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CONTROL OF SCARLET FEVER IN INSTITUTIONS.
1159
(c.cm. of N/10 sodium hydroxide required to which are taken expressly in the cause of humanity. neutralise 100 c.cm. of gastric juice) between this age The authorities of this hospital are now prepared to and 40, after which it falls to a level of about 30 to empower the administration in their hospital of anti35 units. In women 30 to 35 appears to be the tetanic serum in accordance with accepted medical normal level throughout adult life. At the age of knowledge, and the London County Council has 60 some 28 women in every 100 fail to show any free withdrawn accordingly its embargo against the acid on fractional analysis and 23 per cent. of men taking of accident cases to the institution by their Other workers have also ambulances. The journal announces that Sir Arthur are similarly achlorhydric. noted this high percentage of achlorhydria in normal Keith will give the next Stephen Paget memorial persons over 60 years of age, and it has been suggested lecture at the annual general meeting of the Society that this is the result of a senile atrophy of the gastric on Wednesday, June 15th, in the lecture hall of the The authors of this investigation attribute London School of Hygiene and Tropical Medicine. mucosa. it to a hereditary tendency rather than to a morbid process. CONTROL OF SCARLET FEVER IN These studies of gastric acidity certainly provide useful data for future comparison, even if the hope INSTITUTIONS. of the authors that they will be now able to " detect UNTIL a few years ago the measures available for with certainty small abnormalities in the secretory the control of an outbreak of scarlet fever in an power of the stomach due to disease," is not realised. institution or in a children’s ward were limited to It is difficult to believe that small variations in gastric the removal of clinical cases to an isolation block or acidity would ever be of great practical significance. the fever hospital and the quarantining of those As our knowledge of gastric secretion increases it exposed to the disease. The occurrence of dropping appears more and more probable that gastric acidity cases at irregular intervals might prolong this period is at least in part dependent upon a general condition of indefinitely, and meanwhile the work of the body. For example, the high acidity common of quarantine the institution or ward was badly hampered. in duodenal ulcer is more likely to be the predisposing Save by a few rare spirits, the haemolytio streptococcus factor to the formation of the ulcer then a reflex described by the Dicks has been accepted, upon effect produced by the ulcer. It is significant that evidence which is really overwhelming, as the causal the highest acidity is normally found in men between of the disease. As M. L. Blatt and M. L. organism the ages of 20 and 40, at which time the incidence of Dale point out, the subsequent discovery by the duodenal ulcer is highest. As we have already same workers in 1924 of the production of a specific observed2 it is possible that gastric acid secretion toxin and of its antitoxin have together permitted provides one means of maintaining the acid-base of a rational scientific programme for controlling equilibrium of the body, and is thus subject to varia- the disease. Most of the measures now available tions in the blood and tissues outside the stomach. are in routine use in many fever and children’s The data here recorded may therefore be regarded in this hospitals country and have been described in as suggesting rather the soil upon which ulcer or our columns by R. A. O’Brien.2 They were employed carcinoma, for example, may develop, than as provid- systematically and successfully by Blatt and Dale ing a set of standards for the comparison of the in the control of an outbreak in an infant and maternity changes found in gastric disease. The narrow view hospital in Chicago at a period when scarlet fever that various types of test-meal curves are produced was very prevalent in that city. The significance of by local disease in the stomach and are diagnostic periods as long as 19 and 14 days between the first of such disease is giving way to a broader conception four cases did not at first suggest anything unusual of a gastric " constitution " upon which disease to but a fifth case occurred at a further long them, tends to form. interval under conditions which suggested that adult carriers having access to any of the five floors of THE POSITION OF MEDICAL RESEARCH. the institution were the means of transmission. THE Journal of the Research Defence Society, Thereupon rigid preventive measures were instituted. entitled the Fight Against Disease, contains in its All clinical cases had been already removed to a latest issue an analysis of the 1876 Act (Act 39 and fever hospital. The adult patients and staff, amongst 40 Vict. cap 77) under which research involving the whom were discovered seven with positive cultures, use of living animals is permitted in this country. were required to wear, except at meals which they Medical progress has been impeded, and research took together, gauze masks until three platings workers have been harassed with malevolent accusa- upon blood agar could be shown to be negative for tions against them, by vigorous antagonists, but haemolytic streptococci. Children with positive many, if not all, of the points upon which public cultures were isolated in special wards on their opinion asks for information will be found in the respective floors. A Dick test was performed upon wording of the Act, whose relevant passages are everyone in the hospital. Three children amongst cited in the journal. Restrictions upon the perform- those who had been in most recent contact with the ance of experiments on living animals are cate- last cases were found to be positive reactors. These gorical, and so are the provisions under which in were passively immunised with scarlet fever antitoxin certain cases these restrictions may be modified. and a week later active immunisation by means of The issue of the licences, making the research work multiple skin test doses of toxin was begun. All legal, is carefully controlled, and prompt legal pro- other positive reactors amongst patients and attendceedings can be taken against the author of any ants, except three very young infants, were actively experiments in contravention of the Act. The public immunised. The last case of scarlet fever developed is gradually appreciating in greater measure on which two days after these measures were taken ; signifiside truth lies, and the recent action of the Anticantly, in a positive reactor who had not received Vivisection Hospital makes it clear that the opponents antitoxin. The institution was not closed to admisof experimental research, some of them at any rate, sions, but during the succeeding six weeks Dick realise that inhumanity may result from actions ____
1
2
THE
LANCET, Jan. 2nd,
p. 29.
Jour. Amer. Med. Assoc., April 23rd, p. 1437. 2 THE LANCET, 1929, ii., 296.
1160 tests were done and cultures obtained in the case of set up by previous sensitisation. For the reality all new entrants, and if necessary immunisation was of hyperfilariation-a matter which had been concarried out. No further cases developed. Commenting stantly in Sir Patrick Manson’s mind, of its apparent on the procedures Blatt and Dale note that the Dick commonness in young people in endemic areas, and toxin used for active immunisation produced severe of its ability to produce directly or indirectly the reactions in many older children and adults although, blockage which results in elephantiasis and other with one exception, active immunity was brought lymph stases, Dr. O’Connor gave striking evidence. about in a month by five graded doses of toxin at The cumulative effect of the steps in his line of five day intervals. Of the 176 children originally argument-that the filaria is the essential cause of the tested 43 (24 per cent.) were positive. It was possible symptoms constituting the filarial syndrome-was to retest 56 of the original 176 infants six months impressive and met with acceptance. later. The others had presumably left the hospital. Perhaps the most striking point which came out in Of 13 originally immunised Dick-positive reactors a the subsequent discussion was the difficulty of drawing four months old infant, negative one month after safe general conclusions in the present state of knowimmunisation, had again become positive. Of 43 ledge. In Grenada, for instance, the ordinary insect original Dick-negative infants five gavb a positive host is present and can be infected, but the disease test six months later. These " mutations in skin is absent. We are ignorant of what happens to reactivity " in this small series of infants are doubtless the microfilaria in the cryptic hours between midday, to be explained in the same way as similar changes the hour about which, as Dr. O’Connor’s investigations in the sign of the Schick test in infants. They are indicate, parturition takes place when there is microdue in the one case to the inhibiting effect of maternally filarial periodicity, and midnight, the hour about which transmitted passive immunity upon the production of the numbers of -these larvae reach their height in the active immunity and in the other to the gradual blood. The different aspect of the filarial syndrome waning of this passive immunity as the months pass. in different geographical areas was mentioned, with
the
suggestion that the details of the lymphatic system had not perhaps precisely the same structure
THE CAUSES OF FILARIAL SYMPTOMS. in different races of man. That the presence of IN a paper read at Manson House, before the Royal elephantiasis was accompanied by hitherto unsuspected Society of Tropical Medicine and Hygiene on May 19th, biochemical changes was shown by a cited instance Dr. F. W. O’Connor, of the Presbyterian Hospital, in which skin reactions to the dirofilarial antigen Columbia University, New York, dealt with the of Hamilton Fairley (see p. 1167), markedly different factors which underlie the disease syndrome in from the normal, developed when it was injected into infection with Wuchereria bancrofti, as its valid name elephantoid skin. The further investigations which now is. Having pointed out how the original con- Dr. O’Connor is about to carry out in Porto Rico are ception, that the symptoms of filariasis were due to being undertaken in the hope of advancing knowledge the filaria, had tended to give place to one implicating on these and kindred matters by an extension of the bacteria as essential in causation, he marshalled methods which in the hands of his technical staff have evidence, much of it new, against this conclusion. already given such fruitful results. He first pointed out the territorial correlation between the symptoms, the filaria, and the local insect vector, VITAMINS AND RADIATION. and the striking lack of correlation between chronic filariasis and bacteria ; strengthening his argument VITAMIN research has for many years engaged the with similar instances in other lymphatic diseases. attention of physiologists and biochemists and has He surveyed the bacteriological studies made in of late been a field of work chosen by pure organic I connexion with filariasis, and showed how The progress recently made towards the I chemists. even in acute filarial lymphangitis, cultures identification and preparation of these once mysterious blood and from local material have been sterile ; substances has been astonishingly rapid, so much so and it is of course the many instances of failure by that a has already been reached when profitable stage experienced bacteriologists to grow bacteria which attempts may be made to determine their actual are here of positive importance. The successful molecular structure. Physical chemists are now instances he attributed to secondary infections taking up this problem, and F. P. Bowden and of the skin caused by the scratching induced by the C. P. Snow,l of the Laboratory of Physical Chemistry, intense irritation found in this condition so soon as have lately reported a series of experiments Cambridge, acute symptoms cease, scratch marks being a striking which promise to shed light on the constitution feature of these cases. Next followed the inquiryI and possible methods of production of the vitamins. as to whether the clinical and pathological features ’, They employ photochemical and spectroscopical of filariasis were such as to establish the responsibility methods to follow the changes which take place in of the parasite for them. His reading of the histo- the structure and of certain of the vitamins properties logical evidence is that, provided there is lymphatic and pro-vitamins as the result of exposure to radiaobstruction higher up, living worms produce a tions of strictly defined wave-length, the essence polypoid endothelial proliferation of the lymphatic of their technique being to employ monochromatic vessel in which they live, which stops short of comlight as the source of radiation instead of using plete occlusion but nevertheless often suffices to light filters. Their results already suggest that kill the parasite ; when, however, this dies complete they may have accomplished the actual conversion occlusion may be expected. The share of the daily in vitro of the pro-vitamin carotene to vitamin A. death and daily destruction of micronlarise (for On spectrographic analysis carotene shows characterevidence in that direction accumulates) in the istic bands, one of these being situated absorption production of ill-effects needs further study. at 2700 A. A solution of carotene was exposed to Regarding attacks of acute lymphangitis, the con- radiation of about this same wave -length-namely, clusion was reached that they are allergic, and 2650 A, selected from the spectrum of mercury. correspond to a moment when death of worms liberates sufficient protein to overcome the resistance 1 Nature, May 14th, p. 720.
often,
from
I
(c.cm. of N/10 sodium hydroxide required to which are taken expressly in the cause of humanity. neutralise 100 c.cm. of gastric juice) between this age The authorities of this hospital are now prepared to and 40, after which it falls to a level of about 30 to empower the administration in their hospital of anti35 units. In women 30 to 35 appears to be the tetanic serum in accordance with accepted medical normal level throughout adult life. At the age of knowledge, and the London County Council has 60 some 28 women in every 100 fail to show any free withdrawn accordingly its embargo against the acid on fractional analysis and 23 per cent. of men taking of accident cases to the institution by their Other workers have also ambulances. The journal announces that Sir Arthur are similarly achlorhydric. noted this high percentage of achlorhydria in normal Keith will give the next Stephen Paget memorial persons over 60 years of age, and it has been suggested lecture at the annual general meeting of the Society that this is the result of a senile atrophy of the gastric on Wednesday, June 15th, in the lecture hall of the The authors of this investigation attribute London School of Hygiene and Tropical Medicine. mucosa. it to a hereditary tendency rather than to a morbid process. CONTROL OF SCARLET FEVER IN These studies of gastric acidity certainly provide useful data for future comparison, even if the hope INSTITUTIONS. of the authors that they will be now able to " detect UNTIL a few years ago the measures available for with certainty small abnormalities in the secretory the control of an outbreak of scarlet fever in an power of the stomach due to disease," is not realised. institution or in a children’s ward were limited to It is difficult to believe that small variations in gastric the removal of clinical cases to an isolation block or acidity would ever be of great practical significance. the fever hospital and the quarantining of those As our knowledge of gastric secretion increases it exposed to the disease. The occurrence of dropping appears more and more probable that gastric acidity cases at irregular intervals might prolong this period is at least in part dependent upon a general condition of indefinitely, and meanwhile the work of the body. For example, the high acidity common of quarantine the institution or ward was badly hampered. in duodenal ulcer is more likely to be the predisposing Save by a few rare spirits, the haemolytio streptococcus factor to the formation of the ulcer then a reflex described by the Dicks has been accepted, upon effect produced by the ulcer. It is significant that evidence which is really overwhelming, as the causal the highest acidity is normally found in men between of the disease. As M. L. Blatt and M. L. organism the ages of 20 and 40, at which time the incidence of Dale point out, the subsequent discovery by the duodenal ulcer is highest. As we have already same workers in 1924 of the production of a specific observed2 it is possible that gastric acid secretion toxin and of its antitoxin have together permitted provides one means of maintaining the acid-base of a rational scientific programme for controlling equilibrium of the body, and is thus subject to varia- the disease. Most of the measures now available tions in the blood and tissues outside the stomach. are in routine use in many fever and children’s The data here recorded may therefore be regarded in this hospitals country and have been described in as suggesting rather the soil upon which ulcer or our columns by R. A. O’Brien.2 They were employed carcinoma, for example, may develop, than as provid- systematically and successfully by Blatt and Dale ing a set of standards for the comparison of the in the control of an outbreak in an infant and maternity changes found in gastric disease. The narrow view hospital in Chicago at a period when scarlet fever that various types of test-meal curves are produced was very prevalent in that city. The significance of by local disease in the stomach and are diagnostic periods as long as 19 and 14 days between the first of such disease is giving way to a broader conception four cases did not at first suggest anything unusual of a gastric " constitution " upon which disease to but a fifth case occurred at a further long them, tends to form. interval under conditions which suggested that adult carriers having access to any of the five floors of THE POSITION OF MEDICAL RESEARCH. the institution were the means of transmission. THE Journal of the Research Defence Society, Thereupon rigid preventive measures were instituted. entitled the Fight Against Disease, contains in its All clinical cases had been already removed to a latest issue an analysis of the 1876 Act (Act 39 and fever hospital. The adult patients and staff, amongst 40 Vict. cap 77) under which research involving the whom were discovered seven with positive cultures, use of living animals is permitted in this country. were required to wear, except at meals which they Medical progress has been impeded, and research took together, gauze masks until three platings workers have been harassed with malevolent accusa- upon blood agar could be shown to be negative for tions against them, by vigorous antagonists, but haemolytic streptococci. Children with positive many, if not all, of the points upon which public cultures were isolated in special wards on their opinion asks for information will be found in the respective floors. A Dick test was performed upon wording of the Act, whose relevant passages are everyone in the hospital. Three children amongst cited in the journal. Restrictions upon the perform- those who had been in most recent contact with the ance of experiments on living animals are cate- last cases were found to be positive reactors. These gorical, and so are the provisions under which in were passively immunised with scarlet fever antitoxin certain cases these restrictions may be modified. and a week later active immunisation by means of The issue of the licences, making the research work multiple skin test doses of toxin was begun. All legal, is carefully controlled, and prompt legal pro- other positive reactors amongst patients and attendceedings can be taken against the author of any ants, except three very young infants, were actively experiments in contravention of the Act. The public immunised. The last case of scarlet fever developed is gradually appreciating in greater measure on which two days after these measures were taken ; signifiside truth lies, and the recent action of the Anticantly, in a positive reactor who had not received Vivisection Hospital makes it clear that the opponents antitoxin. The institution was not closed to admisof experimental research, some of them at any rate, sions, but during the succeeding six weeks Dick realise that inhumanity may result from actions ____
1
2
THE
LANCET, Jan. 2nd,
p. 29.
Jour. Amer. Med. Assoc., April 23rd, p. 1437. 2 THE LANCET, 1929, ii., 296.
1160 tests were done and cultures obtained in the case of set up by previous sensitisation. For the reality all new entrants, and if necessary immunisation was of hyperfilariation-a matter which had been concarried out. No further cases developed. Commenting stantly in Sir Patrick Manson’s mind, of its apparent on the procedures Blatt and Dale note that the Dick commonness in young people in endemic areas, and toxin used for active immunisation produced severe of its ability to produce directly or indirectly the reactions in many older children and adults although, blockage which results in elephantiasis and other with one exception, active immunity was brought lymph stases, Dr. O’Connor gave striking evidence. about in a month by five graded doses of toxin at The cumulative effect of the steps in his line of five day intervals. Of the 176 children originally argument-that the filaria is the essential cause of the tested 43 (24 per cent.) were positive. It was possible symptoms constituting the filarial syndrome-was to retest 56 of the original 176 infants six months impressive and met with acceptance. later. The others had presumably left the hospital. Perhaps the most striking point which came out in Of 13 originally immunised Dick-positive reactors a the subsequent discussion was the difficulty of drawing four months old infant, negative one month after safe general conclusions in the present state of knowimmunisation, had again become positive. Of 43 ledge. In Grenada, for instance, the ordinary insect original Dick-negative infants five gavb a positive host is present and can be infected, but the disease test six months later. These " mutations in skin is absent. We are ignorant of what happens to reactivity " in this small series of infants are doubtless the microfilaria in the cryptic hours between midday, to be explained in the same way as similar changes the hour about which, as Dr. O’Connor’s investigations in the sign of the Schick test in infants. They are indicate, parturition takes place when there is microdue in the one case to the inhibiting effect of maternally filarial periodicity, and midnight, the hour about which transmitted passive immunity upon the production of the numbers of -these larvae reach their height in the active immunity and in the other to the gradual blood. The different aspect of the filarial syndrome waning of this passive immunity as the months pass. in different geographical areas was mentioned, with
the
suggestion that the details of the lymphatic system had not perhaps precisely the same structure
THE CAUSES OF FILARIAL SYMPTOMS. in different races of man. That the presence of IN a paper read at Manson House, before the Royal elephantiasis was accompanied by hitherto unsuspected Society of Tropical Medicine and Hygiene on May 19th, biochemical changes was shown by a cited instance Dr. F. W. O’Connor, of the Presbyterian Hospital, in which skin reactions to the dirofilarial antigen Columbia University, New York, dealt with the of Hamilton Fairley (see p. 1167), markedly different factors which underlie the disease syndrome in from the normal, developed when it was injected into infection with Wuchereria bancrofti, as its valid name elephantoid skin. The further investigations which now is. Having pointed out how the original con- Dr. O’Connor is about to carry out in Porto Rico are ception, that the symptoms of filariasis were due to being undertaken in the hope of advancing knowledge the filaria, had tended to give place to one implicating on these and kindred matters by an extension of the bacteria as essential in causation, he marshalled methods which in the hands of his technical staff have evidence, much of it new, against this conclusion. already given such fruitful results. He first pointed out the territorial correlation between the symptoms, the filaria, and the local insect vector, VITAMINS AND RADIATION. and the striking lack of correlation between chronic filariasis and bacteria ; strengthening his argument VITAMIN research has for many years engaged the with similar instances in other lymphatic diseases. attention of physiologists and biochemists and has He surveyed the bacteriological studies made in of late been a field of work chosen by pure organic I connexion with filariasis, and showed how The progress recently made towards the I chemists. even in acute filarial lymphangitis, cultures identification and preparation of these once mysterious blood and from local material have been sterile ; substances has been astonishingly rapid, so much so and it is of course the many instances of failure by that a has already been reached when profitable stage experienced bacteriologists to grow bacteria which attempts may be made to determine their actual are here of positive importance. The successful molecular structure. Physical chemists are now instances he attributed to secondary infections taking up this problem, and F. P. Bowden and of the skin caused by the scratching induced by the C. P. Snow,l of the Laboratory of Physical Chemistry, intense irritation found in this condition so soon as have lately reported a series of experiments Cambridge, acute symptoms cease, scratch marks being a striking which promise to shed light on the constitution feature of these cases. Next followed the inquiryI and possible methods of production of the vitamins. as to whether the clinical and pathological features ’, They employ photochemical and spectroscopical of filariasis were such as to establish the responsibility methods to follow the changes which take place in of the parasite for them. His reading of the histo- the structure and of certain of the vitamins properties logical evidence is that, provided there is lymphatic and pro-vitamins as the result of exposure to radiaobstruction higher up, living worms produce a tions of strictly defined wave-length, the essence polypoid endothelial proliferation of the lymphatic of their technique being to employ monochromatic vessel in which they live, which stops short of comlight as the source of radiation instead of using plete occlusion but nevertheless often suffices to light filters. Their results already suggest that kill the parasite ; when, however, this dies complete they may have accomplished the actual conversion occlusion may be expected. The share of the daily in vitro of the pro-vitamin carotene to vitamin A. death and daily destruction of micronlarise (for On spectrographic analysis carotene shows characterevidence in that direction accumulates) in the istic bands, one of these being situated absorption production of ill-effects needs further study. at 2700 A. A solution of carotene was exposed to Regarding attacks of acute lymphangitis, the con- radiation of about this same wave -length-namely, clusion was reached that they are allergic, and 2650 A, selected from the spectrum of mercury. correspond to a moment when death of worms liberates sufficient protein to overcome the resistance 1 Nature, May 14th, p. 720.
often,
from
I