604 CAMPYLOBACTER ENTERITIS IN CENTRAL AFRICA
SIR,-Our laboratory experience1,2 prompted us to investigate the role of Campylobacter in the infantile diarrhreas of developing countries. During October, 1977, we cultured a single stool from each of 262 children living in the area of Kigali, the capital of Rwanda. Kigali has a rural appearance and has no
shantytown.
We looked for Campylobacter by inoculating the stools on sheep blood agar containing novobiocin (5 g/ml), actidione (50 g/ml), colistin (10 units/ml), cephalothin (15g/ml), and bacitracin (25 i.u./ml) and incubating it at 43 °C for 48 h. We followed the first technique described by Simmons3 for generating an appropriate atmosphere. The inoculated plates were put into a sealed jar (2.5 litres) containing an activated BBL ’Gas-Pak’, without a catalyst; this produces an atmosphere of hydrogen and carbon dioxide. There were no explosions. Parasites were sought by direct examination of the fasces. Shigella, Salmonella, and Yersinia were looked for by culture and enrichment procedures. The children investigated were all inpatients or outpatients at the department of paediatrics in the Kigali Hospital Centre (Medical Mission of the University of Brussels). There were 102 cases of gastroenteritis on ambulatory treatment, 18 healthy children coming to be vaccinated (first control group), 54 children admitted to hospital with measles (who always have some diarrhoea), 48 cases of gastroenteritis admitted to hospital, and 40 children admitted with diseases other than gastroenteritis (second control group). The pathogenicity of Campylobacter was confirmed by comparing the findings in children with diarrhoea with those in the controls (see table). The frequency with which Campylobacter was isolated (11% of those with diarrhoea) was remarkable. Among the inpatients with diarrhoea Salmonella was the most prevalent organism apart from parasites. Two explanations can be put forward: Salmonella infection might have been endemic in the hospital population (though only 3 children without diarrhoea were found to be carriers) or the gastroenteritis due to Salmonella might have been more severe and thus justified admission to hospital more frequently. Among the children with measles, the lesions in the digestive tract due to the virus may well have influenced the nature of the bacterial superinfection and so have favoured the multiplication of Salmonella. The frequency of Campylobacter was highest in children aged 12-24 months with diarrhoea, probably reflecting selfinfection with contaminated soil. Campylobacter was the agent most often found in patients whose gastroenteritis lasted more than 2 weeks or who had diarrhoea associated with violent abdominal pain. (The high proportion of children in hospital who were carrying parasites ’
reflects socioeconomic conditions in Rwanda: there was no evidence that the diarrhoeas investigated were due to parasites.) Since Campylobacter are important enteropathogemc bacteria in developing countries this organism should be identified as a target in the struggle against infantile diarrhreal disease in the third world. Laboratory of Microbiology, St. Pierre University Hospital, Brussels, Belgium, and Department of Pædiatrics, Kigali Hospital Centre Laboratory of Kigali Hospital Centre, Rwanda
P. DE MOL E. BOSMANS
CAMPYLOBACTER ENTERITIS IN BRUSSELS
SIR,-Since 1970, we have looked for Campylobacter in 22 000 specimens of human stools using the technique of filtration and culture on a selective medium, but a year ago we gave up filtration and made our medium more selective by adding to it cephalothin, which is inactive against C. jejuni. The new medium includes bacitracin (25 i.u./ml), novobiocin (5 p.g/ml), actidione (50 g/ml), colistin (10 units/mi), and cephalothin (15 g/ml). We used to incubate at 37°C because we were also looking for C. fetus, which grows very poorly at 43 °C.’’ However, we isolated C. fetus intestinalis from only 3 of 22 000 stools so we now incubate at 43 °C which allows C. jejuni to grow in 24 h instead of the 48 h or more needed at 370C. C. jejuni was isolated from 5.9% of diarrhoeal stools and from 1.3% of normal stools. Thus, as with all other enteropathogenic bacteria, there are healthy carriers. The isolationrate varies with the season in Brussels and can increase to 8-9% during July, August, and September. Positive stool cultures may be found among contacts of patients with Campylo.. bacter enteritis, and we have seen outbreaks of Campylobacter enteritis in five day-nurseries in the Brussels region. 20-50% of the infants were infected and had diarrhoea. From seven children from a creche where infection was prevalent, we were able to examine specimens aspirated from different levels of the intestinal tract. In four of the seven children Campylobacter was isolated on the same occasion from both stool and small intestine (stomach, jejunum, and ileum in one, jejunum but not ileum in another, and ileum but not jejunum in the two). All the isolates were C. jejuni, and all had the same biochemical and antigenic characters. The clinical manifestations of campylobacteriosis can vary but diarrhoea lasting several days with or without fever is the most frequent pattern. Though often trivial, the diarrhoea may sometimes be frankly watery or mucosanguinous and accom-
panied by vomiting.33
The mode of transmission of campylobacteriosis involves in1.
Butzler, J. P., Dekeyser, P., Detrain, M., Dehaen,
F. Pediatrics.
1973, 82,
493
Butzler, J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G., Paper presented at joint meeting of the British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow, in 1976. 3. Simmons, N. A. Br. med. J. 1977, ii, 707. 2.
1.
Butzler, J. P., Dekeyser, P., Detrain, M., Dehaen, F. J. Pediat. 1973, 82,
2. 3.
Butzler, J. P. Lancet, 1973, ii, 858. Skirrow, M. B. Br. med. J. 1977, ii, 9.
493.
PREVALENCE OF BACTERIA AND PARASITES IN STOOLS FROM RWANDAN CHILDREN
605 of the organism, carriage in the intestine, and then, sometimes, invasion of the bloodstream.4 Complications may also occur (toxicosis, dehydration) bur those affected-usually recover without antimicrobial treatment. Isolation of Campylobacter from the stools does not automatically imply the need for antibiotics; the decision should be taken on clinical and epidemiological grounds. Nevertheless intestinal infection may sometimes be followed by invasion of bloodstream, perhaps due to diarrhoea, modification of intestinal flora, or immunological deficiency.4 We have seen only seven cases of septicxmia in 5 years. In five of them the same Campylobacter was isolated on the same occasion from both stools and blood. Dr A. Wilson (Edinburgh) has pointed out that Campylobacter bacteraemia may be common in severe enteritis, but that we have been unaware of this because enteritis is most common in children and blood cultures -are not routine when children are admitted to hospital with fever and diarrhoea. Better knowledge of the organism and its cultural requirements may allow bacteriologists to respond to this suggestion.
gestion !
! ,.
S. LAUWERS M. DE BOECK J. P. BUTZLER
Department of Microbiology, St Pierre Hospital, 1000 Brussels, Belgium
SMOKING AND DIABETIC NEPHROPATHY
Sm,—Little is known about factors influencing the course and development of diabetic microangiopathy. One report of a possible relation between cigarette smoking and proliferative retinopathy’ is not wholly convincing because smoking and non-smoking diabetics were not sufficiently matched for type and duration of diabetes. Nephropathy, one manifestation of diabetic microangiopathy, is the most frequent cause of death in young diaPREVALENCE OF NEPHROPATHY IN SMOKING AND NON-SMOKING PATIENTS WITH
INSULIN-DEPENDENT, JUVENILE-ONSET DIABETES
significantly higher frequency of diabetic nephropathy found among cigarette smokers (table). The prevalence of hypertension did not vary with smoking habits. Since nephropathy is the most serious complication in longterm juvenile diabetes2.3 and since cigarette smoking should be avoided for other reasons it would be of interest if other groups were to confirm this observation. J. SANDAHL CHRISTIANSEN Steno Memorial Hospital, DK-2820 Gentofte, Copenhagen, Denmark J. NERUP A
was
MULTIPLE SCLEROSIS AND CANINE DISTEMPER
SiR,—An epidemiological study of familial multiple sclerosis (M.S.) suggesting a possible association between dogs and rt.s.l was criticised in your correspondence columns last year.2-6 Poskanzer et al.2 found no association between house pets and M.s. in the Orkney and Shetland Islands, although they noted that a high proportion of both control and M.s. groups were exposed to house pets. Epidemiological studies have also been done in the United States, the results suggesting an increased exposure of some M.s. patients to dogs with a distemper-likeillness before clinical onset of M.S.l,7,8 Bauer and Wikstrom3 in West Germany did not find a relationship between dogs and M.S., but again they did find more dogs thought to have distemper in the ns.s. group.’ Canine distemper virus (C.D.V.) is a paramyxovirus which can produce a neurological demyelinating disease in dogs with many similarities to M.s.9-13 Clinically distemper may be more common in cold weather,13 and these environmental conditions might increase contact between infectious dogs and man. Many of the characteristics of c.D.v. and its canine vector, in close association with man, could account for some of the geographical and cultural peculiarities seen in M.s. distribution.7,14,15 Preliminary serological studies have shown raised serum antibodies to C.D.v. in M.s. patients, as measured by immunonuorescence (a technique which, however, may not distinguish c.D.v. from other paramyxoviruses, such as measles virus).’ In view of these findings it seems possible that the development of M.s. may involve transmission of a virus from animal to man and that c..v. is a prime candidate.1.7.8,16 With this hypothesis in mind, we have been examining the apparently anomalous prevalence of M.s. in the Orkney and Shetland Islands as compared with the Faeroe Islands, particularly with respect to disease patterns of
distemper.
-
Orkney and Shetland the prevalence of M.s. is as high as 300 per 100 000 population,2 whereas in the Faeroe Islands (population 40 000) some 300 km to the north-west, no cases of M.s. were recorded from 1929 to 1943 and only 2 cases between 1960 and 1974 in the Faeroese" (who have many cultural and other similarities to the inhabitants of the Orkney and Shetland Islands). However, from 1944 to 1960 the Faeroe Islands experienced an "epidemic" of M.s. with 18 definite cases Kurtzke and Hyllesred17 suggested that these In
+C=Daily cigarette smoking for more than one year. -C=Never smoked cigarettes or cigarette smoking less than one year. tChi-square test. ’
so we have looked for a link between cigarette smokand diabetic nephropathy. The prevalence of diabetic ing nephropathy in a consecutive series of 238 insulin-dependent, juvenile-onset (before age 31) diabetics was related to current and previous smoking habits and to duration of disease. Diabetic nephropathy was defined as a raised serum-creatinine and/or persistent proteinuria without a history or clinical signs of non-diabetic renal disease. Cigarette smokers were defined as patients who had smoked at least 10 cigarettes a day for more than a year.
betics,2.3
4. Butzler,
J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G. Paper presented at joint meeting of British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow in 1976. 1. Pantkau, M. E., Boys, T. A. S., Winship, B., Grace, M. Diabetes, 1977, 26,
46. 2. Deckert, T., Poulsen, J. E., Larsen, M. Acta endocr. 1976, suppl. 203, 3. Andersen, A. R., Jensen, J. K., Christiansen, J. S., Deckert, T. ibid.
suppl. 209, p. 1.
p. 15. 1977,
1. Cook, S. D., Dowling, P. C. Lancet, 1977, i, 980. 2. Poskanzer, D. C., Prenney, L. B., Sheridan, J. L. ibid. p. 1204. 3. Bauer, H. J., Wikström, J. ibid. 1977, ii, 1029. 4. Visscher, B., Detels, R. ibid. p. 658. 5. Craelius, W., Newby, N. A. ibid. p. 565. 6. Klauber, M. R., Lyon, J. L. ibid. p. 454. 7. Cook, S. D., Natelson, B. H., Levin, B. E., Chavis, P. S., Dowling, P. C. Ann. Neurol. (in the press). 8. Jotkowitz, S. J. Am. med. Ass. 1977, 238, 854. 9. Innes, J. R. M., Saunders, L Z. Comparative Neuropathology. New York, 1962. 10. McGrath, J. T. Neurological Examination of the Dog. Philadelphia, 1960. 11. Wisniewski, H., Raine, C. S., Kay, W. J. Lab. Invest. 1972, 26, 589. 12. Adams, J. M., Brown, W. J., Snow, H. D., Lincoln, S. D., Sears, A. W., Barenfus, M., Holliday, T. A., Cremer, N. E., Lennette, E. H. Vet. Path.
1975, 12, 220. 13. Appel, M. J. G., Gillespie, J. H. Canine Distemper Virus. Austria, 1972. 14. Chan, W. W.-C. Lancet, 1977, i, 487. 15. Acheson, E. D. Multiple Sclerosis: a Reappraisal. Edinburgh, 1972. 16. Cook, S. D. Vet. Rec. 1977, 101, 314. 17. Kurtzke, J. F., Hyllested, K. Trans. Am. Neurol. Ass. 1975, 100, 213.
SIR,-Our laboratory experience1,2 prompted us to investigate the role of Campylobacter in the infantile diarrhreas of developing countries. During October, 1977, we cultured a single stool from each of 262 children living in the area of Kigali, the capital of Rwanda. Kigali has a rural appearance and has no
shantytown.
We looked for Campylobacter by inoculating the stools on sheep blood agar containing novobiocin (5 g/ml), actidione (50 g/ml), colistin (10 units/ml), cephalothin (15g/ml), and bacitracin (25 i.u./ml) and incubating it at 43 °C for 48 h. We followed the first technique described by Simmons3 for generating an appropriate atmosphere. The inoculated plates were put into a sealed jar (2.5 litres) containing an activated BBL ’Gas-Pak’, without a catalyst; this produces an atmosphere of hydrogen and carbon dioxide. There were no explosions. Parasites were sought by direct examination of the fasces. Shigella, Salmonella, and Yersinia were looked for by culture and enrichment procedures. The children investigated were all inpatients or outpatients at the department of paediatrics in the Kigali Hospital Centre (Medical Mission of the University of Brussels). There were 102 cases of gastroenteritis on ambulatory treatment, 18 healthy children coming to be vaccinated (first control group), 54 children admitted to hospital with measles (who always have some diarrhoea), 48 cases of gastroenteritis admitted to hospital, and 40 children admitted with diseases other than gastroenteritis (second control group). The pathogenicity of Campylobacter was confirmed by comparing the findings in children with diarrhoea with those in the controls (see table). The frequency with which Campylobacter was isolated (11% of those with diarrhoea) was remarkable. Among the inpatients with diarrhoea Salmonella was the most prevalent organism apart from parasites. Two explanations can be put forward: Salmonella infection might have been endemic in the hospital population (though only 3 children without diarrhoea were found to be carriers) or the gastroenteritis due to Salmonella might have been more severe and thus justified admission to hospital more frequently. Among the children with measles, the lesions in the digestive tract due to the virus may well have influenced the nature of the bacterial superinfection and so have favoured the multiplication of Salmonella. The frequency of Campylobacter was highest in children aged 12-24 months with diarrhoea, probably reflecting selfinfection with contaminated soil. Campylobacter was the agent most often found in patients whose gastroenteritis lasted more than 2 weeks or who had diarrhoea associated with violent abdominal pain. (The high proportion of children in hospital who were carrying parasites ’
reflects socioeconomic conditions in Rwanda: there was no evidence that the diarrhoeas investigated were due to parasites.) Since Campylobacter are important enteropathogemc bacteria in developing countries this organism should be identified as a target in the struggle against infantile diarrhreal disease in the third world. Laboratory of Microbiology, St. Pierre University Hospital, Brussels, Belgium, and Department of Pædiatrics, Kigali Hospital Centre Laboratory of Kigali Hospital Centre, Rwanda
P. DE MOL E. BOSMANS
CAMPYLOBACTER ENTERITIS IN BRUSSELS
SIR,-Since 1970, we have looked for Campylobacter in 22 000 specimens of human stools using the technique of filtration and culture on a selective medium, but a year ago we gave up filtration and made our medium more selective by adding to it cephalothin, which is inactive against C. jejuni. The new medium includes bacitracin (25 i.u./ml), novobiocin (5 p.g/ml), actidione (50 g/ml), colistin (10 units/mi), and cephalothin (15 g/ml). We used to incubate at 37°C because we were also looking for C. fetus, which grows very poorly at 43 °C.’’ However, we isolated C. fetus intestinalis from only 3 of 22 000 stools so we now incubate at 43 °C which allows C. jejuni to grow in 24 h instead of the 48 h or more needed at 370C. C. jejuni was isolated from 5.9% of diarrhoeal stools and from 1.3% of normal stools. Thus, as with all other enteropathogenic bacteria, there are healthy carriers. The isolationrate varies with the season in Brussels and can increase to 8-9% during July, August, and September. Positive stool cultures may be found among contacts of patients with Campylo.. bacter enteritis, and we have seen outbreaks of Campylobacter enteritis in five day-nurseries in the Brussels region. 20-50% of the infants were infected and had diarrhoea. From seven children from a creche where infection was prevalent, we were able to examine specimens aspirated from different levels of the intestinal tract. In four of the seven children Campylobacter was isolated on the same occasion from both stool and small intestine (stomach, jejunum, and ileum in one, jejunum but not ileum in another, and ileum but not jejunum in the two). All the isolates were C. jejuni, and all had the same biochemical and antigenic characters. The clinical manifestations of campylobacteriosis can vary but diarrhoea lasting several days with or without fever is the most frequent pattern. Though often trivial, the diarrhoea may sometimes be frankly watery or mucosanguinous and accom-
panied by vomiting.33
The mode of transmission of campylobacteriosis involves in1.
Butzler, J. P., Dekeyser, P., Detrain, M., Dehaen,
F. Pediatrics.
1973, 82,
493
Butzler, J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G., Paper presented at joint meeting of the British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow, in 1976. 3. Simmons, N. A. Br. med. J. 1977, ii, 707. 2.
1.
Butzler, J. P., Dekeyser, P., Detrain, M., Dehaen, F. J. Pediat. 1973, 82,
2. 3.
Butzler, J. P. Lancet, 1973, ii, 858. Skirrow, M. B. Br. med. J. 1977, ii, 9.
493.
PREVALENCE OF BACTERIA AND PARASITES IN STOOLS FROM RWANDAN CHILDREN
605 of the organism, carriage in the intestine, and then, sometimes, invasion of the bloodstream.4 Complications may also occur (toxicosis, dehydration) bur those affected-usually recover without antimicrobial treatment. Isolation of Campylobacter from the stools does not automatically imply the need for antibiotics; the decision should be taken on clinical and epidemiological grounds. Nevertheless intestinal infection may sometimes be followed by invasion of bloodstream, perhaps due to diarrhoea, modification of intestinal flora, or immunological deficiency.4 We have seen only seven cases of septicxmia in 5 years. In five of them the same Campylobacter was isolated on the same occasion from both stools and blood. Dr A. Wilson (Edinburgh) has pointed out that Campylobacter bacteraemia may be common in severe enteritis, but that we have been unaware of this because enteritis is most common in children and blood cultures -are not routine when children are admitted to hospital with fever and diarrhoea. Better knowledge of the organism and its cultural requirements may allow bacteriologists to respond to this suggestion.
gestion !
! ,.
S. LAUWERS M. DE BOECK J. P. BUTZLER
Department of Microbiology, St Pierre Hospital, 1000 Brussels, Belgium
SMOKING AND DIABETIC NEPHROPATHY
Sm,—Little is known about factors influencing the course and development of diabetic microangiopathy. One report of a possible relation between cigarette smoking and proliferative retinopathy’ is not wholly convincing because smoking and non-smoking diabetics were not sufficiently matched for type and duration of diabetes. Nephropathy, one manifestation of diabetic microangiopathy, is the most frequent cause of death in young diaPREVALENCE OF NEPHROPATHY IN SMOKING AND NON-SMOKING PATIENTS WITH
INSULIN-DEPENDENT, JUVENILE-ONSET DIABETES
significantly higher frequency of diabetic nephropathy found among cigarette smokers (table). The prevalence of hypertension did not vary with smoking habits. Since nephropathy is the most serious complication in longterm juvenile diabetes2.3 and since cigarette smoking should be avoided for other reasons it would be of interest if other groups were to confirm this observation. J. SANDAHL CHRISTIANSEN Steno Memorial Hospital, DK-2820 Gentofte, Copenhagen, Denmark J. NERUP A
was
MULTIPLE SCLEROSIS AND CANINE DISTEMPER
SiR,—An epidemiological study of familial multiple sclerosis (M.S.) suggesting a possible association between dogs and rt.s.l was criticised in your correspondence columns last year.2-6 Poskanzer et al.2 found no association between house pets and M.s. in the Orkney and Shetland Islands, although they noted that a high proportion of both control and M.s. groups were exposed to house pets. Epidemiological studies have also been done in the United States, the results suggesting an increased exposure of some M.s. patients to dogs with a distemper-likeillness before clinical onset of M.S.l,7,8 Bauer and Wikstrom3 in West Germany did not find a relationship between dogs and M.S., but again they did find more dogs thought to have distemper in the ns.s. group.’ Canine distemper virus (C.D.V.) is a paramyxovirus which can produce a neurological demyelinating disease in dogs with many similarities to M.s.9-13 Clinically distemper may be more common in cold weather,13 and these environmental conditions might increase contact between infectious dogs and man. Many of the characteristics of c.D.v. and its canine vector, in close association with man, could account for some of the geographical and cultural peculiarities seen in M.s. distribution.7,14,15 Preliminary serological studies have shown raised serum antibodies to C.D.v. in M.s. patients, as measured by immunonuorescence (a technique which, however, may not distinguish c.D.v. from other paramyxoviruses, such as measles virus).’ In view of these findings it seems possible that the development of M.s. may involve transmission of a virus from animal to man and that c..v. is a prime candidate.1.7.8,16 With this hypothesis in mind, we have been examining the apparently anomalous prevalence of M.s. in the Orkney and Shetland Islands as compared with the Faeroe Islands, particularly with respect to disease patterns of
distemper.
-
Orkney and Shetland the prevalence of M.s. is as high as 300 per 100 000 population,2 whereas in the Faeroe Islands (population 40 000) some 300 km to the north-west, no cases of M.s. were recorded from 1929 to 1943 and only 2 cases between 1960 and 1974 in the Faeroese" (who have many cultural and other similarities to the inhabitants of the Orkney and Shetland Islands). However, from 1944 to 1960 the Faeroe Islands experienced an "epidemic" of M.s. with 18 definite cases Kurtzke and Hyllesred17 suggested that these In
+C=Daily cigarette smoking for more than one year. -C=Never smoked cigarettes or cigarette smoking less than one year. tChi-square test. ’
so we have looked for a link between cigarette smokand diabetic nephropathy. The prevalence of diabetic ing nephropathy in a consecutive series of 238 insulin-dependent, juvenile-onset (before age 31) diabetics was related to current and previous smoking habits and to duration of disease. Diabetic nephropathy was defined as a raised serum-creatinine and/or persistent proteinuria without a history or clinical signs of non-diabetic renal disease. Cigarette smokers were defined as patients who had smoked at least 10 cigarettes a day for more than a year.
betics,2.3
4. Butzler,
J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G. Paper presented at joint meeting of British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow in 1976. 1. Pantkau, M. E., Boys, T. A. S., Winship, B., Grace, M. Diabetes, 1977, 26,
46. 2. Deckert, T., Poulsen, J. E., Larsen, M. Acta endocr. 1976, suppl. 203, 3. Andersen, A. R., Jensen, J. K., Christiansen, J. S., Deckert, T. ibid.
suppl. 209, p. 1.
p. 15. 1977,
1. Cook, S. D., Dowling, P. C. Lancet, 1977, i, 980. 2. Poskanzer, D. C., Prenney, L. B., Sheridan, J. L. ibid. p. 1204. 3. Bauer, H. J., Wikström, J. ibid. 1977, ii, 1029. 4. Visscher, B., Detels, R. ibid. p. 658. 5. Craelius, W., Newby, N. A. ibid. p. 565. 6. Klauber, M. R., Lyon, J. L. ibid. p. 454. 7. Cook, S. D., Natelson, B. H., Levin, B. E., Chavis, P. S., Dowling, P. C. Ann. Neurol. (in the press). 8. Jotkowitz, S. J. Am. med. Ass. 1977, 238, 854. 9. Innes, J. R. M., Saunders, L Z. Comparative Neuropathology. New York, 1962. 10. McGrath, J. T. Neurological Examination of the Dog. Philadelphia, 1960. 11. Wisniewski, H., Raine, C. S., Kay, W. J. Lab. Invest. 1972, 26, 589. 12. Adams, J. M., Brown, W. J., Snow, H. D., Lincoln, S. D., Sears, A. W., Barenfus, M., Holliday, T. A., Cremer, N. E., Lennette, E. H. Vet. Path.
1975, 12, 220. 13. Appel, M. J. G., Gillespie, J. H. Canine Distemper Virus. Austria, 1972. 14. Chan, W. W.-C. Lancet, 1977, i, 487. 15. Acheson, E. D. Multiple Sclerosis: a Reappraisal. Edinburgh, 1972. 16. Cook, S. D. Vet. Rec. 1977, 101, 314. 17. Kurtzke, J. F., Hyllested, K. Trans. Am. Neurol. Ass. 1975, 100, 213.
