The direct complement fixation test was performed to follow the antibody response in chickens infected with avian infectious bronchitis virus. Concentrated allantoic fluid (4 units) was used as an antigen and allowed to react with serially diluted antiserum in the presence of two complete units of guinea-pig complement for 3 hr. at 4°C. and ½ hr. at 37°C. before the addition of sensitized cells. Serum was unheated and used either fresh or within one month of storage at −30°C. Individual birds showed a rise and fall of complement-fixing antibody both after primary and secondary inoculations. The complement-fixing antibody was detected as early as the seventh day after primary inoculation. The highest complement fixation titre (1/32 to 1/64) was recorded from 14 to 21 days after inoculation with a subsequent gradual decline.

The results of the direct complement fixation tests have been correlated with the serum neutralization test. The neutralizing antibodies usually appeared by the 14th day but were not detected at a significant titre until the 21st day after primary inoculation. Serum neutralizing antibodies were still present at high titres even after 7 weeks of infection but the complement-fixing antibodies had disappeared by that time.

An estimate for the source of coagulase-negative staphylococci in blood cultures is presented and its use illustrated in two populations. The method estimates the probability that a positive blood culture is positive due to contamination and the probability of it being positive due to bacteraemia. The effect of changes in efficiency of the blood culture technique on these estimates is demonstrated. One of the illustrative populations consists of 537 sample pairs from 273 patients, taken after open-heart surgery in 1978–80. The other consists of 500 consecutive sample pairs taken in one of two hospitals in 1983–4.

An investigation to test the efficiency of chemical closets in treating excreta from typhoid carriers is described. The use of these closets kept a stream, which had in the past frequently contained Salmonella typhi, typhoid free for 24 months. Selenite broth as made in this laboratory, containing a final concentration of 0·8% sodium hydrogen selenite when inoculated with the water sample, was significantly better than commercial selenite brilliant green enrichment broth for the recovery of S. typhi.

Sensitivity, specificity and predictive values of an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against bovine leukaemia virus (BLV) were evaluated using a representative sample of 145 serum pools, comprising from 3 to 48 individual sera. The sample was constituted according to the frequency distribution of the negative and positive pools analysed during a screening involving the whole cattle population of Belgium. Sensitivity and specificity were estimated to 88·9% and 100% and the predicted negative and positive values were 99·9% and 100%, respectively. These results indicate the use of serum pools is suitable for the detection of BLV infected herds in eradication campaigns.

1. In Hong Kong, where scarlet fever is extremely rare, the Dick reactions of a random sample of 921 Chinese were ascertained. Positive reactions were obtained in 19·1 per cent. The distribution of positive reactors in different age groups is recorded; it bears a general similarity to those recorded by various observers in Europe and the U.S.A.

2. A haemolytic streptococcal carrier rate of 6·6 per cent, was determined by nasopharyngeal swabbing of 1600 Hong Kong Chinese. The frequency of haemolytic streptococci was higher during the cooler months of the year and among the younger age groups.

3. Erythrogenic toxin production and fibrinolytic activity were demonstrated in a number of the strains of streptococci isolated from apparently normal throats.

4. The significance of these findings is discussed.

The COVID-19 pandemic has presented a unique opportunity to understand how real-time pathogen genomics can be used for large-scale outbreak investigations. On 12 August 2021, the Australian Capital Territory (ACT) detected an incursion of the SARS-CoV-2 Delta (B.1.617.2) variant. Prior to this date, SARS-CoV-2 had been eliminated locally since 7 July 2020. Several public health interventions were rapidly implemented in response to the incursion, including a territory-wide lockdown and comprehensive contact tracing. The ACT has not previously used pathogen genomics at a population level in an outbreak response; therefore, this incursion also presented an opportunity to investigate the utility of genomic sequencing to support contact tracing efforts in the ACT. Sequencing of >75% of the 1793 laboratory-confirmed cases during the 3 months following the initial notification identified at least 13 independent incursions with onwards spread in the community. Stratification of cases by genomic cluster revealed that distinct cohorts were affected by the different incursions. Two incursions resulted in most of the community transmission during the study period, with persistent transmission in vulnerable sections of the community. Ultimately, both major incursions were successfully mitigated through public health interventions, including COVID-19 vaccines. The high rates of SARS-CoV-2 sequencing in the ACT and the relatively small population size facilitated detailed investigations of the patterns of virus transmission, revealing insights beyond those gathered from traditional contact tracing alone. Genomic sequencing was critical to disentangling complex transmission chains to target interventions appropriately.

Enteric illness outbreaks are complex events, therefore, outbreak investigators use many different hypothesis generation methods depending on the situation. This scoping review was conducted to describe methods used to generate a hypothesis during enteric illness outbreak investigations. The search included five databases and grey literature for articles published between 1 January 2000 and 2 May 2015. Relevance screening and article characterisation were conducted by two independent reviewers using pretested forms. There were 903 outbreaks that described hypothesis generation methods and 33 papers which focused on the evaluation of hypothesis generation methods. Common hypothesis generation methods described are analytic studies (64.8%), descriptive epidemiology (33.7%), food or environmental sampling (32.8%) and facility inspections (27.9%). The least common methods included the use of a single interviewer (0.4%) and investigation of outliers (0.4%). Most studies reported using two or more methods to generate hypotheses (81.2%), with 29.2% of studies reporting using four or more. The use of multiple different hypothesis generation methods both within and between outbreaks highlights the complexity of enteric illness outbreak investigations. Future research should examine the effectiveness of each method and the contexts for which each is most effective in efficiently leading to source identification.

An LD 50 dose S. typhi (strain Ty was injected intraperitoneally into white mice, and the number of micro-organisms was determined after 1 min. and subsequently, in the blood, and after 3 hr. and subsequently, in the spleen and liver. The course of the infection was observed for 34 days.

The number of bacteria gradually increased in the blood stream during the first post-infective hours. It was possible to differentiate by external signs from the sixth post-infective hour and onwards between sick animals and recovering ones. This difference corresponded to the bacterial concentration in the blood stream and internal organs.

In the sick animals the increase in the bacterial count of blood stream continued till 9–10 hr. after the inoculation, when it reached its first peak. During the following 8 hr. a clear decrease in the blood count was evident which was attributed to the ‘clearing mechanism’ of the blood. The onset of a new bacterial rise in the blood stream appeared 18 hr. after the inoculation and reached a second peak during the further 6–8 hr.

In contrast to the observed decrease in the bacterial blood count, a steady and gradual increase in the count of the internal organs was seen; it was steadily progressive till the exitus.

In the recovering animals a steady decrease in the bacterial blood count was recorded. Between 24 and 26 hr. the number of micro-organisms in the blood and spleen was found to be 400 times less in the recovering animals than in the moribund ones. From 48 hr. and onwards a slow and gradual decrease in the bacterial count of the surviving animals was observed. The blood became sterile after 25 days. In the spleen and liver of the surviving animals after 48 hr. a new increase in the bacterial count is evident, accompanied by hyperplasia of the spleen. The number of bacteria reached a new peak in the liver on the third day and in the spleen on the fourth day after the infection.

Subsequently a slow and gradual decrease in the bacterial count was observed in both organs, but even after 34 days a small number of persisting bacteria in the spleen and liver tissue may be found.

Pneumonia is a leading cause of mortality and morbidity worldwide with radiographically confirmed pneumonia a key disease burden indicator. This is usually determined by a radiology panel which is assumed to be the best available standard; however, this assumption may introduce bias into pneumonia incidence estimates. To improve estimates of radiographic pneumonia incidence, we applied Bayesian latent class modelling (BLCM) to a large database of hospitalized patients with acute lower respiratory tract illness in Sa Kaeo and Nakhon Phanom provinces, Thailand from 2005 to 2010 with chest radiographs read by both a radiology panel and a clinician. We compared these estimates to those from conventional analysis. For children aged <5 years, estimated radiographically confirmed pneumonia incidence by BLCM was 2394/100 000 person-years (95% credible interval 2185–2574) vs. 1736/100 000 person-years (95% confidence interval 1706–1766) from conventional analysis. For persons aged ⩾5 years, estimated radiographically confirmed pneumonia incidence was similar between BLCM and conventional analysis (235 vs. 215/100 000 person-years). BLCM suggests the incidence of radiographically confirmed pneumonia in young children is substantially larger than estimated from the conventional approach using radiology panels as the reference standard.

The kernel of modelling transmission dynamics of infectious diseases lies in constructing the force of infection (FOI). Traditionally, it was based on mass-action law. In this paper, we show, based on survey data of Escherichia coli O157 infection on Scottish cattle farms, that the actual form of FOI deviates greatly from mass-action law. Further, control effectiveness deviates qualitatively: the epidemic of mass-action FOI can be controlled with a control effort larger than the so-called herd immunity, while the epidemic inferred from the survey data of E. coli O157 infection was shown to be difficult to control. This indicates that, at least for E. coli O157 infection on cattle farms, it is risky to rely on models of transmission dynamics that were based on mass-action law to design the optimal intervention programme for infectious diseases. This suggests the importance of collecting epidemic data and model selection from data-driven models to infer the most likely model of transmission dynamics.

Mice immunized with a fraction from a culture filtrate of Ps. aeruginosa, then burned and infected with virulent serotypes of Ps. aeroginosa, were protected from septicaemia and death.

The immunogenic fraction killed mice at dosages 400 times those of the minimum protective dosages.

Treatment of the immunogenic fraction with 0·5% formalin reduced its lethal effect for mice and slightly improved its immunizing potency so that the difference between the smallest immunizing dose used and the smallest amount that killed mice was more than 80,000 doses.

Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.

The work began with efforts to isolate a type II Vi phage from local sewage. When this attempt failed, typing material was obtained from Dr J. Craigie and Dr A. Felix.

The typing method was applied to 495 strains of typhoid bacilli, the technique laid down by Craigie being followed throughout.

It was found that in South Africa the distribution of the various types of typhoid bacilli is different from that obtaining in other countries where this typing method has so far been applied.

During further investigations of type F strains the fact came to light that by means of a simple biochemical test type F strains can be subdivided into two sub-types, which subdivision will be useful in further epidemiological work. No such biochemical subdivision was found possible in any other type.

It did not prove possible to type all South African strains with the available phage preparations. Some of these strains must represent new types. Workers in other countries have had similar experiences and it will become necessary to compare all these unusual strains directly with one another in order to reach uniformity in nomenclature. It has already been possible to co-operate with workers in England, and they have been assisted by my finding that a strain, unique in England and supposed to have been brought there by a carrier, who had typhoid fever in South Africa 40 years ago, was endemic in South Africa.

During the course of the work, two outbreaks of typhoid fever occurred in which the typing method proved most useful, not only for linking up a particular carrier with a particular outbreak, but also for excluding an already known carrier who was under grave suspicion.

I have to thank Dr Craigie and Dr Felix for supplying material, and Prof. Pijper, of the Pretoria University, for placing laboratory facilities at my disposal. I thank all others for cultures received for typing.

A short time ago I (1911) described a method for the quantitative estimation of indole. It may be of interest to reproduce the curves obtained by the use of this method, in the study of several strains of Bacterium coli, as curves representing indole-production have seldom been published.

We are still in doubt regarding the exact position of those bacilli which, morphologically and culturally, appear to be identical with the Klebs-Loeffler bacillus but which differ from it only in the absence of specific pathogenic power for laboratory animals. Most writers regard such non-virulent strains as true diphtheria bacilli which have lost their virulence and toxigenic power either temporarily or permanently. Others however are inclined to place them in a group allied to that of the genuine Klebs-Loeffler bacillus and express doubts as to whether they at any time possessed a claim to pathological significance (Graham Smith, 1904).

Enzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components were 34.2% (with 3 components), 34.4% (2 components), and 78.1% (1 component). It appears the immunization strategy for diphtheria and tetanus is satisfactory for herd immunity in New Zealand children. However, the current pertussis strategy may not be providing adequate immunity to 5-year-olds in this country.

The membrane methods described in Report 71 on the bacteriological examination of water supplies (Report, 1969) for the enumeration of coliform organisms and Escherichia coli in waters, together with a glutamate membrane method, were compared with the glutamate multiple tube method recommended in Report 71 and an incubation procedure similar to that used for membranes with the first 4 hr. at 30°C., and with MacConkey broth in multiple tubes. Although there were some differences between individual laboratories, the combined results from all participating laboratories showed that standard and extended membrane methods gave significantly higher results than the glutamate tube method for coliform organisms in both chlorinated and unchlorinated waters, but significantly lower results for Esch. coli with chlorinated waters and equivocal results with unchlorinated waters. Extended membranes gave higher results than glutamate tubes in larger proportions of samples than did standard membranes. Although transport membranes did not do so well as standard membrane methods, the results were usually in agreement with glutamate tubes except for Esch. coli in chlorinated waters. The glutamate membranes were unsatisfactory. Preliminary incubation of glutamate at 30° C. made little difference to the results.

Guinea-pigs are suited to colony management, whether for breeding or maintenance, and single cages are only necessary when experimental or other requirements demand them.

Floor pens are extravagant of space and open to criticism on grounds of hygiene.

Wire floored pens, in batteries of four tiers, have many advantages, both in economy and hygiene, and are compatible with excellent health and breeding performance.

Certain details in the design of such batteries are important; among them being the size of mesh of the wire floor, the avoidance of corners and ledges where soil can accumulate, and the observance of convenient dimensions.

I first saw this method developed by an accredited guinea-pig breeder, Mr Ashton Poole, who has since given up breeding. Although the present battery is a far cry from Mr Poole's pens, the method is the same, and the unblemished health record of his very large stud over a period of some years was impressive. I am glad therefore to acknowledge my indebtedness to him.

Various writers (Burnet, 1928; Burnet and Conseil, 1929; Vercellara, 1929; Huddleson and Hallman, 1929; Meyer and Eddie, 1929,1930; and Weigmann, 1931) using strains of Brucella abortus, have shown that this species is very slightly pathogenic for certain species of monkeys, while Br. melitensis possesses a high degree of virulence for the same animal. I have conducted a few experiments with a view to confirming these results, using a bovine abortus and a human melitensis strain isolated in Tanganyika.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018–2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20–0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018–2020 was 28% (P = 0.0001 for comparison with 2006–2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018–2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.