Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus.

The possibility of immunizing human infants against rotaviruses, which cause severe dehydrating diarrheal disease, may depend on the use of a related rotavirus, derived from another animal species, as a source of antigen. To test the feasibility of this approach, calves were infected in utero with a bovine rotavirus and challenged with bovine or human type 2 rotavirus shortly after birth. Infection in utero with bovine rotavirus induced resistance to diarrheal disease caused by the human virus as well as the homologous bovine virus. These data suggest that the bovine virus is sufficiently related antigenically to the human type 2 virus to warrant further evaluation of the former as a source of vaccine.

Retrospective genetic characterisation of Encephalomyocarditis viruses from African elephant and swine recovers two distinct lineages in South Africa.

Encephalomyocarditis virus (EMCV) outbreaks are rare in southern Africa. Only two have been reported to date from South Africa, both coinciding with rodent irruptions. The first outbreak manifested as acute myocarditis in pigs in 1979, whilst the second, occurring from 1993 to 1994, was linked to the deaths of 64 free-ranging adult African elephants (Loxodonta africana). The P1 genome region, inclusive of the flanking leader (L) and 2A genes, of three South African isolates, one from swine and two from elephants, was characterised by PCR amplification and sequencing of up to 11 overlapping fragments. In addition to the resulting 3329 nucleotide dataset, the 3D region that is widely used in molecular epidemiology studies, was characterised, and three datasets (P1, VP1/3 and 3D), complemented with available homologous EMCV data, were compiled for analyses. Phylogenetic inferences revealed the near-identical elephant outbreak strains to be most closely related to a mengovirus from rhesus macaques (Macaca mulatta) in Uganda, differing from the latter by between 11% (3D) and 15% (VP3/1). The South African pig isolate differed by 4% (3D) and 11% (VP3/1) from available European and Asian pig virus sequences. This study confirms the presence of two genetically distinct EMCV lineages recovered from sporadic outbreaks in wild and domestic hosts in southern Africa, and provides valuable baseline data for future outbreak eventualities in the sub-region.

The spatial distribution of depressive illness in Plymouth.

Diagnostic and demographic data were collected from all 2,298 psychiatric hospital admissions for affective illnesses from private households in the City of Plymouth for the six-year period 1970-1975 inclusive. Intercorrelations of diagnostic subtypes were performed, together with a multiple regression analysis against spatial and ecological data from the 1971 Census. Rate differences were related to the geographic structure of Plymouth. With psychotic illnesses, ecological correlations were low for male and female first admissions and for male readmissions. However, important correlations relating to socio-economic status, housing tenure and structure, population instability, and other sociodemographic features emerged in varying degrees of specificity for reactive and neurotic illness in males, and for all readmissions in females, largely irrespective of diagnostic subtype. Explanations for the processes underlying these patterns are offered in terms of population structure, particularly the differing vulnerability of age and marital status groups, the referral and diagnostic process, social and physical stresses in the lower socioeconomic groups, and urban drift.

Sodium bicarbonate abuse: a case report.

Sodium bicarbonate abuse is unusual, and rarely reported. A patient was extensively investigated at several hospitals for a recurrent hypokalaemic metabolic alkalosis; it transpired that she had been abusing sodium bicarbonate for 8 years and had gained hospital admission at will by taking large amounts. She also showed features of the Munchausen syndrome.

Evaluation of three panels of monoclonal antibodies for the identification of human rotavirus VP7 serotype by ELISA.

Three panels of monoclonal antibodies used for rotavirus serotype identification by enzyme-linked immunosorbent assay (ELISA) were evaluated at the National Institutes of Health, USA, to identify antibodies suitable for distribution to laboratories involved in WHO-sponsored trials of rotavirus vaccines. Two of the panels were comparably effective in identifying the serotype of each of the human rotavirus reference strains of serotype 1, 2, or 3. In addition, one of the panels included a monoclonal antibody that was effective in identifying strains of serotype 4. However, two different lots of a third, commercially available panel were not effective in identifying the eight strains representing the four serotypes. A third shipment of this panel was therefore tested using revised instructions and, under these conditions, it was effective in serotyping seven of the eight reference strains. It appears that a battery of monoclonal antibodies for each serotype may be required to identify antigenic variants within a serotype. Additional studies are needed to assess the extent of antigenic variation in rotavirus field strains.

Detection of coronavirus strain 692 by immune electron microscopy.

Utilization of the technique of immune electron microscopy has enabled the detection of a coronavirus in organ culture harvests derived from a washing from an adult with an acute upper respiratory tract illness; convalescent serum was the source of specific antibody.

New complement-fixation test for the human reovirus-like agent of infantile gastroenteritis. Nebraska calf diarrhea virus used as antigen.

A complement-fixation (C.F.) test for the human reovirus-like agent of infantile gastroenteritis has been developed using the serologically related Nebraska calf diarrhoea virus (N.C.D.V.) as antigen. Most infants and children who shed the agent in stools and/or who demonstrated serological (C.F.) evidence of infection with a reovirus-like-particle-positive human stool-filtrate C.F. antigen also demonstrated serological evidence of infection when a concentrated N.C.D.V. preparation was employed AS C.F. antigen. The N.C.D.V., which was previously shown to be related to the human reovirus-like agent, was found to be related antigenically to the epizootic diarrhoea of infant mice (E.D.I.M.) virus also. Studies on the prevalence of C.F. antibody in sera from infants and young children revealed a pattern of rapid acquisition of antibody to both the human reovirus-like agent and the N.C.D.V. as over 80 percent of these individuals possessed antibody to each agent by 36 months of age. A strong positive association was found in the results obtained with the two antigens. The ready availability of cell-culture grown N.C.D.V., and its ability to serve as a "substitute" C.F. antigen for the human reovirus-like agent, should enable the serodiagnosis of many cases of disease due to the human agent and facilitate seroepidemiological studies of such infections. In addition, the observation that a large proportion of individuals infected with the human reovirus-like agent develop serological evidence of infection not only to the human agent but to the calf agent as well may have important implications in the immunoprophylaxis of disease caused by the human reovirus-like agent.

Direct isolation in cell culture of human rotaviruses and their characterization into four serotypes.

Of 73 rotavirus-positive fecal specimens tested, 39 yielded a human rotavirus that could be cultivated serially in MA104 or primary African green monkey kidney cells or both; 18 were serotyped. Four distinct serotypes were identified by plaque reduction or tube neutralization assay or both, and three of these serotypes were the same as those established previously by plaque reduction, using human rotaviruses cultivated by genetic reassortment with a cultivable bovine rotavirus. Ten human rotavirus strains received from Japan were found to be similar, if not identical, to our candidate prototype strains representing these four human rotavirus serotypes.

Clinical response and tricyclic plasma levels during treatment with clomipramine.

Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly. These findings, together with the fact that significant clinical improvement was observed in only 55% of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.

Prevalence of antibody to the Norwalk agent by a newly developed immune adherence hemagglutination assay.

An immune adherence hemagglutination assay (IAHA) for the detection of antibody to the Norwalk agent of acute epidemic nonbacterial gastroenteritis was developed using as antigen virus purified from stool from an experimentally infected volunteer. The assay was sensitive and specific and was efficient for detecting Norwalk antibody seroresponses. The prevalence of Norwalk antibody in various groups in the United States was studied. Antibody to the Norwalk agent was acquired gradually, beginning slowly in childhood and accelerating in the adult period so that by the fifth decade 50% possessed antibody. This pattern of antibody acquisition contrasted sharply with that for the human rotavirus of infantile gastroenteritis. Rotavirus antibody was acquired during early childhood by almost all individuals in the pediatric groups studied. Antibody to the Norwalk agent was also found in rural Bangladesh; in a small prevalence survey of 39 children and adults 21% possessed Norwalk IAHA antibody, whereas 95% possessed antibody to the human rotavirus.

Antigenic relationships among five reovirus-like (RVL) agents by complement fixation (CF) and development of new substitute CF antigens for the human RVL agent of infantile gastroenteritis.

The human reovirus-like (HRVL) agent, Nebraska calf diarrhea virus (NCDV), epizootic diarrhea of infant mice (EDIM) virus, simian agent (SA)-11, and the "O" (offal) agent were found to be similar, if not identical, in reciprocal complement fixation (CF) tests employing hyperimmune animal sera. In addition, in CF tests with paired sera from 35 diarrhea patients who shed the HRVL agent, 74% developed serologic evidence of infection with the HRVL antigen, 43% with NCDV, 51% with EDIM virus, 57% with SA-11, and 71% with the "O" agent. Thus, in addition to the NCDV, which had previously been described as a suitable substitute CF antigen for the HRVL agent, the SA-11, "O", and EDIM viruses may also be utilized as substitute antigens for the HRVL agent. However, the "O" agent appears to be the most efficient of the four substitute CF antigens and thus should be used preferentially when the HRVL agent is not available. The "O" agent was about as efficient as the HRVL agent and significantly more efficient than the NCDV for detecting seroresponses. The greatest efficiency for detecting infection with the HRVL agent resulted when sera were tested with both the HRVL and "O" agents as 31 (89%) of the patients developed serologic evidence of infection with one or both antigens. The finding of additional substitute CF antigens for the HRVL agent may have implications in the immunoprophylaxis against human disease.

Antigenic characterization of human and animal rotaviruses by immune adherence hemagglutination assay (IAHA): evidence for distinctness of IAHA and neutralization antigens.

An immune adherence hemagglutination assay (IAHA) and a modified enzyme-linked immunosorbent assay for antigenic characterization of human rotaviruses were developed. The designations of type 1 and type 2 were identical to those established previously by specific complement fixation, enzyme-linked immunosorbent assay, and immune electron microscopy. By IAHA (and modified enzyme-linked immunosorbent assay) certain animal rotaviruses were found to be closely related to human rotavirus type 1. The pattern of IAHA reactivity and the cell culture neutralization serotype were found to be distinct properties. The separation of neutralization and IAHA reactivity was apparent when animal rotaviruses which were distinguishable from each other by neutralization assays were found to share IAHA specificity. Further evidence for the dissociation of the neutralization and IAHA specificities was found in studies of human and bovine rotaviruses which underwent genetic reassortment during coinfection. Thus, it appeared that the IAHA and neutralization antigens were coded for by different genes. In view of these findings, we suggest that the term serotype be reversed to identify the antigen that reacts with neutralizing antibodies as is customary for other viruses and that the term subgroup (instead of serotype) be used for the specificity detected by specific complement fixation, enzyme-linked immunosorbent assay, and now IAHA.