key: cord-023622-tul7bonh
authors: nan
title: Rotaviruses of Man and Animals
date: 1975-02-01
journal: Lancet
DOI: 10.1016/s0140-6736(75)91148-4
sha: 
doc_id: 23622
cord_uid: tul7bonh

nan

THE xtiological agents of most of the common viral infectious diseases have by now been identified, but until lately acute infantile gastroenteritis was an unhappy hunting-ground for virologists. This disease, one of the commonest causes of childhood illness throughout the world, is a leading cause of mortality in many underdeveloped countries. Thus, in India 1-4 million children die each year from diarrhoeal diseases, cholera apart.' Mortality in parts of Africa is also particularly high, and preexisting malnutrition and other debilitating diseases are undoubtedly important contributing factors. Certainly bacterial pathogens may cause both sporadic and epidemic gastroenteritis in children, but they cannot be isolated in up to 75% of cases.2, 3 Whilst it is true that some investigations suggest that enteroviruses or adenoviruses may occasionally cause localised outbreaks of gastroenteritis,4-7 others have shown that these viruses may be detected almost as frequently in controls as among patients. [8] [9] [10] [11] Just over a year ago, BISHOP and her colleagues 12 in Melbourne detected reovirus-like particles in thin sections of theepithelium of duodenal mucosal biopsies in 6 of 9 babies in the symptomatic phase of acute non-bacterial gastroenteritis. Their presence coincided with histological abnormalities and depressed duodenal mucosal disaccharidase levels. The viruses were originally classified as orbiviruses-a group of double-stranded-R.N.A. viruses which includes bluetongue, Colorado , tick fever, and African horse sickness viruses. Employing negativestaining techniques on fsecal extracts, FLEWETT and his colleagues found similar particles in children with gastroenteritis in Birmingham 13; indeed, if virologists had only looked at such simply prepared specimens, there is no technical reason why these viruses could not have been detected, say, 15 years ago. Morphologically identical viruses were soon detected in fxcal extracts by numerous other workers in many parts of the world,14-21 and in an analysis of these results on p. 242 this week Dr DAVIDSON and his colleagues 22 report that these viruses were present in faecal extracts of 396 of 827 (48%) children with gastroenteritis but in only 2 of 357 controls. Stools may be extremely rich in virus particles-there may be 109 to 1010 particles per gramme of faeces. These viruses are rarely detected in children over the age of 6 22,23 and are more often encountered in winter, during which time virus may be detected in up to 73% of patients. 22, 23 The disease has an incubation period of approximately 48 hours. Virus excretion is greatest during the third and fourth day of illness and is rarely detectable after the eighth day,22,23 although it has exceptionally been recorded for as long as 23 days after onset of symptoms.24 However, the incidence of infection by these viruses may be underestimated, for the number of particles may sometimes be below the critical threshold for detection by electron microscopy-particularly if specimens are not collected at the height of virus excretion. This may also perhaps explain failure to detect virus in nasopharyngeal secretions. 20 These morphologically identical viruses detected in faecal extracts differ from reoviruses and orbiviruses antigenically 21,23 as well as in their fine structure. The virus consists of a core about 38 nm. in diameter, surrounded by an inner layer of capsomeres which radiate outwards like the spokes of a wheel. An outer layer of capsomeres appears to be attached to the tops of the inner ones, and this gives rise to the characteristic appearance of a sharply defined rim surrounding the virus particle (diameter 60-65 nm.).23,25 Since these virus particles seem to be morphologically distinct from such diplorna-viruses as reoviruses and orbiviruses, and because of their wheel-like appearance, FLEWETT and his colleagues suggested they be called rotaviruses, 25 although the Australian workers now suggest that duoviruses may be more appropriate.22 Whichever term is eventually adopted, the viruses that cause epidemic diarrhoea of infant mice (E.D.I.M.)26 and some outbreaks of neonatal calf and pig diarrhoea,2'-2s

as well as such viruses as the simian SA11 virus and the 0 agent isolated from gut washings in sheep and cattle,30 are indistinguishable from the human virus and must therefore be included in this group.

Neonatal-calf-diarrhoea virus (a double-stranded-R.N.A. virus), like its human counterpart, has a world-wide distribution 31,32 and affects only young animals. Calf diarrhoea is one of the most important causes of economic loss in both dairy and beef herds, mortality-rates varying from nil to 80%.33-35 Furthermore, calves which recover often fail to gain weight adequately. Serological investigations show that babies with gastroenteritis acquire antibodies during the course of their illness. Furthermore, complement-fixation (c.F.) 21 and immunofluorescent (I.F.) 25 lately been shown to replicate in fetal intestinal organ cultures,37 in which virus may be detected by electron microscopy. I.F. work shows that virus-specific antigen is localised in the epithelial lining of the intestinal villi. Virus-infected organ cultures may be used for titrating antibody by I.F., and this provides a method that is rather more sensitive than c.F.; an effective c.F. antigen may be simply prepared from stool extracts rich in virus particles. 21 Techniques by which human rotaviruses may be propagated to high titres in cell cultures are eagerly awaited, since this is a step towards preparation of a vaccine. It is encouraging that an attenuated orally administered vaccine reduces the incidence of newborn-calf diarrhoea under field conditions 38 ; probably this vaccine protects by inducing specific viral antibody at the gut mucosal surface. Rotaviruses are only rarely encountered in specimens obtained from children who have experienced previous gastroenteritis, 17,22 which suggests that immunity may persist.

Thus, existing evidence suggests that rotaviruses are the most important cause of infantile gastroenteritis throughout the world, but as yet only a limited number of specimens have been examined from those tropical areas where mortality-rates are particularly high. Although no other viruses have conclusively been shown to cause gastroenteritis in older children and adults, 22 nm. diameter D.N.A. viruses (parvoviruses) may cause bovine enteritis,39 and viruses of this size have been detected by LE.M. in human StoolS.40 However, they have been detected in patients with and without gastroenteritis, and their role in human disease must remain uncertain.

During an outbreak of gastroenteritis in Norwalk, Ohio, 27 nm. picornavirus-like particles were detected in faecal extracts. Infection was transmitted to volunteers, and I.E.M. studies suggested that both naturally and experimentally infected persons developed antibody during their illness. 41 In addition, cross-challenge studies elsewhere on volunteers with gastroenteritis suggest that the Norwalk agent may be antigenically related to other viruses causing gastroenteritis. 42 Nevertheless, claims by some workers to have detected parvovirus-like or picornaviruslike particles in faeces by electron microscopy must be interpreted with caution, since it is difficult to be certain whether small isometric viruses are bacterial or human viruses, and such particles may be identified readily in both patients and controls. Certainly LE.M. detection of virus-agglutinating antibodies during convalescence, against virus present in the stools, provides useful circumstantial evidence of infection, but not until these viruses can be isolated and specific antisera raised against them can the specificity of the agglutination reaction be confirmed. 43

In addition to rotaviruses, coronaviruses are important causes of enteritis in pigs (transmissible gastroenteritis of piglets) 44 and calves,45 and it is tempting to speculate that coronaviruses may eventually be shown to cause human gastroenteritis. Workers in Melbourne and Birmingham have opened a new vista in both clinical and comparative virology and, until such time as the human virus can be isolated in vitro, much may be learned from work in animals about virus transmission and the immune response it induces. Rotaviruses may now be included in the list of such viruses as herpes, poxviruses, and hepatitis B which may be. reliably and rapidly detected in clinical specimens by electron microscopy.

Home Blood-pressure Recording ALTHOUGH the case is far from proven, the indications are that substantial reductions in mortality and morbidity can be expected from effective treatment of mildly raised blood-pressure (diastolic 95-110 mm. Hg).46 Already the American Heart Association has called for a massive campaign of identification and treatment, and, despite the pessimism of epidemiologists,47 it is probable that population screening programmes will be started and that practitioners will be called upon to manage long-term therapy in many more symptomless patients than at present. As much as 15-20% of the adult population may fall into this category, and if it is true that all these patients are at increased risk and would benefit from therapy then an enormous work-load will be generated. While the casual blood-pressure reading has proved to be an accurate predictor of morbidity and mortality from cardiovascular diseases, the risk will be highest amongst those patients who have a high blood-pressure throughout the day and least (perhaps negligible) in those who react briskly to the circumstances of the measurement. 48 If the work-load is to be kept within reasonable bounds, and if unnecessary treatment of large numbers of essentially normal persons is to be avoided, we need 43. Flewett some method of identifying the truly raised bloodpressure. This demands numerous recordings over long periods and at all times of the normal working day. The only practical way in which this can be achieved is by training the patient to record his own blood-pressure repeatedly 49,50—a concept which also raises the possibility that such patients may be able to regulate their activities, and perhaps even their drug dosage, on the basis of their own recordings. It is not difficult to train lay persons to take their own blood-pressures with an acceptable degree of accuracy (defined as agreement with a doctor's readings), but there are obvious difficulties with technique and equipment. Many different semiautomatic machines which substitute a sound detector built into the arm cuff for the human ears have come on the market and are offered for sale to the public. The accuracy of these instruments is very doubtful and few have come under professional scrutiny. The only published evaluations 51 suggest that most are inaccurate and that they do not compare well with the stethoscope and mercury sphygmomanometer.

Evidently the human ear and its interpretive brain are still more accurate and sensitive than any electronic gadgets. As an alternative to elaborate and expensive equipment, a group of patients with hypertension living in the Harrow area of London have been trained to record their bloodpressure twice daily using an anaeroid sphygmomanometer and a simple diaphragm stethoscope. 52 All these patients were participating in clinic trials of antihypertensive agents. It was found possible to train all but a very few patients to record their pressures accurately, and, with encouragement, 94 out of 100 continued to keep records for periods of up to one year. During this time the therapy was changed, periods of active treatment alternating with periods of placebo therapy. The trials were conducted in a double-blind fashion, and the fact that the patient records followed precisely the direction of the clinic recordings suggested that the patient records were true and not biased by previous recordings or a desire to please the clinic doctor. The patient records were, however, consistently lower than the clinic recordings, and this was particularly so for those patients in whom the initial reading was only slightly raised. This is by no means a new observation,53 but it suggests that blood-pressures recorded by a simple technique by the patient can be as accurate

Acta pœdiat

Oxprenolol in the Treatment of Non-accelerated Essential Hypertension