We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

Fourteen cases of enzootic pneumonia, nearly all of which had presented diagnostic difficulties using the metabolic-inhibition test, were re-examined using specific pig antisera in the passive haemagglutination test (PHA). All proved positive for Mycoplasma suipneumoniae, indicating that the test, used in this manner, might be particularly valuable for routine diagnosis.

The PHA test was also used to demonstrate antibody to M. suipneumoniae in pneumonic tissue and the associated bronchial lymph nodes.

To allay our concern that cross-reactions might interfere with this and other serological tests—the complement-fixation test (CF) and precipitation in agar-gel—the specificity of our reagents and the antigenic relationships of Mycoplasma hyorhinis, Mycoplasma granularum, mycoplasmaB3, Mycoplasma hyopneumoniae and three strains of M. suipneumoniae (including cloned and uncloned isolates of the J strain) were studied in various ways. Antibodies to medium constituents occurred in rabbit antiserum but did not present a problem with pig antisera. These antibodies were successfully absorbed from the rabbit antisera but it was not possible to remove medium constituents from the antigens used to produce antisera in rabbits by repeated washing.

By all these tests, the main species of mycoplasmas studied seemed to be anti-genically distinct. No major antigenic differences between the three strains of M. suipneumoniae were revealed by the PHA test and the CF test; a slight difference in the precipitation lines of one of these strains (MG) in agar-gel might have indicated an antigenic variation or been a measure of some other factor.

From an outbreak of very mild “typhus-like disease” in Pretoria, which strongly resembled the cases of “sporadic” or “mild” typhus occasionally occurring in that town, a virus was isolated which was studied in guinea-pigs and rabbits, and was found to belong to the typhus-group.

This virus in cross-immunity experiments with virus of South African louse-typhus and South African tick-bite fever and also in other respects behaved exactly like the typhus-like virus the authors on a previous occasion isolated from rats in a South African town where cases of “mild” or “ sporadic ” typhus have been known to occur regularly for many years.

This constitutes evidence that South African “mild” or “sporadic” typhus comes from rats and is communicated to man by rat-fleas.

In southern Africa, therefore, one has to reckon with three typhus-like diseases: tick-bite fever, flea-typhus from rats, and louse-typhus. Tick-bite fever has a primary sore, the tick-bite, as a pathognomic symptom, the other two can only be differentiated satisfactorily from one another by cross-immunity tests.

Agglutination reactions and cross-immunity tests show that South African louse-typhus and South African rat- or flea-typhus are not identical with similar diseases in other parts of the world.

Tick-bite fever is a mild typhus-like disease extending from the Cape to South Rhodesia.

The typhus-like disease of Kenya is not tick-bite fever, and seems to be identical with fièvre boutonneuse.

We used data from BioSense, a national electronic surveillance system, to describe pneumonia in hospitalized patients with influenza-like illness (ILI). Ninety-five hospitals from 20 states reported ICD-9-CM-coded inpatient final diagnosis data during the study period of September 2007 to February 2010. We compared the characteristics of persons with and without pneumonia among those with ILI-related hospitalizations. BioSense captured 26 987 ILI-related inpatient hospitalizations; 8979 (33%) had a diagnosis of pneumonia. Analysis of trends showed highest counts of pneumonia during the 2007–2008 season and the second 2009 pandemic wave. Pneumonia was more common with increasing age. Microbiology and pharmacy data were available for a subset of patients; 107 (5%) with pneumonia had a bloodstream infection and 17% of patients were prescribed antiviral treatment. Our findings demonstrate the potential utility of electronic healthcare data to track trends in ILI and pneumonia, identify risk factors for disease, identify bacteraemia in patients with pneumonia, and monitor antiviral use.

This paper describes the study of a mutant of Vibrio cholerae which is shown to be attenuated by its avirulence to mouse, rabbit and chick embryo. This mutant character is stable, and the avirulence of this strain probably results from its inability to multiply actively in the tissues of the infected animals. The need for the study of such attenuated strains as live vaccines in man is discussed, and certain aspects of immunity to cholera are reviewed.

To examine the pathogenesis of USA300 MRSA infection in long-term care residents, we performed a retrospective cohort study of 1691 adult residents of two extended-care facilities from 2003 to 2007 to assess whether the risk of subsequent MRSA infection is higher in USA300 MRSA-colonized residents compared to non-colonized residents or non-USA300 MRSA colonized residents. Six per cent of residents were colonized with USA300 MRSA; 12% of residents were colonized with non-USA300 MRSA; and 101 residents developed MRSA infection. The risk of infection was twofold higher in residents colonized with USA300 MRSA compared to residents not colonized with MRSA [adjusted hazard ratio 2·3, 95% confidence interval (CI) 1·1–4·5]. The risk of infection in USA300 MRSA-colonized residents was similar to USA300 MRSA non-colonized residents (relative risk 1·1, 95% CI 0·5–2·3). Our findings show that colonization with USA300 MRSA increases the risk of MRSA infection suggesting a similar pathogenesis.

In 2013, an unusual increase of paratyphoid fever cases in travellers returning from Cambodia was reported in Japan. From December 2012 to September 2013, 18 cases of Salmonella Paratyphi A infection were identified. Microbiological analyses revealed that most isolates had the same clonal identity, although the epidemiological link between these cases remains unclear. It was inferred that the outbreak was caused by a common and persistent source in Cambodia that was likely to have continued during 2014. The information of surveillance and laboratory data from cases arising in travellers from countries with limited surveillance systems should be timely shared with the country of origin.

1. The virtual sterilization time (v.s.t.) has been used as a measure of the rate of disinfection of Bact. coli cultures by phenol under carefully standardized conditions, and the relationship between this rate and temperature at five phenol concentrations has been examined.

2. The graphs of log (v.s.t.) against temperature reveal that the formula t×θT = A, as usually employed for the calculation of the temperature coefficient of the rate of disinfection, has only a limited applicability for these data. θ and Q10 increased with temperature especially at high concentrations, and at the lowest concentration there was a tendency for them to increase again as the temperature was reduced below a certain point.

3. The other general type of formula, t(T –α)b = a, used for the calculation of biological temperature coefficients, is also of very limited value when applied to these data since b increases with temperature at all concentrations.

4. The magnitude of these temperature coefficients and their manner of variation are considered in relation to previously published data by other authors and the way in which θ should theoretically vary with temperature is discussed.

Estimating the coronavirus disease-2019 (COVID-19) infection fatality rate (IFR) has proven to be particularly challenging –and rather controversial– due to the fact that both the data on deaths and the data on the number of individuals infected are subject to many different biases. We consider a Bayesian evidence synthesis approach which, while simple enough for researchers to understand and use, accounts for many important sources of uncertainty inherent in both the seroprevalence and mortality data. With the understanding that the results of one's evidence synthesis analysis may be largely driven by which studies are included and which are excluded, we conduct two separate parallel analyses based on two lists of eligible studies obtained from two different research teams. The results from both analyses are rather similar. With the first analysis, we estimate the COVID-19 IFR to be 0.31% [95% credible interval (CrI) of (0.16%, 0.53%)] for a typical community-dwelling population where 9% of the population is aged over 65 years and where the gross-domestic-product at purchasing-power-parity (GDP at PPP) per capita is $17.8k (the approximate worldwide average). With the second analysis, we obtain 0.32% [95% CrI of (0.19%, 0.47%)]. Our results suggest that, as one might expect, lower IFRs are associated with younger populations (and may also be associated with wealthier populations). For a typical community-dwelling population with the age and wealth of the United States we obtain IFR estimates of 0.43% and 0.41%; and with the age and wealth of the European Union, we obtain IFR estimates of 0.67% and 0.51%.

The history of the Brown Animal Sanatory Institution was intended originally to be published in book form, and was therefore divided into chapters. For the sake of convenience this division has been continued, even though it is unusual for the term to be employed in scientific periodicals. The history will be published serially in four consecutive issues of the Journal of Hygiene. References have presented a difficulty. In two instances the title of the paper referred to has had to be omitted, because no copy of the original journal in which the article appeared has been obtainable. More important, however, is the failure to give references, beyond the date, to a number of statements in the text, because the information in question has been abstracted from sources that are not available to the general reader.

Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.

In the UK surveillance of AIDS and HIV infection is based on routine reporting systems. Whilst attempts are made to ensure that AIDS data are as complete as possible, numbers of reports fluctuate from month to month for reasons which are described. In 1986 there was an increase in death certificates naming AIDS as a cause of death in patients who were not identifiable in the surveillance data. More active surveillance is now undertaken in order to minimize this and other possible discrepancies.

It is probable that most cases of AIDS are reported and therefore these data can be used to describe trends in the epidemic by ‘risk group’. Laboratory reports of HIV antibody-positive tests could give an earlier indication of trends because of the long incubation period of AIDS. But these laboratory data are difficult to interpret because they represent an incomplete and biased sample of all positive persons.

AIDS cases are still being reported at a rate which is increasing approximately exponentially. Short-term predictions are presented showing a growth in the epidemic which is consistent with previously published predictions. Most cases are in the homosexual risk group. New asymptomatic homosexual patients with HIV antibody are still being identified.

The epidemic of AIDS in haemophilia patients should be of finite size although new cases of AIDS are likely to continue to be diagnosed for several years. AIDS due to blood transfusion given in the UK before donor screening appears to be a much smaller epidemic. The epidemic in drug abusers is increasing. Heterosexually acquired AIDS and HIV infections are being reported in small but increasing numbers.

Children in a residential home whose tonsils had been removed had lower attack rates for streptococcal sore throat than tonsillectomized children. Tonsillectomy did not have a consistent effect on respiratory tract illness.

Tonsillectomy has a similar effect on the outcome of individual exposures to streptococcal infection; the difference was more marked for illness than for simple colonization.

The apparent benefit from tonsillectomy could not be attributed to the ageing of the child, and was considered real. Its magnitude did not seem, however, great enough to justify a policy of extensive tonsillectomy, particularly in view of the possible risks to the child.

A child who had been ill with infection due to one streptococcal type rarely became ill when re-exposed to the same type. In addition there was some evidence in children with tonsils of an immunity, perhaps short lived, which was clearly not type-specific.

1. When coagulase-positive staphylococci are grown on nutrient agar containing fresh mammalian serum and haemoglobin, discrete areas of clearing appear in the medium near to the growth.

2. These ‘plaques’ are due to proteolysis, the haemoglobin acting as a chromoprotein indicator substrate. For convenience the effect is referred to as ‘proteoclast’.

3. The effect is due to the interaction of a diffusible product of the staphylococci with constituents of normal sera. The staphylococcal factor has been obtained in a bacterium-free filtrate and its interaction with serum studied quantitatively. It resists boiling.

4. The number of plaques produced under defined conditions showed a linear correlation with the amount of serum used, but not with the amount of filtrate.

5. By means of serial filtration through Gradocol membranes it was shown that one factor in normal serum required for the proteoclast effect is particulate, having a size of the order 20–70 m μ diameter.

6. It was found that a third factor present in fresh sera was also required.

7. Serum was rendered inactive by conditions of heating and ultra-violet irradiation similar to those required to sterilize vegetative bacteria and viruses.

8. It is suggested that the proteoclast effect is due either to a non-pathogenic virus, or to a hitherto unrecognized particulate enzyme precursor present in sera and activated by the staphylococcal factor.

1. Repeated inoculation of thirty-six guinea-pig does with random blood of guinea-pig bucks failed to produce any demonstrable anti-red cell isoantibodies.

2. A note is included on the blood picture of a small series of newborn guinea-pigs aged between 12 and 24 hr.

The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.

The relationship between chickenpox and yaws epidemics occurring among children in a village in Netherlands New Guinea is analysed using the mathematical model for a simple deterministic epidemic. It is shown that the yaws epidemic accelerated significantly in the month following the chickenpox epidemic, but that it reverted to its previous rate in the succeeding months. The number of yaws cases attributable to the influence of the chickenpox is estimated from the projected course of the yaws epidemic. It is statistically verified that those children contracting chickenpox were more likely to become yaws cases in the subsequent month.

These results point to the danger of yaws's spread being much more rapid among a population which has recently been subject to an epidemic of chickenpox.

The Limulus test detected endotoxins in the plasma of burned and unburned mice infected with different species of gram-negative bacteria. Individual strains of different species of gram-negative bacteria produced different amounts of endotoxin in the plasma of infected mice. Plasma from mice given lethal infections showed very high concentrations of endotoxin. Low concentrations of endotoxin in the plasma were tolerated by mice but high concentrations were invariably fatal. A polyvalent pseudomonas vaccine reduced endotoxin in the plasma of mice given lethal infections of Pseudomonas aeruginosa.

A total of 193 sera were examined for antibody to Mycoplasma pneumoniae by three techniques – complement fixation (CF), haemagglutination (HA) and immunofluorescence (IF), the last method being used to assess IgM, IgG and IgA antibodies. The most reliable single test for diagnosis was HA, and the most useful combination of tests was HA with IF (IgM and IgG). The IgA IF was not found to be diagnostically helpful.

Dishoeck (1935) confirmed the claim for the discovery of nose “opening” rays made by L. Hill (1932), a discovery denied by Dufton and Bedford (1933) and Winslow, Greenburg and Herrington (1934). By means of a blower fan and a well-fitting tube Dishoeck sends a stream of air through one nasal orifice and out through the mouth while the subject holds his breath. The input pressure of the air, meanwhile, is measured by a water manometer which is connected with the air tube just before this enters the nasal orifice. A few seconds suffices to secure such a reading. He calibrates the instrument by measurements made with glass tubes, each about the length of the nasal passage, viz. 6 cm., and fitted with varying diaphragmatic holes.