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Myopericarditis associated with Coxsackie virus infection
COMMENTS CURRENT
ON LITERATURE
Myoper icard i t is associated with Coxsackie virus infection
improved t e c h for virus isolation and identification, progress in the study of the Coxsackie viruses, both group A and group B, has been rapid. Twenty-three types of group A Coxsackie viruses have been identified which are known to be associated with a variety of clinical illnesses, such as herpangina, hand-foot-andmouth disease, aseptic meningitis, the "common cold," pneumonitis of infants, hepatitis, myositis, and infrequently a poliolike syndrome. At least 6 types of Coxsackie virus, group B, have been identified and studied which are associated with such clinical illnesses as pleurodynia, pneumonia, severe systemic infection in young infants resulting in meningoencephalitis, myocarditis, pericarditis, hepatitis, myositis, and occasionally muscle paralysis. As early as 1735, x an epidemic of febrile disease, which seems to have been similar to pleurodynia, was recorded in Schleswig-Holstein. In the mid-1800's descriptions of epidemic myalgia or pleurodynia (Bornholm disease) came from Norway, Denmark, and Iceland, x particularly an epidemic on the island of Bornholm. In Scandinavia in the 1930's the disease reached epidemic proportions, and in this instance cardiac involvement was frequently found in association with the febrile illness. 2, 3 It was not until the 1950's however, that the Coxsackie viruses were implicated definitely in the etiology of these clinical syndromes. 4-s Once a strain of Coxsackie B S I N c E T H E A D V E N T of
niques
Vol. 73, No. 6, pp. 932-935
virus had been identified definitely as the cause of Bornholm disease, the correlation between these viruses and infectious nonrheumatic heart disease became apparent. Some of the earliest observations were made on newborn infants. 9-12 Coxsackie B viruses, particularly, may induce intrauterine or neonatal infection, manifested clinically in newborn infants by evidence of acute myocarditis, and at necropsy by characteristic pathologic changes. This association was first discovered during epidemics of "flulike" illness in South Africa in which newborn infants with myo~ carditis were observed clinically. One outbreak in particular involved 10 infants with myocarditis, 6 of whom developed circulatory collapse and died. Strains of Coxsackie B3 virus were recovered from fecal specimens of 2 surviving infants. Lesions resembling those cansed by group B Coxsackie viruses were observed in suckling mice which had been inoculated with suspensions of brain tissue obtained from each of 2 of the infants who died?, it Further information concerning this infectious myocarditis in the newly born infant was obtained from instances which occurred in a maternity home in Southern Rhodesia. la Coxsackie B+ virus was recovered from fecal specimens of infants who survived, and also at necropsy from some who died. Strains of this virus were recovered also from patients in the community who were ill about the same time with pleurodynia and meningoencephalitis.
Volume 73 Number 6
Likewise, Coxsackie B4 virus was implicated as the etiologic agent in an epidemic of "summer grippe" among adults in Amsterdam (1955). 14, ~ Four fatal cases of myocarditis which occurred in newborn infants during this epidemic were investigated carefully. The clinical diagnosis of myocarditis was supported by electrocardiographic studies during life and by the demonstration at autopsy of acute interstitial myocarditis. Strains of Coxsackie B4 virus were isolated from the heart muscle of all 4 infants and in one instance from the brain, as well. Pathologic changes were apparent also in the liver, pancreas; and adrenal glands. A similar virus isolation was reported in 1956 by Kibrick and Benirschke 12 in which Coxsackie Ba virus was obtained from spinal cord tissue of an infant Who died on the seventh day of life, following delivery by cesarean section. In another instance Coxsackie B4 virus was isolated from a newborn infant with fatal myocarditis. Since these earlier observations, numerous cases of pericarditis or myocarditis caused by the Coxsackie viruses have been reported? 6 Two recent additions to the literature on this subject are interesting and informative. The Mitchell I. Rubin Festschrift issue of the ~merican Journal o[ Diseases of Children iI~cludes a contribution by Berkovich, Rodriguez-Torres, and LinY This article reports detailed virologic study of 12 children with acute myocarditis. Of the 12 children, who ranged in age from 3 months to 12 1ears, the majority were under the age of me year. All 12 showed definite clinical and ~lectrocardiographic evidence of acute non'heumatic myocarditis. Laboratory studies in i of the 12 gave strong evidence of recent ~oxsackie virus infection. In 5 of these 8 :hildren, either a Coxsackie B virus was solated, or there was significant increase, luring the clinical course, in the titer of spe9ific antibody against the strain of Coxsackie virus. In some of these patients, both of :hese findings were obtained. In the case of me child, adenovirus type 1 was recovered, md in another, an agent was isolated which s not yet identified. Coxsackie virus infection vas known to be present in the community;
Comments on current literature 9 3 3
2 of the 12 patients showed serologic evidence of recent infection with more than one strain of Coxsackie B virus. The other recent publication of interest appears in t h e British Medical Journal and comes from the Central Hospital, Kuopio, Finland, and the Virological Laboratory, State Serum Institute, Helsinki. This report by Helin, Savola, and Lapinleimu 18 describes cases of cardiac involvement observed during an epidemic of Coxsackie B virus infection. In the autumn of 1965, a widespread epidemic of Coxsackie B5 virus occurred in Finland. During the epidemic period of about 3 months a large number of patients with pleurodynia and/or meningoencephalitis were seen at the outpatient department of the Kuopio Central Hospital (530 beds), which serves a hospital district of 270,000 inhabitants. Only the most severely ill patients were admitted to the hospital: 20 patients with aseptic meningitis, 18 with carditis, 10 with severe pleurodynia, and 6 patients with evidence of central nervous system involvement, classed as possible cases of encephalitis. The 18 patients with acute myopericarditis, 12 males and 6 females, ranged in age from 8 to 65 years; however, most of these patients were young adults. The interval between the onset of signs and symptoms and admission to the hospital was usually about 10 days. Precordial pain, aggravated by movement and respiration, was present in 12 of the 18 patients before admission to the hospital. All of the patients were febrile on admission. Six showed the characteristic manifestations associated with pericarditis: chest pain, pericardial friction rub, electrocardiographic changes (RS-T changes in 9, and T changes alone in 9), and enlargement of the heart on roentgenographic examination. Changes in the electrocardiogram were observed in all 18 patients. A pericardial rub was heard in 14 patients and a pleural rub in 2 others. Clinical symptoms of cardiac insufficiency were present in 2 of the 18 patients. One patient showed signs of cardiac tamponade. In 8 of the patients, roentgenographic examination revealed enlarged heart. One patient showed linear atelectasis of the
9 34
Comments
on current literature
lower lobe of the right lung, and 2 others had pleural effusion. Five of the 18 patients had central nervous system involvement (aseptic meningitis), in addition to myopericarditis. All 18 patients recovered; in most of these patients, the duration of hospital stay was 3 to 4 weeks. Twelve were re-examined periodically for about a year following discharge from the hospital. All were symptom free, except one patient who still showed ECG changes about one year later. Important clinical and laboratory findings are included by the authors in tabular form. The erythrocyte sedimentation rate was elevated in all 18 cases. Leukocytosis (greater than 10,000 per cubic millimeter) was present in 7 of the patients. No leukopenia was observed. A differential leukocyte count was made in 15 of the 18 patients; neutrophilia was detected in 7, and in 8 the count was normal. The S G O T was considerably elevated in the case of one patient (79 Sf units), and in another, slightly elevated (41 Sf units). The antistreptolysin titer (ASO) was increased in 3 patients (greater than 200 units), and in one of the patients, it was markedly increased (1,600 units). Virus isolations were accomplished by tissue culture methods, with the use of primary human amnion cells, U-cells, an established, continuous human amnion cell line, and monkey kidney cells. Virus identification was also carried out in tissue cultures by virus neutralization tests. Likewise, the antibody response of the patient was followed by means of tissue culture neutralization tests. Coxsackie B~ virus was recovered from fecal specimens of 12 of the 18 patients. In the case of one patient, Coxsackie Ag was recovered. Antibody studies supported the etiologic findings. Attempts to isolate an etiologic agent were unsuccessful in 5 instances; in 4 of these, antibody studies pointed to the likelihood of Coxsackie B~ virus infection. One patient may have experienced recent infection with both Coxsackie B5 and As viruses. In this group of patients reported by Helin, Savola, and Lapinleimu, is males were twice as numerous as females. This incidence ratio
The ]ou'rnal o/ Pediatrics December 1968
has been reported previously. The age distribution also agrees with earlier reports, i.e., predominantly in children and young adults. Since electric potentials do not seem to be associated with the pericardium, changes in the electrocardiogram in pericarditis have been attributed to inflammation of the myocardium. For this reason, the authors favor use of the term myopericarditis in these viral infections. The elevated transaminase levels ( S G O T ) have been reported by other investigators and in the absence of overt liver involvement are thought to be suggestive of severe myocarditis. In summarizing these observations, the authors point out that the pathogenesis of viral myopericarditis is not understood fully. "Whether the heart muscle is affected directly or (as has been suggested) 19 by some sensitivity or immunity reaction, is still far from clear. ''~s The possibility that viral endocarditis also may occur, with damage to the heart valves, has been suggested? 6, 20 The possible relationship between viral myopericarditis in childhood or young adult life and the unexplained occurrence of cardiomyopathies in later life has been mentioned by a number of investigators, and many of them emphasize the need for long-term follow-up studies in patients who have experienced viral infection with cardiac manifestations early in life. RUSSELL J. BLATTNER~ M.D. ~ O U STON', TEXAS
1.
2.
3. 4.
REFERENCES Hannaeus, G.: Dissertation, Doctor of Medicine, Copenhagen, 1735: See Dalldorf, G., and Melnick, J. L.: Coxsackie viruses, chap. 19, p. 474, in Horsfall, F. L., Jr., and Tamm, I. G.: Viral and rickettsial infections of man, ed. 4, Philadelphia, 1965, J. B. Lippincott Company. Sylvest, E.: Den Bornholmske syge: Myalgia epidemica, Levin-Munksgaarde Forlag. Kobenhavn, 1933, English translation by Humphry Milford, London, 1934, Oxford University Press. Bing, H. I.: Epidemical pericarditis, Acta med. scandinav. 80: 29, 1933. Melnlck, J: L., Shaw, E. W., and Curnen, E. C.: A virus isolated from patients diagnosed as non-paralytic poliomyelitis or aseptic meningitis, Proc. Soc. Exper. Biol. & Med. 71: 344, 1949.
C o m m e n t s on current literature
Volume 73 Number 6
5. Curnen, E. C., Shaw, E. W., and Melnick, J. L.: Disease resembling non-paralytic poliomyelitis associated with a virus pathogenic for infant mice, J. A. M. A. 141: 894, 1949. 6. Weller, T. H., Enders, J. F., Buckingham, M., and Finn, J. J.: The etiology of epidemic pleurodynia: A study of two viruses isolated from a typical outbreak, J. Immunol. 65: 337, 1950. 7. Fletcher, E., and Brennan, C. F.: Cardiac complications of Coxsackie virus infection, Lancet 1: 913, 1957. 8. Weinstein, S. B.: Acute pericarditis associated with Coxsackie virus, group B, type 5, New England J. Med. 257: 265, 1957. 9. Gear, J., and Measroch, V.: Cases of meningoencephalitis due to Coxsackie-A like ECHO9 virus, S. African M. J. 32: 1062, 1958. i0. Gear, J., Measroch, V., and Prinsloo, F. R.: The medical and public health importance of the Coxsackie viruses, S. African M. J. 30: 806, 1956. 1I. Javett, S. N., I-Ieymann, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J., Measroch, V., and Kitsch, Z. : Myocarditis in the newborn infant: A study of an outbreak associated with Coxsackie grou p B virus infection in a maternity home in Johannesburg, J. PEDIAT. 48: 1, 1956. t2. Kibrick, S., and Benirsehke, K.: Acute aseptic myocarditis and meningoencephalitis in the
13.
14.
15.
16. 17.
18. 19. 20.
935
newborn child infected with Coxsackie virus, group B, type 3, New England J. Med. 255. 883, 1956. Montgomery, J., Gear, J., Prinsloo, F. R., Kahn, M., and Kirsch, Z.: Myocarditis of the newborn: An outbreak in a maternity home associated with Coxsackie group B virus infection, S. African M. J. 29: 608, 1955. van Creveld, S., and de Jager, H.: Myocarditis in newborns caused by Coxsackie virus: Clinical and pathological data, Ann. Paediat. 187: 100, 1956. Verllnde, J. D., van Tongeren, H. A. E., and Kret, A.: Myocarditis in newborns due to Coxsackie B virus: Virus studies, Ann. Paediat. 187: 113, 1956. Smith, W. G.: Adult heart disease due to Coxsackie virus group B, Brit. Heart J. 28: 204, 1966. Berkovich, S., Rodriguez-Torres, R., and Lin, J.-S.: Virologic studies in children with acute myocarditis, Am. J. Dis. Child. 115: 207, 1968. Helin, M., Savola, J., and Lapinleimu, K.: Cardiac manifestations during a Coxsackie B~ epidemic, Brit. M. J. B: 97, t968. Sanders, V.: Viral myocarditis, Am. Heart J. 66: 707, 1963. Burch, G. E., and DePasquale, N. P.: Viral endocarditis, Am. Heart J. 67: 721, 1964.
ON LITERATURE
Myoper icard i t is associated with Coxsackie virus infection
improved t e c h for virus isolation and identification, progress in the study of the Coxsackie viruses, both group A and group B, has been rapid. Twenty-three types of group A Coxsackie viruses have been identified which are known to be associated with a variety of clinical illnesses, such as herpangina, hand-foot-andmouth disease, aseptic meningitis, the "common cold," pneumonitis of infants, hepatitis, myositis, and infrequently a poliolike syndrome. At least 6 types of Coxsackie virus, group B, have been identified and studied which are associated with such clinical illnesses as pleurodynia, pneumonia, severe systemic infection in young infants resulting in meningoencephalitis, myocarditis, pericarditis, hepatitis, myositis, and occasionally muscle paralysis. As early as 1735, x an epidemic of febrile disease, which seems to have been similar to pleurodynia, was recorded in Schleswig-Holstein. In the mid-1800's descriptions of epidemic myalgia or pleurodynia (Bornholm disease) came from Norway, Denmark, and Iceland, x particularly an epidemic on the island of Bornholm. In Scandinavia in the 1930's the disease reached epidemic proportions, and in this instance cardiac involvement was frequently found in association with the febrile illness. 2, 3 It was not until the 1950's however, that the Coxsackie viruses were implicated definitely in the etiology of these clinical syndromes. 4-s Once a strain of Coxsackie B S I N c E T H E A D V E N T of
niques
Vol. 73, No. 6, pp. 932-935
virus had been identified definitely as the cause of Bornholm disease, the correlation between these viruses and infectious nonrheumatic heart disease became apparent. Some of the earliest observations were made on newborn infants. 9-12 Coxsackie B viruses, particularly, may induce intrauterine or neonatal infection, manifested clinically in newborn infants by evidence of acute myocarditis, and at necropsy by characteristic pathologic changes. This association was first discovered during epidemics of "flulike" illness in South Africa in which newborn infants with myo~ carditis were observed clinically. One outbreak in particular involved 10 infants with myocarditis, 6 of whom developed circulatory collapse and died. Strains of Coxsackie B3 virus were recovered from fecal specimens of 2 surviving infants. Lesions resembling those cansed by group B Coxsackie viruses were observed in suckling mice which had been inoculated with suspensions of brain tissue obtained from each of 2 of the infants who died?, it Further information concerning this infectious myocarditis in the newly born infant was obtained from instances which occurred in a maternity home in Southern Rhodesia. la Coxsackie B+ virus was recovered from fecal specimens of infants who survived, and also at necropsy from some who died. Strains of this virus were recovered also from patients in the community who were ill about the same time with pleurodynia and meningoencephalitis.
Volume 73 Number 6
Likewise, Coxsackie B4 virus was implicated as the etiologic agent in an epidemic of "summer grippe" among adults in Amsterdam (1955). 14, ~ Four fatal cases of myocarditis which occurred in newborn infants during this epidemic were investigated carefully. The clinical diagnosis of myocarditis was supported by electrocardiographic studies during life and by the demonstration at autopsy of acute interstitial myocarditis. Strains of Coxsackie B4 virus were isolated from the heart muscle of all 4 infants and in one instance from the brain, as well. Pathologic changes were apparent also in the liver, pancreas; and adrenal glands. A similar virus isolation was reported in 1956 by Kibrick and Benirschke 12 in which Coxsackie Ba virus was obtained from spinal cord tissue of an infant Who died on the seventh day of life, following delivery by cesarean section. In another instance Coxsackie B4 virus was isolated from a newborn infant with fatal myocarditis. Since these earlier observations, numerous cases of pericarditis or myocarditis caused by the Coxsackie viruses have been reported? 6 Two recent additions to the literature on this subject are interesting and informative. The Mitchell I. Rubin Festschrift issue of the ~merican Journal o[ Diseases of Children iI~cludes a contribution by Berkovich, Rodriguez-Torres, and LinY This article reports detailed virologic study of 12 children with acute myocarditis. Of the 12 children, who ranged in age from 3 months to 12 1ears, the majority were under the age of me year. All 12 showed definite clinical and ~lectrocardiographic evidence of acute non'heumatic myocarditis. Laboratory studies in i of the 12 gave strong evidence of recent ~oxsackie virus infection. In 5 of these 8 :hildren, either a Coxsackie B virus was solated, or there was significant increase, luring the clinical course, in the titer of spe9ific antibody against the strain of Coxsackie virus. In some of these patients, both of :hese findings were obtained. In the case of me child, adenovirus type 1 was recovered, md in another, an agent was isolated which s not yet identified. Coxsackie virus infection vas known to be present in the community;
Comments on current literature 9 3 3
2 of the 12 patients showed serologic evidence of recent infection with more than one strain of Coxsackie B virus. The other recent publication of interest appears in t h e British Medical Journal and comes from the Central Hospital, Kuopio, Finland, and the Virological Laboratory, State Serum Institute, Helsinki. This report by Helin, Savola, and Lapinleimu 18 describes cases of cardiac involvement observed during an epidemic of Coxsackie B virus infection. In the autumn of 1965, a widespread epidemic of Coxsackie B5 virus occurred in Finland. During the epidemic period of about 3 months a large number of patients with pleurodynia and/or meningoencephalitis were seen at the outpatient department of the Kuopio Central Hospital (530 beds), which serves a hospital district of 270,000 inhabitants. Only the most severely ill patients were admitted to the hospital: 20 patients with aseptic meningitis, 18 with carditis, 10 with severe pleurodynia, and 6 patients with evidence of central nervous system involvement, classed as possible cases of encephalitis. The 18 patients with acute myopericarditis, 12 males and 6 females, ranged in age from 8 to 65 years; however, most of these patients were young adults. The interval between the onset of signs and symptoms and admission to the hospital was usually about 10 days. Precordial pain, aggravated by movement and respiration, was present in 12 of the 18 patients before admission to the hospital. All of the patients were febrile on admission. Six showed the characteristic manifestations associated with pericarditis: chest pain, pericardial friction rub, electrocardiographic changes (RS-T changes in 9, and T changes alone in 9), and enlargement of the heart on roentgenographic examination. Changes in the electrocardiogram were observed in all 18 patients. A pericardial rub was heard in 14 patients and a pleural rub in 2 others. Clinical symptoms of cardiac insufficiency were present in 2 of the 18 patients. One patient showed signs of cardiac tamponade. In 8 of the patients, roentgenographic examination revealed enlarged heart. One patient showed linear atelectasis of the
9 34
Comments
on current literature
lower lobe of the right lung, and 2 others had pleural effusion. Five of the 18 patients had central nervous system involvement (aseptic meningitis), in addition to myopericarditis. All 18 patients recovered; in most of these patients, the duration of hospital stay was 3 to 4 weeks. Twelve were re-examined periodically for about a year following discharge from the hospital. All were symptom free, except one patient who still showed ECG changes about one year later. Important clinical and laboratory findings are included by the authors in tabular form. The erythrocyte sedimentation rate was elevated in all 18 cases. Leukocytosis (greater than 10,000 per cubic millimeter) was present in 7 of the patients. No leukopenia was observed. A differential leukocyte count was made in 15 of the 18 patients; neutrophilia was detected in 7, and in 8 the count was normal. The S G O T was considerably elevated in the case of one patient (79 Sf units), and in another, slightly elevated (41 Sf units). The antistreptolysin titer (ASO) was increased in 3 patients (greater than 200 units), and in one of the patients, it was markedly increased (1,600 units). Virus isolations were accomplished by tissue culture methods, with the use of primary human amnion cells, U-cells, an established, continuous human amnion cell line, and monkey kidney cells. Virus identification was also carried out in tissue cultures by virus neutralization tests. Likewise, the antibody response of the patient was followed by means of tissue culture neutralization tests. Coxsackie B~ virus was recovered from fecal specimens of 12 of the 18 patients. In the case of one patient, Coxsackie Ag was recovered. Antibody studies supported the etiologic findings. Attempts to isolate an etiologic agent were unsuccessful in 5 instances; in 4 of these, antibody studies pointed to the likelihood of Coxsackie B~ virus infection. One patient may have experienced recent infection with both Coxsackie B5 and As viruses. In this group of patients reported by Helin, Savola, and Lapinleimu, is males were twice as numerous as females. This incidence ratio
The ]ou'rnal o/ Pediatrics December 1968
has been reported previously. The age distribution also agrees with earlier reports, i.e., predominantly in children and young adults. Since electric potentials do not seem to be associated with the pericardium, changes in the electrocardiogram in pericarditis have been attributed to inflammation of the myocardium. For this reason, the authors favor use of the term myopericarditis in these viral infections. The elevated transaminase levels ( S G O T ) have been reported by other investigators and in the absence of overt liver involvement are thought to be suggestive of severe myocarditis. In summarizing these observations, the authors point out that the pathogenesis of viral myopericarditis is not understood fully. "Whether the heart muscle is affected directly or (as has been suggested) 19 by some sensitivity or immunity reaction, is still far from clear. ''~s The possibility that viral endocarditis also may occur, with damage to the heart valves, has been suggested? 6, 20 The possible relationship between viral myopericarditis in childhood or young adult life and the unexplained occurrence of cardiomyopathies in later life has been mentioned by a number of investigators, and many of them emphasize the need for long-term follow-up studies in patients who have experienced viral infection with cardiac manifestations early in life. RUSSELL J. BLATTNER~ M.D. ~ O U STON', TEXAS
1.
2.
3. 4.
REFERENCES Hannaeus, G.: Dissertation, Doctor of Medicine, Copenhagen, 1735: See Dalldorf, G., and Melnick, J. L.: Coxsackie viruses, chap. 19, p. 474, in Horsfall, F. L., Jr., and Tamm, I. G.: Viral and rickettsial infections of man, ed. 4, Philadelphia, 1965, J. B. Lippincott Company. Sylvest, E.: Den Bornholmske syge: Myalgia epidemica, Levin-Munksgaarde Forlag. Kobenhavn, 1933, English translation by Humphry Milford, London, 1934, Oxford University Press. Bing, H. I.: Epidemical pericarditis, Acta med. scandinav. 80: 29, 1933. Melnlck, J: L., Shaw, E. W., and Curnen, E. C.: A virus isolated from patients diagnosed as non-paralytic poliomyelitis or aseptic meningitis, Proc. Soc. Exper. Biol. & Med. 71: 344, 1949.
C o m m e n t s on current literature
Volume 73 Number 6
5. Curnen, E. C., Shaw, E. W., and Melnick, J. L.: Disease resembling non-paralytic poliomyelitis associated with a virus pathogenic for infant mice, J. A. M. A. 141: 894, 1949. 6. Weller, T. H., Enders, J. F., Buckingham, M., and Finn, J. J.: The etiology of epidemic pleurodynia: A study of two viruses isolated from a typical outbreak, J. Immunol. 65: 337, 1950. 7. Fletcher, E., and Brennan, C. F.: Cardiac complications of Coxsackie virus infection, Lancet 1: 913, 1957. 8. Weinstein, S. B.: Acute pericarditis associated with Coxsackie virus, group B, type 5, New England J. Med. 257: 265, 1957. 9. Gear, J., and Measroch, V.: Cases of meningoencephalitis due to Coxsackie-A like ECHO9 virus, S. African M. J. 32: 1062, 1958. i0. Gear, J., Measroch, V., and Prinsloo, F. R.: The medical and public health importance of the Coxsackie viruses, S. African M. J. 30: 806, 1956. 1I. Javett, S. N., I-Ieymann, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J., Measroch, V., and Kitsch, Z. : Myocarditis in the newborn infant: A study of an outbreak associated with Coxsackie grou p B virus infection in a maternity home in Johannesburg, J. PEDIAT. 48: 1, 1956. t2. Kibrick, S., and Benirsehke, K.: Acute aseptic myocarditis and meningoencephalitis in the
13.
14.
15.
16. 17.
18. 19. 20.
935
newborn child infected with Coxsackie virus, group B, type 3, New England J. Med. 255. 883, 1956. Montgomery, J., Gear, J., Prinsloo, F. R., Kahn, M., and Kirsch, Z.: Myocarditis of the newborn: An outbreak in a maternity home associated with Coxsackie group B virus infection, S. African M. J. 29: 608, 1955. van Creveld, S., and de Jager, H.: Myocarditis in newborns caused by Coxsackie virus: Clinical and pathological data, Ann. Paediat. 187: 100, 1956. Verllnde, J. D., van Tongeren, H. A. E., and Kret, A.: Myocarditis in newborns due to Coxsackie B virus: Virus studies, Ann. Paediat. 187: 113, 1956. Smith, W. G.: Adult heart disease due to Coxsackie virus group B, Brit. Heart J. 28: 204, 1966. Berkovich, S., Rodriguez-Torres, R., and Lin, J.-S.: Virologic studies in children with acute myocarditis, Am. J. Dis. Child. 115: 207, 1968. Helin, M., Savola, J., and Lapinleimu, K.: Cardiac manifestations during a Coxsackie B~ epidemic, Brit. M. J. B: 97, t968. Sanders, V.: Viral myocarditis, Am. Heart J. 66: 707, 1963. Burch, G. E., and DePasquale, N. P.: Viral endocarditis, Am. Heart J. 67: 721, 1964.