Orthobunyaviruses, tri-segmented, negative-sense RNA viruses, have long been associated with mild to severe human disease in Africa, but not haemorrhagic fever. However, during a Rift Valley fever outbreak in East Africa in 1997–1998, Ngari virus was isolated from two patients and antibody detected in several others with haemorrhagic fever. The isolates were used to identify Ngari virus as a natural Orthobunyavirus reassortant. Despite their potential to reassort and cause severe human disease, characterization of orthobunyaviruses is hampered by paucity of genetic sequences. Our objective was to obtain complete gene sequences of two Bunyamwera virus and three Ngari virus isolates from recent surveys in Kenya and to determine their phylogenetic positioning within the Bunyamwera serogroup. Newly sequenced Kenyan Bunyamwera virus isolates clustered closest to a Bunyamwera virus isolate from the same locality and a Central African Republic isolate indicating that similar strains may be circulating regionally. Recent Kenyan Ngari isolates were closest to the Ngari isolates associated with the 1997–1998 haemorrhagic fever outbreak. We observed a temporal/geographical relationship among Ngari isolates in all three gene segments suggesting a geographical/temporal association with genetic diversity. These sequences in addition to earlier sequences can be used for future analyses of this neglected but potentially deadly group of viruses.

In January 2012, an inpatient in a ward of a psychiatric hospital with nearly 300 beds in Kanagawa, Japan, was diagnosed with sputum smear-positive pulmonary tuberculosis (TB). Here we characterise the TB outbreak cases and identify the population at risk. TB was diagnosed when a person tested bacteriologically positive for TB or was determined to have TB by a physician. A latent TB infection (LTBI) case was defined as a person tested positive by interferon-gamma release assay (IGRA). A total of 125 contacts were screened via IGRA and chest X-ray. In all, 15 TB and 15 LTBI cases were found by the end of October 2012, and thereafter no additional TB case was found. Of the 15 TB cases, eight were culture-positive and all the isolates had identical variable number tandem repeat patterns. Twenty-four of the 56 (42.9%, 95% confidence interval (CI) 29.7–56.8) inpatients in the ward had either TB or LTBI with a relative risk of 8.6 (95% CI 1.2–59.3), compared to the staff members who did not work full-time in the ward (one of 20 (5.0%, 95% CI 0.0–24.9)). We recommend that psychiatric hospitals conduct periodic screening of staff members and inpatients for TB to prevent nosocomial TB outbreaks.

Fever is a common adverse event following measles vaccination, more frequent among older children and those receiving Measles-Mumps-Rubella-Varicella vaccine vs. Measles-Mumps-Rubella vaccine, two factors associated with a better antibody response. However, the role of fever in the immunogenicity of measles-containing vaccines (MCV) is unclear. We performed a post-hoc pooled analysis of data of 5 216 11 to 22 month-old children receiving MCV from 2004 to 2012 in Europe and USA to evaluate the association between post-immunisation fever and antibody response, measured by geometric mean concentrations (GMCs). We further evaluated fever as an effect modifier or a mediator in the associations between the type of MCV or the age at first vaccination and vaccine immunogenicity. After the first dose, fever was associated with 60% higher GMCs (95% CI 1.51–1.68). For children vaccinated at ⩾12 months, the fever did not modify and minimally mediated (2% to 3%) the association between age and antibody response. Fever mediated 18% of the association between type of MCV and GMCs. In a model including fever, age and type of vaccine, fever was the strongest predictor of GMCs. These results suggest that fever is associated with a stronger measles antibody response independently of age and type of MCV.

In August 2019, public health surveillance systems in Scotland and England identified seven, geographically dispersed cases infected with the same strain (defined as isolates that fell within the same five single nucleotide polymorphism single linage cluster) of Shiga toxin-producing Escherichia coli O157:H7. Epidemiological analysis of enhanced surveillance questionnaire data identified handling raw beef and shopping from the same national retailer (retailer A) as the common exposure. Concurrently, a microbiological survey of minced beef at retail identified the same strain in a sample of minced beef sold by retailer A, providing microbiological evidence of the link. Between September and November 2019, a further four primary and two secondary cases infected with the same strain were identified; two cases developed haemolytic uraemic syndrome. None of the four primary cases reported consumption of beef from retailer A and the transmission route of these subsequent cases was not identified, although all four primary cases visited the same petting farm. Generally, outbreaks of STEC O157:H7 in the UK appear to be distinct, short-lived events; however, on-going transmission linked to contaminated food, animals or environmental exposures and person-to-person contact do occur. Although outbreaks of STEC caused by contaminated fresh produce are increasingly common, undercooked meat products remain a risk of infection.

The isolation and description of Bacillus coli commune by Escherich a hundred years ago marked the start of a series of scientific investigations which have led to some of the most important discoveries in microbial pathogenicity and genetics that have been made since that time. It is not difficult to find the reasons why so much effort has been concentrated on this organism. Escherichia coli is present in the gut of all warm-blooded animals generally forming the predominant aerobic flora; it is of medical and veterinary importance being responsible for a variety of infections in the human and animal populations and it has provided a useful tool for geneticists.

1. The three organisms B. pyocyaneus, B. fluorescens-liquefaciens and non-liquefaciens form a closely related group of organisms both biologically and also by reason of their behaviour towards disinfectants.

2. Bacteriological observations support the view that germicides can naturally be divided into two classes, viz. “chemical” and “physico-chemical,” their actions on micro-organisms depending respectively on

(1) Chemical reactivity with protoplasmic constituents.

(2) Denaturation or precipitation of the cell proteins.

3. B. fluorescens non-liquefaciens and related organisms are selectively attacked by “physico-chemical” germicides, e.g. phenol, whilst B. coli is less sensitive to their action, but is particularly susceptible to the “chemical” disinfectants, e.g. quinones.

The B. fluor. non-liq. group is also more readily affected by hot water than B. coli.

4. Substitution of various groups into the benzene nucleus in the case of aromatic disinfectants affects the germicidal power on B. coli and B. fluor. non-liq. unequally, with the result that the selective action and differentiation may be obscured or even reversed in the case of the substituted derivatives.

5. B. fluor. non-liq. is more sensitive than B. coli to the action of reducing agents, and this factor also affects the degree and nature of selective action, sometimes resulting in the classification of “chemical” germicides in the “physico-chemical” group.

6. Selective action is not affected by changes in experimental conditions, such as temperature and period of disinfection, nature of culture medium, number of bacteria present, or physical state of the disinfectant. The susceptibility of B. fluor. non-liq. to the action of hot water, and such germicides as phenol and alcohol, is thus probably associated in some way with its internal colloid state.

7. The analogy between the action of hot water and that of the alcohols and phenols is borne out by preliminary experiments with the thermophile bacteria (heat resistant). These organisms are somewhat less sensitive to phenol that B. coli, and more susceptible to p-nitrosodimethylaniline.

A year-long community-based study of diarrhoeal diseases was conducted in Canto Grande, a periurban community in Lima, Peru. In 109 (34%) houses out of 323 that were visited, at least one individual was detected with shigellosis. The frequency of the 161 shigella isolates obtained was as follows: 117 S. flexneri (73%), 21 S. boydii (13%), 15 S. dysenteriae (9%), and 8 S. sonnei (5%). Using a non-radioactive ipaH gene probe as a molecular epidemiological tool, a total of 41 S. flexneri strains were shown to be distributed in 25 intra-family comparisons by pairs (icp). Further subdivision, based on a comparison of the serotype, plasmid profile, antibiotic resistances and ipaH hybridization patterns indicated that Group I, with 11 icp (44%), had strains that were identical, Group II with 8 icp (32%), had strains that were different and Group III with 6 icp (24%), had strains with the same serotype and identical ipaH profiles but with differences in other markers. This data indicates that a diversity of shigella clones circulated in this community resulting from both clonal spread and horizontal transfer of genetic elements. Furthermore, ipaH profiling of isolates can be used not only to differentiate between closely related shigella strains but also with other parameters, help to understand the dynamics of the generation of new clones of pathogenic bacteria.

Daptomycin-non-susceptible enterococci (DNSE) are emerging pathogens. We have previously reported de novo DNSE isolates in patients with agricultural activities and exposure to livestock. We studied the geographical distribution of the residencies of 34 patients with DNSE infections described in a tertiary centre over a 5-year period in an effort to explore the association between patients’ residential locations and agricultural and farm lands. Nine patients had no prior exposure to daptomycin (de novo) and seven of these lived in areas with animal or crop operations. Of those living near an animal or crop operation, the mean number of operations in the proximity of the residence of patients with daptomycin-exposed DNSE was 13·8 (range 1–67) compared to 98·6 (3–529) for those patients with de novo DNSE (P = 0·0486). These data are consistent with previous reports that the transport of daptomycin resistance genes between animals and humans may be a possible mechanism for development of de novo daptomycin resistance in enterococci.

The infectious fevers have, during the last fifty years, been the subject of much epidemiological research, and have thus been made to yield up secrets which have materially affected the whole outlook of preventive medicine. But there yet remains for exploration a vast adjacent territory, that of minor coccal infections of the skin. However, whereas the former, being clearly defined clinically and in many cases subject to compulsory notification, lend themselves well to investigations of this sort, Impetigo, as a type of minor coccal dermatitis, surrounds itself with dificulties. For not only does it vary very much in its appearances by the time it is first seen but it is often of so little severity that it does not come under the observation of a physician at all, so that the influence of missed cases, always an important factor to be reckoned with in the study of epidemics, may assume such proportions as to give quite an erroneous impression of the total incidence of the disease. Consequently the epidemic aspects of impetigo have as yet received very little attention.

We describe a method of working on publicly available data to estimate disease prevalence in small geographic areas using Helicobacter pylori as a model infection. Using data from the Third National Health and Nutrition Examination Survey, risk parameters for H. pylori infection were obtained by logistic regression and validated by predicting 737·5 infections in an independent cohort with 736 observed infections. The prevalence of H. pylori infection in the San Francisco Bay Area was estimated with the probabilities obtained from a predictive logistic model, using risk parameters with individual-level 1990 U.S. Census data as input. Predicted H. pylori prevalence was also compared to gastric cancer incidence obtained from the Northern California Cancer Center and showed a positive correlation with gastric cancer incidence (P<0·001, R2=0·87), and no statistically significant association with other malignancies. By exclusively using publicly available data, these methods may be applied to selected conditions with strong demographic predictors.

The fact that the blood of ordinary laboratory animals exerts a very marked bactericidal effect upon the Bacillus typhosus and the Spirillum cholerae asiaticae, while it exerts little or no effect upon the Staphylococcus and Streptococcus pyogenes, has hardly received the attention which it would seem to merit in view of the circumstance that these facts involve the important problem as to whether the blood exerts its bactericidal action upon pathogenic organisms generally, or only upon certain species of such micro-organisms.

It is greatly to be desired that the causes of the decline of tuberculosis, which has been so striking a feature in the history of that disease in recent times, should be clearly ascertained; for only through an understanding of their nature and relative importance can our efforts to accelerate that decline hope to succeed.

Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

1. A series of 340 cases of scarlet fever was treated under controlled conditions, (a) with sulphanilamide or benzyl-sulphanilamide, and (b) without sulphanilamide.

2. There was an even distribution of the individual cases in respect of factors known to influence the course of the disease, such as (a) the duration of the disease before admission to hospital, and (b) the severity of the infection.

3. Treatment was carried out during the whole period of 4 weeks, which constitutes the average period of hospitalization in scarlet fever.

4. The dose employed was large: (a) patients 5 years of age and over receiving 1 g. 4 hourly (i.e. 5 g. a day) for the first 14 days in hospital, thereafter 1 g. t.i.d. (i.e. 3 g. a day) for 14 days; a maximum total dose of 112 g., and (b) patients under 5 years of age receiving 0.5 g. 4 hourly (i.e. 2.5 g. a day) for the first 14 days in hospital, thereafter 0.5 g., t.i.d. (i.e. 1.5 g. a day) for 14 days; a maximum total dosage of 56 g.

5. The results show that sulphanilamide had no significant effect upon the initial symptoms of scarlet fever, or upon the kind, incidence, or duration of later complications.

6. A large number of toxic reactions followed the use of both sulphanilamide and benzyl-sulphanilamide.

7. In view of all the evidence submitted, it is considered that there is no justification for the employment of sulphanilamide and benzyl-sulphanilamide in the treatment of scarlet fever.

1. A series of 110 patients with staphylococcal infections has been investigated. From 43 patients a penicillin-resistant staphylococcus was isolated: in cultures from 38 patients all staphylococcal colonies tested were penicillin resistant and in five both sensitive and resistant strains were isolated. Seven patients yielded a streptomycin-resistant staphylococcus.

2. Of the 84 strains of staphylococci which could be phage typed, 33 belonged to the group of phages 6/7/47 and 32 were of type 52 A. Of the 32 typable penicillin- resistant strains 18 belonged to the group of phages 6/7/47, and 13 were type 52 A.

3. Of the 115 strains isolated 110 were α-lysinogenic.

4. These results are compared with those found a year previously and the significant changes are discussed.

Close contacts of cases of meningococcal disease are at increased risk of disease themselves. We identified household-like contacts of index cases, to investigate whether relevant target groups are informed, receive and follow recommended chemoprophylaxis and vaccination, and to ascertain the time delay for implementation of these measures. A telephone interview of 172 households of index cases and a questionnaire survey among 634 parents of contacts of cases in institutions were carried out. Results were compared with reports from Medical Officers of Health. In 21% of the cases, Medical Officers reported fewer household-like contacts than were identified in this study. Written information was effective. However, 59% of households, and 36% of parents of contacts in institutions felt a lack of information about how the disease is acquired, the risk and signs of illness. For household-like contacts the coverage rate for chemoprophylaxis with an appropriate drug was 90% and for vaccination 59%. No secondary cases occurred among those treated with chemoprophylaxis, but among those not treated, there were two secondary cases. The study design provided a useful audit methodology to evaluate the completeness of implementation and the success of prophylactic measures for meningococcal disease.

It has long been known that individuals who suffer from such chronic diseases as nephritis and cirrhosis of the liver are very liable to develop an acute infection during the last stages of their illness. These patients rarely die of their chronic ailment. Often in the very last days, or perhaps hours, of the disease pneumonia, a dysentery, an acute endocarditis, or a streptococcus infection sets in, which quickly terminates fatally and must be regarded as the immediate cause of death. So familiar is this course of events that such pneumonias or dysenteries are now known as a fairly definite group of infections, namely, terminal infections. Often they are not recognized before death, but at autopsy their frequency and varying characters have been well shown by Flexner in his statistical and experimental study upon the subject; and though in some cases of terminal septicaemia the portal of entry was not easily found, yet it is important to note how frequently such local infections as leg ulcer or tonsilitis served as a starting point for the general invasion of bacteria. Of still more importance are his observations upon the bactericidal action of the blood of patients who have chronic diseases. The serum from six out of nine such patients showed a distinct decrease in its destructive power toward the Staphylococcus aureus and two of three patients whose serum did not show a diminished bactericidal action left the hospital improved.

A Microscopical study of the skins of mice painted with definite carcinogenic agents and with agents which appear to be incapable of exciting the production of tumours has, in the main, enabled us to confirm the observations of previous workers on the different histological changes which take place. A brief description of our findings will first be given.

Campylobacter jejuni isolates of human, canine, feline, bovine and poultry origin were investigated for their genomic diversity using O-antigen typing (n = 271), SmaI (n = 158) and XhoI (n = 158) macrorestriction analysis and ERIC–PCR (n = 107). The O-antigens O[ratio ]1/44, O[ratio ]2, O[ratio ]4 complex, O[ratio ]37, O[ratio ]40 were identified and 53.7% of the human and 56.1% of the animal strains were typable with the available antisera. Two ERIC–PCR pattern groups were generated representing human and animal strains as well as those exclusively of animal origin. XhoI macrorestriction analysis also distinguished ‘human’ and ‘non-human’ strain clusters, but by SmaI restriction mainly serotype-associated clusters were found. In conclusion, genomic differences may occur between ‘human’ and ‘non-human’ strains and this may reflect their potential to overcome the barrier from animals to humans.

Epidemiological and clinical findings from 1162 serologically confirmed measles cases occurring in Buenos Aires, Argentina in 1997 and 1998 were retrospectively reviewed. From 90 hospitalized children, measles virus was detected by direct RT–PCR from nasopharyngeal secretions. Patients were grouped as follows: (i) not vaccinated: infants < 12 months; (ii) regularly vaccinated: children 1–4 years not covered by the last catch-up; (iii) catch-up vaccinated: patients 5–19 years immunized during the 1993 campaign. Most cases were recorded in non-vaccinated infants (54%), and the lowest in catch-up vaccinated children (16%). Mean age of the 90 hospitalized children was 11·3 months. Pneumonia was the major hospitalization cause followed by pneumonitis. Two children required intensive care and one died. The 1993 catch-up campaign seemed to reduce the number of cases in the 5- to 19-year-old group. Lack of timely follow-up probably led to the accumulation of susceptible individuals allowing measles re-emergence. Direct viral detection by RT–PCR proved to be a sensitive tool for molecular epidemiology surveillance.