Two interesting new phenomena have been observed in suspensions of T4Bo bacteriophage which were frozen to temperatures below the eutectic temperature of the salt (sodium chloride) in the suspending medium. Approximately 10% of the phage appeared to survive such a phase change as determined by plaque titre. However, exposure of these survivors to ultrasonic vibration or repeated freezing showed them to be hypersensitive and thus latently injured. The hypersensitivity was lost on incubating the phage at 37° C. for 3 hr. Furthermore, following a eutectic phase change, the surviving phage could be inactivated by rapid cooling to — 90° C. followed by slow rewarming. Such inactivation cannot be accounted for by accepted theories of freezing injury.

National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other preventable vaccine diseases. The aim of this article is to estimate the vaccine coverage in adults aged 65 years and older and to analyse the factors that could increase or decrease vaccination uptake probability for the three listed vaccines in the national vaccination programme (influenza, tetanus and diphtheria, and pneumococcus) and the full scheme in Mexico. We conducted an analytical cross-sectional study with 2012, 2018, and 2021 rounds from the National Health and Nutrition Survey, in which we calculated the vaccine coverage estimations and performed multivariable logistic regression models to analyse the factors related to vaccine uptake. Tetanus and diphtheria vaccines had the greatest coverage estimation in all years (59–71%), whereas the pneumococcus vaccine had the lowest (32–53%). Full scheme vaccine coverage decreased from 37.80% to 24.77% in 2012 and 2021, respectively. The National Health Card property, morbidity, being a beneficiary of any health system institution, and use of preventive services increased the probability of vaccine uptake. In conclusion, vaccine coverage in older Mexican adults decreased over time, and the Mexican health system plays a strategic role in immunisation.

1. Horgan's (1936) findings with regard to heat sterilization of B. typhosus vaccine are not confirmed.

2. Silver in the form of katadyne or electro-katadyne appears to be an effective sterilizing agent for B. typhosus suspensions.

3. Katadyne and electro-katadyne have no destructive action on Vi, O or H agglutinogens of B. typhosus.

4. Electro-katadyne, even when used in excessive doses, has no detrimental effect on the immunizing activities of Vi antigen.

5. Electro-katadyne sterilized suspensions of V strains of B. typhosus are more effective immunogenic agents than those sterilized by heat and phenol.

6. The bactericidal properties of electro-katadyne, though impaired in 0·85 per cent saline, are adequate as a means for preserving vaccine.

7. It is suggested that katadyne sterilized suspensions of V strains might be of value in testing for the presence of Vi agglutinins in human sera since they are hypersensitive to Vi antibody while retaining most of their resistance to O antibody.

8. In view of the suggestion by Felix that additional antigens with activities similar to those of Vi antigen may exist in bacteria other than B. typhosus, it may be found that the electro-katadyne process has an application in the preparation of vaccines generally, particularly those which have hitherto proved ineffectual in prophylaxis.

An epidemiological study and the simultaneous evaluation of anti-Hav antibody using radio immunoassay (RIA) and immunoadherence hemagglutination assay (IAHA) was performed during three hepatitis A epidemics in the Tours area (France). Fifty-seven sera from 35 subjects with viral hepatitis type A and 16 sera from nine children who did not develop any clinical signs of hepatitis were studied. The more explosive epidemic occurred in an institution for mentally retarded children (attack rate 68%). The two major outbreaks observed were due to the introduction in the institutions of individuals infected with hepatitis A virus. Two out of three of the index cases had a seafood dinner three to four weeks before onset of jaundice. Sera taken one week after jaundice were always found to be anti-HAV positive by both RIA and IAHA, and sera taken more than three days before the appearance of jaundice were negative by both methods. Sera taken at the peak of the transaminase elevation were anti-HAV positive by RIA but only one out of two were positive by Iaha. The anti-HAV titre by RIA increased from the time of the appearance of jaundice and the highest titres, over 1/20000 were seen only after several months. Observations of subjects in close contact with patients who seroconverted without any manifestation of hepatitis, confirmed the existence of clinically mute infections.

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.

Early investigation of travel-related cases in an outbreak of an emerging infectious disease can provide useful information to epidemiologists to characterize the exposure, while they may differ in demographic profiles from cases reported in the country where the outbreak has occurred. During the spring 2011 E. coli outbreak in Germany, we proposed a methodological approach to collect a minimal set of demographic and clinical data that are relatively easy to obtain and available at an early stage of an outbreak investigation. Ninety-eight STEC O104 travel-related cases were reported in a survey by seven EU countries, Switzerland, Canada and the USA. We found a mean incubation period (n = 50) of 8·5 days, which confirmed previous estimations communicated by the Robert Koch Institute. No significant association was found between the duration of the incubation period and possible demographic and clinical factors, although the older the age, the shorter the incubation period that was observed. Such approach and observations are informative for further investigations of outbreaks of enterohaemorrhagic E. coli or other emerging infectious diseases.

Data concerning numerous severe epidemics of poliomyelitis were surveyed for information useful in estimating the size of the immune component of the population by age groups of 1 year. The New York epidemic of 1916 and the Mauritius epidemic of 1945 were chosen as the most suitable for this purpose. It is shown that there was a regularly progressive decline in attack rates for successively older age groups from 2 to 8 years in New York. The attack rate in 8-year-olds was less than 10 % as large as that in 2-year-olds. It is noted that a difference of this magnitude could be accounted for by immunizing infections amounting to 30 % per year for 6 years.

A similar analysis of age specific attack rates during the Mauritius epidemic shows progressive declines of 28, 60, 50 and 53 % for the successive age groups 5–9. An average annual infection rate of 45 % over a 4 year period could account for the ten-fold difference in infection rates between 5-year-olds and 9-year-olds.

An immunizing infection rate of 30 % a year would lead to a pattern of immunity in which the seven youngest age groups had a total susceptible component of 30 % at the beginning of a ‘ poliomyelitis season’. Twenty per cent would remain susceptible at the end of the season when spread of virus terminated.

An annual immunizing infection rate of 45 % would bring about a situation in which 21 % of the five youngest age groups were susceptible at the start of a period of viral prevalence and 12 % at the end. Alternatively, one could consider that on Mauritius there may have been a continuous prevalence of virus in a population in which approximately 15 % of the five youngest age groups were susceptible at any time.

It is suggested that the essentially similar attack rates among children 3–5 years old on Mauritius may have reflected a 3-year period during which homotypic virus was not prevalent, in contrast to its great prevalence during the years prior to that time.

A more detailed discussion and analysis of additional data concerning age-specific attack rates in poliomyelitis will be found in the thesis submitted by Dr Sample to the University of Washington School of Medicine entitled, ‘Some observations on statistical and theoretical epidemiology of infectious diseases, principally poliomyelitis’, in 1955. This is obtainable by Inter-library Loan from the Health Sciences Library, University of Washington, Seattle.

We wish to express our sincere thanks to Dr Blair M. Bennett and Dr William E. Reynolds of the University of Washington for their advice on the statistical and epidemiologic aspects of this study.

Monitoring of malaria intensity in terrain regions of Arunachal Pradesh, India is very difficult as the dynamics of mosquito populations varies to a large extent due to altitude and frequent changes in climatic conditions. There is a scarcity of information on the influence of climatic factors on malaria morbidity in Arunachal Pradesh. Hence, a pilot study was conducted from 2006 to 2010 to understand malaria transmission dynamics, seasonal distribution and disease morbidity. Plasmodium vivax and P. falciparum are the two major parasites for malaria transmission in Arunachal Pradesh. Out of 142 558 malaria cases analysed from 2006 to 2010, P. vivax infection contributed 72·1% followed by P. falciparum (27·9%). However, the overall morbidity of malaria declined from 37/1000 in 2006 to 18/1000 population in 2010. From this study it was observed that the temporal distribution of malaria cases varied between districts and high morbidity rates were reported mostly during the wet season. To understand malaria transmission dynamics in the study area, the Richards model was used to predict malaria cases. The output of the results from this model predicted a higher number of malaria cases (K) during 2006 and a gradual decline in subsequent years. Similarly, the growth rate r, and exponential deviation α, were almost identical for all the years, which shows that the Richards model is the most suitable model for the prediction of malaria cases.

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 evidence for the incubation period of Legionnaires’ disease is based on data from a small number of outbreaks. An incubation period of 2–10 days is commonly used for the definition and investigation of cases. In the German LeTriWa study, we collaborated with public health departments to identify evidence-based sources of exposure among cases of Legionnaires’ disease within 1–14 days before symptom onset. For each individual, we assigned weights to the numbered days of exposure before symptom onset, giving the highest weight to exposure days of cases with only one possible day of exposure. We then calculated an incubation period distribution where the median was 5 days and the mode was 6 days. The cumulative distribution reached 89% by the 10th day before symptom onset. One case-patient with immunosuppression had a single day of exposure to the likely infection source only 1 day before symptom onset. Overall, our results support the 2- to 10-day incubation period used in case definition, investigation, and surveillance of cases with Legionnaires’ disease.

Pneumonia is a leading cause of death in New York City (NYC). We identified spatial clusters of pneumonia-associated hospitalisation for persons residing in NYC, aged ⩾18 years during 2010–2014. We detected pneumonia-associated hospitalisations using an all-payer inpatient dataset. Using geostatistical semivariogram modelling, local Moran's I cluster analyses and χ2 tests, we characterised differences between ‘hot spots’ and ‘cold spots’ for pneumonia-associated hospitalisations. During 2010–2014, there were 141 730 pneumonia-associated hospitalisations across 188 NYC neighbourhoods, of which 43.5% (N = 61 712) were sub-classified as severe. Hot spots of pneumonia-associated hospitalisation spanned 26 neighbourhoods in the Bronx, Manhattan and Staten Island, whereas cold spots were found in lower Manhattan and northeastern Queens. We identified hot spots of severe pneumonia-associated hospitalisation in the northern Bronx and the northern tip of Staten Island. For severe pneumonia-associated hospitalisations, hot-spot patients were of lower mean age and a greater proportion identified as non-Hispanic Black compared with cold spot patients; additionally, hot-spot patients had a longer hospital stay and a greater proportion experienced in-hospital death compared with cold-spot patients. Pneumonia prevention efforts within NYC should consider examining the reasons for higher rates in hot-spot neighbourhoods, and focus interventions towards the Bronx, northern Manhattan and Staten Island.

1. Antisera prepared by immunizing rabbits with C. diphtheriae gravis, mitis, and intermedius and C. hofmannii contain antibodies which will give complement-fixation reactions with alcoholic extracts of the organisms.

2. By means of cross-absorption experiments three different lipoid antigens can be demonstrated: (a) a specific antigen h present only in C. hofmannii; (b) a specific antigen d characteristic of C. diphtheriae mitis but probably present also in small amount in C. diphtheriae gravis and intermedius; and (c) a non-specific or group antigen G present in large amount in C. diphtheriae gravis and intermedius and C. hofmannii, and in small amount in C. diphtheriae mitis; this G antigen is probably made up of a number of components.

3. Sera of human diphtheria convalescents may contain antibodies reacting with alcoholic extracts of C. diphtheriae. Sera from mitis cases usually react only with extracts of G. diphtheriae mitis, i.e. they contain only d antibody, while sera from gravis or intermedius cases usually contain only G antibody and react with extracts of C. diphtheriae gravis, intermedius and C. hofmannii, but not with extracts of G. diphtheriae mitis.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

In this Journal (vol. VII. p. 501) Mr J. A. Craw has recently published a very sharp criticism of my calculations based on experiments by Madsen and Walbum regarding the so-called Danysz Effect.

A Cope-Chat card has been designed and used for the recording and analysis of breeding performance in guinea-pigs.

Modifications required to adapt the card for use with other species are described.

Some general principles of colony management are discussed.

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.

In a recent paper in this Journal by Marshall et al. (1985), which described the bacterial endonuclease DNA analysis (BRENDA) of several Escherichia coli 0126 strains, the following statement was found in the summary: ‘The isolates from the outbreak produced indistinguishable DNA electrophoretic patterns in spite of their assignment to seven different H serotypes… These results support the epidemiological evidence that a single-strain outbreak had occurred, and they cast doubt on the value of H typing for this particular investigation.’ The same 0126 strains that were enterotoxigenic (ST) were treated in two earlier papers (Bettelheim & Reeve, 1982; Bettelheim, 1984) and also on these two earlier occasions the authors raised doubt about the stability of E. coliH typing results.

Readmission of asymptomatic methicillin-resistant Staphylococcus aureus (MRSA) carriers may contribute to the hospital reservoir. Using an electronic alert system, we assessed the weight of readmission of known MRSA carriers on MRSA colonization pressure in a hospital setting. During the 2004–2010 period, 2058 alerts were generated for 1060 inpatients. A total of 486/1060 patients (46%) were readmitted at least once, and 330/486 (64·4%) were readmitted <3 months after discharge. A mean of 20 MRSA patients were present on the same day (from 40 in 2004 to eight in 2010). The number of MRSA patient-days was 34 575, i.e. 2·5% of the 1 366 277 patient-days of the study period, and 17 737 (51·3%) MRSA patient-days were due to readmission of known MRSA carriers. The number of new MRSA cases was partly correlated with the number of MRSA patients hospitalized (R2 = 0·49). Rapid electronic identification of these patients proved essential in decreasing the global burden of MRSA in our hospital.

This study aimed to describe the incidence of Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteremia, distribution of the SBSEC subspecies, and their respective association with colorectal cancer (CRC). A population-based retrospective cohort study of all episodes of SBSEC-bacteremia from 2003 to 2018 in Skåne Region, Sweden. Subspecies was determined by whole-genome sequencing. Medical charts were reviewed. The association between subspecies and CRC were analysed using logistic regression. In total 266 episodes of SBSEC-bacteremia were identified and the average annual incidence was 2.0 per 100 000 inhabitants. Of the 236 isolates available for typing, the most common subspecies was S. gallolyticus subsp. pasteurianus 88/236 (37%) followed by S. gallolyticus subsp. gallolyticus 58/236 (25%). In order to determine the risk of cancer following bacteremia, an incidence cohort of 174 episodes without a prior diagnosis of CRC or metastasised cancer was followed for 560 person-years. CRC was found in 13/174 (7%), of which 9 (69%) had S. gallolyticus subsp. gallolyticus-bacteremia. In contrast to other European studies, S. gallolyticus subsp. pasteurianus was the most common cause of SBSEC-bacteremia. CRC diagnosis after bacteremia was strongly associated with S. gallolyticus subsp. gallolyticus-bacteremia. Identification of SBSEC subspecies can guide clinical decision-making regarding CRC work-up following bacteremia.

In a previous paper (Williams and Hoy, 1927) it was shown that living and virulent tubercle bacilli could be demonstrated in the faeces of six apparently healthy cows from among a total of 391 which were examined. All these cows were living the normal life of the herds in which they were discovered, and three of them were brought to the Institute in order that a study might be made of the frequency with which tubercle bacilli could be found in their faeces.