1. ‘Pure fimbrial antisera’ were prepared for Sh. flexneri strains of O-serotypes 1a, 2b, 3 and 4a and 5, by injecting rabbits with a living fimbriate-phase culture and absorbing the crude immune serum with a non-fimbriate-phase culture of the same strain to remove antibodies for the non-fimbrial (somatic) antigens. These sera gave at high titre a rapid, loosely floccular agglutination of all fimbriate-phase Flexneri cultures, caused adhesion of their fimbriae visible by electron-microscopy and inhibited their haemagglutinating activity. ‘Non-fimbrial antisera’, prepared by injection of non-fimbriate-phase cultures, were devoid of these activities; they gave somatic-type agglutination with fimbriate bacilli at lower titres than with homologous non-fimbriate bacilli, the fimbriae tending to mask the O-antigens and confer relative O-inagglutinability.

2. Heating at 90°C. detached the fimbriae from the bacilli, so that these lost their haemagglutinating activity, fimbrial serum agglutinability and fimbrial agglutinin-binding power. When heated for 21/2 hr. at 100°C., the detached fimbriae retained agglutinin-binding power, but lost their immunogenicity.

3. Cross-agglutination and absorption tests showed that the antigenic composition of the fimbriae was identical in all flexneri strains, irrespective of O-serotype. The flexneri pure fimbrial antisera agglutinated at low titre sixty out of sixty-six fimbriate Bact. coli strains. Absorption tests with a flexneri and three coli pure fimbrial antisera showed that the fimbriae of Sh. flexneri contained a major ‘flexneri-specific antigen’, found in only one coli strain, one or more minor ‘flexneri-coli antigens’ shared by a few coli strains. The coli fimbriae also contained a major, ‘coli type-specific antigen’ shared in groups of several related strains. The flexneri sera did not react with fimbriate strains of Bact. cloacae, Salmonella and Proteus.

4. Fimbrial agglutinins for Sh. flexneri were found in eighty of eighty-one normal human sera at titres from 30 to 1920, and in some pre-immunization rabbit sera at titres of 30 to 60.

Suppose that λ is the average density per unit volume in a suspension of infective particles such as virus particles. To estimate λ the usual method is to make up a series of inocula of various dilutions containing expected numbers of particles …λi−1, λi, λi+1,… which are known multiples of λ. Each of these is then tested by inoculation in a host such as an egg. We consider only the case where the dilution series is twofold (λi=λ2i, say) and the same number of eggs, N, is tested at each dilution. Then if we are sure that an egg is infected if and only if the inoculum contains at least one infective particle, the probability that the egg remains sterile is Pi=exp {− λ2i}. If each particle is not certainly infective but has a probability p of infecting the egg, the probability of sterility of an egg chosen at random is exp {− λp2i} provided that p does not vary from egg to egg. It is then only possible to estimate λp from the results.

The growth of Salmonella typhimurium in mice was studied by performing viable counts on pooled viscera and, in the case of fatally infected mice, by determining the relation between size of dose and mean death time. The results suggested that this system conformed to a general model which postulates (a) that the organisms causing the response (death in the present experiments) increase in vivo at a rate which is constant for all doses, and (b) that the response is certain to occur when their number reaches a constant figure. It follows that logarithm of dose (for doses > 1 ED50) should be linearly related to mean latent period (the interval between inoculation and response). A search of the literature showed that this relation was observed in many reported infective systems.

The interpretation of the observations on partially resistant mice (LD50 = 102.5−106 organisms) was not straightforward for the hypothesis of independent action (Meynell & Stocker, 1957) states that only a random fraction of the inoculum usually initiates each response. Multiplication of this fraction is considered to cause a reduction in host resistance so that other organisms surviving in vivo began to increase in numbers and to contribute to the fatal infection. The observations showed that this could well occur as (i) the counts on all mice, whether fatally infected or not, increased exponentially for 2–3 days after inoculation; (ii) the growth curves of fatally infected mice showed exponential increase of the whole inoculum as postulated; and (iii) the length of the death time was found to be determined by the growth of the whole inoculum and not by the predicted random fraction. The viable count per fatally infected mouse at the time of death was approximately constant at 108.75 organisms. There was no evidence that the course of the infection was influenced by organisms which may have been killed in vivo as the requirements of the model were satisfied by the observed behaviour of the viable organisms alone. The rate of increase of organisms in a fatally infected animal was found to be less, the greater the LD50 of the host; which suggested that the degree of host resistance was determined by successive random events occurring after inoculation.

The latent period/log dose curve provides a new test of the hypothesis of independent action, since this predicts that most responses to doses equal to or less than 1 ED50 are each initiated by only one inoculated organism. Hence, the latent period should become approximately constant at such doses. This was found to be so in the present experiments.

The authors are grateful to the Medical Research Council for meeting part of the expenses of this work by a grant to G. G. M. They also wish to acknowledge the help of Dr W. R. Bryan, Dr B. Mandel, Dr D. B. W. Reid and Dr G. T. Stewart who provided unpublished data.

1. Sera taken from seventy-nine individuals who had been examined for poliomyelitis antibodies shortly before a Type 1 epidemic, were examined for the development of antibodies to polio-virus 6 months after the epidemic.

2. Ten of eleven (91%) susceptibles aged 5–7 years, 44% of those aged 8–9 years, 25% of those aged 10–14 and only one of fifteen (7%) 15 years or more old had developed neutralizing antibodies to Type 1 polio-virus.

3. In the school which the younger subjects attended, one boy developed paralytic poliomyelitis while the school was in session, but the amount of minor illness in the epidemic period was not significantly different from the 3-year average.

4. The comparison between these findings and the notification rate for the province suggested that the chance of an infection with polio-virus during this epidemic, leading to a clinically recognizable attack of the disease, might have been as much as eighteen times higher in adolescents and adults than in the 5–9 age group.

5. The epidemiological significance of these results is discussed.

We have pleasure in acknowledging our indebtedness to Dr J. H. S. Gear for the report on the sera collected before the epidemic, to Dr W. Murphy, Medical Officer of Health, for data about notifications, to Dr A. M. Douglas for assisting by collecting some of the bloods, to the Principal and staff of John McGlashan College for their readiness to assist us at all times and to all those subjects who allowed us to take a further specimen of their blood for this investigation.

1. Of 318 Polish refugees now living in this country 30% gave a history of typhus fever; nearly half of these had complement-fixing antibodies to a titre of 1–5 or more to epidemic typhus. A further 12% without such a history similarly had these antibodies making a total of 22% of 318 refugees. None of the 174 British born controls had antibodies up to this titre.

2. Brill-Zinsser disease may occur from time to time among immigrants or visitors from typhus endemic areas to this country, but it is unlikely to be a serious problem.

3. The clinical diagnosis of Brill-Zinsser disease may not be easy because the characteristic rash is not always to be seen. Any patient of Eastern European origin or who has a history of typhus complaining of fever and severe headache should be examined serologically by the rickettsial agglutination or the complement-fixation test for specific epidemic typhus antibodies. The Weil-Felix reaction may be positive, but a negative result will not exclude a diagnosis of Brill-Zinsser disease.

We acknowledge with gratitude the help, interest and advice of Dr E. S. Murray, of the School of Public Health, Harvard University and Dr Janet Niven and also the technical assistance of Mr J. P. Brooks, FIMLT. We have to thank Messrs Lederle for their kindness in supplying the rickettsial antigens and in addition those who helped us to obtain the specimens and the volunteers who supplied them.

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.

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.

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.

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.

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.

1. A method has been developed for the assay of antisera against influenza viruses.

2. Surviving bits of allantois-on-shell serve as host tissue, eighty to one hundred units being provided by a single egg. The test is set up in plastic trays, and uses a simple synthetic medium.

3. The method has worked equally well with the ten representative strains of influenza virus tested. It surpasses the orthodox techniques of neutralization in mice or whole eggs as regards sensitivity, accuracy and economy.