IN the admirable pioneer studies of Griffith and his colleagues on the epidemiology of streptococcal infections in schools, “no systematic attempt was made to discover the distribution of streptococci amongst the healthy residents. And the observations on carriers were in general confined to those who were suspected to have some catarrhal infection of the upper air passages” (Griffith, 1938). In this paper we report the results of weekly swabbings of the throats of all children in a single dormitory or ward of an orphanage with 350 inmates, during an outbreak of scarlet fever due to Streptococcus pyogenes, serologically type 2 (Griffith). All haemolytic streptococci were typed by the slide agglutination technique, so that fluctuations in the distribution of the epidemic and non-epidemic strains could be followed.

The British Standard Technique for Determining the Rideal-Walker Coefficient of Disinfectants (no. 541—1934), in laying down the procedure to be adopted with regard to the test typhoid bacillus culture, recommends that a fresh culture be obtained each month from the National Collection of Type Cultures. In all probability this is the best procedure; it does, however, sometimes happen that a test is required urgently when a fresh culture is not available. The following notes upon our own experience in maintaining cultures may therefore be of some interest. It is our practice to obtain fresh cultures whenever we are called upon to carry out other than routine tests unless a recent one has been obtained, and many of these cultures have now been running for a number of years. On the arrival of the culture from the N.C.T.C. it is subcultured on to an agar slope and “incubated” at room temperature in a dark cupboard. 2% agar is used in a broth prepared by the tryptic digestion of ox heart. Further subcultures are made at intervals of one month. It is our usual practice to start a series of broth cultures from such slopes not less than 14 days after sowing.

The phenomena produced by colonies of streptococci on blood-agar plates have long been used by medical bacteriologists for classification purposes. An examination of the literature showed that only a few contradictory data were available for the corresponding phenomena induced by the saprophytic lactic acid bacteria. A systematic investigation into the types of “haemolysis” and discoloration phenomena produced by typed cultures of lactic acid bacteria was therefore carried out to ascertain whether the blood-agar plate was of any use in the routine classification of these bacteria. The monograph of Brown (1919), which has been generally accepted as the standard work on the subject, is regarded as a standard of reference in the present paper.

A laboratory investigation of 776 cases of labor pneumonia, mainly among Kenya Africans, over a period of 5 years, revealed a remarkable preponderance of infections due to group IV pneumococci.

Comparison of the total case mortality rate with the case mortality of group IV pneumonia infections suggests that Kenya Africans are not specially susceptible to pneumonia, and that many of the group IV pneumococci which cause pneumonia in Kenya are of high virulence and penetrative power.

A considerable number of group IV pneumococcal types capable of causing severe lobar pneumonia were serologically isolated. A few of these were identified with pneumococcal types prevalent in New York and South Africa.

An experiment was made on a fairly large scale with prophylactic antipneumonia vaccine, made in the same way as Sir Spencer Lister's pneumonia prophylactic which is used with success in the Rand mines, but constituted of the pneumococcal types which had been found to be most prevalent in pneumonia in the Nairobi district. Extensive trials with this vaccine have been made on the labourers of the Kenya gold fields, and elsewhere, and very encouraging reports on the effects of this vaccine in reducing the incidence and case mortality of pneumonia have been received from medical officers who carried out the inoculations.

A technique is described for the use of surface culture suspensions of pneumococci for serological and bile-solubility tests, and advantages are claimed on specified grounds for the use of surface culture suspensions in preparing agglutinating and therapeutic pneumococcal sera.

A method is described for the use of formol-saline suspensions of surface cultures for preserving collections of pneumococcal types, and for correlating pneumococcal types prevalent in different countries.

FRom the point of view of industrial hygiene, it is important to estimate the occurrence of asthma, rhinitis vasomotoria and eczema and of the sensitization to flour amongst unselected groups of bread bakers, cake bakers and millers. For this purpose we have examined 262 flour workers, who formed the entire working staffs of certain bread bakeries, cake bakeries and milling companies in Amsterdam.

In a recently published paper (Kermack & McKendrick, 1937) the observational data relating to epidemics of ectromelia in populations of mice maintained under experimental conditions (Greenwood et al. 1936) has been analysed in the light of a mathematical theory of epidemics developed by us during recent years (Kermack & McKendrick, 1927, 1932, 1933, 1936). It was shown that the life table giving the chance of mice surviving for various lengths of time in infected communities is very closely represented by a formula calculated on the assumption that the various rates—infection rate, recovery rate, death rate, etc.—are constants. It is, of course, realized that this simplifying assumption can only be regarded as approximately true. It renders the application of the general theory practicable, and the result of the investigation justifies its use, in so far as the theory so simplified does actually conform to the experimental results.

Antisera prepared in the rabbit by injection of crystalline horse-serum albumin or crystalline human-serum albumin show a considerable diminution in specificity after more than one course of six to eight injections has been given.

The ratio of precipitate nitrogen to antigen nitrogen at the optimal point is smaller in antisera obtained after one course of injections than in antisera derived from subsequent bleedings.

In the case of antisera obtained from first bleedings, the ratio of precipitate nitrogen to antigen nitrogen determined at the optimal point with homologous antigen is of approximately the same value in both the antigen-antibody systems studied. The increase in the values of the ratios for antisera from subsequent bleedings is also the same for both systems.

1. It seems to be the general opinion of veterinary contributors on the subject that infection of the udder with coliform organisms is rapidly followed by clinical symptoms of mastitis, and marked changes in the appearance of the secretion. There would therefore appear to be little danger of contamination of bulk milk from such sources except during the few hours between infection and the appearance of the clinical symptoms.

2. Injury to the teats or quarters may result in infection of milk with coliform organisms owing to the difficulty of thorough cleaning of the malformed tissue.

3. Several cases of infection of quarters in the entire absence of clinical or other symptoms of disease have been cited. There is no evidence that such cases can be classed as subclinical forms of the disease as is the case in streptococcic mastitis. The evidence in two cases cited indicates that milk drawn from a quarter can remain infected with coliform organisms for a considerable period with no apparent clinical or other symptoms of disease.

4. There is sufficient evidence to warrant the examination of quarter samples in cases where infection of bulk milk with coliform organisms from other more common sources appears to be unlikely.

The knowledge of the nature of vaccinia virus gained in recent years and the methods of preparing relatively pure suspensions of the virus which have been developed justify the hope that the technique of vaccination against smallpox may be improved. The potency of vaccine lymph and its relative freedom from bacterial contaminants have been regulated under the Therapeutic Substances Act for several years past; nevertheless, for prophylactic purposes, it is desirable to introduce the use of pure bacteria-free virus in a measured volume of known potency. The usual method of vaccination which involves scratching the skin and applying to the scratch a variable amount of virus-containing lymph cannot be described as an accurate procedure and, unless proper precautions are taken, may invite local secondary bacterial infection. If it could be shown that a satisfactory immunity follows the intracutaneous injection of a measured amount of a bacteria-free suspension of virus, this method would possess obvious advantages; the usual dressing could be dispensed with, the amount of scarring, and the local secondary bacterial infection which is associated with vaccination would be reduced or abolished. In our opinion, the value of vaccinial scars has been exaggerated; they may be useful as visible evidence that the patient has been successfully vaccinated sometime in the past, but they are not an indication of existing immunity to smallpox. It is not usually suggested that any other measure of prophylactic inoculation should be accompanied by a permanent scar as a record of immunization.

The purpose of the investigation was to examine the reason for the relative age shift in the incidence of diphtheria. The disease has been represented as now concentrating on children of school ages. We analysed, for various quinquennial periods beginning with 1901–5, the statistics of the notifications and deaths according to age and sex in the London boroughs which we classified into four social classes where I to IV represented descending order in the social scale. The conclusions arrived at were:

I. The age shift as represented by the ratio of the mortality at ages 0–4 to ages 5–9 years which has taken place in London has been found to occur mainly in the poorer districts. The ratio in the residential districts has not altered appreciably during the thirty years under review (Table V).

II. The age shift is also indicated by the morbidity statistics for the three quinquennial periods, 1901–5, 1909–13 and 1919–23, as there was a significant increase in the mean age of attack of children under 15 years of age.

The case rate at ages 5–14 during 1929–33 as compared with that in 1901–5 has increased most amongst children in the lowest social group.

III. Each of the variables (a) the decrease in the birth-rate between 1911 and 1931 in each London borough—an index of the change in the size of family—and (b) the decrease in infant mortality—a measurement of environmental improvement—is positively and significantly correlated with (c) the corresponding change in the size of the ratio of the case rates at ages 0–4 to 5–9 years. The coefficients were:

but the partial correlation coefficients

indicate that the change in the size of family is the more important factor as the value of rac.b is fairly large and significant, whereas the correlation between the change in the ratio and the environmental improvement when the effects of the decreasing birth-rate are made constant—rbc.a—becomes statistically unimportant.

Käber's method is, for many purposes, a sufficiently accurate way of determining the median effective dose, when we have a series of doses increasing in a constant ratio and a small number of animals on each. The standard error of the determination may also be rapidly found by a simple approximate method. Illustrative examples are given.

The standard error calculated by the approximate method is based on the assumption that the animals are homogeneous. It must be used with caution when any heterogeneity is suspected. With animals of similar heterogeneity to those used here, the differences between two different toxic-fractions should only be regarded as significant if they are from 3 to 3.5 times their standard errors so calculated.

The statistical theory of virus determination by the dilution method is considered. It is shown that an algebraical method gives a solution which is rather more reliable than that given by the graphical method, and whose standard error may be calculated.

IN a previous communication we (Pulvertaft, Lemon & Walker, 1939), gave an account of a method of sterilizing air by means of finely atomized antiseptic solutions, founded on the principles outlined by Trillat (1938). His claims were fully confirmed.

The mists used in this method may be produced by a number of different appliances, and in the experiments here described were produced by the “Phantomyst” (Andre Components, Ltd.). The essential appliances are:(1) a mechanical compressor, electrically driven, and (2) an atomizer, usually of scent-spray type, provided with (3) a baffling system which returns to the reservoir droplets above a certain size, thus avoiding much wastage.

A sensitive antigen suspension is described for use with a simple slide agglutination method which makes possible a serological diagnosis or exclusion of typhoid fever without recourse to a laboratory. The method has been tested on 414 sera sent to our laboratory; it detected all cases with a titre of 1: 80 or more, and most of those with a titre of 1: 40. The method was further tested on 130 clinically observed cases, in which it gave satisfactory results. The S. A. method gave a positive result with 98 out of 100 sera from patients with typhoid fever, whereas the classical Widal reaction gave a positive result with 68 of them only.

The intensity and rapidity of the slide agglutination reaction provide a rough measure of the titre of a serum. A quick and distinct agglutination indicates a titre of 1: 80 or more and is diagnostic of typhoid fever. A slow and indistinct result is obtained when the titre of the serum is about 1: 40. A negative test indicates with great probablity that a diagnosis of typhoid fever may be excluded.

We think the method succeeds because the nature of the suspension employed and the peculiar behaviour of slide agglutinations permit the detection of O agglutinins as well as H agglutinins.

1. A series of 340 cases of scarlet fever was treated under controlled conditions, (a) with sulphanilamide or benzyl-sulphanilamide, and (b) without sulphanilamide.

2. There was an even distribution of the individual cases in respect of factors known to influence the course of the disease, such as (a) the duration of the disease before admission to hospital, and (b) the severity of the infection.

3. Treatment was carried out during the whole period of 4 weeks, which constitutes the average period of hospitalization in scarlet fever.

4. The dose employed was large: (a) patients 5 years of age and over receiving 1 g. 4 hourly (i.e. 5 g. a day) for the first 14 days in hospital, thereafter 1 g. t.i.d. (i.e. 3 g. a day) for 14 days; a maximum total dose of 112 g., and (b) patients under 5 years of age receiving 0.5 g. 4 hourly (i.e. 2.5 g. a day) for the first 14 days in hospital, thereafter 0.5 g., t.i.d. (i.e. 1.5 g. a day) for 14 days; a maximum total dosage of 56 g.

5. The results show that sulphanilamide had no significant effect upon the initial symptoms of scarlet fever, or upon the kind, incidence, or duration of later complications.

6. A large number of toxic reactions followed the use of both sulphanilamide and benzyl-sulphanilamide.

7. In view of all the evidence submitted, it is considered that there is no justification for the employment of sulphanilamide and benzyl-sulphanilamide in the treatment of scarlet fever.

The process of physical growth in children is manifested by changes in their size, mass and shape. Changes in size are ascertained by measurement, usually, of the standing height of the child, but occasionally of the sitting height, and sometimes, also, of the chest circumference and the width between the hips. Changes in mass are detected by weighing, whilst changes in shape, which are due to unequal rates of growth in height and in mass, are estimated by methods referred to later.

1. The effect of alcohols and of phenol on the succinic acid dehydrogenase of Bact. coli, hitherto recorded qualitatively in the literature, has been studied in greater detail.

2. The effect of heat and of p−chloro−m−cresol, hexyl resorcinol, p−butyl phenol and amyl−m−cresol, has also been studied.

3. The concentrations of these germicides required to inhibit completely the succinic dehydrogenase is such as to allow for a slight excess over the concentrations which are lethal to Bact. coli.

1. The examination of 1100 sera by both the Wassermann reaction and the complement-fixation test with spirochaetes revealed a superior sensitivity of the latter reaction and practically equal specificity of the two tests.

2. Syphilitic serum contains two different antibodies: one reacting with the lipoid antigen of the Wassermann reaction, the other with a specific antigen in the spirochaete.

3. The spirochaetal antibody of syphilitic serum has a complex serological structure, corresponding to spirochaete strains of different antigenic make-up.

4. The existence of this antibody and its specific absorption by the homologous antigen can also be demonstrated by agglutination.

5. The difference between agglutinin titres found in normal and syphilitic sera is not pronounced enough to render this method satisfactory for the practical diagnosis of syphilis.

6. The spirochaete contains, apart from its specific antigen, the ubiquitous lipoid substance representing the Wassermann antigen.

7. A fraction was obtained from spirochaetes by Raistrick and Topley's method which in complement-fixation and precipitation tests reacted actively with spirochaete antisera from rabbits, but which so far failed to react with syphilitic sera.

This work was carried out with the aid of a grant from the Rockefeller Foundation. I wish to thank Prof. Golla, Director of the Central Pathological Laboratory, L.C.C. Mental Hospitals, who rendered this work possible, and Dr Arthur Davies, Director of the Devonport Laboratory, for the hospitality afforded me at his laboratory and for the patients’ sera used in this work. I am indebted to Prof. R. T. Hewlett for his revision of the manuscript, to Prof. Raistrick for advice in chemical matters, and to Dr Amies, of the Lister Institute, for his help with the Sharples centrifuge.