A form of ultramicroscope apparatus is described which enables the evaporation of mist droplets to be followed for long periods. A rough method of estimating the size distribution in aerosols is also given.

The rates of evaporation of particles of various phenol solutions have been studied, the solutions chosen being of possible interest as aerial germicides. It is shown that the typical evaporation curve for a binary mixture consists of three parts, which in actual cases need not all be present. Sometimes the more detailed history of an evaporation can be deduced from the results.

The approximate effective size distributions in mists of hexyl-resorcinol—propylene-glycol solutions have been measured and compared with the evaporation rates.

It is shown that the efficiency of aerial germicides is partly a function of their volatility, and three rough classes are distinguished. But biological evidence is adduced which suggests that the solubility of the germicides in water may be of equal importance, and that the liquid in which the germicide is dissolved is not without effect.

A centrifuge is described which enables the maximum particle size in a mist to be limited to a desired value.

Methods of estimating quantitatively germicidal aerosols are discussed, and a method described which has been found to give reasonably accurate results in practice. Tentative experiments have been made to determine whether the materials studied are likely to cause corrosion of metals, etc., after pro-longed use.

The collision theory of aerial disinfection is discussed, as is also the applicability of Langmuir's treatment of the evaporation of fine particles in mixtures.

The development of the experimental technique involved in the biological investigations appertaining to air disinfection has been discussed, together with the numerous fallacies arising and the means by which these have been overcome.

The construction of a special pair of experimental chambers is described, and details given, both as regards the bacteria and germicides, of the exact experimental conditions under which the most consistent results can be obtained.

The requisite characteristics of germicidal mixtures which could be utilized for air disinfection are considered, and examples of suitable germicides and solvents are given. The method of recording and evaluating the results of a varied assortment of experiments is explained to facilitate inter se comparison.

Examples are given of the lethal effectiveness in the air of several germicides in broth emulsions, both with and without the presence of serum, on stock cultures of selected types of bacteria. The sensitivity to the germicides of the bacteria making up the flora of the average normal saliva is compared with that of broth emulsions of bacteria.

10% hexyl-resorcinol dissolved in propylene-glycol+0·05 % sulphonated lorol (“S2”) was the most effective all round germicidal mixture of those tested. Various other germicides were found equal in germicidal activity in the air, but for reasons stated have been deemed unsuited for use in the presence of man.

The relationship between germicidal efficiency in the air and mist particle size and persistence has been studied by means of centrifuged mists. Particles of 0·5–1·0μ radius are shown to be the most useful in dealing with bacterial particles containing organic matter. Laboratory cultures, emulsified in broth, have been sterilized in mist dispersions by droplets of bactericides at least as small as 0·25μ radius.

Tests on the penetrating abilities of bactericidal mists and bacteria through certain cloths have been performed.

Experiments to demonstrate the surface sterilizing properties of aerosols have been performed, and examples of differences in effect on horizontal and vertical surfaces are noted.

The degree of tolerance of man and animals (mice) for a number of phenolic substances and some organic solvents has been compared with the degree of tolerance of bacteria for the same substances.

The tests on man have been confined to the detection by the special senses of the substances suspended in the air as a fine mist.

The tests on animals were designed to show acute and chronic effects, the results being recorded in terms of clinical symptoms and pathological changes in the organs. A record was also kept of the findings as regards protozoal parasites of the host, and compared with the normal incidence among ordinary laboratory stock.

Tests on bacteria were instituted for the purpose of gaining information on the host-parasite tolerance ratio for our germicides when in the air and when in the test-tube.

Suppose that λ is the average density of virus particles per unit volume. If x is a dilution of this and unit volume is applied to an egg (or plate in other problems) the probability that the egg remains sterile is

provided that if a particle is present, it will infect the egg. To make a dilution assay we choose dilutions x1, …, xm (m levels) and apply these to n1, …, nm eggs. If these result in r1, …, rm sterile eggs we can estimate λ by maximum likelihood. The theory has been given by Barkworth & Irwin (1938), and full references to work on this problem will be found in Finney (1952). If we plot the quantities r1/n1, …, rm/nm against x1, …, xm we get a set of point whose fit to the curve (1) can be tested by a χ2 test. In a number of situations, however, it is found that (1) does not give a good fit. The estimation of λ is then completely invalid. In the present paper we consider why this happens, what types of curve may be fitted to the data and what they imply, and we also give a simple rapid test for such data fitting an exponential curve.

A study of the growth phases of pleuropneumoma has been carried out by two new methods: (1) a new fixing and staining technique, (2) a new dark-ground method. The results obtained by the two methods are in good agreement, and the life cycle of the organism of bovine pleuropneumoma and related microbes as revealed by means of both methods has been described.

Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2–8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.

Attempts were made to isolate viruses from babies' stools that contained adenoviruses detected by electron microscopy. One hundred and fifty-nine specimens from 71 children were studied and adenoviruses of established serotypes were isolated from 81 stools. Serial stool samples containing adenovirus particles were obtained from 35 children, and prolonged shedding of recognized serotypes was common. Simultaneous and sequential infections by different serotypes were also observed. Thirty-six children shed adenoviruses that could not be isolated using cell cultures normally used to detect adenoviruses, and nine of these children also shed adenoviruses of established serotypes. Passage in Chang conjunctival cell cultures allowed characterization of fastidious adenoviruses from 14 children as members of a previously unrecognized serotype.

Mice and rats which are normally resistant to histamine become more susceptible to its lethal action after an injection of H. pertussis. This so-called sensitization to histamine is not an anaphylactic phenomenon. It is due to the action of a component of H. pertussis, the histamine-sensitizing factor (HSF), which in some unknown way overcomes the physiological mechanism in rats and mice that makes them more resistant than other species to histamine. Guinea-pigs which appear not to possess this mechanism and are about 200-fold more susceptible, weight for weight, than rats and mice, were not made more sensitive by H. pertussis.

After a stated dose of vaccine, sensitization was detectable in 48 hr., reached a maximum in 3–4 days, remained at this level for about 2 weeks and gradually disappeared. The effects of dosage, route of injection, and weight and sex of mice have been examined.

The HSF was found in strains of H. pertussis; it was not found in H. parapertussis, H. bronchisepticus or H. influenzae. It was only slightly affected by heating at 70° C. for 1 hr. but was destroyed at 80° C. in ½ hr. It was destroyed when bacteria were disintegrated by shaking with glass beads, or by grinding after being freeze-dried. It was found in the supernatant fluid of a partially autolysed vaccine.

HSF was antigenic. Antisera were prepared in rabbits. Anti-HSF combined with HSF and neutralized its histamine-sensitizing activity. Bacteria treated with antiserum in vitro absorbed anti-HSF and did not thereafter sensitize mice.

Antiserum protected mice passively against the sensitizing action of vaccine, presumably by combining with HSF. After sensitization had developed the sensitive state was not affected by antiserum.

Although HSF is an antigen there was no indication that histamine-sensitization was due to its antigenicity.

The HSF was differentiated from heat-labile and heat-stable toxin, haemagglutinin, capsular material and agglutinogen.

The preparation V 17, which is a small fraction of the disintegrated bacteria, adsorbed on red cell stromata (Pillemer et al. 1954) had a high histamine-sensitizing value. Compared with whole bacterial vaccine it caused little production of agglutinin in mice; in rabbits it caused a slower and smaller production of agglutinin and a faster and greater production of anti-HSF. For this reason immune rabbit sera may have a high agglutinin titre and a low anti-HSF value or vice versa. Anti-HSF rabbit serum protected mice against sensitization by V 17.

Vaccines could be graded according to their histamine-sensitizing activity. This did not always correspond to their grading by agglutinin production in mice. The relation of HSF to the immunizing antigen of H. pertussis and the use of histamine-sensitization to indicate the immunizing potency of pertussis vaccines are discussed.

We wish to thank Glaxo Laboratories Ltd. for the supply of reference vaccine, and the Whooping Cough Immunization Committee of the Medical Research Council for vaccines and sera.

To quantify the host genetic component of meningococcal disease (MD) susceptibility, the sibling risk ratio (λs) was calculated as the ratio of observed MD cases among 845 siblings of 443 UK Caucasian cases to that expected, calculated from age-calendar year specific rates for England and Wales. Twenty-seven siblings contracted MD compared with an expected 0·89, generating a λs value of 30·3. Overestimation of λs due to Neisseria meningitidis exposure was minimized by excluding siblings with MD onset within set time points of the index case. Irrespective of whether siblings contracted MD more than 1, 3, 6, 9 or 12 months after the index case, the λs varied slightly (λs range: 8·2–11·9), suggesting that host genetic factors may contribute approximately one third of the total λs. Social class distribution did not differ between MD cases and the general population of England and Wales. This study is the first to calculate λs for MD and establishes that susceptibility to MD has a significant host genetic component.

The ESEN (European Sero-Epidemiology Network) project was established to harmonize the seroepidemiology of five vaccine preventable infections including measles, mumps and rubella in eight European countries. This involved achieving comparability both in the assay results from testing in different centres and also sampling methodology. Standardization of enzyme immunoassay results was achieved through the development of common panels of sera by designated reference centres. The panels were tested at the reference laboratory and then distributed to each participating laboratory for testing using their routine methods. Standardization equations were calculated by regressing the quantitative results against those of the reference laboratory. Our study found large differences in unitage between participants, despite all using an EIA method standardized against an international or local standard. Moreover, our methodology adjusted for this difference. These standardization equations will be used to convert the results of main serosurvey testing into the reference country unitage to ensure inter-country comparability.

To evaluate the epidemiology of hospital admissions for varicella in children, a 1-year prospective multicentre study was done in Northern France in the pre-varicella vaccine era. The 405 children aged <16 years seen at local hospitals for varicella or herpes zoster were included. Among them, 143 who had varicella and resided in the district were admitted. Admission incidence rates were 28/100000 children aged <16 years (149/100000 infants aged <1 year, 69/100000 children aged 1–4 years, and 2/100000 children aged 5–15 years). Most admissions (57%) were related to complications, usually skin infection (47%). Independent risk factors for admission were place of residence outside the district [adjusted odds ratio (aOR) 8·7], complication at admission (aOR 5·8), recurrent fever (aOR 4·5), recent varicella in a sibling (aOR 4·0), and previous physician visit for the same condition (aOR 2·0).

A total of twenty-five grade cattle were infected experimentally with a strain of rinderpest virus of moderately high virulence (RGK/1). Three methods of introduction of the virus were employed, i.e. subcutaneous or intranasal inoculation (14 animals) and housing in contact with reacting cattle (11 animals).

A quantitative study of the viraemia and of virus excretion by the nasal, urinary and faecal routes, was made by the inoculation of primary calf kidney cultures. All virological data were related to the onset of pyrexia, the incubation period in inoculated animals being 3–5 days, while in those infected by contact it was 8–11 days. Viraemia preceded the first rise of temperature by as much as 2 days in inoculated animals and 1 day in the contact cases. All animals had viraemia by the 4th day of the disease, but thereafter the percentage of positives declined rapidly, reaching nil by the 9th day.

The case mortality rate was 48 % with the majority of animals dying on the 7th to 10th days after reaction.

Virus was detected in the nasal secretions of some animals on the 2nd day preceding pyrexia. The proportion of nasal excretors rose slowly to reach a maximum of 87·5 % on the 4th day and no positives were detected after the 9th day of fever. The titre of virus in nasal discharges reached high levels, often probably in the region of 105·0 to 106·0 TCD 50/ml.

Urinary excretion of virus began on the 1st day of fever in about 25 % of animals; reaching a maximum of 62·5 % on the 7th day. No virus was recovered from the urine after the 8th day of the disease, the rapid decline in the excretor rate being only partially attributable to the death of severe cases. Urinary titres were relatively low; they seldom exceeded 102·0 TCD 50/ml.

Virus was first recovered from the faeces on the 3rd day of pyrexia. Excretion by this route was not constantly associated with the development of diarrhoea, but the rapid decline which occurred in the excretor rate on the 8th and 9th days was undoubtedly attributable to the death of diarrhoeic individuals which took place at that time. The majority of faecal titres were in the approximate range of 103·0 to 104·0 TCD 50/g. but occasional samples attained ca. 106·0 TCD 50/g.

It was calculated, from the clinical and virological data that cattle can excrete virus, at least by the nasal route, as much as 6 days before the appearance of pathognomonic clinical signs, i.e. oral necrosis and erosion.

Our findings for rinderpest were compared with those of other investigators of this disease and also with the available information on canine distemper and human measles.

We are very grateful for their able technical assistance to Messrs L. W. Rowe, C. S. Rampton and R. F. Staple. Particular thanks are due to Mr C. S. Rampton for his preparation of all the figures. We have received considerable and indispensable help from our junior laboratory staff, especially Mr Francis Ngugi Gachuhi and Mr Joash Adero.

This paper is published by permission of Mr H. R. Binns, C.M.G., O.B.E., the Director of the East African Veterinary Research Organization.

The relationship between risk of death following influenza A(H1N1)pdm09 infection and ethnicity and deprivation during the 2009/2010 pandemic period and the first post-pandemic season of 2010/2011 in England was examined. Poisson regression models were used to estimate the mortality risk, adjusted for age, gender, and place of residence. Those of non-White ethnicity experienced an increased mortality risk compared to White populations during the 2009/2010 pandemic [10·5/1000 vs. 6·0/1000 general population; adjusted risk ratio (RR) 1·84, 95% confidence interval (CI) 1·39-2·54] with the highest risk in those of Pakistani ethnicity. However, no significant difference between ethnicities was observed during the following 2010/2011 season. Persons living in areas with the highest level of deprivation had a significantly higher risk of death (RR 2·08, 95% CI 1·49-2·91) compared to the lowest level for both periods. These results highlight the importance of rapid identification of groups at higher risk of severe disease in the early stages of future pandemics to enable the implementation of optimal prevention and control measures for vulnerable populations.

The spread of a 'cream' mutant in a wild population of house mice is reported. The hypothesis that the gene responsible for the colour, extreme chinchilla, ce, has spread because of linkage with a major gene for warfarin-resistance, is tested by a linkage backcross.

The results prove that a major gene does exist, that it is very closely linked with frizzy, fr, in chromosome 7, which in turn is linked with ce, that it is fully dominant in females at 4 months of age, and that its partial dominance in males is under the control of modifiers.

The symbol War is proposed for the gene. Its position in chromosome 7 is analagous with the position of the resistant gene, Rw2, in the rat in the analagous chromosome.

The adaptive significance of this finding is discussed, as also are reports of certain other mutants in wild populations of mice.

Groups of 45 chickens were fed continuously on diets containing 10 or 100mg./kg. of different ‘growth-promoting’ antibiotics and infected orally with a nalidixic acid-resistant mutant of Salmonella typhimurium. The amount of S. typhimurium organisms excreted in their faeces was estimated by culturing them at weekly intervals and in a standard manner on plates of brilliant green agar containing sodium nalidixate, both direct and after enrichment in selenite broth.

All of four groups fed diets containing 100 mg./kg. of nitrovin in three different experiments excreted much larger amounts of S. typhimurium than did groups fed antibiotic-free diets. In some, but not all, experiments, larger amounts were also excreted by groups fed diets containing 10 mg./kg. of nitrovin or 10 or 100 mg./kg. of flavomycin or tylosin. Feeding diets containing 10 or 100 mg./kg. of virginiamycin or bacitracin either did not influence or slightly ncreased the amount of S. typhimurium excreted.

Two groups fed continuously on diets containing 100 or 500 mg./kg. of sulphaquinoxaline for 44 days excreted smaller amounts of the S. typhimurium organisms than did groups fed antibiotic-free diets; no sulphonamide-resistant organisms of the S. typhimurium strain were isolated from the faeces.

A serological survey for the prevalence of hantavirus infections in The Netherlands was carried out on > 10000 sera, from selected human populations, and different feral and domestic animal species. Hantavirus-specific antibodies were found in about 1% of patients suspected of acute leptospirosis, 10% of patients with acute nephropathia, and in less than 0·1% haemodialysis and renal transplant patients. Among individuals with a suspected occupational risk, 6% of animal trappers, 4% of forestry workers, 2% of laboratory workers and 0·4% of farmers were seropositive. The majority of the seropositive individuals lived in rural and forested areas. The main animal reservoir of the infection was shown to be the red bank vole (Clethrionomys glareolus). Epidemiological, clinical and laboratory findings seen in serologically confirmed human cases were similar to those associated with nephropathia epidemica.

Three sources of data (general practice episode data from the Weekly Returns Service of the Royal College of General Practitioners, national hospital admission data for England and national mortality data by date of death) were examined separately in each winter (1994/1995 to 1999/2000) to investigate the impact of influenza on circulatory disease. Weekly data on incidence (clinical new episodes) hospital emergency admissions and deaths certified to circulatory disorders and to respiratory diseases (chapters VII and VIII of ICD9) during influenza epidemic periods (defined from combined clinical/virological surveillance) were examined in age groups 45–64, 65–74 and [ges ]75 years. Data collected in the four winters in which there were substantial influenza A epidemics were consolidated for the period 6 weeks before to 6 weeks after each peak of the epidemic, and associations between the variables at different time lags examined by calculating cross-correlation coefficients. We also examined deaths due to ischaemic heart disease (IHD) as a proportion of all circulatory deaths and deaths due to influenza/pneumonia as a proportion of all respiratory deaths. There were no increases of GP episodes nor of emergency admissions for circulatory disorders in any of the three age groups during epidemic periods. Increased circulatory deaths occurred in all age groups and particularly in the oldest group. The large cross-correlation coefficients of deaths (circulatory and respiratory) with GP respiratory episodes at weekly lags of 0, −1 and 1 were evidence that the deaths and episode distributions were contemporaneous. The ratios of excess circulatory deaths relative to excess respiratory deaths during epidemic periods were 0·74 (age 45–64), 0·72 (65–74) and 0·57 ([ges ]75 years). Increased circulatory deaths contemporary with new incident cases of respiratory episodes but with no concomitant increase in admissions suggests rapid death during the acute phase of illness. Influenza contingency planning needs to take account of these deaths in determining policy for prophylaxis and in providing facilities for cardio-respiratory resuscitation.

In Germany tularemia is a re-emerging zoonotic disease. Therefore, we investigated wild animals and environmental water samples for the presence and phylogenetic diversity of Francisella tularensis in the poorly studied Berlin/Brandenburg region. The phylogenomic analysis of three isolates from wild animals revealed three new subclades within the phylogenetic tree of F. tularensis [B.71 from a raccoon dog (Nyctereutes procyonoides); B.74 from a red fox (Vulpes vulpes), and B.75 from a Eurasian beaver (Castor fiber albicus)]. The results from histological, PCR, and genomic investigations on the dead beaver showed that the animal suffered from a systemic infection. Indications were found that the bacteria were released from the beaver carcass into the surrounding environment. We demonstrated unexpectedly high and novel phylogenetic diversity of F. tularensis in Germany and the fact that the bacteria persist in the environment for at least one climatic season. These findings support a broader host species diversity than previously known regarding Germany. Our data further support the assumption derived from previous serological studies of an underestimated frequency of occurrence of the pathogen in the environment and in wild animals. F. tularensis was isolated from animal species not previously reported as natural hosts in Germany.

A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64·3%) of whom were children aged <10 years; 98% of cases had never been immunized against diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21·4%, and was highest in children aged 0–4 years (42·9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.

In 1976, an epidemic caused by infections with an influenza virus antigenically similar to A/Victoria/75 (H3N2) occurred in Houston, Texas. During this outbreak, 37 families (155 members) enrolled in the Houston Family Study were under observation. The families lived throughout the metropolitan area (Houston, Texas), and were representative of low income groups. The overall frequency of infection in family members was 27·7%. The frequency of infection was the highest for infants under one year of age and for their older siblings, 14 (37·8%) of 37 and 17 (33·3%) of 51, respectively. Eighteen (48·6%) of the 37 families had at least one infected member. Twelve of the 18 ‘infected’ families had school aged children, whereas only three of the 19 ‘non-infected’ families had school aged children (P < 0·01). These infected families were also larger and had increased household density (persons/rooms). The levels of pre-existing HI antibodies to A/Victoria/75 and A/Port Chalmers/73 were inversely related to frequencies of infection and illness associated with A/Victoria/75 virus. Three children required hospitalization as direct consequence of their infection with this H3N2 influenza virus. Antibody response to infection was related to previous experience with antigenically-related influenza A (H3N2) viruses according to Francis', ‘doctrine of original antigenic sin.’

Identifying county-level sociodemographic and economic factors associated with the incidence of enteric disease may provide new insights concerning the dynamics of community transmission of these diseases as well as opportunities for prevention. We used data from the National Notifiable Diseases Surveillance System, the U.S. Census Bureau, and the Health Resources and Services Administration to conduct an ecological analysis of 26 sociodemographic and economic factors associated with the incidence of salmonellosis, shigellosis, and E. coli O157:H7 infections in US counties for the period 1993 to 2002. Our study indicates that race, ethnicity, place of residence, age, educational attainment, and poverty may affect the risk of acquiring one of these enteric bacterial diseases. The lack of specificity of information regarding salmonellae and shigellae serotypes may have led to less specific associations between community-level determinants and reported incidence of those diseases. Future ecological analyses should use serotype-specific data on incidence, which may be available from laboratory-based surveillance systems.

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.