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. 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.

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.

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. 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. Vaccinated rabbits develop serum anti-haemagglutinin after infection. The anti-haemagglutinin is not found to any appreciable titre in normal human and animal sera tested. It is present in the globulin fraction of rabbit serum and is stable at 70° C. for 30 min. but destroyed at 80° C. for 30 min.

2. Observations over a period of 6 months of variations in serum antibodies in vaccinated rabbits demonstrate that whereas the agglutinin, precipitin and complement-fixing antibody varied in parallel with each other, the anti-haemagglutinin varied independently and in general remained more or less steady throughout the period.

3. Some experimental observations of the haemagglutinin anti-haemagglutinin reaction are reported. The haemagglutinin inactivated by immune serum can be reactivated by boiling. Haemagglutinin adsorbed on to red cells can be eluted by subsequent addition of immune serum.

4. Failure to obtain complement fixation with the haemagglutinin anti-haemagglutinin system is recorded.

5. Vaccinia haemagglutinin is distinct from the L-S antigen.

6. By absorption test, it has been shown that the anti-haemagglutinin is a distinct antibody related neither to L or S antibodies nor to neutralizing antibody.

7. It is concluded that vaccinia haemagglutinin represents a new and distinct antigen occurring in a relatively large particulate state in vaccinia infected tissues. The possible theoretical implications of such findings are discussed.

1. A new series of compounds has been found which markedly inhibits the growth of Mycobacterium tuberculosis and M. smegmatis.

2. These substances are strongly haemolytic against human red blood cells.

3. The effectiveness of the antibacterial and haemolytic actions depends upon the length of the alkyl chain.

4. The antibacterial and haemolytic actions are reduced by human serum.

When a number of organisms are exposed in early rapidly multiplying broth cultures to minimally effective bacteriostatic concentrations of a number of antiseptics, almost complete lysis may be demonstrated.

When older cultures are exposed to low concentrations, or young cultures to strong concentrations, lysis does not occur in many cases.

The lytic effect of penicillin is apparently identical with that of the antiseptics tested. The phenomenon appears to depend on the nature of the effect of the antiseptic on metabolic enzymes, autolytic enzymes, or both.

Our data suggest that there are four different thermolabile antigens in S. dysenteriae (Shiga) appearing in different combinations in the five variants described. These antigens are:

1. The agglutination-inhibiting factor ‘I’, found in variants 1 and 3, which is a typical surface antigen.

2. A precipitinogen, ‘N’, probably identical with the neurotoxin, found in variants 1, 2 and 5.

3. A labile precipitinogen, ‘A’, in the extracts of variants 1 and 2, occurring in the deeper layers of the bacterial cell.

4. An additional precipitinogen, ‘B’, found in extracts of variants 1, 2, 3 and 4. It differs from the other labile antigens as its combining- and immunizing-powers are not destroyed by heating at 100° C. for 2 hr.

It has been shown that certain strains of Salmonella grown in nutrient broth containing sulphite and bismuth, develop variants that are incapable of reducing sulphite to sulphides in the media of Wilson & Blair.

The altered strains showed no alterations in their antigenic and biochemical characters.

1. Investigations have been carried out on the bacteriophage method of typing staphylococci developed by Wilson & Atkinson (1945).

2. Strains previously considered as belonging to one phage type, type 42D, or as untypeable, were classified into a number of types by the use of additional phages. This further classification was rendered possible by the acquired phage resistance of some of the strains. All the resistant strains were lysogenic.

3. It was possible to produce a resistant variant of a strain to two phages. Some of these resistant variants carried both phages. Others could be demonstrated to be carrying only one phage.

1. Investigations have been carried out on the bacteriophage method of typing staphylococci developed by Wilson & Atkinson (1945).

2. Acquired phage resistance has been shown to be responsible for the classification of many strains as different phage types.

3. Repeated testing of the same strains showed that the phage types were stable in character when the strains were maintained under laboratory conditions.

4. When two strains of staphylococci, one of which was lysogenic to the other, were grown together in broth, the susceptible strain underwent a change in phage type. As a result of this, it is considered that, in epidemiological studies, infective material should be plated directly on to a solid medium and not incubated first in broth, as is sometimes done. Evidence has been obtained suggesting that this change of type may also take place in the field. This phenomenon may be of some significance in epidemiological studies extending over a long period of time.

5. An attempt has been made to classify staphylococcal strains by phage methods into types that differ other than by virtue of acquired phage resistance. These are called, for convenience, genetic types. Reasons are given for the view that this may not be a satisfactory method of classification in practice.

1. A description is given of active forms and cysts of an amoeba found in wild London rats, and morphologically identical with E. histolytica.

2. When inoculated into the caeca of young rats, the amoebae invade the wall and produce lesions.

3. Acute infections produced in experimental rats respond to treatment with emetine hydrochloride.

4. The naturally infected rats were restricted to a localized focus, in which cases of human amoebiasis were discovered, thus providing circumstantial evidence of the human origin of the infection, and throwing light on the possible role of rats as reservoir hosts.

1. Bacteriological examination of large samples of Perch and Powan from natural and artificial waters has shown that a considerable decline in the normal bacterial flora of the fish occurs during the summer months. Reinfection occurs when the temperature falls.

2. These variations are largely attributable to the effect of temperature upon the immunological responses of the fish.

3. The bacteria concerned appear to be water bacteria, which invade the muscles and body cavity of the fish, as well as the gill and gut-content.

4. The degree of infection is also influenced by the bacterial content of the water.

1. Evidence is given that in recently inoculated persons the Widal reaction, even when serial quantitative tests are done, has no practical value in the diagnosis of enteric fever. Conscription enlarges permanently the inoculated proportion of the whole population.

2. The diagnostic value of any particular titre depends not only on the relative frequencies with which this titre occurs in normal and infected individuals but also on the incidence of enteric fever in the population and on the fashionableness of the Widal test as a diagnostic aid.

3. It is emphasized that blood culture is a more reliable aid to diagnosis than the Widal test.

A study has been made of the epidemic and endemic aspects of infective hepatitis as it affects the civilian population of Palestine. Since the data analysed pertain primarily to Jews who have migrated to the country during the last 25 years, the results must be interpreted in terms of this group, although available data for other segments of the population are presented. The analysis was based on (a) records of persons who were members of the Sick Fund of the General Federation of Jewish Labour (W.S.F.) and the Rural Sick Benefit Fund (R.S.B.F.), (b) records of infants and children under the supervision of the Hadassah Medical Organization (H.M.O.) and the Tel-Aviv municipality, (c) records of persons admitted to H.M.O. hospitals over a 20-year period, and (d) records of the Government Department of Statistics for 1944.

Sick-fund records and those of supervised children afford reasonably reliable incidence rates for these groups in various parts of the country. Hospital records, however, which have been the only source of information regarding other aspects of the disease are affected to an unknown extent by various factors which determine the selection of persons who apply for hospital care. The analysis has brought out the following points:

1. Incidence of infective hepatitis has been estimated at 100 per 10,000 of the people of Palestine. About 2 per 10,000 Jews in the population were hospitalized with the disease. Incidence was significantly greater in rural districts.

2. Incidence rose to epidemic proportions during the years 1941–4 in the various administrative subdistricts inhabited largely by Jews. On the coastal plain the epidemic reached its peak in 1942, but in the interior incidence was highest in 1943. Rates declined in 1944.

3. Fatality was generally low, but the disease may pursue a severe and even fatal course among children and pregnant women.

4. The monthly distribution of hepatitis cases varied somewhat with age and district. In general monthly indices reached their peak in December and January and dropped to a minimum in May, but among young children a subsidiary peak appeared in July and August.

5. Among native Palestinians 50% of the hospitalized patients were under 5 years of age, whereas among those born elsewhere, whether in Europe, the Mediterranean basin or the Near East, some 60% were between 15 and 29 years of age.

6. Males and females born in Palestine were equally affected, but there were more immigrant males than females in the hospitalized group of cases. Unmarried persons evidently acquired the disease sooner after their arrival than did those that were married.

In conclusion it may be said that the information derived from the hospital records suggests that the disease is endemic in Palestine and is usually acquired in childhood. Immigrants from non-endemic regions are likely to become infected soon after their arrival. The monthly distribution of infective hepatitis cases resembles that of the respiratory diseases, but the secondary rise among children in July and August suggests that flies and food contamination may play a part in transmission.