MacDona]d, H., and MacDonald, E. J.: J. Infectious Dis. 53: 328, 1933. DISCUSSION
DR. SILBEIC.--In 980 cases in the last five years I have had only seven cases of whooping cough in those immunized, while from twenty to thirty of my cases each year are in the unimmunized group. DR. S, I. L E B E A U , PITTSBURGH.--Are there any dangers in the use of pertussis vaccine? I think there is the possibility of severe reactions. CHAIRMAN T O O M E Y . - - I f whooping cough immunization were simple, the dlsease should be easy t o control. DR. S H A W . - - W h e n a patient has been exposed to whooping cough, I think that he should be given an extra dose as this raises the titer. DR: I. A. ABT. : ' N o man living can write the history of his contemporaries." Nobody present can estimate the efficacy of many of these preventive measures.
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DR. SHAW.--Vaceine (Sauer) should be given early. The younger the patients are, the poorer the immune response. The maximum risk is under 1 year of age. Using vaccine by Krueger, I have had no success at all either prophylactically or in treatment. I know nothing about topagcn vaccine. DR. F A I R F A X HALL, NEW ROCHELLE, N. Y . - - I use topagen instead of injections in treatment. DR. G. N. H O E F F E L , BosToN.--There is no evidence except emotion to say that Sauer vaccine has done any good. DR. H. A. BECK, DETROIT. On a W P A project in Michigan where the nurses did a careful checkup with the help of the physicians on district cases, the results obtained with vaccine were very satisfactory. The diagnoses were confirmed by doctors, and Dr. Kendrick was in immediate charge of the project. DR. S H A W . - - I t is possible that there may be some danger in group whooping cough vaccine, but this is not likely. A single series by Bradford showed considerable value from convalescent serum. Sauer's vaccine should still be used even though proof of its true value is lacking. DR. O S T E R L I N . - - W h a t is the status in treatment of whooping cough by undenatured bacterial antigen~ DR. S H A W . - - U n d e n a t u r e d bacterial antigen has not been proved to be of any value. DR. J. S. HUNT, CHARLOTTE,N. C.--What is the value of large doses of vitamin C in the treatment of whooping cough~ CHAIRMAN TOOMEY.--There has been no deilnite evidence along this line. DR. H A L L - - W h a t order of immunization do you advocate ? CHAIRMAN TOOMEY.--This is contained in the l~eport of the Committee on Immunization and Therapeutic Procedures for Acute Infectious Diseases which may be obtained from the American Academy of Pediatrics: ' ' 1. Vaccine against smallpox at any age during an epidemic but routinely any time between 3 and 12 months. ~' 2. Immunize against diphtheria between 9 and 18 months. Tetanus toxoid may be used in combination with diphtheria toxoid. c, 3. Vaccinate against pertussis between 6 and .9 months. " 4 . Do a Schick test between 18 and 24 months. Reimmunize against diphtheria if necessary. ' ' 5 . Repeat the Schiek test and smallpox vaccination at 6 years or during epidemic periods, l~eimmunize against diphtheria and revaccinate if necessary. " 6 . I f tetanus toxoid is desired, it may be given at any age period, but the reactions are not so severe if given between 2 and 6 years. I f combined with diphtheria toxoid, it may be given at the same time. Scarlet fever toxin might be given in epidemics and to groups previously indicated. Typhoid fever vaccine may be given when and where i n d i c a t e d . "
16-18,
1939
Round Table Discussion on the Preventio~ of Contagious Diseases
Chairman: J.A. Toomey, M.D., Cleveland, Ohio Assistants : E.B. Shaw, M.D., San Francisco, Calif. G. W. Kutscher, Jr., M.D., Asheville, N. C. C. F. McKhann, M.D., Boston, Mass. J. S. Baird, M.D., Pittsburgh, Pa. H. T. Price, M.D., Pittsburgh, Pa. Secretaries : Ralph E. Pray, M.D., Fargo, N. D. A. S. Traisman, M.D., Chicago, Ill. Convalescent Mumps Serum G. W. Kutscher, Jr., M.D., Asheville, N. C. A l t h o u g h there is n o t h i n g new concerning the etiology, diagnosis, a n d treat. m e n t of p a r o t i t i s in t h e p a s t fifteen years, some progress h a s been m a d e in the p r o p h y l a x i s a g a i n s t t h e disease. The l a t t e r is i l l u s t r a t e d b y a n experience in a b o y s ' camp t h i s l a s t s u m m e r . One h u n d r e d a n d ~wenty-five boys a t t e n d e d t h i s camp, a n d fifty-two of t h e m had n e v e r h a d m u m p s . T h i r t e e n d a y s a f t e r the camp opened, m u m p s was dlscovered in a boy who h a d suffered a n e c k i n j u r y . The orthopedic surgeon had applied a r e s t r a i n i n g b a n d a g e w h i c h included t h e lower j a w as well as the neck. F e v e r developed w h i c h could not be explained on t h e b a s i s of injury. The dressi n g s were removed, a n d b i l a t e r a l p a r o t i t i s was discovered. T h i s boy h a d been visited in t h e i n f i r m a r y b y every fellow camper susceptible to m u m p s ; hence, all were exposed. The problem t h e n p r e s e n t e d i t s e l f : W h a t should be done for the r e m a i n i n g fifty-one s u s c e p t i b l e boys, some of w h o m were 300 miles f r o m home? Three of the camp directors who h a d h a d m u m p s in recent y e a r s (one had recovered only one m o n t h previously) offered t h e i r blood. F i f t e e n h u n d r e d cubic c e n t i m e t e r s were collected, and f r o m t h i s 500 c.c. of c o n v a l e s c e n t s e r u m was obtained. The serum was found sterile and W a s s e r m a n n negative, and the samples were pooled. On t h e f o u r t h d a y a f t e r the first case of m u m p s w a s discovered, t h e convalescent serum was administered. The ages of these boys were b e t w e e n 9 and 16 years. To those y o u n g e r and of l i g h t e r w e i g h t 8 c.c. of the s e r u m were a d m i n i s t e r e d i n t r a g l u t e a l l y ; to the older a n d h e a v i e r boys, 10 c.c. Those w i t h a h i s t o r y of a l l e r g y were g i v e n skin tests, w i t h o u t s h o w i n g a n y reaction. There were no delayed serum r e a c t i o n s or m a r k e d local t e n d e r n e s s at the site of t h e injections. There was no increase in t e m p e r a t u r e , s a v e in one i n s t a n c e , w h e n f o u r t e e n d a y s a f t e r exposure a n d t e n d a y s a f t e r r e c e i v i n g a dose of t h e serum, a n o t h e r case of m u m p s developed. A l t h o u g h t h e r e 'was f a i l u r e to protect here, there w a s also a h i s t o r y of a possible outside exposure. This boy developed a v e r y mild a t t a c k of t h e disease. The late A l f r e d Hess, in 1915, was the first to report upon t h e prophylactic use of c o n v a l e s c e n t whole blood in parotitis. The s e v e n t e e n children in his series 405
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w e r e 100 p e r c e n t p r o t e c t e d b y t h e u s e of f r o m 6 to 8 c.c. of blood. Reagan~ in 1925, w a s t h e first to r e p o r t on t h e u s e of c o n v a l e s c e n t s e r u m p r o p h y l a c t i c a l l y in d o s e s o f f r o m 2 to 4 c.c., w i t h p r a c t i c a l l y 100 p e r c e n t success. R e a g a n a d v i s e s t h e u s e of t h e s e r u m b e f o r e t h e s e v e n t h d a y f o l l o w i n g e x p o s u r e . T h e l i t e r a t u r e c o n t a i n s s e v e r a l a d d i t i o n a l r e f e r e n c e s to t h e u s e o f c o n v a l e s c e n t s e r u m a g a i n s t mumps. P o s s i b l y t h e dose of f r o m 8 to 10 c.e. of s e r u m g i v e n in t h i s s t u d y w a s l a r g e r t h a n n e c e s s a r y . H a l f of t h e dose m i g h t h a v e b e e n a d e q u a t e . 14owever~ s i n c e o n l y one o f t h e d o n o r s w a s a r e c e n t c o n v a l e s c e n t , i t w a s t h o u g h t w i s e to u s e t h e l a r g e r dose, e s p e c i a l l y s i n c e it w a s a v a i l a b l e . W i t h a r e c o g n i z e d i n f e e t l o n i n c i d e n c e of b e t w e e n 20 a n d 50 p e r c e n t f o l l o w i n g i n t i m a t e e x p o s u r e , i t is b e l i e v e d t h a t t h i s p r o c e d u r e p r o t e c t e d b e t w e e n f i f t e e n a n d t w e n t y - f i v e b o y s a g a i n s t t h e disease. T h e one f a i l u r e to p r o t e c t allows a p r o t e c t i o n i n c i d e n c e in t h i s s t u d y of 98.04 p e r cent. I n o t h e r w o r d s , f i f t y o u t o f f i f t y - o n e s u s c e p t i b l e a n d e x p o s e d b o y s w e r e p r o % e t e d a g a i n s t m u m p s . Since it is well k n o w n t h a t c o n v a l e s c e n t m e a s l e s s e r u m will o f t e n p r o l o n g t h e i n c u b a t i o n p e r i o d f o l l o w i n g e x p o s u r e to m e a s l e s , t h i s f a c t w a s k e p t i n m i n d i n t h i s s t u d y . B e c a u s e o f t h e f a c t t h a t no a d d i t i o n a l c a s e s d e v e l o p e d in t h e r e m a i n i n g five w e e k s o f c a m p f o l l o w i n g t h e a d m i n i s t r a t i o n of t h e s e r u m , i t is b e l i e v e d t h a t doses of f r o m 8 to 10 e.e. of c o n v a l e s c e n t s e r u m will a d e q u a t e l y p r o t e c t b o y s o f t h i s a g e a g a i n s t t h e disease. S u c h a course a l l o w e d u s to k e e p t h e c a m p open for the season.
DISCUSSION DR. J. W. BRUCE~ LOUISVILT,E.--In the differential diagnosis of mumps~ milking a l o n g S t e n s e n ' s d u c t p r o d u c e d a p u r u l e n t s e c r e t i o n in n o n e p i d e m i e p a r o t i t i s . DR. 3/I. Z E L I G S , CINCINNATI.--In a b o a r d i n g school where t h e r e were eighty-five boys, two cases of m u m p s developed. F i f t y boys g a v e histories of never h a v i n g h a d m u m p s . F r o m 5 to 10 c.e. of convalescent s e r u m were given to every one of t h e eighty-five boys~ a n d t h e r e were no other cases of m u m p s i n t h e i n s t i t u t i o n . C H A I R M A N T O O M E Y . - - I n a n o r p h a n a g e n u m b e r i n g 410 children~ two cases of m u m p s developed. A l t h o u g h p r o p h y l a x i s a n d p a s s i v e i m m u n i t y were n o t employed~ no other cases developed. DR. S. K A R E L I T Z , NEW u cubic c e n t i m e t e r s of s e r u m were adminis. tered to f o u r t e e n y o u n g s t e r s u n d e r 5 y e a r s of a g e who h a d developed m u m p s . O f t h e fourteen~ five were n o t modified b y t h e serum. O n l y local r e a c t i o n s were obtained. F r o m these f a c t s I a m u n a b l e to d r a w a n y definite conclusions. DR. S H A W . - - I t should be given.
seems p l a u s i b l e t h a t as t h e a g e of t h e child increases more s e r u m
DR. A. F. ABT~ CHICAG0.--The m a i n t h i n g is to increase t h e dose with increase in w e i g h t . DR. H. T R E M A I N E , B O I S E . - - F r o m o b s e r v a t i o n s it seems t h a t t h e y o u n g e r t h e patients, the better the results. DR. G. L. D R E N N A N , J-;kCKSONVILLE~ I s L - - M u m p s is a f a i r l y c o m m o n c a u s e of d e a f n e s s . I n a s t u d y o f 10,000 d e a f children above 2 y e a r s of age, f r o m 2 to 3 per cent of acquired deafness followed mumps. DR. S t t A W . - - I t is p r o b a b l y similar to t h a t w h i c h follows m e n i n g i t i s a n d proba b l y is due to d a m a g e in t h e cochlea a n d is s e c o n d a r y to t h e v e r y c o m m o n m e n i n g e a l involvement.
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DR. A. S. T R A I S M A N , CHIOAGo.--What is the frequency of recurrent epidemic parotitls ? DR. K U T S C t I E R . - - I do not have exact figures, but it is rare. DR. Y. V. G R E E N E B A U M , CINCn~NATL--I-Iave you ever seen p u r p u r a in m u m p s ? CHAIRMAN TOOMEY.--No. DR. T. P. S A L T I E L , C m c A o o . - - W h a t is the procedure to follow when a susceptible f a t h e r and mother have been exposed to a child with m u m p s ? DR. K U T S C I t E R . - - T h e supposition, of course, is t h a t the f a t h e r and m o t h e r h a v e not h a d m u m p s . I f t h e y h a v e n o t h a d m u m p s , t h e same procedure should be followed as in the case of children.
Poliomyelitis Joseph S. ]Baird, M.D., Pittsburgh, Pa. We had two or three cases of poliomyelitis late in July. New cases are still giving trouble even now in November. There were, in all, about forty cases in the city, and twenty-three cases from outside the city came in for care. All were children. The twenty-three cases occurred along the river, and at no time were there two children in one family who were stricken with the disease at the same time. No contacts were indicated between eases. ~ Nine deaths, all bulbar types, were reported. Dr. I~[enry T. Price at Children's ]:Iospital in Pittsburgh had ten patients on whom he used the respirator. Four made good recovery. The average number of respiratory days was 280. During the past month~ he reported five cases even though there has been frost. Recently there has been no work on the prevention of poliomyelitis that has been of any value. From work done at Detroit it may be concluded that convalescent serum does no good. The Public t t e a l t h m e n in M i c h i g a n h a v e verified this opinion. T h e y report t h a t n a s a l s p r a y used as p r e v e n t i o n h a s a c t u a l l y done d a m a g e a n d been of no benefit.
Dr. Albert Sabin, Cincinnati, Ohio The shortest comment on the present status of prophylaxis and specific therapy of poliomyelitis would be that there isn't any. When we inquire why there isn't any~ we find that as regards prophylaxis experimental studies both in monkeys and man established that available vaccines were either ineffective or dangerous, or both, that little or no protection can be expected from immune~ convalescent, or adult sera i and that, while certain nasal chemical sprays can protect monkeys against infection by the olfactory route, similar sprays in human beings have yielded no evidence of protection against the natural disease. Although it has been glibly stated in recent years that the virus invades the human nervous system by the olfactory pathway, there is no evidence derived from studies on human beings that such is actually the case. ]V[y own studies on more than 2,000 serial sections of olfactory bulbs from ten cases of human poliomyelitis failed to reveal the lesions which I have always been able to find in monkeys whose nervous systems were infected via the olfactory route. I mention this not as conclusive evidence against the olfactory portal of virus entry in man, but rather to indicate that there is as yet no good evidence for it. All this is brought up here because a n y hope t h a t m a y possibly be e n t e r t a i n e d f o r the prophy]actlc effects of the spraying or instillation of certain chemical substances into the nose is dependent upon the v i r u s i n v a d i n g the h u m a n n e r v o u s s y s t e m b y t h e o l f a c t o r y route.
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Specific i m m u n e s e r u m t h e r a p y a f t e r s i g n s a n d s y m p t o m s of t h e disease, e i t h e r p r e p a r a l y t i c or p a r a l y t i c , a r e a p p a r e n t h a s n e i t h e r t h e o r e t i c a l n o r p r a c t i c a l b a s i s a t t h e p r e s e n t t i m e . T h e o r e t i c a l l y , t h e r e is e v e r y r e a s o n to b e l i e v e t h a t m o s t of t h e cells t h a t a r e g o i n g to be a f f e c t e d b y t h e v i r u s a r e i n v a d e d s e v e r a l d a y s be. f o r e t h e a p p e a r a n c e of c l i n i c a l s i g n s a n d t h a t n o t e v e n l a r g e a m o u n t s of a n t i b o d y c a n i n f l u e n c e t h e effects of t h e i n t r a c e l l u I a r v i r u s or p r e v e n t i t f r o m s p r e a d i n g to o t h e r cells. T h e b e s t e v i d e n c e f o r t h i s as r e g a r d s p o l i o m y e l i t i s is f o u n d in m o n k e y s w h i c h develop s i g n i f i c a n t a m o u n t s o f n e u t r a l i z i n g a n t i b o d y as a r e s u l t o f v a c c i n a t i o n a n d y e t a r e f u l l y s u s c e p t i b l e to n a s a l i n s t i l l a t i o n o f t h e v i r u s . P r a c t i c a l l y , as is well k n o w n b y now, t h e r e s u l t s o f p r o p e r l y c o n t r o l l e d s t u d i e s in m a n s h o w e d no effect of c o n v a l e s c e n t s e r u m e i t h e r in t h e p r e p a r a l y t i c or paralytic stages. The suggestion that injections of vitamin C can prevent the d e v e l o p m e n t of p a r a l y s i s in m o n k e y s h a s n o t b e e n c o n f i r m e d in c a r e f u l l y cont r o l l e d e x p e r i m e n t s in w h i c h i t w a s f o u n d t h a t n e i t h e r l a r g e n o r s m a l l a m o u n t s o f t h e n a t u r a l or s y n t h e t i c v i t a m i n m o d i f i e d t h e c o u r s e of t h e e x p e r i m e n t a l d i s ease in any way. DISCUSSION C H A I R M A N T O O M E Y . - - D o e s s e r u m do a n y good? t h a t n o t e n o u g h s e r u m is used.
L e v i n s o n of Chicago t h i n k s
DR. M c E : H A N N . - - M o n k e y s a n d h u m a n b e i n g s are n o t the same. Therefore, the work done on m o n k e y s does not show w h a t can be done on h u m a n beings. I n Boston, t h e v i r u s h a s been i n j e c t e d i n t r a s p i n a l l y ( i n t r a c e r e b r a l l y ) a n d c o n v a l e s c e n t s e r u m (]50 c.c.) h a s been g i v e n with no benefit. C H A I R M A N T O O M E Y . - - I f one i n t r o d u c e s poliomyelitis virus in t h e e x p e r i m e n t a l a n i m a l b y w a y of the g a s t r o i n t e s t i n a l t r a c t a n d t h e n gives serum~ poliomyelitis does n o t result. DR. S H A W . - - S e r u m does some good. The real a r g u m e n t is, Can a n y a m o u n t of s e r u m g i v e n do a n y good? Should it be p o u r e d in, w i t h no set a m o u n t s given? No one h a s ever s t a n d a r d i z e d the a m o u n t s to be a d m i n i s t e r e d . R e m e m b e r t h a t m u c h of t h e s e r u m m a y have no potency, m a y n o t be h y p e r i m m u n e serum. I t h a s been m y experience t h a t p a t i e n t s who are given s e r u m do b e t t e r t h a n those who receive none. E x p e r i m e n t s on h u m a n b e i n g s cannot, of course, c o m p a r e with those on monkeys. P o l i o m y e l i t i s m a y n o t be j u s t a disease of t h e c e n t r a l nervous system. T h e r e is a s y s t e m i c phase. I f there is, we should c e r t a i n l y u s e serum. DR. M c K H A N N . - - I believe t h a t s e r u m m i g h t influence the p r e p a r a l y t i c , b u t I h a v e no a d e q u a t e b a c k g r o u n d f o r t h i s s t a t e m e n t . DR. I. A. ABT, CuIcAOO.--Belief in a t h e r a p e u t i c procedure dies h a r d . W h y not f a c e t h e f a c t s ? W e have no p r o p h y l a c t i c n o r c u r a t i v e t r e a t m e n t s . W e know nothi n g a b o u t it. DR. E. G. H O R T O N , Co~mMBUS.--The L o r d is m e r c i f u l in our cases of poliomyelitis. I h a v e lost f a i t h in m y a b i l i t y to do a n y t h i n g a b o u t it. E v e n severe cases have come t h r o u g h t h i s year. DR. H. B. S I L V E R , NEWAKK, N. g . - - D r . K r a m e r of B r o o k l y n s a y s t h a t n a s a l w a s h i n g s w i t h ephedrine do some good. T h i s t r e a t m e n t m a y be used some day. Diphtheri~, It. T. Price, M.D., P i t t s b u r g h , ' P a . W h a t s t a g e is d i p h t h e r i a in a n d w h a t is i t ? W i l l it be r e l e g a t e d to a h e a p of u n k n o w n s . ~ T h a t is a l w a y s a p o s s i b i l i t y , t h o u g h a r a r e one. T h e first t h i n g to
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do is to s t a m p o u t t h e focus. T h e l a c k of c o o p e r a t i o n of t h e m e d i c a l p r o f e s s i o n in p r o t e c t i n g c h i l d r e n m a y r e s u l t i n a s e v e r e e p i d e m i c . F i r s t t o x i n - a n t i t o x i n w a s used, a n d n o w t o x o i d , b u t t h e u s e of e i t h e r is a l w a y s f o l l o w e d b y a S e h i c k t e s t . R e m e m b e r t h a t s t r e p t o c o c c i c t h r o a t i n f e c t i o n s w e r e o f t e n c a l l e d l a r y n g e a l dipht h e r i a i n d a y s g o n e by. W e n o w realize m o r e w h a t d i p h t h e r i a is. I f we do diagnose i t p r o p e r l y , s e r u m s h o u l d g i v e r e s u l t s . DISCUSSION C H A I R M A N T O O M E Y . - - H o w m u c h of our p r e s e n t decrease in m o r b i d i t y is due to a n a t u r a l lull r a t h e r t h a n to p r o p h y l a c t i c m e a s u r e s ? W e a r e p r o b a b l y in a ~rough of t h e disease. D R . G. I:L F E L L M A N , MILWAUK~E.--We m a y h a v e a n experience similar to the one in "Vienna in 1933. T h e r e the s e r u m proved of no value. DR. K A R E L I T Z . - - R e f u g e e children c o m i n g into t h i s c o u n t r y now f r e q u e n t l y give a h i s t o r y o f h a v i n g h a d diphtheria. N o n e have been g i v e n p r o p h y l a x i s , a n d t h e y have a b o u t t h e s a m e n u m b e r of d i p h t h e r i a cases with no p r o p h y l a x i s as we do with it. D R . A. D. K A I S E R , ROCt{ESTEI{, N. u before or a f t e r the Schiek test.
or two i n o c u l a t i o n s should be given
DR. @ R E E N E B A U ] V L - - I t is good practice to give t h e combined d i p h t h e r i a a n d t e t a n u s toxoid i f the follow-up Schick test is positive. DR. 1 V [ c K H A N N . - - R e p e a t e d Schick t e s t s give p s e u d o r e a c t i o n s . W h e n one is goi n g to r e p e a t a Schick test, there should be a n i n t e r v a l of f r o m two to f o u r weeks. DR. I. A. A B T . - - 1 a m n o t sure t h a t t h i s is a lull in d i p h t h e r i a . I t m a y be perm a n e n t . W e m a y wake u p to find ourselves in a n epidemic o f r e f r a c t o r y cases. A u s t r i a did n o t i m m u n i z e at all. Despite this, there was no d i p h t h e r i a there f o r t e n years. T h e n a f t e r t h a t t h e r e was a terrific epidemic. DR. tI. B. M E T T E L , I~DIA~A>OLIS.--Whether the Schick test is n e g a t i v e or positive, we have only a skin reading. I t does not m e a n t h a t t h e child is protected 9t g a i n s t diphtheria. DR. F E L L M A N . - - H o w
m a n y are u s i n g combined d i p h t h e r i a a n d t e t a n u s toxoid?
DR. K U T S C H E R . - - I would not give s e r u m f o r p u n c t u r e w o u n d s if I h a d given t e t a n u s - d i p h t h e r i a c o m b i n a t i o n s before. DR. t t O R T O N . - - S o m e p r a c t i c i n g p h y s i c i a n s do n o t know d i p h t h e r i a . p r o t e s t a g a i n s t t h e single shot i m m u n i z a t i o n s .
I should
DR. I. A. A B T . - - I n t e t a n u s , m a k e every p u n c t u r e w o u n d a n open wound, clean it out, a n d incise it. T h e n you w o n ' t need passive i m m u n i t y a n d y o u c a n avoid t h e use of so m u c h serum. DR. Z E L I G S . - - D o y o u feel t h a t two h y p o d e r m i c s o f a l u m - p r e c i p i t a t e d toxoid would raise t h e t i t e r i f u s e d at t w o - m o n t h i n t e r v a l s i n s t e a d of three-week i n t e r v a l s ? DR. P R I C E . - - T h e m e t h o d is to use t h e second dose o f toxoid in three weeks. T h e n do a Schick test. I f positive, r e p e a t t h e toxoid. DR. S H A W . - - T h e c a p a c i t y of the p a t i e n t to p r o d u c e a n t i t o x i n f r o m shots is the all-determining factor.
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DR. M. L. C O O P E R , CINCINNATL--Merety t h e a d m i n i s t r a t i o n of a Schiek test gives elevated t i t e r in the blood. DR. M e K H A N N . - - I n m y experience several p a t i e n t s with n e g a t i v e Schiek t e s t s have developed d i p h t h e r i a . However, the Schiek t e s t indicates some resistance to diphtheria. DR. B A I R D . - - A recent P u b l i c H e a l t h c o n v e n t i o n s u m m a r y s t a t e d t h a t two doses o f a l u m toxoid g i v e n f r o m t h r e e to f o u r weeks a p a r t are more effective t h a n t h r e e doses of toxold plain. DR. G. F. P A T T E R S O N , CINC~NNArrI.--Of 123 children, o n e - f o u r t h were imm u n i z e d w i t h t o x i n - a n t i t o x i n . The o t h e r s were i m m u n i z e d with toxold. F o r t e n y e a r s t h e c h i l d r e n h a d Sehick t e s t s each year. T h e entire g r o u p h a s r e m a i n e d n e g a tive u n t i l t h i s y e a r when t h e r e were seven positives. D R . F . B. M I N E R , FLINT, M i c h . - - S k i n s e n s i t i v i t y s o m e t i m e s gives a f a l s e p o s i t i r e S e h i c k t e s t . Give t w o d o s e s of a l u m t o x o i d , one a t 9 m o n t h s of a g e a n d t h e second dose at 10 m o n t h s . R e p e a t t h e Schiek t e s t on e n t e r i n g school. DR. D R E N N A N . - - W h a t
dose of p r e c i p i t a t e d toxoid is u s e d ?
C H A I R M A N T O O M E Y . - - T h i s dose h a s b e e n v a r i a b l e . T h e doses r e c o m m e n d e d b y t h e C o m m i t t e e on I m m u n i z a t i o n a n d T h e r a p e u t i c P r o c e d u r e s f o r A c u t e I n f e c t i o u s D i s e a s e s o f t h e A m e r i c a n A c a d e m y of P e d i a t r i c s are as f o l l o w s : " T h r e e t y p e s o f m a t e r i a l a r e u s e d to i m m u n i z e a g a i n s t d i p h t h e r i a : (1) d i p h t h e r i a t o x o i d a n d (2) a l u m - p r e c l p i t a t e d t o x o i d f o r c h i l d r e n u n d e r 10 y e a r s of age, e a c h t o x o i d m a t e r i a l to be i n j e c t e d i n doses of 0.5 e.c., 1 e.e., a n d 1 e.e. a t two- to f o u r - w e e k i n t e r v a l s . V a r i a t i o n s of t h e s e doses o f t h e t o x o i d s h a v e b e e n u s e d i f r e a c t i o n s f o l l o w t h e i n i t i a l i n j e c t i o n . O n e - t e n t h c u b i c c e n t i m e t e r , 0.2 e.e. a n d 0.5 e.c. a r e g i v e n e v e r y t w o to f o u r w e e k s , a n d a n a d d i t i o n a l dose o f 1.0 c.e. m a y be g i v e n i f t h e r e a c t i o n s a r e n o t too severe. (3) A h o r s e a n d g o a t t o x i n - a n t l t o x l n f o r p e r s o n s o v e r :10 y e a r s of a g e i n j e c t e d s u b c u t a n e o u s l y i n doses o f 0.5 e.e. a n d 1 e.e. a t two- to f o u r - w e e k i n t e r v a l s . " DR. R. P. EOGERS~ GREENWIGIt, C o N N . - - W h a t is t h e relative reaction f o l l o w i n g a Schick t e s t a n d t h a t a f t e r a dose of toxoid in a child n e g a t i v e to t h e Sehick t e s t ? C H A I R M A N T O O M E Y . - - T h e r e have been no r e a c t i o n s in children n e g a t i v e to t h e Sehick test, b u t t h e r e will a l w a y s be some reaction, a l t h o u g h o f t e n slight, to a n i n j e c t i o n o f toxoid. DR. I. R. C O H N , TOLEDO.--Is p r e c i p i t a t e d toxoid p r e f e r r e d over fluid toxoid? H o w a b o u t t h e v a l u e of d i p h t h e r i a - t e t a n u s toxoid? CHAIRMAN TOOMEY.--I t h e m a t e r i a l of choice. DR. I. P . B R O N S T E I N , protect ?
believe t h a t p r e c i p i t a t e d toxoid m i x t u r e will become
CHICAGO.--I%r how l o n g a period will t e t a n u s toxoid
D R . S t I A W . - - T h l s h a s n o t b e e n d e t e r m i n e d as y e t . I n c a s e s of t e t a n u s , a n t i t o x i n g i v e s a p r o t e e t l o ~ f o r o n l y a s h o r t a n d v a r i a b l e p e r i o d of t i m e . Medicol e g a l c o n s i d e r a t i o n s l e a d t o t h e u s e o f m a n y d o s e s o f t e t a n u s a n t i t o x i n , b u t it is h a r d to p r o v e h o w m u c h i m m u n i t y o f a n y v a l u e is a c t u a l l y t h u s p r o v i d e d . A good m a n y c a s e s of t e t a n u s h a v e b e e n g i v e n t e t a n u s a n t i t o x i n as a p r o p h y l a c t i c . I t seems reasonably assured that the patient who has been given tetanus toxoid, and t h e n f o l l o w i n g i n j u r y h a s b e e n g i v e n a s e c o n d dose o f toxoid, h a s a b e t t e r prosp e c t o'f b e i n g c o m p l e t e l y p r o t e c t e d a g a i n s t t e t a n u s t h a n one w h o is g i v e n : o n l y tetanus antitoxin.
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DR. M. F. OSTERLIN, TR&VEI~SECITY, MIc:I.--How many shots of toxoid should be given to obtain a negative Schick test? I had a p a t i e n t to whom I gave the injections without obtaining a negative Schick test. C H A I R M A N T O O M E Y . - - V e r y frequently those persons who seem problems iu immunization are really nothing more than p a t i e n t s who have become sensitive to the products c o n t a i n e d i n the broth in which the b a c t e r i a grew, and it will be f o u n d . t h a t the m a j o r i t y of these p a t i e n t s who still show reaction a f t e r immunizatiou are sensitive to these products. Prevention of Measles Charles F. lYIcKhann, M.D., Boston, Mass. Deaths from measles are usually to cmnplications of the disease, especially pulmouary disorders caused b y the streptococcus or pneumococcus. ~Iany of these complications m i g h t be prevented b y adequate iso]atlon of measles patients. P a t i e n t s with measles should not be placed t o g e t h e r on group isolation, but should be on individual precautions in separate rooms, i f possible. Thus, patients w i t h measles will not carry the disease to one another, but they may by coughing or sneezing disseminate , either by direct contact or b y air-borne infections~ secondary organisms to their bed neighbors. Since deaths are more numerous at the younger ages~ precautions should be especially stringent in these groups. ~/Iasks of proper filtering design wl]l help to prevent the spread of dangerous organisms from the personnel to the p a t i e n t . Investigations as to the role of air-borne infection in the spread of measles and its complications have been carried on in the past three years. Definite s t a t e m e n t s as to ~he rMative proportion of direct personnelto-patient infection and of air-borne infection in the dissemination of measles and complicating organisms, as well as an appraisal of the value of ultraviolet light in prevention of transmission, cannot as yet be made. Sulfanilamide and sulfapyridine have been observed not to have any effect on the course of measles, but may be effective in the t r e a t m e n t of streptococcal or pneumococeal complications. Some authors have recommended the use of these drugs throughout the course of the febrile eruptive stage as a preventive of serious complications. Should such a procedure be proved relatively free from danger and effective, its wide adoption would f u r t h e r minimize the dangers of the disease and render the search for bio]oglc p r e v e n t i v e s less important. Specific t r e a t m e n t of measles is not as yet possible a f t e r the appearance of tile eruption. Large doses of sermn may be effective in m i t i g a t i n g the severity of the attack, i f given before the rash appears. An active immunization is urgently needed and is promised b y the work of Wenekebach and others who claim to have cultivated the v i r u s in chick embryos and to have observed t h a t a f t e r cultivation the virus becomes a t t e n u a t e d and an injection into susceptible persons produces a modified disease. When measles virus, either a t t e n u a t e d or of normal strength, becomes available, inoculation of p a t i e n t s with subsequent partial immunization of p a t i e n t s who have received full s t r e n g t h virus will be justified. P r e v e n t i o n or modification of the disease b y the use of human immune bodies in the form of convalescent serum, adult immune serum, or immune globulin (placental e x t r a c t ) remains the only reasonably dependable prophylactic procedure. Yet w i t h the diminution in complications following b e t t e r isolation of measles p a t i e n t s and with successful therapy available for some of the more severe complications, even the prevention or modification of measles by the use of serum need be used only in selected instances. Convalescent serum an~[ human immune globulin (placental extract) seem to be somewhat more effective than adult immune serum, while convalescent serum
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has the a d v a n t a g e over immune globulin of being more uniform in its potency and it seldom causes a local reaction at the point of injection. The dosage of any o f these agents is determined, in addition to potency, b y the time of administration, age and sex of the patient, and possibly b y the degree of exposure. Convalescent serum is usually effective in from 4- to 6-c.e. dosage; immune globulin from 2 to ~ c.c.; and adult immune serum, from 15 to 20 c.e. I m m u n i t y resu]tlng from the administration of these substances is passive in character and of short duration, seldom lasting more than two or three weeks. The time o f a d m i n i s t r a t i o n is a factor of great importance in determining w h e t h e r prevention or modification of the disease will be induced. E a r l y in the incubation period, the injection in the doses given above will usually p r e v e n t the disease, while later in the incubation period larger amounts are needed; and a f t e r the onset of symptoms, still larger amounts are required i f any effect is to be achieved. I n measles modified by the use of serum, the incubation period is often prolonged,. necessitating the lengthening of the quarantine period of children who receive the serum. S e v e r i t y of the disease is reduced o f t e n t i m e s so much t h a t the typical features of the disorder are not observed. Complications are usually avoided. W h e t h e r the extreme modification which is sometimes obtained results in active p e r m a n e n t immunity has not been definitely determined. However, in general, the a t t e n u a t e d disease is thought to give p e r m a n e n t immunity and is, therefore, the desirable result of serum administrations. I n certain types of patients, notably institutional cases, or acutely or chronically ill debilitated children, especially those between 6 months and 2 years of age, during which time the death rate in measles is high, protection through the use of serum should be obtained if possible. DISCUSSION DR. I. B. SILBE]~, CLEVP,LANI).--Reaction from imumne globulin has seemed to aggravate some cases. DR. K A R E L I T Z . - - T h e extraction of globulin from human blood seems a good prospect. Then standardized doses would be possible. Blood from the cord, third labor stage, and laked blood could provide the source. No two workers in measles are able to compare their results as far as doses, effect, etc., are concerned. I believe that schools are not good controls. DR. COI-IN.--Should sulfanilamide be given as treatment of measles.~ DR. M c K I I A N N . - - I feel that sulfanilamide should be given to those persons who have complications of this disease. ])R. GREENEBAU1VL--Is there any value in the use of immune globulin by mouth ? DR. McKHANN.
I do not believe so.
DR. K U T S C H E R . - - W h a t is the duration of immunity following serum to modify nmasles? DR. M c K H A N N . - - T h i s is merely a passive immune principle and such immunity may be lost within a few weeks. DR. COI-IN.--Is natural immunity present in some children? DR. M c K H A N N . - - T h e r e is a possibility that some children may be immun% but the number is so few that, for practical purposes, it may be ignored.
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Scarlet Fever John A. Toomey, M.D., Cleveland, Ohio There have been many complaints about the reactions which follow injections o f s c a r l e t f e v e r t o x i n d u r i n g t h e p r o c e s s of a c t i v e i m m u n i z a t i o n . T h a t r e a c t i o n s occur is o b v i o u s s i n c e m a n y p r o c e d u r e s h a v e b e e n r e c o m m e n d e d to a v o i d t h e m . T h e D i c k s n o w g r o w t h e i r o r g a n i s m s i n b r o t h - f r e e m e d i a , a n d a f t e r J a n . 1~ 1940, all i m m u n i z i n g t o x i n s will be of t h i s t y p e . P r i c e a n d h i s a s s o c i a t e s at C h i l d r e n ' s t t o s p i t a l in P i t t s b u r g h a r e a t t e m p t i n g to c o n c e n t r a t e a n d p u r i f y t h e s e t o x i n s . They claim good results with their product. I t m a y be s t a t e d in p a s s i n g t h a t t h e 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 is i n t e r e s t e d in a toxoid, t t o w e v e r , t h e o n l y t h i n g a p r a c t i c i n g p h y s i c i a n c a n n o w o b t a i n is t h e s t a n d a r d i z e d t o x i n of t h e S c a r l e t F e v e r C o m m i s s i o n . T h e r e is no d o u b t in m y m i n d t h a t we c a n i m m u n i z e p e r s o n s w h o h a v e p o s i t i v e s k i n t e s t s to t h e p o i n t w h e r e t h e i r t e s t s b e c o m e n e g a t i v e a n d t h a t t h i s i m m u n i z a tion p r o c e d u r e is of p r a c t i c a l v a l u e . I n t h e p a s t , 25 p e r c e n t o f t h e n u r s e s w h o c a m e on o u r w a r d s a n d w h o w e r e e x p o s e d to s c a r l e t f e v e r c o n t r a c t e d t h e disease. S i n c e 1926 we h a v e i m m u n i z e d n e a r l y 2,000 n u r s e s w h o h a d p o s i t i v e t e s t s a n d h a v e h a d o n l y e i g h t f a i l u r e s of i m m u n i z a t i o n . S o m e b e l i e v e t h a t s u c h p e r s o n s a r e r e n d e r e d n e g a t i v e to s k i n t e s t s , b u t are m a d e m o r e s u s c e p t i b l e to local inf e c t i o n s . T h i s h a s n o t b e e n our e x p e r i e n c e . N u r s e s w i t h u p p e r r e s p i r a t o r y i n f e c tions-throat, e t c . - - a t t h e C i t y H o s p i t a l h a v e b e e n d i r e c t l y a d m i t t e d to t h e C o n t a g i o u s t t o s p i t a ] f o r t h e p a s t t h r e e y e a r s , a n d t h e r e h a s b e e n no m a r k e d inc r e a s e in t h e n u m b e r of u p p e r r e s p i r a t o r y i n f e c t i o n s . The economic benefits received by the hospital and the patient more than compensate for the reactions suffered. M a n y o f t h e n u r s e s h a d b o t h local a n d g e n e r a l r e a c t i o n s , f a i r l y s e v e r e a t t i m e s w i t h a r t h r i t i s , a d e n i t i s , etc., a n d i m m u n i z a t i o n h a d to be s t o p p e d i n t w e n t y - f i v e i n s t a n c e s . O v e r 99 p e r c e n t of t h e s e p e r s o n s w h o h a d a n e g a t i v e D i c k t e s t a f t e r t h e y h a d b e e n a c t i v e l y i m m u n i z e d did n o t c o n t r a c t s c a r l e t f e v e r . On t h e o t h e r hand, many persons with negative Dick tests who have not been immunized have c o n t r a c t e d t h e d i s e a s e . I n s h o r t , a n e g a t i v e D i c k t e s t is n o t as i n d i c a t i v e as a p o s i t i v e one in a n u n i m m u n i z e d i n d i v i d u a l , b u t i t is still a p r a c t i c a l t e s t . S c a r l e t f e v e r a n t i t o x i n s were so b u l k y a n d c a u s e d so m a n y r e a c t i o n s (6,000 u n i t s in 20 c.c. of h o r s e s e r u m ) t h a t we d i s c o n t i n u e d t h e i r u s e f o r s e v e r a l y e a r s . A f e w y e a r s ago i t w a s d i s c o v e r e d t h a t s c a r l e t f e v e r a n t i t o x i n could be conc e n t r a t e d a n d t h a t m o s t of t h e f a c t o r s c a u s i n g t h e r e a c t i o n s we o b j e c t e d to could be d i g e s t e d o u t b y e n z y m e s a n d t h e r e m a i n i n g a l b u m i n d i a l y z e d , precipitated~ a n d filtered a w a y . T h e L e d e r l e L a b o r a t o r i e s c o n c e n t r a t e d t h e i r m a t e r i a l d o w n to a p p r o x i m a t e l y 3 c.c. W e t r i e d t h i s a n t i t o x i n i n o v e r 800 c a s e s ( L e d e r l e ) , i n j e c t i n g i t i n t r a m u s c u l a r l y , a n d we w e r e a s t o n i s h e d a t t h e r e s u l t s o b t a i n e d a f t e r i t s use. T h e t e m p e r a t u r e u s u a l l y d r o p p e d to n o r m a l w i t h i n t w e l v e h o u r s a f t e r inj e c t i o n ; t h e r e w a s a d e c r e a s e in t h e n u m b e r o f c o m p l i c a t i o n s ; t h e p a t i e n t s f e l t s u b j e c t i v e l y b e t t e r w i t h i n t h e s a m e p e r i o d of t i m e , a n d t h e r a s h o f t e n disap~ p e a r e d w i t h i n t w e n t y - f o u r h o u r s or w a s g r e a t l y modified. T h e n u m b e r of Serum r e a c t i o n s w a s n o t m o r e t h a n f r o m 8 to ]1 p e r c e n t , t h e a p p r o x i m a t e r e s rate we o b t a i n e d in p a t i e n t s w h o h a d b e e n g i v e n c o n c e n t r a t e d d i p h t h e r i a s e r a of h i g h potency. P a r k e , D a v i s & Co. also c o n c e n t r a t e d t h e i r a n t i t o x i n to a p p r o x i m a t e l y 3 c.c. W e also n s e d t h i s ' a n t i t o x i n in 800 c a s e s a n d c a n s t a t e t h a t t h e r e s u l t s w e r e e q u a l l y as good as t h o s e w i t h t h e L e d e r l e m a t e r i a l . W e n o w h a v e a t l e a s t t w o a n t i t o x i n s ( L e d e r ] e a n d P a r k e , D a v i s ) w h i c h we f e e l a r e m u c h b e t t e r t h a n conv a l e s c e n t s e r u m . T h e l a t t e r is e x p e n s i v e a n d n o t a l w a y s e a s y to o b t a i n . F u r t h e r -
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more, it m u s t be pooled material, a n d it c a n n o t be standardized. The dose of c o n v a l e s c e n t serum in v a r i o u s localities r a n g e s front 25 to 75 cents for 1 c.e. A t h e r a p e u t i c dose of 50 c.e. would cost f r o m $12.50 to $37.50. A t h e r a p e u t i c dose of commercial scarlet f e v e r a n t i t o x i n costs front $8.89 to $10.00. Commercial a n t i t o x i n s can be s t a n d a r d i z e d at a c e r t a i n s t r e n g t h , a n d t h i s s t a n d a r d i z a t i o n can be r e p e a t e d easily; hence their use seems m o s t practicable. DISCUSSION DR. K A R E L I T Z . Would horse antibody serum administered intravenously give the same r e s u l t s as 50 c.c. of h u m a n c o n v a l e s c e n t s e r u m ? I n other words, would it drop the t e m p e r a t u r e in e i g h t e e n hours? Since t h e r a s h a n d f e v e r of scarlet f e v e r m a y d i s a p p e a r in f r o m twelve to e i g h t e e n hours a f t e r f r o m 50 to 60 c.c. of c o n v a l e s c e n t serum is i n j e c t e d i n t r a v e n o u s l y , t h e u s u a l t i t e r of t h i s s e r u m is a b o u t 5 u n i t s per cubic centimeter. Can y o u o b t a i n equally good results w i t h such small a m o u n t s of horse serum a n t i t o x i n ? I g e t larger areas of b l a n c h i n g w i t h f r o m 1 to 2 u n i t s of h u m a n scarlet f e v e r a n t i b o d y t h a n w i t h 5 u n i t s of horse serum a n t i t o x i n . This m a y be explained b y the g r e a t e r diffusibility of the h u m a n serum. DR. D R E N N A N . - - H o w does the new scarlet fever antitoxin compare with h u m a n convalescent serum? C H A I R M A N T O O M E Y . - - W e feel it is much more efficient. Temperature comes down very rapidly. I t is less expensive; it is a product t h a t is easily standardized and easily kept, and the physician can secure it any time he wishes. DR. T R A I S M A N . - - H a v e you had any experience with intradermal immunization? Is it preferred over the regular method ? C H A I R M A N T O O M E Y . - - D r . Earl introduced the intradermal method. I t has been a theory t h a t the skin is a better organ of immunization t h a n other tissues, b u t this point has not been ascertained definitely. There is no clinical evidence along this line. DR. C O H N . - - D o immunized nurses have more sore throats t h a n usual? C H A I R M A N T O O M E Y . - - N o . All persons in the N u r s e s ' T r a i n i n g School, Cleveland City Hospital, with upper respiratory infections are admitted to the Contagious Hospital. We have had no relative increase in the number of patients admitted with sore throats. T h e P r e v e n t i o n of P e r t u s s i s b y t h e U s e of B a c t e r i a l Vaccines E d w a r d B. Shaw, M.D., S a n f r a n c i s c o , Calif. The control of p e r t u s s l s h a s a l w a y s p r e s e n t e d a n u r g e n t a n d difficult problem for t h e physician. The success of i m m u n o l o g i c m e t h o d s for t h e control of some other i n f e c t i o n s has, u n t i l t h e l a s t f e w years, s i m p l y emphasized t h e i n u t i l i t y of similar m e t h o d s i n w h o o p i n g cough. Saner, in r e v i v i n g a n d i m p r o v i n g the use of bacterial vaccine for t h e p r e v e n t i o n of t h i s disease, p r e s e n t e d a m e a s u r e whose value a n d l i m i t a t i o n s e n g a g e the i n t e r e s t of e v e r y p e d i a t r i c i a n . I t would be v e r y t i m e - c o n s u m i n g to outline t h e complete h i s t o r y of t h i s development. V a c c i n e s p r e p a r e d f r o m the B o r d e t - G e n g o u bacillus h a v e long b e e n used for a t t e m p t e d i m m u n i z a t i o n . One should especially credit t h e f u n d a m e n t a l w o r k of M a d s e n l a n d H u e n e k e n s , e' b u t t h i s use w a s p r e v i o u s l y r e s t r i c t e d m o s t l y to t h e i n t e r v a l b e t w e e n exposure a n d t h e onset of cough. S a n e r ' s especial c o n t r i b u t i o n was the d e v e l o p m e n t of a s t a n d a r d m e t h o d e m b r a c i n g t h e use of f r e s h l y isolated
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strains of especial antigenic properties, grown in such a manner as to preserve their autigenielty; the employment of tremendously large dosage; and performance of immunization prior to exposure. Since the introduction of these m~thods, numerous studies have been made to determine their precise value. Significant observations are based on methods which substantially follow those of Sauer. I t has been stated t h a t the complement fixation response3 is significant evidence of immunity but even if this is unquestioned, it does not provide a method for t e s t i n g immunity as simple and effective as the Schiek test. The only feasible method by which the effectiveness of immunity can be estimated {s the comparison of disease incidence in vaccinated groups and similarly constituted control groups. I t is almost impossible to constitute experimental groups of children so as to control adequately all of the p o t e n t i a l variables in such a study. The capacity for immunization varies w i t h respect to constitution, age, race, other infections i etc. Constant antigenicity of the vaccine has been f a i r l y well assured, but the pertussis bacillus is a notably poor antigen. Degree of exposure influences the likelihood of attack and is affected by such factors as duration and location of contact, the amount and i n t e n s i t y of coughing, and the stage of the disease of the patient. The complexities of this problem make it impossible to arrive quickly at an arithmetical expression for the likelihood of producing immunity. A number of groups have been honestly studied, w i t h the production of a wide range of coneluslons. Observers agree t h a t the injection of these vaccines is almost p e r f e c t l y safe and is accompanied by very little discomfort. I t is also agreed t h a t the production of an immune response adequate to protect against ordinary exposure is a useful objective which justifies such minor discomfort, risk, and expense as is involved. The effectiveness and duration of protection are open to considerable disagreement. I t is a mistake, as F a b e r says,4 to insist upon or expect a " s o l i d '~ immunity.
Hemophilus pertussis is a poor antigen, and even the i m m u n i t y induced by the disease is often inadequate to prote~t~ after a time, against intimate exposure. In order for vaccine to prove its value, it is necessary only to demonstrate t h a t it increases the resistance against attack; when this is agreed upon, modification of method and extension of application may be expected to improve results. I t is doubtless improper to accept any single series as conclusive, but a careful perusal of all of the published reports leads almost inescapably to the conviction t h a t the use of vaccine appreciably and beneficially affects the immune state of the individual. The figures of Sauerp who has probably the largest total experience, of I~endriek and Eldering,s Schermerhorn,~ lViiller,s and Singer-Brooks 9 all persuasively support the value of vaccines. Doull and his co-workers~o alone have presented a series with extremely adverse conclusions. They found the incidence of the disease not demonstrably affected and its severity to be questionably benefited. This result is in such contrast to other experiences as to raise the question of w h e t h e r technical differences (preparation of vaccine?) contribute to the discrepancy. An opinion need not be based entirely on comparison of vaccinated with unvaccinated patients. The experience of S a u e r ~ and of several others has demons t r a t e d poor protection in those given small doses, and augmented effect has been shown in one series using extremely large dosage.~s One can thus compare a series using small dosage w i t h one using large dosage. An experiment of SingerBrooks was also very convincing; using siblings for controls, she compared the incidence of pertussis in those actually exposed who had had no vaccine, who had been given Saner-type vaccine, or who had been given a bacterial .extract of altogether different antigenic nature. Tremendously b e t t e r results were apparent
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in the vaccine group as compared with the control group or those given the other antigen, the latter p a t i e n t s constituting an even b e t t e r control group than those to which nothing was done. An opinion of the value of vaccines need not rest solely on the comparison of huge groups. Whooping cough is extremely contagious and a history of a t t a c k is notably reliable. Experiences in small groups multiply over and over to add to the conviction of the average pediatrician t h a t vaccine is of value; this, at least, is my personal observation. A most convincing small-scale experiment was carried out b y the MacDonalds, who used their own four children as experimental subjects. Two children, one a twin, were immunized with Sauer vaccine; the other twin and another child were not immunized. A f t e r a lapse of tlve months, all four children were inoculated intranasally w i t h living pertussis bacillus. The two who were not immunized developed typical pertussis; the two who were given vaccine were resistant not only to inoculation, but to continued exposure in the household to the other two children. E v e n i f one is not justified in drawing extensive conclusions from this experiment, it seems to me to demonstrate convincingly t h a t vaccine is capable of producing immunity. E v e n i f we conclude t h a t vaccine increases resistance, however, we cannot quickly arrive at an estimate of the duration of this effect. I t is safe to say t h a t protection varies and is not prolonged. The probability is great (although c e r t a i n t y is lacking) that, i f immunity has once been effectively stimulated, it can be enhanced dependably later on b y reinjection of vaccine, perhaps by only a single dose. F a b e r proposes t h a t this be done annually; this is not conducive to childhood friendships. I t might be adequate to reinject vaccine only in the f a c t of known exposure when once a basic i m m u n i t y had been produced. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. ]1. 12. 13.
Madsen, T.: J. A. M. A. 101: ]87, 1933. Huenekens, E. J.: Am. J. Dis. Child. 14: 283, 1917. Daughtry-Denmark, L.: Am. J. Dis. Child. 52: 587, 1936. Faber, H. K.: J. I~ 13: 277, 1938. Sauer, L. W.: J. A. M. A. 112: 305, 1939. Kendrick, P., and Eldering, G.: Am. J. Pub. H e a l t h 26: 8, 1936. Schermerhorn, L. J.: J. PEDIAT. 13: 279, 1938. Miller, J. J.: J. PEDIAT. 13: 290, 1938. Singer-Brooks, C.: J. PEDIAT. 13: 292, 1938. Doull, J. A., a n d others: Am. J. Dis. Child. 58: 691, 1939. Sauer, L., and Hambrecht, L.: J. A. M. A. 91: 1861, 1928. Silverthorn, N., and Fraser, D. T.: Canad. 1Y[. J. 38: 556, 1938. MacDona]d, H., and MacDonald, E. J.: J. Infectious Dis. 53: 328, 1933. DISCUSSION
DR. SILBEIC.--In 980 cases in the last five years I have had only seven cases of whooping cough in those immunized, while from twenty to thirty of my cases each year are in the unimmunized group. DR. S, I. L E B E A U , PITTSBURGH.--Are there any dangers in the use of pertussis vaccine? I think there is the possibility of severe reactions. CHAIRMAN T O O M E Y . - - I f whooping cough immunization were simple, the dlsease should be easy t o control. DR. S H A W . - - W h e n a patient has been exposed to whooping cough, I think that he should be given an extra dose as this raises the titer. DR: I. A. ABT. : ' N o man living can write the history of his contemporaries." Nobody present can estimate the efficacy of many of these preventive measures.
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DR. SHAW.--Vaceine (Sauer) should be given early. The younger the patients are, the poorer the immune response. The maximum risk is under 1 year of age. Using vaccine by Krueger, I have had no success at all either prophylactically or in treatment. I know nothing about topagcn vaccine. DR. F A I R F A X HALL, NEW ROCHELLE, N. Y . - - I use topagen instead of injections in treatment. DR. G. N. H O E F F E L , BosToN.--There is no evidence except emotion to say that Sauer vaccine has done any good. DR. H. A. BECK, DETROIT. On a W P A project in Michigan where the nurses did a careful checkup with the help of the physicians on district cases, the results obtained with vaccine were very satisfactory. The diagnoses were confirmed by doctors, and Dr. Kendrick was in immediate charge of the project. DR. S H A W . - - I t is possible that there may be some danger in group whooping cough vaccine, but this is not likely. A single series by Bradford showed considerable value from convalescent serum. Sauer's vaccine should still be used even though proof of its true value is lacking. DR. O S T E R L I N . - - W h a t is the status in treatment of whooping cough by undenatured bacterial antigen~ DR. S H A W . - - U n d e n a t u r e d bacterial antigen has not been proved to be of any value. DR. J. S. HUNT, CHARLOTTE,N. C.--What is the value of large doses of vitamin C in the treatment of whooping cough~ CHAIRMAN TOOMEY.--There has been no deilnite evidence along this line. DR. H A L L - - W h a t order of immunization do you advocate ? CHAIRMAN TOOMEY.--This is contained in the l~eport of the Committee on Immunization and Therapeutic Procedures for Acute Infectious Diseases which may be obtained from the American Academy of Pediatrics: ' ' 1. Vaccine against smallpox at any age during an epidemic but routinely any time between 3 and 12 months. ~' 2. Immunize against diphtheria between 9 and 18 months. Tetanus toxoid may be used in combination with diphtheria toxoid. c, 3. Vaccinate against pertussis between 6 and .9 months. " 4 . Do a Schick test between 18 and 24 months. Reimmunize against diphtheria if necessary. ' ' 5 . Repeat the Schiek test and smallpox vaccination at 6 years or during epidemic periods, l~eimmunize against diphtheria and revaccinate if necessary. " 6 . I f tetanus toxoid is desired, it may be given at any age period, but the reactions are not so severe if given between 2 and 6 years. I f combined with diphtheria toxoid, it may be given at the same time. Scarlet fever toxin might be given in epidemics and to groups previously indicated. Typhoid fever vaccine may be given when and where i n d i c a t e d . "