Norwalk-like viruses

In a prospective 1-year study of acute infantile gastroenteritis, adenoviruses were detected in the stools or by seroconversions, or both, in 56 of 416 (13.5%) ill children. By use of DNA restriction enzyme analysis, enzyme immunoassay, and culture techniques, 33 of 56 (59%) adenovirus specimens were identified as enteric adenoviruses 40 and 41 (Ad40 and Ad41). They were found as the sole recognizable cause of diarrhea in 30 of 416 (7.2%) ill children and in 0 of 200 controls. Three additional ill children had enteric adenoviruses as a part of a dual infection. Evidence for established adenoviruses (Ad1 through Ad39) in gastroenteritis was found in 15 of 416 (3.6%) ill children but also in 3 of 200 (1.5%) controls. Eight adenovirus specimens remained untyped. Seroconversions were demonstrated in 17 of 18 (94%) paired serum samples from patients shedding enteric adenoviruses. The predominant symptom of infections with enteric adenoviruses was diarrhea, with a mean duration of 8.6 days (Ad40) and 12.2 days (Ad41). One-third of the children with Ad41 infections had prolonged symptoms (greater than or equal to 14 days). The frequency of respiratory symptoms was low (21%). The established adenoviruses presented a different clinical picture, characterized by diarrhea of shorter duration, higher fever, and significantly increased occurrence of respiratory symptoms (79%). In conclusion, enteric adenoviruses appear to be an important cause of acute infantile gastroenteritis, second only to rotaviruses in this study.

Importance of enteric adenoviruses 40 and 41 in acute gastroenteritis in infants and young children.

The initial experiments by Rowe and his colleagues that led to the discovery of adenoviruses also provided fundamental data on the prevalence of these agents. Surgically removed adenoids from 53 children in Washington, DC were explanted in tissue culture. After an observation period of 4 weeks, 33 of the cultures showed a slowly progressive cytopathic effect. The agent isolated from these cultures was appropriately designated the adenoid-degenerating (AD) agent (Rowe et al. 1953). An etiologic relation to acute respiratory disease (ARD) was also soon established for adenoviruses (Hilleman and Werner 1954). The two fundamental properties of human adenoviruses — the acute respiratory infection and the persistent infection of lymphatic tissue — were thus recognized at an early stage.

Molecular epidemiology of human adenoviruses.

About 200 antigenically related adenoviruses were isolated from cases of infantile diarrhoea in the Netherlands and North-West Germany. The viruses were fastidious and failed to replicate serially in human diploid fibroblasts and in primary human embryonic kidney cells. A number of strains were established in HeLa, HEp-2, Graham (293), cynomolgus monkey kidney, and Chang conjunctival cells. The viruses were mammalian adenoviruses by the usual criteria. No relationship to the 39 known human adenovirus species was found, either by neutralization tests or by haemagglutination inhibition tests. Neutralization tests showed two distinct variants, represented by strains Tak and Dugan. The variants were identical in haemagglutination inhibition tests. DNA restriction enzyme analysis showed Tak and Dugan to have considerably different genomes, indicating that these variants should be classified as different species (Wadell et al, 1983). It is proposed that the variants should be called Mastadenovirus h 40 (with reference strains Dugan and Hovi X) and Mastadenovirus h 41 (with reference strain Tak). Neutralization and haemagglutination inhibition tests demonstrated that the viruses from Glasgow and Helsinki (Hovi X) described by Johansson et al [1980] and by Kidd and Madeley [1981] belong to these two adenovirus species.

Candidate adenoviruses 40 and 41: fastidious adenoviruses from human infant stool.

Rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus diarrhoea in developing countries and the possible impact of these vaccines in reducing diarrhoeal morbidity and mortality among infants and young children. We examined the epidemiology and disease burden of rotavirus diarrhoea among hospitalized and clinic patients in African countries through a review of 43 published studies of the etiology of diarrhoea. The studies were carried out from 1975 through 1992, and only those in which a sample of more than 100 patients with diarrhoea were specifically screened for rotavirus by using an established diagnostic test were included. Rotavirus was detected in a median of 24% of children hospitalized for diarrhoea and in 23% who were treated as outpatients; 38% of the hospitalized patients with rotavirus were < 6 months and 81% were < 1 year of age. Rotavirus was detected year-round in nearly every country and generally exhibited distinct seasonal peaks during the dry months. In 5 countries where rotavirus strains had been G-typed, 74% of strains were of one of the four common serotypes (G1 to G4), G1 was the predominant serotype, and 26% were non-typeable. This cumulative experience from 15 African countries suggests that rotavirus is the most important cause of severe diarrhoea in African children and that most strains in circulation today belong to common G types that are included in reassortant vaccines. Wherever large numbers of cases of rotavirus diarrhoea occur early in infancy, immunization at birth may protect the children before their first symptomatic infection.

Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization.

Stools from 183 babies under 2 years of age admitted to Ruchill Hospital with diarrhoea were examined by electron microscopy, virus culture, bacterial culture and light microscopy. As far as possible, several stools were examined from each patient and the results showed rotaviruses, astroviruses and other viruses in association with symptoms, as well as the expected bacterial pathogens. Examination of several stools from the same patient also showed that in this age group the viral flora of the gut changes rapidly and that the viruses seen by electron microscopy were only rarely grown in cell culture and vice versa. This phenomenon was particularly noted with adenoviruses. In 30% of cases no microbial pathogen was identified and in the remainder the presence of the infecting organism did not always coincide with the symptoms. It is concluded that, with viruses at least, presence of the organism does not constitute proof of causation.

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Stool viruses in babies in Glasgow. 1. Hospital admissions with diarrhoea.

Twenty-seven babies from one deprived housing area in Glasgow were followed-up regularly, for periods varying between 2 months and 11 months (mean 7 months), in a prospective study of the viruses to be found in their stools by electron microscopy. Weekly stool specimens were collected in the home together with a history of the baby's health. Additional stool specimens were obtained, up to a maximum of one per day, during admissions to hospital. Over 500 specimens were obtained at home and another 320 in hospital. A wide variety of viruses (over 200 recognizates) were detected and it has been possible to plot their temporal relation to disease episodes. It became apparent that virus excretion was frequently unaccompanied by evidence of illness and it has not been possible to describe a typical illness syndrome associated with any of the morphological types of virus observed. The results suggest that, in one area of Glasgow at least, patterns of virus excretion in young babies are complex and will need further elucidation before the need for a vaccine to prevent infantile diarrhoea could be defined.

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Stool viruses in babies in Glasgow. 3. Community studies.

The stools of 37 newborn babies born in hospital were examined for the presence of virus. An extract of every stool passed by each baby was examined in the electron microscopy and inoculated into cell cultures. The babies were delivered in four separate maternity units (A-D). All the babies from unit A and C(9 babies) were found to be excreting rotavirus though none showed any evidence of diarrhoea. Two of the babies also excreted astrovirus. Subsequently unit A was closed for cleaning and, on reopening with more restrictions on visitors, a further 19 babies were examined. No virus was found in any of their stools, nor was virus observed in the stools of babies from units B and D, where visiting was also more restricted. Visiting restrictions in these units excluded older siblings of the babies. No virus was cultured from any stools in this study.

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B. P. Cosgrove

Papers

Stool viruses in babies in Glasgow. 1. Hospital admissions with diarrhoea.

Stool viruses in babies in Glasgow. 3. Community studies.

Stool viruses in babies in Glasgow 2. Investigation of normal newborns in hospital.

Viruses demonstrated in children in Tanzania: studies in diarrhoea and measles.