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Rheumatic Fever: a Summary of Present-Day Concepts
RHEUMATIC FEVER: A SUMMARY OF PRESENT-DAY CONCEPTS
ARLIE R. BARNES THE prevalence of rheumatic fever in the armed forces has emphasized again that it is a major medical problem. The decision had to be reached not to reject for military service those individuals who had had an attack of rheumatic fever provided evidence of heart disease was absent. Since an attack of rheumatic fever is evidence that the selectee is a "susceptible" and hence bears a greater than average liability of recurrence of rheumatic fever, such a plan is not ideal from a public health point of view. However, administrative problems involved in the rejection of such selectees appeared to make their exclusion impractical. The medical personnel of the armed services is confronted with the problem of diagnosis and prevention of rheumatic fever and of the disposal of those individuals who have an attack while in the service. EPIDEMIOLOGY
Rheumatic fever occurs most commonly in childhood and adolescence, the average time of the first attack being in the seventh or eighth year of life. A distinct familial incidence is conceded, in which respect the disease is like tuberculosis. Wilson, 7 and others have presented much evidence that heredity isa very important factor in predisposing to its occurrence. Much evidence is available that there are marked sectional and climatic differences in the incidence of rheumatic fever. The disease has a high incidence in the Rocky Mountain and New England states but fewer cases occur in the warmer southern portion of the United States.. The disease has its lowest incidence in the summer months and its greatest prevalence in the cold and wet months of the year. Rheumatic fever is believed to be more common among the less favored economic groups in which the ill t~d, the ill clothed and the ill housed are included. Wilson did not find this to be true and the British Medical Research Counci15 did not find this economic factor to be of prime importance in the occurrence of the disease. Rheumatic fever should b~ regarded as an epidemic disease. There is a close association of initial and recurrent attacks of rheumatic fever and infections caused by hemolytic streptococci. If careful sampling of throat cultures of new recruits reveals a high incidence of infection due to hemolytic streptococci, the prediction may be made that rheumatic fever will appear in the group in considerable incidence in from ten days to three weeks (Massell and Jones4 ). A considerable number of patients known to be susceptible to. rheumatic fever and exposed to such an epidemic likewise will have a recurrence of the disease. 923
924
ARLIE R. BARNES
ETlOLOGY
At the present time the cause of rheumatic fever is unknown. Much evidence suggests a causal relation with hemolytic streptococci. Also, there is much to indicate that allergic reactions play an important role in its production. Investigators postulate an individual in a state of hypervulnerability or allergic irritability (Swift, Derick and Hitchcock 6 ) or they conceive that the disease results from an allergic response of tissues which have been sensitized previously by a specific or nonspecific streptococcic infection. 7 The occurrence of group A beta-hemolytic streptococci in respiratory infections, which frequently precede rheumatic fever, is well established according to Massell and J ones but the specific relation of these organisms to rheumatic fever awaits experimental reproduction of the disease. DIAGNOSIS
The diagnosis of rheumatic fever presents real difficulty at times. One has to guard against the error of dismissing minor evidences of the disease with consequent failure to recognize the disease on the one hand, and, on the other, the error of concluding that rheumatic fever exists on the basis of inadequate clinical grounds with all the unfortunate consequences which such a mistaken diagnosis entails. The diagnosis of rheumatic fever probably rests on a sound basis if several of the following manifestations are present in a case (Jones 2 ): 1. Carditis. Evidence of carditis is definite cardiac enlargement, significant cardiac murmurs, pericarditis or congestive heart failure. Electrocardiographic changes which include prolongation of the auriculoventricular conduction time, inversion of the T waves and the peculiar elevation of the S-T junction (pericarditis) are important evidence of myocardial injury and constitute corroborative evidence of carditis. 2. Arthralgia. Tender, red, swollen joints, particularly if there is a migratory character to their involvement, are strongly suggestive of rheumatic fever. However, as Jones remarked, in cases in which this manifestation constitutes the only symptom one must remain skeptical. 3. Chorea. Since chorea develops in half of the cases of rheumatic fever in which the patients are young persons and since definite evidence of rheumatic fever (Jones) eventually develops in threefourths of the cases of chorea, this symptom is very important, when present, in corroborating the diagnosis. 4. Recurrence of rheumatic fever. The presence of mild symptoms of rheumatic fever occurring in an individual with a definite history of the disease or signs of rheuma~ic heart disease are very significant evidence for a positive diagnOSIS.
Not every patient who has rheumatic fever has the combined symptoms of respiratory infection with sore throat, migratory swelling and redness of the joints, chorea and fever. There are many cases in which respiratory infection and sore throat are followed only by vague
RHEUMATIC FEVER
925
articular pains with perhaps only one or two joints involved and with little redness or swelling of a very transitory nature. This articular involvement may be so slight as to be overlooked by the patient and physician unless a high index of suspicion of rheumatic fever is entertained. A low-grade fever, which may not exceed 1.5° F., may persist longer than would be expected with the usual infection of the upper part of the respiratory tract. In such cases rheumatic fever must be suspected and the patients must be kept under observation for a considerable time. This is especially important if the patient is one of a group in which an epidemic infection with beta-hemolytic streptococci or an epidemic of scarlet fever is known to exist or if the patient is one of a group in which an epidemic of rheumatic fever is prevalent. When such patients are kept under observation the sedimentation rate of the erythrocytes may remain elevated, electrocardiographic evidence of delayed auriculoventricular conduction may appear and evidence of cardiac involvement in the form of significant murmurs, pericarditis and cardiac enlargement eventually may appear. Unless more suspicion is attached to these innocent attacks in young adults, many instances of rheumatic fever will be overlooked and many patients will be deprived of a proper convalescent program which would afford them the maximal protection from serious cardiac damage. It must be emphasized that an unwarranted diagnosis of rheumatic fever should not be made. The connotation of an unwarranted diagnosis is such that, although the diagnosis later is disproved, the patient is left with a cardiac neurosis that it is next to impossible to eradicate in many instances. Since other diseases, such as rheumatoid arthritis, tuberculosis, lupus erythematosis and undulant fever, to mention only a few, may give rise to symptoms simulating rheumatic fever, observation of the patients for months or years may be required to arrive at a true diagnosis (Jones). TREATMENT
Rest still remains the essence of the treatment of rheumatic fever. Its optimal duration is scarcely the same in any two cases but certainly it must be continued until fever and involvement of the joints disappear, until the sedimentation rate is normal and until the electrocardiographic changes have disappeared. Persistent cardiac enlargement or any evidence of myocardial failure are indications for prolonged rest. Salicylates administered by mouth in large doses reduce the fever and relieve pain but there is no evidence that they shorten the attack. Recently, Coburn1 has advised the intravenous administration of large amounts of salicylates with a view to maintaining a high concentration of the drug in the blood stream. His preliminary observations arouse hopes that this method may be very effective, but further ex-
926
ARLIE R. BARNES
perience with this type of treatment will be required to determine and establish its efficacy. PREVENTION OF RHEUMATIC FEVER
The work of Jones 3 indicates the close relation that exists between certain outbreaks of respiratory infection in which hemolytic streptococci are concerned and the subsequent development of rheumatic fever in many of the individuals so infected. It is only by careful bacteriologic studies that the evidence of a high incidence of hemolytic streptococci in individuals with respiratory infection can be established. Once the presence of these organisms is established, segregation may be feasible. There is evidence that the spread of infection is particularly prone to occur during sleeping hours and especially when large numbers of people are sleeping in a single room. It is not known as yet whether the administration of sulfonamide drugs to groups of people known to harbor hemolytic streptococci in their respiratory passages will reduce the likelihood of contagion or prevent the occurrence of rheumatic fever subsequently in individuals so infected. However, this is an approach that is receiving careful study. Jones said that there is some evidence that the daily administration of salicylates, starting at the time of a respiratory infection with hemolytic strepococci,may in some way greatly decrease the probability that rheumatic fever will develop subsequently. Just as susceptibility of individuals and families to rheumatic fever is an accepted fact, it also can be said that one who has had rheumatic fever is more liable to a subsequent attack. It appears, moreover, that such an individual runs his greatest hazard if he acquires a respiratory infection due to hemolytic streptococci. There are numerous reports, hard to evaluate it is true, indicating that the daily administration of a sulfonamide drug to such an individual greatly limits such respiratory infections and hence reduces his chance of having a recurrent infection with rheumatic fever. To offset the possible advantages of such a program is the danger of developing drug sensitivity and drug fast strains so that its adoption on a large scale must await much more study of not only its effectiveness but of its possible dangers. Some effort can be made to minimize the exposure of persons who have had rheumatic fever to respiratory infection and particularly to infections due to hemolytic streptococci. The studies of the British Medical Research Council and of Wilson indicate that recurrences are less common among persons who are well housed, well clothed and well fed. There is considerable evidence that recurrences are diminished if the patient can be moved to a warmer and possibly drier climate. This procedure has been utilized by the armed services but it is not as feasible for the civilian population for economic reasons. It is desirable that susceptible soldiers not be quartered with new recruits, among whom epidemics of respiratory infections are common in the
RHEUMA TIC FEVER
927
first few weeks after induction. Whenever possible, individual sleeping quarters or sleeping quarters with only one other person reduce the chances that a susceptible individual will acquire a respiratory infection. INSTRUCTION OF PATIENTS WHO HAVE RECOVERED FROM RHEUMATIC FEVER
One of the gravest responsibilities that confronts a physician is the advice he gives a patient who has recovered from rheumatic fever. Physicians are seeing too many civilians, and particularly too many discharged soldiers, who have derived wittingly or unwittingly nothing but hopelessness from this advice. It is difficult to disabuse their mind of its anxieties, and without such corrective measures these individuals become confirmed cardiac neurotics and suffer far more from this neurosis than they ever will from their heart disease. It is well to bear in mind that only a small percentage of patients who have had rheumatic fever become disabled by heart disease and succumb by mid-adult life. Since this observation applies to children and since the incidence of serious heart disease following rheumatic fever which occurs first in adult life appears to be less than it is in children, it is with these adults that one should be particularly careful that the matter is presented in a proper manner. If they recover with a heart that is normal in size, notwithstanding the fact that they may have a cardiac murmur, it should be pointed out to them that such a situation is usually compatible with a life of normal activity and usefulness provided they do not have one or more recurrent rheumatic infections. They should be warned that their special problem is the avoidance of, and the meticulous care of, respiratory infections. Although physicians do not know as much about the prevention of such infections as can be hoped that the future will provide, the patients can be warned against conditions of exposure, unnecessary exposure in crowds during epidemics of respiratory infection, loss of sleep and all other unhygienic measures which are believed to lower resistance. If feasible, they may be advised that residence in the warmer or drier latitudes of the United States will afford some measure of protection. Above all, physicians have an obligation to orient the patient to his illness and its relation to his future life so that one more will not be added to the already overlarge population of neurotics. SUMMARY
Rheumatic fever is a huge problem not only in civilian life but in the armed forces. It is a disease in which individual and familial susceptibility plays a large role. It is related to climatic conditions and is prevalent at that time of year when respiratory infections attain their greatest proportions. Although its cause is not known, there are many facts which suggest that it follows in the wake of respiratory infection due to hemolytic streptococci. The clue to the prevention of initial and recurrent attacks may lie in a more precise knowledge of
ARLTE R. BARNES
this relationship and in measures which may permit physicians to prevent rheumatic fever once they know that respiratory infections due to hemolytic streptococci are at hand. It is possible that the sulfonamide drugs, salicylates or other drugs yet unknown will be found either to limit the incidence of such respiratory infections or provide a cure for rheumatic fever itself. Certainly, more productive investigation of these possibilities is being stimulated by the problems presented in the armed services. Too much emphasis cannot be directed to the responsibilities physicians have to instruct all who have recovered satisfactorily from rheumatic fever in such a way that they do not become cardiac neurotics. Such an attitude in these patients is tragic and easily can be avoided if only a little time is taken with each patient to orient him in a proper outlook on his situation. REFERENCES 1. Coburn, A. F.: Salicylate therapy in rheumatic fever; rational technique. Bull.
Johns Hopkins Hosp. 73:435-464 (Dec.) 1943. 2. Jones, T. D.: The diagnosis of rheumatic fever. J.A.M.A. 126:481---484 (Oct. 21) 1944.
3. Jones, T. D.: Personal communication to the author. 4. Massell, B. F. and Jones, T. D.: Some practical aspects of the rheumatic fever problem which have an important bearing in military medicine. Am. Heart J. 27:575-587 (Apr.) 1944. 5. Medical Research Council: Child life investigations; social conditions and acute rheumatism. Special Report Series, No. 114, London, 1927, 108 pp. 6. Swft, H. F., Derick, C. L. and Hitchcock, C. H.: Rheumatic fever as a manifestation of hypersensitiveness (allergy or hyperergy) to streptococci. Tr. A. Am. Physicians 43:192-202, 1928. 7. Wilson, May G.: Rheumatic fever; studies of the epidemiology, manifestations, diagnosis, and treatment of the disease during the first three decades. New York, The Commonwealth Fund, 1940.595 pp.
ARLIE R. BARNES THE prevalence of rheumatic fever in the armed forces has emphasized again that it is a major medical problem. The decision had to be reached not to reject for military service those individuals who had had an attack of rheumatic fever provided evidence of heart disease was absent. Since an attack of rheumatic fever is evidence that the selectee is a "susceptible" and hence bears a greater than average liability of recurrence of rheumatic fever, such a plan is not ideal from a public health point of view. However, administrative problems involved in the rejection of such selectees appeared to make their exclusion impractical. The medical personnel of the armed services is confronted with the problem of diagnosis and prevention of rheumatic fever and of the disposal of those individuals who have an attack while in the service. EPIDEMIOLOGY
Rheumatic fever occurs most commonly in childhood and adolescence, the average time of the first attack being in the seventh or eighth year of life. A distinct familial incidence is conceded, in which respect the disease is like tuberculosis. Wilson, 7 and others have presented much evidence that heredity isa very important factor in predisposing to its occurrence. Much evidence is available that there are marked sectional and climatic differences in the incidence of rheumatic fever. The disease has a high incidence in the Rocky Mountain and New England states but fewer cases occur in the warmer southern portion of the United States.. The disease has its lowest incidence in the summer months and its greatest prevalence in the cold and wet months of the year. Rheumatic fever is believed to be more common among the less favored economic groups in which the ill t~d, the ill clothed and the ill housed are included. Wilson did not find this to be true and the British Medical Research Counci15 did not find this economic factor to be of prime importance in the occurrence of the disease. Rheumatic fever should b~ regarded as an epidemic disease. There is a close association of initial and recurrent attacks of rheumatic fever and infections caused by hemolytic streptococci. If careful sampling of throat cultures of new recruits reveals a high incidence of infection due to hemolytic streptococci, the prediction may be made that rheumatic fever will appear in the group in considerable incidence in from ten days to three weeks (Massell and Jones4 ). A considerable number of patients known to be susceptible to. rheumatic fever and exposed to such an epidemic likewise will have a recurrence of the disease. 923
924
ARLIE R. BARNES
ETlOLOGY
At the present time the cause of rheumatic fever is unknown. Much evidence suggests a causal relation with hemolytic streptococci. Also, there is much to indicate that allergic reactions play an important role in its production. Investigators postulate an individual in a state of hypervulnerability or allergic irritability (Swift, Derick and Hitchcock 6 ) or they conceive that the disease results from an allergic response of tissues which have been sensitized previously by a specific or nonspecific streptococcic infection. 7 The occurrence of group A beta-hemolytic streptococci in respiratory infections, which frequently precede rheumatic fever, is well established according to Massell and J ones but the specific relation of these organisms to rheumatic fever awaits experimental reproduction of the disease. DIAGNOSIS
The diagnosis of rheumatic fever presents real difficulty at times. One has to guard against the error of dismissing minor evidences of the disease with consequent failure to recognize the disease on the one hand, and, on the other, the error of concluding that rheumatic fever exists on the basis of inadequate clinical grounds with all the unfortunate consequences which such a mistaken diagnosis entails. The diagnosis of rheumatic fever probably rests on a sound basis if several of the following manifestations are present in a case (Jones 2 ): 1. Carditis. Evidence of carditis is definite cardiac enlargement, significant cardiac murmurs, pericarditis or congestive heart failure. Electrocardiographic changes which include prolongation of the auriculoventricular conduction time, inversion of the T waves and the peculiar elevation of the S-T junction (pericarditis) are important evidence of myocardial injury and constitute corroborative evidence of carditis. 2. Arthralgia. Tender, red, swollen joints, particularly if there is a migratory character to their involvement, are strongly suggestive of rheumatic fever. However, as Jones remarked, in cases in which this manifestation constitutes the only symptom one must remain skeptical. 3. Chorea. Since chorea develops in half of the cases of rheumatic fever in which the patients are young persons and since definite evidence of rheumatic fever (Jones) eventually develops in threefourths of the cases of chorea, this symptom is very important, when present, in corroborating the diagnosis. 4. Recurrence of rheumatic fever. The presence of mild symptoms of rheumatic fever occurring in an individual with a definite history of the disease or signs of rheuma~ic heart disease are very significant evidence for a positive diagnOSIS.
Not every patient who has rheumatic fever has the combined symptoms of respiratory infection with sore throat, migratory swelling and redness of the joints, chorea and fever. There are many cases in which respiratory infection and sore throat are followed only by vague
RHEUMATIC FEVER
925
articular pains with perhaps only one or two joints involved and with little redness or swelling of a very transitory nature. This articular involvement may be so slight as to be overlooked by the patient and physician unless a high index of suspicion of rheumatic fever is entertained. A low-grade fever, which may not exceed 1.5° F., may persist longer than would be expected with the usual infection of the upper part of the respiratory tract. In such cases rheumatic fever must be suspected and the patients must be kept under observation for a considerable time. This is especially important if the patient is one of a group in which an epidemic infection with beta-hemolytic streptococci or an epidemic of scarlet fever is known to exist or if the patient is one of a group in which an epidemic of rheumatic fever is prevalent. When such patients are kept under observation the sedimentation rate of the erythrocytes may remain elevated, electrocardiographic evidence of delayed auriculoventricular conduction may appear and evidence of cardiac involvement in the form of significant murmurs, pericarditis and cardiac enlargement eventually may appear. Unless more suspicion is attached to these innocent attacks in young adults, many instances of rheumatic fever will be overlooked and many patients will be deprived of a proper convalescent program which would afford them the maximal protection from serious cardiac damage. It must be emphasized that an unwarranted diagnosis of rheumatic fever should not be made. The connotation of an unwarranted diagnosis is such that, although the diagnosis later is disproved, the patient is left with a cardiac neurosis that it is next to impossible to eradicate in many instances. Since other diseases, such as rheumatoid arthritis, tuberculosis, lupus erythematosis and undulant fever, to mention only a few, may give rise to symptoms simulating rheumatic fever, observation of the patients for months or years may be required to arrive at a true diagnosis (Jones). TREATMENT
Rest still remains the essence of the treatment of rheumatic fever. Its optimal duration is scarcely the same in any two cases but certainly it must be continued until fever and involvement of the joints disappear, until the sedimentation rate is normal and until the electrocardiographic changes have disappeared. Persistent cardiac enlargement or any evidence of myocardial failure are indications for prolonged rest. Salicylates administered by mouth in large doses reduce the fever and relieve pain but there is no evidence that they shorten the attack. Recently, Coburn1 has advised the intravenous administration of large amounts of salicylates with a view to maintaining a high concentration of the drug in the blood stream. His preliminary observations arouse hopes that this method may be very effective, but further ex-
926
ARLIE R. BARNES
perience with this type of treatment will be required to determine and establish its efficacy. PREVENTION OF RHEUMATIC FEVER
The work of Jones 3 indicates the close relation that exists between certain outbreaks of respiratory infection in which hemolytic streptococci are concerned and the subsequent development of rheumatic fever in many of the individuals so infected. It is only by careful bacteriologic studies that the evidence of a high incidence of hemolytic streptococci in individuals with respiratory infection can be established. Once the presence of these organisms is established, segregation may be feasible. There is evidence that the spread of infection is particularly prone to occur during sleeping hours and especially when large numbers of people are sleeping in a single room. It is not known as yet whether the administration of sulfonamide drugs to groups of people known to harbor hemolytic streptococci in their respiratory passages will reduce the likelihood of contagion or prevent the occurrence of rheumatic fever subsequently in individuals so infected. However, this is an approach that is receiving careful study. Jones said that there is some evidence that the daily administration of salicylates, starting at the time of a respiratory infection with hemolytic strepococci,may in some way greatly decrease the probability that rheumatic fever will develop subsequently. Just as susceptibility of individuals and families to rheumatic fever is an accepted fact, it also can be said that one who has had rheumatic fever is more liable to a subsequent attack. It appears, moreover, that such an individual runs his greatest hazard if he acquires a respiratory infection due to hemolytic streptococci. There are numerous reports, hard to evaluate it is true, indicating that the daily administration of a sulfonamide drug to such an individual greatly limits such respiratory infections and hence reduces his chance of having a recurrent infection with rheumatic fever. To offset the possible advantages of such a program is the danger of developing drug sensitivity and drug fast strains so that its adoption on a large scale must await much more study of not only its effectiveness but of its possible dangers. Some effort can be made to minimize the exposure of persons who have had rheumatic fever to respiratory infection and particularly to infections due to hemolytic streptococci. The studies of the British Medical Research Council and of Wilson indicate that recurrences are less common among persons who are well housed, well clothed and well fed. There is considerable evidence that recurrences are diminished if the patient can be moved to a warmer and possibly drier climate. This procedure has been utilized by the armed services but it is not as feasible for the civilian population for economic reasons. It is desirable that susceptible soldiers not be quartered with new recruits, among whom epidemics of respiratory infections are common in the
RHEUMA TIC FEVER
927
first few weeks after induction. Whenever possible, individual sleeping quarters or sleeping quarters with only one other person reduce the chances that a susceptible individual will acquire a respiratory infection. INSTRUCTION OF PATIENTS WHO HAVE RECOVERED FROM RHEUMATIC FEVER
One of the gravest responsibilities that confronts a physician is the advice he gives a patient who has recovered from rheumatic fever. Physicians are seeing too many civilians, and particularly too many discharged soldiers, who have derived wittingly or unwittingly nothing but hopelessness from this advice. It is difficult to disabuse their mind of its anxieties, and without such corrective measures these individuals become confirmed cardiac neurotics and suffer far more from this neurosis than they ever will from their heart disease. It is well to bear in mind that only a small percentage of patients who have had rheumatic fever become disabled by heart disease and succumb by mid-adult life. Since this observation applies to children and since the incidence of serious heart disease following rheumatic fever which occurs first in adult life appears to be less than it is in children, it is with these adults that one should be particularly careful that the matter is presented in a proper manner. If they recover with a heart that is normal in size, notwithstanding the fact that they may have a cardiac murmur, it should be pointed out to them that such a situation is usually compatible with a life of normal activity and usefulness provided they do not have one or more recurrent rheumatic infections. They should be warned that their special problem is the avoidance of, and the meticulous care of, respiratory infections. Although physicians do not know as much about the prevention of such infections as can be hoped that the future will provide, the patients can be warned against conditions of exposure, unnecessary exposure in crowds during epidemics of respiratory infection, loss of sleep and all other unhygienic measures which are believed to lower resistance. If feasible, they may be advised that residence in the warmer or drier latitudes of the United States will afford some measure of protection. Above all, physicians have an obligation to orient the patient to his illness and its relation to his future life so that one more will not be added to the already overlarge population of neurotics. SUMMARY
Rheumatic fever is a huge problem not only in civilian life but in the armed forces. It is a disease in which individual and familial susceptibility plays a large role. It is related to climatic conditions and is prevalent at that time of year when respiratory infections attain their greatest proportions. Although its cause is not known, there are many facts which suggest that it follows in the wake of respiratory infection due to hemolytic streptococci. The clue to the prevention of initial and recurrent attacks may lie in a more precise knowledge of
ARLTE R. BARNES
this relationship and in measures which may permit physicians to prevent rheumatic fever once they know that respiratory infections due to hemolytic streptococci are at hand. It is possible that the sulfonamide drugs, salicylates or other drugs yet unknown will be found either to limit the incidence of such respiratory infections or provide a cure for rheumatic fever itself. Certainly, more productive investigation of these possibilities is being stimulated by the problems presented in the armed services. Too much emphasis cannot be directed to the responsibilities physicians have to instruct all who have recovered satisfactorily from rheumatic fever in such a way that they do not become cardiac neurotics. Such an attitude in these patients is tragic and easily can be avoided if only a little time is taken with each patient to orient him in a proper outlook on his situation. REFERENCES 1. Coburn, A. F.: Salicylate therapy in rheumatic fever; rational technique. Bull.
Johns Hopkins Hosp. 73:435-464 (Dec.) 1943. 2. Jones, T. D.: The diagnosis of rheumatic fever. J.A.M.A. 126:481---484 (Oct. 21) 1944.
3. Jones, T. D.: Personal communication to the author. 4. Massell, B. F. and Jones, T. D.: Some practical aspects of the rheumatic fever problem which have an important bearing in military medicine. Am. Heart J. 27:575-587 (Apr.) 1944. 5. Medical Research Council: Child life investigations; social conditions and acute rheumatism. Special Report Series, No. 114, London, 1927, 108 pp. 6. Swft, H. F., Derick, C. L. and Hitchcock, C. H.: Rheumatic fever as a manifestation of hypersensitiveness (allergy or hyperergy) to streptococci. Tr. A. Am. Physicians 43:192-202, 1928. 7. Wilson, May G.: Rheumatic fever; studies of the epidemiology, manifestations, diagnosis, and treatment of the disease during the first three decades. New York, The Commonwealth Fund, 1940.595 pp.