1. Silver nitrate or sodium merthiolate can be used for the sterilization of suspensions of B. typhosus and neither have any immediate destructive effect on the Vi, O or H antigens.

2. Two methods of employing silver nitrate as a sterilizing agent are described.

3. Physiological saline solution with silver nitrate added is bactericidal for B. typhosus and the staphylococcus but has no inhibitory action on the growth of moulds.

4. Vaccines sterilized and preserved with silver nitrate after storage for 6 months at 7° C. were found to have retained their Vi antibody stimulating properties.

5. A vaccine sterilized and preserved with “katadyn” after storage for 18 months at 7° C. still contained some Vi antigen and was superior as an immunogenic agent to a freshly prepared heat-killed-phenolized vaccine.

6. It would appear that the stability of Vi antigen is increased by the addition of silver within certain limits, but this effect is only obtained if low temperature storage conditions are maintained.

7. A vaccine sterilized and preserved with sodium merthiolate after 6 months' storage at 7°C. failed to stimulate any Vi antibody in the rabbit.

The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016–2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7–16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2–5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0–7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6–5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0–1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.

Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.

We report the development of a regression model to predict the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies on a population level based on self-reported symptoms. We assessed participant-reported symptoms in the past 12 weeks, as well as the presence of SARS-CoV-2 antibodies during a study conducted in April 2020 in Ischgl, Austria. We conducted multivariate binary logistic regression to predict seroprevalence in the sample. Participants (n = 451) were on average 47.4 years old (s.d. 16.8) and 52.5% female. SARS-CoV-2 antibodies were found in n = 197 (43.7%) participants. In the multivariate analysis, three significant predictors were included and the odds ratios (OR) for the most predictive categories were cough (OR 3.34, CI 1.70–6.58), gustatory/olfactory alterations (OR 13.78, CI 5.90–32.17) and limb pain (OR 2.55, CI 1.20–6.50). The area under the receiver operating characteristic curve was 0.773 (95% CI 0.727–0.820). Our regression model may be used to estimate the seroprevalence on a population level and a web application is being developed to facilitate the use of the model.

Finally, I must express my hearty thanks to the many medical men and others who have given me aid and hospitality in my wanderings after the truth about beriberi. I must mention particularly Dr Giddy and Captain Vincent on Christmas Island, Drs Ellis, Leask and Murray Robertson in Singapore, Drs Travers, Gimlette, Watson, McClosky and Mr Galloway in Selangor, and Drs M. J. Wright and Connolly in Perak, and Messrs Mason, Ponsford, Sanderson, and Hembrey in Pahang, without whose aid and kindness I could have seen but little. I must also thank my friend Dr G. S. Buchanan, Secretary of the Royal Commission on Arsenical Poisoning, for forwarding me much information.

It would seem from my observations that certain of the current theories of the causation of beriberi will not account for the conditions which have been encountered by me. The dietetic or physiological, the unsound food, the arsenical, and the emanation theories all appear to be insufficiently in accordance with the attendant circumstances to have accounted for the spread of the disease.

It is suggested that certain articles of diet, by virtue especially of containing phosphorised and fatty matters, may tend to ward off the disease when given in sufficient amounts. So far as there was any semblance of a positive result in the observations it is suggestive that beriberi is communicated from person to person more or less directly or through fomites as an actual infection. This infection is not of the nature of a septicaemia (since the internal organs at death prove sterile), but to a surface condition about the upper air passages. From the observation of the throats of a number of patients it is surmised that the redness which is therein seen, especially in early cases, may be intimately connected with the disease. The appearances and disappearances of beriberi and the more or less seasonal waves of prevalence of the disease are not unlike those which are seen in the case of the infective diseases which we meet with in this country. The proneness of the newcomer to suffer fits in also with such a view. The difficulty in tracing out the source of infection in a disease like diphtheria is often great, especially since we know that the causative organism may be carried by unsuspected refractory of immune persons or animals.

With considerations such as these it is held by the writer that there is no inherent impossibility in explaining many of the circumstances connected with the spread of beriberi.

Observed facts seem to show that beriberi should rather be considered in the light of a “gang” or “institutional” disease than as a “place” or “house” disease.

This study proposed a novel ensemble analysis strategy to improve hand, foot and mouth disease (HFMD) prediction by integrating environmental data. The approach began by establishing a vector autoregressive model (VAR). Then, a dynamic Bayesian networks (DBN) model was used for variable selection of environmental factors. Finally, a VAR model with constraints (CVAR) was established for predicting the incidence of HFMD in Chengdu city from 2011 to 2017. DBN showed that temperature was related to HFMD at lags 1 and 2. Humidity, wind speed, sunshine, PM10, SO2 and NO2 were related to HFMD at lag 2. Compared with the autoregressive integrated moving average model with external variables (ARIMAX), the CVAR model had a higher coefficient of determination (R2, average difference: + 2.11%; t = 6.2051, P = 0.0003 < 0.05), a lower root mean-squared error (−24.88%; t = −5.2898, P = 0.0007 < 0.05) and a lower mean absolute percentage error (−16.69%; t = −4.3647, P = 0.0024 < 0.05). The accuracy of predicting the time-series shape was 88.16% for the CVAR model and 86.41% for ARIMAX. The CVAR model performed better in terms of variable selection, model interpretation and prediction. Therefore, it could be used by health authorities to identify potential HFMD outbreaks and develop disease control measures.

In extensive cohort studies, the ascertainment of covariate information on all individuals can be challenging. In hospital epidemiology, an additional issue is often the time-dependency of the exposure of interest. We revisit and compare two sampling designs constructed for rare time-dependent exposures and possibly common outcomes – the nested exposure case-control design and exposure density sampling. Both designs enable efficient hazard ratio estimation by sampling all exposed individuals but only a small fraction of the unexposed ones. Moreover, they account for time-dependent exposure to avoid immortal time bias. We evaluate and compare their performance using data of patients hospitalised in the neuro-intensive care unit at the Burdenko Neurosurgery Institute in Moscow, Russia. Three different types of hospital-acquired infections with different prevalence are considered. Additionally, inflation factors, a primary performance measure, are discussed. We enhance both designs to allow for a competitive analysis of combined and competing endpoints compared to the full cohort approach while substantially reducing the amount of necessary information. Nonetheless, exposure density sampling outperforms the nested exposure case-control design concerning efficiency and accuracy in most considered settings.

The etiology of tetanus and gas gangrene presents a biological problem of an unusual nature. When the organisms which cause these diseases are deprived of toxin, by washing in tap-water saline or by washing and then heating, they are non-pathogenic to laboratory animals. In a recent investigation of the problem we have shown that soluble ionisable calcium salts enable detoxicated B. tetani, B. Welchii, B. oedematiens and vibrion septique to exert their pathogenic powers. We concluded that calcium owes this property to its local action on the tissues.

A Canadian outbreak investigation was initiated in January 2022 after a cluster of cases of Shiga-toxin-producing Escherichia coli (STEC) O157 was identified through whole genome sequencing (WGS). Exposure information was collected through case interviews. Traceback investigations were conducted, and samples from case homes, retail, and the manufacturer were tested for STEC O157. Fourteen cases were identified in two provinces in Western Canada, with isolates related by 0–5 whole genome multi-locus sequence typing allele differences. Symptom onset dates ranged from 11 December 2021 to 7 January 2022. The median age of cases was 29.5 (range 0–61); 64% were female. No hospitalisations or deaths were reported. Of 11 cases with information available on fermented vegetable exposures, 91% (10/11) reported consuming Kimchi Brand A during their exposure period. The traceback investigation identified Manufacturer A in Western Canada as the producer. One open and one closed sample of Kimchi Brand A tested positive for STEC O157, with isolates considered genetically related by WGS to the outbreak strain. Napa cabbage within the kimchi product was hypothesised as the most likely source of contamination. This paper summarises the investigation into this STEC O157 outbreak associated with kimchi, the first reported outside of East Asia.

The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7–5.4%) at the individual animal-level and 24% (95% CI 17.5–32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8–4.5) and 6.6 (95% CI 3.0–12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.

The plague suppressive campaign which is now drawing to a close in San Francisco has been conducted almost entirely on the principle that the great factor in the spread and continuance of the disease is the rat. The fact that the epidemic among human beings ceased within four months after the beginning of active operations and that in spite of the distribution of the disease in almost every quarter of the city, only one hundred and fifty-nine cases, with seventy-seven deaths occurred, proves the wisdom of this policy. The campaign has been conducted by the United States Public Health and Marine Hospital Service.

1. Cultures of Gärtner's bacillus grown on broth do not excrete any large amount of toxin into the fluid medium.

2. Suspension in broth made from ordinary agar cultures and killed by means of heat (30 mins. at 60°C.) are fairly toxic.

3. The most toxic preparations were obtained by autolysis of the bacilli, especially in the presence of toluol.

4. Cultures grown on agar and killed by means of chloroform vapour lose their toxicity to a considerable extent.

5. Autolysis takes place best in the presence of distilled water or of normal saline.

6. Autolysed material sterilised by heat is more toxic than the filtrate obtained from the same digest.

7. Shaking the bottles during the process of autolysis increases the yield of toxic substances.

8. Gärtner toxin withstands heating to 100°C. for 30 mins.

9. Paratyphoid B. bacillus cultures on autolysis yield a filtrate quite as toxic as those from the Gärtner bacillus itself.

10. Paratyphoid toxin is also heat resistant (100° for 30 mins.).

11. A colon bacillus gave a toxin which was fatal to mice. It was not heat resistant.

12. Feeding experiments with Gärtner-infected meat, both cooked and uncooked, proved successful.

13. So far as the present experiments go the connection between virulence and toxicity does not appear to be very definite.

14. The Gärtner bacillus contains a toxin of the endotoxin type as is shown in comparing results 1 and 3. This toxin gives rise to very definite clinical symptoms of which the gluing together of the eyelids and the prolonged narcosis before death are the most notable. The post-mortem signs have much in common with those arising from other intestinal intoxications.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42·6 vs. 39·2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P = 0·02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

On February 10th, 1911, the attention of the Medical Officer of Health was called by the practitioner in charge to an outbreak of diarrhoea in a family named R. residing in Paddington. The note made at the interview was to the effect that cases had occurred on the 8th, 9th, and 10th (2 cases) of the month, the four patients having violent diarrhoea and passing much blood. The onset was quite sudden in every case. It was thought that “food poisoning” could be excluded, and the main object in directing attention to the outbreak was to ascertain if any defective drainage existed at the house. Incidentally it may be remarked that the house drainage, etc. had been completely overhauled in 1907 and that no defects existed in February last except one leaky joint on a waste pipe.

Surveillance is a key public health function to enable early detection of infectious disease events and inform public health action. Data linkage may improve the depth of data for response to infectious disease events. This study aimed to describe the uses of linked data for infectious disease events. A systematic review was conducted using Pubmed, CINAHL and Web of Science. Studies were included if they used data linkage for an acute infectious disease event (e.g. outbreak of disease). We summarised the event, study aims and designs; data sets; linkage methods; outcomes reported; and benefits and limitations. Fifty-four studies were included. Uses of linkage for infectious disease events included assessment of severity of disease and risk factors; improved case finding and contact tracing; and vaccine uptake, safety and effectiveness. The ability to conduct larger scale population level studies was identified as a benefit, in particular for rarer exposures, risk factors or outcomes. Limitations included timeliness, data quality and inability to collect additional variables. This review demonstrated multiple uses of data linkage for infectious disease events. As infectious disease events occur without warning, there is a need to establish pre-approved protocols and the infrastructure for data-linkage to enhance information available during an event.

1. Field trials suggest that 3-monthly operations against rats in sewers using either 0·25% sodium fluoracetate or 2% fluoracetamide as a direct poison are more effective than 6-monthly treatments with 2·5% zinc phosphide or 10% arsenious oxide using the pre-baiting method.

2. In six paired trials 2% fluoracetamide gave better results (an apparent 100% clearance in five instances) than 0·25% sodium fluoracetate.

3. There is no evidence, at present, that direct poisoning treatments with 2% fluoracetamide or 0·25% sodium fluoracetate are improved by the addition of mould inhibiting substances to the bait.

The work described above was made possible only by the co-operation of a large number of local authority councils and their staffs, to whom we are therefore much indebted. We wish to thank also, Mr J. D. Riley who gave considerable help during the early stages of the trials.

Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients.

Information is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.

Mass gatherings (MG) present a number of challenges to public health authorities and governments across the world with sporting events, tournaments, music festivals, religious gatherings and all other MG having historically posed a risk to the spread and amplification of a range of infectious diseases. Transmission of gastrointestinal, respiratory, waterborne and sexually transmitted infectious diseases pose a particular risk: all have been linked to MG events [1–4]. Infection risk often depends on the nature of the mass gathering, and on the profile and behaviour of its participants. The interaction between environmental, psychological, biological and social factors plays a vital part. The risk of outbreaks particularly as a result of respiratory transmission remains high at MG, with the majority of outbreaks over the last two decades resulting from a variety of respiratory and vaccine preventable pathogens [5–7]. Concerns about the spread of infectious diseases at MG are often focussed on crowding, lack of sanitation and the mixing of population groups from different places. Sporting events, which have in recent decades become more complex and international in nature, pose a challenge to the control of communicable disease transmission [8]. Despite this, large scale outbreaks at sporting events have been rare in recent decades, particularly since the rise of more robust public health planning, prevention, risk assessment and improved health infrastructures in host countries [9].

1. African pouched rats (Cricetomys gambianus) are very suitable animals for plague experiments on account of their tolerance of captivity and their extreme susceptibility. After inoculation with small doses of plague culture of ordinary virulence they always die.

2. Broth-grown vaccine was much more efficient as a prophylactic than agar-grown vaccine. When two doses were given a survival rate of 56 per cent, was obtained with the former and 25 per cent, with the latter.

3. A vaccine composed of carbolised spleen pulp from animals, which had died of acute plague, was rather more efficient than broth vaccine, giving a survival rate of 75 per cent. But it is not likely to be of practical value, as preparation is difficult, there are undesirable local effects and its superiority over broth vaccine is not very great. Its efficiency is attributed to the fact that the organisms which it contains are a true “body strain.” The method of preparation is similar to that of Hindle's yellow fever prophylactic.

4. A number of experiments are described in which virulence was abolished or reduced by passage through immune or partially immune rats. This occurred only when the passage animal showed a considerable degree of immunity, as indicated by the length of the survival period after the test infection. Cultures made from the abscess at the site of infection were less often attenuated than those from the liver of an immunised animal, but this was observed only in the case of large well-defined abscesses. It is suggested that a firm abscess wall protects organisms inside it against the action of antibodies appearing in the general circulation.

A culture attenuated by passage through an immunised rat was restored to normal virulence by successive passages through normal rats, but the process was slower than in the case of cultures attenuated by long cultivation, five passages being required in the former case and only one in the latter.

5. Cultures used in the later work, unlike those used in the earlier work, lost virulence rapidly when kept at room temperature. Experiments and observations are described which suggest that old strains, even when subjected to rat passage, are less stable as regards virulence than those recently isolated from human epidemic cases, and that the high temperature of the Gold Coast has an adverse effect upon virulence.

6. Attempts to isolate stable variants of B. pestis were not successful. Colonies vary much in form. Three types of colony are mentioned, but all intermediate grades were observed. Certain old avirulent strains had a greater tendency to produce large irregular colonies than recent strains, but the relation was so loose that the form of colony gave little indication of the degree of virulence. In old avirulent strains the bacilli tend to become longer and filaments of great length may be present. Salt stability tends to become less as a strain grows old and avirulent, but the change is not very marked and is apt to be masked by individual fluctuations.