1. Considerable differences in antigenic efficiency are encountered among batches of (1) diphtheria toxoid, and (2) Cl. welchii (perfringens) toxins prepared under standardized conditions. These differences were revealed in the results of hyperimmunization of horses.

2. Such differences in antigenic efficiency in batches of diphtheria toxoid were also detected by means of injections into guinea-pigs. Two injections, each of 2 Lf doses, were given at an interval of 28 days, and the response measured by means of antitoxin titrations on bleedings taken 10 days later.

3. A general correlation was found between antigenic efficiency as measured by these two methods.

4. A method is described for comparing the affinity for antitoxin, of batches of diphtheria toxoid, by determining the test dose of mixtures containing 9 Lf doses of toxoid and 1 Lr dose of a fixed toxin. The greater the avidity of the antitoxin, the more toxoid entered into combination with it.

5. A correlation was found to exist between affinity for antitoxin and antigenic efficiency of toxoid, as measured both by the response of horses to hyperimmunization and the response of guinea-pigs to two spaced injections.

6. It is tentatively suggested that crude toxoids may contain molecules possessing varying degrees of affinity for antitoxin, due to slight steric structural differences.

1. The association of the α type of Bact. coli, an organism similar to Bact. neapolitanum or to D433 Taylor, Powell and Wright, with gastro-enteritis of infants is further confirmed.

2. A new type of Bact. coli called the β type and differing from the α type in certain of its cultural characteristics and antigenically is described as also associated with cases with similar symptoms.

3. The antigenic structure of the α and β types has been examined, and both types show a well-marked specificity.

4. Either organism can be readily isolated from faeces during an acute phase of the disease, but there may be some difficulty in recovering either during a subacute stage.

5. Both organisms usually disappear from the intestinal contents as convalescence is established, but a certain number of cases have been discharged still carrying them.

6. These organisms can rarely be found in faeces from infants ill with diseases other than infantile gastro-enteritis, or in specimens from adults. When they are found the cases from which they were isolated have usually some history of contact with gastro-enteritis.

7. The actual significance of the association of these organisms with gastro-enteritis has not been determined, but their isolation points to a diagnosis of infantile gastro-enteritis.

8. In cubiclized and open wards the examination of faecal specimens for these organisms provides a means of controlling nursing technique and determining whether or not intestinal cross-infection has occurred.

1. The present inquiry was designed to provide information on the relative frequency of infection in non-pulmonary tuberculosis with the human and bovine type of tubercle bacillus throughout the whole of England. A total of 149 pathologists at 120 collecting centres and 32 bacteriologists at 27 typing centres took part in the scheme. Two questionnaires relating to each patient were used, one to be filled in by the laboratory workers and one by the Tuberculosis Officer or other responsible official.

1. Tubercle bacilli were isolated and typed from 112 patients in Wales. of these strains, 19 or 17·0 % belonged to the bovine and 93 or 83 % to the human type (Table 16).

The post-war need for large numbers of dwellings has promoted renewed inquiry into the basic criteria by which good practice in the design and construction of buildings may be judged. More emphasis than ever before is now being put upon the functional characteristics of buildings regarded as living-spaces rather than as structures.

1. Naturally occurring agglutinins to paracolon bacilli have been found in seven out of ten sera from non-immunized rabbits and in one anti-Salmonella and two anti-paracolon immune rabbits' sera after complete absorption with the immunizing strain.

2. The a antigen of Stamp & Stone, which is known to occur as a natural agglutinin, has been demonstrated in one out of nine paracolon bacilli.

3. Rabbits which before immunization show agglutinins to the immunizing strain or to an α antigen should not be used for the preparation of diagnostic antisera for intestinal Gram-negative bacilli.

1. The presence of a new thermolabile an named β antigen has been demonstrated in motile and non-motile coliform, paracolon and Proteus strains, and in Shigella bacilli (Sh. flexneri Sh. flexneri V1 and D19). This antigen can be frequently found in the above types.

2. The characteristics of the β antigen have been described, and its dissimilarity to H, O, Vi, 2, A, B and α antigens has been established.

3. A high incidence of β antibodies was demonstrated in normal human and rabbit sera.

4. β strains of paracolon and coliform b injected intraperitoneally into mice were shown to be more virulent to mice than β minus forms of the same strains.

5. It is suggested that unrecognized presence of β antigen in cultures and β antibody in human and rabbit sera may cause errors in bacteriological and serological diagnoses of enteric infections.

1. A series of experiments is described in whichthe efficacy of vaccination with the vole acid-fast bacillus against tuberculosis in cattle has been studied. Various methods of vaccination have been tried and intravenous inoculation has proved to be the most satisfactory.

2. A single intravenous inoculation of 5 mg. of vole bacilli can raise the resistance of cattle to infection with the bovine bacillus to a high degree, this resistance being evidenced by a complete absence of infection or by a marked diminution in the severity of lesions following exposure to artificial or natural infection.

3. The resistance takes time to develop, reaches its maximum between 6 and 18 months after vaccination and then slowly wanes. The resistance induced by a single inoculation is of insufficient duration in many animals to warrant the practice of single vaccination being used in the field except in special circumstances.

4. Revaccination can intensify resistance provided that it is delayed until the end of the fourth week. A long-term experiment is being carried out to determine if revaccination, in addition to intensifying the initial resistance, can also lengthen its duration.

5. The degree of resistance set up in cattle is correlated with the virulence of the vaccinating strain of vole bacillus for its natural host. This fact will necessitate that any strain used for vaccine purposes will have to be maintained at a high level of virulence by repeated passage through its native host.

6. Care is necessary in the selection of a strain of the vole bacillus for vaccine purposes, for we have encountered one strain, G564, which can set up a fatal infection in calves. Nothing has been noted which would contra-indicate the use of strain LV 285.

7. The histopathological changes pathognomic of tuberculous infection which follow the intravenous inoculation of vole bacilli are mainly confined to the lungs and thoracic glands. They reach their maximum about the 28th day and have undergone resolution by the 84th day.

8. The changes which occur in the cells of the reticulo-endothelial system following vaccination have been described. These changes must be taken into consideration in deciding the optimal time and dosage for revaccination and a further study of them is advisable.

Our thanks are due to Prof. T. Dalling for his unfailing interest in our work and for much helpful advice, and also io Dr A. Q. Wells for suppfyihg cultures of vole bacilli and for the loan of his multiple-puncture instrument. We are indebted to Dr V. D. Davies for painstaking examination of the joint lesions and to Dr J. R. M. Innes, who examined many histological sections of vole-inoculated animals and drew up a short report of which we have made much use. Mr V. L. Mastin was associated with us during part of the work and we gratefully acknowledge the help he gave. We also owe a deep debt of gratitude to our technical assistants, particularly Mr W. Nicholson and Mr C. Spurgeon, much of the routine bacteriological work being done by the former whilst the latter prepared the bulk of the histological sections. The local slaughterhouse officials of the Ministry of Food, particuiarfy Mr Bacchus, the slaughterhouse manager, and Mr C. Rose, the foreman slaughterman, have been most co-operative over the arrangements for the slaughter of many animals. Our thanks are also due to the farmers who allowed us to expose experimental animals to natural infection on their farms, and to these and other farmers who have placed their herds at our disposal for the purpose of field trials.

The cost of these investigations was met mainly by grants from the Agricultural Research Council, but partly from the funds of the Institute of Animal Pathology.

1. The reaction horse serum and a pool of rabbit antihorse serum exhibiting four α procedure optima has been investigated with a view to analysing the antigens involved in the production of the multiple zones.

2. The following conclusions have been reached regarding the antigenic constitution of horse serum, a horse serum-albumin preparation and a horse serum-globulin preparation: Horse serum consists of at least five antigens. The horse serum-albumin preparation contains three antigens, two of which are probably impurities, one of these being a globulin. The horse serum-globulin preparation consists of three antigens and evidence was obtained of a fourth. Electrophoretic analysis of these protein preparations gave concordant result.

3. Multiple zones of rapid particulation in the precipitation reaction are due to the independent activity of multiple antigens and their homologous antibodies.

4. The absorption of precipitin from a mixture of antibodies by a mixture of antigens at a single α procedure optimum is both a useful and a practicable procedures.

5. Attention is drawn to the fact that the method of antigenic analysis used in the present series of experiments, involving the correlation of α; procedure optima occurring in the parallel titrations of a single antiserum against a mixed antigen and equivalent concentrations of physically or chemically prepared fractions of it supplemented by absorption of precipitins at individual and multiple α precedure optima and retitration of the absorbed sera, could be applied to the identification and nomenclature of proteins occurring in natural mixtures, and also to the quantitative and qualitative appraisal of the purity of proteins prepared by physical or chemical means. The method does not rely on the preparation of highly purified protein samples containing a single antigen.

The numbers and types of bacteria in thirty-nine samples of dried whale meat of the 1946–7 and 1947–8 Antarctic whaling seasons have been investigated.

The total number of bacteria was low for this type of product and there were about equal numbers of clostridia and aerobic bacteria.

A detailed examination of the clostridia present showed that they were of types commonly found in material from mammalian sources.

No Clostridium pathogenic to the mouse was found, although some cultures on prolonged incubation killed mice by ammonia poisoning. Ammonia poisoning was produced by injection of cultures and never by oral administration.

(a) A field investigation into an outbreak of poliomyelitis in Auckland in the summer of 1947–8 is described.

(b) The object of the investigation was to study the background of the epidemic in the general population, to discover how it had commenced, and how much minor illness related to poliomyelitis had occurred (i) amongst household contacts, (ii) in other persons residing in the same neighbourhood, and (iii) in those parts of the urban area least affected by the epidemic.

(c) Conclusions reached have been detailed in the preceding section. A relationship was established between minor (‘suspect’) illnesses and positive cases; the ratio of ‘suspect’ to positive cases at different age levels has been calculated, and an estimate is given of the extent to which the population as a whole was affected. Reasons are adduced for believing that, during an epidemic, mode of life and personal habits may be of more importance in determining the fate of the individual than previously acquired immunity.

(d) It is suggested that indoor dust-borne infection, at school and in the home, may be important, and that the results of recent research into threadworm infestation may throw light on this factor.

The usefulness of the complement-fixation test in differential diagnosis between vesicular stomatitis and foot-and-mouth disease has been demonstrated on two ‘field’ specimens of virus from Mexico. Examples are given of the practical applications of the other methods for this differential diagnosis.

1. Nineteen rabbit does were inoculated each with the whole blood of a buck to which they were later mated.

2. They were observed over a period of 10 months which included three pregnancies: (a) for the appearance and behaviour of anti-red cell isoanti-body in their sera; and (6) for the effect of such an antibody on the offspring, especially those inheriting a paternal red cell antigen incompatible with their mother's antiserum.

3. The does' antisera were examined for antibodies capable of directly agglutinating red cells and for ‘incomplete’ antibodies which might sensitize cells without causing agglutination. The latter were identified by an indirect antiglobulin sensitization test.

4. Nine does formed antibodies in their sera, six of these antisera directly agglutinated the appropriate red cells, but in three cases the antibodies were demonstrated only by the indirect antiglobulin sensitization test. Of the six antisera which directly agglutinated red cells three had antibodies which caused direct agglutination of red cells undiluted or in their lower dilutions, but in higher dilutions were shown to be capable of sensitizing cells without agglutinating them.

5. Four does, who had produced antibody in their sera, had between them seven litters in which the red cells of the young inheriting a paternal antigen incompatible with their mother's antiserum reacted to a direct antiglobulin sensitization test. This reaction is discussed and it is concluded that a positive direct antiglobulin sensitization test means that maternal isoantibody is attached to the infants' red cells. The offspring whose red cells reacted positively were, nevertheless, clinically normal.

6. A proportion of the young were killed at 3 days and 24 days old. A full peripheral blood examination was made and imprints taken from the liver and spleen. The bone marrow was also examined. Specimens were taken from liver, spleen, suprarenal, kidneys, femur, and, in some cases, brain for histological examination after an autopsy had been performed. Fifteen normal rabbits were similarly examined at 3 days old and four at 24 days old.

7. The range and average figures for the various haematological examinations made are given and the findings in the experimental animals compared with the normals.

8. A few differences were found between the experimental and the normal animals as a result of this experiment. The significance of these is discussed.

Several species of Leptospira have been studied by means of the electron microscope. Their morphology is described. The Leptospira consists in a long homogeneous cylinder of protoplasm, enveloped in a very thin anistic membrane and wrapped around a slender axistyle. Vibratile structures and granules generally are lacking.

The appearance of Leptospiras differs according to different methods of fixation used and according to different physical or chemical treatments to which they are subjected.

1. The preparation and characteristics of a tellurite medium, containing, in addition to a peptone and Lemco agar base, a tryptie hydrolysate of casein, sodium lactate, L-cystine, sheep serum, an extract of sheep red blood corpuscles and 0·01% potassium tellurite, is described for use in the identification and isolation of Corynebacterium diphtheriae.

2. The colonial appearances of the three types of C. diphtheriae on the medium are described, and the distinguishing features between these and the colonial appearances of diphtheroids and other organisms liable to occur on pathological material are indicated.

3. Recommendations are made concerning what has so far proved to be the most suitable manner of inoculation of pathological material on to the medium.

The author would like to express his thanks to Prof. F. C. Happold for suggesting the problem, to Dr R. E. Jones for encouragement during the course of the work, to Miss K. Gilliver, M.A., for assistance in the preparation of the manuscript and to Miss G. M. Jenkins for technical assistance.

‘And the hand of the Lord was heavy upon the Azotians, and he destroyed them, and afficted Azotus and the coasts thereof with emerods. And in the villages and fields in the midst of that country, there came forth a multitude of mice; and there was the confusion of a great mortality in the city.

1. Anti-mallein sera produced in thirteen species of mammals (including man) and one species of bird have been examined by the haemolytic complement fixation test using guinea-pig complement, and by the conglutinating complement absorption test using pig, horse and cat complements. Two methods of fixation have been used and compared, namely, fixation for half an hour at room temperature and fixation overnight at 4° C.

2. The complement of the horse proved to be the most sensitive in nearly every case in demonstrating the specific antibodies in the different sera; in the few instances where it was not markedly the most sensitive it was for practical purposes the equal of any other complement used, independent of the method of fixation. This is clearly indicated in the text figures.

3. The effects of overnight fixation on the titres obtained with the different complements are discussed.

4. The sera of six fowls inoculated with mallein failed to show fixation of any of the four complements in the presence of the homologous antigen. The presence of immune bodies was demonstrated however by the Indirect Complement Fixation technique of Rice (1948b).

It has been shown that the L-form of Streptobacillus moniliformis is filerable through gradocol membranes which retain the bacillary A-form completely. From the filtration analysis carried out as described it would appear that the particle size of the L-form of Strep. monilifprmis ranges with the larger viruses while the bacillary A-form ranges with Bact. prodigiosum.

The results of a field survey of herpes zoster over a period of 18 months are described and the difficulties of such a survey mentioned.

A total of 246 patients with herpes zoster, only 16% of whom had attended hospital, is reported. It is calculated that the yearly incidence in the population was approximately 2 per 1000.

Full investigation and ‘follow up’ was undertaken in 184 cases. These are classified according to the site of the zoster—the dorsal, supra-orbital and cervical regions being affected in almost 90%, the dorsal region alone accounting for 53·3%.

Herpes generalisatus occurred in 7, or 38%, of the cases, recurrent herpes zoster in 6, or 3·3%, while there was one case of motor paralysis affecting lower limb.

The majority of patients were apparently well at the onset of the zoster, but 27 had some associated disease; 5 gave a history of trauma prior to the onset and 2 were related to pregnancy.

The seasonal and geographical distribution is given and, while the numbers are too small for statistical analysis, the disease in 1947 showed two peaks of higher incidence, the one in May and the other in October. Crowding or density of population did not appear to be important, and the disease occurred sporadically rather than in epidemic form.

There was a higher proportion of female cases, but when related to the population as a whole no sex differentiation was observed. Of the patients 60% were over 45 years of age.

There was no evidence that housing conditions or occupation were of aetiological significance or that the disease was more common among any particular section of the community.

Eleven patients had been associated with other cases of herpes zoster before developing the disease, while 3 gave a suggestive history of prior contact with chickenpox.

A condition indistinguishable from chickenpox occurred among the contacts of 10 patients, 12 individuals being affected, and there was one instance of concurrent herpes zoster and chickenpox. Other infections such as mumps, measles and rubella, while as common in association with the onset of herpes zoster, were not so frequently found as the chickenpox condition amongst contacts of the disease.

The results of the survey as regards the relationship of chickenpox and herpes zoster are discussed. It is considered that the evidence does not favour a significant association with chickenpox prior to the onset of herpes zoster, but that the facts are consistent with the view that a condition indistinguishable from chickenpox may follow contact with herpes zoster. It is suggested, however, that this may be a generalized manifestation of the virus of zoster rather than true chickenpox.

An antibiotic elaborated by Pfeifferella whitmori is described. This principle is active in vitro against the H37RV strain of Mycobacterium tuberculosis, but in several other respects closely resembles penicillin. It has given encouraging results in a small-scale therapeutic trial in experimental guinea-pig diphtheria.