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Twenty-four episodes of disease exacerbation in 19 children suffering from systemic juvenile chronic arthritis were studied. Sixteen of these were preceded by an infection (chi 2 = 20.14, p less than 0.001), mostly of the upper respiratory tract. In the 10 cases seen during an infection causative agents were identified in 5 (herpes simplex, rhinovirus, and on 3 occasions streptococcus). The total number of infections was not increased when compared with infection rates predicted by several reported studies. In the absence of clinical infection, specific antibody titres to a panel of microbial antigens were similar to those of a control group but with a trend toward higher titres in patients with hypergammaglobulinaemia. Interferon (IFN) responses were not defective, though sequential in-vitro IFN production from peripheral blood mononuclear cells (PBM) fluctuated considerably in the same patients, occasionally being absent with no obvious clinical correlate. IFN-alpha was induced by stimulation with Newcastle disease virus (NDV), and the mean responses of the patients were significantly greater than those of controls. IFN-gamma production on phytohaemagglutinin (PHA) stimulation was similar in patients and control groups. IFN was not detected in any of the sera from patients or controls. [ABSTRACT FROM PUBLISHER]

Eighteen patients with active systemic juvenile chronic arthritis (JCA) were studied for periods of up to 1 year to see whether any relationships existed between the interferon (IFN) response, the course of the underlying disease and intercurrent infections. The control group consisted of 23 children who were each seen on one occasion. IFN-α production by mononuclear cells (MNC) cultured in vitro was stimulated with Newcastle disease virus (NDV). Comparison of the mean IFN-α responses from all patients with control responses showed that MNC from the JCA group produced significantly more IFN-α. Furthermore, MNC obtained from JCA patients at times of systemic flare produced significantly higher titres of IFN-α than at times when the patients were clinically stable. IFN-α production by MNC from individual patients fluctuated considerably from occasion to occasion whereas IFN-γ production by MNC induced with phytohaemagglutinin (PHA) remained more stable. There was no significant difference between patients and controls with respect to IFN-γ responses and no relationship with clinical condition. Serum IFN was not detected either by sensitive bioassays for IFN-α and IFN-γ or by an immunoradiometric assay for IFN-α. [ABSTRACT FROM AUTHOR]

The interaction of influenza virus and human lymphoid cells has been studied by electron microscopy. The result suggest that virus is inactivate by lymphocytes after uptake of virus into cytoplasmic vare\culls, Over a period of 24hr, the virus particles are processed by the cell, the vast majority becoming undetectable by electron microscopy. [ABSTRACT FROM AUTHOR]

Small groups of volunteers were inoculated intranasally with live-attenuated, and parenterally with detergent-split-saline or with whole-virus-oil-adjuvant influenza A2/HK (H3N2) vaccines after the prevalence of Hong Kong strains. Antibody titres in nasal secretions and serum were measured by HI, antineuraminidase and neutralization tests. The oil adjuvant vaccine produced large rises in antibodies and the other two vaccines produced small rises. The volunteers given oil adjuvant and live vaccine were both well protected against challenge with a partly attenuated strain. Statistical analysis showed that resistance to infection was predicted best by high titres of antibody in the serum, but the presence of antibody did not seem to explain completely resistance to infection. [ABSTRACT FROM PUBLISHER]

In the foregoing paragraphs I have discussed in outline several areas where biochemistry has been able to make a positive contribution to fungal taxonomy. The review is not intended to be exhaustive, but rather to alert classical fungal taxonomists to the contribution biochemists may make to their specialty. The number of species studied, although still very small compared with the number of species described, is steadily increasing, and it is therefore expected that comparative biochemistry will in the future play an increasingly important role in fungal taxonomy. [ABSTRACT FROM AUTHOR]

Four agents which were obtained from adults with common colds were cultivated and identified—one was influenza type B and the others were parainfluenza viruses of types 2 and 4. Their cultivation was assisted by the use of organ cultures of human embryo tracheal or nasal epithelium. They infected and caused typical common colds in volunteers. [ABSTRACT FROM PUBLISHER]

Skin reactions have been produced in normal subjects by the injection of highly purified influenza A and B viruses. The reactions reached a maximum at 24–48 hr. and the histological pattern was compatible with a delayed hypersensitivity reaction. There was no close relation between skin test results and circulating antibodies. Twenty-seven subjects were challenged intranasally with attenuated influenza A (H3N2): 5 of 14 skin-test-negative subjects were infected, but none of 13 skin-test-positive subjects. [ABSTRACT FROM PUBLISHER]

Six of 12 men wintering at an isolated Antarctic base sequentially developed symptoms and signs of a common cold after 17 weeks of complete isolation. Examination of specimens taken from the men in relation to the outbreak has not revealed a causative agent. [ABSTRACT FROM PUBLISHER]

Respiratory disease on Tristan da Cunha has been observed since the islanders returned in 1962. An epidemic of unprecedented severity occurred in the winter of 1971 and involved 273 (96%) of 284 islanders, 92 of whom had two attacks. The epidemic was apparently introduced by the Tristania.The illness of both first and second attacks ranged from mild to severe but there were some differences. There were two deaths, both in elderly persons with chronic chest disease and heart failure. Serological evidence suggests that this was due to influenza A2 of the Hong Kong serotype H3N2 [ABSTRACT FROM PUBLISHER]

Forty-nine subjects were vaccinated with either live attenuated, detergent split, or oil adjuvant A2/Hong Kong influenza vaccines, or a saline influenza B vaccine as control. Respiratory symptoms occurred more frequently in subjects who received the live vaccine but in total there was little difference between the symptoms in the four groups. Antibody titres hi nasal washings and serum were measured by haemagglutination inhibition, neuraminidase inhibition and virus neutralization tests. The oil adjuvant vaccine stimulated larger antibody responses than the other procedures. Six weeks after vaccination the volunteers were challenged with partially attenuated live A2/Hong Kong influenza virus administered intranasally. The live attenuated and oil adjuvant vaccines provided the best protection against challenge. [ABSTRACT FROM PUBLISHER]

Thirty-seven volunteers were inoculated intranasally with living attenuated influenza A 2 viruses. Rising titres of circulating antineuraminidase (AN) were detected in 14 of 17 infected volunteers. AN was also found in nasal secretions. Statistical analysis showed that there was a correlation between the titres of haemagglutination-inhibituig antibody (HI) and AN in nasal washings, and between AN in blood and washings. Resistance to infection could be predicted from antibody titres in 29 of 37 volunteers and blood AN alone predicted the outcome of 25 volunteers. [ABSTRACT FROM PUBLISHER]

Records of seven common-cold outbreaks on the island of Tristan da Cunha are compared with the corresponding time courses given by the mathematical model of Kermack & McKendrick (1927) and with an alternative model that directly involves a constant average duration of individual infection. Using computer simulation techniques the latter model is shown to be preferred and is then closely matched to the field data to obtain values for the model parameters. Consideration is then given to the intensity of epidemics predicted by the model and to the distribution of the actual epidemics relative to the theoretical epidemic threshold. [ABSTRACT FROM PUBLISHER]

Eight epidemics of respiratory disease have been observed among islanders of Tristan da Cunha. They seem to be initiated by the arrival of ships and transmission seemed to occur as a result of close human contact but could not always be traced. Islanders suffered from less colds than those in less isolated communities. [ABSTRACT FROM PUBLISHER]

Studies of the effect of Hong Kong (HK) influenza vaccine were made in adults and children in Great Britain during 1968 and 1969. The vaccines were administered intramuscularly and also by intranasal spray. The serum antibody response was studied in 284 subjects. Most developed rising titres to vaccine given intramuscularly and few to vaccine given intranasally. Deoxycholate-split vaccine was as potent as conventional whole virus vaccine. Antibody titres were maintained for months. Over 4000 subjects in factories, offices and schools were observed during the epidemic. The incidence of disease was not significantly reduced by either form of vaccination. A survey was made of epidemics in boarding schools in which some of the pupils had been vaccinated, in six with commercial polyvalent vaccine and in five with HK; there was a lower incidence of influenza in two schools vaccinated 2 or 4 weeks earlier with HK vaccine. [ABSTRACT FROM PUBLISHER]

A trial of an experimental live influenza B vaccine has been described.The virus it contained was active and produced infections, antibody rises and clinical reactions.Second and third vaccinations had much less effect than the first. Resistance to revaccination was only partially reflected in the serological response.It seems that another factor, probably local antibody, exerts a considerable influence on resistance to infection with influenza viruses.We are greatly indebted to Dr P. G. Higgins of the Public Health Laboratory, Cirencester, who went to much trouble to provide us with specimens from patients with influenza; to Dr H. G. Pereira of the National Institute for Medical Research for the antigenic analysis of the vaccine virus; to Messrs Sankey Ltd., Bilston, Wolverhampton, for their unfailing courtesy and forbearance throughout the trial; to the volunteers for their enthusiastic co-operation in the face of some discom forts; and to Messrs Pfizer Ltd., Sandwich, for originally providing facilities for the preparation of the vaccine.In particular we wish to record our gratitude for the invaluable technical help of Miss Pamela Ball of the Common Cold Research Unit, Mrs Maria Gregory of the Bacteriology Department of Liverpool University, Mrs L. Johnson of the Virus Laboratory of New Cross Hospital, Wolverhampton, and Mr A. Westoby, an assistant in the practice of Dr Tyler. [ABSTRACT FROM PUBLISHER]

Sera were obtained from about half of the Tristan da Cunha islanders on reaching Cape Town in October 1961, a few months after reaching Britain and before returning to the Island in 1963.After vaccination against current influenza A 2 and B serotypes antibodies were evoked against earlier serotypes, in particular against influenza A1 of 1951 with which the islanders had almost certainly been infected. Those who failed to develop antibody against A 2 and B after vaccination developed it later presumably owing to natural infection.Almost all islanders developed antibodies against parainfluenza 3 and 1 and some against parainfluenza 2 and coxsackie A 21 viruses. There were no antibody rises against reoviruses. [ABSTRACT FROM PUBLISHER]

The amount of virus in nasal and other secretions after infection with coxsackievirus A 21 has been measured daily in ten volunteers. Most virus was found in nasal secretion, less in throat secretion and small amounts were found intermittently in the saliva and faeces.Virus administered as small drops or on a swab was more infectious for man if put on to the nasal mucosa than on to the throat or outside the nose. It was also infectious by the conjunctival route.Virus was sprayed in droplets of about the same size range as those found in a natural sneeze. Virus survived better in larger (> 4 μ) than in smaller droplets. About one tissue culture infectious dose of virus in such droplets also infected volunteers.The symptoms produced by these experimental infections have been analysed. The disease produced was largely independent of the dosage and route of infection. Those with pre-existing antibody resisted infection better than those with no antibody. Antibody rises were detected in about two-thirds of infected volunteers.Volunteers with colds shed virus in large drops on sneezing, or into the handkerchief on blowing the nose, but virus was recovered from the air only after simulated sneezes by volunteers with high concentrations of virus in their nasal secretions. Virus died off rapidly on fabric at room temperature and humidity, and was only resuspended as airborne droplets when large doses such as 0·02 ml. of virus of high titre (107·5 TCD 50/ml.) were used.Infection was transmitted from an infected volunteer to an uninfected partner living in the same flat in three out of twenty tests. Infection was not transmitted in experiments when volunteers mixed for a few hours with subjects with colds, or inhaled air into which a subject with a cold had just sneezed. [ABSTRACT FROM PUBLISHER]

An attempt has been made to study quantitatively the mechanisms by which infectious materials may enter the body by the upper respiratory tract and be shed during a cold.The rapid clearance of tracers, spores of B. mycoides and bacteriophage type T3, has been measured after adding them in small drops to the nose, conjunctiva and mouth.Tracers placed in the nose pass rapidly down the throat, but are found in only small amounts in the saliva. They are dispersed by blowing the nose and, more efficiently, by sneezing. Nearly all are shed as coarse droplets. About 0·1% are shed in droplets small enough to remain airborne and just over half of these are in the size range likely to be trapped in the upper respiratory tract. The droplets are apparently formed mainly in the nose. The larger amounts of droplets formed in the mouth carried relatively few infectious particles.Testing by experiments in a model system it was concluded that most of the coarse droplets produced by a sneeze or by an experimental spray fall rapidly to the floor. A few of the larger droplets were trapped on a moistened microscope slide intended to mimic the possible trapping of droplets on the conjunctive. The spores in these represented only a small proportion of those found in droplets which remained airborne and were collected by an air sampler.We wish to thank Miss P. D. Ball for technical assistance and Dr J. E. Lovelock for helpful discussion in the early stages of this work. We are also grateful to Sir Victor Negus and Dr B. Wyke for discussing the physiology of the nose with us, and to Mr K. R. May for his advice on methods of air sampling. The air samplers were loaned by the Microbiological Research Establishment, Porton, and the photographs taken by the Chemical Defence Experimental Establishment, Porton. [ABSTRACT FROM PUBLISHER]

Experiments reported here were performed on the sera of thirty-three volunteers who were infected or inoculated intranasally or intramuscularly in groups of five to nine with one of two enteroviruses, namely, echovirus 11 and coxsackievirus A21 or with one of three rhinoviruses, namely, M viruses P.K. and ECHO 28, and H virus D.C. Antibody responses occurred against the virus administered, and rarely against the other viruses used. It was concluded that although these viruses are related biologically the antibody responses in the volunteers were largely specific. [ABSTRACT FROM PUBLISHER]

Eighteen volunteers were given live adenovirus attenuated by passage in pig kidney tissue culture. Thirteen were given adenovirus Type 7 and five were given adenovirus Type 4. All volunteers who were given Type 7 and who had no homologous neutralizing antibody on inoculation showed antibody rises. Except in one volunteer not in isolation no signficant symptoms were seen.It is suggested that adenoviruses attenuated in this way might be useful for large-scale vaccination programmes. [ABSTRACT FROM PUBLISHER]

Re-examination of the U-virus of Philipson & Wesslén has shown it to be a typical ECHO virus closely related to Type 11 of this group. Ultrafiltration and ultra-centrifugation techniques indicate that the virus particle has a diameter of about 27 mν and serological studies confirm its antigenic relationship to the ECHO group.The virus has been successfully transmitted via the nasal route to volunteer adult subjects. All of them became infected but the clinical picture showed no more than a very mild gastro-intestinal illness or a slight disturbance of the general well-being.Passage in monkey kidney cells appeared to attenuate significantly when compared with short-term passage in human embryo-lung culture, and this seemed to affect the isolation rate from subjects so infected.The virus is highly immunogenic. Antibodies to the U-virus have been found in normal persons residing in Great Britain.We wish to thank the volunteers for their willing co-operation and Miss J. B. Macdonald for help with the clinical observations. Dr A. D. Macrae supplied the ECHO Type 11 prototype virus and immune serum and Prof. C. H. Stuart-Harris supplied the pooled human sera. The Director, Microbiological Research Establishment, Porton, afforded the use of the ultracentrifuge. Monkey kidneys were supplied by the M.R.C. polio vaccine control laboratories. Mr M. C. Brebner and Miss P. K. Pearce assisted with the laboratory work. [ABSTRACT FROM PUBLISHER]

1. Sixteen cases of paralytic poliomyelitis and twenty-four cases of aseptic meningitis (‘non-paralytic poliomyelitis’) occurring in the Sheffield area were studied clinically and by virological methods.2. Poliovirus was isolated from thirteen of the sixteen cases of paralytic poliomyelitis and from three of the twenty-four cases of aseptic meningitis. In another two of the cases of paralytic poliomyelitis and another six of the cases of aseptic meningitis serological evidence of poliovirus infection was obtained.3. Serological evidence of Coxsackie virus infection was found in four of the cases of aseptic meningitis; but in one there was also clear-cut evidence of poliovirus Type 3 infection, and in another it seemed that the infection was contracted in hospital. Evidence of Coxsackie virus infection was also obtained in five cases of paralytic poliomyelitis.4. Serological evidence of Adenovirus infection was found in one case of aseptic meningitis.5. No acceptable evidence was found of infection with Columbia SK or related viruses, or with the virus of lymphocytic choriomeningitis.6. From one patient with aseptic meningitis an unidentified virus was isolated.We wish to thank Dr J. Kennedy for permission to study patients and Prof. C. P. Beattie and Prof. C. H. Stuart-Harris for help in preparing the manuscript. [ABSTRACT FROM PUBLISHER]

1.The results are reported of a study cases of pneumonia, of upper respiratory indection and of family contacts of cases of pneumoia for evidence of influenza-virus infection between October 1947 and April 1949.2. During an inter-epidemic period in relation to influenza, two sporadic cases of influenza-virus A infection were detected, one in a case of pneumo-coccal pneumonia and the other in a family contact of a case of pneumonia. These were the only instances of virus infection detected amoung 158 individuals including seventy-eight cases of pneumonia.3. The epidemic of influenza from February to April 1949 was associated with an increase in number of notified cases of pneumonia, particularly in those over 45 years of age compared with the notifications in 1948. Deaths from pneumonia also increased, particularly in those of 65years or over.4. During the period of influenza prevalence, direct tests of specimens in eggs and serological tests gave positive evidence of influenza prevalence, direct tests of specimens in eggs and serological tests gave positve evidence of influenza virus A infection in many instances. Twenty-six of forty-one cases of upper respiratory infection between February and April 1949 were positive for influenza A and one was a case of influenza B.5. Eifgteen of fifty-five cases of pneumococcal and staphyococcal pneumoniaccal and staphylococcal pneumonia, eight of fifteen cases of bronchitis, one of two cases of bronchiectasis and four of six cases of congestive heart failure gave serological or cultural evidence of influenza virus A infection during the period of February to April 1949.6. The mechanism of influenza-virus infection in relation to bacterial infection of the lower respiratory tract is discussed. [ABSTRACT FROM PUBLISHER]

An illness consisting of vomiting, fever, and mild diarrhoea after a short incubation period was observed in a boarding school and reproduced in volunteers who received filtered extracts of faeces from a typical case. The main discriminatory diagnostic feature of the illness in volunteers was vomiting. The faeces contained no pathogenic bacteria nor any virus that could be detected in tissue cultures and there was no evidence that an infective agent could be grown in organ cultures of human intestine. The agent was shown to be ether stable and passed a 50-nm filter. Laboratory studies on another agent of uncertain significance and obtained in other epidemics are briefly described. [ABSTRACT FROM PUBLISHER]

Influenza strains produced by recombination and tested as possible live vaccine candidates were studied in organ cultures of trachea. Two strains which proved to be too virulent in human volunteers regularly caused damage to the ciliated epithelium and viruses grew to high titre. Two strains which proved to be attenuated for volunteers did not cause appreciable damage, although they replicated to low titre in the epithelium. Similar results were obtained with influenza A virus attenuated by passage in the presence of horse sera. The method may be of value for detecting virulent live influenza vaccine candidates without risking severe illness in volunteers. [ABSTRACT FROM AUTHOR]

The nasal washings from 52 volunteers were tested. Twelve had received a partly attenuated A2 influenza Leningrad/4/65 and 37 a similar B England/101/ 62 strain. Interferon was detected by titration with rhinovirus type 2 in human fibroblasts and with Sindbis virus in a continuous line (V 3) of monkey kidney cells. In volunteers given influenza B, interferon was found in specimens collected 4 days after inoculation in 12 of 22 infected volunteers and 2 of 15 uninfected volunteers. There was no relation between the presence of interferon in infected volunteers and the clinical severity of illness but volunteers who developed higher titres of antibody in convalescence had had higher peak interferon titres in the acute phase of the illness than those who developed low titres. Interferon was also detected in the nasal secretion, blood and urine of a volunteer with a naturally acquired cold and in volunteers infected with rhinovirus type 2 and influenza virus. It was found in nasal secretion from 1 to 5 days after infection and not on the 6th. Low levels of interferon-like activity were also found in a few volunteers before inoculation-the significance of this is not understood. [ABSTRACT FROM AUTHOR]

Attempts were made to grow certain viruses in organ cultures of Fallopian tube. Influenza A and B, parainfluenza type 2, rhinovirus type 2, ECHO virus type 11 and adenovirus type 7 were observed to multiply, but poliovirus type 1, a human 'coronavirus' and rhinovirus type 3 did not. [ABSTRACT FROM AUTHOR]

A strain of HeLa cells, L 132 cells and roller tube cultures of human embryo respiratory epithelium were compared with standard laboratory systems for the propagation of certain rhinoviruses, parainfluenza viruses and some others. [ABSTRACT FROM AUTHOR]

The conditions for the cultivation of the 229-E respiratory virus in tissue culture are described. The virus multiplies only in human tissue culture systems, but a variety of cell types are sensitive to it. The virus has been isolated in three continuous cell lines and a plaque assay has been developed in one of these. This cell line (L 132) derived from human embryo lung, was also used to isolate three other viruses of similar morphology which had previously been cultivated only in organ cultures of human respiratory epithelium. High rates of isolation of these viruses were made in L 132 cells using nasal washings from experimentally inoculated volunteers. It is concluded that this cell line is a valuable tool in the study of viruses of this group. [ABSTRACT FROM AUTHOR]

It has been confirmed that plaque assays of rhinoviruses may be performed using M-HeLa cells and 30 mM MgCl. Eighty-seven pools of rhinoviruses grown in human diploid cell strains (HDCS) or organ cultures or as human nasal washings were inoculated into HDCS and M-HeLa cells with 30 mM additional MgCl in the medium. Cytopathic effects were produced in HDCS and in M-HeLa cells by 78 pools, in HDCS only by one, in M-HeLa only by one, and in neither cell type by seven pools. A micro metabolic inhibition test was developed which was satisfactory for the titration of rhinoviruses and neutralizing antibody and for identifying rhinovirus strains with specific antisera. Preliminary observations show that rhinovirus type 2 multiplies in suspension cultures of M-HeLa cells. It is concluded that the use of M-HeLa cells with additional MgCl instead of HDCS should facilitate the laboratory diagnosis of rhinovirus infections. [ABSTRACT FROM AUTHOR]