1. For each case of streptococcal illness—sore throat, otitis, or other respiratory tract illness—observed in a 30-month study in a large children's home an attempt was made to enumerate the infected contacts from whom the infection might have been derived.

2. Of 459 illnesses, 10·5% seemed to be relapses of a previous illness, and in 10·0% the child was known to have been carrying streptococci for more than 7 days before sickening, so that the causal relation of the streptococcus is in doubt.

3. Of the 365 other illnesses, 31·5% could be attributed with varying degrees of confidence to infection from one specified carrier, 36·8% could have been derived from one or more recognized contacts although there was not sufficient evidence to specify one in particular. For 17·5% no infected contacts were recognized, but infection with the particular streptococcus was known to be present in the community; and for 9·3% there were no contacts and the streptococcus was not known to be present in the Village.

4. Of the ninety-four illnesses for which the source could be specified as one particular carrier, 66% were derived from heavy nasal, 19% from light nasal, and 15% from throat carriers. Persons incubating a streptococcal illness and healthy carriers were each responsible for 31% of the illnesses and convalescent carriers for 38%.

5. It seemed that at least 50% of all illnesses could have been contracted from contacts within the cottage; the proportion due to school infection was much more difficult to estimate but was at least 12%.

In a residential home for children, 367 cases of streptococcal illness were observed in a period of 30 months. The children lived in groups of about twelve in separate cottages. There were 194 occasions on which a streptococcus was thought to have been newly introduced into and produced illness in a cottage; on 132 of these 194 occasions there were no secondary cases of illness. The remaining 62 cottage introductions were followed by one or more secondary cases.

In 27% of the 194 introductions, the primary case of illness seemed to have been infected from a healthy person in the cottage. In all, 30% of introductions of a new streptococcus into a cottage could be attributed to recognized contacts with one or more known infected children.

The most important factor determining spread within the cottage seemed to be the carrier state of the primary case, spread following more often when the primary case had streptococci in the nose either on admission to hospital, or in convalescence.

There was no evidence that spread within cottage bedrooms was of great importance.

In about 35% of the incidents with spread, the initial spread to secondary cases seemed to be from the incubation-stage carriage of the introducer; in 42% it was from his or her convalescent carriage.

The carrier rate in the healthy cottage-contacts was generally higher in cottages experiencing clinical spread of infection than in those that had single-case introductions. There was a strong correlation between the carrier rate in the first week after an introduction and the final bacteriological attack rate, and a weaker correlation with the final clinical attack rate.

Continued spread of infection in a cottage was commonly due to the arrival of new children and was almost always associated with the presence of nasal carriers of streptococci.

The 194 cottage introductions could be grouped into sixty-three overlapping Village epidemics, each apparently derving from a new importation of the particular type into the Village, although the evidence for this was often merely the absence of known infections within the previous few months. Only 13% of the introductions resulted in more than 10 cases, and some 80% had 5 or fewer. Introductions were more frequent in the cottages receiving children new to the homes than in those for the more permanent residents.

The principal factor found as determining the spread from the first cottage to others was the attack rate in the first cottage. Introductions in cottages for school-age children, and especially those in which a child attending the school in the Village grounds was the first to be attacked, also seemed to lead to spread more often than others.

The interval between successive Village introductions of one type did not appear to affect the extent of spread at the second; but the number of cases occurring in the first of two introductions had a notable effect: in no case did two successive introductions both result in a large number of cases of illness.

The concentration of viable cells in an aerosol of micro-organisms is reduced by physical loss and biological decay. To study biological decay it is necessary to distinguish between the two processes. The preferred way of doing this is to mix the test aerosol with a tracer which is subject only to physical loss: the tracer and test cells should be mixed before dissemination.

The recommended tracers for bacterial clouds are bacteria made radioactive by growing on a medium containing 32P, then killed with formaldehyde and washed. To ensure closest identity of physical behaviour it is necessary that the tracer should be of the same species as the cells under test.

We are grateful to Mr E. O. Powell for helpful comment during the preparation of this paper.

From 117 cases of smallpox 140 sera have been examind for antihaemagglutinin, for complement-fixing and for variola-neutralizng antibody.

In smallpox patients who had not been vaccinated prior to infection, variola-neutralizing antibody and vaccinial antihaemagglutinin were present in all sera examined after the sixth day of illness. Complement-fixing antibody was not found until the eighth day of illness but was present in all examined after the ninth day.

In previously revaccinated smallpox patients variola-neutralizing antibody was present in all sera examined after the third day of illness and antihaemagglutinins in all after the fourth day. Complement-fixing antibody was present by the seventh day and was found in all sera examined after the ninth day. Not only did antibody in general appear earlier in previously vaccinated smallpox patients but the titres were generally considerably higher. In ten fatal cases antibody titres were low except in two in whom the level of variola-neutralizing antibody was quite high—in one case on the second day and in the other on the fourth day of illness.

In six variola contacts, who suffered febrile attacks without rash, antibody studies indicated the variolous nature of their illnesses. In these and other atypical smallpox infections, when laboratory confirmation of clinical diagnosis is only requested at a late stage of the disease, a high titre of antibody, particularly complement-fixing antibody, may enable a firm diagnosis to be made.

We wish to acknowledge our indebtedness to Dr W. H. Bradley of the Ministry of Health; Dr E. C. Benn of Seacroft Hospital, Leeds; Dr D. C. Liddle of Monsall Fever Hospital, Manchester; Dr E. R. Peirce of Liverpool and other Medical Officers for information concerning smallpox patients. Our thanks are also due to Dr F. O. MacCallum of the Virus Reference Laboratory, Colindale, who kindly sent us sera from some of the cases in the 1950 smallpox outbreak in Brighton.

1. Microscopical examination of the kidneys of 850 Rattus norvegicus killed in various parts of England and Wales showed an infection rate of 43% with leptospires, assumed to be Leptospira icterohaemorrhagiae for reasons stated.

2. Infection rates calculated from the whole series were the same for rural, urban and sewer rats, but there were some local differences as between one area and another for both surface and sewer rats.

3. An unusual feature was the finding of a 35% infection rate among young rats.

4. In another series of 219 rats taken alive, agglutination tests and kidney cultures gave an infection rate of 43%. Kidney sections of 69 of these rats were also examined microscopically and the results of the different methods of examination were analysed.

5. A similar survey was made on R. rattus. Only 2 of 88 caught in London were positive, compared with 31 of 35 killed in other towns. An additional 98 R. rattus killed during the fumigation of ocean-going steamers were examined, and 69 were found to be infected.

I should like to record my thanks to the following members of staff at the Infestation Control Division of the Ministry of Agriculture, Fisheries and Food, Tolworth, Surbiton, Surrey, for their help in this survey: Mr C. J. Armour, Dr E. W. Bentley, Dr W. P. Crowcroft, Mr R. A. Davis, Miss Y. Larthe and Miss M. Lawrence. Also to the following Field Officers of the Ministry who supplied material for this investigation: Mr A. F. R. Brown, Mr R. J. Clark, Mr G. R. Hill, Mr A. C. Hopkins, Mr R. S. Jailler, Miss B. B. Jones, Miss M. Neve, Mrs J. C. Russell and Mr S. R. Surtees.

I wish also to acknowledge the valuable assistance received from members of my technical staff, especially Miss Joan Messum and Mr R. J. Reed.

For a study of the process of formaldehyde disinfection, cotton threads were used as test objects. These were, in most experiments, impregnated with a heavy suspension of a coagulase-negative micrococcus in 1% gelatin solution or in 90% horse serum, and dried. In other experiments Mycobacterium tuberculosis, Bacillus subtilis or smallpox virus was used. After exposure to formaldehyde, quarter-inch lengths of the threads were cut off and cultivated on agar plates; individual threads were recorded as fertile or sterile and the mean number of organisms per thread was estimated statistically. Neutralization of the formaldehyde was found to be unnecessary except when strong concentrations were used.

In laboratory tests there was a linear relation between the concentration of formaldehyde and the killing rate. Little effect was observed on the speed of disinfection from variation in temperature over the range 0–30°C. There was some suggestion of an optimum relative humidity for disinfection at about 80–90%, but no great increase in disinfection rate was obtained by increasing the relative humidity above 58%. Threads impregnated from a suspension of the cocci in 90% serum were disinfected much more slowly than those impregnated with cocci suspended in a solution of gelatin. Covering the threads with several layers of blanket also slowed the killing rate considerably.

Tests were made of the sterilization of the threads in full-size disinfectors. Mattresses and other bedding absorbed a large quantity of formaldehyde so that the amount supplied had to be greatly in excess of that estimated from laboratory tests to provide a lethal concentration. A disinfector working at ambient temperature was found to kill over 99.99% of the micrococci on threads exposed on the surface of mattresses. The destruction of micrococci on threads placed under pillows or blankets was less, as was that of tubercle bacilli on fully exposed threads.

A disinfector in which the air temperature could be raised to about 100°C. was found to be more effective, partly because the increased temperature allowed much greater penetration of fabrics by the formaldehyde vapour; but the relative contribution of the heat and the formaldehyde to the disinfection process could not be fully determined.

In both the laboratory and the field experiments it was found difficult to obtain completely reproducible results. This constitutes one of the most disconcerting features of disinfection by formaldehyde. The process is influenced by so many different factors that it is impossible to predict with real assurance the result under any given set of conditions.

It is concluded that disinfection by formaldehyde vapour should be used only when no other method is available. It certainly cannot be recommended for disinfection of fabric contaminated with smallpox virus or with anthrax spores, when complete destruction has to be ensured; and unless carried out with special care it is not really suitable for woollen garments and toys soiled with tubercle bacilli.

1. A collection of 1389 strains of Staphylococcus aureus of human origin was examined by the following tests: phage typing, antibiotic resistance, ability to inhibit the growth of Corynebacterium diphtheriae, the egg-yolk reaction and the serum opacity reaction.

2. Nearly all strains of Staph. aureus Type 71 were penicillin resistant, inhibited C. diphtheriae, gave a negative egg-yolk reaction, and produced a zone of opacity on horse-serum agar.

3. The penicillin resistance of Type 71 strains is unlikely to have arisen as a result of the therapeutic use of penicillin, and is probably a natural characteristic of the type.

4. Staph. aureus strains which gave a negative egg-yolk reaction and a positive serum opacity reaction occurred almost exclusively in superficial lesions. The majority of them were members of Type 71, or were penicillin-resistant members of phage-group III. It is suggested that these organisms can cause superficial inflammation, but are usually unable to invade deeper tissues.

I wish to thank Dr A. J. H. Tomlinson for valuable information about his unpublished work on impetigo. Thanks are also due to many colleagues who have provided cultures and clinical information, to Dr R. E. O. Williams for typing phages, and to Mr L. E. Simmons for technical assistance.

Techniques for the production of experimental pneumonia are briefly reviewed. A new method of intra-oral inoculation in the anaesthetized mouse is described and its advantages with particular reference to the danger of aerial contamination and facility of technique discussed. An application of this method to virulence studies is indicated and other possible applications suggested.

The author would like to express gratitude to Dr I. Friedmann for having made this work possible and for his advice and help at all stages. He would also like to thank the late Sir E. L. Kennaway, Dr F. Fulton and Dr D. A. Osborn for helpful suggestions, Prof. E. T. C. Spooner for the kind loan of the Bourdillon apparatus, Dr S. T. Cowan for an N.C.T.C. strain of Klebsiella, Mr P. Payne for statistical advice and Mr D. Connolly for the photomicrograph.

The immediate dispersal of a fluid delivered to anaesthetized mice by the intranasal and intra-oral techniques has been studied by means of a radio-active tracer method. The results clearly show that the intra-orally inoculated animal accepts a larger proportion of the total volume inoculated and that a significantly higher fraction of this reaches the lungs than in mice inoculated by the intra-nasal technique.

The authors would like to thank Dr I. Friedmann and Dr H. A. B. Simons for having made this work possible; also, Mr D. Arnott for a generous gift of labelled di-iodofluorescein, and Dr D. A. Osborn and Dr K. Weinbren for helpful suggestions.

A numerical investigation of three contagious distributions characteristic of epidemic data has been made using an electronic computer.

All three show a modified threshold effect such that the proportion of a community affected tends to 100% as its size increases though there is no abrupt change of form.

We would like to thank Mr M. J. R. Healy for assistance with one of the programmes, and Miss Molly Fretton for her help with the computing.

Folpmers's glutamic acid medium and the lactose modification described by Burman & Oliver (1952) have been compared with MacConkey broth in the pre-sumptive coliform test of 4421 samples of water examined at six different laboratories in England and Wales. As compared with MacConkey broth, both glutamic acid media gave between 8 and 10% more isolations of Bact. coli I; the glucose medium additionally gave an increase of 6% in other coliform organisms, but this was associated with a very heavy excess (232%) of false positive results; lactose glutamic acid satisfactorily controlled false positive reactions, giving a reduction of 36%, but also suppressed by 35% the isolations of coliform organisms other than Bact. coli I.

MacConkey broth gave the largest early (18 hr.) yield of positive results, but the results at the end of 24 hr. were approximately the same with all three media. Preliminary warming of the inoculated tube had only a trivial effect on the rapidity with which the organisms grew, but the warming resulted in a slightly higher total yield of Bact. coli I in the glutamic acid media. Incubation at 42° C. for 18 hr. followed by 37° C. for 30 hr. was found to be inferior to incubation at 37° C. for 48 hr. in the case of lightly polluted waters, in that true coliform organisms were suppressed without any compensating advantage in the yield of Bact. coli I.

Ultra-centrifugation of emulsions from suckling mouse brains infected with the MEF1 strain of poliomyelitis virus separates a non-infective antigen, or soluble antigen, from infective virus. This antigen is responsible for most of the complement fixation and explains the high titres obtained. On the other hand, the same virus, and also Mahoney, Type 1 poliomyelitis virus, grown in monkey kidney tissue culture, fail to produce this soluble antigen, and this is probably a factor in the low complement-fixing titres obtained in tests with these fluids.

The author would like to express her appreciation of Miss M. Butchart's valuable technical assistance.

It is shown that bits of allantois-on-shell cut from any one egg do not differ either in susceptibility to infection by influenza viruses or in yield of haemagglutinin. For this reason the dose-response curve within any egg is Poissonian.

Bits cut from different eggs vary both in susceptibility and in haemagglutinin yield. Unlike in whole eggs however, the scatter is so small that it can be demonstrated only by refined tests done on a large number of subjects. For practical purposes the dose-response curve may still be taken as Poissonian.

Susceptibility and yield vary independently of one another.

The data are used to define the accuracy of infectivity tests in bits of allantois-on-shell; the expected errors are given both for straight replication and for tests done with different reagents, by different operators, or at different times.

1. Additional quantitative studies of the survival of micro-organisms in aerosols are reported.

2. Substitution of nitrogen for oxygen in the ambient medium decreases k′2, the rate of secondary loss of viability of M. candidus, Esch. coli and S. marcescens, by 30–50%.

3. The rate of primary decay (k′1) of Esch. coli does not appear to be affected by a similar change of atmosphere.

4. The rate of secondary decay, k′2, of M. candidus appears to increase two-to three-fold for 10°C. increments in temperature.

5. Treatment of suspensions of Esch. coli with petroleum ether alone or containing lipid material increases k′1 in aerosols generated from such suspensions.

6. Treatment of Myco. phlei with petroleum ether appears to lower resistance to subsequent sonic irradiation.

These observations are consistent with the hypothesis that differences in the physical and chemical structure of micro-organisms are reflected in constants k′1, k′2 and b.

We gratefully acknowledge the effective interest of two former assistants, T. Grant Maple and Eugene Mills, as well as the careful, effective, and conscientious work of our technical assistants, Ann Barr, Nora Galins, Cynthia Hartwig, Grace C. Leigh, Elizabeth Neidhardt, Paulette Slaney and Martha Szerslip, who have at different times helped secure the data presented here. Mrs Joseph J. Ecker deserves special thanks for care in the preparation of the manuscript.

The antigenic response of guinea-pigs to live poliomyelitis viruses of all three types has been studied and the loss of antigenicity involved in inactivation by formaldehyde and by ultra-violet light have been determined.

We wish to acknowledge the debt we owe to the late Prof. M. van den Ende for his great help and interest in this work, and we are grateful for the assistance received from Dr H. Malherbe and Ruth Harwin in carrying out many of the titrations, and from Dr T. Mead for synthesizing some 1:4-diphenylbutadiene for use as a filter for ultra-violet light.

We also have to thank G. S. Turner, T. Norcott, Doreen Deeks and Margaret Pakes for their technical help.

Various techniques have been used in studying antibody responses following infection with pox viruses. Of the in vitro tests the complement fixation and haemagglutination inhibition techniques have proved most convenient, but the antibodies concerned are apparently diiferent from neutralizing antibody (Chu, 1948). Estimation of this antibody to certain members of the group, such as ectromelia and vaccinia viruses, may be made in susceptible animals. Variola virus does not, however, produce lesions in the common laboratory animals with sufficient regularity to make such neutralization tests practicable. But it does constantly give rise to recognizable focal lesions on the chorio-allantois of developing chick embryos. This tissue, susceptible to most members of the pox group, has therefore been used in previous studies (McCarthy & Downie, 1948; Downie & McCarthy, 1950), employing the technique developed by Burnet and his colleagues for vaccinia and other viruses (Burnet, 1936; Keogh, 1936; Burnet, Keogh & Lush, 1937; Burnet & Lush, 1939).

The inactivation rates of tissue-culture polio virus have been determined and these have been applied to the irradiation of formalinized vaccine, as an additional inactivation process, using a simple irradiator.

The antigenic potency of the vaccine was apparently unimpaired.

We wish to thank the late Prof. van den Ende for his keen interest and criticism; Dr H. Malherbe and his staff for carrying out many of the titrations; Dr P. D. Winter for co-operation in irradiating samples of vaccine, and Margaret Pakes for invaluable technical assistance.

It is shown that the assay for infectivity in bits of allantois-on-shell, which has been standardized on the BEL strain, is optimal also for nine representative strains of influenza virus tested.

On the average, the sensitivity of the technique is the same as of orthodox allantoic infectivity tests; its precision is always higher. The relative sensitivity of the two tests varies from strain to strain, the log tray/egg differences being SW (+0.88), MEL (+0.51), CAM (+0.31), PR8 (0.28), WSE (+0.25), HUT (−0.02), BEL (−0.22), FMI (−0.35), LEE (−0.47), BON (−1.02). This gradient is the same for fully infective and incomplete forms of influenza virus.

The tray/egg gradient of susceptibility is negatively correlated with the variation in host resistance.

The differences in susceptibility are not due to any effect of the plastic trays, to thermal inactivation of the virus, to differences in adsorption or viropexis in the two test systems or to the effect of allantoic fluid on the virus particle. The critical step has been shown to occur during the intracellular stage of multiplication.

Two strains of adenovirus Type 3 were isolated from fifty-nine patients suffering from epidemic kerato-conjunctivitis. Serological examination of a further group of fifty-nine patients revealed that neutralizing antibody to adenovirus Type 8 usually developed when the duration of the disease exceeded 14 days, and that at the same time a smaller number of patients also developed low titre neutralizing antibody to Type 3 adenovirus. From the evidence presented it is suggested that adenovirus Type 8 was the infecting organism in the majority of cases, and that when neutralizing antibody to Types 3, 6 or 7 adenovirus was present this probably represented a non-specific effect of stimulation by a heterotypic strain of adenovirus. Insignificant antibody titres by C.F. tests were frequently associated with high titres of neutralizing antibody hi the late convalescent phase of the illness.

I would like to express my gratitude for assistance in obtaining material for the investigation to the following clinicians: Dr J. Winning, Dr J. Marshall, Dr A. Mellick and Dr A. M. W. Thomson of the Eye Infirmary, Glasgow, and to Dr E. McNaught of the Ophthalmic Institution, Glasgow; for supplies of adenovirus seed to Dr B. E. Andrews, Central Public Health Laboratory, Colindale and Dr D. A. J. Tyrrell, Virus Research Laboratory, Sheffield; and for technical assistance to C. McLean, F.I.M.L.T., H. G. Carson, F.I.M.L.T. and J. Kerr.

Four out of fifty acute respiratory infections occurring in forty-five adult volunteers in a teaching hospital, from October 1956 to July 1957, were associated with infection by a member of the adenovirus group. In three of these adenovirus infections the clinical picture was quite distinct from that of the common cold, but not from other syndromes of unknown aetiology; in the fourth case the clinical picture was not easily distinguishable from the common cold.

It is suggested on the basis of this study that adenovirus vaccines would do little towards reducing sporadic acute respiratory infections in this type of community.

Complement-fixing and neutralizing antibody patterns to adenovirus Types 1–7, 9 and 10 were determined in paired sera from forty-four of the forty-five volunteers.

I wish to thank all the volunteers who took part in this investigation, Mrs Audrey Rae, A.I.M.L.T., for expert technical assistance, Dr Nuala Crowley and Prof. K. R. Hill, Pathology Department, Royal Free Hospital, Dr H. G. Pereira, National Institute for Medical Research, Mill Hill, and Dr F. K. Sanders, M.R.C. Virus Research Unit, London School of Hygiene, for advice and help.