A study was made in liquid medium over 7 days at 37° C. of the inhibitory action of nineteen antibacterial, antifungal and antiprotozoal drugs on twenty strains of M. gallisepticum, eight other avian mycoplasmata, six mammalian mycoplasmata, two saprophytic mycoplasmata and the L-form of Streptobacillus moniliformis (L–1).

The twenty strains of M. gallisepticum from Britain and other countries showed a similar range of drug sensitivity except where resistant strains were included. Tylosin and demethylchlortetracycline appeared to have the highest inhibitory action, followed by erythromycin, spiramycin, tetracycline, chlortetracycline, oxytetracycline and ethidium bromide. A ‘Zone Phenomenon’ frequently occurred with sodium aurothiomalate, inhibition often being observed between 0·1 and 2·0 μg./ml. Polymixin and nystatin had no inhibitory effect on the growth of any mycoplasmata tested. With the exception of erythromycin and streptomycin in some cases, the pattern of sensitivity observed with the mycoplasmata of diverse origin was similar to that of M. gallisepticum, most strains, however, being somewhat more resistant than M. gallisepticum to many of the drugs.

The relative susceptibility of the LLC-MK2 cell line and primary rhesus monkey kidney cultures to thirty-eight prototype strains of human enteroviruses is described; of these strains only ECHO types 16, 18, 21 and 23 failed to cause CPE in the continuous cell line. The efficiency of the two tissues for the isolation of enteroviruses from faecal extracts is compared. The results show that the LLC-MK2 cell line is very satisfactory for the isolation of Coxsackie B and polioviruses, but not so useful for the isolation of ECHO viruses. The identification of enteroviruses by neutralization tests in LLC-MK2 cells is successful.

Sera from two rabbits bled after one, two and three inoculations of concentrated type 1 poliovirus tissue culture fluid were assayed for neutralizing activity by a quantal and a plaque method. The plaque counts in these tests have been shown to approximate to a Poisson distribution as determined by the relationship between the variance and the mean of replicate counts. However, there is a considerable scatter of the points in such a comparison and this accounts for the absence of the expected increase in accuracy of this plaque method over the quantal.

The relationship between the antibody content of the sera determined by the two methods is non-linear. This can be attributed to inhomogeneity of the antibody produced which increases with the number of antigenic stimuli given.

In a survey of enterovirus and adenovirus excretion in normal children in 1961–62, 25,600 faecal specimens were examined, 25,589 of them in cell culture and 17,596 in newborn mice.

Polioviruses were isolated from 156 (0·86%) specimens before Sabin vaccination was introduced in February 1962 and from 389 (5·27%) specimens after this. Coxsackie A viruses were isolated from 894 (5·08%) specimens, Coxsackie B viruses from 196 (0·77%), echoviruses from 278 (1·09%) and adenoviruses from 128 (0·50%).

The isolation rates of these viruses varied with sex, age, geographical area, type of local authority area and season.

The isolation rate of polioviruses before the introduction of Sabin vaccination was the same as in a previous survey carried out in 1957–58, although the rate was lower in Salk vaccinated children than in unvaccinated children. After Sabin vaccination began the isolation rate increased and Type 3 virus replaced Type 1 virus as the most prevalent virus type.

A co-operative study was made of the incidence of infection acquired by patients in medical wards. Records were collected of 6740 admissions to 21 wards in 13 hospitals.

There were 384 clinical infections (5·7 per 100 patients admitted); 135 of them (35%) were infections of the lower respiratory tract, 72 (19%) were septic skin lesions or infected wounds, and 81 (21%) were urinary tract infections.

Infection was believed to have contributed to the death of 59 patients—17% of those infected or 8% of those dying in hospital. Nearly three-quarters of the deaths were attributed to ‘pneumonia’.

Acquired infections were most common and most severe at the extremes of age. There was an excess of males over females in staphylococcal infections and in infections of the lower respiratory tract, and of females over males in urinary tract infections.

The incidence of infection was above average in patients suffering from malignant disease, diabetes, rheumatoid arthritis, cerebral thrombosis and haemorrhage, and from diseases of the urinary tract and of the skin.

There were 110 acquired infections with Staph, aureus and 12 deaths were attributed to them. Over half of these infections were due to staphylococcal strains which caused only one clinical infection in a ward in the course of a year.

Pneumonia was difficult to diagnose in severely ill or moribund patients, and its clinical significance was hard to assess. It was not possible to obtain a reliable estimate of the part played by bacterial infection in its causation.

The incidence of purulent staphylococcal infections at a large Swedish university hospital was followed during 3 years and has been described as an expression of the incidence of hospital infections.

A marked decrease in the relative number of infections was found. The decrease was most evident among infections with ‘80/81’ strains and other antibiotic resistant hospital strains and was parallel in all the departments investigated. This is taken as an evidence for the assumption that the lowering of the amount of staphylococcal infections was brought about by a factor that was active throughout the hospital, probably some hygienic preventive measure.

Samples of lesions containing viable myxoma virus were collected from 222 infected wild rabbits captured in 80 counties of Britain during October–November 1962. They were dispatched by air to Australia and passaged once in domestic rabbits before being tested for their virulence by the intradermal inoculation of groups of six laboratory rabbits with small doses of virus.

The results showed that a wide range of viruses of differing properties now coexist in Britain. Their virulence ranges from very high (99 % lethal) to low (about 50 %), but the majority of strains fall into the grade III virulence group, with estimated case mortality rates varying between 70 and 95%. The viruses also produce disease of varying symptomatology, skin lesions being very prominent, raised or flat. There was no obvious association between lesion type and virulence.

Tests made on the wild rabbits from which the samples were obtained, and on Inoculated domestic rabbits, showed that virulence could not be predicted by gel-diffusion tests.

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.

The findings are described of a combined clinical, bacteriological and virological study which included all children admitted to the City Hospital, Edinburgh, with acute respiratory infection and whooping cough during the winters 1961–62 and 1962–63. During the first winter 131 cases aged 0–12 years and in the second winter 133 aged 0–6 years were examined. The respiratory illnesses were divisible into upper respiratory tract infection, bronchitis, pneumonia, and whooping cough; many of the cases of whooping cough had respiratory complications with bronchitis or pneumonia.

Paired sera, a throat swab and a faecal specimen were taken from each child and investigated vircdogically. Over both winters the highest total virus isolation rate was found in the group suffering from upper respiratory disease. Approximately two-thirds of the total number of patients from whom virus was isolated and from whom both acute and convalescent sera were available gave a serological response to the homologous virus; the highest proportion of these patients occurred in the pneumonia and URTI groups. The groups of viruses associated with a fourfold or greater rise in antibodies occurred in the following proportions of the cases: myxovirus 9 %; adeno virus 7 %; entero virus 4 %; herpes simplex 3 %.

Bacterial pathogens were isolated from 37 % of patients in 1961–62 and from 49 % in 1962–63, Staph. pyogenes being the most common pathogen. Isolation of pneumococci was facilitated during the second year by the examination of a nasal swab. Pre-admission chemotherapy did not significantly alter the bacterial isolation rates. Agglutination studies were carried out on forty clinical cases of whooping cough admitted during the two winters and thirty-two showed significant stable titres to Bordetella pertussis; only 9 (18 %) of these cases gave a history of prophylactic immunization.

A third of the patients had neither bacterial nor viral pathogens.

The findings in this survey illustrate the need for further intensive virological and bacteriological studies of acute respiratory infections in early childhood.

The protection afforded by a combined enteric and cholera vaccine administered by the intradermal route, and demonstrated by active and passive mouse protection tests and agglutination titres, is excellent and equal to that given individually by the component TAB and cholera vaccines.

In order to reduce the number of injections required and the unpleasant reactions provoked it is suggested that combined enteric and cholera vaccine administered by the intradermal route is of value, where appropriate, for the vaccination of travellers, and for the rapid protection of non-immune persons in the event of natural disasters or mobilization.

Determinations were made of the age distribution of antibody to swine virus and representatives of the various families of human influenza A virus in 1961–62 collections of human sera and paired sera from forty individuals taken in 1952 and 1963:

(a) The existence of cohorts of the population, each with a dominant antibody type related to strains of virus first encountered in childhood, was confirmed.

(b) The basic epidemiological pattern was similar to that previously detected in 1954. However, it seemed that antibody to swine virus had been reinforced but not antibody to A and A1 strains.

(c) Neutralizing and HI antibodies to A/Equine/Miami/63 virus were detected only in the sera of older people (65 years or over) collected in 1964. No antibodies were found to A/Equine/Prague/56 or two duck viruses.

(d) Relatively constant levels of antibody to A, A1 and A 2 viruses were present in sera from aged persons but antibody to swine virus diminished with age. This could be attributed to a lack of swine antibody in the older females.

A hygienic programme, which has been developed and maintained during several years at a large Swedish university hospital, is presented in detail. The composition and working methods of the Infection Control Committee are described and some economic calculations given. The possible connexion between the hygienic measures and a marked decrease of the incidence of infections is discussed. This decrease did not occur until a satisfactory method for the routine hand disinfection had been introduced, using a commercial antibacterial cleaner containing 3% hexachlorophene.

Rappaport's magnesium chloride/malachite green medium was employed in the cultural examination of 2476 faecal specimens in parallel with selenite F broth enrichment and direct plate culture on deoxycholate citrate agar. The use of the medium increased the salmonella isolation rate by 26% over the number of isolations from the other two methods, but proved of no additional value in the isolation of shigella organisms. The addition of Rappaport medium is recommended in routine faecal examination.

Foot-and-mouth disease virus of Type SAT 1 (strain Turkey 323/62) was passaged serially 34 times in cattle previously vaccinated with increasing doses of formol-treated vaccine of the homologous strain. Primary vesicles developed in all the partly immunized animals and secondary lesions occurred in the majority. Virus from the 34th passage was capable of reinfecting a steer only 76 days after primary infection early in the passage series. Virus isolated from the second infection of this animal differed from that isolated from the primary infection in complement-fixing properties and in sensitivity to antiserum, and these differences were of a degree indicative of subtype variation.

The variant strain was transmissible by contact, and virus titres in tongue and foot lesions of partly immunized animals were of the same order as those encountered in susceptible cattle.

These observations suggest one way in which variant strains may arise in the field.

A variola minor outbreak in a 36-bed hospital-ward comprised seven cases of overt variola after the first case. Clinical and epidemiological findings were typical, seven of the eight cases of overt variola being confirmed by virus isolation or antibody titrations. In addition, thirteen definite and seven possible instances of subclinical variola were deduced from complement-fixation or haemagglutination-inhibition tests. A discussion is made of the validity of serological criteria of variolous and vaccinial infections.

A method is given for obtaining the approximate standard error of the anti-serum (or antigen) maxima titre in the complement fixation test when the maxima line is determined by only two points; the same formulae may be used to obtain a conservative estimate of the standard error when more than two points are available. If the degree of lysis in each reaction mixture can be scored more finely than into the three simple states of ‘no lysis’, ‘partial lysis’ and ‘complete lysis’, then more accurate estimates can be obtained. A method is also given for estimating the concentration of one antiserum (or antigen) relative to that of another when they react homologously.

1. The susceptibility of sheep to infection with Langat virus has been studied. No viraemia or symptoms were detected in sheep inoculated either subcutaneously or intracerebrally.

2. Only those sheep inoculated intracerebrally with 106·0–108·0 mouse IC LD 50 of virus developed significant quantities of neutralizing antibody.

3. Two-thirds of sheep vaccinated with varying doses of Langat virus withstood subcutaneous challenge of louping-ill virus followed by intracerebral starch. All the intracerebrally vaccinated sheep survived this form of challenge but no sheep, whether vaccinated subcutaneously or intracerebrally, withstood intracerebral challenge of louping ill.

4. In a field trial, three of ten hoggs vaccinated with Langat virus and exposed to natural louping ill infection at Camlarg and Dalcairnie died of the disease compared with all eight of the non-vaccinated hoggs. At Knockgray, there was no louping ill infection, but 93% of the hoggs from this hirsel developed louping ill antibody after transfer to Camlarg.

5. Monkeys infected intracerebrally, subcutaneously or orally with Langat virus showed a low titre viraemia without clinical symptoms or histological changes in the brain and developed high titres of antibody. Vaccinated monkeys challenged with either Central European tick-borne encephalitis or Kyasanur Forest disease viruses remained healthy compared with control monkeys which showed evidence of disease.

A method of micro-titration for cytolytic antibodies is described. Standard drops of diluent are placed on a subdivided siliconed slide and dilutions are made by rotating a wire loop holding 1 drop of serum in each drop sequentially. One drop of a mixture of cells and complement is then added. The slide is incubated in a moist chamber for 90 min at 37° C. after which a small cover-slip is placed on each drop and the amount of cell lysis, judged by phase-contrast microscopy, is graded.

An analysis of variance of the method has been performed and the method has been found to be reliable, accurate and unbiased.

It allows accurate estimates of cytolytic activity in sera using cell concentrations of 104 to 105 cells per ml. Eight ten-dilution titrations can be carried out with 1 ml. of such a suspension.

Over a 2-year period a dermatology department was shown to be a valid model for the long-term study of hospital cross-infection. In the absence of specific anti-bacterial measures, consistently high levels of Staph. aureus and Gram-negative bacilli were found throughout the environment. ‘Broadcasts’ of Staph. aureus were particularly evident in the bathrooms, and notable sites of heavy, cumulative contamination were the communal baths, bedding, settled dust, and the hands of the staff.

Cross-infection of lesions occurred in ninety-four of the 233 ‘uncontrolled’ patients—15 cases being due to Gram-negative bacilli. Autogenous infection occurred in another fifteen cases. Nasal carriage of Staph. aureus developed in fifty-one patients after admission.

In one of the two main wards nasal disinfection (with ‘Soframycin’ nebulizers) was used for 4 months, and was effective in the treatment and prevention of nasal carriage; but it produced no change in the level of environmental contamination or in the incidence of cross-infection—even though efficient cleansing of the baths was also instituted. In contrast, during two separate periods of the work disinfection of skin lesions (with ‘Rikospray Antibiotic’) markedly reduced the counts of pathogens in the environment, and virtually abolished both cross-infection and the development of nasal carriage.

Cattle were infected with rinderpest virus by housing them for 24 hr. in stalls containing donor animals which had been reacting to the disease for 3–5 days. They were then transferred to individual clean stalls and killed on the 2nd to 10th days following first exposure. Various tissues were collected, particularly those of the upper and lower respiratory tracts, and their virus content was estimated in calf-kidney tissue cultures.

Virus was recovered from 15 of 35 animals tested and in eight of these generalization had occurred, although only two had begun to show a pyrexial response. The stage of the infection could not be predicted from the time that had elapsed following exposure, since early, limited proliferation was encountered on the 3rd to the 10th days.

It was considered that seven animals gave indications of the pathways by which natural infection had occurred. In each of these virus proliferation was established very early in the pharyngeal lymph node; in three the submaxillary lymph node was similarly involved and in four the palatal tonsil. It was suggested that these data probably indicated that infection always occurred via the upper respiratory tract.

In three cases virus titres were highest in the bronchial or costocervical lymph nodes; this was construed as evidence for the additional involvement of the lower respiratory tract in primary infection.

No infectivity could be demonstrated in the mucosae or lung parenchyma associated with the above-mentioned lymph nodes and this, together with previously published data, was accepted as strong presumptive evidence that the infecting virus passes through the mucosae without producing a local lesion or proliferating there. These results were compared briefly with those of Bedson & Duckworth (1963) for rabbit pox.