The agglutination of red cells of seventeen animal species by influenza and Newcastle disease viruses has been quantitatively investigated. The peculiar behaviour of one group of red cells, illustrated by ox, toward influenza virus heated for 30 min. at 56° C. and toward purified N.D.V. has been studied in detail. It is concluded that heated influenza virus acquires an apparently increased titre against ox cells because it has lost its eluting power. Similarly, purified N.D.V. is less readily eluted from red cells, due to the elimination of an ‘elution-hastening factor’ present in infected fluid. The present study illustrates the importance of careful adjustment of all possible variable conditions for individual viruses and individual red cell systems.

1. Ninety-three cases of primary infective gastroenteritis are reviewed. In only one instance was a known pathogen isolated.

2. The clinical features, epidemiology and postmortem findings are discussed.

3. A serologically homogeneous strain of Bact. coli is described which was isolated in over 90% of cases.

4. A discussion follows on the significance of these findings.

1. Experiments in laboratory animals are described, which were made to determine the specific antibody production following injections of diphtheria and pertussis antigens separately or in combination.

2. Agglutinins to H. pertussis vaccine were not increased or otherwise changed by combining H. pertussis vaccines with either diphtheria anatoxine or A.P.T.

3. A striking enhancement of diphtheria antitoxin production occurred when diphtheria prophylactics were used combined with pertussis vaccine. Such improvement in antitoxin production was most marked in the case of diphtheria anatoxine, but was also shown following the use of A.P.T. in combination with pertussis vaccine.

4. Diphtheria anatoxine combined with H. pertussis vaccine gave no better antitoxin response than did a.p.t. alone.

1. The field epidemiology is described of two epidemics of smallpox which occurred in Tripolitania during 1946.

2. Control was effected by the ‘expanding ring’ method instead of mass vaccination of the population.

3. Five hundred cases were admitted to hospital and statistics are given of mortality in relation to age, sex and vaccination state.

4. A new clinical classification is described which enables a reliable prognosis to be made and provides a guide to treatment.

5. Controlled experiments were made on the use of penicillin in treatment. Although it is without effect on the viraemia and in general does not significantly affect mortality, it has the power of suppressing suppuration and reducing the effect of secondary sepsis. It also minimizes the amount of permanent scarring of the skin.

6. Evidence is presented to show that the period of maximum infectivity is the stage of the pre-eruptive fever. The mildest cases are infectious, but only for a short time.

The virus contained in dried scabs is not considered to be an important source of infection; it may, be modified in some way by passage through the skin.

7. Although not protected by successful vaccination many contacts showed a considerable resistance to infection. Amongst the older people this may have been due to previous clinical or subclinical attacks. Amongst the younger persons evidence is produced to show that many were relatively refractory to vaccination and experienced the disease in a different way, suggesting that there is natural partial immunity to smallpox in this particular population.

8. The complex problem of immunity in smallpox is discussed, and it is suggested that three factors operate, an anti-invasion factor, an anti-dissemination factor and a local skin immunity mechanism. A photograph is given of a model made to show the interaction of these three factors in producing the immunity levels which determine the type of disease. It also accounts for the immunity reactions in vaccinia and in smallpox in the vaccinated subject, both when vaccinated successfully during the incubation period of smallpox and when vaccinated successfully some time prior to contact.

It was perhaps unfortunate that this work had to be done under Service conditions without access to literature such as Ricketts & Byles's (1908) classic The Diagnosis of Smallpox, or Marsden's works, particularly his review of vaccination (1946). The lack of authoritative guidance, however, was compensated for by the enthusiasm of all concerned.

I am especially grateful to Lt.-Col. W. McN. Graves-Morris, R.A.M.C., P.M.O. Tripolitania, for allowing me the opportunity to experiment and to use such a large proportion of the territory's supply of penicillin.

I am indebted to Col. W. W. Sharpe, R.A.M.C., D.D.H., M.E.L.F., for enabling me to return to Tripolitania for a short time to complete the records, and to Capt. J. Macbeth, R.A.M.C., Capt. W. L. Forbes, R.A.M.C., Capt. J. Anderson, R.A.M.C. and the late Capt. J. LaFerla, R.A.M.C, who assisted at different stages and in different ways.

1. Elementary body suspensions of vaccinia and ectromelia were obtained from rabbit skin and chick embryo or mouse liver and chick embryo respectively and used to immunize rabbits.

2. Judged by the complement fixation and haemagglutination tests, the viruses from different hósts were very similar antigenically. Ectromelia and vaccinia appeared closely related, the heterologous virus titres being usually lower than the homologous.

3. Elementary body suspension agglutination tests did not reveal a similar relationship between the two viruses, but were not satisfactory on account of the low antibody content of the antiectromelia sera.

4. Highly active ectromelia antisera were not obtained and there was no evidence of multiplication of this virus in rabbits.

5. Only slight neutralizing activity was demonstrated in the antisera.

6. Elementary body suspensions of ectromelia virus prepared from mouse livers, as well as the crude liver extracts, were soon inactivated. Egg membrane preparations were relatively stable.

This paper records the results of systematic pneumococcus typing over a 7-year period in children from 4 days to 12 years of age in the R.H.S.C., Glasgow. Strains typed include those from respiratory tract lesions, from pus in middle ears, meninges, joints, serous sacs and miscellaneous purulent foci. A series of strains from normal throats serves for comparison.

The constant prevalence year by year of types 6, 19, 1 and 23 in all types of disease is striking. On dividing the cases into those under and over 2 years, the incidence of type 1 in the older children is four times that in the younger group. Conversely in those over 2 the incidence of the higher types (21–32) is only half that in the younger patients. No other significant difference in type distribution is observed on comparing the two age groups. Group IV pneumococci are commonly carried in the healthy nasopharynx, and are potential pathogens in young children in whom broncho pneumonia is generally an endogenous infection. There is evidence that the same type of pneumococcus frequently invades the entire respiratory tract and the middle ears. Only thirty of our cases were in the neonatal period and the apparent immunity of the newborn to the pneumococcus is discussed.

1. Methods of rat destruction devised in the United Kingdom during the war were applied to combat plague in Malta.

2. The species were Rattus norvegicus Berkenhout, and R. rattus L. The first is the more common and played an important part in carrying plague.

3. In the last 7 months of 1945, 75 cases of plague were diagnosed. In 1946, 5 cases occurred. A marked fall in the incidence of flea-borne (murine) typhus occurred in 1946.

4. Systematic rat destruction began at the end of August 1945. The method was prebaiting, followed by poisoning with baits and poisons of known efficacy and change of both bait and poison for follow-up treatments. For this purpose a large organization in which the Navy, Army and R.A.F. took part, as well as the Medical and Health Department, was set up under unified control. This made it possible for large blocks and areas to be treated as a whole and within a short space of time.

5. Evidence is given that the degree of clearance achieved by these methods was satisfactory. Comparison of the figures of baiting points visited in first and second baiting treatments suggests, in most instances, a satisfactory kill; this is confirmed by the fact that third treatments, when they were carried out, were found to be unnecessary. Reports from the public and house-to-house inquiry also suggest a very great reduction in rat population.

6. In January 1947, 9 tests for reinfestation were carried out in areas which had been treated between 6 and 17 months before. These tests indicated that few or no rats were present. It is therefore suggested that not only had a good initial clearance been achieved but that the effect was a lasting one.

The author is indebted to Mr W. McA. Gracie, Director of Infestation Control, who also visited Malta in 1945, for making possible the publication of this paper; to Dr A. C. Briffa, Deputy Chief Government Medical Officer, and Mr Paul Cauchi, Rodent Control Officer, for answering many involved questions by post and for carrying out tests of reinfestation; and to Mr A. H. Bathard, formerly officer in charge of the R.A.M.C. Sanitary Section, Malta, for help in analysing the records. Thanks are also due to A. G. Jenson, F.R.I.B.A., for drawing the map and the figures.

Progressive heat inactivation of N.D.V. at 54–58° C. for 15 min. is accompanied by parallel destruction of its haemagglutinating activity. Progressive heat inactivation of Lee virus at 50–54° C. for 15 min. is accompanied by parallel loss of eluting power and ‘enzymic’ action on ‘Francis inhibitor’. Formalin in low concentrations rapidly inactivates both N.D.V. and Lee virus without appreciable impairment of their haemagglutinating activity or ‘enzymic’ function. Higher formalin concentrations acting over several days may, however, produce a slow deterioration of the haemagglutinin of both viruses. It is suggested that heat destroys the infectivity of N.D.V. and influenza virus primarily by abolishing their haemagglutinating ‘enzyme’. The possibility of the existence of independent virus components, all of which are essential for full infectivity of these viruses, is discussed.

1. Two long-continued epidemics of mousepox were set up with different strains of the virus and maintained for 190 and 290 days respectively. Considerable differences were observed between the behaviour of the two strains of virus, the Moscow strain being much more virulent and more highly infective than the Hampstead strain.

2. The two strains of virus maintained their original characters through the experiments.

3. Life tables were constructed for both epidemics, specific and non-specific deaths being dealt with separately. They show that high and durable immunity follows recovery from infection.

4. Two mice which had recovered from infection were found to harbour small quantities of the virus in the lungs, and in one case in the spleen also, suggesting that chronic latent carriers of the virus may occur.

1. Earlier work on forecasting epidemics of smallpox in India, based on the study of the previous rainfall and humidity, has been confirmed and extended by the present study and a few instances which did not conform to the general rule have been explained as due to the spread of the disease from an adjacent province.

2. An extension of the inquiry to other tropical countries of the British Empire indicates that in tropical countries in general with well-marked dry and wet seasons, the annual decline of smallpox incidence to a low minimum in relation to high absolute humidities during the rainy season is the rule; for it is absent in equatorial Uganda with rains throughout the year, and both the monsoon period and the monthly incidence of smallpox are reversed in such a Southern Hemisphere country as Nyassaland in accordance with the general rule.

3. Where smallpox is endemic in such countries increased prevalence in any year may usually be foreseen by watching the meteorological records in time to control the expected increase to some extent by increased use of vaccination.

4. Other air-borne diseases are worthy of study on similar lines in countries with suitable vital statistics and climatic conditions.

1. In a material consisting of 417 cases of typhoid fever and 1055 cases of paratyphoid B investigated over a period of 28 years, infection with S. typhi was found to be considerably more serious than infection with S. paratyphi B. In childhood and among young folk the S. paratyphi B mortality was low, but in the age group over 30 it reached 5%. But even in childhood infection with S. typhi gave a mortality of 8·5%, rising at a higher age to 16%.

2. Of the 1387 patients surviving the infections 13·3% were found to be excreters during convalescence, 11% being temporary and 2·3 % being chronic carriers.

3. Of the temporary carriers, 7·9% were faecal and 3·7 % were urinary carriers. The percentage of temporary excreters was approximately the same for the typhoid and paratyphoid B patients—40% were men and 60% were women. The number of temporary carriers rose with the patients' age, and in the age group over 30 years, about 15% were temporary carriers in the case of both infections.

4. Of the temporary carriers, only one-tenth discharged the specific germ for more than 4 weeks after the cessation of the illness. After an interval of 3 months, it is most exceptional for the carrier state to cease spontaneously. We may, therefore, feel justified in fixing this interval as the dividing line between the temporary and the chronic carrier state.

5. Of the typhoid patients 3·3%, and of the paratyphoid B patients 1·9%, became chronic carriers. Thirty-one of them were faecal and only one was a urinary excreter. There was only one child found to be a chronic typhoid carrier. Chronic carriers were also rare among young folk, and the incidence of this state rose much with age, as many as twelve of the total of thirty-two chronic carriers being over the age of 50. Eleven of these twelve were women, five being typhoid and six being paratyphoid B carriers.

6. Most of the chronic carriers have been kept under control for a long time. The only chronic typhoid carrier to recover spontaneously was a woman, aged 52. Cholecystectomy was performed on fourteen chronic carriers. In all the cases in which the carrier state had lasted for at least a year, gall-stones and chronic cholecystitis were found, and the specific germ was obtained in pure culture from the gall-bladder. A woman who had continued to discharge S. typhi for more than 1½ years after the operation, ceased to do so after this interval. The object of the operation was not achieved in one case.

1. The participation times of a series of mixtures of horse serum and a pool of rabbit antihorse serum have been determined. The results have been presented in a table and isochrones drawn. Four distinct α procedure optima were found, suggesting that there may be at least four different antigen-antibody reactions concerned when horse serum reacts with a rabbit antihorse serum.

2. The reaction between horse serum crystalbumin and the same pooled rabbit antihorse serum has been investigated, and recorded-similarly.

3. Inhibition of precipitation was found to be more marked in the region of antigen excess than in the region of antiserum excess. Evidence is presented in support of the view that the occurrence of multiple zones may obscure this observation.

4. The results are compatible with the view that the second stage of the precipitation reaction is specific.

5. The isochrones correspond with Boyd's R type.

Three sets of experiments were carried out on undergraduate medical students at Oxford, Cambridge and Liverpool during the years 1941–4 in order to supplement the information obtained previously (Downie et al. 1941) on the comparative antitoxin response of those given active immunization alone (Group A) and those given combined active and passive immunization (Group A+P). A summary of each of the experiments has already been given in the text, so that it is unnecessary here to do more than recapitulate briefly the main results.

1. The first experiment showed that in Group A the antitoxin response was not appreciably greater in students receiving doses of 0·3 and 0·3–0·5 ml. of A.P.T. at 4 weeks’ interval than in those receiving doses of only 0·1 and 0·3 ml. In Group A + P no difference was noticed in the antitoxin content of the serum 6–8 weeks after the second injection of A.P.T., but 10–12 weeks after the second injection there was a difference in favour of the students receiving the larger doses of A.P.T., though it was below the conventional level of statistical significance.

2. The second experiment showed that when the doses of A.P.T. were spaced by 2 instead of by 4 weeks the antitoxin response was much less in both the A and the A + P groups, though the difference was less in the latter group, particularly when the measurements were made 10–12 weeks after the second inoculation of A.P.T.

3. The third experiment showed that a dose of 5000 units of diphtheria antiserum given at the time of the first injection of A.P.T. inhibited antitoxin production to a greater extent than a dose of 400–500 units, though the difference was much less when the measurements were made at 12 weeks after the second inoculation than at 4 weeks.

A compilation of the results obtained during 1940–2 in groups of students receiving active and those receiving active plus passive immunization shows that the antitoxin production in the first group (Group A) was much higher than in the second group (Group A + P) 6–8 weeks after the second injection of A.P.T., but that 10–12 weeks after the second inoculation the difference, though still significant, was considerably less. The final Schick-test results at 10–12 weeks gave a Schick-conversion rate of 98.0% in Group A and of 90.9% in Group A + P.

A review of the results obtained during the years 1939–44 on about 450 students at Oxford, Sheffield and Liverpool leads to the conclusion that the effect of giving diphtheria antiserum at the time of the first injection of A.P.T. is to cause a delay and some degree of inhibition in the antitoxin response of the subject. The larger the amount of antiserum given, the greater is this effect. With a dose of 500 units, though the delay in antitoxin formation is very obvious 4 weeks after the second injection of A.P.T., the final degree of immunity attained, as judged by the antitoxin concentration of the blood serum and by the Schick-conversion rate, is not greatly inferior to that resulting from active immunization alone; and even with a dose of 5000 units, the Schick-conversion rate reaches 81 % 12 weeks after the second injection of A.P.T. It is clear, therefore, that the antiserum, even when given in a dose as large as 5000 units, does not neutralize more than a small part of the antigenic activity of the first dose of A.P.T. Its main effect is apparently to diminish the rate of sensitization of the tissues, so that when a second dose of A.P.T. is given 4 weeks later, the rise in the antitoxin content of the blood serum is considerably delayed. Our experiments suggest that by increasing the size of the first dose of A.P.T., some of this delay may be avoided.

The partial neutralization of the first dose of A.P.T. will result in a decrease in the total antigenic stimulus and a delay in the time at which ït comes into operation. It is suggested that, provided the tissues have not been previously sensitized to diphtheria toxin, the result may be that the two doses will act virtually as a single dose. Such an explanation, however, must remain unproven till further observations have been made (see p. 35).

The practical value of combined active and passive immunization, especially when joined with temporary segregation of healthy carriers, in combating outbreaks of diphtheria in schools and other institutions for children has been clearly shown by Fulton, Taylor, Wells & Wilson (1941). Our present experiments lead us to suggest that, when applying the method in practice, it would be wise to give an initial dose of 0·5 ml. of A.P.T., together with 500 units of diphtheria antiserum injected at a different site, followed 6 weeks later by a second dose of 0.5 ml. A.P.T. It is probable that children treated in this way will develop approximately the same ultimate degree of immunity as those actively immunized with doses of 0·3 and 0·5 ml. of A.P.T. at 4 weeks’ interval.

We should like to express our thanks to Prof. A. D. Gardner and Prof. H. R. Dean for permitting observations to be made on the students in the pathology classes at Oxford and Cambridge; and to the students themselves at Oxford, Cambridge and Liverpool, for their ready co-operation in the inquiry.

1. The genus Corynebacterium is common in the vagina. In direct smears forms with exaggerated curvature and staining Gram-negatively may easily be mistaken for vibrios.

2. Attention is drawn to the not infrequent presence of Gram-negative cocci in direct vaginal smears. From these cases Diplococcus crassus, a commensal member of the genus Neisseria, has been isolated. These cocci could be mistaken for gonococci.

3. An unusual organism seen in two direct smears from the vagina is described, and the suggestion is made that it may be Streptobacillus moniliformis.

Quantitative studies have been made of the survival of foot-and-mouth disease virus in beef and beef offals after storage at temperatures employed in the imported-meat trade.

The survival of virus is closely associated with the hydrogen-ion concentration of the tissue; thus the acidity of rigor mortis of muscular tissue rapidly causes inactivation. Quick-freezing of beef suspends acid formation and active virus was demonstrated for so long as the meat was kept frozen.

Thawing of quick-frozen meat initiates the suspended acid formation at an accelerated rate and rapidly produces a medium unsuitable for virus survival.

Liver, kidney, rumen, lymph node and blood from diseased cattle have all been shown to be highly infective and to remain so if stored frozen. Acid formation in these tissues and in blood is not on the same scale as in muscle, and prolonged survival of virus is more likely even with delay in freezing and after thawing. This remains true of lymph node and of residual blood in vessels of a carcass in which the development of rigor mortis is complete.

Feeding of infective offal to swine under experimental conditions resulted in the appearance of the disease.

The significance of these observations is discussed in relation to the distribution of these products constituting a risk of spreading foot-and-mouth disease.

We are indebted to Dr Ian A. Galloway, Director of this Institute, Mr L. B. A. Grace, Chief Technical Adviser on Meat Inspection of the Ministry of Food and Mr R. Bremner, Chief Executive Officer of the Meat Importers' National (Defence) Association, Ltd., for their help and advice while this work was in progress.

It is a pleasure to acknowledge the technical assistance of Mr W. J. Brownsea.

1. Standard Bact. coli cultures have been heated at 51° C. in phosphate buffered media having pH values ranging from 2·8 to 8·8, and survivor curves obtained.

2. Except at pH 3·9, the first continuous decline in viable numbers was followed by the establishment of a small fluctuating residual population which was apparently permanent.

3. The colony counts showed a moderate excess of unduly high values of x2, the bulk of which were encountered when the mortality was between 95 and 99·999%.

4. Prolonged incubation of the plates led to increased colony counts, but the rise was confined to the active disinfection phase. It occurred chiefly in the 95–99·999% mortality range and was moderate in degree. The x2 values were little affected.

5. The log survivors-time graphs of the disinfection phase were convex in type but approached linearity in the faster reactions. The logarithmic death-rate became maximal at about 90 % mortality and thereafter remained constant, though under the more acid conditions a somewhat lower rate was maintained. At pH 7·0 and 6·4 the curves were exceptionally straight.

6. Standardization of all the curves revealed a continuous change in shape with pH but, nevertheless, they could be placed in three closely knit overlapping groups which were best revealed by the variation in maximum death-rate.

7. The 50–99·99% mortality times were obtained either from the calculated regressions of log survivors on time over the linear portions of the curves or, outside that range, from the freehand curves. Maximum survival at all mortality levels occurred at about pH 6·5–6·6, i.e. close to the neutral point of pure water at 51° C. On both sides of this point sensitivity increased regularly but was abnormally high at pH 7·0 and 6·4.

8. Within these zones of abnormally high sensitivity the assessment of the effect of a given change in pH varied in amount and direction according to the mortality level chosen.

9. The enhanced resistance of a culture regenerated from the survivors of a disinfection at 51° C. and pH 7.0, as previously reported, could possibly have been largely due to a small increase in acidity but not to a slight shift towards alkalinity.

1. Six cases of haemolytic disease in newborn foals apparently due to iso-immunization of pregnancy are described from their clinical, serological, haematological and pathological aspects. The findings agree closely with those seen in the same disease in newborn mules.

2. The disease may be diagnosed serologically by demonstrating the in vivo iso-sensitization of the foal's red cells by means of the direct antiglobulin-sensitization test. It is quite possible that after further investigation a modification of Diamond's albumin tube test may also be of value. Immune anti-red cell iso-antibodies of more than one specificity may be demonstrated in the dams' sera.

3. Despite the acute haemolytic process, very few reticulocytes and no erythroblasts are seen in the peripheral blood.

4. The morbid histology of the tissues of foals dying with the disease exhibits various points of interest which are discussed.

5. The clinical aspect is not described in this paper in any detail. However, a programme is suggested which would enable a successful exsanguino-transfusion of compatible blood to be carried out at very short notice. At present this seems to be the logical and most practical method of specific treatment.

Two different types of nucleus are found to occur in bacteria. The first is a spherical, central or eccentric body occurring in some types of cocci and in Corynebacteria. By analogy with a similar structure in Azotobacter, it is considered that the nucleus may be of vesicular form, surrounded by chromatinic granules, and resembling the nuclear vacuole of certain yeasts.

The second type of nucleus consists of paired chromosomes, usually either one or two pairs. These chromosomes form fusion nuclei within which chromosome divisions take place; they are then redistributed to a number of daughter cells.

The majority of rod-shaped Eubacteria, including the lanceolate-celled streptococci, have this type of nucleus, which is also found in Myxobacteria. The nuclear cycle is quite distinct from the cytological processes which accompany spore and microcyst formation and germination.

1. Specific vaccinia haemagglutinin has been identified in vaccinia materials derived from chick embryo, rabbit skin, rabbit testis and sheep skin.

2. The haemagglutinin is distinct from, and apparently unassociated with, the elementary bodies.

3. Centrifugation studies indicate that the haemagglutinin activity is associated with particles of the order of 65 μ in diameter and having an approximate density value of 1·;1.

4. Vaccinia haemagglutinin retains its haemagglutinating activity after boiling for 10 min. It is stable within the pH range 5·92–9·79.

5. The behaviour of vaccinia haemagglutinin to various chemical procedures and an attempt at its purification are described.

1. A food-borne outbreak of streptococcal infection in a cavalry regiment is described.

2. A controlled therapeutic experiment was carried out on the forty-nine patients admitted to hospital. Those given chemotherapy recovered more quickly than the controls, recovery being most rapid in the group given intramuscular penicillin.

3.Typical scarlatiniform eruptions were seen in ten cases. Streptococcal antitoxin appeared to prevent the occurrence of rashes, but had no significant effect on the duration of fever and toxaemia.

4. Upper respiratory complications supervened in ten cases. Evidence is presented which suggests that they were due to cross-infection.