This investigation was initiated when twelve miners who were working in a certain part of the Mill Close Lead Mine complained of smarting of the eyes associated with marked congestion of the conjunctivae. They also suffered from a stinging sensation in the nose and throat. The particular area in which they were working differed from other parts of the mine in that there was a strong smell of sulphuretted hydrogen present. After recovery, and when the ventilation had been improved, the men were able to continue working in that area without experiencing further discomfort. The interesting part of the investigation was tracing the origin of the sulphuretted hydrogen. The odour proceeded from collections of mine water which the miners very appropriately called “stink water”. In this there was a deposit of sulphur mixed with black sludge which also smelt strongly of H2S. The sludge consisted of slightly gelatinous black masses mixed with a whitish felt work of a filamentous organism. On microscopical examination the filaments were seen to contain sulphur globules, and often to arise from a mass of black material. This black material consisted of sulphur and inorganic salts in a slimy matrix, the black colour being due to the presence of ferrous sulphide. On further examination these masses were found to be teeming with other bacteria, Gram-negative bacilli and spirilla, both of which were motile, the spirilla being actively so.

The degree of protection provided by various air movement control systems, as applied to isolation and treatment rooms, has been assessed. The main factors influencing the efficiency of isolation were the air supply rate to the room and the time the door was left open. The effect of some other possible factors, such as temperature differences and method of air distribution, are discussed.

The type of facilities provided must depend on the type of patient and economics, but prediction equations, which allow the assessment of positive, negative and balanced ventilation systems, are presented. The ventilation requirements for isolation rooms should be assessed individually, but for a treatment room a balanced system of ventilation with between 500 and 1000 ft.3/min. should be very effective. Precautions should be taken to ensure the air quantities are balanced and temperature differences are minimized. An air lock should not be necessary for balanced systems provided these rooms are in a mechanically ventilated ward.

We thank Mr W. Carson and members of the Building Services Research Unit for their help and advice and Sister M. F. D. Muir and the staff of the experimental ward for their co-operation. This work was sponsored by the Nuffield Provincial Hospitals Trust.

Requests for reprints, or a fuller description of the ward unit and test results, should be addressed to George Baird, Building Services Research Unit, 3 Lilybank Gardens, Glasgow, W. 2.

On February 10th, 1911, the attention of the Medical Officer of Health was called by the practitioner in charge to an outbreak of diarrhoea in a family named R. residing in Paddington. The note made at the interview was to the effect that cases had occurred on the 8th, 9th, and 10th (2 cases) of the month, the four patients having violent diarrhoea and passing much blood. The onset was quite sudden in every case. It was thought that “food poisoning” could be excluded, and the main object in directing attention to the outbreak was to ascertain if any defective drainage existed at the house. Incidentally it may be remarked that the house drainage, etc. had been completely overhauled in 1907 and that no defects existed in February last except one leaky joint on a waste pipe.

We have heard much in recent times of the decrease of tuberculosis and of the increase in mortality from cancer. I propose on the basis of data from some great cities and other areas of the German-speaking world to ascertain whether, if attention is paid to age distribution, cancer really presents so striking a contrast with other causes of mortality. With a view to solving the problem let us enquire whether the undoubted absolute increase may not be a mere function of the ageing of the population, a feature common to all civilised countries. Most weight will be placed upon the statistical data derived from cities because of the greater reliability of the diagnoses in hospitals, and because, as a rule, the death certificate is filled up by the practitioner who actually attended the patient.

1. The principle cause of post-scarlatinal diptheria is the admission into the scarlet fever wards of patients who, whether suffering from clinical diphtheria or not, are carriers of virulent diphtheria bacilli.

2. In large centres of population, where diphtheria always exists, diphtheria bacilli are to be found in a not inconsiderable proportion of school-children. In the absence both of evidence of clinical diphtheria and of a history of exposure to that affection, the bacilli are, in the majority of cases, of the non-virulent or saprophytic type and of little hygienic importance; in cases, on the other hand, where the clinical supports the bacteriological examination the bacilli are almost certainly virulent, and therefore dangerous; while in cases where the patient is known to have been exposed to infection the chances are great that the organisms are of the pathogenic variety, and such cases should always be regarded with grave suspicion.

3. On account of the prevalence of the non-virulent bacillus and the fallacies of single cultures, it may be doubted whether a routine bacteriological examination of throat and nose of all patients on admission would prove of sufficient value to repay the labour involved. Chief reliance must be placed on a careful inspection on admission, not only of the throat, but also of the nasal cavities, bacteriological examination being resorted to in cases of doubt.

4. In eradicating infection from an invaded ward bacteriological methods are, on the other hand, of prime importance, since children with apparently healthy throats and noses are often found to have acquired the virulent bacillus. An attempt to stamp out any outbreak of diphtheria by bacteriological examination of the throat alone is, however, futile, owing to the frequent infection of the nasal cavities.

5. Fibrinous rhinitis, which appears to be a not infrequent, though often unrecognised, affection of children is a common form of postscarlatinal diphtheria.

6. Although the treatment of diphtheria in the same hospital has no appreciable influence on the incidence of this complication of scarlet fever, it is advisable that precautions should be taken lest nurses harbouring diphtheria bacilli carry infection from the diphtheria to the scarlet fever wards.

7. To limit the risk of exposure to infection many-bedded wards should be avoided, and the mixing of patients from different wards prevented.

A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission.

The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs.

The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.

The experiments here described proved that preparations made from widely different classes of bacteria are capable of inducing immunity in mice against pneumococci. The success of these preparations was found to depend on the differential separation of an active immunizing antigen from another bacterial constituent—an ‘opposition factor’—which interferes with immunization. Further investigation and comparison depend largely on the discovery of a really effective method for the isolation and purification of the active antigen. Until its chemical nature is determined, the identity of the pneumococcal species antigen with similarly acting substances found in other bacteria remains unproved.

Pathogenic bacteria depend for their virulence and invasiveness on certain products individual to the species or type, and specific immunity is due to the development of the appropriate antibodies. But chemotherapy, as in the case of the sulphonamides, interferes with a less specialized metabolic process of the microbes and is neither species nor type specific in action. It is reasonable to infer that bacteria may possess in common a vital process associated with the presence of a common constituent which may be antigenic. ‘Species antigen’ may be a substance of this nature.

In view of the wide distribution of ‘species antigen’ among bacteria generally, it is probable that this constituent has already been separated and named in accordance with its presence in a particular species, but irrespective of its potential immunizing capacity.

So far as pneumococci are concerned, there is good evidence that species antigen may be identical with the species C carbohydrate. Tillett (1927) found that rabbits injected with successive courses of heat-killed pneumococci, whether of types I, II, III or of avirulent rough strains, developed an equal increase of resistance to infection by type III Pneumococcus. In 1936 Enders, Wu & Shaffer varied the procedure, and by injections of rough pneumococci prepared an antiserum which gave passive protection to rabbits against infection by type III Pneumococcus. This antiserum lost its protective power after absorption with the species C carbohydrate.

When individual responses in a biological assay show considerable variation associated with the values of a concomitant variate, covariance analysis may be used in order to adjust the mean responses and to improve the precision of the assay. Usually this is preferable to the choice of an adjustment which involves an arbitrary assumption about the effect of variations in the concomitant variate on the measured response. Published accounts of the process are open to certain theoretical objections, though they may be sufficiently exact for most practical purposes.

The present paper describes a method of calculating the relative potency, and its precision, which may be a little more laborious, but which is in full accord with standard statistical practice. The computations are illustrated on data from a prolactin assay by the pigeon crop-gland technique, in which the final crop-gland weight showed a positive correlation with the body weight at the start of the assay. The results are compared with those obtained either from the unadjusted crop-gland weights or from these weights expressed as proportions of body weights. The covariance method leads to a more precise estimate of the potency of the test preparation than do either of the others; there is evidence, however, that the increase in precision will not necessarily be large unless the correlation between the response and the concomitant variate is very close.

In a final section, the full statistical tests of assay validity in the covariance analysis are described; these are lengthy, and fortunately are required only when the validity is in considerable doubt.

The methods of adjustment have been described in this paper with respect to an assay depending upon parallel regression lines of responses on the logarithms of doses. They may be adapted for use with ‘slope-ratio’ assays (Bliss, 1946; Finney, 1945; 1948; Wood & Finney, 1946), in which the regression of response on dose itself is linear. So far the need for adjusting for concomitant variation in these assays seems not to have arisen, and discussion of computational details may be postponed until the need is felt.

1. We have investigated bacteriologically the conditions in a central meals kitchen from which about 3000 meals were issued daily to some 65 departments.

2. Plate counts showed that the containers in which the meals were sent out contained large numbers of organisms, from several thousand to several hundred thousand per container.

3. Counts of this order were obtained both before and after the routine method of washing.

4. These counts were reduced to the order of a few hundred or less per container by steam sterilization.

5. Exposure for 2–3 min. to steam from a simple jet sterilizer was effective for all except large insulated lids which required at least 5 min.

6. Treatment for 5 min. in a chamber filled with steam from a boiler was effective with all types of containers and lids tested.

7. If containers are to be sterilized at all they must be sterilized each time they are to be used.

8. A great improvement in the bacteriological counts can be achieved by attention to the hygiene of washing, e.g. by the use of plenty of hot water with soap and soda or perhaps preferably with detergents, with a second sink of very hot water for rinsing, and by using fresh sterilized dish-cloths each time the washing water is changed.

9. Counts almost as good as those given by steam sterilization were obtained by washing with soap and water at 48–50° C., wiping with a sterilized dish-cloth and then rinsing in a second sink of water at 75–80° C.

10. The arguments for and against steam sterilization are discussed.

This investigation was greatly helped by the co-operation of the Leicester Education Department.

In autumn 1978 an epidemic of respiratory disease resembling allergic alveolitis occurred in a small Finnish community. The disease was caused by repeated exposures to tap water aerosol. The raw water of the community and the sand filters of the purification system were heavily contaminated with mesophilic actinomycetes. Fourteen different strains of actinomycetes were isolated. Exposed persons with and without symptoms as well as unexposed control persons were tested for antibodies against five of these actinomycetes and against Enterobacter agglomerans. Both the exposed and the control persons had antibodies to actinomycetes but the exposed persons had antibodies against more actinomycete strains than the control persons. Precipitating antibodies against E. agglomerans were also found in control persons as well as in patients. There was a significant difference between the patients and the exposed healthy persons in bacterial agglutination tests with flagellar antigen of one E. agglomerans strain. However, the role of mesophilic actinomycetes and E. agglomerans in the aetiology of the disease could not be firmly established.

1. The fall in the refractive index of mineral oils recovered after injection into the peritoneal cavity of mice is usually accompanied by a fall in the density proportional to the fall in the index.

2. With straight distillates from the crude oil the ratio of index fall to density fall is on an average about 0·85 to 1. Wide deviations from these figures were rarely found except when dealing with oils of low toxicity. The ratio tends to be above the mean when the actual index fall is low and consequently below the mean when the index fall is high.

3. The refractivity of the original oil, the index fall of the recovered oil and the density fall of the recovered oil give information as to the carcinogenic potency for mice of the original oil of about equal value, but the two lastmentioned tests are far superior to the first for assessing the probable dermatitic potency of the oil.

4. Other things being equal, the index and density fall are closely dependent upon the index, density and viscosity of the original oil.

5. The index and density fall gradually become larger as the experiment progresses, but within each 24-hour interval the fall gradually becomes less. The ratio of index fall to density fall remains fairly constant for each individual oil during the course of the experiment.

6. Titration of mineral oils in vitro with sulphuric acid and alcohol provides residual oils of lower index and density than the original oil, but the ratio of the fall in index to the fall in density is low, especially when the treatments are not severe.

7. Oxidation of mineral oils tends to raise the density without affecting the index to an appreciable extent. On the other hand reduction tends to lower the index without affecting the density to anything like the same extent.

8. In general terms the animal reacts upon the chemically treated oils in an additive manner, so that if by the chemical treatment we have the ratio of index fall to density fall low, the oil recovered from the animal will have the ratio high, and vice versa. The end product of the severe treatment of a mineral oil with acid and clay is a white oil which for practical purposes may be considered to be fully saturated. The end product of an oil recovered from the animal is probably similar in nature, although the process involved in arriving at this end product is presumably different chemically and physically.

9. Synthetic oils recovered from the animal after inj ection showed a marked rise in density but no corresponding rise in index.

10. The animal reaction to an injected oil was not materially accelerated by emulsification of the oil.

11. Some chemically pure non-carcinogenic compounds were very rapidly changed or eliminated from the peritoneal cavity.

12. All alcohol extracts of mineral oils tested showed an increase in index, density and refractivity, but not always in viscosity compared with the original oil, the residues, of course, having characteristics in an opposite direction. The latter were in every instant less toxic for the animal than the original oil, whether applied to the skin or injected.

13. A mineral oil recovered from animals 7 days after injection, when reinjected into a second series of animals, was altered as regards its physical characters in a normal manner. Thus whether allowed to remain in the peritoneal cavity of an animal of the first series or recovered and reinjected into an animal of the second series, the ultimate index and density fall in a given time were approximately similar.

14. The free oil in the peritoneal cavity becomes, from day to day, less. This is at least partly due to local trapping by the proliferating endothelium. The fall in index of the trapped oil is approximately similar to that of the free oil.

15. The alteration of the physical characteristics of mineral oils by the animal is probably brought about by a chemical reaction followed by removal of the changed product.

The list of bacteria recorded as causative agents in enteric fever and “food-poisoning” increases steadily, and the proved pathogens already number eleven types, of which three have been found in both continued fever and food-poisoning, three in continued fever alone, and five in food-poisoning alone. This list will undoubtedly be added to when cultural methods for the diagnosis of these conditions are more widely employed, especially in the tropics.

An epidemic of paratyphoid B fever occurred in Dundee during the period from 19 February to 19 October 1941. There were 373 notifications and 357 patients were admitted for investigation and treatment to King's Cross (Infectious Diseases) Hospital. Information was also received of the occurrence of eight cases in other areas, and there is evidence that they were infected in Dundee.

Reactions so far reported after the use of oil emulsion (OE) foot-and-mouth disease (FMD) vaccines in pigs have been infrequent and quick to resolve themselves. Although tentatively ascribed to anaphylaxis, these reactions have received little attention and their mechanism of causation has not been established conclusively.

1. The incidence produced during 1926 by two epidemics of diphtheria, in a remote and unsalted country district, was equivalent to 30 years of the London endemic morbidity.

2. The cases arose in two distinct groups. An autumn outbreak with a definite concentration of infection on the school age, and probably disseminated by droplet infection, followed by an epidemic in the succeeding spring which was more severe, probably milk-borne, and in which the frequency of cases was higher among infants and adults than school children.

3. The effect of a long drive over bad roads caused a deterioration of the diluted toxin which was used for a Schick test investigation. The use of this toxin led at first to false conclusions regarding the immunity of the children, since it only caused reactions in the most susceptible members of the community.

4. As a result of retesting with a fully potent toxin it was estimated that the figure of 40 per cent. susceptible which was found with the weak toxin would have been about 80, if full strength toxin had been used.

5. The attempt to immunise actively those children who had reacted to the weak Schick toxin was found to have failed in 72 per cent. of a group which was retested 7 months later. The prophylactic course was identical with one which had succeeded in inducing Schick immunity, within 4 months, in 100 per cent. of the susceptible children in the Dunedin orphanages.

6. The slow rate of immunisation at Kaitangata is attributed to two causes, (a) the low original herd immunity of the district, (b) the selection by the weak toxin of only the most sensitive reactors which were almost certainly the most “unresponsive” members of the total Schick positive population.

7. By a comparison of the rate of response to a small dose of toxin-anti-toxin mixture, in those positive Schick reactors (a) who had, and (b) who had not, received previous prophylactic injections, it was shown that the principle of “primary and secondary” antigenic stimuli held good for human subjects, as well as for experimental animals.

8. Careful examination of the known data led to the conclusion that the air-borne autumn epidemic had increased the herd immunity of the population, in spite of the fact that the subsequent milk-borne spring outbreak produced as high a morbidity and a more severe type of diphtheria.

9. The practical lessons which may be learnt from this study are: (a) That unless a special buffered diluent is used, the toxin used for Schick testing must be freshly diluted near the place where it is to be used, (b) Active immunisation of remote unsalted communities against diphtheria requires more time, and more intensive courses of prophylactic, than areas where diphtheria has been endemic for some years, (c) In such places with a low original herd immunity, it is essential, even more than in endemic centres, never to omit retesting those who have been inoculated, in order to be certain that any attempt made to induce active immunity to diphtheria may be successful. (d) Estimations of the relative efficiency of diphtheria prophylactics, which are based on the rapidity with which samples of children become immune, are worthless unless all the observations have been made in the same environment on groups having the same original herd immunity, (e) An immunity, good enough to withstand droplet infection in a day school environment, may be broken down by massive doses of diphtheria bacilli in milk.

10. The study of outbreaks of disease in communities which are not too large to prevent a complete supervision of the whole population and environment, enable one to visualise imaginary mechanisms of infection very much more easily than in large populous areas, where so many more factors have to be left unexamined, or remain unsuspected. The hypotheses, perhaps better termed surmises, which the facts suggest, are only intended to be purely tentative and temporary. Their practical value is that they indicate to the investigator a plan of campaign and suggest what to look for, in the lucky event of his ever again meeting with a similar combination of circumstances. In epidemiology in general, as illustrated by this particular instance, opportunities arise and pass, often never to recur, and much is missed, or left undone that might have been done, if only the knowledge and hints gained during the passage of the epidemic itself had been known before its advent.

(1) Killed agglutinable broth cultures of the various dysentery bacilli may be prepared by the formalin and cold storage process and may be standardized by the method elaborated by Prof. Dreyer for the typhoid and paratyphoid bacilli.

(2) Since formalin (0·1 %) usually causes a gradual loss of sensitiveness to agglutination during the early life of the emulsion, a certain period (two months) must be allowed to elapse before the emulsion can be used as standard.

(3) After such a period the sensitiveness of the emulsions remains unaltered for at least ten months, and probably much longer.

(4) By none of the other methods of preparation investigated could satisfactory standard agglutinable cultures be made.

The blood of plague-infected rats may contain an enormous number of plague bacilli, even as many as 100,000,000 per c.c. having been found before death. On the other hand rats occasionally die from plague with little or no septicaemia. An insect sucking the blood of most rats shortly before death would imbibe a large number of bacilli.

While the blood of a rat may have as many as 100,000,000 organisms in a c.c. the urine may have none at all, or at least less than 10 per c.c. Plague bacilli were discovered in the urine in 29 per cent. of the cases. When the urine does contain plague bacilli they are always present in much fewer numbers than in the blood.

The faeces of rats dead of plague and the blood of which contained abundant bacteria are not highly infective and would appear to play little part in the spreading of the epizootic.

During a filariasis survey conducted in northern Fiji in 1968–9 examinations were made for microfilaraemia, enlarged lymph nodes and elephantiasis. Analysis of the microfilarial densities at different ages and the number of anatomical sites showing lymph gland enlargement or elephantiasis have been used to provide evidence on the clustering of infections and pathogenesis.

Although there is no evidence of clustering of risk of infection, there is evidence favouring the clustering of adult filariae in individuals. Nevertheless the number of sites of lymph node enlargement do not correspond with this finding and statistical evidence suggests that lymph-node enlargement is not necessarily associated with the near presence in the body of adult filariae, whether dead or alive.

Males of Indian ethnic origin showed a higher prevalence of elephantiasis than males of Fijian ethnic origin, but women of either ethnic race showed prevalences lower than those of men.

The onset of elephantiasis at a site does not directly reflect the number of infections sustained in the local area, but it appears that filariasis first induces for a limited period a proneness to elephantiasis. During this period a random and discrete event may induce the onset of elephantiasis. The nature of the event is unknown, but it probably is not trauma.