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Epidemic—cerebro-spinal meningitis
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PUI~LIC H E A L T H .
*EPIDEMIC--CEREBRO-SPINAL MENINGITIS. BY
O. 1VIAR'rIN BEATTIe, M.A. (N.Z.), M.D. (Edin.), P r o f e s s o r of Bacteriology, University of Liverpool, B a c t e r i o l o g i s t to the City of Liverpool. T o the medical officer of health the mode of infection, the means of prevention and the t r e a t m e n t of Cerebro-Spinal i'VIeningitis are of the first importance, and, it is to these aspects of the disease, that I propose to confine myself in this paper. It is f o r t u n a t e tha~:, in dealing with this disease, unlike measles and scarlet fever, we c o m m a n d the situation. W e know its bacterial cause, have adequate means of detecting even the early stages of the disease, and, as I hope to prove, we are acquainted with the mode of infection and t r a n s f e r e n c e and we have made considerable progress in the m e t h o d s of prevention and t r e a t m e n t . CAUSE.--The meningococcus is, of course, the essential causal factor, but as o n l y a small proportion of individuals who h a r b o u r the m e n i n g o c o c c u s are attacked by the disease, t h e r e must be subsidiary causes such as fatique, overcrowding, and, in no small measure, c o n c u r r e n t r e s p i r a t o r y affections of slighter degree. ~'~ODE OF INFECTION.--- It is generally agreed that the meningo'coccus e n t e r s the body by way of the mucous m e m b r a n e of the nasopharynx and leaves it by the secretions f r o m that m e m b r a n e . No o t h e r a v e n u e of e n t r a n c e or exit has been established. T h e organism passes from the naso-pharynx to the base of the brain by way of the lymphatic or blood c h a n n e l s - - w h i c h , has not been clearly proved. Possibly it may travel hy either, though the more c o m m o n way is by the lymphatic connections which extend along the o l f a c t o r y nerves. T h e occurrence, during epidemics of metastatic inflammations such as arthritis, endocarditis, &c., certainly suggests a distribution of the organism by the blood stream. It has been said, and I think truly, that " e v e r y case Of epidemic meningitis develops oclt of a c a r r i e r . " The organism multiplies in * A paper read before a Meeti*~g of the North-Western Branch at Liverpool on 9th January, 1920.
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the nase-pl!arynx before i t invades' t h e meninges, and the m a j o r i t y of careful observers agree that, in e v e r y case of cerebr62 spinal meningitis, the organism can befoun~t in the naso-pharyngeaI mucosa, if ~properly looked for. On several occasions I h a v e b e e n able to obtain cultures f r o m the nago'~ pharynx, when I failed, f o r various reasons, to obtain the organism f r o m the cerebr0-spinal fluict. In dealing with the carrier, tlaere are tW6 classes of c a s e s - - t h e one with meningitis, and' the one who is a p p a r e n t l y quite healthy. The" latter is, from the point of view of the medieg~l officer of health, the m o r e important. The f o r m e r is confined to bed and his power.:0f infection is limited to a smaJ1 area r0tmd his bed---the latter is u n h a m p e r e d in h i s movements, and may spread the infection o v e r a wide area. Isolated cases of cerebro-spinal meningitis have, for tong periods, b e e n a d m i t t e d t o our general hospitals, and t h e r e has been v e r y little evidence that o t h e r patients have been infected from them. In fact, many medical men still regard the disease as non,contagious. A v e r y c u r s o r y glance, however, a t . t h e literature of the subject shews that t h e disease has, at times, become epidemic in m a n y a r e a s R e c e n t l y t h e r e have been o u t b r e a k s which assumed alarming dimensions among young recruits, and several of the F r e n c h e[~idemics of p a s t years were a m o n g this class. S o m e of my readers will at once recall the severe epidemic in Dublin which o c c u r r e d a m o n g the recruits of the Royal Irish Constabulary, stationed at the police barracks, at Phoenix Park, many y e a r s ago. As I have a l r e a d y stated, t h e r e is practically no doubt thai: the habitat of the Organism is the mu.cous m e m b r a n e of the n a s o - p h a r y n x a n d "the mechanism of dissemination c0nsists in the ejection of the naso-pharyngeal secretions into the s u r r o u n d i n g atmosphere. D r o p l e t s of the infected material may pass from one individual t o a n o t h e r by the " mouth' s p r a y " in coughing and sneezing, a n d a l s o directly by spitting. T h o u g h this ~is" tihe c o m m o n mode of t r a n s f e r e n c e , we mtlst n0tJ neglect the carriage by way of t h e ban:dls soiled by secretions, or by flies which h a v e ' f e d on the secretion. T h e viability of- ttie:
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o r g a n i s m outside the body is feeble and t h e r e fore direct infection f r o m one individual to a n o t h e r in the i m m e d i a t e n e i g h b o u r h o o d is. as we would anticipate, the m o s t usual m e t h o d df infection. This connection between the s p r a y i n g of the c o n t a m i n a t e d secretion and the o c c u r r e n c e of infection has been quite definitely established by m a n y o b s e r v e r s , but F l e x n e r points out that, in addition; it has been proved t h a t an i n c r e a s e d n u m e r i c a l relationship exists between violent s p r a y i n g a n d c a r r i e r production. " C h r o n i c c a r r i e r s or p e r s o n s suffering f r o m meningitis, who suffered at the s a m e t i m e f r o m a severe cough, g a v e rise to m o r e c a r r i e r s and c o n t a m i n a t e d p e r s o n s o v e r a g r e a t e r a r e a than has been f o u n d o t h e r w i s e to be the case." T h e risk o f infection m a y not be v e r y great, but t h a t t h e r e is a risk has been a b u n d a n t l y proved. In investigations carried out for the Medical R e s e a r c h C o m m i t t e e , it was f o u n d t h a t two o b s e r v e r s who a l m o s t daily s w a b b e d carriers, without wearing masks, t h e m s e l v e s g a v e positive swabs a f t e r 10 and 14 d a y s respectively. E x p I o s i v e respiration, s n e e z i n g and coughing g a v e positive c u l t u r e s on plates held directly in the line of flee. In dealing with the p e r s o n s n a t u r a l l y infected it is v e r y difficult to d r a w definite conclusions as to the m o d e of infection. M a j o r S a l m o n r e p o r t s the case of a nurse who developed c e r e b r o - s p i n a t f e v e r while n u r s i n g a soldier suffering f r o m the disease. Similar o b s e r v a t i o n s have been m a d e by. o°thers, but there m a y have been a c o m m o n source for both cases, and Major S a l m o n admits, that a p a r t f r o m the one instance, no two of his o t h e r cases could be c o n n e c t e d . In one of m y c a s e s at S e a f o r t h Military Hospital, all the patients and a t t e n d a n t s in a w a r d in which a m a n had died of cerebro-spinal meningitis w e r e s w a b b e d and positive results w e r e obtained f r o m two c a s e s o n l y - - o n e of t h e s e was the patient in the adjoining bed and the o t h e r was the o r d e r l y who had been in a t t e n d a n c e on the patient. This is fairly good evidence but I h a v e no m e a n s of knowing w h e t h e r these two men had been previous carriers. T h e y both cleared up v e r y quicldy u n d e r o r d i n a r y t h r o a t s p r a y i n g - - t h i s suggesting, at any rate, that they w e r e r e c e n t l y infected.
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BaCTERIOLOOY. - - W i t h the differentiation of the m e n i n g o c o c c i into types, the evidence of this t r a n s m i s s i o n f r o m individual to individual h a s been s t r e n g t h e n e d . In one of o u r military hospitals I was asked to see a n u r s e with c e r e b r o - s p i n a l fever. It w a s a c o m p a r a t i v e l y small hospital, a n d I decided to swab the whole o f the patients as well as the n u r s i n g staff. T w o positive cases w e r e found, both f r o m the w a r d in which the n u r s e has been working. One of t h e s e proved to be a r e s i s t a n t c a r r i e r and the o r g a n i s m isolated f r o m his nasop h a r y n x w a s of the s a m e t y p e (Type II.) as t h a t obtained f r o m the c e r e b r o - s p i n a t fluid of the nurse. T h e o t h e r man also has the s a m e type o r g a n i s m but in a couple of d a y s he was quite free. T h e r e s i s t a n t c a r r i e r c a m e f r o m the S o u t h - - f r o m an a r e a in which cerebro-spinal f e v e r had been v e r y severe. I have little doubt t h a t this man was the infecting a g e n t in my case. A n o t h e r case o c c u e r e d in p r i v a t e - - a lady died very s u d d e n l y with definite evidence of cecebro-spinal fever. Fluid o b t a i n e d by l u m b a r p u n c t u r e g a v e a m e n i n g o c o c c u s which agglutinated, in high titre, G o r d o n ' s T y p e I., and also g a v e s o m e agglutination, though to a m u c h less degree, with T y p e I I I . M e m b e r s of the h o u s e hold and visitors who had been in the house at the time o f the d e a t h were swabbed. Two positive cases, a m o n g the eight who w e r e swabbed, w e r e f o u n d - - t h e s e two being the h u s b a n d and the d a u g h ' t e r - - t h e only two who had been in direct c o n t a c t with the patient and had been kissing her before death. The o r g a n i s m f r o m t'he d a u g h t e r failed to g r o w in s u b c u l t u r e and agglutination could not b e c a r r i e d out. T h e o r g a n i s m f r o m the h u s b a n d gave exactly the s a m e agglutination reactions and to the s a m e d e g r e e as the o r g a n i s m isolated f r o m the patient. H e r e again is, I think, a c l e a r c a s e of infection f r o m one individual to another, w h e t h e r the wife to the husband or the h u s b a n d to the wife is again uilcertain. }¢Iartin F t a c k gives several similar cases, but I record only two of these. I. Case 4 was treated at h o m e for f a t i g u e and possibly s u n s t r o k e for 14 days before a diagnosis of c e r e b r o - s p i n a l f e v e r was made. On the seventh day of the disease his m o t h e r , who was n u r s i n g tlim, developed similar
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symptomsandsubsequentlydied. From thecerebro-spinaI fluid of both cases a m e n i n g o c o c c u s (Type II.) was grown. H i s brother, sister and the m a n who had slept n e a r him in his q u a r t e r s were all f o u n d to be c a r r i e r s o f T y p e II. II. C a s e 14 was isolated e a r l y in D e c e m b e r f r o m c o n t a c t s of a n o t h e r case. H e had been sleeping in the next bed to the case. On J a n u a r y 24th, six weeks a f t e r being isolated, he developed the disease. T h e t y p e o r g a n i s m in both c a s e s was the s a m e ( T y p e I.) T h e s e c a s e s a r e I think sufficient to establish m y point t h a t direct infection m a y take place f r o m individual to individual. SPREAD OF THE DISEASE.-- D u r i n g the w a r we had a b u n d a n t evidence t h a t the m o v e m e n t s of large bodies of troops played an i m p o r t a n t part in the s p r e a d of the disease, and it is g e n e r a l l y the c a r r i e r who migrates. I n v e s t i g a t i o n of the e a r l y o u t b r e a k s at S a l i s b u r y Plain s e e m s to indicate t h a t the infection w a s b r o u g h t by C a n a d i a n t r o o p s - and t h e r e is evidence that cerebro-spinal f e v e r had o c c u r r e d a m o n g these troops before they left C a n a d a and on the v o y a g e over, but we c a n n o t a t t r i b u t e the whole origin to t h e s e C a n a d i a n c a r r i e r s . Lieut. J o h n s t o n states t h a t the first t h r e e c a s e s on the plain w e r e in C a n a d i a n s , but that, in only 18 per cent. of his o t h e r 65 cases, could even p r o b a b l e association with C a n a d i a n s be established. Sporadic c e r e b r o - s p i n a l meningitis has always been with us, and t h e r e f o r e we too have had o u r c a r r i e r s T h e a g g r e g a t i o n of o u r own people in c a m p s - often o v e r c r o w d e d and in bad s i t u a t i o n s - - - m u s t h a v e played a considerable p a r t in the s p r e a d of this disease. Capt. Allan (Chester) states t h a t his c a s e s were m o s t l y a m o n g t the civilian hosts of billeted soldiers, who were t h e m s e l v e s well. I had been having isolated cases at one of our c a m p s - - a l w a y s in new r e c r u i t s - - a n d a f t e r finding and isolating c a r r i e r s it was decided to close the c a m p to r e c r u i t s f o r a given period. No new c a s e s o c c u r r e d ; I p r o p o s e d s w a b b i n g all the m e n left in the c a m p at the end of this period, but in the last week of o u r isolation the W a r Office sent 140 new recruits to the camp. T h e following d a y we had a case of c e r e b r o spinal f e v e r in one of these recruits, and s w a b s taken f r o m the r e m a i n i n g 139 g a v e a positive
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finding in 19. I n v e s t i g a t i o n s h e w e d that these men had been sent f r o m a c a m p in which t h e r e had been a considerable n u m b e r of c a s e s of c e r e b r o - s p i n a l f e v e r ; and the m a n With e a r l y s y m p t o m s c a m e with the others. Againl in this c a m p a f t e r a period in which no c e r e b r o spinal fever had occurred, I s w a b b e d o v e r 300 m e n and found no c a r r i e r s and no l u t h e r c a s e s o c c u r r e d in the c a m p for several m o n t h s , when a n o t h e r new r e c r u i t developed thd disease. CARRIERS IN THE CIVILIAN POPULATION.--
A m o n g the n o n - c o n t a c t c a s e s which I e x a m i n e d I f o u n d v e r y few carriers. I examined, as I have a l r e a d y stated, 300 at one c a m p a f t e r a f r e e d o m , for several mmlths, f r o m cerebro-spinal fever, a n d f o u n d no c a r r i e r s . I also e x a m i n e d 200 m e n f r o m 10 different c a m p s in which no c e r e b r o - s p i n a l f e v e r had o c c u r r e d , again with a n e g a t i v e result. Dr. Gamlin, wortdng in my l a b o r a t o r y , e x a m i n e d 100 c o n v a l e s c e n t children f r o m f e v e r hospitals. T h e r e had been no c a s e s of c e r e b r o - s p i n a l f e v e r a m o n g these children. H e found 3 with o r g a n i s m s like the m e n i n g o c o c c u s but only one c o r r e s p o n d e d with any of G o r d o n ' s types. Dr. E a s t w o o d e x a m i n e d 480 n o n - c o n t a c t s at St. B a r t h o l o m e w ' s H o s p i t a l (out-patients in the dept. of d i s e a s e s of the e a r and in-patients in the general wards). H e f o u n d in 10.2 per cent. of the e a s e s o r g a n i s m s culturally indistinguisable f r o m the m e n i n g o c o c c u s . S c o t t e x a m i n e d 138 n o n - c o n t a c t s in L a m b e t h I n f i r m a r y and found 13"7 per cent. of carriers. Dr. S c o t t also e x a m i n e d 56 chihtren in a rural school and found only one doubtful carrier. T h e p e r c e n t a g e s of E a s t w o o d and S c o t t are, I think, v e r y h i g h f o r t h e n o n - c o n t a c t population, but t h e r e is evidence that the n o n - c o n t a c t perc e n t a g e of positive c a r r i e r s is highest during the period in which t h e d i s e a s e i s m o s t prevalent. E a s t w o o d ' s o b s e r v a t i o n s w e r e c a r r i e d out partly in the spring when c e r e b r o - s p i n a l meningitis was practically epidemic in certain areas. WEATHER CONDITIONS.--There is no evidence t h a t the influence of the w e a t h e r plays a n y special part in the s p r e a d of the disease--except the indirect action t h a t it keeps men indoors in o v e r c r o w d e d and ill ventilated huts, g e n e r a l l y with closed windows. OVERCROWDING LATION :--lVlost
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o v e r c r o w d i n g and lack of ventilation are powerful p r e d i s p o n e n t s to the disease. T h e evidence on this point is so s t r o n g and so u n a n i m o u s t h a t I n e e d mention only a few facts. Lieut. J o h n s t o n (Salisbury P l a i n area) gives the following figures : , Conlacts,IPositive. Per ce~t~. M a r k e d o v e r c a - o w d i n g I 406 { 81 I 19"3 M o d e r a t e o v e r c r o w d i n g / 194" 22" / 11"3 No overcrow.ding [ 542 33 6"0 Walker Hail (Bristol), Hutchens at Newcastle, and V ining (Leeds) s h e w that men q u a r t e r e d in billets with.a limited floor s p a c e give positive c o n t a c t s in 27"9, 17"8 and 16 per cent. In huts a n d b a r r a c k s w h e r e the floor space per man was g r e a t e r , 8"3, 13"3 and 13'6 per cent. U n d e r c a n v a s or in hospitals, 3"1, 6"4 and 2"7 per cent. M a c M a h o n (York), in relation to 3 cases, gives the following f a c t s : O n l y one of these was f r o m o v e r c r o w d e d and unhygienic surroundingsl and this man g a v e 15"5 per cent. c o n t a c t s ; the c o n t a c t s Of the o t h e r two were 9 per cent. and 3"6 pet" cent. CLOSENESS OF CONTACT.--I have a l r e a d y m e n t i o n e d c a s e s u n d e r my own charge. F i n l a y s o n (Brighton) " r e c o r d s 2 c a s e s which o c c u r r e d i n a hut of 360 men. O f the 21 men who slept a d j a c e n t to the cases, 6 (28'5 pet' cent.) had m e n i n g o c o c c i in t h e i r n a s o - p h a r y n x . T h e r e m a i n i n g 339 g a v e only 8 (2"4 pet" Cent.) carriers. Lieut. T r e a d g o l d r e p o r t s t h a t out of a batch of 39 c o n t a c t s he found a m o n g 32 who slept in the s a m e r o o m with the original case t h e r e were 21 c a r r i e r s (136 per cent.) T h e r e m a i n i n g 7 were only occasional contacts, and of these only two were positive and these two w e r e men who a t e at the s a m e table as the patient. Dr. Claridge (Norwich) s a y s the l a r g e s t p r o p o r t i o n of positive c a r r i e r s he m e t with was in a g r o u p Of 7 m e n billetted in a b o a r d i n g house. One d e v e l o p e d c e r e b r o - s p i n a l f e v e r and of the other 6, 5 p r o v e d to be c a r r i e r s (i.e. 83"3 per cent.) Capt. Glover, who has w o r k e d specially at this question of o v e r c r o w d i n g , gives a n u m b e r Of e x t r e m e l y i n t e r e s t i n g f a c t s in an official c'ommunication of March, 1918, and in a p a p e r in the " British Medical J o u r n a l , " N o v e m b e r , 1918.
Apa*L,
A m o n g Capt. G l o v e r ' s conclusions are these : (1) A high c a r r i e r r a t e usually d e n o t e s overcrowding and d a n g e r o u s l y u n h y g i e n i c conditions. (2) S e v e r e o v e r c r o w d i n g will p r o b a b l y be a c c o m p a n i e d by a c a r r i e r rate (Serological) of at least 20 pet" cent. This p e r c e n t a g e s h o u l d be r e g a r d e d as a signal f o r p r o m p t and effective action to diminish overcrowding and to i m p r o v e ventilation. (3) Q u i t e ' a m o d e r a t e d e g r e e o f " s p a c i n g o u t " of beds, c o m b i n e d with simple m e t h o d s for i m p r o v i n g ventilation, are highly efficient a g e n t s in r e d u c i n g high c a r r i e r rates. T h e cycle of e v e n t s which leads to infection is clear. A c a r r i e r , who m a y be a p e r f e c t l y h e a l t h y individual, is i n t r o d u c e d i~to a g r o u p of people, s o m e of whom are susceptible. A certain n u m b e r b e c o m e infected f r o m the n a s o - p h a r y n g e a l secretiQn which he ejects. A variable n u m b e r of these develop acute meningitis, but a l a r g e r n u m b e r b e c o m e either t e m p o r a r y or c h r o n i c c a r r i e r s . T h e patient who is c o n v a l e s c e n t f r o m an acute attack is for an indefinite period a carrier. T h e incid e n c e of the o c c u r r e n c e of the disease is g o v e r n e d by the o p p o r t u n i t i e s afforded by the t r a n s f e r of the coccus f r o m individual to i n d i v i d u a l - - s u c h as the closer c o n t a c t b r o u g h t a b o u t by indoor association during the winter a n d e a r l y spring, when the disease is m o s t p r e v a l e n t , and p a r t i c u l a r l y by o v e r c r o w d i n g in living rooms, schools, a n d places of a m u s e m e n t . T h e c a r r i e r question in this disease is of p r i m a r y i m p o r t a n c e , and, in e v e r y case o f c e r e b r o - s p i n a l meningitis, a careful e x a m i n a tion of all. i m m e d i a t e c o n t a c t s should be made, in o t h e r words, a s e a r c h m u s t be m a d e f o r the infecting agent. In m a n y cases, he .will be t r a c e d and he should be isolated. R e c o v e r e d c a s e s of c e r e b r o - s p i n a l meningitis should be detained in hospital until the n a s o - p h a r y n x is declared f r e e f r o m m e n i n g o c o c c i by a c o m p e t e n t bacteriologist, a n d all n u r s e s and o t h e r s who h a v e been in i m m e d i a t e c o n t a c t with the c a s e s should also be e x a m i n e d for meningococci, p a r t i c u l a r ! y if t h r o a t disinfection has not been c a r r i e d out r e g u l a r l y 1)3, them. TREATNIENT.--THE A c u f v DISEASE: 1 shall not spend t i m e in dealing with the past, s a v e
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to say t h a t in the epidemics in this c o u n t r y tip t o the end of 1915, the a v e r a g e m o r t a l i t y of t h e v a r i o u s o b s e r v e r s w a s 50 p e r cent. and this in spite o f : t h e use of a n t i - m e n i n g o c o c c i serum. A n d e r s o n r e p o r t s ten cases t r e a t e d w i t h L i s t e r s e r u m with 50 per cent. mortality, six with Burroughs-Wellcome s e r u m w i t h 66.6 per cent. mortality, and f o u r with M u m f o r d ' s s e r u m w i t h 75 per cent. mortality. A y e a r later, O c t o b e r , 1915-1916, Adshead treated, by i n t r a t h e c a l injection of polyvalent s e r u m , t w e n t y - t w o c a s e s at the R o y a l N a v a l H o s p i t a l with eighteen r e c o v e r i e s , and in 1916-17, 49 cases with F l e x n e r s ' p o l y v a l e n t s e r u m with 34 r e c o v e r i e s , i.e., n e a r l y 70 per cent. recoveries. During 1916-I7 I saw ten c a s e s - - f i v e r e c o v e r e d and five died. T h r e e of these died within t w e n t y - f o u r h o u r s of o n s e t and received no t r e a t m e n t ; two received only two injections of s e r u m . O n l y One of the fatal cases was t r e a t e d s a t i s f a c t o r y as f a r as s e r u m injections were c o n c e r n e d . H e shewed a b s o l u t e l y no i m p r o v e m e n t t h r o u g h o u t - - t h e type of the o r g a n i s m w a s not d e t e r m i n e d , but the patient received L i s t e r polyvalent s e r u m . In r e g a r d to the five recoveries, all received polyvalent s e r u m on several occasions, but m y g e n e r a l note on the c a s e s was t h a t the l u m b a r p u n c t u r e played a g r e a t e r part in the r e c o v e r y that~ the s e r u m , in fact, in two c a s e s the s e r u m w a s s t o p p e d because t h e r e a p p e a r e d to be no i m p r o v e m e n t , but l u m b a r p u n c t u r e was continued e v e r y day or e v e r y o t h e r day. My l a t e r e x p e r i e n c e led me to m o d i f y this view. D u r i n g the y e a r s 1917 and t919, I had available °the special type s e r a m a d e f r o m o r g a n i s m s of G o r d e n ' s types. T h e g e n e r a l plan was to l u m b a r p u n c t u r e as early as possible, inject p o t y v a t e n t s e r u m and a f t e r deternaination of the type of the o r g a n i s m present, to c o n t i n u e the t r e a t m e n t with the h o m o l o g o u s serum. In all, I had t w e n t y - s e v e n definite cases, with s e v e n t e e n r e c o v e r i e s and ten d e a t h s - - a m o r tality of 37 per cent. An a n a l y s i s of the d e a t h s s h e w s t h a t one received no serunl t r e a t m e n t , a n d five died within t w e n t y - f o u r h o u r s a f t e r they w e r e seen by me (three of these r e c e i v e d no s e r u m , one received one dose, and one received two doses).
HEALTH.
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T h e s e then m a y be fairly excluded, and this brings the d e a t h r a t e down to u n d e r 15 per cent. D u r i n g 1918-1919, I saw only 6 c a s e s . O n e of t h e s e had been t r e a t e d on board a New Zealand transport withserum and w a s practically Convalescent when I first s a w him. T h e o t h e r 5 w e r e seen at the e a r l y stage Of the disease and were t r e a t e d r e g u l a r l y with Serum for f r o m 4 to 9 d a y s - - o n e with L i s t e r - p o l y v a l e n t - - 4 with a p r e l i m i n a r y d o s e of Lister, followed by the h o m o l o g o u s type s e r u m , a n d in all t h e r e was a rapid and c o m p l e t e r e c o v e r y . T h e evidence put f o r w a r d , I think, shews t h a t the m o r t a l i t y of c e r e b r o - s p i n a l f e v e r need not~ be high if the c a s e s a r e seen e a r l y a n d r e g u l a r t r e a t m e n t with a n t i - m e n i n g o c o c c i c s e r u m is c a r r i e d out. T h e r e c o m m e n d a t i o n s of t h o s e who have worked m o s t at this s u b j e c t a r e t h a t ltimbar p u n c t u r e and injection of a n t i - m e n i n g o c o c c i c s e r u m should be d o n e daily for 5 or 6 days, no m a t t e r what the condition of the patient m a y be. Certain varieties of p o l y v a l e n t s e r u m s e e m v e r y effective. T h o u g h theoretically, it would s e e m b e t t e r , w h e r e ~ o n d i t i o n s m a k e it possible, to d e t e r m i n e the type of the causal o r g a n i s m and inject an h o m o l o g o u s s e r u m , yet the results so f a r obtained do not shew t h a t the r e c o v e r y rate is much, if at all, impi*oved by this m e t h o d of t r e a t m e n t . At the s a m e time, it is advisable, in m y opinion, to g i v e a m o r e extended t r i a l to the " h o m o l o g o u s s e r u m " t r e a t m e n t . T h e r e s u l t s of t h i s f o r m of t r e a t m e n t , which have been collected by Col. M e r v y n G o r d o n , are still unpublished, and t h e r e f o r e , though, t h r o u g h the kindness of Col. G o r d o n , I h a v e seen s o m e of h i s tables, I c a n n o t record them. It can, however, be said t h a t the results with certain t y p e s of the s e r a have been s a t i s f a c t o r y , a n d the best results with all types a r e o b t a i n e d when the cases ' a r e got early, and when e n e r g e t i c a n d syst'ehaatic s e r u m t r e a t m e n t is adopted. T h e results s o f a r obtaine d withl s e r t nn t r e a t m e n t a r e .most e n c o u r a g i n g and we are justified in looldng to a still f u r t h e r diminution in the rage'i Of m o r t a l i t y f r o m this disease in the neat- futm:e. T H e CARRIZR.--The only metfaod o f " i m p o r t a n c e in the t r e a t m e n t of the c a r r i e r is disinfection of the n a s o - p h a r y n x . S t a t i s t i c s on the s u b j e c t are not too reliable, for all w o r k e r s at the
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subject recognise that m a n y positive c o n t a c t cases clear up in a few d a y s with any simple t h r o a t s p r a y or even without a n y f o r m of t r e a t m e n t . T h e r e is, however, a class of cases, the true carrier, who resists t r e a t m e n t to a very considerable degree. One of the most experienced workers on the subject in a private letter to me said " N o t h i n g s e e m s to have the slightest effect on these c h r o n i c c a r r i e r s . " Various f o r m s of steam a t o m i s e r were used ; were strongly praised by one a n d almost as strongly c o n d e m n e d by others. My own experience with the steam atomiser, supplied to c o n t a c t c e n t r e s by the W a r Office, was that it was quite ineffective and t h a t it had practically no effect on the bacterial flora of the naso-pharynx. A considerable n u m b e r of e x p e r i m e n t s were carried out, both in the C o n t a c t C e n t r e to which I was bacteriologist and in my own laboratory. The experiments proved that the irritation, which was always a p p a r e n t in the conjunctival and nasal m e m b r a n e s of those subjected to this spray, was due to f o r m a l d e h y d e produced by the action of b u r n i n g spirit in a c h a m b e r of red hot copper, and not, as was generally supposed, to the action of the antiseptics in the droplets of spray. D u r i n g the time I was in c h a r g e of the C o n t a c t Centre, I never c a m e a c r o s s a really chronic carrier, t h o u g h one or two resisted t r e a t m e n t for a week or ten days. This I attribute partly to the healthy s u r r o u n d i n g s of the C e n t r e and to the use of " E ! e c t r o s o l "
APRIL,
with a hand s p r a y at f r e q u e n t intervals. T h e effects of " E l e c t r o s o l " and its mode of p r e p a r a t i o n a r e d e s c r i b e d in a c o m m u n i c a t i o n by F. C . Lewis and myself in the " B r i t i s h Medical J o u r n a l , " F e b r u a r y 24th, 1917. In t h e " d o u r n a l of Hygiene;" April 27th, 1914, Mr. L e w i s described a l a b o r a t o r y a p p a r a t u s for the disinfection of cultures, etc. This was in c o n s t a n t use in m y t a b o v a t o r y a n d had proved most eËficient. E a r l y in the war, when discussion was going on between the a d v o c a t e s of the use of hypertonic saline and the chlorine preparations in the disinfection of Wounds, it o c c u r r r d to me to try a combination of the two methods, and I suggested to Mr. Lewis that the solution prepared by electrolysis in the l a b o r a t o r y a p p a r a t u s might have a much wider application, if the salt solution could be so standardised as to g u a r a n t e e a chlorine c o n t e n t about equal to that of c h l o r a m i n e in a h y p e r t o n i c saline solution. After some experiments, we decided to use as our c o m m e n c i n g solution a 3 per cent. saline, and eventually we succeeded in producing a solution which seemed to come up to the s t a n d a r d we had set out to establish. This " E l e c t r o s o t " w e used regularly in diphtheria with results a l r e a d y r e c o r d e d in the paper r e f e r r e d to above, E v e n t u a l l y , at the suggestion of the officer in c h a r g e of the cerebro-spinal work at the W a r ONce, we selected four Centres for experiments on chronic carriers. The solution, with instructions for its use, were supplied to these Centres. In one C e n t r e it was not used,
Lecithin 1 to 5 % Chronic ~.~ Carriers. I N ~ : -" P .... W .... F.... A.... H. As . . . . V. . . .
~ :IN
= ~----~._.~ :
~ = ~=
= :
:~ =
Eleet~osol. ~
=~ o9
: :~
~: . . ~. . ~ "Z°
++ ++--++++ + +++--+++ ++ + + q-++--+--+--+--+ +q-++++++ +++++__ +++++++__++ +++ Readmitted q- qq-__ q +__q- q- q- q- q-__q-____q- q- q. . . . q-__q- _ _ _ q - _ q- q- q- + q+ + + - - + + . - - + + ÷ - - + + q- + _ + + + L + + . _ _ + + _ +. q - _ _ + ÷
•
~
~
~, = ~
~
~
+++--+--+-q+4
+ _ q - + + + + + + _ _ + + q - + + +
NI . . . .
L....
+q._+++
J .... Ha .... H o ....
q---+ q-++ q-++++q-
q - . - . •. -.
+ --,- + q---
--@
Carriers at Crystal Palace
.
31 c a s e s - - p o s i t i v e con t a c t s to a case in t he L o n d o n a re a on 23rd Nov, S w a b s taken 23rd Nov., 4th Dec., 6th D e c ., 10th Dec., 17th Dec. 3 r e m a i n e d positive titl swab of 6th Dec. 4 r e m a i n e d positive till 10th Dec. 1 r e m a i n e d positive tilI 17th Dec. All o t h e r s were free on 4th Dec.
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b e c a u s e no s u i t a b l e c a s e s w e r e a v a i l a b l e ; a t a s e c o n d , t h e officer in c h a r g e n e v e r h e a r d of t h e the solution; in t h e t h i r d , a p r e l i m i n a r y "encouraging" r e p o r t w a s r e c e i v e d , b u t no details were ever sent. L a t e r , t h e officer w r o t e s a y i n g t h a t , a t f i r s t , he g o t g o o d r e s u l t s , eventually, with more forcible swabbing menin g o c o c c i w e r e f o u n d in c a s e s w h i c h he t h o u g h t h a d c l e a r e d up. N o r e c o r d s h a v e b e e n r e c e i v e d f r o m him a n d no s t a t e m e n t a s to t h e m a n n e r in w h i c h , o r t h e l e n g t h of t i m e t h e p a t i e n t s were treated. From the fourth Centre a detailed report was sent. The patients were sprayed three times a d a y f o r five m i n u t e s a t a s i t t i n g , a n d t h e following table shows the results which were obtained. A f t e r t h e c l o s i n g o f his C e n t r e this o f f i c e r again wrote as follows :--"The " Electrosol " was used first only for very chronic carriers, a n d r e s u l t e d , in t h e c a s e s of 12 s e l e c t e d m e n , all c a r r i e r s o f o v e r t h r e e m o n t h s , in r a p i d clearance. W i t h t h e e x c e p t i o n o f two m e n , all w e r e f r e e f r o m t h e m e n i n g o c o c c u s in t h e n a s o - p h a r y n x in t w o o r t h r e e w e e k s . With t h e o r d i n a r y i n f e c t e d c o n t a c t , it w a s f o u n d t h a t in p r a c t i c a l l y all c a s e s t h e s e c l e a r e d w i t h i n t w o weeks." THE
CURE
OF CEREBRO-SPINAL MENINGITIS.*
Diagnosis of the type o r g a n i s m by a simple r a p i d method and t r e a t m e n t by univalent serum. BY H . STANLEY BANKS, M.A., M.B., Ch.B., D . P . H . , M e d i c a l Officer of H e a l t h , Motherwell ; Medical Superintendent, B u r g h H o s p i t a l , Motherwell ; L a t e Bacteriologist, B . E . F . , Salonika. R e f e r e n c e to case 2 described hereunder, will, I think, show- that as regards t y p e 1 of the disease, at least there is some justification for the title of this article. T h e r e m a r k a b l e possibilities contained in the treatment, of cerebro-spinal Meningitis, by a n t i - meningococcic t y p e serum, and also the ease of diagnosis of the type organism by simole laboratory methods, are things which are * A paper read before the Scottish Branch of the Society of Medical Officers of Health. The full paper, with illustrations, has been accepted for publication by " T h e Lancet."
I ~
I
not yet widely known, and which well deserve to be. T h i s article refers more p a r t i c u l a r l y to type 1 of the disease. GORDON'S FOUR T Y p E s . - - A m o n g the advances made b y medical science during, and a s a consequence of, the war, not the least i m p o r t a n t is G o r d o n ' s discovery of the four types of the rneningococcus. T h i s has led to a more exact classification of the disease. F o r m e r l y we were content to classify the cases clinically as " f u l m i n a ting," "acute," and "sub-acute," or chronic. N o w we h a v e a bacteriological classification of the disease into cerebro-spinat meningitis, types 1, 2, 3 and 4, and with a little more experience a fairly reliable clit¢ic~l classification, corresponding to these types, m a y also be a r r i v e d at. A few observations on this point have a l r e a d y been made. Thus, Kennedy and Worster D r o u g h t 1 investigated the relation of the t y p e of meningococcus to the clinical picture in 22 cases and found that 8 cases infected with G o r d o n ' s t y p e 1 were all g r a v e l y ill, with fatal issue in 6 ; that of 6 cases with type 3, some were severe and some moderately severe, and that the 8 dases of type 2, all r e c o v e r e d ; of type 4 there were no cases. T h e observations suggest that the types 1 and 3 (Nicolle type A ) are more virulent as regards the meninges, and that t y p e s 2 and 4 (Nicolle t y p e B, or p a r a m e n i n g o c o c c u s ) are specially prone to cause s e p t i c a e m i a and extrameningeal metastases. T h e evidence of other writers, such as Rolleston 2 and A d s h e a d ~ on the point is more conflicting, and no constant relationship can be regarded as established. T h e process of differentiation of the type is similar to what is already fairly well established, for the E n t e r i c a group of fevers, viz. : T y p h o i d , P a r a t y p h o i d A., and P a r a t y p h o i d B., in each of which a distinctive clinical picture is frequently obtained, enabling a p r e s u m p t i v e clinical differentiation to be made. T h e s a m e can be said of the D y s e n t e r i c a group of bacillary dysenteries, at least as regards the broad clinical distinction between the S h i g a and F l e x n e r sub-groups. I n the cerebro-spinal group of fevers, however, the the differentiation is of infinitely g~eater practical importance to the patient, for upon it rests the question of specific t r e a t m e n t by the u n i v a l e n t t y p e serum, and this is p r i m a facie' the only t r e a t m e n t which affords a substantial prospect of success.
PUI~LIC H E A L T H .
*EPIDEMIC--CEREBRO-SPINAL MENINGITIS. BY
O. 1VIAR'rIN BEATTIe, M.A. (N.Z.), M.D. (Edin.), P r o f e s s o r of Bacteriology, University of Liverpool, B a c t e r i o l o g i s t to the City of Liverpool. T o the medical officer of health the mode of infection, the means of prevention and the t r e a t m e n t of Cerebro-Spinal i'VIeningitis are of the first importance, and, it is to these aspects of the disease, that I propose to confine myself in this paper. It is f o r t u n a t e tha~:, in dealing with this disease, unlike measles and scarlet fever, we c o m m a n d the situation. W e know its bacterial cause, have adequate means of detecting even the early stages of the disease, and, as I hope to prove, we are acquainted with the mode of infection and t r a n s f e r e n c e and we have made considerable progress in the m e t h o d s of prevention and t r e a t m e n t . CAUSE.--The meningococcus is, of course, the essential causal factor, but as o n l y a small proportion of individuals who h a r b o u r the m e n i n g o c o c c u s are attacked by the disease, t h e r e must be subsidiary causes such as fatique, overcrowding, and, in no small measure, c o n c u r r e n t r e s p i r a t o r y affections of slighter degree. ~'~ODE OF INFECTION.--- It is generally agreed that the meningo'coccus e n t e r s the body by way of the mucous m e m b r a n e of the nasopharynx and leaves it by the secretions f r o m that m e m b r a n e . No o t h e r a v e n u e of e n t r a n c e or exit has been established. T h e organism passes from the naso-pharynx to the base of the brain by way of the lymphatic or blood c h a n n e l s - - w h i c h , has not been clearly proved. Possibly it may travel hy either, though the more c o m m o n way is by the lymphatic connections which extend along the o l f a c t o r y nerves. T h e occurrence, during epidemics of metastatic inflammations such as arthritis, endocarditis, &c., certainly suggests a distribution of the organism by the blood stream. It has been said, and I think truly, that " e v e r y case Of epidemic meningitis develops oclt of a c a r r i e r . " The organism multiplies in * A paper read before a Meeti*~g of the North-Western Branch at Liverpool on 9th January, 1920.
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the nase-pl!arynx before i t invades' t h e meninges, and the m a j o r i t y of careful observers agree that, in e v e r y case of cerebr62 spinal meningitis, the organism can befoun~t in the naso-pharyngeaI mucosa, if ~properly looked for. On several occasions I h a v e b e e n able to obtain cultures f r o m the nago'~ pharynx, when I failed, f o r various reasons, to obtain the organism f r o m the cerebr0-spinal fluict. In dealing with the carrier, tlaere are tW6 classes of c a s e s - - t h e one with meningitis, and' the one who is a p p a r e n t l y quite healthy. The" latter is, from the point of view of the medieg~l officer of health, the m o r e important. The f o r m e r is confined to bed and his power.:0f infection is limited to a smaJ1 area r0tmd his bed---the latter is u n h a m p e r e d in h i s movements, and may spread the infection o v e r a wide area. Isolated cases of cerebro-spinal meningitis have, for tong periods, b e e n a d m i t t e d t o our general hospitals, and t h e r e has been v e r y little evidence that o t h e r patients have been infected from them. In fact, many medical men still regard the disease as non,contagious. A v e r y c u r s o r y glance, however, a t . t h e literature of the subject shews that t h e disease has, at times, become epidemic in m a n y a r e a s R e c e n t l y t h e r e have been o u t b r e a k s which assumed alarming dimensions among young recruits, and several of the F r e n c h e[~idemics of p a s t years were a m o n g this class. S o m e of my readers will at once recall the severe epidemic in Dublin which o c c u r r e d a m o n g the recruits of the Royal Irish Constabulary, stationed at the police barracks, at Phoenix Park, many y e a r s ago. As I have a l r e a d y stated, t h e r e is practically no doubt thai: the habitat of the Organism is the mu.cous m e m b r a n e of the n a s o - p h a r y n x a n d "the mechanism of dissemination c0nsists in the ejection of the naso-pharyngeal secretions into the s u r r o u n d i n g atmosphere. D r o p l e t s of the infected material may pass from one individual t o a n o t h e r by the " mouth' s p r a y " in coughing and sneezing, a n d a l s o directly by spitting. T h o u g h this ~is" tihe c o m m o n mode of t r a n s f e r e n c e , we mtlst n0tJ neglect the carriage by way of t h e ban:dls soiled by secretions, or by flies which h a v e ' f e d on the secretion. T h e viability of- ttie:
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o r g a n i s m outside the body is feeble and t h e r e fore direct infection f r o m one individual to a n o t h e r in the i m m e d i a t e n e i g h b o u r h o o d is. as we would anticipate, the m o s t usual m e t h o d df infection. This connection between the s p r a y i n g of the c o n t a m i n a t e d secretion and the o c c u r r e n c e of infection has been quite definitely established by m a n y o b s e r v e r s , but F l e x n e r points out that, in addition; it has been proved t h a t an i n c r e a s e d n u m e r i c a l relationship exists between violent s p r a y i n g a n d c a r r i e r production. " C h r o n i c c a r r i e r s or p e r s o n s suffering f r o m meningitis, who suffered at the s a m e t i m e f r o m a severe cough, g a v e rise to m o r e c a r r i e r s and c o n t a m i n a t e d p e r s o n s o v e r a g r e a t e r a r e a than has been f o u n d o t h e r w i s e to be the case." T h e risk o f infection m a y not be v e r y great, but t h a t t h e r e is a risk has been a b u n d a n t l y proved. In investigations carried out for the Medical R e s e a r c h C o m m i t t e e , it was f o u n d t h a t two o b s e r v e r s who a l m o s t daily s w a b b e d carriers, without wearing masks, t h e m s e l v e s g a v e positive swabs a f t e r 10 and 14 d a y s respectively. E x p I o s i v e respiration, s n e e z i n g and coughing g a v e positive c u l t u r e s on plates held directly in the line of flee. In dealing with the p e r s o n s n a t u r a l l y infected it is v e r y difficult to d r a w definite conclusions as to the m o d e of infection. M a j o r S a l m o n r e p o r t s the case of a nurse who developed c e r e b r o - s p i n a t f e v e r while n u r s i n g a soldier suffering f r o m the disease. Similar o b s e r v a t i o n s have been m a d e by. o°thers, but there m a y have been a c o m m o n source for both cases, and Major S a l m o n admits, that a p a r t f r o m the one instance, no two of his o t h e r cases could be c o n n e c t e d . In one of m y c a s e s at S e a f o r t h Military Hospital, all the patients and a t t e n d a n t s in a w a r d in which a m a n had died of cerebro-spinal meningitis w e r e s w a b b e d and positive results w e r e obtained f r o m two c a s e s o n l y - - o n e of t h e s e was the patient in the adjoining bed and the o t h e r was the o r d e r l y who had been in a t t e n d a n c e on the patient. This is fairly good evidence but I h a v e no m e a n s of knowing w h e t h e r these two men had been previous carriers. T h e y both cleared up v e r y quicldy u n d e r o r d i n a r y t h r o a t s p r a y i n g - - t h i s suggesting, at any rate, that they w e r e r e c e n t l y infected.
HEALTH.
APRIL,
BaCTERIOLOOY. - - W i t h the differentiation of the m e n i n g o c o c c i into types, the evidence of this t r a n s m i s s i o n f r o m individual to individual h a s been s t r e n g t h e n e d . In one of o u r military hospitals I was asked to see a n u r s e with c e r e b r o - s p i n a l fever. It w a s a c o m p a r a t i v e l y small hospital, a n d I decided to swab the whole o f the patients as well as the n u r s i n g staff. T w o positive cases w e r e found, both f r o m the w a r d in which the n u r s e has been working. One of t h e s e proved to be a r e s i s t a n t c a r r i e r and the o r g a n i s m isolated f r o m his nasop h a r y n x w a s of the s a m e t y p e (Type II.) as t h a t obtained f r o m the c e r e b r o - s p i n a t fluid of the nurse. T h e o t h e r man also has the s a m e type o r g a n i s m but in a couple of d a y s he was quite free. T h e r e s i s t a n t c a r r i e r c a m e f r o m the S o u t h - - f r o m an a r e a in which cerebro-spinal f e v e r had been v e r y severe. I have little doubt t h a t this man was the infecting a g e n t in my case. A n o t h e r case o c c u e r e d in p r i v a t e - - a lady died very s u d d e n l y with definite evidence of cecebro-spinal fever. Fluid o b t a i n e d by l u m b a r p u n c t u r e g a v e a m e n i n g o c o c c u s which agglutinated, in high titre, G o r d o n ' s T y p e I., and also g a v e s o m e agglutination, though to a m u c h less degree, with T y p e I I I . M e m b e r s of the h o u s e hold and visitors who had been in the house at the time o f the d e a t h were swabbed. Two positive cases, a m o n g the eight who w e r e swabbed, w e r e f o u n d - - t h e s e two being the h u s b a n d and the d a u g h ' t e r - - t h e only two who had been in direct c o n t a c t with the patient and had been kissing her before death. The o r g a n i s m f r o m t'he d a u g h t e r failed to g r o w in s u b c u l t u r e and agglutination could not b e c a r r i e d out. T h e o r g a n i s m f r o m the h u s b a n d gave exactly the s a m e agglutination reactions and to the s a m e d e g r e e as the o r g a n i s m isolated f r o m the patient. H e r e again is, I think, a c l e a r c a s e of infection f r o m one individual to another, w h e t h e r the wife to the husband or the h u s b a n d to the wife is again uilcertain. }¢Iartin F t a c k gives several similar cases, but I record only two of these. I. Case 4 was treated at h o m e for f a t i g u e and possibly s u n s t r o k e for 14 days before a diagnosis of c e r e b r o - s p i n a l f e v e r was made. On the seventh day of the disease his m o t h e r , who was n u r s i n g tlim, developed similar
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symptomsandsubsequentlydied. From thecerebro-spinaI fluid of both cases a m e n i n g o c o c c u s (Type II.) was grown. H i s brother, sister and the m a n who had slept n e a r him in his q u a r t e r s were all f o u n d to be c a r r i e r s o f T y p e II. II. C a s e 14 was isolated e a r l y in D e c e m b e r f r o m c o n t a c t s of a n o t h e r case. H e had been sleeping in the next bed to the case. On J a n u a r y 24th, six weeks a f t e r being isolated, he developed the disease. T h e t y p e o r g a n i s m in both c a s e s was the s a m e ( T y p e I.) T h e s e c a s e s a r e I think sufficient to establish m y point t h a t direct infection m a y take place f r o m individual to individual. SPREAD OF THE DISEASE.-- D u r i n g the w a r we had a b u n d a n t evidence t h a t the m o v e m e n t s of large bodies of troops played an i m p o r t a n t part in the s p r e a d of the disease, and it is g e n e r a l l y the c a r r i e r who migrates. I n v e s t i g a t i o n of the e a r l y o u t b r e a k s at S a l i s b u r y Plain s e e m s to indicate t h a t the infection w a s b r o u g h t by C a n a d i a n t r o o p s - and t h e r e is evidence that cerebro-spinal f e v e r had o c c u r r e d a m o n g these troops before they left C a n a d a and on the v o y a g e over, but we c a n n o t a t t r i b u t e the whole origin to t h e s e C a n a d i a n c a r r i e r s . Lieut. J o h n s t o n states t h a t the first t h r e e c a s e s on the plain w e r e in C a n a d i a n s , but that, in only 18 per cent. of his o t h e r 65 cases, could even p r o b a b l e association with C a n a d i a n s be established. Sporadic c e r e b r o - s p i n a l meningitis has always been with us, and t h e r e f o r e we too have had o u r c a r r i e r s T h e a g g r e g a t i o n of o u r own people in c a m p s - often o v e r c r o w d e d and in bad s i t u a t i o n s - - - m u s t h a v e played a considerable p a r t in the s p r e a d of this disease. Capt. Allan (Chester) states t h a t his c a s e s were m o s t l y a m o n g t the civilian hosts of billeted soldiers, who were t h e m s e l v e s well. I had been having isolated cases at one of our c a m p s - - a l w a y s in new r e c r u i t s - - a n d a f t e r finding and isolating c a r r i e r s it was decided to close the c a m p to r e c r u i t s f o r a given period. No new c a s e s o c c u r r e d ; I p r o p o s e d s w a b b i n g all the m e n left in the c a m p at the end of this period, but in the last week of o u r isolation the W a r Office sent 140 new recruits to the camp. T h e following d a y we had a case of c e r e b r o spinal f e v e r in one of these recruits, and s w a b s taken f r o m the r e m a i n i n g 139 g a v e a positive
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finding in 19. I n v e s t i g a t i o n s h e w e d that these men had been sent f r o m a c a m p in which t h e r e had been a considerable n u m b e r of c a s e s of c e r e b r o - s p i n a l f e v e r ; and the m a n With e a r l y s y m p t o m s c a m e with the others. Againl in this c a m p a f t e r a period in which no c e r e b r o spinal fever had occurred, I s w a b b e d o v e r 300 m e n and found no c a r r i e r s and no l u t h e r c a s e s o c c u r r e d in the c a m p for several m o n t h s , when a n o t h e r new r e c r u i t developed thd disease. CARRIERS IN THE CIVILIAN POPULATION.--
A m o n g the n o n - c o n t a c t c a s e s which I e x a m i n e d I f o u n d v e r y few carriers. I examined, as I have a l r e a d y stated, 300 at one c a m p a f t e r a f r e e d o m , for several mmlths, f r o m cerebro-spinal fever, a n d f o u n d no c a r r i e r s . I also e x a m i n e d 200 m e n f r o m 10 different c a m p s in which no c e r e b r o - s p i n a l f e v e r had o c c u r r e d , again with a n e g a t i v e result. Dr. Gamlin, wortdng in my l a b o r a t o r y , e x a m i n e d 100 c o n v a l e s c e n t children f r o m f e v e r hospitals. T h e r e had been no c a s e s of c e r e b r o - s p i n a l f e v e r a m o n g these children. H e found 3 with o r g a n i s m s like the m e n i n g o c o c c u s but only one c o r r e s p o n d e d with any of G o r d o n ' s types. Dr. E a s t w o o d e x a m i n e d 480 n o n - c o n t a c t s at St. B a r t h o l o m e w ' s H o s p i t a l (out-patients in the dept. of d i s e a s e s of the e a r and in-patients in the general wards). H e f o u n d in 10.2 per cent. of the e a s e s o r g a n i s m s culturally indistinguisable f r o m the m e n i n g o c o c c u s . S c o t t e x a m i n e d 138 n o n - c o n t a c t s in L a m b e t h I n f i r m a r y and found 13"7 per cent. of carriers. Dr. S c o t t also e x a m i n e d 56 chihtren in a rural school and found only one doubtful carrier. T h e p e r c e n t a g e s of E a s t w o o d and S c o t t are, I think, v e r y h i g h f o r t h e n o n - c o n t a c t population, but t h e r e is evidence that the n o n - c o n t a c t perc e n t a g e of positive c a r r i e r s is highest during the period in which t h e d i s e a s e i s m o s t prevalent. E a s t w o o d ' s o b s e r v a t i o n s w e r e c a r r i e d out partly in the spring when c e r e b r o - s p i n a l meningitis was practically epidemic in certain areas. WEATHER CONDITIONS.--There is no evidence t h a t the influence of the w e a t h e r plays a n y special part in the s p r e a d of the disease--except the indirect action t h a t it keeps men indoors in o v e r c r o w d e d and ill ventilated huts, g e n e r a l l y with closed windows. OVERCROWDING LATION :--lVlost
AND
observers
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are
VENTI-
agreed
that
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o v e r c r o w d i n g and lack of ventilation are powerful p r e d i s p o n e n t s to the disease. T h e evidence on this point is so s t r o n g and so u n a n i m o u s t h a t I n e e d mention only a few facts. Lieut. J o h n s t o n (Salisbury P l a i n area) gives the following figures : , Conlacts,IPositive. Per ce~t~. M a r k e d o v e r c a - o w d i n g I 406 { 81 I 19"3 M o d e r a t e o v e r c r o w d i n g / 194" 22" / 11"3 No overcrow.ding [ 542 33 6"0 Walker Hail (Bristol), Hutchens at Newcastle, and V ining (Leeds) s h e w that men q u a r t e r e d in billets with.a limited floor s p a c e give positive c o n t a c t s in 27"9, 17"8 and 16 per cent. In huts a n d b a r r a c k s w h e r e the floor space per man was g r e a t e r , 8"3, 13"3 and 13'6 per cent. U n d e r c a n v a s or in hospitals, 3"1, 6"4 and 2"7 per cent. M a c M a h o n (York), in relation to 3 cases, gives the following f a c t s : O n l y one of these was f r o m o v e r c r o w d e d and unhygienic surroundingsl and this man g a v e 15"5 per cent. c o n t a c t s ; the c o n t a c t s Of the o t h e r two were 9 per cent. and 3"6 pet" cent. CLOSENESS OF CONTACT.--I have a l r e a d y m e n t i o n e d c a s e s u n d e r my own charge. F i n l a y s o n (Brighton) " r e c o r d s 2 c a s e s which o c c u r r e d i n a hut of 360 men. O f the 21 men who slept a d j a c e n t to the cases, 6 (28'5 pet' cent.) had m e n i n g o c o c c i in t h e i r n a s o - p h a r y n x . T h e r e m a i n i n g 339 g a v e only 8 (2"4 pet" Cent.) carriers. Lieut. T r e a d g o l d r e p o r t s t h a t out of a batch of 39 c o n t a c t s he found a m o n g 32 who slept in the s a m e r o o m with the original case t h e r e were 21 c a r r i e r s (136 per cent.) T h e r e m a i n i n g 7 were only occasional contacts, and of these only two were positive and these two w e r e men who a t e at the s a m e table as the patient. Dr. Claridge (Norwich) s a y s the l a r g e s t p r o p o r t i o n of positive c a r r i e r s he m e t with was in a g r o u p Of 7 m e n billetted in a b o a r d i n g house. One d e v e l o p e d c e r e b r o - s p i n a l f e v e r and of the other 6, 5 p r o v e d to be c a r r i e r s (i.e. 83"3 per cent.) Capt. Glover, who has w o r k e d specially at this question of o v e r c r o w d i n g , gives a n u m b e r Of e x t r e m e l y i n t e r e s t i n g f a c t s in an official c'ommunication of March, 1918, and in a p a p e r in the " British Medical J o u r n a l , " N o v e m b e r , 1918.
Apa*L,
A m o n g Capt. G l o v e r ' s conclusions are these : (1) A high c a r r i e r r a t e usually d e n o t e s overcrowding and d a n g e r o u s l y u n h y g i e n i c conditions. (2) S e v e r e o v e r c r o w d i n g will p r o b a b l y be a c c o m p a n i e d by a c a r r i e r rate (Serological) of at least 20 pet" cent. This p e r c e n t a g e s h o u l d be r e g a r d e d as a signal f o r p r o m p t and effective action to diminish overcrowding and to i m p r o v e ventilation. (3) Q u i t e ' a m o d e r a t e d e g r e e o f " s p a c i n g o u t " of beds, c o m b i n e d with simple m e t h o d s for i m p r o v i n g ventilation, are highly efficient a g e n t s in r e d u c i n g high c a r r i e r rates. T h e cycle of e v e n t s which leads to infection is clear. A c a r r i e r , who m a y be a p e r f e c t l y h e a l t h y individual, is i n t r o d u c e d i~to a g r o u p of people, s o m e of whom are susceptible. A certain n u m b e r b e c o m e infected f r o m the n a s o - p h a r y n g e a l secretiQn which he ejects. A variable n u m b e r of these develop acute meningitis, but a l a r g e r n u m b e r b e c o m e either t e m p o r a r y or c h r o n i c c a r r i e r s . T h e patient who is c o n v a l e s c e n t f r o m an acute attack is for an indefinite period a carrier. T h e incid e n c e of the o c c u r r e n c e of the disease is g o v e r n e d by the o p p o r t u n i t i e s afforded by the t r a n s f e r of the coccus f r o m individual to i n d i v i d u a l - - s u c h as the closer c o n t a c t b r o u g h t a b o u t by indoor association during the winter a n d e a r l y spring, when the disease is m o s t p r e v a l e n t , and p a r t i c u l a r l y by o v e r c r o w d i n g in living rooms, schools, a n d places of a m u s e m e n t . T h e c a r r i e r question in this disease is of p r i m a r y i m p o r t a n c e , and, in e v e r y case o f c e r e b r o - s p i n a l meningitis, a careful e x a m i n a tion of all. i m m e d i a t e c o n t a c t s should be made, in o t h e r words, a s e a r c h m u s t be m a d e f o r the infecting agent. In m a n y cases, he .will be t r a c e d and he should be isolated. R e c o v e r e d c a s e s of c e r e b r o - s p i n a l meningitis should be detained in hospital until the n a s o - p h a r y n x is declared f r e e f r o m m e n i n g o c o c c i by a c o m p e t e n t bacteriologist, a n d all n u r s e s and o t h e r s who h a v e been in i m m e d i a t e c o n t a c t with the c a s e s should also be e x a m i n e d for meningococci, p a r t i c u l a r ! y if t h r o a t disinfection has not been c a r r i e d out r e g u l a r l y 1)3, them. TREATNIENT.--THE A c u f v DISEASE: 1 shall not spend t i m e in dealing with the past, s a v e
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to say t h a t in the epidemics in this c o u n t r y tip t o the end of 1915, the a v e r a g e m o r t a l i t y of t h e v a r i o u s o b s e r v e r s w a s 50 p e r cent. and this in spite o f : t h e use of a n t i - m e n i n g o c o c c i serum. A n d e r s o n r e p o r t s ten cases t r e a t e d w i t h L i s t e r s e r u m with 50 per cent. mortality, six with Burroughs-Wellcome s e r u m w i t h 66.6 per cent. mortality, and f o u r with M u m f o r d ' s s e r u m w i t h 75 per cent. mortality. A y e a r later, O c t o b e r , 1915-1916, Adshead treated, by i n t r a t h e c a l injection of polyvalent s e r u m , t w e n t y - t w o c a s e s at the R o y a l N a v a l H o s p i t a l with eighteen r e c o v e r i e s , and in 1916-17, 49 cases with F l e x n e r s ' p o l y v a l e n t s e r u m with 34 r e c o v e r i e s , i.e., n e a r l y 70 per cent. recoveries. During 1916-I7 I saw ten c a s e s - - f i v e r e c o v e r e d and five died. T h r e e of these died within t w e n t y - f o u r h o u r s of o n s e t and received no t r e a t m e n t ; two received only two injections of s e r u m . O n l y One of the fatal cases was t r e a t e d s a t i s f a c t o r y as f a r as s e r u m injections were c o n c e r n e d . H e shewed a b s o l u t e l y no i m p r o v e m e n t t h r o u g h o u t - - t h e type of the o r g a n i s m w a s not d e t e r m i n e d , but the patient received L i s t e r polyvalent s e r u m . In r e g a r d to the five recoveries, all received polyvalent s e r u m on several occasions, but m y g e n e r a l note on the c a s e s was t h a t the l u m b a r p u n c t u r e played a g r e a t e r part in the r e c o v e r y that~ the s e r u m , in fact, in two c a s e s the s e r u m w a s s t o p p e d because t h e r e a p p e a r e d to be no i m p r o v e m e n t , but l u m b a r p u n c t u r e was continued e v e r y day or e v e r y o t h e r day. My l a t e r e x p e r i e n c e led me to m o d i f y this view. D u r i n g the y e a r s 1917 and t919, I had available °the special type s e r a m a d e f r o m o r g a n i s m s of G o r d e n ' s types. T h e g e n e r a l plan was to l u m b a r p u n c t u r e as early as possible, inject p o t y v a t e n t s e r u m and a f t e r deternaination of the type of the o r g a n i s m present, to c o n t i n u e the t r e a t m e n t with the h o m o l o g o u s serum. In all, I had t w e n t y - s e v e n definite cases, with s e v e n t e e n r e c o v e r i e s and ten d e a t h s - - a m o r tality of 37 per cent. An a n a l y s i s of the d e a t h s s h e w s t h a t one received no serunl t r e a t m e n t , a n d five died within t w e n t y - f o u r h o u r s a f t e r they w e r e seen by me (three of these r e c e i v e d no s e r u m , one received one dose, and one received two doses).
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T h e s e then m a y be fairly excluded, and this brings the d e a t h r a t e down to u n d e r 15 per cent. D u r i n g 1918-1919, I saw only 6 c a s e s . O n e of t h e s e had been t r e a t e d on board a New Zealand transport withserum and w a s practically Convalescent when I first s a w him. T h e o t h e r 5 w e r e seen at the e a r l y stage Of the disease and were t r e a t e d r e g u l a r l y with Serum for f r o m 4 to 9 d a y s - - o n e with L i s t e r - p o l y v a l e n t - - 4 with a p r e l i m i n a r y d o s e of Lister, followed by the h o m o l o g o u s type s e r u m , a n d in all t h e r e was a rapid and c o m p l e t e r e c o v e r y . T h e evidence put f o r w a r d , I think, shews t h a t the m o r t a l i t y of c e r e b r o - s p i n a l f e v e r need not~ be high if the c a s e s a r e seen e a r l y a n d r e g u l a r t r e a t m e n t with a n t i - m e n i n g o c o c c i c s e r u m is c a r r i e d out. T h e r e c o m m e n d a t i o n s of t h o s e who have worked m o s t at this s u b j e c t a r e t h a t ltimbar p u n c t u r e and injection of a n t i - m e n i n g o c o c c i c s e r u m should be d o n e daily for 5 or 6 days, no m a t t e r what the condition of the patient m a y be. Certain varieties of p o l y v a l e n t s e r u m s e e m v e r y effective. T h o u g h theoretically, it would s e e m b e t t e r , w h e r e ~ o n d i t i o n s m a k e it possible, to d e t e r m i n e the type of the causal o r g a n i s m and inject an h o m o l o g o u s s e r u m , yet the results so f a r obtained do not shew t h a t the r e c o v e r y rate is much, if at all, impi*oved by this m e t h o d of t r e a t m e n t . At the s a m e time, it is advisable, in m y opinion, to g i v e a m o r e extended t r i a l to the " h o m o l o g o u s s e r u m " t r e a t m e n t . T h e r e s u l t s of t h i s f o r m of t r e a t m e n t , which have been collected by Col. M e r v y n G o r d o n , are still unpublished, and t h e r e f o r e , though, t h r o u g h the kindness of Col. G o r d o n , I h a v e seen s o m e of h i s tables, I c a n n o t record them. It can, however, be said t h a t the results with certain t y p e s of the s e r a have been s a t i s f a c t o r y , a n d the best results with all types a r e o b t a i n e d when the cases ' a r e got early, and when e n e r g e t i c a n d syst'ehaatic s e r u m t r e a t m e n t is adopted. T h e results s o f a r obtaine d withl s e r t nn t r e a t m e n t a r e .most e n c o u r a g i n g and we are justified in looldng to a still f u r t h e r diminution in the rage'i Of m o r t a l i t y f r o m this disease in the neat- futm:e. T H e CARRIZR.--The only metfaod o f " i m p o r t a n c e in the t r e a t m e n t of the c a r r i e r is disinfection of the n a s o - p h a r y n x . S t a t i s t i c s on the s u b j e c t are not too reliable, for all w o r k e r s at the
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subject recognise that m a n y positive c o n t a c t cases clear up in a few d a y s with any simple t h r o a t s p r a y or even without a n y f o r m of t r e a t m e n t . T h e r e is, however, a class of cases, the true carrier, who resists t r e a t m e n t to a very considerable degree. One of the most experienced workers on the subject in a private letter to me said " N o t h i n g s e e m s to have the slightest effect on these c h r o n i c c a r r i e r s . " Various f o r m s of steam a t o m i s e r were used ; were strongly praised by one a n d almost as strongly c o n d e m n e d by others. My own experience with the steam atomiser, supplied to c o n t a c t c e n t r e s by the W a r Office, was that it was quite ineffective and t h a t it had practically no effect on the bacterial flora of the naso-pharynx. A considerable n u m b e r of e x p e r i m e n t s were carried out, both in the C o n t a c t C e n t r e to which I was bacteriologist and in my own laboratory. The experiments proved that the irritation, which was always a p p a r e n t in the conjunctival and nasal m e m b r a n e s of those subjected to this spray, was due to f o r m a l d e h y d e produced by the action of b u r n i n g spirit in a c h a m b e r of red hot copper, and not, as was generally supposed, to the action of the antiseptics in the droplets of spray. D u r i n g the time I was in c h a r g e of the C o n t a c t Centre, I never c a m e a c r o s s a really chronic carrier, t h o u g h one or two resisted t r e a t m e n t for a week or ten days. This I attribute partly to the healthy s u r r o u n d i n g s of the C e n t r e and to the use of " E ! e c t r o s o l "
APRIL,
with a hand s p r a y at f r e q u e n t intervals. T h e effects of " E l e c t r o s o l " and its mode of p r e p a r a t i o n a r e d e s c r i b e d in a c o m m u n i c a t i o n by F. C . Lewis and myself in the " B r i t i s h Medical J o u r n a l , " F e b r u a r y 24th, 1917. In t h e " d o u r n a l of Hygiene;" April 27th, 1914, Mr. L e w i s described a l a b o r a t o r y a p p a r a t u s for the disinfection of cultures, etc. This was in c o n s t a n t use in m y t a b o v a t o r y a n d had proved most eËficient. E a r l y in the war, when discussion was going on between the a d v o c a t e s of the use of hypertonic saline and the chlorine preparations in the disinfection of Wounds, it o c c u r r r d to me to try a combination of the two methods, and I suggested to Mr. Lewis that the solution prepared by electrolysis in the l a b o r a t o r y a p p a r a t u s might have a much wider application, if the salt solution could be so standardised as to g u a r a n t e e a chlorine c o n t e n t about equal to that of c h l o r a m i n e in a h y p e r t o n i c saline solution. After some experiments, we decided to use as our c o m m e n c i n g solution a 3 per cent. saline, and eventually we succeeded in producing a solution which seemed to come up to the s t a n d a r d we had set out to establish. This " E l e c t r o s o t " w e used regularly in diphtheria with results a l r e a d y r e c o r d e d in the paper r e f e r r e d to above, E v e n t u a l l y , at the suggestion of the officer in c h a r g e of the cerebro-spinal work at the W a r ONce, we selected four Centres for experiments on chronic carriers. The solution, with instructions for its use, were supplied to these Centres. In one C e n t r e it was not used,
Lecithin 1 to 5 % Chronic ~.~ Carriers. I N ~ : -" P .... W .... F.... A.... H. As . . . . V. . . .
~ :IN
= ~----~._.~ :
~ = ~=
= :
:~ =
Eleet~osol. ~
=~ o9
: :~
~: . . ~. . ~ "Z°
++ ++--++++ + +++--+++ ++ + + q-++--+--+--+--+ +q-++++++ +++++__ +++++++__++ +++ Readmitted q- qq-__ q +__q- q- q- q- q-__q-____q- q- q. . . . q-__q- _ _ _ q - _ q- q- q- + q+ + + - - + + . - - + + ÷ - - + + q- + _ + + + L + + . _ _ + + _ +. q - _ _ + ÷
•
~
~
~, = ~
~
~
+++--+--+-q+4
+ _ q - + + + + + + _ _ + + q - + + +
NI . . . .
L....
+q._+++
J .... Ha .... H o ....
q---+ q-++ q-++++q-
q - . - . •. -.
+ --,- + q---
--@
Carriers at Crystal Palace
.
31 c a s e s - - p o s i t i v e con t a c t s to a case in t he L o n d o n a re a on 23rd Nov, S w a b s taken 23rd Nov., 4th Dec., 6th D e c ., 10th Dec., 17th Dec. 3 r e m a i n e d positive titl swab of 6th Dec. 4 r e m a i n e d positive till 10th Dec. 1 r e m a i n e d positive tilI 17th Dec. All o t h e r s were free on 4th Dec.
P U B L I C HEA LTH.
I92o.
b e c a u s e no s u i t a b l e c a s e s w e r e a v a i l a b l e ; a t a s e c o n d , t h e officer in c h a r g e n e v e r h e a r d of t h e the solution; in t h e t h i r d , a p r e l i m i n a r y "encouraging" r e p o r t w a s r e c e i v e d , b u t no details were ever sent. L a t e r , t h e officer w r o t e s a y i n g t h a t , a t f i r s t , he g o t g o o d r e s u l t s , eventually, with more forcible swabbing menin g o c o c c i w e r e f o u n d in c a s e s w h i c h he t h o u g h t h a d c l e a r e d up. N o r e c o r d s h a v e b e e n r e c e i v e d f r o m him a n d no s t a t e m e n t a s to t h e m a n n e r in w h i c h , o r t h e l e n g t h of t i m e t h e p a t i e n t s were treated. From the fourth Centre a detailed report was sent. The patients were sprayed three times a d a y f o r five m i n u t e s a t a s i t t i n g , a n d t h e following table shows the results which were obtained. A f t e r t h e c l o s i n g o f his C e n t r e this o f f i c e r again wrote as follows :--"The " Electrosol " was used first only for very chronic carriers, a n d r e s u l t e d , in t h e c a s e s of 12 s e l e c t e d m e n , all c a r r i e r s o f o v e r t h r e e m o n t h s , in r a p i d clearance. W i t h t h e e x c e p t i o n o f two m e n , all w e r e f r e e f r o m t h e m e n i n g o c o c c u s in t h e n a s o - p h a r y n x in t w o o r t h r e e w e e k s . With t h e o r d i n a r y i n f e c t e d c o n t a c t , it w a s f o u n d t h a t in p r a c t i c a l l y all c a s e s t h e s e c l e a r e d w i t h i n t w o weeks." THE
CURE
OF CEREBRO-SPINAL MENINGITIS.*
Diagnosis of the type o r g a n i s m by a simple r a p i d method and t r e a t m e n t by univalent serum. BY H . STANLEY BANKS, M.A., M.B., Ch.B., D . P . H . , M e d i c a l Officer of H e a l t h , Motherwell ; Medical Superintendent, B u r g h H o s p i t a l , Motherwell ; L a t e Bacteriologist, B . E . F . , Salonika. R e f e r e n c e to case 2 described hereunder, will, I think, show- that as regards t y p e 1 of the disease, at least there is some justification for the title of this article. T h e r e m a r k a b l e possibilities contained in the treatment, of cerebro-spinal Meningitis, by a n t i - meningococcic t y p e serum, and also the ease of diagnosis of the type organism by simole laboratory methods, are things which are * A paper read before the Scottish Branch of the Society of Medical Officers of Health. The full paper, with illustrations, has been accepted for publication by " T h e Lancet."
I ~
I
not yet widely known, and which well deserve to be. T h i s article refers more p a r t i c u l a r l y to type 1 of the disease. GORDON'S FOUR T Y p E s . - - A m o n g the advances made b y medical science during, and a s a consequence of, the war, not the least i m p o r t a n t is G o r d o n ' s discovery of the four types of the rneningococcus. T h i s has led to a more exact classification of the disease. F o r m e r l y we were content to classify the cases clinically as " f u l m i n a ting," "acute," and "sub-acute," or chronic. N o w we h a v e a bacteriological classification of the disease into cerebro-spinat meningitis, types 1, 2, 3 and 4, and with a little more experience a fairly reliable clit¢ic~l classification, corresponding to these types, m a y also be a r r i v e d at. A few observations on this point have a l r e a d y been made. Thus, Kennedy and Worster D r o u g h t 1 investigated the relation of the t y p e of meningococcus to the clinical picture in 22 cases and found that 8 cases infected with G o r d o n ' s t y p e 1 were all g r a v e l y ill, with fatal issue in 6 ; that of 6 cases with type 3, some were severe and some moderately severe, and that the 8 dases of type 2, all r e c o v e r e d ; of type 4 there were no cases. T h e observations suggest that the types 1 and 3 (Nicolle type A ) are more virulent as regards the meninges, and that t y p e s 2 and 4 (Nicolle t y p e B, or p a r a m e n i n g o c o c c u s ) are specially prone to cause s e p t i c a e m i a and extrameningeal metastases. T h e evidence of other writers, such as Rolleston 2 and A d s h e a d ~ on the point is more conflicting, and no constant relationship can be regarded as established. T h e process of differentiation of the type is similar to what is already fairly well established, for the E n t e r i c a group of fevers, viz. : T y p h o i d , P a r a t y p h o i d A., and P a r a t y p h o i d B., in each of which a distinctive clinical picture is frequently obtained, enabling a p r e s u m p t i v e clinical differentiation to be made. T h e s a m e can be said of the D y s e n t e r i c a group of bacillary dysenteries, at least as regards the broad clinical distinction between the S h i g a and F l e x n e r sub-groups. I n the cerebro-spinal group of fevers, however, the the differentiation is of infinitely g~eater practical importance to the patient, for upon it rests the question of specific t r e a t m e n t by the u n i v a l e n t t y p e serum, and this is p r i m a facie' the only t r e a t m e n t which affords a substantial prospect of success.