124
Letters
to
the Editor
VIRUSES IN INFANTILE GASTROENTERITIS
SiR,—The report by Dr Appleton and Dr Higgins p. 1297) of 20-30 nm. particles in the stools of
(June 7,
babies with mild gastroenteritis prompts us to add some data from an investigation of the faecal flora of normal babies and those with gastroenteritis. Faeces from 121 cases of gastroenteritis in children under 2 years of age admitted to Ruchill Hospital were examined by direct electron microscopy: 45 (37%) were excreting rotaviruses either on admission or subsequently. A further 36 (29%) had round virus-like objects in their stools: of these, 23 (19%) contained particles, often in very large numbers, which had several features in common. They were very uniform in size (analysis of 1021 particles gave a mean diameter of 28 nm.rbO-5 nm.) and, though basically " small round viruses " (s.R.v.s), often showed a faint surface structure apparently due to hollows on the virus surface which fill with stain. These hollows are seen at the periphery and give the impression of a crude five or six pointed star superimposed on the virus particles (fig. 1).
Fig. 1-Small round virus showing star-shaped surface structure: (a) untouched print; (b) outline accentuated. x 500,000.
The remaining 13 patients excreted round virus-like objects 25-30 nm. in diameter, mostly in small numbers. Not all of these may in fact be viruses as they lacked distinguishing features and they did not show the same homogeneity. Some were probably the enteroviruses, mostly echoviruses, which were subsequently isolated from 3 patients. S.R.V.S were also found in association with several small outbreaks of gastroenteritis in the nursery of a maternity ward. 18 out of 27 patients (67%) were excreting S.R.V.S and 2 patients were excreting other round virus-like objects. 5 babies were excreting rotaviruses, in 1 case as well as S.R.V.S. 19 normal babies in the same unit and which showed no signs of gastroenteritis at any time were also examined: 4 were excreting S.R.V.s and in 2 of these rotaviruses were also present. A 5th baby was excreting rotaviruses only. Finally, 9 neonates in 2 nurseries were examined; all 9 excreted rotaviruses at one time or another, mostly from the second day, and 2 excreted S.R.V.s as well. Virus was found in the stool usually for 2-3 days -and all the babies remained symptom-free. A full account of this work is in preparation, but some observations may be made now. Our S.R.v.s appear to be very similar to the viruses described by Dr Appleton and Dr Higgins (the small observed difference in size may be due to variations between laboratories) and there is primafacie evidence that they may be a contributory cause of
Fig. 2-Small round viruses showing concentration of particles that may be seen in centrifuged fsecal extract. x 65,000.
infantile gastroenteritis. Our observations of both S.R.V.S and rotaviruses in the stools of symptom-free neonates suggests that their presence alone may not cause gastroenteritis and that other factors, at present unidentified, may be required to precipitate overt symptoms. It is difficult to prove that round structures seen on the grid of an electron microscope are viruses. We are indebted to our colleague, Dr E. J. Bell, for attempts to grow our S.R.V.s. These have so far been unsuccessful, but the vast numbers present (fig. 2), their uniformity, and the surface features we have described persuade us that they are viruses, are unlikely to be bacteriophages, and are probably not bacteriocins. They are quite distinct in appearance from the coliphage, X-174, and they are also larger than the 22 nm. particles of Paver et al.,l while smaller than the 40 nm. particles described by Flewett et al.2 Further study is needed to understand the ecological patterns of these viruses and to establish their epidemiological significance. Because they are present in neonatal stools in such very large numbers it is likely that they will provide an immunological stimulus to the host whether or not they cause gastroenteritis. For this reason and because a proportion of the particles seen in stool preparations appear to be clumped together without the addition of specific serum, serological studies may prove difficult both to do and to interpret. We are grateful to Dr I. W. Pinkerton and Dr M. J. Patrick for the opportunity to study patients under their care.
Regional Virus Laboratory and University Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB.
C. R. MADELEY B. P. COSGROVE.
ROTAVIRUS INFECTIONS IN OBSTETRIC HOSPITALS the past 18 months it has been established SIR,-During that a reovirus-like particle (" rotavirus or "duovirus ") is an important sitiological agent in acute sporadic enteritis in infants and children throughout the world.3 We have evidence that this virus is also an important cause of endemic and epidemic diarrhoea in nurseries for the newborn in Melbourne, Australia. During January-May, 1975, diarrhceal faeces were collected from 148 neonates in five Melbourne obstetric "
1.
Paver, W. K., Caul, E. O., Ashley, C. R., Clarke, S. K. R. Lancet, 1973,
1, 237.
Flewett, T. H., Bryden, A. S., Davies, H. A. J. clin. Path. 1974, 27, 603. 3. See Lancet, 1975, i, 257. 2.
125 THE DOCTOR IN THE HOSPITAL
hospitals. Electron microscopy of faecal extracts showed duovirus particles in 82 babies. No recognised bacterial "
"
pathogens
were
isolated.
During these months, diarrhoea has been endemic in four of the hospitals and epidemics of diarrhoea of 2-3 weeks’ duration have occurred in four hospitals. In affected babies, the illness lasted only 12-48 hours with the passage of watery fasces often positive for sugar by ’Clinitest ’.4 These findings will be reported elsewhere in more detail. The incidence of this reovirus-like particle and of the recently reported 29-30 nm. particle5 in babies with diarrhoea remains to be determined. Further studies on the aetiology of neonatal diarrhcea should employ electron microscopy of faecal extracts, routine tissue culture, and standard bacteriological techniques in order to assess the relative importance of viral and bacterial pathogens. Department of Gastroenterology,
Royal Children’s Hospital, Melbourne, Australia 3052. Department of Microbiology, University of Melbourne, Australia 3052.
D. R. G. R.
J. S. CAMERON F. BISHOP P. DAVIDSON R. W. TOWNLEY.
I. H. HOLMES B. J. RUCK.
VIRAL ANTIBODIES IN THYROTOXICOSIS
SIR,-The pathogenesis of thyrotoxicosis is unknown. Since, to our knowledge, viral antibodies have not been studied in patients with thyrotoxicosis we undertook a preliminary investigation. The titres of complementfixing antibodies against influenza A and B, mumps, and measles, and hxmagglutination-inhibiting antibodies against rubella were determined in sera from 88 patients with thyrotoxicosis (77 with Graves’ disease, and 11 with toxic multinodular goitre). All patients were thyrotoxic at the time blood was collected, but a few had been diagnosed several years previously. These results were compared with sera from age and sex matched hospital inpatients with non-thyroidal disease, collected over the same period. The results are shown in the accompanying table. The frequency of antibodies to influenza B was much greater in the thyrotoxic group. These results are obviously preliminary and the difference in influenza-B antibodies cannot at this stage be accepted as of pathogenetic significance. However, the results do suggest that a more extensive study is warranted. A. JOASOO. Department of Medicine, Division of Microbiology,
Department of Nuclear Medicine, Prince of Wales Hospital, Randwick, N.S.W., Australia.
P. ROBERTSON.
LABORATORY
SIR,-Your leading article (June 14, p. 1327) highlights of the problems facing chemical pathology and chemical pathologists. Chemical pathology is not a popular career choice for medical graduates, possible reasons being the hybrid nature of the job and the relatively poor financial some
rewards.
The chemical
pathologist
have clinical
emphasise one role for the chemical pathologist, that of a metabolic physician, although this aspect of training has been emphasised previously.l You fail to point out the consultant role of a chemical pathologist in advising his clinical. colleagues on chemical investigations. In the setting of a teaching hospital it is difficult to appreciate this role, but in the district hospital the chemical pathologist acts as a consultant to general practitioners and consultants. Why do we need a medical graduate to head a chemical pathology laboratory ? You rightly say that in some quarters few tears would be shed if this were not so. One of the most important functions of a chemical pathologist in the future is a combination of clinical and managerial skills. Equipment and tests are becoming more costly, so the chemical pathologist must carefully evaluate whether the setting up of new tests is justified or whether older tests can be dropped. It is, of course, arguable that this could be equally well performed by non-medical graduates, but only a medical graduate can prevent a completely on-demand service. With regard to the United States, my experience is admittedly limited to private, prepaid, and Government services in certain areas, but in these there is expansion of medical control rather than retraction for the reasons I have stated. Clinical Laboratories, Stanford University Medical Center, and Palo Alto Veterans Administration Hospital, California 94304, U.S.A.
TOM HARGREAVES.
OUTPATIENT SURGERY
SIR,-Your leading article (June 21, p. 1366) on day-case gives a balanced view of the advantages and problems. It is essential, however, for those responsible surgery
for allocation of nurses to realise that doing hernias and similar operations as a day case does not relieve the pressure on the general surgical wards. In fact it makes it worse, because a higher proportion of patients on the ward are having major surgery and therefore need more intensive
nursing. I. P. C. MURRAY.
Charing Cross Hospital, Fulham Palace Road, London W6 8RF.
4. 5.
must
knowledge to help clinicians solve clinical problems and also be well versed in chemical techniques. He or she is also the managerial head of a complex organisation. You
Kerry, K. R., Anderson, C. M. ibid. 1964, i, 987. Appleton, H., Higgins, P. G. ibid. 1975, i, 1297.
FREQUENCY
1.
Hargreaves, T. Lancet, 1967, ii, 1409.
AND LOG. TITRES OF ANTIBODIES
A. G. JOHNSON.
Letters
to
the Editor
VIRUSES IN INFANTILE GASTROENTERITIS
SiR,—The report by Dr Appleton and Dr Higgins p. 1297) of 20-30 nm. particles in the stools of
(June 7,
babies with mild gastroenteritis prompts us to add some data from an investigation of the faecal flora of normal babies and those with gastroenteritis. Faeces from 121 cases of gastroenteritis in children under 2 years of age admitted to Ruchill Hospital were examined by direct electron microscopy: 45 (37%) were excreting rotaviruses either on admission or subsequently. A further 36 (29%) had round virus-like objects in their stools: of these, 23 (19%) contained particles, often in very large numbers, which had several features in common. They were very uniform in size (analysis of 1021 particles gave a mean diameter of 28 nm.rbO-5 nm.) and, though basically " small round viruses " (s.R.v.s), often showed a faint surface structure apparently due to hollows on the virus surface which fill with stain. These hollows are seen at the periphery and give the impression of a crude five or six pointed star superimposed on the virus particles (fig. 1).
Fig. 1-Small round virus showing star-shaped surface structure: (a) untouched print; (b) outline accentuated. x 500,000.
The remaining 13 patients excreted round virus-like objects 25-30 nm. in diameter, mostly in small numbers. Not all of these may in fact be viruses as they lacked distinguishing features and they did not show the same homogeneity. Some were probably the enteroviruses, mostly echoviruses, which were subsequently isolated from 3 patients. S.R.V.S were also found in association with several small outbreaks of gastroenteritis in the nursery of a maternity ward. 18 out of 27 patients (67%) were excreting S.R.V.S and 2 patients were excreting other round virus-like objects. 5 babies were excreting rotaviruses, in 1 case as well as S.R.V.S. 19 normal babies in the same unit and which showed no signs of gastroenteritis at any time were also examined: 4 were excreting S.R.V.s and in 2 of these rotaviruses were also present. A 5th baby was excreting rotaviruses only. Finally, 9 neonates in 2 nurseries were examined; all 9 excreted rotaviruses at one time or another, mostly from the second day, and 2 excreted S.R.V.s as well. Virus was found in the stool usually for 2-3 days -and all the babies remained symptom-free. A full account of this work is in preparation, but some observations may be made now. Our S.R.v.s appear to be very similar to the viruses described by Dr Appleton and Dr Higgins (the small observed difference in size may be due to variations between laboratories) and there is primafacie evidence that they may be a contributory cause of
Fig. 2-Small round viruses showing concentration of particles that may be seen in centrifuged fsecal extract. x 65,000.
infantile gastroenteritis. Our observations of both S.R.V.S and rotaviruses in the stools of symptom-free neonates suggests that their presence alone may not cause gastroenteritis and that other factors, at present unidentified, may be required to precipitate overt symptoms. It is difficult to prove that round structures seen on the grid of an electron microscope are viruses. We are indebted to our colleague, Dr E. J. Bell, for attempts to grow our S.R.V.s. These have so far been unsuccessful, but the vast numbers present (fig. 2), their uniformity, and the surface features we have described persuade us that they are viruses, are unlikely to be bacteriophages, and are probably not bacteriocins. They are quite distinct in appearance from the coliphage, X-174, and they are also larger than the 22 nm. particles of Paver et al.,l while smaller than the 40 nm. particles described by Flewett et al.2 Further study is needed to understand the ecological patterns of these viruses and to establish their epidemiological significance. Because they are present in neonatal stools in such very large numbers it is likely that they will provide an immunological stimulus to the host whether or not they cause gastroenteritis. For this reason and because a proportion of the particles seen in stool preparations appear to be clumped together without the addition of specific serum, serological studies may prove difficult both to do and to interpret. We are grateful to Dr I. W. Pinkerton and Dr M. J. Patrick for the opportunity to study patients under their care.
Regional Virus Laboratory and University Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB.
C. R. MADELEY B. P. COSGROVE.
ROTAVIRUS INFECTIONS IN OBSTETRIC HOSPITALS the past 18 months it has been established SIR,-During that a reovirus-like particle (" rotavirus or "duovirus ") is an important sitiological agent in acute sporadic enteritis in infants and children throughout the world.3 We have evidence that this virus is also an important cause of endemic and epidemic diarrhoea in nurseries for the newborn in Melbourne, Australia. During January-May, 1975, diarrhceal faeces were collected from 148 neonates in five Melbourne obstetric "
1.
Paver, W. K., Caul, E. O., Ashley, C. R., Clarke, S. K. R. Lancet, 1973,
1, 237.
Flewett, T. H., Bryden, A. S., Davies, H. A. J. clin. Path. 1974, 27, 603. 3. See Lancet, 1975, i, 257. 2.
125 THE DOCTOR IN THE HOSPITAL
hospitals. Electron microscopy of faecal extracts showed duovirus particles in 82 babies. No recognised bacterial "
"
pathogens
were
isolated.
During these months, diarrhoea has been endemic in four of the hospitals and epidemics of diarrhoea of 2-3 weeks’ duration have occurred in four hospitals. In affected babies, the illness lasted only 12-48 hours with the passage of watery fasces often positive for sugar by ’Clinitest ’.4 These findings will be reported elsewhere in more detail. The incidence of this reovirus-like particle and of the recently reported 29-30 nm. particle5 in babies with diarrhoea remains to be determined. Further studies on the aetiology of neonatal diarrhcea should employ electron microscopy of faecal extracts, routine tissue culture, and standard bacteriological techniques in order to assess the relative importance of viral and bacterial pathogens. Department of Gastroenterology,
Royal Children’s Hospital, Melbourne, Australia 3052. Department of Microbiology, University of Melbourne, Australia 3052.
D. R. G. R.
J. S. CAMERON F. BISHOP P. DAVIDSON R. W. TOWNLEY.
I. H. HOLMES B. J. RUCK.
VIRAL ANTIBODIES IN THYROTOXICOSIS
SIR,-The pathogenesis of thyrotoxicosis is unknown. Since, to our knowledge, viral antibodies have not been studied in patients with thyrotoxicosis we undertook a preliminary investigation. The titres of complementfixing antibodies against influenza A and B, mumps, and measles, and hxmagglutination-inhibiting antibodies against rubella were determined in sera from 88 patients with thyrotoxicosis (77 with Graves’ disease, and 11 with toxic multinodular goitre). All patients were thyrotoxic at the time blood was collected, but a few had been diagnosed several years previously. These results were compared with sera from age and sex matched hospital inpatients with non-thyroidal disease, collected over the same period. The results are shown in the accompanying table. The frequency of antibodies to influenza B was much greater in the thyrotoxic group. These results are obviously preliminary and the difference in influenza-B antibodies cannot at this stage be accepted as of pathogenetic significance. However, the results do suggest that a more extensive study is warranted. A. JOASOO. Department of Medicine, Division of Microbiology,
Department of Nuclear Medicine, Prince of Wales Hospital, Randwick, N.S.W., Australia.
P. ROBERTSON.
LABORATORY
SIR,-Your leading article (June 14, p. 1327) highlights of the problems facing chemical pathology and chemical pathologists. Chemical pathology is not a popular career choice for medical graduates, possible reasons being the hybrid nature of the job and the relatively poor financial some
rewards.
The chemical
pathologist
have clinical
emphasise one role for the chemical pathologist, that of a metabolic physician, although this aspect of training has been emphasised previously.l You fail to point out the consultant role of a chemical pathologist in advising his clinical. colleagues on chemical investigations. In the setting of a teaching hospital it is difficult to appreciate this role, but in the district hospital the chemical pathologist acts as a consultant to general practitioners and consultants. Why do we need a medical graduate to head a chemical pathology laboratory ? You rightly say that in some quarters few tears would be shed if this were not so. One of the most important functions of a chemical pathologist in the future is a combination of clinical and managerial skills. Equipment and tests are becoming more costly, so the chemical pathologist must carefully evaluate whether the setting up of new tests is justified or whether older tests can be dropped. It is, of course, arguable that this could be equally well performed by non-medical graduates, but only a medical graduate can prevent a completely on-demand service. With regard to the United States, my experience is admittedly limited to private, prepaid, and Government services in certain areas, but in these there is expansion of medical control rather than retraction for the reasons I have stated. Clinical Laboratories, Stanford University Medical Center, and Palo Alto Veterans Administration Hospital, California 94304, U.S.A.
TOM HARGREAVES.
OUTPATIENT SURGERY
SIR,-Your leading article (June 21, p. 1366) on day-case gives a balanced view of the advantages and problems. It is essential, however, for those responsible surgery
for allocation of nurses to realise that doing hernias and similar operations as a day case does not relieve the pressure on the general surgical wards. In fact it makes it worse, because a higher proportion of patients on the ward are having major surgery and therefore need more intensive
nursing. I. P. C. MURRAY.
Charing Cross Hospital, Fulham Palace Road, London W6 8RF.
4. 5.
must
knowledge to help clinicians solve clinical problems and also be well versed in chemical techniques. He or she is also the managerial head of a complex organisation. You
Kerry, K. R., Anderson, C. M. ibid. 1964, i, 987. Appleton, H., Higgins, P. G. ibid. 1975, i, 1297.
FREQUENCY
1.
Hargreaves, T. Lancet, 1967, ii, 1409.
AND LOG. TITRES OF ANTIBODIES
A. G. JOHNSON.
