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Diphtheria: A consideration of the relationship between the Klebs-Löffler and other organisms
PUBLIG HEALTH: 3ourna! of tBe 3ncorporat¢ oc|¢t t e ica! Omcera of lbealtl . Von. XV.
No. 10.
of
JTJL-~', 1908.
EDITORIAL. D I P H T H E R I A : A CONSIDERATION OF T H E RELATIONSHIP B E T W E E N THE K L E B S - L O F F L E R AND O T H E R ORGANISMS. THE disease known to us as diphtheria appears to have been prevalent, under various names, from the earliest times, but it was not until Bretonneau described an epidemic which he observed in Tours in 1818-1821 that the name " diphthgrie," from the formation of membranes, became attached to it. In the early eighties Klebs and Lhflter published the results of their bacteriological investigation of the disease, and since then it has been generally recognised that "diphtheria is a specific infectious disease due to a local infection by the Bacillt~s diphtherias." The universal acceptance of this organism as the cause of the disease has been of great service both in treatment and prophylaxis, for it has not only afforded a basis on which a rational treatment could be built up, but it has also been the means of demonstrating that a considerable number of cases in which no false membrane is found are yet due to a diphtherial infection, and hence capable of spreading the disease. Further, bacteriological investigation has also shown that the power to form a membrane is not a property possessed by the diphtheria bacillus alone, and that streptococci and staphylococci may be the only organisms present in some instances. It appears, therefore, that the only satisfactory criterion by which it can be decided that a case is or is not diphtheria is a bacteriological one, and the foundation in recent years of numerous laboratories throughout ~he country, where a bacteriological diagnosis can be made, is evidence that Ihose responsible are fully alive to this fact. In a communication published in 1887, LbfIler reported that he 38
562
T h e Relationship between the
tPab,oHealth
had isolated an organism which, while closely resembling the diphtheria bacillus morphologically, was non-pathogenic to animals. Hofmann about the same date investigated the subject, and succeeded in isolating a pseudo-diphtheria bacillus not only from the mouths of some diphtheria patients, but also from a certain proportion of healthy people. Other observers subsequently confirmed these results, and from time to time attempts have been made to decide the relationship of this organism to the Klebs-LSffier bacillus, but up to the present with no satisfactory result. Several papers in the present and recent issues of PCBLIC HEA~,Tg have again raised the question, and, in view of the importance of the subject to medical officers of health and others responsible for the control of infectious diseases, a general summary of our knowledge with regard to this question appears advisable. Two antagonistic views are held and each has numerous adherents. While on the one hand, the pseudo-diphtheria bacillus is regarded by some as a non-pathogenic involution form of the true diphtheria bacillus, capable of becoming virulent under suitable conditions, on the other it is held that there is no proof of this, and that the pseudo-diphtheria bacillus is .a distinct organism, which never, under any circumstances, can give rise to an attack of true diphtheria. The supporters of the first view quote as evidence in support of it, the fact that the pseudo-diphtheria bacillus is very frequently met with in the throats of persons convalescing from diphtheria, although relatively infrequent during the acute stage of an attack, and, further, that an epidemic of true diphtheria is sometimes preceded by a prevalence of " sore throat," due apparently to infection by the pseudo-diphtheria bacillus. It is also argued by some that infection by the Hofmann bacillus may, at least to a certain extent, act as a protective against true diphtheria. Again, it has been stated that certain of the symptoms of true diphtheria, such as irregularity and feebleness of heart action and tendency to faintness, may be detected on careful examination in cases of angina due to the pseudo.bacillus. Cases have also been quoted where one member of a family has apparently been infected with unmistakable diphtheria by another who only showed ttofmann's bacillus in cultures from the throat. In answer to these arguments it is stated, by those who oppose the view that the Hofmann bacillus is but a modified form of the Klebs-LSffler, that the two organisms may exist side by side, but that in the acute stages of diphtheria the pseudo-bacillus is generally overlooked because the typical virulent organism is in excess, and consequently easily discovered.
juay,1903j
Klebs,Loffler and other Organisms
563
On the other hand, when the diphtheria bacilli are disappearing, or have not multiplied to any extent, the pseudo-diphtheria bacillus is more.obvious, and is at once detected. Any protection afforded by an attack of apparently pseudo-diphtherial angina is attributed by them to an accompanying, but slight, true diphtherial infection. It is contended, however, that it is not the experience of most observers that Hofmann's bacillus can confer immunity against diphtheria, and it is also pointed out that diphtheria antitoxin has been found to have no effect either as a prophylactic or as a curative agent against the pseudo-diphtheria bacillus. The fact that throat affections due to ttofmann's bacillus are always mild in character, free from complication, end in recovery, and are not followed by paralysis or other sequelae of diphtheria, is also advanced as an argument in support of the non-identity of the two orgauisms. It is now, however, admitted by most clinicians who hold this view that pseudo-diphtheria is mildly infectious, especially when the environment is insanitary. Turning to the more purely bacteriological side of the question, it is necessary to point out that a good deal of the divergence of opinion of various authorities is no doubt due to lack of uniformity in description, and it is certain that, at least in the earlier days of the controversy, more than one organism was described under the name "pseudo-diphtheria bacillus." The most satisfactory description is that given by Escherich. According to him the pseudo-diphtheria bacillus, when grown on serum, occurs as rods, closely resembling the short diphtheria bacillus, but shorter and thicker. It shows less tendency to form clubs and segments, but has a marked tendency to parallel grouping, and is not virulent for guinea-pigs. The growth of the organism on glycerine agar is more profuse and spreading than that of the Klebs-LSffler bacillus, and on potato there is a fairly abundant d r y growth. When culivated in broth the pseudo-bacillus, during the first two to three days of growth, causes an increased alkalinity of the medium, best seen in glucose litmus broth, while the true diphtheria bacillus brings about a diminished alkalinity. On gelatine there is a luxuriant growth, and broth becomes rapidly turbid. Very few observers in publishing accounts, either of their bacteriological investigations of cases or laboratory experiments on this sLJbject, have stated whether the organisms they were describing complied with the conditions enumerated by Escherich, and in many cases reliance has been placed on morphological characters alone. That this is unsatisfactory is obvious when the well-known pleomorphism of the diphtheria bacillus is remembered. 38--2
564
T h e Relationship between the
~bno ao~a~
The bacteriological evidence in favour of the pseudo-diphtheria bacillus of LSfller and Itofmann being an altered diphtheria bacillus is, first, the close resemblance that exists morphologically between the short diphtheria bacillus and the pseudo-bacillus; secondly, the similarity of their growth on most media; and, thirdly, the known variation in virulence of the true diphtheria bacillus. Against this it is urged that morphological similarity does not necessarily imply bacteriological identity, for B. typhosis and B. colt, although closely resembling each other, are yet regarded as distinct organisms. Again, typical cultures of the pseudo-diphtheria bacillus differ appreciably from cultures of the true bacillus, especially on certain media, and notably in glucose litmus broth; finally, although it is admitted that a non-virulent Xlebs-LSffier bacillus is met with, under certain circumstances, this altered form still retains the other characters of the true bacillus, and can be distinguished from Hofmann's organism by suitable means. The crucial question, however, is, Can a virulent diphtheria bacillus be converted into a typical LSffler-Hofmann bacillus ? and, conversely, Can an undoubted pseudo-diphtheria bacillus be changed into a virulent Klebs-LSffler ? Several observers have published the results of their experiments in this direction, and in three instances it is claimed that their efforts have been rewarded by success. Roux and ¥ersin were the first to devote attention to the subject, and they stated that by growing a virulent cuIture under unfavourable conditions in a current of air, they were able to obtain a non-pathogenic organism which produced no toxin. As their experiments were carried out in the early days before the morphological and cultural characters of the pseudo-diphtheria bacillus had been fully worked out, too great stress must not be laid upon them ; in fact, it is probable that they only succeeded in producing a non-virulent diphtheria bacillus, and not a pseudo-bacillus at all, as we now understand the term. Later, Hewlett and Knight published experiments, in which they believed that they had transformed diphtheria bacilli into Hofmann bacilli, and had also effeeted the reverse process. But they were not successful in attempting to repeat their experiments, and it appears possible that their investigations were not carried out with pure cultures in the first instance. Still more recently, Richmond and Salter claimed to have effected a gradual transformation from the pseudodiphtheria bacillus of ttofmann to the virulent Klebs-LSffier by repeated passage through small birds, but here again attempts to repeat the experiments were not successful. This question, then, cannot be considered to have been answered
Jllly, 1903]
Klebs,L6Ifler and other Organisms
565
satisfactorily, and at present there is no conclusive evidence either one way or the other. The most that can be said is that the pseudo-diphtheria bacillus is one of a group of organisms closely allied to the true diphtheria bacillus, but differing from it in several important particulars. In this same group, but distinguished by certain cultural characters and their pathogenic effects, both from the Klebs-LSffier, and Hofmann bacilli, there are several other bacteria. The most frequently met with and best known of these latter is the B. xerosis of Neisser and Kuschbert. This organism is frequently met with in the nose and conjunetival sac, and, although similar in appearance to the short diphtheria bacillus, is non-pathogenic for animals, and can be distinguished in culture by its slow and scanty growth. Broth cultures always remain clear, and acid-production is usually absent. The bacillus appears to only accompany and not to cause the xerosis processes in the eye; in fact, it is a common inhabitant of the healthy conjunctival sac. Somewhat similar are the B. pseudo-tuberculosis o~:is of Preisz, the B. pseudotuberculvsis murium of Kutscher, and a B. pseudo-diphtheri~ of Klein. These organisms resemble the B. xerosis in their slow and scanty growth, and only differ slightly in their morphology from the short diphtheria bacillus. As already mentioned, the name "pseudo. diphtheria bacillus" originally included more than one organism, and there is no doubt that the B. xerosis, and possibly some of the other organisms named above, were frequently classified as pseudodiphtheria bacilli. In order to avoid any possibility of confusion in the future, it would be an advantage if, as Dr. Goodall "~ has suggested, the name " pseudo-diphtheria" were dropped and some other term of a non-committal character universally adopted to denote the LSffler-Hofmann pseudo-diphtheria bacillus and the angina tpwhich it gives rise. Such an understanding would clear the issue, and, while not favouring either theory as to the true relationship between the Klebs-LSffier and Hofmann bacilli, would enable different observers to compare their results. The question is of such importance to the public health, and the material for its investigation so abundant, that it is not too much to hope that if the subject were taken seriously in hand by the medical officers throughout the country, especially in those districts where a competent bacteriologist could be obtained to lend assistance in the laboratory investigations, a satisfactory solution of the difficulty would be speedily arrived at. In the meantime, since clinical experience has shown that cases of pseudo-diphtherial angina are infectious, it would be well to See p. 572 of presen~ issue.
,566 T h e Klebs.L0ffler and other Organisms
EPubn~H~th
adopt at leas~ a modified form of isolation, although it would probably be inexpedient to admit them to a general diphtheria ward. Some form of supervision, such as that advocated by Dr. J. C. Heaven in the June number of PUt, LIe H~ALTH,* appears to answer satisfactorily, and, while avoiding the expense and inconvenience attendant on isolation in hospital, serves to impress on the patien~ and his friends the infectious nature of the disease. F r e s h air and sunshine are Nature's own disinfectants, and since there is no risk of serious consequences to the patient himself in getting about, an open-air life and avoidance of close contact with other people in a vitiated atmosphere is probably the best form of treatment for such cases.
DIPHTHERIA BACILLI IN EAR DISCHARGESFOLLOWINGSCARLETFEYER. r--Dr. Duncan Forbes. gives (Journcd o~fPc~thology and• Bacteriology),. the results of the bacteriological examination during November and December, 1902, of forty post-scarlatinal ear discharges at Monsall Fever Hospital, Manchester. Thirty-two of these contained diphtheria bacilli in almost pure culture. During the five weeks in which the observations were made, a daily average of 440 scarlet fever cases were in hospital, compared with a daily average for the year of 327 cases. The hospital was comparatively crowded, and, as is usually the case, post-scarlatinal faucial diphtheria was at its maximum. The infection of the ear discharge is believed to be due to inspiration of the bacilli into the nose and their spread along the Eustachian tubes. Patients suffering from an injected ear discharge show no clinical sign of diphtheria, and seem to be immune from the subsequent faucial or laryngeal infection, and antitoxin acts neither as a prophylactic nor a curative agent. LOCAL APPLICATIONS OF DIPHTHERIA ANTITOXINS.--M. L. Martin of the Pasteur Institute has brought forward a method of treatment by employing antitoxic serum as a dressing to the false membranes of diphtheria. M. Martin obtains his serum in a different way from the method of Behring and Roux, as he injects directly into the veins of the horse the microbes of diphtheria which have been heated up to 100 ° C. The serum thus obtained has an agglutinating power very superior to that obtained by Roux's method. When this serum is applied to the diphtheritic membranes in the throat it causes them to swell, to become yellow, and quickly to fall off, and the pain is greatly diminished. In order to render the effect more prolonged 13~. Martin proposes to incorporate his serum with gum so as to form a jujube which can be slowly sucked. M. Martin hopes that this method of applying diphtheritic serum, without dispensing with the injection of serum in definite cases of diphtheria, may diminish very largely both the gravity and the duration of the malady. The use of such jujubes may act as a preventive in times of epidemic if used by persons exposed ~Q infection. PUBLIC HEALTH,V0]. XV.,p. 516.
No. 10.
of
JTJL-~', 1908.
EDITORIAL. D I P H T H E R I A : A CONSIDERATION OF T H E RELATIONSHIP B E T W E E N THE K L E B S - L O F F L E R AND O T H E R ORGANISMS. THE disease known to us as diphtheria appears to have been prevalent, under various names, from the earliest times, but it was not until Bretonneau described an epidemic which he observed in Tours in 1818-1821 that the name " diphthgrie," from the formation of membranes, became attached to it. In the early eighties Klebs and Lhflter published the results of their bacteriological investigation of the disease, and since then it has been generally recognised that "diphtheria is a specific infectious disease due to a local infection by the Bacillt~s diphtherias." The universal acceptance of this organism as the cause of the disease has been of great service both in treatment and prophylaxis, for it has not only afforded a basis on which a rational treatment could be built up, but it has also been the means of demonstrating that a considerable number of cases in which no false membrane is found are yet due to a diphtherial infection, and hence capable of spreading the disease. Further, bacteriological investigation has also shown that the power to form a membrane is not a property possessed by the diphtheria bacillus alone, and that streptococci and staphylococci may be the only organisms present in some instances. It appears, therefore, that the only satisfactory criterion by which it can be decided that a case is or is not diphtheria is a bacteriological one, and the foundation in recent years of numerous laboratories throughout ~he country, where a bacteriological diagnosis can be made, is evidence that Ihose responsible are fully alive to this fact. In a communication published in 1887, LbfIler reported that he 38
562
T h e Relationship between the
tPab,oHealth
had isolated an organism which, while closely resembling the diphtheria bacillus morphologically, was non-pathogenic to animals. Hofmann about the same date investigated the subject, and succeeded in isolating a pseudo-diphtheria bacillus not only from the mouths of some diphtheria patients, but also from a certain proportion of healthy people. Other observers subsequently confirmed these results, and from time to time attempts have been made to decide the relationship of this organism to the Klebs-LSffier bacillus, but up to the present with no satisfactory result. Several papers in the present and recent issues of PCBLIC HEA~,Tg have again raised the question, and, in view of the importance of the subject to medical officers of health and others responsible for the control of infectious diseases, a general summary of our knowledge with regard to this question appears advisable. Two antagonistic views are held and each has numerous adherents. While on the one hand, the pseudo-diphtheria bacillus is regarded by some as a non-pathogenic involution form of the true diphtheria bacillus, capable of becoming virulent under suitable conditions, on the other it is held that there is no proof of this, and that the pseudo-diphtheria bacillus is .a distinct organism, which never, under any circumstances, can give rise to an attack of true diphtheria. The supporters of the first view quote as evidence in support of it, the fact that the pseudo-diphtheria bacillus is very frequently met with in the throats of persons convalescing from diphtheria, although relatively infrequent during the acute stage of an attack, and, further, that an epidemic of true diphtheria is sometimes preceded by a prevalence of " sore throat," due apparently to infection by the pseudo-diphtheria bacillus. It is also argued by some that infection by the Hofmann bacillus may, at least to a certain extent, act as a protective against true diphtheria. Again, it has been stated that certain of the symptoms of true diphtheria, such as irregularity and feebleness of heart action and tendency to faintness, may be detected on careful examination in cases of angina due to the pseudo.bacillus. Cases have also been quoted where one member of a family has apparently been infected with unmistakable diphtheria by another who only showed ttofmann's bacillus in cultures from the throat. In answer to these arguments it is stated, by those who oppose the view that the Hofmann bacillus is but a modified form of the Klebs-LSffler, that the two organisms may exist side by side, but that in the acute stages of diphtheria the pseudo-bacillus is generally overlooked because the typical virulent organism is in excess, and consequently easily discovered.
juay,1903j
Klebs,Loffler and other Organisms
563
On the other hand, when the diphtheria bacilli are disappearing, or have not multiplied to any extent, the pseudo-diphtheria bacillus is more.obvious, and is at once detected. Any protection afforded by an attack of apparently pseudo-diphtherial angina is attributed by them to an accompanying, but slight, true diphtherial infection. It is contended, however, that it is not the experience of most observers that Hofmann's bacillus can confer immunity against diphtheria, and it is also pointed out that diphtheria antitoxin has been found to have no effect either as a prophylactic or as a curative agent against the pseudo-diphtheria bacillus. The fact that throat affections due to ttofmann's bacillus are always mild in character, free from complication, end in recovery, and are not followed by paralysis or other sequelae of diphtheria, is also advanced as an argument in support of the non-identity of the two orgauisms. It is now, however, admitted by most clinicians who hold this view that pseudo-diphtheria is mildly infectious, especially when the environment is insanitary. Turning to the more purely bacteriological side of the question, it is necessary to point out that a good deal of the divergence of opinion of various authorities is no doubt due to lack of uniformity in description, and it is certain that, at least in the earlier days of the controversy, more than one organism was described under the name "pseudo-diphtheria bacillus." The most satisfactory description is that given by Escherich. According to him the pseudo-diphtheria bacillus, when grown on serum, occurs as rods, closely resembling the short diphtheria bacillus, but shorter and thicker. It shows less tendency to form clubs and segments, but has a marked tendency to parallel grouping, and is not virulent for guinea-pigs. The growth of the organism on glycerine agar is more profuse and spreading than that of the Klebs-LSffler bacillus, and on potato there is a fairly abundant d r y growth. When culivated in broth the pseudo-bacillus, during the first two to three days of growth, causes an increased alkalinity of the medium, best seen in glucose litmus broth, while the true diphtheria bacillus brings about a diminished alkalinity. On gelatine there is a luxuriant growth, and broth becomes rapidly turbid. Very few observers in publishing accounts, either of their bacteriological investigations of cases or laboratory experiments on this sLJbject, have stated whether the organisms they were describing complied with the conditions enumerated by Escherich, and in many cases reliance has been placed on morphological characters alone. That this is unsatisfactory is obvious when the well-known pleomorphism of the diphtheria bacillus is remembered. 38--2
564
T h e Relationship between the
~bno ao~a~
The bacteriological evidence in favour of the pseudo-diphtheria bacillus of LSfller and Itofmann being an altered diphtheria bacillus is, first, the close resemblance that exists morphologically between the short diphtheria bacillus and the pseudo-bacillus; secondly, the similarity of their growth on most media; and, thirdly, the known variation in virulence of the true diphtheria bacillus. Against this it is urged that morphological similarity does not necessarily imply bacteriological identity, for B. typhosis and B. colt, although closely resembling each other, are yet regarded as distinct organisms. Again, typical cultures of the pseudo-diphtheria bacillus differ appreciably from cultures of the true bacillus, especially on certain media, and notably in glucose litmus broth; finally, although it is admitted that a non-virulent Xlebs-LSffier bacillus is met with, under certain circumstances, this altered form still retains the other characters of the true bacillus, and can be distinguished from Hofmann's organism by suitable means. The crucial question, however, is, Can a virulent diphtheria bacillus be converted into a typical LSffler-Hofmann bacillus ? and, conversely, Can an undoubted pseudo-diphtheria bacillus be changed into a virulent Klebs-LSffler ? Several observers have published the results of their experiments in this direction, and in three instances it is claimed that their efforts have been rewarded by success. Roux and ¥ersin were the first to devote attention to the subject, and they stated that by growing a virulent cuIture under unfavourable conditions in a current of air, they were able to obtain a non-pathogenic organism which produced no toxin. As their experiments were carried out in the early days before the morphological and cultural characters of the pseudo-diphtheria bacillus had been fully worked out, too great stress must not be laid upon them ; in fact, it is probable that they only succeeded in producing a non-virulent diphtheria bacillus, and not a pseudo-bacillus at all, as we now understand the term. Later, Hewlett and Knight published experiments, in which they believed that they had transformed diphtheria bacilli into Hofmann bacilli, and had also effeeted the reverse process. But they were not successful in attempting to repeat their experiments, and it appears possible that their investigations were not carried out with pure cultures in the first instance. Still more recently, Richmond and Salter claimed to have effected a gradual transformation from the pseudodiphtheria bacillus of ttofmann to the virulent Klebs-LSffier by repeated passage through small birds, but here again attempts to repeat the experiments were not successful. This question, then, cannot be considered to have been answered
Jllly, 1903]
Klebs,L6Ifler and other Organisms
565
satisfactorily, and at present there is no conclusive evidence either one way or the other. The most that can be said is that the pseudo-diphtheria bacillus is one of a group of organisms closely allied to the true diphtheria bacillus, but differing from it in several important particulars. In this same group, but distinguished by certain cultural characters and their pathogenic effects, both from the Klebs-LSffier, and Hofmann bacilli, there are several other bacteria. The most frequently met with and best known of these latter is the B. xerosis of Neisser and Kuschbert. This organism is frequently met with in the nose and conjunetival sac, and, although similar in appearance to the short diphtheria bacillus, is non-pathogenic for animals, and can be distinguished in culture by its slow and scanty growth. Broth cultures always remain clear, and acid-production is usually absent. The bacillus appears to only accompany and not to cause the xerosis processes in the eye; in fact, it is a common inhabitant of the healthy conjunctival sac. Somewhat similar are the B. pseudo-tuberculosis o~:is of Preisz, the B. pseudotuberculvsis murium of Kutscher, and a B. pseudo-diphtheri~ of Klein. These organisms resemble the B. xerosis in their slow and scanty growth, and only differ slightly in their morphology from the short diphtheria bacillus. As already mentioned, the name "pseudo. diphtheria bacillus" originally included more than one organism, and there is no doubt that the B. xerosis, and possibly some of the other organisms named above, were frequently classified as pseudodiphtheria bacilli. In order to avoid any possibility of confusion in the future, it would be an advantage if, as Dr. Goodall "~ has suggested, the name " pseudo-diphtheria" were dropped and some other term of a non-committal character universally adopted to denote the LSffler-Hofmann pseudo-diphtheria bacillus and the angina tpwhich it gives rise. Such an understanding would clear the issue, and, while not favouring either theory as to the true relationship between the Klebs-LSffier and Hofmann bacilli, would enable different observers to compare their results. The question is of such importance to the public health, and the material for its investigation so abundant, that it is not too much to hope that if the subject were taken seriously in hand by the medical officers throughout the country, especially in those districts where a competent bacteriologist could be obtained to lend assistance in the laboratory investigations, a satisfactory solution of the difficulty would be speedily arrived at. In the meantime, since clinical experience has shown that cases of pseudo-diphtherial angina are infectious, it would be well to See p. 572 of presen~ issue.
,566 T h e Klebs.L0ffler and other Organisms
EPubn~H~th
adopt at leas~ a modified form of isolation, although it would probably be inexpedient to admit them to a general diphtheria ward. Some form of supervision, such as that advocated by Dr. J. C. Heaven in the June number of PUt, LIe H~ALTH,* appears to answer satisfactorily, and, while avoiding the expense and inconvenience attendant on isolation in hospital, serves to impress on the patien~ and his friends the infectious nature of the disease. F r e s h air and sunshine are Nature's own disinfectants, and since there is no risk of serious consequences to the patient himself in getting about, an open-air life and avoidance of close contact with other people in a vitiated atmosphere is probably the best form of treatment for such cases.
DIPHTHERIA BACILLI IN EAR DISCHARGESFOLLOWINGSCARLETFEYER. r--Dr. Duncan Forbes. gives (Journcd o~fPc~thology and• Bacteriology),. the results of the bacteriological examination during November and December, 1902, of forty post-scarlatinal ear discharges at Monsall Fever Hospital, Manchester. Thirty-two of these contained diphtheria bacilli in almost pure culture. During the five weeks in which the observations were made, a daily average of 440 scarlet fever cases were in hospital, compared with a daily average for the year of 327 cases. The hospital was comparatively crowded, and, as is usually the case, post-scarlatinal faucial diphtheria was at its maximum. The infection of the ear discharge is believed to be due to inspiration of the bacilli into the nose and their spread along the Eustachian tubes. Patients suffering from an injected ear discharge show no clinical sign of diphtheria, and seem to be immune from the subsequent faucial or laryngeal infection, and antitoxin acts neither as a prophylactic nor a curative agent. LOCAL APPLICATIONS OF DIPHTHERIA ANTITOXINS.--M. L. Martin of the Pasteur Institute has brought forward a method of treatment by employing antitoxic serum as a dressing to the false membranes of diphtheria. M. Martin obtains his serum in a different way from the method of Behring and Roux, as he injects directly into the veins of the horse the microbes of diphtheria which have been heated up to 100 ° C. The serum thus obtained has an agglutinating power very superior to that obtained by Roux's method. When this serum is applied to the diphtheritic membranes in the throat it causes them to swell, to become yellow, and quickly to fall off, and the pain is greatly diminished. In order to render the effect more prolonged 13~. Martin proposes to incorporate his serum with gum so as to form a jujube which can be slowly sucked. M. Martin hopes that this method of applying diphtheritic serum, without dispensing with the injection of serum in definite cases of diphtheria, may diminish very largely both the gravity and the duration of the malady. The use of such jujubes may act as a preventive in times of epidemic if used by persons exposed ~Q infection. PUBLIC HEALTH,V0]. XV.,p. 516.