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The prevention of poliomyelitis
PUBLIC ~HEALTH, M a r c h , I955 skilled in preventive medicine, and t h a t his financial reward should be commensurate with the importance of his responsibility. This being granted, a great difficulty of recruitment may be overcome. Much of what I have said has been very p e r s o n a l - occasionally maybe facetious, but do not think me priggish if, in conclusion, I appeal to all who are already in the School Health Service and those who may enter later, to " Suffer little children . . . for of such is the Kingdom of Heaven." THE PREVENTION OF POLIOMYELITIS * By DENNIS H. GEFFEN, O.B.E., M.D., D.P.H.
Medical Officer of Health .St:. Pancras and Hampstead Metropolitan Boroughs I hope that the title of this lecture has not led you to believe that I shall be able this afternoon to describe methods of preventing poliomyelitis. At the time of writing such a happy stage has not yet been reached. I can only inform you of preventive measures that are being tried and give you information of various research projects that are being pursued with vigour and a sense of urgency. Virology Poliomyelitis is caused by a virus of which there are three types, Brunhilde (I), Lansing (II), and Leon (III), and various strains have been recognised in each of these types. It is important to realise this basic fact when dealing with either active or passive immunisation, for an attack or outbreak of poliomyelitis may be due to any of the three types of virus. T o be effective active or passive immunity must provide protection against all three types. Pathogenesis For many years it was considered that the infection o f poliomyelitis was a droplet infection and that it entered the h u m a n body through the nose and reached the brain via the olfactory lobes from which it spread to parts of the brain or the cord. Recent research, however, has shown that virus cannot be recovered from the olfactory lobes in experimental animals unless, as in the case of rhesus monkeys, they have been infected by intranasal installation of t h e virus. It is not recovered from the olfactory lobes from fatal cases in man, and post-mortem studies rarely show involvement of olfactory centres. Virus is recovered, however, in the faeces of a considerable proportion of cases in man and experimental animals and is present in large quantities. To-day we tend to consider poliomyelitis as an alimentary infection forming its first habitat in the gut where it grows and from which it is excreted. Its further spread in the gut is a matter of some controversy. At one time it was thought that the virus travelled up or along nerve routes and in fact in experimental animals it does do so. This theory assumed that at no time did the virus invade the blood stream, a viewpoint supported by the fact that virus had not been recovered from the blood of patients suffering from clinical poliomyelitis nor from experimental animals. A few years ago Bodian postulated the theory that inability to recover the virus from blood was due to the fact that it had not been looked for at the right time. He recovered the virus from experimental animals in the pre-paralytic stage and it has been found in the blood stream of cynomolgus monkeys and chimpanzees four to six days after being fed the virus (land2). Furthermore 10 children suffering from minor illnesses later diagnosed as abortive cases of poliomyelitis, and one infant with no symptoms, were found to have type 1 virus circulating in their blood streams 8 It is now more or less accepted that viraemia occurs in the pre-paralytic stage of poliomyelitis. This brings us to the theory which is now supported by sound practical research that the virus is ingested, that it proliferates in the intestines, that it spreads from there to
* Address to the Metropolitan Branch, Society of M.O.H.
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the blood, where it causes a viraemia and that in certain cases it enters the central nervous system at points where penetration is less difficult. One of these points is the area postrema in the medulla oblongata. When dealing with host factors I will enlarge on these points and indicate some influences which may render the central nervous system or parts of it more penetrable by the virus. Possible There which I (1) (2) (3)
Methods of Prevention are three methods in the prevention of poliomyelitis would like to consider. T h e y are : - T h e production of passive immunity. T h e achievement of active immunity. Host factors.
Passive Immunity Individuals who have had poliomyelitis develop antibody in their blood. This antibody is specific to the type of virus to which they have been exposed or by which they have been infected. It is possible, however, that when the host develops antibody to one type of virus the immunity to other types is also raised. These antibodies are said to be long lasting. Specific agglutinins are also formed but their presence in the blood is of shorter duration. Gear of South Africa has stated rather picturesquely that " an individual's past experience of infections is clearly inprinted in his blood and by appropriate tests it can be revealed." 4 Melnick of the University of Yale delivered papers in Rome and Buffalo in which he stated that by examination of the blood of a representative proportion of a community it was possible to assess the extent to which that community had been exposed to or suffered from poliomyelitis and the particular types of virus involved. If agglutinins (short lived) and antibodies (long lived) were present infection or exposure was recent. If only antibodies (long lived) were present then infection or exposure was some years back. Not only could he indicate the history qua specific infection of the community but he could predict the future if further exposure took place 5 These points are important because if poliomyelitis is associated with a viiaemia and the production of protective antibodies then it should be possible by giving blood containing antibodies, or some extract thereof such as gammaglobulin, to provide immunity to infection if sufficient be given at the right time and under the right circumstances. Experimentally Bodian passively immunised groups of cynoI.nolgus monkeys with human gammaglobulin and immediately fed them with poliomyelitis virus. E q u a l numbers served as controls. In 104 monkeys receiving gammaglobulin no paralysis occurred. In 97 control animals 27 became paralysed. 6 Attempts have been~made to prevent poliomyelitis in human communities by giving gammaglobulin. In, 1952 54,772 children were inoculated, of whom half received gammaglobulin and the other half were given gelatin. T h e clinical investigators were not aware which substance txad been inoculated into individual children until after the study had been completed. A total of 104 cases of paralytic poliomyelitis occurred during the follow u p period of 14 weeks. From the second to the fifth week the investigators stated that there was significant though not a complete degree of protection. Paralysis appeared in seven children who had received gammaglobulin as compared with 39 who had been inoculated with gelatin. After the eighth week no protection was found to exist. T h e y admitted that the injection of gelatin was associated with an increase of paralysis in the limb of injection. In 1953, 235,000 children were inoculated. T h e members of the National Advisory Committee appointed for the evaluation of gammaglobulin were of the opinion that their analysis of the data did not yield statistically measurable results. From analysis of information on the efficacy of gammaglobulin given to family contacts, the committee decided that admiinstered by this method, with the pro-
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portions involved and in the dosages used, it had n o apparent effect o n t h e incidence or severity of paralysis developing in subsequent cases, v I had t h e advantage o f hearing various speakers on the subject o f g a m m a globulin in R o m e and quite candidly I was unable to persude myself that at t h e present m o m e n t there is m u c h to be said for the use of g a m m a globulin to protect communities from paralytic poliomyelitis. It has been suggested in England that it might be useful given to contacts, nurses, medical students, babies exposed to infection soon after birth, and children in hospital wards in which a case of poliomyelitis develops. Even if it does produce increased antibody titre the effect lasts for a maxim u m period of eight weeks and probably not m o r e than five. T h e r e was some controversy originally as to w h e t h e r g a m m a globulin prepared in E n g l a n d would, contain antibodies to all three types of poliomyelitis virus in that fewer individuals have been exposed to infection in England than in the U n i t e d States of America. An assurance was given, however, that the g a m m a globulin had been tested and contained antibodies to all three types of virus. I do not think the prevention of paralytic poliomyelitis rests in passive immunity. It is expensiVe, uncertain, unreliable, and at the best the i m m u n i t y it gives is shortlived. T h e r e may be, however, exceptional and particular circumstances. G a m m a globulin was given to Q u e e n Elizabeth and the D u k e of E d i n b u r g h when t h e y visited Australia, their exposure to possible infection being controlled and of limited duration.
Active Immunity Active i m m u n i t y has b e e n attempted by the production of : - (1) A live vaccine (2) A dead vaccine. You will be aware that a live vaccine against yellow fever has been produced and at one t i m e most research workers were attempting to repeat this satisfactory result in relation to poliomyelitis. I n a paper which Jonas Salk read in R o m e he stated that his group worked on an attenuated type of living virus vaccine until it was shown that in h u m a n beings a non-infectious or dead virus preparation could stimulate a serological response similar to, and even greater than that which follows natural infection. As a result further work on the live virus vaccine was postponed and his group concentrated on a vaccine killed w i t h formalin. S u c h a vaccine m u s t fulfil the following criteria. 9 (1) T h e virus must be completely killed ; (2) T h e vaccine must have no deleterious effects and (3) It m u s t produce i m m u n i t y to the three known types of poliomyelitis viruS. It is not easy to be sure that in all batches of vaccine produced on a commercial scale the virus will be dead, and in fact in trials of a vaccine some years ago in America some 12 children did develop poliomyelitis after injection, paralysis affecting chiefly the limb of injection or the contralateral limb. I think it was agreed that the virus in this trial had not been killed. T h e difficulty lies in exposing the living virus to a sufficient concentration of disinfectant, in this case of formalin, to kill it, yet nevertheless to preserve its antigenic properties. T h e virus is g r o w n on monkey kidney tissue and again one has to be sure that there will be no nephrotoxic reaction. T h e vaccine m u s t contain strains of each of the three known poliomyelitis types of virus and each of these types must produce antigenic response. T h e vaccine, having been prepared, was given small scalo trials. It was found that the antibody titre in the blood to all three types of virus was increased, after three injections at suitable intervals, to a height which exceeded that obtained in natural infection. M a y I say immediately that the path of Salk and his team has been by no means easy. T h e r e were those who said ttiat the vaccine was dangerous in that there was no definite p r o o f that the virus had been killed or would be so in sub-
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sequent batches. T h e r e were others w h o argued that there m i g h t be nephrotoxic reactions, and a further school that have said that there is no certain knowledge that the imm u n i t y produced will either be lasting or adequate to prevent an attack of clinical paralytic poliomyelitis. Let me see how m u c h of this I c a n answer. I have listened to all three schools who have raised ob~ jections to the formalised vaccine and whilst I can appreciate their arguments I think the answer m u s t be this. T h e Salk or formalised vaccine has now been given to over 600,000 individuals and to date no untoward effect has been noted. I admit that this is no guarantee of the future, but I am satisfied that insofar as it is possible to say of any vaccine that it is safe, that statement as to safety can be m a d e of this vaccine. I do not think anyone denies that it produces antibody response of a high level. I want. however, to be clear on this point. T h e Salk team have not stated that the formalised vaccine will prevent clinical poliomyelitis. On the occasions w h e n I have heard h i m speak, Salk himself has made no such claim. H e has stated that his vaccine is safe, that adequate precautions were taken to secure that it should be so and remain so and that it produces a high antibody response. T h e question as to w h e t h e r it will prevent poliomyelitis is now being assessed by Dr. T h o m a s Francis, Jr., Prof. of Epidemiology at A n n Arbor, Michigan, and a team of expert observers, and I hope that between M a r c h and J u n e of 1955 we shall be informed of the results of the experiments that took place in 1954. T h e r e has been some criticism tha~ there have been no published results on chimpanzees or monkeys which have been vaccinated w i t h the formalised vaccine and then challenged w i t h a virulent strain of poliomyelitis. T h i s is true, but in an interview w i t h Salk he did s h o w m e the results of experiments in which he challenged inoculated monkeys with intravenous injections of living virus. Eight out of 10 of those vaccinated survived. T h e two who died developed little a n t i b o d y . O f the controls six out of 10 died. 1~ I think it is unfortunate that these results, which are only a sm"att portion of Salk's work on this vaccine, have not been published. It is understandable that no observer can publish everything. Like m a n y others Salk has a large collection of data awaiting the time w h e n he will haye sufficient leisure to edit and publish. I think all research workers will understand and appreciate this particular difficulty. Let m e give you s o m e examples of the test that has been carried out in A m e r i c a during 1954. T h e figures I am presenting are round numbers and only approximately correct. 210,000 children were given the Salk vaccine and are being compared with a similar number who have been given an injection of solution identical with the vaccine except for the presence of virus and monkey kidney tissue (solution 199 used for the cultivation of virus). Another 400,000 children in grade 2 in schools throughout America have been given the vaccine and are being compared with 400,000 in grade 1 and 400,000 in grade 3. You will see that some 650,000 children have been inoculated and are being compared with 1,200,000 controls, some of whom have been given a placebo vaccine. The trial, therefore, embraces 1,800,000 children. The figures include children who did not complete the trial. Every one of these children has now got to be followed up. I am told that no less than 150,000 persons will have assisted in the total vaccine programme. These include clinicians, epidemiologists, health officers, physical therapists, virologists, school teachers and administrators. 14,000 schools co-operated and a staff of 100 operators are engaged on a 24 hour basis---clerks, coding experts and statisticians. Grants in excess of 850,000 dollars (approximately s have been made to the University of Michigan. This is part of the total of 7,500,000 dollars (over 2~ million pounds) granted by the National Foundation for Infantile Paralysis of America for the vaccine programme. T h e results will be placed before a C o m m i t t e e u n d e r the chairmanship of Dr. Francis and I have no hesitation in stating that whatever information is received through Dr. Francis' c o m m i t t e e will be based on the soundest and most unbiased principles.
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T h i ~ p r o b l e m of following u p 1,800,000 c h i l d r e n is a n e n o r m o u s one. I t will b e necessary to find out w h e t h e r or n o t a n y o f t h e s e c h i l d r e n d e v e l o p e d poliomyelitis d u r i n g 1954, w h e t h e r t h e attack was paralytic or non-paralytic a n d w h a t muscles were involved. I n a d d i t i o n cases diagnosed as suffering f r o m clinical poliomyelitis in t h e a p p r o p r i a t e g r o u p s of p r o t e c t e d o r coiatrol c h i l d r e n will h a v e t h e diagnosis c o n f i r m e d b y b l o o d a n d stool examination. A n t i b o d y titres of c h i l d r e n before a n d a f t e r inoculation have also b e e n carried out. I t h i n k t h a t whilst we m u s t possess ourselves i n patience I m a y q u o t e o n e or two remarks. Salk stated in a lecture in Rome 11. " T h a t there is still much to be learnt is clear indeed. Nevertheless it ~oes appear that by suitable manipulation of the dose of vaccine and of the intervals between inoculations, it should be possible with relatively few injections, properly spaced, to provide long term immunity. T h e ultimate object is not merely a reduction in the amount of crippling and death from poliomyelitis but also the elimination of these as a cause of fear. It will be clear, therefore, that the problem will not have been fully solved until a means is available that will with certainty and for life make this possible." D r . T h o m a s Rivers x2 in a v e r y excellent p a p e r m a d e t h e following s t a t e m e n t : - " A group of experts under the guidance of Dr. Francis has been established to evaluate the protective effects of the formalised vaccine. The final report will not be available for some months. However, there are reasons to believe that the vaccine will be effective. If it proves to be ineffective most workers will contend that a good one can be obtained soon." T h i s I t h i n k s u m m a r i s e s t h e situ~ation as w e k n o w it at present. I a m h o p e f u l of t h e o u t c o m e of t h e p r e s e n t trials, a l t h o u g h I d o n o t t h i n k t h e y witl b e 100% effective. I know, however, t h a t t h e vaccine is b e i n g i m p r o v e d at t h e p r e s e n t m o m e n t a n d t h a t it c a n n o t b e long before t h e e n d of t h e road is i n sight. Trials with a Living Vaccine
W o r k is energetically p r o c e e d i n g w i t h live vaccines. O n e t e a m of r e s e a r c h workers u n d e r Mil~zer x3 is experim e n t i n g o n a t r i v a l e n t vaccine inactivated b y ultra-violet light. M o s t interesting work, however, o n live vaccines is b e i n g carried o u t b y S a b i n ~t C i n c i n n a t i ? 4 H e has f o u n d t h a t b y passing v i r u l e n t strains of virus t h r o u g h m o n k e y k i d n e y tissue i n r a p i d succession, a vaccine c a n be p r e p a r e d w h i c h has antigenic p r o p e r t y b u t w h i c h will n o t cause paralysis w h e n injected directly into t h e b r a i n of c y n o m o l g u s m o n k e y s . T h e vaccine h e was u s i n g had b e e n m a d e u p b y r a p i d k i d n e y tissue inoculations; 33 t i m e s w i t h t y p e 1 virus, 51 t i m e s w i t h t y p e 2, a n d 34 t i m e s w i t h t y p e 3. A more painstaking and persistent worker than Sabin I h a v e n e v e r m e t . I t h i n k his a i m is to p r o d u c e a vaccine w h i c h will be effective w h e n given b y m o u t h , a n d I have t h e greatest faith t h a t S a b i n a n d his t e a m will u l t i m a t e l y achieve t h e success w h i c h t h e y u n d o u b t e d l y m e r i t . Host Factors U n d e r this h e a d i n g I w o u l d like to c o n s i d e r w h y it is t h a t w h e n I00 p e o p l e b e c o m e i n f e c t e d w i t h t h e v i r u s of poliomyelitis p e r h a p s 9 0 % r e m a i n symptomless, 9 % s h o w signs of disease v a r y i n g f r o m a sore t h r o a t a n d intestinal u p s e t to stiffness of t h e neck, w h i l s t 1% s h o w definite paralysis. W h y is it t h a t 9 9 % escape paralysis or alternatively w h y is it t h a t 1 ~o b e c o m e paralysed W e are apt to forget t h a t poliomyelitis is possibly t h e least serious of all infectious diseases w i t h t h e exception of t h a t o n e c o m p l i c a t i o n or e x t e n s i o n of t h e disease w h i c h destroys m o t o r cells in t h e b r a i n or cord a n d causes paralysis. A p a r t f r o m this it appears to b e a mild infection lasting a few days, t h e s y m p t o m s of w h i c h are possibly less serious t h a n a cold in t h e head, a n d f r o m w h i c h recovery is c o m p l e t e
89 a n d iiximunity lasting. I f we could b e s u r e t h a t a n i n d i v i d u a l c o n t r a c t i n g poliomyelitis w o u l d n o t b e c o m e paralysed t h e n t h e r e m i g h t b e m u c h to b e said for s p r e a d i n g t h e disease in o r d e r t h a t a c o m m u n i t y s h o u l d o b t a i n n a t u r a l i m m u n i t y . It is only its capability of causing paralysis t h a t m a k e s t h e virus of poliomyelitis a serious p a t h o g e n i c o r g a n i s m . T h e r e are certain h o s t factors w h i c h are generally accepted : - (1) Paralytic poliomyelitis is known to follow operations for the removal of tonsils and adenoids and then to be of the bulbar variety. (2)
Pregnant women are susceptible to poliomyelitis and may contract it in severe form.
(3)
It is associated with undue exertion, fatigue and chill.
(4)
It may follow body insults such as injection, fracture and operative procedures, when paralysis will show localisation referred to the area of insult. (15,16).
I w a n t to carry these observations a little b i t f u r t h e r . G a y l o r d A n d e r s o n , Prof. of P u b l i c H e a l t h in M i n n e s o t a , has w r i t t e n two p a p e r s in w h i c h he shows t h a t : - (a) Persons with the bulbar type of poliomyelitis give a history of removal of tonsils and adenoids more frequently than do persons with other forms of poliomyelitis. (b) " If a tonsillectomised person develops clinically recognisable poliomyelitis, the likelihood of bulbar involvements is four times as great as in one where the tonsils are in situ. (c)
This higher proportion of bulbar cases in tonsillectomised persons occurs at all ages and regardless of the time that has elapsed since the operation.
(d)
T h e higher proportion of bulbar cases in older persons is due primarily to absence of tonsils rather than to age per se.
H e r e is a s t a t e m e n t to t h e effect t h a t b o d i l y i n j u r y has a localising effect o n paralysis w h e n an i n d i v i d u a l is attacked b y poliomyelitis irrespective of h o w long a t i m e it is since t h a t i n j u r y was suffered. A t h e o r y is p r o p o u n d e d t h a t w h e n t h e host is s u b j e c t e d to a local injury, s u c h as tonsillectomy, a p e r m a n e n t c h a n g e takes place in t h e n e r v e cells e n e r v a t i n g t h a t area, w h i c h has r e n d e r e d t h e m , or t h e i r s u r r o u n d i n g b l o o d vessels, m o r e p e r m e a b l e to t h e virus of poliomyelitis, or less able to resist its cell d e s t r o y i n g "(cytopathogenic) p r o p e r t i e s . G a y l o r d A n d e r s o n has followed this a step f u r t h e r in c o n n e c t i o n w i t h p e r s o n s w h o c o n t r a c t e d paralytic poliomyelitis a n d have h a d t h e i r a p p e n d i x r e m o v e d at s o m e p r e v i o u s date. H e expected t h a t t h e right leg w o u l d b e i n v o l v e d m o r e often t h a n t h e left. H e failed, however, to find t h a t this was
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M y o w n experience in p e r s o n s c o n t r a c t i n g poliomyelitis i n t h e t h r e e weeks following a p p e n d i c e c t o m y is t h a t t h e a b d o m i n a l muscles a n d d i a p h r a g m are usually i n v o l v e d a n d t h e r e m a y b e a paralytic ileus. I h a v e no data o n t h e long t e r m effect of a p p e n d i c e c t o m y in localising poliomyelitis. Bodian i n Baltimore has carried o u t s o m e very i n t e r e s t i n g work in c o n n e c t i o n w i t h poliomyelitis following injection, is His e x p e r i m e n t s h a v e b e e n d o n e o n c y n o m o l g u s m o n k e y s a n d h e has i n j e c t e d v i r u s directly into t h e h e a r t ( M a h o n y strains of type 1). Paralysis occurs i n 5 0 % of m o n k e y s so t r e a t e d a n d i n at least 2 0 % t h e initial paralysis is i n t h e face. If, however, t h e s e m o n k e y s have b e e n injected w i t h various i r r i t a n t s u b s t a n c e s i n c l u d i n g gelatin, cortisone, penicillin a n d d i p h t h e r i a - p e r t u s s i s - t e t a n u s vaccine w i t h i n one to t h r e e weeks p r i o r to t h e giving of t h e virus, he finds t h a t n o t o n l y is t h e r e a n u n d u e p r o p o r t i o n of cases wh~re paralysis affects t h e l i m b of i n j e c t i o n (the h i n d l i m b ) b u t t h a t instead of 5 0 % of t h e m o n k e y s d e v e l o p i n g poliomyelitis t h e figure is n o w raised to 8 0 % . N o t only has the risk of d e v e l o p i n g paralysis in t h e l i m b of i n j e c t i o n b e e n increased, b u t t h e risk of t h e h o s t d e v e l o p i n g paralytic poliomyelitis has been increased.
9o P e r s o n a l l y I have always believed t h a t a n injection o f d i p h t h e r i a - p e r m s s i s vaccine n o t only localises t h e paralysis of p e r s o n s infected w i t h virus b u t also increases the attack rate, t h o u g h I m u s t a d m i t I have n o figures to prove this for t h e y are n o t easily obtainable. B o d i a n ' s e x p e r i m e n t s w i t h c y n o m o l g u s m o n k e y s lends s u p p o r t to this view. I t h i n k B o d i a n c o n s i d e r e d t h a t w h e n a p e r s o n suffers a n i n j u r y s u c h as a n injection, t h e b l o o d vessels or t h e a n t e r i o r h o r n cells s u p p ! y i n g the i n j u r e d part b e c o m e m o r e p e n e t r a b l e to virus. I n this c o n n e c t i o n I w o u l d like to m e n t i o n o n e p o i n t t h a t ties u p w i t h G a y l o r d A n d e r s o n ' s work o n t h e f a r - r e a c h i n g effects of tonsillectomy. I n t h e course of his work i n injecting m o n k e y s intracardially w i t h virus, B o d i a n writes : - - " O f considerable i n t e r e s t i n this c o n n e c t i o n is t h e fact t h a t t h r e e i n s t a n c e s of t h e p r o v o k i n g effect of l o n g - s t a n d i n g t r a u m a a p p a r e n t l y have o c c u r r e d i n o u r c y n o m o l g u s m o n k e y s w h i c h were inoculated intravascularly. O n e a n i m a l w i t h a n old healed tibial f r a c t u r e a n d o n e w i t h a n old h e a l e d accidental a m p u t a t i o n at t h e ankle, were initially paralysed in t h e c o r r e s p o n d i n g leg.. A t h i r d a n i m a l w h o was received w i t h a n old right eye injury, i n c l u d i n g corneal opacity, was paralysed initially in the r i g h t facial muscles, b o t h u p p e r a n d lower." I t h i n k we shall have to pay v e r y considerable a t t e n t i o n to t h e f a r - r e a c h i n g paralytic effects o f bodily insult o n t h e host exposed to t h e virus of poliomyelitis. T h e last r e s e a r c h studies to w h i c h I w o u l d like to d r a w a t t e n t i o n are associated w i t h p y r i d o x i n a n d cortisone.
Pyridoxin P y r i d o x i n or "Vitamin B6 occurs in yeast, liver, rice a n d b r a n a n d c a n be p r e p a r e d synthetically. I t is a n importan~ factor i n n u t r i t i o n a n d deficiency m a y give rise to a s y m p t o m c o m p l e x in w h i c h m u s c u l a r weakness a n d rigidity are p r o m i n e n t . A deficiency of V i t a m i n B6 decreases h u m a n reaction to i n f e c t i o n a n d lowers, antigenic response in t h e host. B o d i a n reports : - - 19 (1) T h a t paralytic poliomyelitis occurred in an uninoculated laboratory rhesus monkey that was being deprived of pyridoxin. Poliomyelitis in uninoculated rhesus monkeys (with one doubtful exception) had previously not been known to occur. (2) T h e virus isolated from this monkey was shown to be of the Brunhilde type, that is type 1, and was in use in the laboratory at the time of infection and probably present in the environment of the animal quarters. (3) In that this appeared to be the first known natural or laboratory spread of poliomyelitis in rhesus monkeys an attempt was made to see if the deficiency of pyridoxin was the causal factor. Eleven rhesus monkeys were treated with desoxy-pyridoxine. This has the same effect as depriving them of pyridoxin. T h e monkeys were then fed orally with Brunhilde virus. Two succumbed to paralytic poliomyelitis although this species of monkey is known ordinarily to be insusceptible to poliomyelitis as a result of oral feeding. H e r e is a possible example of a n association b e t w e e n a v i t a m i n deficiency a n d e n h a n c e d liability to c o n t r a c t poliomyelitis a n d you m a y care to c o n s i d e r this in relation to t h e fact t h a t c o m m u n i t i e s living i n civilised a n d hygienic c o n d i t i o n s t e n d to sophisticate t h e i r food a n d are m o r e p r o n e to poliomyelitis t h a n t h o s e living in u n h y g i e n i c s u r r o u n d i n g s . I m u s t a d m i t t h a t I have n o evidence t h a t sophistication of food results in a deficiency of pyridoxin. I n a n interview, m o r e o v e r , t h a t I h a d recently w i t h B o d i a n h e felt t h a t his findings o n m o n k e y s d e p r i v e d of p y r i d o x i n m i g h t easily b e d u e to t h e fact t h a t t h e 11 ~,nonkeys were receiving n u m e r o u s injections daily of d e s o x y - p y r i d o x i n a n d t h a t t h e s e i n j e c t i o n s - i n t h e m s e l v e s m i g h t have r e n d e r e d t h e m o n k e y s m o r e p r o n e to develop poliomyelitis. I a m n o t entirely c o n v i n c e d o n this p o i n t a n d I h o p e t h a t f u r t h e r work will b e carried out o n t h e effect of p y r i d o x i n a n d susceptibility to poliomyelitis. Cor tison e Lastly I w o u l d refer to some excellent work t h a t has b e e n carried o u t b y S h w a r t z m a n in t h e M o u n t Sinai Hospital in N e w York. S~
PUBLIC
HEALTH,
March,
z955
Previous e x p e r i m e n t s h a d s u g g e s t e d a relationship b e t w e e n e n d o c r i n e i m b a l a n c e a n d p r e d i s p o s i t i o n to poliomyelitis. C u r l e y a n d Ayaock i n 1946 ~1 h a d r e p o r t e d t h a t c a s t r a t i o n in m o n k e y s i n d u c e d a g r e a t e r susceptibility to t h e intranasal i n o c u l a t i o n of t h e v i r u s whilst t r e a t m e n t of t h e castrates w i t h o e s t r o g e n increased t h e i r resistance. I n 1939 H o r a c e H o d e s h a d d e m o n s t r a t e d : - - ~ (1) T h a t virgin and pregnant Swiss mice were equally susceptable to intracerebral inoculation of St. Louis encephalitis virus. (2) T h a t following subcutaneous vaccination with the St. Louis virus the great majority of virgin Swiss mice became immune. (3) T h a t the majority of pregnant mice though vaccinated "did not become so immune. (4) That pregnancy not only interferes with the development of acquired immunity but also diminishes a previous established immunity. It is generally accepted t h a t p r e g n a n t w o m e n have decreased resistance to i n f e c t i o n w i t h poliomyelitis a n d V e n n i n g in 1946 s h o w e d that t h e r e is a greatly e n h a n c e d adreno-cortical f u n c t i o n d u r i n g p r e g n a n c y w i t h h y p e r p r o d u c t i o n of cortisone. S h w a r t z m a n set out to see if t h e r e was a relationship b e t w e e n cortisone a n d liability to c o n t r a c t poliomyelitis, or, to p u t it r o u n d t h e o t h e r way, if cortisone lowered resistance to infection w i t h poliomyelitis virus. H e chose a n a n i m a l w h i c h is generally refractory to poliomyelitis, namely, t h e S y r i a n golden h a m s t e r . I f t h e s e b e inoculated intracerebrally w i t h t h e L a n s i n g t y p e of poliomyelitis virus, a b o u t 25% die. I f t h e y b e injected w i t h cortisone t h e m o r t a l i t y rate can b e raised to n e a r l y 8 0 % . I n t r a p e r i t o n e a l injection of massive doses of L a n s i n g strain of poliomyelitis fails to cause disease in n o r m a l golden Syrian h a m s t e r s . I f t h e y b e g i v e n injections of c o r t i s o n e a n d t h e n a n i n t r a peritoneal ~inoculation of virus a severe disease is elicited. S h w a r t z m a n ' s w o r k is e x t r e m e l y i m p o r t a n t w h e n we consider host factors i n relation to resistance to poliomyelitis infection. W e already k n o w of t h e .effects of pregnancy, chill, operation, fatigue a n d local i n j u r y or insult s u c h as injection. T h e s e are conditions of stress in w h i c h t h e r e m a y b e h y p e r p r o d u c t i o n of cortisone. T h i s m u s t b e t a k e n into a c c o u n t w h e n we c o n s i d e r t h e p r e v e n t i o n o f poliomyelitis. So far g a m m a g l o b u l i n has n o t p r o v e d a practical m e a n s of p r e v e n t i n g poliomyelitis in a c o m m u n i t y . M a y this n o t be due to t h e fact t h a t it was given in insufficient q u a n t i t y or t h a t " sufficiency " of a n t i b o d y is variable, d e p e n d i n g o n t h e c o n d i t i o n of t h e host at t h e p a r t i c u l a r t i m e t h e g a m m a globulin is given ? Is it n o t possible t h a t a vaccine m a y p r o d u c e a n t i b o d i e s w h i c h t h o u g h a d e q u a t e to secure p r o t e c t i o n at one t i m e m a y b e i n a d e q u a t e at a n o t h e r ? I f g a m m a g l o b u l i n a n d vaccines, e i t h e r killed o r active, fail to control poliomyelitis we m a y yet h a v e to t u r n to t h e h o s t facto r a n d find out w h y i t is t hat the re are t i m e s w h e n indi~:iduats, w h i l s t n o r m a l l y r e s i s t a n t to t h e i n v a s i o n of t h e virus, fail in t h e b a t t l e against t h i s disease. Is this possibly d u e to " stress," e n d o c r i n e imbalance, or dietary deficiency ? I a m m u c h i n d e b t e d to o u r A m e r i c a n colleagues for t h e i r k i n d n e s s a n d c o u r t e s y a n d grateful for all t h e help I kave received. I stood a m a z e d at t h e c o n c e n t r a t i o n a n d energy w i t h w h i c h t h e y are c o n d u c t i n g r e s e a r c h o n t h e o t h e r side of t h e Atlantic a n d I c a n n o t b e o t h e r t h a n optimistic t h a t t h e t i m e is n o t too f a r d i s t a n t w h e n poliomyelitis will b e a preventabl 9 disease. REFERENCES
1 SAnIN, D. 0952.) Amer. J. Hyg., 55, 414. HO~TMAN.W, D. M. (1952.) Proc. Soc. Exper. Biol. ~ 79, 417. ~ , & McCuLLUM, R. W. (1953.) Proc. Soc. Biol. ~ Med., 82. GnAa, J, H.. S. : International Poliomyelitis Conference, 195~:i'!:-~ :~:%: MEL.WICg, J . L. Annual Congress American Public Association, 1954. 6 BODIAN, D. (1952.) Amer. ft. Hyg., $6, No. 1, 78-9.
Med., Exper. Rome, Health
PUBLIC
HEAL'IH,
March,
1955
7J.A.M.A. (1954.) x54, 1086. s Ministry of Health, Poliomyelitis, Medical Memorandum, July, 1954. 9 SALK, JONAS. International Poliomyelitis Conference, Rome, 1954. a0 , Personal communication 1954. n . International Poliomyelitis Conference, Rome, 1954. ~z RIvzas, THOMAS. International Poliomyelitis Conference, Rome, 1954. ~a MILZXR, A., et al. (1954.) Amer. J. Publ. Hlth., 44, 26. x4 SAraN, A. B. International Poliomyelitis Conference, Rome. ~5 GEFFEN, D . H . (1950.) Med. Off. 83, 137. as McCLOSKY, B. P. (1950). Lancet i, 659. 9 (19.52). Ibid. i, 1187. 17ANDERSON, GAYLORD W. (1954.) Bull. Umv. Minnesota, 26.2.54. ~8 BODEAN, D. (1954.) Amer. J. Hyg. Awaiting Publication. ~9 . (1948.) Amer. J. [-fvg., 48, 87-93. ~" SWHARTZMAY,GREGORY. Columbia University Press, 1953. ea CURLEY, F. J. & AYCOCK, W. L. (1946). Endocrinology, 39, 414. ..z HOPES, H . L . (1939). J. Exper. Med., 69, 533-543. 23 VENNING, E . H . (1946.) Endocrinology, 39, 203.
LOCAL POPULATION ESTIMATES FOR x954 The Registrar-General has issued his estimates of the populations of counties, boroughs and urban and rural districts in England and Wales as at June 30th, 1954". Grouped figures are given for the standard regions, conurbations and density aggregrates and by sex and age for the country as a whole. This publication is designed to meet a general demand for an early issue of up-to-date figures of local populations, and in particular to assist local councils and other administrative authorities, manufacturers, and distributors. The figures are the final estimates which will later be embodied in the Registrar-General's Statistical Review for the year 1954. lit has already been announced that the home population of England and Wales at June 30th, 1954, is estimated to have been 44,274,000 of whom 21,288,000 were males and 22,986,000 females and that the total shows an increase of 184,000 over the figure for mid-1953. Comparison with the estimates for previous years indicate certain trends in the internal movement of the population9 The population of the Administrative County of London continued to decline, dropping from 3,343,000 in 1953 to 3,322,000 in 1954. This decline is reflected to a certain extent in the increase in the populations of those areas which contain I,.C.C. Housing Estates : Borough of Romford by 1,752, Rural District of Elstree by 1,820 and Borough of Reigate by 2,720. The slight decline in the population of the Administrative County of Middlesex, which began in 1953, continued in 1954, the figure being 2,256,000 compared with a peak of 2,270,000 in 1952. Within the Administrative County of Essex (the population of which increased from 1,644,100 in 1953 to 1,672,500 in 1954) the Urban District of Billericay, containing the New Town of Basildon, increased by 2,590, and the Rural District of Epping, containing Harlow New Town, by 6,330. Similarly within the Administrative County of Hertfordshire (population 651,500 in 1953 and 671,700 in 1954), the Borough of Hemel Hempstead and the Urban Districts of Stevenage and Welwyn Garden City, each of which contains a New Town, increased by 3,460, 2,790 and 1,420 respectively, while, in the Administrative County of Sussex West, the Rural District of Horsham, containing the New Town of Crawley, increased by 4,740. *The Registrar-General's Estimates of the Population of England and Wales--PopuIations of each Administrative Area at June 30th, 1954, H.M. Stationery Office, price 9d. net (or by post from P.O. Box 569, London, S.E.I., price 10~.d.)
Sir Alexander Macgregor, formerly M.P.H., Glasgow, and a Past-President of the Society, on March 3 i s t gives up the chairmanship of the Scottish Western Regional Hospital Board, which be has held since its establishment in 1948. The Secre~arv of State has expressed gratitude for Sir Alexander's ':sure touch and general acceptance" during his period of office.
,4 Correetion.--in the report of the M. & C.W. Groups (Publi,: Health, February, I955, page 82) the word 'dead,' seven lines from foot of left hand column, should have read 'deaf.'
91
Society of Medical Officers of Health ORDINARY MEETING, NOVEMBER An Ordinary Meeting of the Society was held in the Council Chamber of the British Medical Association, Tavistock House, Tavistock Square, W.C.1, on Friday, November 26th, 1954. 1. Minutes of Last Meeting.--The minutes of the Ordinary Meeting, held on September 16th, 1954, were confirmed and signed by the President. 2. Life Membership.~The following were elected fully-paid I.ife Members of the Society on the nomination of the Council and of their Branches : Dr. J. F. Macdonald, Lt.-Col. E. F. W. Mackenzie and Dr. J. B. Lowe. 3. Elections.--The following candidates, having been proposed and seconded, were duly taken into membership : - Fellows.--Drs. Islay Cecil Barnem, Alexander David Christian Stewart Cameron, David Miller Cathie, Catherine H. Coutts Milne, Raymond Joseph Donaldson, Thomas Christie Falconer, Kate Gray, Edmund Monk Hamilton, Herbert James, J. A. Linden, Thomas Aloysius McVey, Charles Nicholson Minto, Stuart Love Morrison, Basil John Lloyd Moss, Anne Boyd Perkins, Lewis Bernard Peters, Irene Tomina Joan Ruxton, Elizabeth Schonberger, Hope B. Scott, William Sharpe, John Anthony Slattery, Henry Ellis Smith, Donald Shrewsbury ToddWhite, Robert Webster, B. N. Williams, Arthur Leslie Thrower, Alfred Yarrow and Sydney Maxwell Young. Assoeiates.--Drs. William Robert Samuel Robertson, and Ernest Ward.
Temporary
Members
attending
D.P.H.
Courses.--Drs.
A.
Bukhari and A. F. Mowafi. Nominations for the next electionwere reported and the meeting terminated. A N N U A L GENERAL MEETING The Annual General Meeting of the Society for the Session 1953-54 was held in the Committee Room of the Society, Tavistock House, London, W.C.1, on Friday, January 14th, 1955, at 12.45 p.m. The President, Dr. Jean M. Mackintosh, was in the Chair and there were also present 12 members of the Society. 1. Minutes of Last Annual General Meeting.--The Minutes of the Annual General Mee, ting, held on December 10th, 1953, were confirmed and signed by the President. 2. Annual Reports and Accounts.--The Annual Report of the Council, the Treasurer, and of the Editor of PUBLIC HEALTH, were received and adopted, together with the Balance Sheet as at September 30th, 1954, and the Income and Expenditure Account for the year ended September 30th, 1954. 3. Appointment of Auditors.--Messrs. Greene, Clements & Co., Chartered Accountants, of 20, Bloomsbury Square, London, W.C.1, were re-appointed the Auditors of the Society. 4. Life Membership.--The following members were elected to fully-paid Life Members of the Society, on the nomination of the Council and their Branches : - Drs. Muriel H. Radford, H. W. Barnes, H. S. Banks, Mary Kidd, H. L. Cronk, C. M. Richardson, H. G. Trayer, E. H. Walker, C. E. E. Herington and A. F. Adamson. 5. Elections.--The following candidates, having been duly proposed and seconded were elected to Membership of the Society : - Fellows.--Drs. June Patricia Cooper, Isobel Beatrice Craighead, Margaret Rosemary Farrell, Marie P. S. Grant, Arthur John Isbell Kelynack, Donald Gordon Noble, Douglas Stuart Parken, Thomas Alun PhilJips, George Lee Ritchie, Francis Simm, James Taylor and Eric Dudley Birch Wolfe. Temporary Fellows, attending D 9 Courses.--Drs. Edwin lnman Blenkinsop, Maureen Henderson, Joyce Heather Hindmarsh, John McCormack and Helen Herbison Reid. Nominations for the next election were reported and the Meeting terminated at 1 p.m.
President:
EAST A N G L I A N B R A N C H Dr. Kathleen M. Harding (Dist. M.P.H.,
E.
Suffolk).
Hon. Secretary : Dr. G. R. Holtby (Dist. M . P . H . , Norfolk).
A meeting of the Branch was held at The Scole Inn, Scole, on Saturday, September 18th, 1954, at 3 p.m. The retiring President, (Dr. K. F. Alford) was in the chair and 20 members were present.
Medical Officer of Health .St:. Pancras and Hampstead Metropolitan Boroughs I hope that the title of this lecture has not led you to believe that I shall be able this afternoon to describe methods of preventing poliomyelitis. At the time of writing such a happy stage has not yet been reached. I can only inform you of preventive measures that are being tried and give you information of various research projects that are being pursued with vigour and a sense of urgency. Virology Poliomyelitis is caused by a virus of which there are three types, Brunhilde (I), Lansing (II), and Leon (III), and various strains have been recognised in each of these types. It is important to realise this basic fact when dealing with either active or passive immunisation, for an attack or outbreak of poliomyelitis may be due to any of the three types of virus. T o be effective active or passive immunity must provide protection against all three types. Pathogenesis For many years it was considered that the infection o f poliomyelitis was a droplet infection and that it entered the h u m a n body through the nose and reached the brain via the olfactory lobes from which it spread to parts of the brain or the cord. Recent research, however, has shown that virus cannot be recovered from the olfactory lobes in experimental animals unless, as in the case of rhesus monkeys, they have been infected by intranasal installation of t h e virus. It is not recovered from the olfactory lobes from fatal cases in man, and post-mortem studies rarely show involvement of olfactory centres. Virus is recovered, however, in the faeces of a considerable proportion of cases in man and experimental animals and is present in large quantities. To-day we tend to consider poliomyelitis as an alimentary infection forming its first habitat in the gut where it grows and from which it is excreted. Its further spread in the gut is a matter of some controversy. At one time it was thought that the virus travelled up or along nerve routes and in fact in experimental animals it does do so. This theory assumed that at no time did the virus invade the blood stream, a viewpoint supported by the fact that virus had not been recovered from the blood of patients suffering from clinical poliomyelitis nor from experimental animals. A few years ago Bodian postulated the theory that inability to recover the virus from blood was due to the fact that it had not been looked for at the right time. He recovered the virus from experimental animals in the pre-paralytic stage and it has been found in the blood stream of cynomolgus monkeys and chimpanzees four to six days after being fed the virus (land2). Furthermore 10 children suffering from minor illnesses later diagnosed as abortive cases of poliomyelitis, and one infant with no symptoms, were found to have type 1 virus circulating in their blood streams 8 It is now more or less accepted that viraemia occurs in the pre-paralytic stage of poliomyelitis. This brings us to the theory which is now supported by sound practical research that the virus is ingested, that it proliferates in the intestines, that it spreads from there to
* Address to the Metropolitan Branch, Society of M.O.H.
87
the blood, where it causes a viraemia and that in certain cases it enters the central nervous system at points where penetration is less difficult. One of these points is the area postrema in the medulla oblongata. When dealing with host factors I will enlarge on these points and indicate some influences which may render the central nervous system or parts of it more penetrable by the virus. Possible There which I (1) (2) (3)
Methods of Prevention are three methods in the prevention of poliomyelitis would like to consider. T h e y are : - T h e production of passive immunity. T h e achievement of active immunity. Host factors.
Passive Immunity Individuals who have had poliomyelitis develop antibody in their blood. This antibody is specific to the type of virus to which they have been exposed or by which they have been infected. It is possible, however, that when the host develops antibody to one type of virus the immunity to other types is also raised. These antibodies are said to be long lasting. Specific agglutinins are also formed but their presence in the blood is of shorter duration. Gear of South Africa has stated rather picturesquely that " an individual's past experience of infections is clearly inprinted in his blood and by appropriate tests it can be revealed." 4 Melnick of the University of Yale delivered papers in Rome and Buffalo in which he stated that by examination of the blood of a representative proportion of a community it was possible to assess the extent to which that community had been exposed to or suffered from poliomyelitis and the particular types of virus involved. If agglutinins (short lived) and antibodies (long lived) were present infection or exposure was recent. If only antibodies (long lived) were present then infection or exposure was some years back. Not only could he indicate the history qua specific infection of the community but he could predict the future if further exposure took place 5 These points are important because if poliomyelitis is associated with a viiaemia and the production of protective antibodies then it should be possible by giving blood containing antibodies, or some extract thereof such as gammaglobulin, to provide immunity to infection if sufficient be given at the right time and under the right circumstances. Experimentally Bodian passively immunised groups of cynoI.nolgus monkeys with human gammaglobulin and immediately fed them with poliomyelitis virus. E q u a l numbers served as controls. In 104 monkeys receiving gammaglobulin no paralysis occurred. In 97 control animals 27 became paralysed. 6 Attempts have been~made to prevent poliomyelitis in human communities by giving gammaglobulin. In, 1952 54,772 children were inoculated, of whom half received gammaglobulin and the other half were given gelatin. T h e clinical investigators were not aware which substance txad been inoculated into individual children until after the study had been completed. A total of 104 cases of paralytic poliomyelitis occurred during the follow u p period of 14 weeks. From the second to the fifth week the investigators stated that there was significant though not a complete degree of protection. Paralysis appeared in seven children who had received gammaglobulin as compared with 39 who had been inoculated with gelatin. After the eighth week no protection was found to exist. T h e y admitted that the injection of gelatin was associated with an increase of paralysis in the limb of injection. In 1953, 235,000 children were inoculated. T h e members of the National Advisory Committee appointed for the evaluation of gammaglobulin were of the opinion that their analysis of the data did not yield statistically measurable results. From analysis of information on the efficacy of gammaglobulin given to family contacts, the committee decided that admiinstered by this method, with the pro-
88
portions involved and in the dosages used, it had n o apparent effect o n t h e incidence or severity of paralysis developing in subsequent cases, v I had t h e advantage o f hearing various speakers on the subject o f g a m m a globulin in R o m e and quite candidly I was unable to persude myself that at t h e present m o m e n t there is m u c h to be said for the use of g a m m a globulin to protect communities from paralytic poliomyelitis. It has been suggested in England that it might be useful given to contacts, nurses, medical students, babies exposed to infection soon after birth, and children in hospital wards in which a case of poliomyelitis develops. Even if it does produce increased antibody titre the effect lasts for a maxim u m period of eight weeks and probably not m o r e than five. T h e r e was some controversy originally as to w h e t h e r g a m m a globulin prepared in E n g l a n d would, contain antibodies to all three types of poliomyelitis virus in that fewer individuals have been exposed to infection in England than in the U n i t e d States of America. An assurance was given, however, that the g a m m a globulin had been tested and contained antibodies to all three types of virus. I do not think the prevention of paralytic poliomyelitis rests in passive immunity. It is expensiVe, uncertain, unreliable, and at the best the i m m u n i t y it gives is shortlived. T h e r e may be, however, exceptional and particular circumstances. G a m m a globulin was given to Q u e e n Elizabeth and the D u k e of E d i n b u r g h when t h e y visited Australia, their exposure to possible infection being controlled and of limited duration.
Active Immunity Active i m m u n i t y has b e e n attempted by the production of : - (1) A live vaccine (2) A dead vaccine. You will be aware that a live vaccine against yellow fever has been produced and at one t i m e most research workers were attempting to repeat this satisfactory result in relation to poliomyelitis. I n a paper which Jonas Salk read in R o m e he stated that his group worked on an attenuated type of living virus vaccine until it was shown that in h u m a n beings a non-infectious or dead virus preparation could stimulate a serological response similar to, and even greater than that which follows natural infection. As a result further work on the live virus vaccine was postponed and his group concentrated on a vaccine killed w i t h formalin. S u c h a vaccine m u s t fulfil the following criteria. 9 (1) T h e virus must be completely killed ; (2) T h e vaccine must have no deleterious effects and (3) It m u s t produce i m m u n i t y to the three known types of poliomyelitis viruS. It is not easy to be sure that in all batches of vaccine produced on a commercial scale the virus will be dead, and in fact in trials of a vaccine some years ago in America some 12 children did develop poliomyelitis after injection, paralysis affecting chiefly the limb of injection or the contralateral limb. I think it was agreed that the virus in this trial had not been killed. T h e difficulty lies in exposing the living virus to a sufficient concentration of disinfectant, in this case of formalin, to kill it, yet nevertheless to preserve its antigenic properties. T h e virus is g r o w n on monkey kidney tissue and again one has to be sure that there will be no nephrotoxic reaction. T h e vaccine m u s t contain strains of each of the three known poliomyelitis types of virus and each of these types must produce antigenic response. T h e vaccine, having been prepared, was given small scalo trials. It was found that the antibody titre in the blood to all three types of virus was increased, after three injections at suitable intervals, to a height which exceeded that obtained in natural infection. M a y I say immediately that the path of Salk and his team has been by no means easy. T h e r e were those who said ttiat the vaccine was dangerous in that there was no definite p r o o f that the virus had been killed or would be so in sub-
PUBLIC HEALTH,
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sequent batches. T h e r e were others w h o argued that there m i g h t be nephrotoxic reactions, and a further school that have said that there is no certain knowledge that the imm u n i t y produced will either be lasting or adequate to prevent an attack of clinical paralytic poliomyelitis. Let me see how m u c h of this I c a n answer. I have listened to all three schools who have raised ob~ jections to the formalised vaccine and whilst I can appreciate their arguments I think the answer m u s t be this. T h e Salk or formalised vaccine has now been given to over 600,000 individuals and to date no untoward effect has been noted. I admit that this is no guarantee of the future, but I am satisfied that insofar as it is possible to say of any vaccine that it is safe, that statement as to safety can be m a d e of this vaccine. I do not think anyone denies that it produces antibody response of a high level. I want. however, to be clear on this point. T h e Salk team have not stated that the formalised vaccine will prevent clinical poliomyelitis. On the occasions w h e n I have heard h i m speak, Salk himself has made no such claim. H e has stated that his vaccine is safe, that adequate precautions were taken to secure that it should be so and remain so and that it produces a high antibody response. T h e question as to w h e t h e r it will prevent poliomyelitis is now being assessed by Dr. T h o m a s Francis, Jr., Prof. of Epidemiology at A n n Arbor, Michigan, and a team of expert observers, and I hope that between M a r c h and J u n e of 1955 we shall be informed of the results of the experiments that took place in 1954. T h e r e has been some criticism tha~ there have been no published results on chimpanzees or monkeys which have been vaccinated w i t h the formalised vaccine and then challenged w i t h a virulent strain of poliomyelitis. T h i s is true, but in an interview w i t h Salk he did s h o w m e the results of experiments in which he challenged inoculated monkeys with intravenous injections of living virus. Eight out of 10 of those vaccinated survived. T h e two who died developed little a n t i b o d y . O f the controls six out of 10 died. 1~ I think it is unfortunate that these results, which are only a sm"att portion of Salk's work on this vaccine, have not been published. It is understandable that no observer can publish everything. Like m a n y others Salk has a large collection of data awaiting the time w h e n he will haye sufficient leisure to edit and publish. I think all research workers will understand and appreciate this particular difficulty. Let m e give you s o m e examples of the test that has been carried out in A m e r i c a during 1954. T h e figures I am presenting are round numbers and only approximately correct. 210,000 children were given the Salk vaccine and are being compared with a similar number who have been given an injection of solution identical with the vaccine except for the presence of virus and monkey kidney tissue (solution 199 used for the cultivation of virus). Another 400,000 children in grade 2 in schools throughout America have been given the vaccine and are being compared with 400,000 in grade 1 and 400,000 in grade 3. You will see that some 650,000 children have been inoculated and are being compared with 1,200,000 controls, some of whom have been given a placebo vaccine. The trial, therefore, embraces 1,800,000 children. The figures include children who did not complete the trial. Every one of these children has now got to be followed up. I am told that no less than 150,000 persons will have assisted in the total vaccine programme. These include clinicians, epidemiologists, health officers, physical therapists, virologists, school teachers and administrators. 14,000 schools co-operated and a staff of 100 operators are engaged on a 24 hour basis---clerks, coding experts and statisticians. Grants in excess of 850,000 dollars (approximately s have been made to the University of Michigan. This is part of the total of 7,500,000 dollars (over 2~ million pounds) granted by the National Foundation for Infantile Paralysis of America for the vaccine programme. T h e results will be placed before a C o m m i t t e e u n d e r the chairmanship of Dr. Francis and I have no hesitation in stating that whatever information is received through Dr. Francis' c o m m i t t e e will be based on the soundest and most unbiased principles.
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T h i ~ p r o b l e m of following u p 1,800,000 c h i l d r e n is a n e n o r m o u s one. I t will b e necessary to find out w h e t h e r or n o t a n y o f t h e s e c h i l d r e n d e v e l o p e d poliomyelitis d u r i n g 1954, w h e t h e r t h e attack was paralytic or non-paralytic a n d w h a t muscles were involved. I n a d d i t i o n cases diagnosed as suffering f r o m clinical poliomyelitis in t h e a p p r o p r i a t e g r o u p s of p r o t e c t e d o r coiatrol c h i l d r e n will h a v e t h e diagnosis c o n f i r m e d b y b l o o d a n d stool examination. A n t i b o d y titres of c h i l d r e n before a n d a f t e r inoculation have also b e e n carried out. I t h i n k t h a t whilst we m u s t possess ourselves i n patience I m a y q u o t e o n e or two remarks. Salk stated in a lecture in Rome 11. " T h a t there is still much to be learnt is clear indeed. Nevertheless it ~oes appear that by suitable manipulation of the dose of vaccine and of the intervals between inoculations, it should be possible with relatively few injections, properly spaced, to provide long term immunity. T h e ultimate object is not merely a reduction in the amount of crippling and death from poliomyelitis but also the elimination of these as a cause of fear. It will be clear, therefore, that the problem will not have been fully solved until a means is available that will with certainty and for life make this possible." D r . T h o m a s Rivers x2 in a v e r y excellent p a p e r m a d e t h e following s t a t e m e n t : - " A group of experts under the guidance of Dr. Francis has been established to evaluate the protective effects of the formalised vaccine. The final report will not be available for some months. However, there are reasons to believe that the vaccine will be effective. If it proves to be ineffective most workers will contend that a good one can be obtained soon." T h i s I t h i n k s u m m a r i s e s t h e situ~ation as w e k n o w it at present. I a m h o p e f u l of t h e o u t c o m e of t h e p r e s e n t trials, a l t h o u g h I d o n o t t h i n k t h e y witl b e 100% effective. I know, however, t h a t t h e vaccine is b e i n g i m p r o v e d at t h e p r e s e n t m o m e n t a n d t h a t it c a n n o t b e long before t h e e n d of t h e road is i n sight. Trials with a Living Vaccine
W o r k is energetically p r o c e e d i n g w i t h live vaccines. O n e t e a m of r e s e a r c h workers u n d e r Mil~zer x3 is experim e n t i n g o n a t r i v a l e n t vaccine inactivated b y ultra-violet light. M o s t interesting work, however, o n live vaccines is b e i n g carried o u t b y S a b i n ~t C i n c i n n a t i ? 4 H e has f o u n d t h a t b y passing v i r u l e n t strains of virus t h r o u g h m o n k e y k i d n e y tissue i n r a p i d succession, a vaccine c a n be p r e p a r e d w h i c h has antigenic p r o p e r t y b u t w h i c h will n o t cause paralysis w h e n injected directly into t h e b r a i n of c y n o m o l g u s m o n k e y s . T h e vaccine h e was u s i n g had b e e n m a d e u p b y r a p i d k i d n e y tissue inoculations; 33 t i m e s w i t h t y p e 1 virus, 51 t i m e s w i t h t y p e 2, a n d 34 t i m e s w i t h t y p e 3. A more painstaking and persistent worker than Sabin I h a v e n e v e r m e t . I t h i n k his a i m is to p r o d u c e a vaccine w h i c h will be effective w h e n given b y m o u t h , a n d I have t h e greatest faith t h a t S a b i n a n d his t e a m will u l t i m a t e l y achieve t h e success w h i c h t h e y u n d o u b t e d l y m e r i t . Host Factors U n d e r this h e a d i n g I w o u l d like to c o n s i d e r w h y it is t h a t w h e n I00 p e o p l e b e c o m e i n f e c t e d w i t h t h e v i r u s of poliomyelitis p e r h a p s 9 0 % r e m a i n symptomless, 9 % s h o w signs of disease v a r y i n g f r o m a sore t h r o a t a n d intestinal u p s e t to stiffness of t h e neck, w h i l s t 1% s h o w definite paralysis. W h y is it t h a t 9 9 % escape paralysis or alternatively w h y is it t h a t 1 ~o b e c o m e paralysed W e are apt to forget t h a t poliomyelitis is possibly t h e least serious of all infectious diseases w i t h t h e exception of t h a t o n e c o m p l i c a t i o n or e x t e n s i o n of t h e disease w h i c h destroys m o t o r cells in t h e b r a i n or cord a n d causes paralysis. A p a r t f r o m this it appears to b e a mild infection lasting a few days, t h e s y m p t o m s of w h i c h are possibly less serious t h a n a cold in t h e head, a n d f r o m w h i c h recovery is c o m p l e t e
89 a n d iiximunity lasting. I f we could b e s u r e t h a t a n i n d i v i d u a l c o n t r a c t i n g poliomyelitis w o u l d n o t b e c o m e paralysed t h e n t h e r e m i g h t b e m u c h to b e said for s p r e a d i n g t h e disease in o r d e r t h a t a c o m m u n i t y s h o u l d o b t a i n n a t u r a l i m m u n i t y . It is only its capability of causing paralysis t h a t m a k e s t h e virus of poliomyelitis a serious p a t h o g e n i c o r g a n i s m . T h e r e are certain h o s t factors w h i c h are generally accepted : - (1) Paralytic poliomyelitis is known to follow operations for the removal of tonsils and adenoids and then to be of the bulbar variety. (2)
Pregnant women are susceptible to poliomyelitis and may contract it in severe form.
(3)
It is associated with undue exertion, fatigue and chill.
(4)
It may follow body insults such as injection, fracture and operative procedures, when paralysis will show localisation referred to the area of insult. (15,16).
I w a n t to carry these observations a little b i t f u r t h e r . G a y l o r d A n d e r s o n , Prof. of P u b l i c H e a l t h in M i n n e s o t a , has w r i t t e n two p a p e r s in w h i c h he shows t h a t : - (a) Persons with the bulbar type of poliomyelitis give a history of removal of tonsils and adenoids more frequently than do persons with other forms of poliomyelitis. (b) " If a tonsillectomised person develops clinically recognisable poliomyelitis, the likelihood of bulbar involvements is four times as great as in one where the tonsils are in situ. (c)
This higher proportion of bulbar cases in tonsillectomised persons occurs at all ages and regardless of the time that has elapsed since the operation.
(d)
T h e higher proportion of bulbar cases in older persons is due primarily to absence of tonsils rather than to age per se.
H e r e is a s t a t e m e n t to t h e effect t h a t b o d i l y i n j u r y has a localising effect o n paralysis w h e n an i n d i v i d u a l is attacked b y poliomyelitis irrespective of h o w long a t i m e it is since t h a t i n j u r y was suffered. A t h e o r y is p r o p o u n d e d t h a t w h e n t h e host is s u b j e c t e d to a local injury, s u c h as tonsillectomy, a p e r m a n e n t c h a n g e takes place in t h e n e r v e cells e n e r v a t i n g t h a t area, w h i c h has r e n d e r e d t h e m , or t h e i r s u r r o u n d i n g b l o o d vessels, m o r e p e r m e a b l e to t h e virus of poliomyelitis, or less able to resist its cell d e s t r o y i n g "(cytopathogenic) p r o p e r t i e s . G a y l o r d A n d e r s o n has followed this a step f u r t h e r in c o n n e c t i o n w i t h p e r s o n s w h o c o n t r a c t e d paralytic poliomyelitis a n d have h a d t h e i r a p p e n d i x r e m o v e d at s o m e p r e v i o u s date. H e expected t h a t t h e right leg w o u l d b e i n v o l v e d m o r e often t h a n t h e left. H e failed, however, to find t h a t this was
s o . 17
M y o w n experience in p e r s o n s c o n t r a c t i n g poliomyelitis i n t h e t h r e e weeks following a p p e n d i c e c t o m y is t h a t t h e a b d o m i n a l muscles a n d d i a p h r a g m are usually i n v o l v e d a n d t h e r e m a y b e a paralytic ileus. I h a v e no data o n t h e long t e r m effect of a p p e n d i c e c t o m y in localising poliomyelitis. Bodian i n Baltimore has carried o u t s o m e very i n t e r e s t i n g work in c o n n e c t i o n w i t h poliomyelitis following injection, is His e x p e r i m e n t s h a v e b e e n d o n e o n c y n o m o l g u s m o n k e y s a n d h e has i n j e c t e d v i r u s directly into t h e h e a r t ( M a h o n y strains of type 1). Paralysis occurs i n 5 0 % of m o n k e y s so t r e a t e d a n d i n at least 2 0 % t h e initial paralysis is i n t h e face. If, however, t h e s e m o n k e y s have b e e n injected w i t h various i r r i t a n t s u b s t a n c e s i n c l u d i n g gelatin, cortisone, penicillin a n d d i p h t h e r i a - p e r t u s s i s - t e t a n u s vaccine w i t h i n one to t h r e e weeks p r i o r to t h e giving of t h e virus, he finds t h a t n o t o n l y is t h e r e a n u n d u e p r o p o r t i o n of cases wh~re paralysis affects t h e l i m b of i n j e c t i o n (the h i n d l i m b ) b u t t h a t instead of 5 0 % of t h e m o n k e y s d e v e l o p i n g poliomyelitis t h e figure is n o w raised to 8 0 % . N o t only has the risk of d e v e l o p i n g paralysis in t h e l i m b of i n j e c t i o n b e e n increased, b u t t h e risk of t h e h o s t d e v e l o p i n g paralytic poliomyelitis has been increased.
9o P e r s o n a l l y I have always believed t h a t a n injection o f d i p h t h e r i a - p e r m s s i s vaccine n o t only localises t h e paralysis of p e r s o n s infected w i t h virus b u t also increases the attack rate, t h o u g h I m u s t a d m i t I have n o figures to prove this for t h e y are n o t easily obtainable. B o d i a n ' s e x p e r i m e n t s w i t h c y n o m o l g u s m o n k e y s lends s u p p o r t to this view. I t h i n k B o d i a n c o n s i d e r e d t h a t w h e n a p e r s o n suffers a n i n j u r y s u c h as a n injection, t h e b l o o d vessels or t h e a n t e r i o r h o r n cells s u p p ! y i n g the i n j u r e d part b e c o m e m o r e p e n e t r a b l e to virus. I n this c o n n e c t i o n I w o u l d like to m e n t i o n o n e p o i n t t h a t ties u p w i t h G a y l o r d A n d e r s o n ' s work o n t h e f a r - r e a c h i n g effects of tonsillectomy. I n t h e course of his work i n injecting m o n k e y s intracardially w i t h virus, B o d i a n writes : - - " O f considerable i n t e r e s t i n this c o n n e c t i o n is t h e fact t h a t t h r e e i n s t a n c e s of t h e p r o v o k i n g effect of l o n g - s t a n d i n g t r a u m a a p p a r e n t l y have o c c u r r e d i n o u r c y n o m o l g u s m o n k e y s w h i c h were inoculated intravascularly. O n e a n i m a l w i t h a n old healed tibial f r a c t u r e a n d o n e w i t h a n old h e a l e d accidental a m p u t a t i o n at t h e ankle, were initially paralysed in t h e c o r r e s p o n d i n g leg.. A t h i r d a n i m a l w h o was received w i t h a n old right eye injury, i n c l u d i n g corneal opacity, was paralysed initially in the r i g h t facial muscles, b o t h u p p e r a n d lower." I t h i n k we shall have to pay v e r y considerable a t t e n t i o n to t h e f a r - r e a c h i n g paralytic effects o f bodily insult o n t h e host exposed to t h e virus of poliomyelitis. T h e last r e s e a r c h studies to w h i c h I w o u l d like to d r a w a t t e n t i o n are associated w i t h p y r i d o x i n a n d cortisone.
Pyridoxin P y r i d o x i n or "Vitamin B6 occurs in yeast, liver, rice a n d b r a n a n d c a n be p r e p a r e d synthetically. I t is a n importan~ factor i n n u t r i t i o n a n d deficiency m a y give rise to a s y m p t o m c o m p l e x in w h i c h m u s c u l a r weakness a n d rigidity are p r o m i n e n t . A deficiency of V i t a m i n B6 decreases h u m a n reaction to i n f e c t i o n a n d lowers, antigenic response in t h e host. B o d i a n reports : - - 19 (1) T h a t paralytic poliomyelitis occurred in an uninoculated laboratory rhesus monkey that was being deprived of pyridoxin. Poliomyelitis in uninoculated rhesus monkeys (with one doubtful exception) had previously not been known to occur. (2) T h e virus isolated from this monkey was shown to be of the Brunhilde type, that is type 1, and was in use in the laboratory at the time of infection and probably present in the environment of the animal quarters. (3) In that this appeared to be the first known natural or laboratory spread of poliomyelitis in rhesus monkeys an attempt was made to see if the deficiency of pyridoxin was the causal factor. Eleven rhesus monkeys were treated with desoxy-pyridoxine. This has the same effect as depriving them of pyridoxin. T h e monkeys were then fed orally with Brunhilde virus. Two succumbed to paralytic poliomyelitis although this species of monkey is known ordinarily to be insusceptible to poliomyelitis as a result of oral feeding. H e r e is a possible example of a n association b e t w e e n a v i t a m i n deficiency a n d e n h a n c e d liability to c o n t r a c t poliomyelitis a n d you m a y care to c o n s i d e r this in relation to t h e fact t h a t c o m m u n i t i e s living i n civilised a n d hygienic c o n d i t i o n s t e n d to sophisticate t h e i r food a n d are m o r e p r o n e to poliomyelitis t h a n t h o s e living in u n h y g i e n i c s u r r o u n d i n g s . I m u s t a d m i t t h a t I have n o evidence t h a t sophistication of food results in a deficiency of pyridoxin. I n a n interview, m o r e o v e r , t h a t I h a d recently w i t h B o d i a n h e felt t h a t his findings o n m o n k e y s d e p r i v e d of p y r i d o x i n m i g h t easily b e d u e to t h e fact t h a t t h e 11 ~,nonkeys were receiving n u m e r o u s injections daily of d e s o x y - p y r i d o x i n a n d t h a t t h e s e i n j e c t i o n s - i n t h e m s e l v e s m i g h t have r e n d e r e d t h e m o n k e y s m o r e p r o n e to develop poliomyelitis. I a m n o t entirely c o n v i n c e d o n this p o i n t a n d I h o p e t h a t f u r t h e r work will b e carried out o n t h e effect of p y r i d o x i n a n d susceptibility to poliomyelitis. Cor tison e Lastly I w o u l d refer to some excellent work t h a t has b e e n carried o u t b y S h w a r t z m a n in t h e M o u n t Sinai Hospital in N e w York. S~
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March,
z955
Previous e x p e r i m e n t s h a d s u g g e s t e d a relationship b e t w e e n e n d o c r i n e i m b a l a n c e a n d p r e d i s p o s i t i o n to poliomyelitis. C u r l e y a n d Ayaock i n 1946 ~1 h a d r e p o r t e d t h a t c a s t r a t i o n in m o n k e y s i n d u c e d a g r e a t e r susceptibility to t h e intranasal i n o c u l a t i o n of t h e v i r u s whilst t r e a t m e n t of t h e castrates w i t h o e s t r o g e n increased t h e i r resistance. I n 1939 H o r a c e H o d e s h a d d e m o n s t r a t e d : - - ~ (1) T h a t virgin and pregnant Swiss mice were equally susceptable to intracerebral inoculation of St. Louis encephalitis virus. (2) T h a t following subcutaneous vaccination with the St. Louis virus the great majority of virgin Swiss mice became immune. (3) T h a t the majority of pregnant mice though vaccinated "did not become so immune. (4) That pregnancy not only interferes with the development of acquired immunity but also diminishes a previous established immunity. It is generally accepted t h a t p r e g n a n t w o m e n have decreased resistance to i n f e c t i o n w i t h poliomyelitis a n d V e n n i n g in 1946 s h o w e d that t h e r e is a greatly e n h a n c e d adreno-cortical f u n c t i o n d u r i n g p r e g n a n c y w i t h h y p e r p r o d u c t i o n of cortisone. S h w a r t z m a n set out to see if t h e r e was a relationship b e t w e e n cortisone a n d liability to c o n t r a c t poliomyelitis, or, to p u t it r o u n d t h e o t h e r way, if cortisone lowered resistance to infection w i t h poliomyelitis virus. H e chose a n a n i m a l w h i c h is generally refractory to poliomyelitis, namely, t h e S y r i a n golden h a m s t e r . I f t h e s e b e inoculated intracerebrally w i t h t h e L a n s i n g t y p e of poliomyelitis virus, a b o u t 25% die. I f t h e y b e injected w i t h cortisone t h e m o r t a l i t y rate can b e raised to n e a r l y 8 0 % . I n t r a p e r i t o n e a l injection of massive doses of L a n s i n g strain of poliomyelitis fails to cause disease in n o r m a l golden Syrian h a m s t e r s . I f t h e y b e g i v e n injections of c o r t i s o n e a n d t h e n a n i n t r a peritoneal ~inoculation of virus a severe disease is elicited. S h w a r t z m a n ' s w o r k is e x t r e m e l y i m p o r t a n t w h e n we consider host factors i n relation to resistance to poliomyelitis infection. W e already k n o w of t h e .effects of pregnancy, chill, operation, fatigue a n d local i n j u r y or insult s u c h as injection. T h e s e are conditions of stress in w h i c h t h e r e m a y b e h y p e r p r o d u c t i o n of cortisone. T h i s m u s t b e t a k e n into a c c o u n t w h e n we c o n s i d e r t h e p r e v e n t i o n o f poliomyelitis. So far g a m m a g l o b u l i n has n o t p r o v e d a practical m e a n s of p r e v e n t i n g poliomyelitis in a c o m m u n i t y . M a y this n o t be due to t h e fact t h a t it was given in insufficient q u a n t i t y or t h a t " sufficiency " of a n t i b o d y is variable, d e p e n d i n g o n t h e c o n d i t i o n of t h e host at t h e p a r t i c u l a r t i m e t h e g a m m a globulin is given ? Is it n o t possible t h a t a vaccine m a y p r o d u c e a n t i b o d i e s w h i c h t h o u g h a d e q u a t e to secure p r o t e c t i o n at one t i m e m a y b e i n a d e q u a t e at a n o t h e r ? I f g a m m a g l o b u l i n a n d vaccines, e i t h e r killed o r active, fail to control poliomyelitis we m a y yet h a v e to t u r n to t h e h o s t facto r a n d find out w h y i t is t hat the re are t i m e s w h e n indi~:iduats, w h i l s t n o r m a l l y r e s i s t a n t to t h e i n v a s i o n of t h e virus, fail in t h e b a t t l e against t h i s disease. Is this possibly d u e to " stress," e n d o c r i n e imbalance, or dietary deficiency ? I a m m u c h i n d e b t e d to o u r A m e r i c a n colleagues for t h e i r k i n d n e s s a n d c o u r t e s y a n d grateful for all t h e help I kave received. I stood a m a z e d at t h e c o n c e n t r a t i o n a n d energy w i t h w h i c h t h e y are c o n d u c t i n g r e s e a r c h o n t h e o t h e r side of t h e Atlantic a n d I c a n n o t b e o t h e r t h a n optimistic t h a t t h e t i m e is n o t too f a r d i s t a n t w h e n poliomyelitis will b e a preventabl 9 disease. REFERENCES
1 SAnIN, D. 0952.) Amer. J. Hyg., 55, 414. HO~TMAN.W, D. M. (1952.) Proc. Soc. Exper. Biol. ~ 79, 417. ~ , & McCuLLUM, R. W. (1953.) Proc. Soc. Biol. ~ Med., 82. GnAa, J, H.. S. : International Poliomyelitis Conference, 195~:i'!:-~ :~:%: MEL.WICg, J . L. Annual Congress American Public Association, 1954. 6 BODIAN, D. (1952.) Amer. ft. Hyg., $6, No. 1, 78-9.
Med., Exper. Rome, Health
PUBLIC
HEAL'IH,
March,
1955
7J.A.M.A. (1954.) x54, 1086. s Ministry of Health, Poliomyelitis, Medical Memorandum, July, 1954. 9 SALK, JONAS. International Poliomyelitis Conference, Rome, 1954. a0 , Personal communication 1954. n . International Poliomyelitis Conference, Rome, 1954. ~z RIvzas, THOMAS. International Poliomyelitis Conference, Rome, 1954. ~a MILZXR, A., et al. (1954.) Amer. J. Publ. Hlth., 44, 26. x4 SAraN, A. B. International Poliomyelitis Conference, Rome. ~5 GEFFEN, D . H . (1950.) Med. Off. 83, 137. as McCLOSKY, B. P. (1950). Lancet i, 659. 9 (19.52). Ibid. i, 1187. 17ANDERSON, GAYLORD W. (1954.) Bull. Umv. Minnesota, 26.2.54. ~8 BODEAN, D. (1954.) Amer. J. Hyg. Awaiting Publication. ~9 . (1948.) Amer. J. [-fvg., 48, 87-93. ~" SWHARTZMAY,GREGORY. Columbia University Press, 1953. ea CURLEY, F. J. & AYCOCK, W. L. (1946). Endocrinology, 39, 414. ..z HOPES, H . L . (1939). J. Exper. Med., 69, 533-543. 23 VENNING, E . H . (1946.) Endocrinology, 39, 203.
LOCAL POPULATION ESTIMATES FOR x954 The Registrar-General has issued his estimates of the populations of counties, boroughs and urban and rural districts in England and Wales as at June 30th, 1954". Grouped figures are given for the standard regions, conurbations and density aggregrates and by sex and age for the country as a whole. This publication is designed to meet a general demand for an early issue of up-to-date figures of local populations, and in particular to assist local councils and other administrative authorities, manufacturers, and distributors. The figures are the final estimates which will later be embodied in the Registrar-General's Statistical Review for the year 1954. lit has already been announced that the home population of England and Wales at June 30th, 1954, is estimated to have been 44,274,000 of whom 21,288,000 were males and 22,986,000 females and that the total shows an increase of 184,000 over the figure for mid-1953. Comparison with the estimates for previous years indicate certain trends in the internal movement of the population9 The population of the Administrative County of London continued to decline, dropping from 3,343,000 in 1953 to 3,322,000 in 1954. This decline is reflected to a certain extent in the increase in the populations of those areas which contain I,.C.C. Housing Estates : Borough of Romford by 1,752, Rural District of Elstree by 1,820 and Borough of Reigate by 2,720. The slight decline in the population of the Administrative County of Middlesex, which began in 1953, continued in 1954, the figure being 2,256,000 compared with a peak of 2,270,000 in 1952. Within the Administrative County of Essex (the population of which increased from 1,644,100 in 1953 to 1,672,500 in 1954) the Urban District of Billericay, containing the New Town of Basildon, increased by 2,590, and the Rural District of Epping, containing Harlow New Town, by 6,330. Similarly within the Administrative County of Hertfordshire (population 651,500 in 1953 and 671,700 in 1954), the Borough of Hemel Hempstead and the Urban Districts of Stevenage and Welwyn Garden City, each of which contains a New Town, increased by 3,460, 2,790 and 1,420 respectively, while, in the Administrative County of Sussex West, the Rural District of Horsham, containing the New Town of Crawley, increased by 4,740. *The Registrar-General's Estimates of the Population of England and Wales--PopuIations of each Administrative Area at June 30th, 1954, H.M. Stationery Office, price 9d. net (or by post from P.O. Box 569, London, S.E.I., price 10~.d.)
Sir Alexander Macgregor, formerly M.P.H., Glasgow, and a Past-President of the Society, on March 3 i s t gives up the chairmanship of the Scottish Western Regional Hospital Board, which be has held since its establishment in 1948. The Secre~arv of State has expressed gratitude for Sir Alexander's ':sure touch and general acceptance" during his period of office.
,4 Correetion.--in the report of the M. & C.W. Groups (Publi,: Health, February, I955, page 82) the word 'dead,' seven lines from foot of left hand column, should have read 'deaf.'
91
Society of Medical Officers of Health ORDINARY MEETING, NOVEMBER An Ordinary Meeting of the Society was held in the Council Chamber of the British Medical Association, Tavistock House, Tavistock Square, W.C.1, on Friday, November 26th, 1954. 1. Minutes of Last Meeting.--The minutes of the Ordinary Meeting, held on September 16th, 1954, were confirmed and signed by the President. 2. Life Membership.~The following were elected fully-paid I.ife Members of the Society on the nomination of the Council and of their Branches : Dr. J. F. Macdonald, Lt.-Col. E. F. W. Mackenzie and Dr. J. B. Lowe. 3. Elections.--The following candidates, having been proposed and seconded, were duly taken into membership : - Fellows.--Drs. Islay Cecil Barnem, Alexander David Christian Stewart Cameron, David Miller Cathie, Catherine H. Coutts Milne, Raymond Joseph Donaldson, Thomas Christie Falconer, Kate Gray, Edmund Monk Hamilton, Herbert James, J. A. Linden, Thomas Aloysius McVey, Charles Nicholson Minto, Stuart Love Morrison, Basil John Lloyd Moss, Anne Boyd Perkins, Lewis Bernard Peters, Irene Tomina Joan Ruxton, Elizabeth Schonberger, Hope B. Scott, William Sharpe, John Anthony Slattery, Henry Ellis Smith, Donald Shrewsbury ToddWhite, Robert Webster, B. N. Williams, Arthur Leslie Thrower, Alfred Yarrow and Sydney Maxwell Young. Assoeiates.--Drs. William Robert Samuel Robertson, and Ernest Ward.
Temporary
Members
attending
D.P.H.
Courses.--Drs.
A.
Bukhari and A. F. Mowafi. Nominations for the next electionwere reported and the meeting terminated. A N N U A L GENERAL MEETING The Annual General Meeting of the Society for the Session 1953-54 was held in the Committee Room of the Society, Tavistock House, London, W.C.1, on Friday, January 14th, 1955, at 12.45 p.m. The President, Dr. Jean M. Mackintosh, was in the Chair and there were also present 12 members of the Society. 1. Minutes of Last Annual General Meeting.--The Minutes of the Annual General Mee, ting, held on December 10th, 1953, were confirmed and signed by the President. 2. Annual Reports and Accounts.--The Annual Report of the Council, the Treasurer, and of the Editor of PUBLIC HEALTH, were received and adopted, together with the Balance Sheet as at September 30th, 1954, and the Income and Expenditure Account for the year ended September 30th, 1954. 3. Appointment of Auditors.--Messrs. Greene, Clements & Co., Chartered Accountants, of 20, Bloomsbury Square, London, W.C.1, were re-appointed the Auditors of the Society. 4. Life Membership.--The following members were elected to fully-paid Life Members of the Society, on the nomination of the Council and their Branches : - Drs. Muriel H. Radford, H. W. Barnes, H. S. Banks, Mary Kidd, H. L. Cronk, C. M. Richardson, H. G. Trayer, E. H. Walker, C. E. E. Herington and A. F. Adamson. 5. Elections.--The following candidates, having been duly proposed and seconded were elected to Membership of the Society : - Fellows.--Drs. June Patricia Cooper, Isobel Beatrice Craighead, Margaret Rosemary Farrell, Marie P. S. Grant, Arthur John Isbell Kelynack, Donald Gordon Noble, Douglas Stuart Parken, Thomas Alun PhilJips, George Lee Ritchie, Francis Simm, James Taylor and Eric Dudley Birch Wolfe. Temporary Fellows, attending D 9 Courses.--Drs. Edwin lnman Blenkinsop, Maureen Henderson, Joyce Heather Hindmarsh, John McCormack and Helen Herbison Reid. Nominations for the next election were reported and the Meeting terminated at 1 p.m.
President:
EAST A N G L I A N B R A N C H Dr. Kathleen M. Harding (Dist. M.P.H.,
E.
Suffolk).
Hon. Secretary : Dr. G. R. Holtby (Dist. M . P . H . , Norfolk).
A meeting of the Branch was held at The Scole Inn, Scole, on Saturday, September 18th, 1954, at 3 p.m. The retiring President, (Dr. K. F. Alford) was in the chair and 20 members were present.