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Diphtheria immunisation
PUBLIC HEALTH.
1935.
411
Diphtheria Immunisation. By D. J.
Medical Officer of Health, Acton. The submission of this paper at a meeting of the Home Counties Branch aroused great interest and led to a keen discussion in which a large number of members took part. Dr. Thomas raises and considers a number of points important and interesting at the present juncture, and his opening contribuiio« to the discussion will be found iniormative and worthy of study. THOMAS, l\LR.C.S., LoR.C.P., D.P.H.,
of those who have attended discusM OST sions on the subject have been convinced of the utility of immunisation, but until a district is visited by an epidemic of virulent diphtheria, immunisation is not practical politics.
As long as the type of diphtheria is mild and responds to the use of antitoxin, it is not easy to reason with or to convince the public of the risk which they unnecessarily run. The danger is too remote. The presence of virulent diphtheria in certain towns in Yorkshire and other northern and midland counties does not make the slightest appeal to those living some hundreds of miles away. Even an outbreak of a virulent type of diphtheria in the nearest district but one to us did not arouse any feelings of apprehension. It is such an easy matter to say that the time to irnmunise is during an inter-epidemic
period, but very few districts have a public which can be reasoned into such a course in the absence of a virulent type of the disease in their midst. A small percentage of the residents may, of course, wish to protect their children against diphtheria, but this small number is not going to affect the course of the disease if the bacillus gravis is introduced amongst a community whose immunity is low. Between 1922 and 1932 our district had been comparatively free of diphtheria. The type which prevailed amongst us was mild, and the fatality low. In the autumn of 1932 the conditions changed, and we had an outbreak of the most virulent type of diphtheria. In the last week of September we had five cases, three of which proved 'fatal. This was the beginning of our troubles. The swabs from some of these cases were " typed " by Dr. O'Brien of the Wellcorne Research Laboratories, and most of them were of the
gravis type. The conditions were particularly favourable for the introduction of the gravis bacillus as far as the bacillus was concerned, and particularly unfavourable as far as the community was concerned. \Ve had had ten years 'of minimum prevalence, during which the district had been comparatively free of diphtheria, and therefore the herd immunity was probably very low. Between September, 1932 and June, 1933 (both inclusive) we had 229 notifications and 40 deaths. The situation regarding immunisation was completely changed. Whereas formerly the public were not ripe for immunisation, now they demanded protection. Whatever views we may have held concerning immunisation, we should have , had an uncomfortable time if . we had limited our activities to segregation of patients and the detection of carriers and other sources of infection. , From an administrative as well as the treatment point of view. the former methods are not entirely successful in the grave forms of the disease. The early administration of serum, the swabbing of contacts, and the separations of carriers, controlled the spread of the disease and averted a fatal issue. Antitoxin given within 48 hours of the onset of symptoms would result in neutralising the toxin. nut the graver form is an intensely rapid disease and antitoxin given as early as 24 hours after the onset of symptoms is frequently of no avail. Experiments have been carried out in which large amounts of toxin or culture of gravis and mitis strains have been injected into guinea-pigs, and ordinary antitoxin given at intervals of two hours after injection saved all animals j after eight hours it saved none. In the intervening periods there was no significant difference between the percentage saved in the gravis and the mitis group of animals.
412
PUBLIC HEALTH.
In spite of this, many if not most clinicians now admit that recentl y there has been admitted to hospital a large number of severe cases which formerly were few and far between. In these severe cases antitoxin does not have the same beneficial effect even when it is administered early. We have seen cases in which the disease has progressed so rapidly that death has occurred within 24 hours and even twelve hours of the time the doctor was called in . The return of malignant diphtheria has presented us with many problems, and evidently ls teaching us the necessity of a revision of our views with regard to the nature of diphtheria and diphtheria immunity. Judging from the recent articles which have appeared, the scientific bases of diphtheria immunity have again become uncertain, after we had attained what was supposed to be something -definite. This phase of the subject is mentioned because it is just as well that we should be cautious in our estimates. The Sellick test, we are told, is not an absolutely reliable measure of immunity. \Ve knew that Schick-negative children may occasionally fall itt, but the Schick test is the most usual method of distinguishing between immunity and susceptibility, and we cannot escape using the Schick test for want of a better. It is impossible in the case of mass immunisation to estimate the antitoxin present in the blood, and even if we could, we should not know the exact amount which would be necessary to avoid an attack. Dr. Parish in a recent paper has shown that the figure often quoted for the Schick level, viz., 1(30 unit per c.cm , is greatly over-estimated. Some individuals with 1/250 or even 1/500 unit per c.cm. are stated to have' g-iven a Schick-negative reaction, whilst some children who showed an antitoxin content of one or more antitoxin units per c.cm, have been said to develop diphtheria. These views may be disturbing, and may possibly deter some from embarking on a scheme of immunisation. Certain figures from actual practice may therefore be helpful. We commenced on our scheme in October, 1932, and up to December, 1934, we had done a , preliminary Schick test on 2,469, and a posterior Schick .on 2,063. Of the preliminary Schicks, 1,075 were negative, and we had given the following inoculations : -
SEPTEMBF..H,
lsI d(lu. 2nd dose . 3rd dose. 4,052 3,840 3,631 It will be noticed that our immunisations outnumber our Schick tests, and the reason \5 that after our experience in the first infants' department Schick tested, we decided not to do a preliminary Schick test in children under seven years of age. \Ve do a post-Schick test on all those imrnunised. This method is a matt er of controversv, and the procedure depends partly upon tile amount of assistance on which one can rely, but there are other considerations which favour our procedure. A Schi ck test is a more terrifying and difficult incident to the small child than the administration of a dose of the immunising agent. The argument of a saving of expense is not a convincing one. The objection that carries most weight is that local reactions are more likelv to occur in Schick-negative pati ents . \Ve have had sufficient local reaction s in patients who have been subsequently found Schick-negative to warrant the assumption that a Schick-negative case is more liable to give an unfavourable reaction than a Schick-positive. When we have had a local reaction after the first and second dose, we S chick-t est hefore giving another dose, and invariahlv that child is found to be Sckicknegative : It is, of course, well known that patients who previously have had diphtheria are very liable to give reactions both constitutional and local. and it has been assumed that this was due to protein sensitiveness, because antitoxin had previously been given. This is a matter for the bacteriologists and is beyond our purview, but certain clinical facts would seem to show that the liability to local reactions is not due to protein sensitiveness per se. We have inoculated over 300 children in the scarlet fever wards, and in most instances they had been given scarlet fever antitoxin on admission. The first dose of immunising material was given at varying intervals after the antitoxin; sometimes as early as two days and as late as 14 days. \Ve endeavoured to give the three doses before the patients were discharged from the hospitals. In only three instances was there any local reaction following the inoculation. There was no temperature or any other sign of constitutional disturbance; only a slight redness of toe arm. In one instance a small local abscess developed. _ A.t tfie start we confined ourselves almost
1935.
PUBLIC HEALTH.
entirely to the use of T.A.M. As far as immediate results were concerned, it could be said to be successful. Out of 2,063 children post-Schicked , 2,050 were negative and only 13 positive. There may be some scepticism at such a high percentage of Schick-negatives, but after our first experience of post-Schicking, we decided to check this wit~ ~ome preliminary Schick-testing so as to eliminate any error. We find that our percentage of positives in the preliminary Schicks with the same toxin corresponds fairly closely with the usual figures given for different ages. We have no figures for relapsing or reverting negatives. Our experience has been too recent, and we have not the staff to carry out repeated Schick testing. It is important to ascertain the duration of the Schicknegative state. In a recent paper 5 per cent. of children Schick-negative after immunisation and 1 per cent. of those naturally Schicknegative had reverted to Schlck-positive one to seven years later. More recently, considerable variation in relapse rates has been found, e.g ; 0, 4'G and 14 per cent. within a year of immunisation, amongst children in different communities, in spite of the fact that a much greater number of L.f. units of formol toxoid, or its equivalent, had been used for immunisation than formerly, Our figures of diphtheria in inoculated children are given in a subsequent page, and these tend to show that the longer the period which has elapsed, the better the figures. Probably the relapse r,ates depend upon t1~e facilities which the children have to remain immune by contracting sub-doses of infection in the community, but we have no evidence so far that the immunity which has been conferred has relapsed. In the beginning, we confined ourselves almost entirely to T.A.M. For most of the adults we used T.A.F., and occasionally, if the arm had shown a slight redness after the first dose of T .A.M., we gave a second and third dose of T.1\.F . Although T .A.M. appeared to be quite successful as shown by our high percentage of Schick-negatives, we have recently used formol toxoid for the pre-school children. We are gradually trying, to push up the age for the use of formol toxoid, so as ultimately to use it in the pre-school child and in the infants' departments. The change over from T .A.M. to formol
413
toxoid in younger children is made not because of any practical advantage which we have noticed, but as a result of the advocacy of such a procedure on the part of those who are concerned with the experimental part of the work. \Ve usually allow an interval of three weeks between the first and second inoculation , and four weeks between the second and third inoculation. In the Medical Research Council Report (Special Report Series, No. 195) it is suggested that it might be better to "g ive the second and third inoculations of the customary prophylactic course five and ten weeks after the first inoculation, instead of the more usual two and four weeks. The report adds thougfi, that the matter is largely one of expediency, because intervals longer than a fortnight are said to increase administrative difficulties, Therefore, unless ver y material benefit accrues, long intervals are to be avoided. Five and ten week intervals would undoubtedly increase the administrative difficulties in schools. We try and do all the infants' departments every term, and it is advisable to do the three inoculations in the same term; it would be difficult to attain this if the third dose were given ten weeks after the first. We have been fortunate in the way of freedom from unfavourable reactions. As far as we can gather there were only three cases reported who had had any constitutionat reactions. Fortunately, I was able to examine two of them personally, and in both cases it was simply an anxiety on the part of the child which had caused a little vomiting on the night after his first inoculation. A message came one morning to see a boy, who was stated to have been sick in the nigfit, following inoculation. On arrival at the house the boy was sitting up in 'bed enjoying a meal of sausages and mashed potatoes. There was not a sign of any local reaction even at tile site of the inoculation; " It was a case of a nervous boy and an over-anxious mother. The excitement of the inoculation had caused the slight vomiting. He received a second and third inoculation and there were no unfavourable symptoms. The second case was somewhat similar and the boy was away from school for one day. He also received the full dose . The third case was attended by a private doctor. The boy was stated to have
414
PUBLIC HEALTH.
been sick and to have had a temperature for some days. He was a boy of twelve, and the parents refused to let him have the second inoculation. We have had local reactions, but these exhibited no symptoms of any serious import. The usual reaction was a slight redness around the site of inoculation. J n a few instances the redness extended as far as the elbow, but we have had no hard brawny swelling, and th e inflammatory COndition had subsided in almost every instance within 48 hours. There was not a single instance in which the swelling had not disappeared at the end of the fourth day. In the case of one boy there was a very small local abscess. It occurred in one of our hospital cases. There had been no redness after the inoculation, but in about a week a small superficial abscess developed. Some apprehension has been felt among general practitioners regarding the effect of immunisation on the subsequent administration of serum in the irnrnunised subject. Anaphylaxis is a condition which seems to have some hypnotic influence on some persons, but in our experience previous immunisation does not appear to have any effect when serum has to be subsequently administered. This does not mean that irnmunised patients do not suffer from some kind of serum sickness, but the percentage of serum sickness is not higher amongst the immunised than it is among the non-imrnunised, Recently, serum rashes after scarlet fever antitoxin have been frequent and general. In the summer of 1934, from one batch of antitoxin, almost every patient had a late serum rash; they were so bad that we tried the serum of a firm other than that from which we usually obtained our supplies, but with no better result. If these had occurred amongst previously immunised persons we should naturally have suspected immunisation as the cause. But they were almost all of them amongst nonirnmunised persons, and the worst rashes occurred in adults. "W e do not always report these unfortunate results to the makers, and in this we are not quite fair, for they naturally complain that clinicians do not give them the assistance and help "wh ich are their due. This fact is mentioned because of the frequency of late serum rash in the last 18 months. The cause is ~ot the " increase ~f i~munisation, but probably some inherent factor connected with the serum.
SEPTEMBER,
, It is, a .platitude to say that before any immumsanon scheme is a permanent success, you must succeed in immunising a large percentage of the pre-school children and of the children in the infants' departments. That is the ideal which is sought to be attained hy everyone, hut it is not easy to maintain the herd immunity of the ),oung-er ch ild ren . We immuniscd a hig-her percentage of child ren under seven years in 19:14 than we did in 19:32 and 19:1:1, as the following- figures show:19:J2 and 193:} Under r) 7-15 5-7 1,678 406 619 1934 377 203 The relative number under five who were immunised was much higher than in the first vear , This is due to the fact that we have Ieft the junior and senior departments alone and have concentrated upon the infants' departments and the welfare centres. In spite of this, the herd immunity of some of the infants' departments was lowered, as the following figures will show:32S
Percentage immunised in the Infants Departments at the end of December, 1933 and 1934, respectively. Decernber, December,
A.'V.
B.P.
n
JJ
J,P.
I' R
S
1933,
1934.
24':1 64'; :n' 6 7./j ':} 63'1 43'1 35'5
44'6 52'9 24'9 r,t '4
58'8
52'3
58'0
50"0 33'8
We circularise the infants' departments at the beginning of every term, but the kind o~ response we receive does not entirely depend upon the head mistress. Almost alt the head mistresses of our infants' departments are very helpful to us, but even their help does not always conduce towards the desired end. A more potent factor is the occurrence of a bad type of diphtheria in a child whose parents had refused to have the child inoculated. But the very success of any scheme militates against its continued and further success, paradoxical though this may seem . Amongst a small class of the popUlation, figures which show the comparative freedom of the .d istrict from diphtheria fOllowing a certain procedure may appeal to thelll, but the
1935.
PUBLIC HEALTH.
bulk of the population are apathetic. In the absence of diphtheria in the neighbourhood it is a difficult matter to keep up the herd immunity. The immunity which will occur from sub-clinical doses is not existent and the herd immunity is lowered, and as there are no cases in the school or neighbourhood, the element of risk and immediate danger is absent. It therefore becomes a d ifficult matter to persuade the parents to have th eir children artificially immunised. We have not adopted any particular form of propaganda but have tried to make use of any and every opportunity as it arises. We circularised the parents of the pre-school children and of those in the infants' departments. Practically all the opposition we encountered comes from the fathers, and especially those who served in the army during the war. Human nature abhors compulsion, and compulsory inoculation has left as its legacy the present opposition. The mothers are almost all in favour of immunisation , but frequentl y tell us that the father objects. The children themselves seem to enjoy the experience because there is practically no pain. It is had policy to economise on syringe needles. During 1934 there were 86 notifi cations and seven deaths in Acton. I n the first half of 1935 there have heen :n notifications and three deaths j 24 notifications -in the first quarter and seven in the second. The records of the incidence of diphtheria in Acton since 1890 show that there have been irregular periods of maximum and minimum prevalence of the disease. The last period of maximum prevalence was in 1920-22-and this followed a period of comparatively low incidence of only four years-but continued for three years. The outbreak of 1932 followed a very long period of minimum prevalence (nine years), and it was reasonable to assume that the period of maximum prevalence would be a prolonged one. Judging by our notifications it appears that the period of maximum prevalence has been considerably shortened. It has been suggested that artificial immunisation will raise the number of virulent carriers in the population. I t is reasonable to assume that any factors which will raise the herd immunity will increase the carriers, because the immunity is a toxin immunity and not a germ immunity. It is. a common experience that whenever diphtheria makes its appearance in
415
a school the number of carriers increase after a very short time. This, of course, is due to two probable factors at least, namely, infecThe second tion and raised immunity. phenomenon would be operative in the case of artificial immunity, but there is no ground for the suggestion that artificial immunisation will he th e means of abnormally increasing the numbers of carriers. We recently swabbed the two schools in which there were the highest and lowest percentage of inoculated children and, curious ly the school with the higher number had a smaller percentage of children carrying morphological K.L.B. A virulence test was not made. The percentage in both schools was lower than that usually found in London elementary schools. Although we may have our individual opinion upon the effect upon the community, we are on safer grounds when we consider the individual. As far as our figures are concerned, there is no doubt whatever as to the effect upon him. With regard to those post-Schicked after immunisation, we had onl y one case in 1933, and four cases in 1934, with no deaths. One had extensive membrane on both tonsils, but no signs of toxzemla. The others were mild cases. Of the cases who had been found to be naturally Schick-negative, we had five cases in 1933, and none in 1934. There were · no deaths. \Vith one exception they were mild cases. In none of the naturally Schicknegatives, or in the unirnmunised Sclilcknegatives, was there any complication, such as paralysis or cardiac complications. At the end of six months after the last dose, three doses are for all practical purposes a protection, though not an absolute protection, against an attack. Those who appreciate the value of artificial immunisation are by no means eager to press it unduly, and do not desire to exaggerate the results which can be obtained. Certain questions remain obscure at present. The Schick-test is not an absolute criterion of immunity or susceptibility to an attack. It is possible that a Schick-negative who is immune to the milder form of diphtheria may suffer from the graver form, but the attack is usually a mild one. This has been our experience. All the cases which occurred in inoculated children in 1934 were mild, and in the latter half of the year no immunised child contracted the disease even in a mild form.
1935.
411
Diphtheria Immunisation. By D. J.
Medical Officer of Health, Acton. The submission of this paper at a meeting of the Home Counties Branch aroused great interest and led to a keen discussion in which a large number of members took part. Dr. Thomas raises and considers a number of points important and interesting at the present juncture, and his opening contribuiio« to the discussion will be found iniormative and worthy of study. THOMAS, l\LR.C.S., LoR.C.P., D.P.H.,
of those who have attended discusM OST sions on the subject have been convinced of the utility of immunisation, but until a district is visited by an epidemic of virulent diphtheria, immunisation is not practical politics.
As long as the type of diphtheria is mild and responds to the use of antitoxin, it is not easy to reason with or to convince the public of the risk which they unnecessarily run. The danger is too remote. The presence of virulent diphtheria in certain towns in Yorkshire and other northern and midland counties does not make the slightest appeal to those living some hundreds of miles away. Even an outbreak of a virulent type of diphtheria in the nearest district but one to us did not arouse any feelings of apprehension. It is such an easy matter to say that the time to irnmunise is during an inter-epidemic
period, but very few districts have a public which can be reasoned into such a course in the absence of a virulent type of the disease in their midst. A small percentage of the residents may, of course, wish to protect their children against diphtheria, but this small number is not going to affect the course of the disease if the bacillus gravis is introduced amongst a community whose immunity is low. Between 1922 and 1932 our district had been comparatively free of diphtheria. The type which prevailed amongst us was mild, and the fatality low. In the autumn of 1932 the conditions changed, and we had an outbreak of the most virulent type of diphtheria. In the last week of September we had five cases, three of which proved 'fatal. This was the beginning of our troubles. The swabs from some of these cases were " typed " by Dr. O'Brien of the Wellcorne Research Laboratories, and most of them were of the
gravis type. The conditions were particularly favourable for the introduction of the gravis bacillus as far as the bacillus was concerned, and particularly unfavourable as far as the community was concerned. \Ve had had ten years 'of minimum prevalence, during which the district had been comparatively free of diphtheria, and therefore the herd immunity was probably very low. Between September, 1932 and June, 1933 (both inclusive) we had 229 notifications and 40 deaths. The situation regarding immunisation was completely changed. Whereas formerly the public were not ripe for immunisation, now they demanded protection. Whatever views we may have held concerning immunisation, we should have , had an uncomfortable time if . we had limited our activities to segregation of patients and the detection of carriers and other sources of infection. , From an administrative as well as the treatment point of view. the former methods are not entirely successful in the grave forms of the disease. The early administration of serum, the swabbing of contacts, and the separations of carriers, controlled the spread of the disease and averted a fatal issue. Antitoxin given within 48 hours of the onset of symptoms would result in neutralising the toxin. nut the graver form is an intensely rapid disease and antitoxin given as early as 24 hours after the onset of symptoms is frequently of no avail. Experiments have been carried out in which large amounts of toxin or culture of gravis and mitis strains have been injected into guinea-pigs, and ordinary antitoxin given at intervals of two hours after injection saved all animals j after eight hours it saved none. In the intervening periods there was no significant difference between the percentage saved in the gravis and the mitis group of animals.
412
PUBLIC HEALTH.
In spite of this, many if not most clinicians now admit that recentl y there has been admitted to hospital a large number of severe cases which formerly were few and far between. In these severe cases antitoxin does not have the same beneficial effect even when it is administered early. We have seen cases in which the disease has progressed so rapidly that death has occurred within 24 hours and even twelve hours of the time the doctor was called in . The return of malignant diphtheria has presented us with many problems, and evidently ls teaching us the necessity of a revision of our views with regard to the nature of diphtheria and diphtheria immunity. Judging from the recent articles which have appeared, the scientific bases of diphtheria immunity have again become uncertain, after we had attained what was supposed to be something -definite. This phase of the subject is mentioned because it is just as well that we should be cautious in our estimates. The Sellick test, we are told, is not an absolutely reliable measure of immunity. \Ve knew that Schick-negative children may occasionally fall itt, but the Schick test is the most usual method of distinguishing between immunity and susceptibility, and we cannot escape using the Schick test for want of a better. It is impossible in the case of mass immunisation to estimate the antitoxin present in the blood, and even if we could, we should not know the exact amount which would be necessary to avoid an attack. Dr. Parish in a recent paper has shown that the figure often quoted for the Schick level, viz., 1(30 unit per c.cm , is greatly over-estimated. Some individuals with 1/250 or even 1/500 unit per c.cm. are stated to have' g-iven a Schick-negative reaction, whilst some children who showed an antitoxin content of one or more antitoxin units per c.cm, have been said to develop diphtheria. These views may be disturbing, and may possibly deter some from embarking on a scheme of immunisation. Certain figures from actual practice may therefore be helpful. We commenced on our scheme in October, 1932, and up to December, 1934, we had done a , preliminary Schick test on 2,469, and a posterior Schick .on 2,063. Of the preliminary Schicks, 1,075 were negative, and we had given the following inoculations : -
SEPTEMBF..H,
lsI d(lu. 2nd dose . 3rd dose. 4,052 3,840 3,631 It will be noticed that our immunisations outnumber our Schick tests, and the reason \5 that after our experience in the first infants' department Schick tested, we decided not to do a preliminary Schick test in children under seven years of age. \Ve do a post-Schick test on all those imrnunised. This method is a matt er of controversv, and the procedure depends partly upon tile amount of assistance on which one can rely, but there are other considerations which favour our procedure. A Schi ck test is a more terrifying and difficult incident to the small child than the administration of a dose of the immunising agent. The argument of a saving of expense is not a convincing one. The objection that carries most weight is that local reactions are more likelv to occur in Schick-negative pati ents . \Ve have had sufficient local reaction s in patients who have been subsequently found Schick-negative to warrant the assumption that a Schick-negative case is more liable to give an unfavourable reaction than a Schick-positive. When we have had a local reaction after the first and second dose, we S chick-t est hefore giving another dose, and invariahlv that child is found to be Sckicknegative : It is, of course, well known that patients who previously have had diphtheria are very liable to give reactions both constitutional and local. and it has been assumed that this was due to protein sensitiveness, because antitoxin had previously been given. This is a matter for the bacteriologists and is beyond our purview, but certain clinical facts would seem to show that the liability to local reactions is not due to protein sensitiveness per se. We have inoculated over 300 children in the scarlet fever wards, and in most instances they had been given scarlet fever antitoxin on admission. The first dose of immunising material was given at varying intervals after the antitoxin; sometimes as early as two days and as late as 14 days. \Ve endeavoured to give the three doses before the patients were discharged from the hospitals. In only three instances was there any local reaction following the inoculation. There was no temperature or any other sign of constitutional disturbance; only a slight redness of toe arm. In one instance a small local abscess developed. _ A.t tfie start we confined ourselves almost
1935.
PUBLIC HEALTH.
entirely to the use of T.A.M. As far as immediate results were concerned, it could be said to be successful. Out of 2,063 children post-Schicked , 2,050 were negative and only 13 positive. There may be some scepticism at such a high percentage of Schick-negatives, but after our first experience of post-Schicking, we decided to check this wit~ ~ome preliminary Schick-testing so as to eliminate any error. We find that our percentage of positives in the preliminary Schicks with the same toxin corresponds fairly closely with the usual figures given for different ages. We have no figures for relapsing or reverting negatives. Our experience has been too recent, and we have not the staff to carry out repeated Schick testing. It is important to ascertain the duration of the Schicknegative state. In a recent paper 5 per cent. of children Schick-negative after immunisation and 1 per cent. of those naturally Schicknegative had reverted to Schlck-positive one to seven years later. More recently, considerable variation in relapse rates has been found, e.g ; 0, 4'G and 14 per cent. within a year of immunisation, amongst children in different communities, in spite of the fact that a much greater number of L.f. units of formol toxoid, or its equivalent, had been used for immunisation than formerly, Our figures of diphtheria in inoculated children are given in a subsequent page, and these tend to show that the longer the period which has elapsed, the better the figures. Probably the relapse r,ates depend upon t1~e facilities which the children have to remain immune by contracting sub-doses of infection in the community, but we have no evidence so far that the immunity which has been conferred has relapsed. In the beginning, we confined ourselves almost entirely to T.A.M. For most of the adults we used T.A.F., and occasionally, if the arm had shown a slight redness after the first dose of T .A.M., we gave a second and third dose of T.1\.F . Although T .A.M. appeared to be quite successful as shown by our high percentage of Schick-negatives, we have recently used formol toxoid for the pre-school children. We are gradually trying, to push up the age for the use of formol toxoid, so as ultimately to use it in the pre-school child and in the infants' departments. The change over from T .A.M. to formol
413
toxoid in younger children is made not because of any practical advantage which we have noticed, but as a result of the advocacy of such a procedure on the part of those who are concerned with the experimental part of the work. \Ve usually allow an interval of three weeks between the first and second inoculation , and four weeks between the second and third inoculation. In the Medical Research Council Report (Special Report Series, No. 195) it is suggested that it might be better to "g ive the second and third inoculations of the customary prophylactic course five and ten weeks after the first inoculation, instead of the more usual two and four weeks. The report adds thougfi, that the matter is largely one of expediency, because intervals longer than a fortnight are said to increase administrative difficulties, Therefore, unless ver y material benefit accrues, long intervals are to be avoided. Five and ten week intervals would undoubtedly increase the administrative difficulties in schools. We try and do all the infants' departments every term, and it is advisable to do the three inoculations in the same term; it would be difficult to attain this if the third dose were given ten weeks after the first. We have been fortunate in the way of freedom from unfavourable reactions. As far as we can gather there were only three cases reported who had had any constitutionat reactions. Fortunately, I was able to examine two of them personally, and in both cases it was simply an anxiety on the part of the child which had caused a little vomiting on the night after his first inoculation. A message came one morning to see a boy, who was stated to have been sick in the nigfit, following inoculation. On arrival at the house the boy was sitting up in 'bed enjoying a meal of sausages and mashed potatoes. There was not a sign of any local reaction even at tile site of the inoculation; " It was a case of a nervous boy and an over-anxious mother. The excitement of the inoculation had caused the slight vomiting. He received a second and third inoculation and there were no unfavourable symptoms. The second case was somewhat similar and the boy was away from school for one day. He also received the full dose . The third case was attended by a private doctor. The boy was stated to have
414
PUBLIC HEALTH.
been sick and to have had a temperature for some days. He was a boy of twelve, and the parents refused to let him have the second inoculation. We have had local reactions, but these exhibited no symptoms of any serious import. The usual reaction was a slight redness around the site of inoculation. J n a few instances the redness extended as far as the elbow, but we have had no hard brawny swelling, and th e inflammatory COndition had subsided in almost every instance within 48 hours. There was not a single instance in which the swelling had not disappeared at the end of the fourth day. In the case of one boy there was a very small local abscess. It occurred in one of our hospital cases. There had been no redness after the inoculation, but in about a week a small superficial abscess developed. Some apprehension has been felt among general practitioners regarding the effect of immunisation on the subsequent administration of serum in the irnrnunised subject. Anaphylaxis is a condition which seems to have some hypnotic influence on some persons, but in our experience previous immunisation does not appear to have any effect when serum has to be subsequently administered. This does not mean that irnmunised patients do not suffer from some kind of serum sickness, but the percentage of serum sickness is not higher amongst the immunised than it is among the non-imrnunised, Recently, serum rashes after scarlet fever antitoxin have been frequent and general. In the summer of 1934, from one batch of antitoxin, almost every patient had a late serum rash; they were so bad that we tried the serum of a firm other than that from which we usually obtained our supplies, but with no better result. If these had occurred amongst previously immunised persons we should naturally have suspected immunisation as the cause. But they were almost all of them amongst nonirnmunised persons, and the worst rashes occurred in adults. "W e do not always report these unfortunate results to the makers, and in this we are not quite fair, for they naturally complain that clinicians do not give them the assistance and help "wh ich are their due. This fact is mentioned because of the frequency of late serum rash in the last 18 months. The cause is ~ot the " increase ~f i~munisation, but probably some inherent factor connected with the serum.
SEPTEMBER,
, It is, a .platitude to say that before any immumsanon scheme is a permanent success, you must succeed in immunising a large percentage of the pre-school children and of the children in the infants' departments. That is the ideal which is sought to be attained hy everyone, hut it is not easy to maintain the herd immunity of the ),oung-er ch ild ren . We immuniscd a hig-her percentage of child ren under seven years in 19:14 than we did in 19:32 and 19:1:1, as the following- figures show:19:J2 and 193:} Under r) 7-15 5-7 1,678 406 619 1934 377 203 The relative number under five who were immunised was much higher than in the first vear , This is due to the fact that we have Ieft the junior and senior departments alone and have concentrated upon the infants' departments and the welfare centres. In spite of this, the herd immunity of some of the infants' departments was lowered, as the following figures will show:32S
Percentage immunised in the Infants Departments at the end of December, 1933 and 1934, respectively. Decernber, December,
A.'V.
B.P.
n
JJ
J,P.
I' R
S
1933,
1934.
24':1 64'; :n' 6 7./j ':} 63'1 43'1 35'5
44'6 52'9 24'9 r,t '4
58'8
52'3
58'0
50"0 33'8
We circularise the infants' departments at the beginning of every term, but the kind o~ response we receive does not entirely depend upon the head mistress. Almost alt the head mistresses of our infants' departments are very helpful to us, but even their help does not always conduce towards the desired end. A more potent factor is the occurrence of a bad type of diphtheria in a child whose parents had refused to have the child inoculated. But the very success of any scheme militates against its continued and further success, paradoxical though this may seem . Amongst a small class of the popUlation, figures which show the comparative freedom of the .d istrict from diphtheria fOllowing a certain procedure may appeal to thelll, but the
1935.
PUBLIC HEALTH.
bulk of the population are apathetic. In the absence of diphtheria in the neighbourhood it is a difficult matter to keep up the herd immunity. The immunity which will occur from sub-clinical doses is not existent and the herd immunity is lowered, and as there are no cases in the school or neighbourhood, the element of risk and immediate danger is absent. It therefore becomes a d ifficult matter to persuade the parents to have th eir children artificially immunised. We have not adopted any particular form of propaganda but have tried to make use of any and every opportunity as it arises. We circularised the parents of the pre-school children and of those in the infants' departments. Practically all the opposition we encountered comes from the fathers, and especially those who served in the army during the war. Human nature abhors compulsion, and compulsory inoculation has left as its legacy the present opposition. The mothers are almost all in favour of immunisation , but frequentl y tell us that the father objects. The children themselves seem to enjoy the experience because there is practically no pain. It is had policy to economise on syringe needles. During 1934 there were 86 notifi cations and seven deaths in Acton. I n the first half of 1935 there have heen :n notifications and three deaths j 24 notifications -in the first quarter and seven in the second. The records of the incidence of diphtheria in Acton since 1890 show that there have been irregular periods of maximum and minimum prevalence of the disease. The last period of maximum prevalence was in 1920-22-and this followed a period of comparatively low incidence of only four years-but continued for three years. The outbreak of 1932 followed a very long period of minimum prevalence (nine years), and it was reasonable to assume that the period of maximum prevalence would be a prolonged one. Judging by our notifications it appears that the period of maximum prevalence has been considerably shortened. It has been suggested that artificial immunisation will raise the number of virulent carriers in the population. I t is reasonable to assume that any factors which will raise the herd immunity will increase the carriers, because the immunity is a toxin immunity and not a germ immunity. It is. a common experience that whenever diphtheria makes its appearance in
415
a school the number of carriers increase after a very short time. This, of course, is due to two probable factors at least, namely, infecThe second tion and raised immunity. phenomenon would be operative in the case of artificial immunity, but there is no ground for the suggestion that artificial immunisation will he th e means of abnormally increasing the numbers of carriers. We recently swabbed the two schools in which there were the highest and lowest percentage of inoculated children and, curious ly the school with the higher number had a smaller percentage of children carrying morphological K.L.B. A virulence test was not made. The percentage in both schools was lower than that usually found in London elementary schools. Although we may have our individual opinion upon the effect upon the community, we are on safer grounds when we consider the individual. As far as our figures are concerned, there is no doubt whatever as to the effect upon him. With regard to those post-Schicked after immunisation, we had onl y one case in 1933, and four cases in 1934, with no deaths. One had extensive membrane on both tonsils, but no signs of toxzemla. The others were mild cases. Of the cases who had been found to be naturally Schick-negative, we had five cases in 1933, and none in 1934. There were · no deaths. \Vith one exception they were mild cases. In none of the naturally Schicknegatives, or in the unirnmunised Sclilcknegatives, was there any complication, such as paralysis or cardiac complications. At the end of six months after the last dose, three doses are for all practical purposes a protection, though not an absolute protection, against an attack. Those who appreciate the value of artificial immunisation are by no means eager to press it unduly, and do not desire to exaggerate the results which can be obtained. Certain questions remain obscure at present. The Schick-test is not an absolute criterion of immunity or susceptibility to an attack. It is possible that a Schick-negative who is immune to the milder form of diphtheria may suffer from the graver form, but the attack is usually a mild one. This has been our experience. All the cases which occurred in inoculated children in 1934 were mild, and in the latter half of the year no immunised child contracted the disease even in a mild form.