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Modern methods of diphtheria prevention
1937
PUBLIC
HEALTH
Modern Methods of Diphtheria Prevention* By W. A. MURPHY, M.B.,B.CH., B.A.O., D.P.H.
Medical Officer of Health, Ogmore and Garw, U.D. It is, I suppose, because of the failure of the isolation hospital to control to any extent the prevalence of infectious diseases that search has been made for some alternative methods. This has been exemplified more particularly in the case of diphtheria, since the discovery of the Schick test in 1921 has placed at our disposal a means to measure the success or failure of our efforts to produce at any rate individual immunity to this disease. How far these efforts have been successful in protecting the community has, in my opinion, yet to be decided. I commenced to practise artificial immunisation against diphtheria in January, 1928, and I have continued this work up to the present time, so that a short account of my experience may be of interest. At the outset I did not think that any useful purpose would be served by excessive propaganda : my district is a small one, and the individual members of the public health staff are known to the majority of the residents, so that I depended more or less on their personal efforts to make this new protective method known to the parents: at the same time I made every effort to interest the teaching profession in the process. It is thanks to the ready help which I have received from the sanitary inspectors, health visitors, and teachers that I have attained some measure of success. 4,282 cases have been dealt with: of these, 1,572 were pre-Schick tested: 776 were Schicknegative and 796 were Schick-positive : 763 of the positive reactors were immunised : the remaining 33 failed to complete the immunising course. In addition to these cases, 2,710 children, the majority of whom were under 7 years of age, were immunised without a primary Schick test.
Types of Antigen Used At first I made use of toxoid-antitoxin mixture in three injections, each of 1 c.c., at intervals of one week : with this antigen I obtained reasonably good results--83 per cent. were post-Schick negative after one course of injections, and a total of 88 per cent. were negative after a further injection had been given to the positive reactors. It will be noted that there is no question of 90 per cent. or 95 per cent. found to be immune with this antigen. *Presidential Address to the Welsh Branch, October 9th, 1936.
After some years experience with T.A.M., I considered it advisable to endeavour to make a trial of some other type of antigen for two reasons. In the first place, I had had experience of serum sickness occurring in immunised patients after the administration of antitoxin and I was of opinion that this was more severe than in the case of unimmunised patients : it is, of course, now well known that this tendency can be controlled almost entirely by the injection of 5 c.e. of a 10 per cent. solution of magnesium or sodium thiosulphate simultaneously with the serum and that any late reactions quickly clear up with oral administration of sodium thiosulphate crystals in a dose of 5 to 15 grains according to the age of the patient. I now use this solution as a routine measure in the course of serum administration. In the second place, I found that the repeated injections tended to frighten small children, and as I was particularly anxious to extend immunisation to children under five, I decided to make trial of an antigen that would produce immunity in one or two injections. At first, I tried formol-toxoid in two injections of 1 c.c., but the reactions which resulted were somewhat intense and the results on post-Schick testing gave no grounds for belief that this method could be regarded as reliable. On consideration, therefore, of the experience gained in the United States, I deciddd" to give a trial to alum-precipitated diphtheria toxoid. I have immunised 704 children with this antigen, of whom 518 were under 6 years of age. The preparation was first issued as a single dose of 1 c.c. and 133 children were immunised with this dosage ; later it was issued for use in a single dose of 0-5 c.c., and the remaining'571 children were immunised with this. There is, of course, much more tendency to local reaction with this antigen as compared with T.A.M. ; in practically every instance a small induration appears at the site of injection, which persists for about a fortnight and gradually disappears; in some instances the reaction is more intense, as is evidenced by a red areola surrounding the induration : in four cases in my series abscess formation occurred at the site of injection. There was no constitutional disturbance in any of the children. On the whole, the local reaction is negligible and there is much less tendenc~ to severe reaction with the concentrated antigen in a dose of 0"5 c.c. There remained, then, the question of whether the immunity conferred by the single injection 121
PUBLIC HEALTH was equal to that conferred by the three injections of T . A . M . Post-Schick tests were carried out in 325 children and of these 293 or 90 per cent. were found to be Schiek-negative. T h e s e results seem to me sufficiently satisfactory to justify the continued use of this antigen. I am aware that my results are at variance with those of other workers, but these are my findings. I am not in a position to offer any evidence as to the persistence of the immunity conferred by this method. Whatever method of immunisation is adopted, it is inevitable that some cases of d!phtheria will occur amongst those supposedly immune. I have had 23 cases in my series of 4,282, and it may be of interest briefly to set out the details of t h e s e : two cases occurred in pre-Schiek negative c h i l d r e n ; these were eases of simple diphtheritic tonsillitis and exhibited no toxaemic symptoms w h a t e v e r ; eight cases occurred in post-Schick negative reactors; one of these was f o u n d Schick-positive at the time of infection, the i m m u n i t y having waned some 7 years after i m m u n i s a t i o n ; six of the other eases had fairly severe local conditions but showed no evidence of toxaemia in the course of the disease ; one child had a severe attack of diphtheria with toxaemic complications (her unimmunised brother died of diphtheria); five cases occurred within a few months of immunisation ; one ease occurred within a week of receiving an injection of 0-5 c.c. alumtoxoid, and presumably was infected in the negative phase following the injection; one case occurred twelve months after receiving an injection of 0.5 c.c. alum-toxoid but before a post-Sehick test; the local condition here was severe but there were no toxaemic complications; six cases occurred in children who were Schick-positive after immunisation and were, therefore, not protected. It is essential to emphasise the necessity for post-Schick testing whatever antigen may be used for i m m u n i s a t i o n ; without routine post-Schick testing it is impossible to know for certain whether i m m u n i t y has or has not developed and the occurrence of cases of diphtheria in supposedly i m m u n e persons may tend to throw the practice into disrepute. In conclusion, I plead guilty to confining myself to details of m o d e r n methods of diphtheria prevention, but I have done this deliberately because I consider that in this case it is possible to check the results obtained, and on the success or failure of diphtheria immunisation to control this disease in the community will depend our line of attack on other infectious diseases in the future. Dr. J.Greenwood Wilson (Cardiff),proposing a vote of thanks, mentioned that 98.7 per cent. of the cases treated with T.A.F. antigen in Cardiff had been proved
1~
JANUARY to be immune amongst those who had been post-Schicktested and that a whooping cough vaccine was being used in a children's institution in the city with the object of preventing the spread of whooping cough. Dr. T. D. Llewellyn (Port Talbot), supporting, stated that he had used alum-precipitated toxoid in a large number of cases and in his experience the reactions were hardly worth calling such.
Smallpox and Scarlet Fever Outbreaks The Ministry of Health have recently issued the following announcements : Smallpox at Oldham.--Four cases of smallpox (variola major) occurred in early December at Oldham. The first case was that of an unvaccinated married woman who worked in the cardroom of a cotton mill in Chadderton. The other three cases are those of the woman's husband, who v~as vaccinated in 1916; her son, aged 15, who had never been vaccinated ; and an unvaccinated woman who had been in contact with the original case. All these patients have been removed to hospital. The diagnosis of smallpox in the first patient was not established sufficiently early to ensure the successful vaccination of contacts, of whom there were at least 98 in the woman's place of work and 12 at her home. The medical practitioners and public vaccinators in the districts concerned have all been notified of this outbreak, and arrangements have been made to keep all the known contacts under daily supervision until the period of danger has passed. The original case has not been traced to any human source of infection, and it appears not improbable that the infection was conveyed in the raw cotton which this patient handled. Cotton as a vehicle of infection of smallpox has frequently been suspected in the past, and in 1918 cases of this disease were reported in Oldham which were probably caused by infection from cotton. Scarlet Fever at Doncaster.--An outbreak of scarlet fever is reported from Doncaster, 152 eases having occurred up to date (December 21st) in the county borough and in the neighbouring rural district. All these patients had consumed raw milk from the same source, and it is reported that a milker on the farm in question has been found to be suffering from illness which is probably of scarlatinal origin. The local authorities have arranged for all milk from this source to be pasteurised before delivery, and a Medical Officer of the Ministry has visited Doncaster to give any necessary advice or assistance. It is probable that the majority of the primary eases have now been accounted for. Notices of Group Meetings.--The programmes for meetings of the Fever Hospital, Maternity and Child Welfare and Dental Officers Groups to be held this month appear on page 185. The following members of the Society have satisfied the examiners in the recent examination for the degree of Mastery of Midwifery conferred by the Society of Apothecaries of London :--D6sir6e Muriel Barbara Gross, M.D. (LEEDS), D.P.H. (LOND.) (Assistant M.O.H., Ilford) ; and Katherine Mary Hirst, M.B., B.S. (LOND.), D.P.H. (Assistant M.O.H., Birmingham).
PUBLIC
HEALTH
Modern Methods of Diphtheria Prevention* By W. A. MURPHY, M.B.,B.CH., B.A.O., D.P.H.
Medical Officer of Health, Ogmore and Garw, U.D. It is, I suppose, because of the failure of the isolation hospital to control to any extent the prevalence of infectious diseases that search has been made for some alternative methods. This has been exemplified more particularly in the case of diphtheria, since the discovery of the Schick test in 1921 has placed at our disposal a means to measure the success or failure of our efforts to produce at any rate individual immunity to this disease. How far these efforts have been successful in protecting the community has, in my opinion, yet to be decided. I commenced to practise artificial immunisation against diphtheria in January, 1928, and I have continued this work up to the present time, so that a short account of my experience may be of interest. At the outset I did not think that any useful purpose would be served by excessive propaganda : my district is a small one, and the individual members of the public health staff are known to the majority of the residents, so that I depended more or less on their personal efforts to make this new protective method known to the parents: at the same time I made every effort to interest the teaching profession in the process. It is thanks to the ready help which I have received from the sanitary inspectors, health visitors, and teachers that I have attained some measure of success. 4,282 cases have been dealt with: of these, 1,572 were pre-Schick tested: 776 were Schicknegative and 796 were Schick-positive : 763 of the positive reactors were immunised : the remaining 33 failed to complete the immunising course. In addition to these cases, 2,710 children, the majority of whom were under 7 years of age, were immunised without a primary Schick test.
Types of Antigen Used At first I made use of toxoid-antitoxin mixture in three injections, each of 1 c.c., at intervals of one week : with this antigen I obtained reasonably good results--83 per cent. were post-Schick negative after one course of injections, and a total of 88 per cent. were negative after a further injection had been given to the positive reactors. It will be noted that there is no question of 90 per cent. or 95 per cent. found to be immune with this antigen. *Presidential Address to the Welsh Branch, October 9th, 1936.
After some years experience with T.A.M., I considered it advisable to endeavour to make a trial of some other type of antigen for two reasons. In the first place, I had had experience of serum sickness occurring in immunised patients after the administration of antitoxin and I was of opinion that this was more severe than in the case of unimmunised patients : it is, of course, now well known that this tendency can be controlled almost entirely by the injection of 5 c.e. of a 10 per cent. solution of magnesium or sodium thiosulphate simultaneously with the serum and that any late reactions quickly clear up with oral administration of sodium thiosulphate crystals in a dose of 5 to 15 grains according to the age of the patient. I now use this solution as a routine measure in the course of serum administration. In the second place, I found that the repeated injections tended to frighten small children, and as I was particularly anxious to extend immunisation to children under five, I decided to make trial of an antigen that would produce immunity in one or two injections. At first, I tried formol-toxoid in two injections of 1 c.c., but the reactions which resulted were somewhat intense and the results on post-Schick testing gave no grounds for belief that this method could be regarded as reliable. On consideration, therefore, of the experience gained in the United States, I deciddd" to give a trial to alum-precipitated diphtheria toxoid. I have immunised 704 children with this antigen, of whom 518 were under 6 years of age. The preparation was first issued as a single dose of 1 c.c. and 133 children were immunised with this dosage ; later it was issued for use in a single dose of 0-5 c.c., and the remaining'571 children were immunised with this. There is, of course, much more tendency to local reaction with this antigen as compared with T.A.M. ; in practically every instance a small induration appears at the site of injection, which persists for about a fortnight and gradually disappears; in some instances the reaction is more intense, as is evidenced by a red areola surrounding the induration : in four cases in my series abscess formation occurred at the site of injection. There was no constitutional disturbance in any of the children. On the whole, the local reaction is negligible and there is much less tendenc~ to severe reaction with the concentrated antigen in a dose of 0"5 c.c. There remained, then, the question of whether the immunity conferred by the single injection 121
PUBLIC HEALTH was equal to that conferred by the three injections of T . A . M . Post-Schick tests were carried out in 325 children and of these 293 or 90 per cent. were found to be Schiek-negative. T h e s e results seem to me sufficiently satisfactory to justify the continued use of this antigen. I am aware that my results are at variance with those of other workers, but these are my findings. I am not in a position to offer any evidence as to the persistence of the immunity conferred by this method. Whatever method of immunisation is adopted, it is inevitable that some cases of d!phtheria will occur amongst those supposedly immune. I have had 23 cases in my series of 4,282, and it may be of interest briefly to set out the details of t h e s e : two cases occurred in pre-Schiek negative c h i l d r e n ; these were eases of simple diphtheritic tonsillitis and exhibited no toxaemic symptoms w h a t e v e r ; eight cases occurred in post-Schick negative reactors; one of these was f o u n d Schick-positive at the time of infection, the i m m u n i t y having waned some 7 years after i m m u n i s a t i o n ; six of the other eases had fairly severe local conditions but showed no evidence of toxaemia in the course of the disease ; one child had a severe attack of diphtheria with toxaemic complications (her unimmunised brother died of diphtheria); five cases occurred within a few months of immunisation ; one ease occurred within a week of receiving an injection of 0-5 c.c. alumtoxoid, and presumably was infected in the negative phase following the injection; one case occurred twelve months after receiving an injection of 0.5 c.c. alum-toxoid but before a post-Sehick test; the local condition here was severe but there were no toxaemic complications; six cases occurred in children who were Schick-positive after immunisation and were, therefore, not protected. It is essential to emphasise the necessity for post-Schick testing whatever antigen may be used for i m m u n i s a t i o n ; without routine post-Schick testing it is impossible to know for certain whether i m m u n i t y has or has not developed and the occurrence of cases of diphtheria in supposedly i m m u n e persons may tend to throw the practice into disrepute. In conclusion, I plead guilty to confining myself to details of m o d e r n methods of diphtheria prevention, but I have done this deliberately because I consider that in this case it is possible to check the results obtained, and on the success or failure of diphtheria immunisation to control this disease in the community will depend our line of attack on other infectious diseases in the future. Dr. J.Greenwood Wilson (Cardiff),proposing a vote of thanks, mentioned that 98.7 per cent. of the cases treated with T.A.F. antigen in Cardiff had been proved
1~
JANUARY to be immune amongst those who had been post-Schicktested and that a whooping cough vaccine was being used in a children's institution in the city with the object of preventing the spread of whooping cough. Dr. T. D. Llewellyn (Port Talbot), supporting, stated that he had used alum-precipitated toxoid in a large number of cases and in his experience the reactions were hardly worth calling such.
Smallpox and Scarlet Fever Outbreaks The Ministry of Health have recently issued the following announcements : Smallpox at Oldham.--Four cases of smallpox (variola major) occurred in early December at Oldham. The first case was that of an unvaccinated married woman who worked in the cardroom of a cotton mill in Chadderton. The other three cases are those of the woman's husband, who v~as vaccinated in 1916; her son, aged 15, who had never been vaccinated ; and an unvaccinated woman who had been in contact with the original case. All these patients have been removed to hospital. The diagnosis of smallpox in the first patient was not established sufficiently early to ensure the successful vaccination of contacts, of whom there were at least 98 in the woman's place of work and 12 at her home. The medical practitioners and public vaccinators in the districts concerned have all been notified of this outbreak, and arrangements have been made to keep all the known contacts under daily supervision until the period of danger has passed. The original case has not been traced to any human source of infection, and it appears not improbable that the infection was conveyed in the raw cotton which this patient handled. Cotton as a vehicle of infection of smallpox has frequently been suspected in the past, and in 1918 cases of this disease were reported in Oldham which were probably caused by infection from cotton. Scarlet Fever at Doncaster.--An outbreak of scarlet fever is reported from Doncaster, 152 eases having occurred up to date (December 21st) in the county borough and in the neighbouring rural district. All these patients had consumed raw milk from the same source, and it is reported that a milker on the farm in question has been found to be suffering from illness which is probably of scarlatinal origin. The local authorities have arranged for all milk from this source to be pasteurised before delivery, and a Medical Officer of the Ministry has visited Doncaster to give any necessary advice or assistance. It is probable that the majority of the primary eases have now been accounted for. Notices of Group Meetings.--The programmes for meetings of the Fever Hospital, Maternity and Child Welfare and Dental Officers Groups to be held this month appear on page 185. The following members of the Society have satisfied the examiners in the recent examination for the degree of Mastery of Midwifery conferred by the Society of Apothecaries of London :--D6sir6e Muriel Barbara Gross, M.D. (LEEDS), D.P.H. (LOND.) (Assistant M.O.H., Ilford) ; and Katherine Mary Hirst, M.B., B.S. (LOND.), D.P.H. (Assistant M.O.H., Birmingham).