In principle, an unknown date of infection can be estimated from individual response times, provided some function of these with suitable origin is symmetrically distributed. Observed times are always skewly distributed, and either logarithm or reciprocal of time can be used to produce symmetry. Either is equally justifiable but the resulting estimates are not only very imprecise but are also inconsistent, so that neither is of practical value.

Two outbreaks of salmonella food poisoning are described. In one, involving 55 persons, the infecting organism was Salmonella reading, and in the other, involving 39 persons, S. tennessee. In both, epidemiological and bacteriological evidence pointed to imported cans of cooked meat as the source. The role of contaminated shop equipment in furthering the spread of infection is particularly emphasized.

Attention is drawn to the severity of the symptoms and prolonged excretion of the organism in a number of the patients infected with S. reading.

The addition of a parapertussis component to diphtheria–tetanus–pertussis vaccine reduces the agglutinogenic potency of the pertussis component in mice. The loss is evident when the amount of the parapertussis component added is 25% of that of the pertussis component, while the influence of relatively lower amounts of parapertussis organisms is less striking.

The parapertussis component in these vaccines, amounting to 2–25% of the pertussis component, does not affect the protective power of the pertussis component in mice.

RK 13 and primary PMK and VMK cell cultures were compared for the isolation of RV by means of the simultaneous inoculation of original specimens and early passage material. RK 13 was found to be the most sensitive and reliable and provided a result for both isolation and neutralization in the shortest time. As the interpretation of CPE and the propagation of these cultures is sometimes difficult, the simultaneous use of a second system in which RV is easy to identify, e.g. VMK or PMK cell cultures, is recommended. Both PMK cell cultures and LLC-RK1 were suitable for isolating RV from clinical specimens. Preliminary studies with LLC-RK 1 indicate that it may provide an even more sensitive alternative to RK 13, but further studies employing clinical material require to be carried out before firm conclusions can be reached.

This paper describes the study of a mutant of Vibrio cholerae which is shown to be attenuated by its avirulence to mouse, rabbit and chick embryo. This mutant character is stable, and the avirulence of this strain probably results from its inability to multiply actively in the tissues of the infected animals. The need for the study of such attenuated strains as live vaccines in man is discussed, and certain aspects of immunity to cholera are reviewed.

Between October 1963 and April 1965, 113 children with respiratory disease and 113 children with diarrhoeal disease were matched for age and time of entry into hospital and studied by virus isolation and serological techniques.

Infections with respiratory syncytial (RS) virus, parainfluenza virus and herpes simplex virus respectively were found in 29, 11 and 12 children in the respiratory illness group but in only 1, 2 and 4 children in the diarrhoeal group. Rhinoviruses were isolated from 10 children in each group and in seven cases were associated with lower respiratory disease. Adenovirus infections were found in nine children with respiratory disease and eight with diarrhoea. Of the 40 enteroviruses isolated 16 were associated with respiratory disease and 24 with diarrhoea.

A poor or delayed serological response in children under 4 months with RS virus infection was observed. Addition of unheated rabbit serum increased the sensitivity of the neutralization test with RS virus.

These findings indicate that respiratory syncytial and parainfluenza virus infections were clearly associated with respiratory illness but the pathogenic role of the other viruses was not clear.

Because the international basic set of staphylococcus typing phages includes only one member of group IV—phage 42 D—the group is insufficiently characterized. This set of phages is therefore not suitable for typing bovine strains of Staph. aureus. The addition of several further group IV phages would remedy this deficiency.

For maximum utilization of deep cultures to produce FMD virus it was important to have adequate control of culture temperature and pH. Culture temperature should be controlled within the range 34·25°7–35°C. and culture pH at 7·2. The culture system became less efficient as the cell concentration was increased from 1 × 106·0 to 9 × 106·0 cells/ml. A cell concentration of 2·5 × 106·0 cells/ml. represented a working compromise between efficiency and antigen titre/ml. for inactivated FMD vaccine production.

The input virus/cell ratio had no effect on the time or titre of peak virus yield in the range 1:1 to 1:320. This makes the production of seed virus from small numbers of monolayer cultures feasible and economical.

Virus yield was improved by the addition of 5% serum. It would be more satisfactory if a serum-free cell strain could be developed.

Young men were immunized against cholera, typhoid, paratyphoid A, and paratyphoid B. Agglutinating antibodies were measured 3 weeks after completion of the immunization schedule. Two injections separated by a 4-week interval were found to be as efficient as three injections with 1-week intervals.

Intracutaneous immunization with one-fifth of the standard subcutaneous dose was just as efficient as the standard subcutaneous immunization and did not cause greater general or local reaction.

Forty-one children in an Edinburgh nursery were observed for evidence of respiratory illness from November 1963 to April 1964. During this period serial specimens of serum from these children were examined for virus antibodies and serial throat swabs were investigated for the presence of virus. Well-defined outbreaks of respiratory illness occurred and could be associated with respiratory syncytial virus, parainfluenza 3 virus and influenza C virus infection. Infection with adenovirus followed a more endemic pattern. The antibody response in infants to respiratory syncytial virus as measured by the standard complement-fixation test was found to be much poorer than the response to parainfluenza 3 virus. It is suggested that this may play a part in the severity of respiratory syncytial virus infection in infants.

The literature of human infection with Salmonella choleraesuis in China was fully reviewed with special reference to those written in Chinese language which are inaccessible to many readers. Compared with other regions of the world the ratio of S. choleraesuis to other salmonella infection in Hong Kong is high and is parallel to that in China. Dietetic habits of the local population apparently contribute to the high incidence. The clinical manifestations of 47 cases were outlined and details of the biochemical reactions and in vitro drug sensitivities of these strains were described. Two diphasic H2S-positive strains were encountered.

Between 1964 and 1966 comparative studies were carried out in Aberdeen, Scotland, and in village settlements in Fiji on the clinico-epidemiological features of molluscum contagiosum. In Aberdeen there was a positive correlation between this disease and attendance of patients at public swimming baths. The preponderance of male patients in Aberdeen was attributed to their more frequent indulgence in swimming. Household spread of the condition was rare in Aberdeen but common in Fiji. Lesions frequently occurred unilaterally or were situated on opposing skin surfaces. They were mainly central in distribution in Aberdeen, the axilla being a site of predilection. In Fijians, peripheral lesions were fairly common though palms and soles were not affected. Peak age incidence in Aberdeen was 10–12 years, contrasting with a peak at 2–3 years in Fiji. Opportunity for contagious exposure appeared to be the main factor determining transmission of molluscum contagiosum between hosts, this opportunity occurring frequently and early in life in Fiji but only under special circumstances and later in childhood in Aberdeen. However, the age distributions in the two populations suggested the possible operation of immunological as well as environmental factors in determining the overall pattern of disease in the community.

We should like to express our thanks to the following people whose support and co-operation made this joint study possible: Dr K. J. Gilchrist, Principal of the Fiji School of Medicine; Prof J. A. R. Miles, Department of Microbiology, University of Otago; Dr C. H. Gurd, Director of Medical Services, Fiji; and Prof. A. Macdonald, Department of Bacteriology, University of Aberdeen. We are indebted to Dr T. E. Anderson and Dr R. A. Main of the Aberdeen Royal Infirmary for referring patients, to Mr W. Hodgkiss of the Torry Research Station, Aberdeen for carrying out the electron microscopy and to Dr Peter Bennett, Nuffield Foundation Scholar in Tropical Medicine from Aberdeen in 1962, who brought to the attention of the Aberdeen workers the prevalence of molluscum contagiosum in Fiji. Part of the work was supported by a grant to R. Postlethwaite from the British Empire Cancer Campaign for Research. Mr (now Dr) Ian Simpson and Miss Helen Adam were supported by Nuffield Foundation Scholarships in Tropical Medicine, and Dr J. A. Watt by a Garden Research Fellowship from the University of Aberdeen.

Experiments were made to find out whether the common communion cup is likely to serve as a vehicle for the transmission of infection.

A silver chalice and sacramental wine containing 14·5% of alcohol were used. Observations with volunteers showed that the number of organisms deposited on the rim of the chalice varied from person to person, but was usually quite small—less than 100.

Rotation of the cup was of no benefit except to those partaking during the first round, since the saliva deposited on the rim by each person in turn remained to contaminate the cup during the second round, and the combined effect of the alcohol and the silver of the chalice was not rapid enough to destroy the contaminating organisms before rotation of the cup was completed.

On the other hand the use of a linen cloth or purificator led to a diminution of about 90% in the bacterial count of the cup.

Organisms in saliva deposited on the interior of the dry chalice suffered some diminution in numbers within 8 min., presumably as the result of the disinfectant action of the silver, but the effect was too small to be of significance.

When suspended in wine and deposited on the internal surface of the chalice Escherichia coli suffered a substantial reduction within 3 min., Streptococcus pyogenes was destroyed completely; but Staphylococcus aureus was affected to a much less extent.

Various experiments designed to measure the disinfectant action of wine, and of silver and wine together, showed that the augmenting effect of silver on the disinfectant action of the alcohol was quite small. Strep. pyogenes proved to be far more sensitive to alcohol than Esch. coli, Staph. aureus and Serratia marcescens. Under the conditions of the experiment these last three organisms were not destroyed for 10–12 min., whereas Strep. pyogenes perished within 1½ min.

The results of our work are in general agreement with those of previous workers, and show that the organisms deposited on the rim of the communion cup are not destroyed within the short time—5 sec. as an average—elapsing between the partaking of the sacrament by each successive communicant.

It must therefore be admitted that the common communion cup may serve as a means of transmitting infection. Reasons are given, however, for believing that the risk of transmission is very small, and probably much smaller than that of contracting infection by other methods in any gathering of people.

Such risk as there is could be greatly diminished by the use of a purificator for wiping the cup between each communicant, and could be abolished completely by substituting individual cups or by the practice of intinction.

Immunization of men with various amounts of salmonella antigens gave a linear relationship between the logarithm of the dose and the logarithm of the titres of the antibodies produced. No secondary response was observed for any of the doses used. These doses of salmonella vaccine did not interfere with or stimulate simultaneous primary or secondary vaccination with tetanus and diphtheria vaccine.

Four strains of Edwardsiella tarda, a recently described member of the Entero-bacteriaceae, were studied, They were isolated from four out of 832 children during a 3-year survey of juvenile diarrhoea at Vellore, S. India. Three of the four children had diarrhoea when the organisms were isolated and one was convalescent from bacillary dysentery. From this study and a review of the literature it appears that Ed. tarda is found only infrequently in man and that its main reservoir may be in animals such as snakes and seals. It is suggested that this organism should be specifically looked for in cases of diarrhoea to determine its etiological role, particularly when the major intestinal pathogens are not isolated.

This work forms part of the studies on the etiology of diarrhoeal infections in children for the Ph.D thesis of P.B., and the grant from the Indian Council for Medical Research towards these studies is gratefully acknowledged. We also wish to thank Dr Sakazaki for serotyping the strains.

An investigation into the antibiotic sensitivity of B. abortus biotypes to polymyxin B sulphate, amphotericin B, and bacitracin has shown that the dye-sensitive strains are also antibiotic-sensitive; and preliminary experiments suggest that these two properties are not genetically related.

The results suggest that biotype 2 can be subdivided on the basis of antibiotic sensitivity pattern, and that this could be of epidemiological significance.

Investigation into the antibiotic sensitivity pattern of the dye-sensitive variant B. abortus, biotype 4, leads us to believe that this strain should be reclassified as a separate biotype and provisionally called biotype 10.

Minimum inhibitory concentrations of tetracycline to 256 tetracycline-resistant strains of Staphylococcus aureus were determined. M.I.C.'s tetracycline were appreciably higher among mercury resistant than among mercury sensitive strains.

Mercury resistant strains representing various M.I.C.'s tetracycline grew significantly better in peptone water containing a therapeutic concentration of tetracycline than mercury sensitive strains representing the same range of resistance. The experiment was repeated after both groups had been adapted—or ‘trained’—to grow on agar containing tetracycline, 100µg./ml. The mercury sensitive strains now grew better than the mercury resistant group.

The significance of these findings is discussed. It is concluded that tetracycline resistance is more stable and efficient in mercury resistant strains, and that it is probably genetic in origin—the result of mutation and selection. Tetracycline resistance in mercury sensitive strains is possibly the result of ‘training’.

The associations and significance of both mercury resistance and tetracycline resistance in Staphylococcus aureus are discussed.

The Lf values of diphtheria toxoid alone and in combination with tetanus toxoid or tetanus toxoid plus pertussis vaccine, dried by sublimation in vacuo, sealed under nitrogen, exposed to elevated temperature and rehydrated thereafter were not altered. Lf values declined in samples sealed under air. The values for Kf in the above preparations increased in relation to increased temperatures of exposure for a given time or following exposure to a given temperature for increased time intervals. The sensitivity of the system of testing used was greater following the addition of ‘helper’, a fast flocculating solution of diphtheria toxin, and in the case of dried diphtheria toxoid stored under adverse conditions (sealed under air) for two years, the addition of ‘helper’ was necessary to obtain a flocculation reaction. In general, the results obtained indicated a very high stability for preparations sealed under nitrogen, and a significantly lower stability for preparations sealed under air.

1. The strain HFEM of herpes simplex virus is highly virulent for the 5-week-old mouse when inoculated intracerebrally; the LD50 and the ID50 both being close to the egg infectious unit. It is also virulent when given intraspinally.

2. When inoculated peripherally it seldom causes nervous symptoms in the normal mouse but regularly does so if inoculated into skin which has previously been given a subcutaneous injection of 10% sodium chloride.

3. After intradermal inoculation of pretreated mice with strain HFEM, the paralysis is preceded by the appearance of infective virus in the blood, the sciatic nerve and the central nervous system. Invasion of the central nervous system is prevented by interruption of the local peripheral nerve.

4. There is no evidence that virus enters the central nervous system by way of the lymphatics or by direct extension through the tissues.

5. After intravenous inoculation virus does not invade the central nervous system unless (a) massive inocula are used or (b) the brain is traumatized by injecting sterile saline. After peripheral inoculation insufficient virus to infect even traumatized brain seems to circulate in the cerebral vessels. Paralysis and invasion of the central nervous system are not prevented by circulating neutralizing antibody given 18 hours after inoculation.

It therefore appears that invasion of the central nervous system takes place only by way of the peripheral nerve.

By the negative staining technique both Bittner and influenza viruses are pleomorphic and have similar fringed surfaces. The present study revealed that Bittner virus had one characteristic form consisting of a head approximately 1000 Å. in diameter and a tail up to 3000 Å. long. On storage at −20° C. Bittner virus broke down to reveal a round internal component of 750 Å. diameter. Influenza virus did not break down on storage at −20° C. but a small number of spontaneously disrupted particles revealed that the internal component was in the form of a coil. The circular internal component of Bittner virus is presumed to be spherical and corresponds to the previously described type A particles as seen by negative staining. The complete enveloped particle corresponds to the type B particle of thin sectioning. It is suggested that the thinly sectioned mature type B particle may be a degenerate form of the so-called immature type B particle. In addition, it is suggested that certain murine RNA tumour viruses may have a morphology distinctive to them.