- Email: [email protected]
II. THE RELATIONSHIP OF SCARLET FEVER TO OTHER STREPTOCOCCAL INFECTIONS.
748 from scarlatinal and non-scarlatinal conditions afford some protection against living cultures of scarlet fever streptococci and their toxins.
of the source of origin of the strain, upon its virulence, the site of inoculation, and the state of immunity of the host, and that such effects as are neutralisable can be neutralised Protective Action of Streptococcal Antitoxin against Fatal by one antitoxin. In this paper we wish to elaborate Septicaemia due to Various H aemolytic Streptococci. this conception and discuss some of its clinical The acute fatal septicaemias produced in rabbits implications. by strains from cases of acute infectious pharyngitis, The Essential Similarity of Hcemolytic Streptococci fi-oiiz suppurative lymphangitis, malignant endocarditis, Different S’ocree. puerperal fever, erysipelas, &c., can be controlled by To the haemolytic streptococci are ascribed certain scarlet fever antitoxin, and by serum made from toxins from other strains of haemolytic streptococci. so-called " specific " diseases such as scarlet fever and In these experiments the infecting dose for the rabbit erysipelas, and conditions such as cellulitis, puerperal ranged from 1 to 20 c.cm. of 9 to 20 hours tryptic fever, and acute pharyngitis which are not usually digest broth cultures of haemolytic streptococci from looked upon as specific. Many unsuccessful attempts various sources. The dose selected, which was almost have been made to classify the haemolytic streptococci ; always from 1 to 5 c.cm., depended on the virulence morphologically and on biochemical grounds they are of the organisms, and probably represented in most indistinguishable, and it is becoming increasingly experiments from 2 to 5 times the " minimal lethal obvious that they do not lend themselves to being dose " for the majority of animals. Serum was given classified in terms of the diseases they produce. Work in doses of 5 to 15 c.cm., usually 5 c.cm. in the case on the agglutination reaction has elicited many of concentrated antitoxins, and 15 c.cm. of uncon- interesting facts, some of which may have a practical centrated antitoxins. It will be seen from Table III. application, but, as in the case of the diphtheria and that scarlet fever, and to a lesser extent other strepto- tetanus bacilli, no evidence has been produced so far coccal antitoxic sera, have considerable protective to show that there is any subclassification of taxonomic effect against haemolytic streptococci of diverse origin, importance. It has been shown that the specific signs of scarlet the acute septicaemia which follows the intravenous scarlatinoid syndrome "-rash, inoculation of the culture being modified, as in the fever, the so-called first series of experiments, into a subacute infection albuminuria, and even haematuria—can be produced of which arthritis is the most. prominent feature. in susceptible human subjects as the result of an Nearly all the strains have been tested for their injection of sterile scarlet fever toxin. If we take ability to produce streptococcal toxin as demonstrated the symptoms due to the toxin away from scarlet by a Dick test on human subjects, and have been fever we are left with a well-known clinical condition proved to be capable of so doing to a greater or lesser -viz., acute infectious streptococcal angina. Many cases of sore-throat without rash simulate scarlet degree. In Table IV. the results of experiments recorded fever in their infectiousness, severity, and complicain Table III. are summarised with reference to the tions. Some of these are found to propagate scarlet relative protection given by scarlet fever and other fever, and can be called " scarlet fever sine eruptione.’’ streptococcal antitoxins. As shown by the percentages As a rule, however, they propagate sore-throat and of the total rabbits injected which survived for 3 and not scarlet fever, yet the streptococcus that causes for 6 days, scarlet fever antitoxin was of greater value them has all the essential properties of a scarlet fever than any of the various samples of erysipelas, puerperal streptococcus. This is illustrated by the following fever, and pyogenes antitoxins which were used for case. A child caught an acute pharyngitis from a case of sorethis work. throat. The onset was sudden with high fever, frequent Summary. and furred tongue ; the infection spread rapidly 1. Hsemolytic streptococci obtained from various pulse, and relatively painlessly to both middle ears. The child sources-scarlet fever, erysipelas, cellulitis, puerperal gave severe sore-throat to two individuals ; no rash, however, similar lesions of a pyogenic appeared in any case. An almost pure culture of haemolytic fever, &c.-produce nature when injected intradermally in rabbits. We streptococci grew from the swabs of all three cases. The have been unable to demonstrate that sera prepared interesting point in this outbreak was that all the streptococci fairly good producers of Dick toxin in vitro. The against either toxin or bacterial bodies contain a were clinical condition was scarlet fever without scarlatinal specific antibody which will prevent the development tomia ; a toxin was obtained from the streptococci of the pyogenic skin reactions. had it been injected into the patient, would have which, 2. Scarlet fever and other streptococcal antitoxins produced a disease clinically identical with scarlet fever. protect rabbits from the acute phases of the septi- The potentiality for producing the complete scarlet fever caemia following the intravenous injection of the syndrome was there, but for some reason the particular scarlet fever streptococcus, and from deaths due to strain of streptococcus, while a reasonably good toxin producer in vitro, could not produce any significant quantity scarlet fever toxin. 3. They have also a significant protective action in vivo. The production of Dick toxin is by no means a against the septicaemia due to haemolytic streptococci from conditions other than scarlet fever. peculiarity of scarlet fever strains, and results are 4. All haemolytic streptococci appear to be identical rapidly accumulating which suggest that one toxic in their " toxic " action. There is strong evidence product can be obtained to a greater or less degree that the protective action of streptococcal antitoxic from many, if not all, human heemolytic streptococci, sera is due to one antitoxin, which has been produced which is indistinguishable from Dick toxin by the in horses in varying degree in response to immunisation usual tests. A few workers-e.g., Kirkbride and with toxic filtrates of varying potency. Wheeler, 1925-have suggested a plurality of toxins, References.—Birkhaug, K. E. : Bull. Johns Hopkins Hosp., but the results can probably be interpreted as due 1925, xxxvii., 307. Parish, H. J., and Okell, C. C., THE LANCET, to quantitative rather than qualitative differences 1927, i., 71 ; Jour. Path. and Bact., 1927, xxx., 521. between the toxins. It must be admitted that, if scarlet fever is due to a specific streptococcus, the means of identifying the streptococcus is by only II. the impracticable test of its power to produce infectious THE RELATIONSHIP OF SCARLET FEVER TO scarlet fever with rash in susceptible human subjects. We are led to the conclusion that the ordinarv OTHER STREPTOCOCCAL INFECTIONS. of the specificity of the streptococcal conceptions BY C. C. OKELL AND H. J. PARISH. diseases are well worth challenging. We suggest the hypothesis that the various streptococcal infections IN the preceding communication attention was are all due to essentially the same species of bacteria. drawn to experiments in rabbits which suggest that Their pathogenic effect varies with certain accidental quantitative, such as invasiveness and haemolytic streptococci from various human diseases factors, mainly on the part of the strain and local or in the conditions toxigenicity clinical to rise may give
independently but depending
"
rabbit,
749
general susceptibility on the part of the host. We thus attempt to revive and extend views often held in the past and to ascribe the differences in the human diseases due to hsemolytic streptococci to variables which, though little understood, are at least universally allowed to both parasite and host. We do not wish to minimise the clinical nor even the epidemiological differences between the streptococcal diseases. Our purpose is rather to explain a maximum number of facts on a minimum number of suppositions ; in other words, to formulate a working hypothesis which will serve as a basis for further work and at the same time suggest a rational therapy of the streptococcal diseases. In the following table an attempt is made to apply these ideas to some of the clinical entities due to infection with the haemolytic streptococcus. The sign + in the first column indicates that the streptococcus produces enough toxin to produce a rash if the patient is fully susceptible to Dick toxin. is meant that, though the streptococcus By probably produces a certain amount of toxin in vivo, it does not produce sufficient to give rise to obvious clinical signs of scarlatinal toxaemia. The degree of infectiousness is roughly indicated in the second column.
have contracted erysipelas when in attendance upon of puerperal fever. Moreover, a comparison of the registered deaths from erysipelas, puerperal fever, and pysemia shows a sufficient correspondence to suggest that a relationship between these diseases exists. Again, a true cutaneous erysipelas cannot be sharply separated from phlegmonous erysipelas ; nor can the latter disease be always separated from allied septic inflammations." nurses
cases
Several other authors have drawn attention to the
close correspondence between the annual and seasonal
incidences of the deaths from scarlet fever, erysipelas,
and puerperal fever-e.g., Longstaff, 1891, Geddes, 1912 and 1926. McKinlay (1928), however, does not consider that this correspondence should be taken as supporting the idea of a common aetiological factor. One more piece of evidence in favour of the unity
of
erysipelas streptococci with the other haemolytic streptococci has recently been produced by the Dicks (1927), who have succeeded in producing experimental sore-throat by painting erysipelas streptococci on the
throats of human volunteers. As we pointed out in the previous paper, the results of our experiments in rabbits are at variance with those of Birkhaug. The erysipelas-like lesions in the rabbit are produced by all the strains we tried, whatever their origin. The peculiarity of the lesions was, so far as we could judge, entirely dependent on the virulence of the strain used and the layer of the skin that was injected. One
Identifiable Therapeutic Antibody to Hcemolytic Streptococci, generally known as Scarlet Fever
Antitoxin. It may be asked in what way this " unitarian theory of the hsemolytic streptococci would modify existing views on the specific treatment of streptococcal disease. It has been our experience that all haemolytic streptococci make the same toxin and that there is only one identifiable antibody-namely, what is generally known as scarlet fever antitoxin. The antitoxins produced in horses by injecting filtrates of streptococci from scarlet fever, puerperal fever, septic wounds, and other conditions, are qualitaUnder a "unitarian" theory the relationship tively indistinguishable ; but since scarlet fever between puerperal fever and puerperal scarlet fever strains are usually more active toxin producers in becomes more defined. The known clinical entities vitro, the highest grade sera are made in response to injections of their filtrates. can be divided into:We ascribe the pathogenic activities of the haemolytic 1. Primary faucial infection with rash and with to (1) their invasive function, over which streptococci infection of the uterus. secondary the antitoxin has only a limited control; and (2) their 2. Primary infection of the uterus with a streptowhich the antitoxin has full power coccus of any origin which is markedly toxigenic toxigenic function, to In neutralise. our rabbit experiments we were in the uterus-usually without secondary faucial unable to discover a specific method for neutralising involvement. It may be mentioned that all the puerperal strains the invasion of the skin with heemolytic streptococci. In human subjects a limited anti-invasive property we have examined have been able to produce Dick is shown by the fact that those who have been protoxin in vitro. take scarlet fever, According to such a view a streptococcus from a tected with the antitoxin do not scarlet fever case might, under suitable conditions, and usually show no signs of infections with the although it is believed that under produce erysipelas or puerperal fever or cellulitis, streptococci, and vice versa a hsemolytic streptococcus associated certain conditions a sore-throat can be produced in with any disease, if it underwent the requisite modi- Dick-immune persons (Stevens and Dochez, 1926 ; fication in virulence and toxigenicity, might be Nicholls, 1926 ; Kinloch, Smith, and Taylor, 1927). conceived as producing scarlet fever and maintaining It is generally admitted that the septic complications this capacity during a considerable epidemic period. of scarlet fever are very little affected by antitoxin It is by no means unusual for an epidemic of scarlet treatment. In the rabbit the development of arthritis fever to start with atypical cases, slowly to attain is uninfluenced by the injection of serum, even in to normal clinical pathogenicity, and then to fade large doses. We would lay particular stress on the observation, away again to atypical cases before it suffers extincreferred to in the first part of this paper, already tion. Goodall and Washbourn in the 1896 edition of their " Manual of Infectious Diseases," p. 330, that an acute and rapidly fatal septicaemia in the rabbit may be converted by antitoxin into a subacute state :that When looked at from a clinical point of view, erysipelas and relatively benign infection. It is probable some degree of scarlatinal toxaemia is present in all at first to be a definite disease with appears specific sight characteristic symptoms. Nevertheless, there are many streptococcal infections, although it may not be For example, the salmon-pink facts in connexion with its aetiology and pathology which obvious clinically. show that it cannot be considered on quite the same footing lymphatics occurring in acute cellulitisare undoubtedly as other specific fevers. The latter diseases are specific in due to the removal of Dick toxin along these channels, the sense that they " breed true." A case of rubeola, for and the appearance can be closely imitated by example, will in other persons give rise only to rubeola, injections of sterile Dick toxin. and not to any other disease. A case of erysipelas is often It seems obvious that, since so-called scarlet fever the origin of erysipelas in other patients, but under certain circumstances it may cause an entirely different type of antitoxin is the only demonstrable therapeutic disease. Nurses suffering from erysipelas have conveyed antibody to the whole group of haemolytic streptopuerperal fever to lying-in women, and medical men and cocci, it should be used in all streptococcal infections,
I
"
-1
750 of the high-frequency current to their surgical arsenal. I do so the more readily since electro-coagulation in other departments of surgery has yielded such valuable results ; for example, in the treatment of cancer of the tongue and the oral cavity, growths of the vocal cords, breast, womb, and many other organs. In reports of these treatments it has been asserted that: (1) operative damage could be comsidered of small importance in comparison with that of other surgical methods of treatment; (2) bleeding could be fully controlled; (3) scars, as the result of the coagulation, are supple; (4) a subsequent operation by the same or by a different method is not impossible. By surgical diathermy with a blunt electrode tissue can be either heated en masse, even as far as boilingpoint, after which the necrotic tissue is cast off sponConclu.sions. or it can be severed with a thin needle. taneously, 1. The haemolytic streptococci of human origin Our treatment of the hypertrophic prostate aimed represent one species of bacteria with common at the massive necrosis, as did Weijtlandt’s, although pathogenic potentialities. The balance of " phasic the methods differ considerably in many respects. variations " on the part of the bacterium with local Up till now we have treated with electro-coagulation and general susceptibility on the part, of the host 52 patients suffering from disease of the prostate. " clinical Four have would explain the apparently " specific died ; in 8 cases the treatment has not conditions which result from infection. ended or no good results are evident; all the yet 2. A single antitoxin generally known as scarlet others benefited treatment, greatly by this fever antitoxin corresponds with the single toxin. inasmuch as all of them could simple urinate very well This may be depended upon to neutralise the specific after the treatment. Originally we submitted to toxaemia, and possibly has limited anti-invasive this treatment only those patients for whom operaproperties as well. It is the only streptococcal anti- tion with the scalpel was deemed too dangerousbody with any acceptable experimental and theravery old people, those suffering from heart peutic credentials, and should be given a more extensive e.g., disease and diseases of the blood-vessels, and more trial in all severe streptococcal infections, particularly those with deficient function of the kidneys. in general septicaemia. It is also suggested that it especially should be used in the prophylactic treatment of The Operative Treatment. wounds received while performing post-mortem We make it a rule in the Coolsingel Hospital that examinations or surgical operations on septic cases. prior to all prostatectomies the function of the internal organs, and especially those of the kidneys, References. Dick, G. F., and Dick G. H. : Jour. Amer. Med. Assoc., 1927, shall be improved as far as possible by preliminary lxxxix., 1135. treatment, and we consider that the lowering of the Geddes, G. : Statistics of Puerperal Fever and Allied Diseases, nitrogen percentage of the blood serum, which is 1912 ; Puerperal Septicæmia, Bristol, 1926. Goodall, E. W., and Washbourn, J. W. : Manual of Infectious nearly always greatly increased at the time of admission, is of the utmost importance. Diseases, London, 1896. Kinloch, J. P., Smith, J., and Taylor, J. S. : Jour. Hygiene, We insist on a sequence of treatments, such as 1927, xxvi., 327. of the bladder, self-containing catheter, irrigation and M. W. : Proc. Soc. Biol. M. B., Wheeler, Exp. Kirkbride, Med., 1925, xxii., 85; Jour. Immunology, 1926, xi., 477 ; diet, drugs and complete rest, until a series of conibid., 1927, xiii., 19. secutive tests have shown the urea percentage to be Longstaff, G. B. : Studies in Statistics, London, 1891. about 350 mg. per litre, or less, and not until then is McKinlay, P. L. : Jour. Hygiene, 1928, xxvii., 186. Nicholls, E. E. : Jour. Clin. Investigation, Baltimore, 1926, prostatectomy considered justifiable. We have reason to be very satisfied with this mode of preliminary v., 411. Stevens, F. A., and Dochez, A. R. : Jour. Amer. Med. Assoc., treatment, the operative mortality being 1 case in 2137. 1926, lxxxvii., 50 prostatectomies. All the others came through the operation very well and were dismissed completely cured. A certain number of patients, however, THE TREATMENT OF can never be treated by operation, even after a proCOMPLETE RETENTION OF URINE OF longed sojourn in hospital. It is not to be wondered at that we looked for other means to give relief PROSTATIC ORIGIN BY ELECTROto those " stayers " with their total obstruction, to try to enable them to live outside the hospital COAGULATION. without the self-retaining catheter. This means BY J. G. REMIJNSE, we think we have found in electro-coagulation with
in acute septicaemias where there is a treatment We have already seen a limited number of clinical reports claiming that excellent results have followed treatment with scarlet fever serum in such conditions as puerperal septicaemia, septicaemia from wounds, and erysipelas. It is true that we cannot attach much importance to isolated clinical trials, but it is interesting to know that the evidence, such as it is, points to a common therapeutic antibody. One special application for the streptococcal antitoxin would be its use in the prophylactic treatment of wounds received while performing postmortem examinations or septic surgical operations, in the hope of being able to parallel the rabbit effect and prevent the development of a fatal septicaemia.
particularly demand for
serum
HEAD SURGEON TO THE COOLSINGEL
HOSPITAL, ROTTERDAM.
the diathermy apparatus. In February, 1927, we had in our wards two patients Geneeskunde of 77 and 80 years old, who had been there for quite a
IN the 11 ederlandsch Tijdschrift voor June llth, 1927 (p. 3228), Dr. J.A. Weijtlandtdescribes a patient, 76 years of age, who suffered from prostatic disease, which had caused complete retention of urine within a very short time. Dr. Weijtlandt treated this man successfully by diathermy applied through McCarthy’s cystoscope, and by so doing showed that this method of treatment deserves general attention as much for its thoroughness as for its simplicity and lack of danger. It is a treatment which will probably find considerable scope in the near future. I have therefore been encouraged to publish the results obtained by us at the Coolsingel Hospital in the treatment of prostatic diseases with electrocoagulation, although we are well aware of the fact that the time that has elapsed since we started this mode of treatment is altogether too short for us to regard the results obtained as final. The provisional outcome, however, is so encouraging that others might find it worth while to add this new application
number of months and who showed all the symptoms of a prostatic hypertrophy dating from a long time back. One of them had been operated upon for diverticulum of the bladder and vesical calculi. Both were suffering from emphysema of the lungs, arterio-sclerosis, and cystitis. The complete retention had persisted, notwithstanding dieting, irrigation of the bladder, and the self-retaining catheter. One had a small, the other a large, prostate. Both suffered from boils and showed a high urea percentage in their blood. In February, 1927, we coagulated the prostate in both cases ; the patient with the enlarged prostate was submitted to two subsequent treatments in February and March ; the patient with the small prostate was given one more treatment, but not until May, because he had developed an epididymitis. Both patients left the hospital in good condition, able to pass water spontaneously, although a small amount of residual urine still remained.
of the source of origin of the strain, upon its virulence, the site of inoculation, and the state of immunity of the host, and that such effects as are neutralisable can be neutralised Protective Action of Streptococcal Antitoxin against Fatal by one antitoxin. In this paper we wish to elaborate Septicaemia due to Various H aemolytic Streptococci. this conception and discuss some of its clinical The acute fatal septicaemias produced in rabbits implications. by strains from cases of acute infectious pharyngitis, The Essential Similarity of Hcemolytic Streptococci fi-oiiz suppurative lymphangitis, malignant endocarditis, Different S’ocree. puerperal fever, erysipelas, &c., can be controlled by To the haemolytic streptococci are ascribed certain scarlet fever antitoxin, and by serum made from toxins from other strains of haemolytic streptococci. so-called " specific " diseases such as scarlet fever and In these experiments the infecting dose for the rabbit erysipelas, and conditions such as cellulitis, puerperal ranged from 1 to 20 c.cm. of 9 to 20 hours tryptic fever, and acute pharyngitis which are not usually digest broth cultures of haemolytic streptococci from looked upon as specific. Many unsuccessful attempts various sources. The dose selected, which was almost have been made to classify the haemolytic streptococci ; always from 1 to 5 c.cm., depended on the virulence morphologically and on biochemical grounds they are of the organisms, and probably represented in most indistinguishable, and it is becoming increasingly experiments from 2 to 5 times the " minimal lethal obvious that they do not lend themselves to being dose " for the majority of animals. Serum was given classified in terms of the diseases they produce. Work in doses of 5 to 15 c.cm., usually 5 c.cm. in the case on the agglutination reaction has elicited many of concentrated antitoxins, and 15 c.cm. of uncon- interesting facts, some of which may have a practical centrated antitoxins. It will be seen from Table III. application, but, as in the case of the diphtheria and that scarlet fever, and to a lesser extent other strepto- tetanus bacilli, no evidence has been produced so far coccal antitoxic sera, have considerable protective to show that there is any subclassification of taxonomic effect against haemolytic streptococci of diverse origin, importance. It has been shown that the specific signs of scarlet the acute septicaemia which follows the intravenous scarlatinoid syndrome "-rash, inoculation of the culture being modified, as in the fever, the so-called first series of experiments, into a subacute infection albuminuria, and even haematuria—can be produced of which arthritis is the most. prominent feature. in susceptible human subjects as the result of an Nearly all the strains have been tested for their injection of sterile scarlet fever toxin. If we take ability to produce streptococcal toxin as demonstrated the symptoms due to the toxin away from scarlet by a Dick test on human subjects, and have been fever we are left with a well-known clinical condition proved to be capable of so doing to a greater or lesser -viz., acute infectious streptococcal angina. Many cases of sore-throat without rash simulate scarlet degree. In Table IV. the results of experiments recorded fever in their infectiousness, severity, and complicain Table III. are summarised with reference to the tions. Some of these are found to propagate scarlet relative protection given by scarlet fever and other fever, and can be called " scarlet fever sine eruptione.’’ streptococcal antitoxins. As shown by the percentages As a rule, however, they propagate sore-throat and of the total rabbits injected which survived for 3 and not scarlet fever, yet the streptococcus that causes for 6 days, scarlet fever antitoxin was of greater value them has all the essential properties of a scarlet fever than any of the various samples of erysipelas, puerperal streptococcus. This is illustrated by the following fever, and pyogenes antitoxins which were used for case. A child caught an acute pharyngitis from a case of sorethis work. throat. The onset was sudden with high fever, frequent Summary. and furred tongue ; the infection spread rapidly 1. Hsemolytic streptococci obtained from various pulse, and relatively painlessly to both middle ears. The child sources-scarlet fever, erysipelas, cellulitis, puerperal gave severe sore-throat to two individuals ; no rash, however, similar lesions of a pyogenic appeared in any case. An almost pure culture of haemolytic fever, &c.-produce nature when injected intradermally in rabbits. We streptococci grew from the swabs of all three cases. The have been unable to demonstrate that sera prepared interesting point in this outbreak was that all the streptococci fairly good producers of Dick toxin in vitro. The against either toxin or bacterial bodies contain a were clinical condition was scarlet fever without scarlatinal specific antibody which will prevent the development tomia ; a toxin was obtained from the streptococci of the pyogenic skin reactions. had it been injected into the patient, would have which, 2. Scarlet fever and other streptococcal antitoxins produced a disease clinically identical with scarlet fever. protect rabbits from the acute phases of the septi- The potentiality for producing the complete scarlet fever caemia following the intravenous injection of the syndrome was there, but for some reason the particular scarlet fever streptococcus, and from deaths due to strain of streptococcus, while a reasonably good toxin producer in vitro, could not produce any significant quantity scarlet fever toxin. 3. They have also a significant protective action in vivo. The production of Dick toxin is by no means a against the septicaemia due to haemolytic streptococci from conditions other than scarlet fever. peculiarity of scarlet fever strains, and results are 4. All haemolytic streptococci appear to be identical rapidly accumulating which suggest that one toxic in their " toxic " action. There is strong evidence product can be obtained to a greater or less degree that the protective action of streptococcal antitoxic from many, if not all, human heemolytic streptococci, sera is due to one antitoxin, which has been produced which is indistinguishable from Dick toxin by the in horses in varying degree in response to immunisation usual tests. A few workers-e.g., Kirkbride and with toxic filtrates of varying potency. Wheeler, 1925-have suggested a plurality of toxins, References.—Birkhaug, K. E. : Bull. Johns Hopkins Hosp., but the results can probably be interpreted as due 1925, xxxvii., 307. Parish, H. J., and Okell, C. C., THE LANCET, to quantitative rather than qualitative differences 1927, i., 71 ; Jour. Path. and Bact., 1927, xxx., 521. between the toxins. It must be admitted that, if scarlet fever is due to a specific streptococcus, the means of identifying the streptococcus is by only II. the impracticable test of its power to produce infectious THE RELATIONSHIP OF SCARLET FEVER TO scarlet fever with rash in susceptible human subjects. We are led to the conclusion that the ordinarv OTHER STREPTOCOCCAL INFECTIONS. of the specificity of the streptococcal conceptions BY C. C. OKELL AND H. J. PARISH. diseases are well worth challenging. We suggest the hypothesis that the various streptococcal infections IN the preceding communication attention was are all due to essentially the same species of bacteria. drawn to experiments in rabbits which suggest that Their pathogenic effect varies with certain accidental quantitative, such as invasiveness and haemolytic streptococci from various human diseases factors, mainly on the part of the strain and local or in the conditions toxigenicity clinical to rise may give
independently but depending
"
rabbit,
749
general susceptibility on the part of the host. We thus attempt to revive and extend views often held in the past and to ascribe the differences in the human diseases due to hsemolytic streptococci to variables which, though little understood, are at least universally allowed to both parasite and host. We do not wish to minimise the clinical nor even the epidemiological differences between the streptococcal diseases. Our purpose is rather to explain a maximum number of facts on a minimum number of suppositions ; in other words, to formulate a working hypothesis which will serve as a basis for further work and at the same time suggest a rational therapy of the streptococcal diseases. In the following table an attempt is made to apply these ideas to some of the clinical entities due to infection with the haemolytic streptococcus. The sign + in the first column indicates that the streptococcus produces enough toxin to produce a rash if the patient is fully susceptible to Dick toxin. is meant that, though the streptococcus By probably produces a certain amount of toxin in vivo, it does not produce sufficient to give rise to obvious clinical signs of scarlatinal toxaemia. The degree of infectiousness is roughly indicated in the second column.
have contracted erysipelas when in attendance upon of puerperal fever. Moreover, a comparison of the registered deaths from erysipelas, puerperal fever, and pysemia shows a sufficient correspondence to suggest that a relationship between these diseases exists. Again, a true cutaneous erysipelas cannot be sharply separated from phlegmonous erysipelas ; nor can the latter disease be always separated from allied septic inflammations." nurses
cases
Several other authors have drawn attention to the
close correspondence between the annual and seasonal
incidences of the deaths from scarlet fever, erysipelas,
and puerperal fever-e.g., Longstaff, 1891, Geddes, 1912 and 1926. McKinlay (1928), however, does not consider that this correspondence should be taken as supporting the idea of a common aetiological factor. One more piece of evidence in favour of the unity
of
erysipelas streptococci with the other haemolytic streptococci has recently been produced by the Dicks (1927), who have succeeded in producing experimental sore-throat by painting erysipelas streptococci on the
throats of human volunteers. As we pointed out in the previous paper, the results of our experiments in rabbits are at variance with those of Birkhaug. The erysipelas-like lesions in the rabbit are produced by all the strains we tried, whatever their origin. The peculiarity of the lesions was, so far as we could judge, entirely dependent on the virulence of the strain used and the layer of the skin that was injected. One
Identifiable Therapeutic Antibody to Hcemolytic Streptococci, generally known as Scarlet Fever
Antitoxin. It may be asked in what way this " unitarian theory of the hsemolytic streptococci would modify existing views on the specific treatment of streptococcal disease. It has been our experience that all haemolytic streptococci make the same toxin and that there is only one identifiable antibody-namely, what is generally known as scarlet fever antitoxin. The antitoxins produced in horses by injecting filtrates of streptococci from scarlet fever, puerperal fever, septic wounds, and other conditions, are qualitaUnder a "unitarian" theory the relationship tively indistinguishable ; but since scarlet fever between puerperal fever and puerperal scarlet fever strains are usually more active toxin producers in becomes more defined. The known clinical entities vitro, the highest grade sera are made in response to injections of their filtrates. can be divided into:We ascribe the pathogenic activities of the haemolytic 1. Primary faucial infection with rash and with to (1) their invasive function, over which streptococci infection of the uterus. secondary the antitoxin has only a limited control; and (2) their 2. Primary infection of the uterus with a streptowhich the antitoxin has full power coccus of any origin which is markedly toxigenic toxigenic function, to In neutralise. our rabbit experiments we were in the uterus-usually without secondary faucial unable to discover a specific method for neutralising involvement. It may be mentioned that all the puerperal strains the invasion of the skin with heemolytic streptococci. In human subjects a limited anti-invasive property we have examined have been able to produce Dick is shown by the fact that those who have been protoxin in vitro. take scarlet fever, According to such a view a streptococcus from a tected with the antitoxin do not scarlet fever case might, under suitable conditions, and usually show no signs of infections with the although it is believed that under produce erysipelas or puerperal fever or cellulitis, streptococci, and vice versa a hsemolytic streptococcus associated certain conditions a sore-throat can be produced in with any disease, if it underwent the requisite modi- Dick-immune persons (Stevens and Dochez, 1926 ; fication in virulence and toxigenicity, might be Nicholls, 1926 ; Kinloch, Smith, and Taylor, 1927). conceived as producing scarlet fever and maintaining It is generally admitted that the septic complications this capacity during a considerable epidemic period. of scarlet fever are very little affected by antitoxin It is by no means unusual for an epidemic of scarlet treatment. In the rabbit the development of arthritis fever to start with atypical cases, slowly to attain is uninfluenced by the injection of serum, even in to normal clinical pathogenicity, and then to fade large doses. We would lay particular stress on the observation, away again to atypical cases before it suffers extincreferred to in the first part of this paper, already tion. Goodall and Washbourn in the 1896 edition of their " Manual of Infectious Diseases," p. 330, that an acute and rapidly fatal septicaemia in the rabbit may be converted by antitoxin into a subacute state :that When looked at from a clinical point of view, erysipelas and relatively benign infection. It is probable some degree of scarlatinal toxaemia is present in all at first to be a definite disease with appears specific sight characteristic symptoms. Nevertheless, there are many streptococcal infections, although it may not be For example, the salmon-pink facts in connexion with its aetiology and pathology which obvious clinically. show that it cannot be considered on quite the same footing lymphatics occurring in acute cellulitisare undoubtedly as other specific fevers. The latter diseases are specific in due to the removal of Dick toxin along these channels, the sense that they " breed true." A case of rubeola, for and the appearance can be closely imitated by example, will in other persons give rise only to rubeola, injections of sterile Dick toxin. and not to any other disease. A case of erysipelas is often It seems obvious that, since so-called scarlet fever the origin of erysipelas in other patients, but under certain circumstances it may cause an entirely different type of antitoxin is the only demonstrable therapeutic disease. Nurses suffering from erysipelas have conveyed antibody to the whole group of haemolytic streptopuerperal fever to lying-in women, and medical men and cocci, it should be used in all streptococcal infections,
I
"
-1
750 of the high-frequency current to their surgical arsenal. I do so the more readily since electro-coagulation in other departments of surgery has yielded such valuable results ; for example, in the treatment of cancer of the tongue and the oral cavity, growths of the vocal cords, breast, womb, and many other organs. In reports of these treatments it has been asserted that: (1) operative damage could be comsidered of small importance in comparison with that of other surgical methods of treatment; (2) bleeding could be fully controlled; (3) scars, as the result of the coagulation, are supple; (4) a subsequent operation by the same or by a different method is not impossible. By surgical diathermy with a blunt electrode tissue can be either heated en masse, even as far as boilingpoint, after which the necrotic tissue is cast off sponConclu.sions. or it can be severed with a thin needle. taneously, 1. The haemolytic streptococci of human origin Our treatment of the hypertrophic prostate aimed represent one species of bacteria with common at the massive necrosis, as did Weijtlandt’s, although pathogenic potentialities. The balance of " phasic the methods differ considerably in many respects. variations " on the part of the bacterium with local Up till now we have treated with electro-coagulation and general susceptibility on the part, of the host 52 patients suffering from disease of the prostate. " clinical Four have would explain the apparently " specific died ; in 8 cases the treatment has not conditions which result from infection. ended or no good results are evident; all the yet 2. A single antitoxin generally known as scarlet others benefited treatment, greatly by this fever antitoxin corresponds with the single toxin. inasmuch as all of them could simple urinate very well This may be depended upon to neutralise the specific after the treatment. Originally we submitted to toxaemia, and possibly has limited anti-invasive this treatment only those patients for whom operaproperties as well. It is the only streptococcal anti- tion with the scalpel was deemed too dangerousbody with any acceptable experimental and theravery old people, those suffering from heart peutic credentials, and should be given a more extensive e.g., disease and diseases of the blood-vessels, and more trial in all severe streptococcal infections, particularly those with deficient function of the kidneys. in general septicaemia. It is also suggested that it especially should be used in the prophylactic treatment of The Operative Treatment. wounds received while performing post-mortem We make it a rule in the Coolsingel Hospital that examinations or surgical operations on septic cases. prior to all prostatectomies the function of the internal organs, and especially those of the kidneys, References. Dick, G. F., and Dick G. H. : Jour. Amer. Med. Assoc., 1927, shall be improved as far as possible by preliminary lxxxix., 1135. treatment, and we consider that the lowering of the Geddes, G. : Statistics of Puerperal Fever and Allied Diseases, nitrogen percentage of the blood serum, which is 1912 ; Puerperal Septicæmia, Bristol, 1926. Goodall, E. W., and Washbourn, J. W. : Manual of Infectious nearly always greatly increased at the time of admission, is of the utmost importance. Diseases, London, 1896. Kinloch, J. P., Smith, J., and Taylor, J. S. : Jour. Hygiene, We insist on a sequence of treatments, such as 1927, xxvi., 327. of the bladder, self-containing catheter, irrigation and M. W. : Proc. Soc. Biol. M. B., Wheeler, Exp. Kirkbride, Med., 1925, xxii., 85; Jour. Immunology, 1926, xi., 477 ; diet, drugs and complete rest, until a series of conibid., 1927, xiii., 19. secutive tests have shown the urea percentage to be Longstaff, G. B. : Studies in Statistics, London, 1891. about 350 mg. per litre, or less, and not until then is McKinlay, P. L. : Jour. Hygiene, 1928, xxvii., 186. Nicholls, E. E. : Jour. Clin. Investigation, Baltimore, 1926, prostatectomy considered justifiable. We have reason to be very satisfied with this mode of preliminary v., 411. Stevens, F. A., and Dochez, A. R. : Jour. Amer. Med. Assoc., treatment, the operative mortality being 1 case in 2137. 1926, lxxxvii., 50 prostatectomies. All the others came through the operation very well and were dismissed completely cured. A certain number of patients, however, THE TREATMENT OF can never be treated by operation, even after a proCOMPLETE RETENTION OF URINE OF longed sojourn in hospital. It is not to be wondered at that we looked for other means to give relief PROSTATIC ORIGIN BY ELECTROto those " stayers " with their total obstruction, to try to enable them to live outside the hospital COAGULATION. without the self-retaining catheter. This means BY J. G. REMIJNSE, we think we have found in electro-coagulation with
in acute septicaemias where there is a treatment We have already seen a limited number of clinical reports claiming that excellent results have followed treatment with scarlet fever serum in such conditions as puerperal septicaemia, septicaemia from wounds, and erysipelas. It is true that we cannot attach much importance to isolated clinical trials, but it is interesting to know that the evidence, such as it is, points to a common therapeutic antibody. One special application for the streptococcal antitoxin would be its use in the prophylactic treatment of wounds received while performing postmortem examinations or septic surgical operations, in the hope of being able to parallel the rabbit effect and prevent the development of a fatal septicaemia.
particularly demand for
serum
HEAD SURGEON TO THE COOLSINGEL
HOSPITAL, ROTTERDAM.
the diathermy apparatus. In February, 1927, we had in our wards two patients Geneeskunde of 77 and 80 years old, who had been there for quite a
IN the 11 ederlandsch Tijdschrift voor June llth, 1927 (p. 3228), Dr. J.A. Weijtlandtdescribes a patient, 76 years of age, who suffered from prostatic disease, which had caused complete retention of urine within a very short time. Dr. Weijtlandt treated this man successfully by diathermy applied through McCarthy’s cystoscope, and by so doing showed that this method of treatment deserves general attention as much for its thoroughness as for its simplicity and lack of danger. It is a treatment which will probably find considerable scope in the near future. I have therefore been encouraged to publish the results obtained by us at the Coolsingel Hospital in the treatment of prostatic diseases with electrocoagulation, although we are well aware of the fact that the time that has elapsed since we started this mode of treatment is altogether too short for us to regard the results obtained as final. The provisional outcome, however, is so encouraging that others might find it worth while to add this new application
number of months and who showed all the symptoms of a prostatic hypertrophy dating from a long time back. One of them had been operated upon for diverticulum of the bladder and vesical calculi. Both were suffering from emphysema of the lungs, arterio-sclerosis, and cystitis. The complete retention had persisted, notwithstanding dieting, irrigation of the bladder, and the self-retaining catheter. One had a small, the other a large, prostate. Both suffered from boils and showed a high urea percentage in their blood. In February, 1927, we coagulated the prostate in both cases ; the patient with the enlarged prostate was submitted to two subsequent treatments in February and March ; the patient with the small prostate was given one more treatment, but not until May, because he had developed an epididymitis. Both patients left the hospital in good condition, able to pass water spontaneously, although a small amount of residual urine still remained.