Clostridium difficile diarrhoea is an urgent threat to patients, but little is known about the role of antibiotic administration that starts in emergency department observation units (EDOUs). We studied risk factors for antibiotic-associated diarrhoea (AAD) and C. difficile infection (CDI) in EDOU patients. This prospective cohort study enrolled adult patients discharged after EDOU antibiotic treatment between January 2013 and 2014. We obtained medical histories, EDOU treatment and occurrence of AAD and CDI over 28 days after discharge. We enrolled and followed 275 patients treated with antibiotics in the EDOU. We found that 52 (18·6%) developed AAD and four (1·5%) had CDI. Patients treated with vancomycin [relative risk (RR) 0·52, 95% confidence interval (CI) 0·3–0·9] were less likely to develop AAD. History of developing diarrhoea with antibiotics (RR 3·11, 95% CI 1·92–5·03) and currently failing antibiotics (RR 1·90, 95% CI 1·14–3·16) were also predictors of AAD. Patients with CDI were likely to be treated with clindamycin. In conclusion, AAD occurred in almost 20% of EDOU patients with risk factors including a previous history of diarrhoea with antibiotics and prior antibiotic therapy, while the risk of AAD was lower in patients receiving treatment regimens utilizing intravenous vancomycin.

The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 103-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

The emergence of type 6B Streptococcus pneumoniae resistant to five antibiotics (penicillin, chloramphenicol, trimethoprim–sulphamethoxazole, erythromycin and tetracycline) in both the Northern Territory and Queensland prompted an investigation of the genetic relatedness and patterns of migration of the isolates. Pulsed field gel electrophoresis of genomic DNA of 74 multiple drug-resistant (MDR) isolates cultured in both regions between August 1988 and June 1997 showed that 100% of MDR isolates from the Northern Territory and 96% of MDR strains from Queensland were genetically indistinguishable or closely related to the index strain. None of a further 65 type 6B isolates that were resistant to one or two, or susceptible to all of the above antibiotics, were clonally related to the MDR pneumococci. The geographical distribution of the MDR type 6B clone increased over time. The index strain, first isolated in Darwin in August 1988, was identified in Brisbane, 2900km distant, less than 4 years later and subsequently in other Queensland centres. Surveillance programmes are important to monitor the emergence and spread of potentially invasive MDR pneumococcal clones in countries that are well serviced by air and road transport.

In June 1935, certain problems arose concerning the fumigation of houses with hydrogen cyanide for the destruction of bedbugs. Workmen reconditioning houses in Rochester, which had been given the customary 24 hr. aeration after fumigation with hydrogen cyanide “disks”, had complained of sickness during their work. The walls, cavities and floor spaces of some of these houses had been tested by Mr Topping, the Chief Sanitary Inspector of Rochester, who, using benzidine acetate-copper acetate paper, had obtained a strong positive reaction indicative of the presence of hydrogen cyanide after 24 hr. aeration.

This study aimed to estimate the disease burden of hepatitis E in a rural region in China. A total of 489 hepatitis E cases were reported according to a community-based survey in an active hepatitis surveillance system between 2008 and 2015, the questionnaire and record-review methods were constructed to evaluate the economic and health burden of hepatitis E virus infections from societal perspectives. All costs were converted to US$ in 2015. The age-standardized cumulative incidence rate was 107·9/100 000, and the median age-standardized annual incidence rate was 16·5/100 000. The median direct, indirect, and intangible cost were $1046·0, $49·1, and $77·3/patient, respectively, and the median economic burden per patient was $1836·5, which accounted for 51·2% of per capita disposable income. Moreover, the median quality-adjusted life year and visual analogue scale score were 0·7 and 70·0/case, respectively. Both economic burden and health burden of inpatients was more serious than that of outpatients (P < 0·001). Disease burden of hepatitis E is heavy on patients, their families, and society. More studies on the disease burden of hepatitis E are necessary to increase social awareness of the disease and confirm reasonable disease-control measures.

Hepatitis B core antigen (HBcAg) synthesised in Escherichia coli by recombinant DNA techniques was compared with HBcAg prepared from infected livrer tissue. The two antigens were used in radioimmunoassays (RIA) to detect antibody to HBcAg (anti-HBc) in sera from patients attending a clinic for sexually transmitted diseases. Out of 2151 sera tested, 260 were anti-HBc positive with both HBcAg preparations but seven were positive with the liver-derived antigen alone. Reasons for these discrepant results are discussed. The slight loss of sensitivity of the anti-HBc RIA using E. coli HBcAg was not considered significant when compared with the potential advantages of a synthetic antigen.

The presence of other hepatitis B markers in the 267 anti-HBc positive sera was determined: 25 contained HBsAg, 220 anti-HBs and, of the 22 that were HBsAg/anti-HBs negative, 12 contained anti-HBe. In the 10 remaining sera, anti-HBc was the only hepatitis B marker that could be found.

Detailed screening of the patients and staff in a unit specializing in liver disease was carried out over a year to ascertain whether transmission of the serum hepatitis virus was occurring and whether the situation was comparable in any way to that found in a Renal Haemodialysis Unit. Of the 154 patients with liver disease tested on admission, 6% were found to have Australia antigen in the serum and throughout the year there were rarely less than two patients in the ward at any one time with positive serum. No instances of clinical hepatitis were detected in the other patients following their stay in the ward or in their attendant medical, nursing and lay staff. Six staff members were found to have Australia antigen in their serum. In four of these, all nurses, it was present in the first sample tested and so the infection may have been acquired earlier. Temporary elevations in both plasma bilirubin and serum aspartate aminotransferase levels were found in another five staff members whose serum was negative for Australia antigen and who clinically were well. In a further eight and apparently healthy staff members, an isolated but persistent elevation of the plasma bilirubin was noted. In both groups these changes could represent the spread of subclinical infectious hepatitis and it is recommended that in units dealing with ‘liver patients’ not only should considerable care be taken during diagnostic and therapeutic procedures but the medical and nursing staff should be screened at regular intervals.

C. botulinum types A and B toxins required larger amounts of antitoxin for neutralization when fractions of the test dose of toxin were used than would be expected.

The degree of this dilution effect, i.e. the dilution ratio, varied with different sera. The dilution ratios with type A sera could be improved by allowing a greater time for combination to occur, or by mixing toxin and antitoxin in high concentration and diluting these mixtures.

The dilution ratios of type A sera from horses rose as immunization proceeded, the greatest rise occurring during the 3-month rest period following three small doses of toxoid.

A type A serum could be separated into fractions of different dilution ratio by precipitation with increasing concentrations of ammonium sulphate.

Type A antitoxins prepared by immunization of groups of guinea-pigs with two doses of toxoid, had dilution ratios far lower than those found in hyperimmune horse sera.

The dilution ratios of sera were lower when tested against a toxic toxin than against a more toxoided one.

A number of type A sera were tested at one level of test against a number of test toxins. There was no evidence of heterogeneity of the toxins and antitoxins tested.

The serum ratios were found to be correlated with the dilution ratios except where the serum ratios exceeded 0·64. Flocculation time was slow and varied from 6 to 48 hr. with different sera tested against the same toxoid.

I am greatly indebted to Miss M. Barr for her constant advice and encouragement in the execution of this work and in the preparation of this paper. I am grateful to Dr M. Sterne for the supply of C. botulinum type A and B toxins and for the benefit of his experience of animal botulism.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case–contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Despite being a vaccine-preventable disease for decades, pertussis control is still a public health challenge. A pertussis outbreak emerged in Jerusalem (n = 257 cases, January to June 2023). Most cases were young children (median age 1.5 years), and 100 were infants under 1 year. The hospitalisation rate of infants was 24%, which was considerably higher than that of cases aged 1 year and above (3.8%). There was one fatality in an unvaccinated, 10-week-old infant whose mother had not received pertussis vaccination during pregnancy. Most children were unvaccinated and resided in Jewish ultra-orthodox neighbourhoods in Jerusalem district. An intervention programme and vaccination campaign are ongoing.

Plasmids belonging to the FIme incompatibility group were found in seven different serogroups of multiply antimicrobial-resistant Escherichia coli isolated from patients with urinary tract infection (UTI) and living in south-east London. Although widespread in Salmonella spp., FIme plasmids have only previously been described in E. coli in a strain of serogroup O15 K52 H1 responsible for an extensive and protracted outbreak of invasive community-acquired infection in south-east London in 1986. Our findings suggest either a wider background occurrence of FIme plasmids in E. coli associated with UTI than previously reported or alternatively, the dissemination and subsequent molecular diversification of the FIme plasmid associated with the epidemic strain of serogroup O15 K52 H1.

A variant of variola virus is described which produces a late polypeptide of 25 kDa instead of one of 27 kDa and which has an additional endonuclease cleavage site for SalI in the viral DNA. These markers were shown to be genetically independent and to characterize 14 of the 48 variola strains which were examined. The variant strains were isolated from smallpox outbreaks originating in or from Pakistan between 1961 and 1974 and also from two cases at a Mission Hospital in Vellore, India in 1964. No variant strains were found among 9 other isolates from cases of variola major occurring in other parts of India or in Bangladesh, nor among 4 isolates from Indonesia, 15 from Africa or 6 isolates of variola minor.

A 14-month survey was undertaken in a diagnostic bacteriology laboratory to determine the incidence of Serratia spp. in routine clinical specimens. Gram-negative organisms with enterobacteria-like colonies were tested by a simple screening procedure. Fifty-eight strains of S. marcescens and two strains of S. liquefaciens were isolated from 59 patients. The strains were usually nonpigmented and exhibited multiple antibiotic resistance. Serotyping and determination of bacteriocine sensitivity patterns revealed that the majority of infections were sporadic, although episodes of cross-infection did occur.

S. marcescens was considered to contribute significantly to morbidity and mortality in 53% of patients and appears to be of increasing importance in hospital-acquired infections.

(1) There were nineteen cases and eight deaths at the depot during the epidemic.

One doubtful case during this period recovered, and a sporadic case in June due to Type I also recovered; these are not included in the above, nor is one man who went on leave to Blackpool, and developed the disease (Type II) on arrival.

(2) So far the reserve battalions have had three cases only, with two deaths, although a high carrier-rate wave has been detected in two.

(3) All the cases (except the June case) at the depot occurred during exceptionally cold weather. In the chart the cases appear to lie in thetrough of a great depression of the curve of mean weekly temperature (broken line). They also follow immediately upon exceptional crowding (black line).

(4) There was a well-marked premonitory rise in the carrier-rate in December 1916, before the first case occurred, and an enormous rise before the epidemic was really established.The carrier-rate, which was 19·25% on December 23rd, reache dwhat is usually considered the danger point of 20% (see War OfficeMemorandum on Cerebro-spinal Fever, page 2) just six days before the first case occurred.

It would appear that estimations of the carrier-rate by means of large sample swabbings afford a reliable warning of the imminence or danger of an epidemic.

(5) The cases in the epidemic were nearly all due to the meningococcus of Type II, the organism present in the outbreak of 1916.

The rise in the carrier-rate was also chiefly due to the increase ofcarriers of this type. Freshly joined recruits showed few carriers at all and very few Type II carriers when swabbed before having slept in the barracks.

(6) During the epidemic, the carrier-rate among non-contacts was substantially the same as amongst the actual contacts of cases, averaging34% for the period, in each case.

(7) The proportion of agglutinable strains to inagglutinable strains of organisms morphologically indistinguishable from the meningococcus increased very markedly during the epidemic period.

(8) The treatment of the whole population by the steam zinc sulphate solution spray (which was carried out daily for two seven-day periods with an interval of a fortnight), was followed by a satisfactory drop in the carrier-rate, and by a temporary cessation of cases on each occasion.

(9) 60% of the actual patients suffering from the disease were in their first month of service.

40% of the patients had either been inoculated or vaccinated within seven days of onset (three on the same day); 60% within afortnight.

(10) Previous and concurrent epidemics of German measles, influenza and bronchitis had helped (by causing coughing and sneezing and by lowering vitality) to produce the great rise in the carrier-rate, which culminated in the case epidemic.

1. A study of the natural bacterial flora of the house-fly appears to be essential in forming a correct estimate of the part played by flies in transmitting pathogenic bacteria.

2. The house-fly may carry at least 27 varieties of Bacillus coli, by far the most frequent of which are B. coli communis and MacConkey's bacillus No. 71.

3. As far as can be judged from the character of these colon bacilli the house-fly derives its bacterial flora equally from excremental matter and from other sources.

4. Certain non-lactose fermenting bacilli appear to be capable of multiplying in the intestine of the house-fly. Of these Morgan's bacillus No. 1 is a not infrequent inhabitant of the fly's intestine and B. paratyphosus β has been found on two occasions.

The hygiene and marketing of fresh cream in England and Wales was investigated by a working party of the Public Health Laboratory Service (PHLS) between 1 October 1968 and 31 July 1969. Thirty-one cream-producing dairies were visited and observations made in the light of the Code of Practice published by the Milk and Milk Products Technical Advisory Committee of the Ministry of Agriculture, Fisheries and Food, and the Scottish Home and Health Department. Suggestions are made in this report to strengthen the code.

A total of 5184 samples of fresh cream comprising 4385 heat-treated, 282 clotted and 517 untreated were examined. Details of production, age of the cream, distance and mode of distribution along the retail chain were available for most samples, and this history was, as far as possible, related to the laboratory findings. In the laboratory the samples were examined by the methylene blue test, colony count, conform and Escherichia coli I test and for pathogens. Staphylococcus aureus was grown from 59 out of 3417 samples of cream; 54 of these were from untreated cream. Phage typing indicated that a proportion of these strains were of animal, presumably bovine, origin. Other human pathogens isolated included one each of Salmonella typhimurium, Brucella abortus, E. coli type O126 and Clostridium welchii.

It appeared that heat-treated cream was much better, bacteriologically, than untreated; and that large dairies, in general, had better premises, more hygienic methods of preparation and the advantages of mechanical filling and capping of cartons; thus they offered the consumer a better product, bacteriologically, than some of the smaller dairies.

A statistical analysis of the results of the tests used showed the methylene blue test, in spite of some anomalies, to be of more use as a screening test than any of the others. As this test is cheap and easy to carry out, the working party thought that it should be the test of choice. In view of the known anomalies, however, the working party recommends that the test should remain a screening or advisory test and have no penal function. Results should be reported as follows: cream not decolorizing the dye in 4 hr. at 37° C. (± 0·5°) after overnight incubation at 20° C. (± 0·5°) would be accepted as satisfactory; between ½ and 4 hr. at 37° C. (± 0·5°) as fairly satisfactory; but if the dye were decolorized at the end of the overnight incubation the sample would be provisionally classified as ‘unsatisfactory; requires further investigation’. A repeat sample would then be examined. If samples were repeatedly unsatisfactory, consultations would be arranged between the local authority, the laboratory and the dairy, with perhaps inspection of the dairy premises and retail storage conditions and further, more searching tests on samples made in an effort to eradicate production faults.

1. Faeces from apparently healthy Bantu school children of a periurban district of Johannesburg were examined eight times at regular intervals over a period of 1 year.

2. Of 75 children, 29·3 % experienced at least one salmonella infection and 2·7 % one shigella infection. It is suggested that over a year nearly all children will have one, and many of them several, infections with these pathogens. The infections occurred at a low rate throughout the year.

3. In most cases the infections were asymptomatic. A few of the children showed evidence of being salmonella carriers of long standing.

4. Eighteen different salmonella types were recovered. Salmonella typhi, S. paratyphi B and S. paratyphi C were absent. The organisms were highly resistant to penicillin, erythromycin and novobiocin and a few strains were also resistant to chloramphenicol and tetracycline.

5. The drinking water was of poor quality and may well be implicated in the transmission of the infections.

Our thanks are due to the Director of this Institute, Dr J. H. S. Gear, for permission to publish this paper; to Mr R. G. Robinson for assessing the microorganisms'sensitivity to antibiotics; and to the South African Council of Scientific and Industrial Research, Pretoria, for a grant enabling us to meet the transport expenses.

This study recognises periodic outbreaks of measles continue to affect conflict and fragile zones in the least developed countries. This study set out to provide evidence for the indirect costs or economic loss associated with measles-related deaths among children aged 0–14 years in Somalia. Using epidemiologic and economic data, the indirect cost was calculated based on the framework of the World Health Organisation guide of identifying the economic consequences of disease and injury. The baseline indirect cost was computed as the product of discounted future productive years of life lost (PYLL), non-health gross domestic product per capita (NHGDPPC) and the estimated total measles deaths (ETMD). The model was adjusted for conflict and fragility conditions and further extension considered a finite and stable upper limit growth of the instability-adjusted NHGDPPC. To discount future costs, a rate of 3% was applied. Using a ±20% variability assumption of the epidemiologic and economic factor inputs, a sensitivity analysis was conducted to account for uncertainty. In 2015 values, the ETMD of 3723 measles deaths of children aged 0–14 years could decrease non-health GDP of the country by $23.46 million, a potential loss of $6303 per death over the discounted PYLL. The loss would increase by 5.3% when adjusted for conflict and fragility conditions. Assuming growth, the future adjusted loss is expected to be $35.91 million in 2015 values. Girl-child deaths accounted for 51.2% of the burden. Results are robust to the variations in the model inputs, although sensitivity analyses suggest the proportion of total measles deaths and the discount rate accounted for greater uncertainty of the loss than do the proportion of growth and instability assumption. Conflict and fragility accounted for the least uncertainty, perhaps confirming their relative perpetuity in Somalia. Results show significant indirect cost related to measles deaths of children, exacerbated by conflict and fragility. This is an economic burden, but one which the health system, policy-makers, government and other stakeholders should be prepared to colossally discount by collectively taking measles surveillance and security measures now to reduce further deaths in the future.

Historical enquiry into diseases with morbidity or mortality predilections for particular demographic groups can permit clarification of their emergence, endemicity, and epidemicity. During community-wide outbreaks of hepatitis A in the pre-vaccine era, clinical attack rates were higher among juveniles rather than adults. In community-wide hepatitis E outbreaks, past and present, mortality rates have been most pronounced among pregnant women. Examination for these characteristic predilections in reports of jaundice outbreaks in the USA traces the emergence of hepatitis A and also of hepatitis E to the closing three decades of the 19th century. Thereafter, outbreaks of hepatitis A burgeoned, whereas those of hepatitis E abated. There were, in addition, community-wide outbreaks that bore features of neither hepatitis A nor E; they occurred before the 1870s. The American Civil War antedated that period. If hepatitis A had yet to establish endemicity, then it would not underlie the jaundice epidemic that was widespread during the war. Such an assessment may be revised, however, with the discovery of more extant outbreak reports.

1. Salmonella paratyphi A possesses a specific Vi antigen essentially similar to that of the Vi antigen of Salm. typhi.

2. O-insensitive strains of Salm. paratyphi A contain more Vi antigen, and are more virulent for mice, than O-sensitive strains.

3. The most suitable strains for the preparation of paratyphoid-A vaccine are those that develop both the Vi and the O antigens in maximum quantities. The methods of selecting the vaccine strain of Salm. paratyphi A and routinely examining the cultures are essentially the same as those applied to the virulent Vi+O form of Salm. typhi.

4. Pure A Vi antiserum is destined to assume importance in the identification of Salm. paratyphi A strains.

5. Kauffmann's erroneous conclusion that Salm. paratyphi A does not develop Vi antigen is critically reviewed.