Finally I wish to draw particular attention to the following facts:—

1. The striking diminution in the case-mortality at the Mile End Hospital which followed the systematic use of antitoxin.

2. The subsidence of the epidemic during the season when diphtheria is commonly most prevalent.

3. The opening of the schools in September without any increase in the prevalence of the disease.

4. The persistence of diphtheria bacilli for long periods in certain of the convalescents and contacts.

5. The success of preventive measures based upon the belief that diphtheria is spread mainly by personal contact, and through the inter-mediation of healthy persons and other who by the means usually employed are not recognised to be suffering from the disease.

Dengue fever (DF) has been a growing public-health concern in China since its emergence in Guangdong Province in 1978. Of all the regions that have experienced dengue outbreaks in mainland China, the city of Guangzhou is the most affected. This study aims to investigate the potential risk factors for dengue virus (DENV) transmission in Guangzhou, China, from 2006 to 2014. The impact of risk factors on DENV transmission was qualified by the q-values calculated using a novel spatial-temporal method, the GeoDetector model. Both climatic and socioeconomic factors were considered. The impacts on DF incidence of each single factor and the interaction of two factors were analysed. The results show that the number of days with rainfall of the month before last has the highest determinant power, with a q-value of 0.898 (P < 0.01); the q-values of the other factors related to temperature and precipitation were around 0.38–0.50. Integrating a Pearson correlation analysis, nonlinear associations were found between the DF incidence in Guangzhou and the climatic factors considered. The coupled impact of the different variables considered was enhanced compared with their individual effects. In addition, an increased number of tourists in the city were associated with a high incidence of DF. This study demonstrates that the number of rain days in a month has great influence on the DF incidence of the month after next; the temperature and precipitation have nonlinear impacts on the DF incidence in Guangzhou; both the domestic and overseas tourists coming to the city increase the risk of DENV transmission. These findings are useful in the risk assessment of DENV transmission, to predict DF outbreaks and to implement preventive DF reduction strategies.

In our investigation of our subject we have perused the literature, analysed the data of other workers, conducted a number of animal experiments, considered the bearings clinical and pathological of a case of presumed toluene poisoning, and conducted an investigation into the blood state and symptoms of co-workers with this case and yet are unable to give a categorical answer to the question. What are the relative toxicities of toluene and benzene? We would almost feel inclined to echo the words of another worker in the experimental field with regard to benzene, Neumann (1915), who concludes: “The fact that my results so often do not correspond either with one another or with those of Selling, so often indeed do not correspond to expectation, justifies the conclusion that, although benzene is to be regarded as a powerful leucotoxin, it manifests great individual differences in its mode of action and it is very difficult to lay down exactly what action is to be expected.”

We should be inclined to put the case somewhat differently however and put forward the following view as our tentative finding.

The actions of benzene and toluene are very similar. That of benzene is the more powerful because it is a more volatile substance and can therefore reach higher concentration than toluene. This greater volatility at the same time is a reason why it is eliminated more quickly and its effects are less lasting than those produced by toluene. The action of both these substances is on young body cells, probably whatever they are and wherever they may be found, but is most easily discoverable because of its action on the young bone marrow cell and the consequent effect on the cells of the peripheral blood. It is not a specific action but operates, according to circumstances, on the stem cells of the myeloid leucocyte or the erythrocyte. This does not mean that the substances have little or no effect on the lymphocyte, for the lymphoid tissue in the body is so very abundant that it would only be in extreme cases that the effect on that cell would be manifest peripherally. Like many poisons, indeed like many of the drugs which are used in Medicine, the first effects of these substances are stimulating. Leucocytosis, erythrocytosis and possibly thrombocytosis are early manifestations or the manifestation of slighter action, with histological evidence of hyperplasia. This is succeeded by the truly toxic or destructive action and the production of leucopenia, anaemia, thrombopenia and the effects due to action on other organs. The ultimate result in clinical terms is an agranulocytic anaemia accompanied by purpura haemorrhagica and, as the pathological manifestation an aplastic bone marrow. The fatal termination is commonly an infection to which there is no resistance possible in an individual deprived of defence cells and possibly also of defensive substances in the body fluids. Powerful solvents of fat as both these chemical substances are, they produce an action through this means also, on nerve cells, capillary endothelium and parenchyma of organs with consequences represented in nervous symptoms and in haemorrhages. This then is our reading of the results of our investigation and explanation of the variability which may be found, a variability which is regarded mainly as one of phase, although we do not exclude idiosyncrasy altogether as explanation.

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the ‘Fiebig staging system’ has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying ‘sensitivity’. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define ‘stages’ of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.

The theory of assigning an upper limit to the estimate of the degree of contamination of a medium is briefly explained. Tables to save computational labour are presented and their use elucidated by examples.

A bacteriological study was carried out on the first Leisure Centre swimming pools in the United Kingdom to be disinfected with ozone/chlorine. Results suggested that a free chlorine concentration of approximately 0·8 mg/l was necessary to maintain the pools in a bacteriologically satisfactory condition. This amount of free chlorine was similar to that required when the pool was disinfected with chlorine alone. However, the associated amount of combined chlorine was much lower when disinfection was by ozone/chlorine and this gave more acceptable bathing conditions. Implications for the management of pools disinfected by this method are discussed.

A retrospective space–time permutation model with non-Euclidean distance criteria was applied within a high-complexity hospital setting to quantitatively explore cluster patterns of 273 patients infected with or colonized by carbapenemase-producing Klebsiella pneumoniae during 4 years. Results were compared to standard nosocomial active-surveillance methods. Two clusters were identified in the period, suggesting that space–time strategies for cluster quantification within confined environments may be useful.

Twenty progesterone-treated TO mice were infected intravaginally with Mycoplasma pulmonis. One month later, ten of the mice were given oestradiol which changed the reproductive cycle to the oestrous phase and within a week resulted in eradication of the organisms from six of them; vaginal persistence in the other mice may have been due, at least in part, to reinoculation of organisms from the oropharynx, a site heavily infected in all the mice. The majority of the mice not treated with oestradiol continued to shed the organisms from the vagina for at least 91 days. In another experiment, 19 oestradiol-treated BALB/c mice were infected intravaginally with M. hominis. One month later, nine of the mice were given progesterone which changed the reproductive cycle to the dioestrous phase and eradicated the organisms from seven within 2 weeks and from all of them within about a month. This was in contrast to the mice not given progesterone, the majority of which continued to shed the organisms for at least 167 days.

Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km × 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination ($\hat{\psi }_{{\rm north}}$ = 0.00, s.e. = 0.15), managed areas had low RABV occupancy ($\hat{\psi }_{{\rm managed}}$ = 0.20, s.e. = 0.29) and enzootic areas had the highest level of RABV occupancy ($\hat{\psi }_{{\rm south}}$ = 0.83, s.e. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained.

The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.

The post-war need for large numbers of dwellings has promoted renewed inquiry into the basic criteria by which good practice in the design and construction of buildings may be judged. More emphasis than ever before is now being put upon the functional characteristics of buildings regarded as living-spaces rather than as structures.

A detailed analysis of equine (H3N8) influenza viruses isolated in Nigeria during early 1991 has been undertaken. Antigenic analysis and the complete nucleotide sequence of the HA gene of three Nigerian equine influenza viruses A/eq/Ibadan/4/91, A/eq/Ibadan/6/91 and A/eq/Ibadan/9/91 are presented and limited sequence analysis of each of the genes encoding the internal polypeptides of the virus has been carried out. These results establish that, despite the geographical location from which these viruses were isolated, two were similar to the viruses which were concurrently causing disease in Europe in 1989 and 1991 and were related to viruses that have been predominating in horses since 1985. The third was more closely related to viruses isolated from 1991 onward in Europe but also in other parts of the globe. A comparison of the nucleotide sequence of two of the viruses isolated in Nigeria (A/eq/Ibadan/4/91 and A/eq/Ibadan/6/91) with a European strain (A/eq/Suffolk/89) showed limited variation in the haemagglutinin gene which caused amino acid substitutions in one of the antigenic sites: this mutation resulted in the potential production of a new glycosylation site in antigenic site A. The other Nigerian virus (A/eq/Ibadan/9/91) showed only a single one amino acid change from another European strain (A/eq/Arundel/12369/91). The two distinct Nigerian viruses had several amino acid substitutions in the antigenic sites of the haemagglutinin glycoprotein.

This study aimed to identify an appropriate simple mathematical model to fit the number of coronavirus disease 2019 (COVID-19) cases at the national level for the early portion of the pandemic, before significant public health interventions could be enacted. The total number of cases for the COVID-19 epidemic over time in 28 countries was analysed and fit to several simple rate models. The resulting model parameters were used to extrapolate projections for more recent data. While the Gompertz growth model (mean R2 = 0.998) best fit the current data, uncertainties in the eventual case limit introduced significant model errors. However, the quadratic rate model (mean R2 = 0.992) fit the current data best for 25 (89%) countries as determined by R2 values of the remaining models. Projection to the future using the simple quadratic model accurately forecast the number of future total number of cases 50% of the time up to 10 days in advance. Extrapolation to the future with the simple exponential model significantly overpredicted the total number of future cases. These results demonstrate that accurate future predictions of the case load in a given country can be made using this very simple model.

Susceptible mice have been placed in contact with infective individuals of the same species, separated from them after a definite period, and placed in contact with a further group of normal mice. This process has then been repeated again and again, the number of groups exposed varying, in different experiments, from three to twelve. In this way the spread of infection has been limited to that occurring between any one group and the group immediately following it.

Under these circumstances infection has spread far less readily than was the cases in other experiments, in which the mice were retained as a single population, and in which infection could spread in any direction among all the individuals at risk.

1. A new colicine type (type 15) of Shigella sonnei is described.

2. The epidemiological circumstances associated with its appearance in Edinburgh and Glasgow are summarized.

3. Our indices of reliability as an epidemiological marker are fulfilled by this new type.

A total of 21 rubella seronegative children vaccinated subcutaneously with Wistar RA 27/3 strain live attenuated rubella vaccine in a family study of vaccine virus transmissibility were reviewed after 6 years. Haemagglutinating inhibiting (HAI) antibody titres of sera collected 46 days, 2 years and 6 years after vaccination were compared. Antibody titres in the vaccinated subjects were not significantly influenced by time, infection in susceptible siblings or revaccination.

Epidemic forecasting provides an opportunity to predict geographic disease spread and counts when an outbreak occurs and plays a key role in preventing or controlling their adverse impact. However, conventional prediction models based on complex mathematical modelling rely on the estimation of model parameters, which yields unreliable and unsustainable results. Herein, we proposed a simple model for predicting the epidemic transmission dynamics based on nonlinear regression of the epidemic growth rate and iterative methods, which is applicable to the progression of the COVID-19 outbreak under the strict control measures of the Chinese government. Our model yields reliable and accurate results as confirmed by the available data: we predicted that the total number of infections in mainland China would be 91 253, and the maximum number of beds required for hospitalised patients would be 62 794. We inferred that the inflection point (when the growth rate turns from positive to negative) of the epidemic across China would be mid-February, and the end of the epidemic would be in late March. This model is expected to contribute to resource allocation and planning in the health sector while providing a theoretical basis for governments to respond to future global health crises or epidemics.

Recent studies have established that the occurrence of common cold epidemics amongst men in Antarctica shows a pattern similar to that seen in other isolated communities such as Tristan da Cunha (Cameron & Moore, 1968; Shibli, Gooch, Lewis & Tyrrell, 1971). Colds occur during relief periods when ships and aircraft call, and disappear during the months of winter isolation, but no statistical analysis of the incidence of such colds is available.

A third nationally representative serosurvey was performed to study the changes in Toxoplasma gondii (T. gondii) seroprevalence in the Netherlands over a 20-year time span and to identify and confirm risk factors for acquired toxoplasmosis. This cross-sectional study (conducted in 2016/2017) was designed similarly to the previous two studies (1995/1996 and 2006/2007) and included a questionnaire and serum sampling among Dutch residents. Factors associated with seropositivity for T. gondii were determined using multivariable analysis of the questionnaire-derived data. The earlier observed decrease in T. gondii seroprevalence between 1995/1996 and 2006/2007 (from 40.5% to 26.0%) did not continue into 2016/2017 (29.9%). Similarly to the previous studies, the seroprevalence increased with age and varied among regions. In all studies, higher T. gondii seropositivity was associated with increasing age, lower educational level, not living in the Southeast, and eating raw or semi-cooked pork. The incidence of congenital toxoplasmosis was estimated at 1.3/1000 (95% CI 0.9–1.8) live-born children in 2017. As the seroprevalence of T. gondii in the Netherlands did not decrease over the last decade, an increase in public health awareness is needed and prevention measures may need to be taken to achieve a further reduction in T. gondii infections in the Netherlands.

The following experiments constitute an attempt to follow out in detail the stages by which immunity is established, in the course of a generalised bacterial infection (Pseudotuberculosis of rabbits). Two aspects of immunity are considered, firstly the presence, in the circulating fluids, of specific antibacterial substances, and secondly the power of rapidly producing such substances in answer to the specific stimulus. That is to say, attention is directed, not only to the quantity of specific antibodies present on any day of the disease, but also to the response which the animal can make to various doses of bacterial vaccine. For the immune animal is both more vigorous and more sensitive than the normal, in its reaction to a renewed dose of poison (Wassermann and Citron, 1905). Naturally the facts established with regard to one disease only, cannot be predicated at once of other diseases, in other animals. Still it is hoped that the systematic study of one disease may give some help in coordinating the large but somewhat disjointed mass of clinical observation which is already available.