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.

A total of 475 Salmonella strains belonging to 5 serovars, isolated from a pig farm which had been heavily contaminated with Salmonella for the past 2 years were tested for antibiotic susceptibility and detection of R plasmids. Thirty-three Escherichia coli isolates from the same farm were also examined in a similar way.

Out of 475 strains 348 (73·2%) were resistant to one or more antibiotics such as tetracycline (Tc), streptomycin (Sm), sulfadimethoxine (Su), chloramphenicol (Cm) and kanamycin (Km), and 247 (85·2%) out of 290 strains belonging to 3 serovars examined harboured conjugative R plasmids. There was no change in the pattern of drug resistance during this survey nor any variation in the pattern of resistance of R plasmids, whatever the serovar. The antibiogram pattern Tc Sm Su, mainly S. typhimurium, was common among Salmonella strains. Among the transferred resistance patterns, the thermosensitive R plasmids conferring the Te marker detected in this study were Fi-, and belonged to incompatibility group H1, whereas the R plasmids conferring Sm Su resistances which coexisted in the same host were Fi+, and compatible with the reference R plasmids tested. The la plasmid conferring Cm resistance alone was isolated from S. anatum and the FII plasmid conferring Sm Km resistances was also isolated from S. typhimurium. In contrast, the 33 E. coli strains examined were resistant to three or five antibiotics and most of the resistance markers were located on conjugative R plasmids. la plasmids conferring Cm resistance alone or FIT plasmids conferring Cm or Km markers were common in the E. coli strains. H1 and H2 plasmids conferring multiple resistance markers were also found in them. The genetic properties of R plasmids derived from Salmonella or E. coil strains are compared, and the potential spread of R plasmids between strains of Salmonella andE. coli is discussed.

The single intradermal comparative cervical tuberculin (SICCT) test and post-mortem examination are the main diagnostic tools for bovine tuberculosis (bTB) in cattle in the British Isles. Latent class modelling is often used to estimate the bTB test characteristics due to the absence of a gold standard. However, the reported sensitivity of especially the SICCT test has shown a lot of variation. We applied both the Hui–Walter latent class model under the Bayesian framework and the Bayesian model specified at the animal level, including various risk factors as predictors, to estimate the SICCT test and post-mortem test characteristics. Data were collected from all cattle slaughtered in abattoirs in Northern Ireland in 2015. Both models showed comparable posterior median estimation for the sensitivity of the SICCT test (88.61% and 90.56%, respectively) using standard interpretation and for post-mortem examination (53.65% and 53.79%, respectively). Both models showed almost identical posterior median estimates for the specificity (99.99% vs. 99.80% for SICCT test at standard interpretation and 99.66% vs. 99.86% for post-mortem examination). The animal-level model showed slightly narrower posterior 95% credible intervals. Notably, this study was carried out in slaughtered cattle which may not be representative for the general cattle population.

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.

A study has been made of the properties of soluble antigen in the brains of infant mice infected intracerebrally with the Flury strain of rabies virus.

Soluble antigen is produced at the same time as infective virus, and reaches a high concentration in a period of 2–3 days.

It can be partially purified by precipitation at pH 4·3. It is partially resistant to the action of trypsin, RNAse and DNAse. It is relatively stable at pH 6–10.

Experimental results suggest that the soluble antigen remains antigenically active after heating at 56° C. and treatment with 0·5% phenol or 0·35% formal-dehyde, but that such heating markedly reduces the ability to stimulate formation of neutralizing antibody.

Rabbits and mice appear to differ in the production of neutralizing antibody following immunization against soluble antigen in which residual live virus was inactivated by heat, phenol or formaldehyde.

It is suggested that this difference may depend on the different susceptibility to traces of incompletely inactivated virus remaining in the immunizing antigens.

The authors are grateful to Miss T. Madsen for her assistance in some aspects of this work. Dr N. Sapeika kindly made available facilities for the in vitro anaphylaxis experiments.

Financial assistance was received from the Nkana-Kitwe and Chingola Poliomyelitis Research Funds.

The primary study objective was to investigate three decades from 1985 to 2014 of changes in pregnancies among HIV-infected women. The secondary objective was to assess risk factors associated with preterm delivery and severe small-for-gestational-age (SGA) infants in HIV-infected women. A retrospective review of deliveries among pregnant HIV-infected women at the University of Genoa and IRCCS San Martino-IST in Genoa between 1985 and 2014 was performed. Univariate and multivariable analyses were used to study the variables associated with neonatal outcomes. Overall, 262 deliveries were included in the study. An increase in median age (26 years in 1985–1994 vs. 34 years in 2005–2014), in the proportion of foreigners (none in 1985–1994 vs. 27/70 (38·6%) in 2005–2014), and a decrease in intravenous drug use (75·2% (91/121) in 1985–1994 vs. 12·9% (9/70) in 2005–2014) among pregnant HIV-infected women was observed. Progressively, HIV infections were diagnosed sooner (prior to pregnancy in 80% (56/70) of women in the last decade). An increase in combined antiretroviral therapy (cART) prescription during pregnancy (50% (27/54) in 1995–2004 vs. 92·2% (59/64) in 2005–2014) and in HIV-RNA <50 copies/ml at delivery (19·2% (5/26) in 1995–2004 vs. 82·3% (53/64) in 2005–2014) was observed. The rate of elective caesarean section from 1985 to 1994 was 9·1%, which increased to 92·3% from 2004 to 2015. Twelve (10·1%) mother-to-child transmissions (MTCT) occurred in the first decade, and six (8·3%) cases occurred in the second decade, the last of which was in 2000. Preterm delivery (<37 weeks gestation) was 5% (6/121) from 1985 to 1994 and increased to 17·1% (12/70) from 2005 to 2014. In univariate and multivariable logistic regression analyses, advancing maternal age and previous pregnancies were associated with preterm delivery (odds ratio (OR) 2·7; 95% confidence intervals (CI) 1–7·8 and OR 2·6; 95% CI 1·1–6·7, respectively). In the logistic regression analysis, use of heroin or methadone was found to be the only risk factor for severe SGA (OR 3·1; 95% CI 1·4–6·8). In conclusion, significant changes in demographic, clinical and therapeutic characteristics of HIV-infected pregnant women have occurred over the last 30 years. Since 2000, MTCT has decreased to zero. An increased risk of preterm delivery was found to be associated with advancing maternal age and previous pregnancies but not with cART. The use of heroin or methadone has been confirmed as a risk factor associated with severe SGA.

Stepwise non-pharmaceutical interventions and health system changes implemented as part of the COVID-19 response have had implications on the incidence, diagnosis, and reporting of other communicable diseases. Here, we established the impact of the COVID-19 outbreak response on gastrointestinal (GI) infection trends using routinely collected surveillance data from six national English laboratory, outbreak, and syndromic surveillance systems using key dates of governmental policy to assign phases for comparison between pandemic and historic data. Following decreases across all indicators during the first lockdown (March–May 2020), bacterial and parasitic pathogens associated with foodborne or environmental transmission routes recovered rapidly between June and September 2020, while those associated with travel and/or person-to-person transmission remained lower than expected for 2021. High out-of-season norovirus activity was observed with the easing of lockdown measures between June and October 2021, with this trend reflected in laboratory and outbreak systems and syndromic surveillance indicators. Above expected increases in emergency department (ED) attendances may have reflected changes in health-seeking behaviour and provision. Differential reductions across specific GI pathogens are indicative of the underlying routes of transmission. These results provide further insight into the drivers for transmission, which can help inform control measures for GI infections.

Chlorhexidine-containing cream is often used as an antimicrobial barrier to ascending urinary tract infection in patients with indwelling urethral catheters. The cream is dispensed in small tubes for personal use but repeated use of a tube still entails a potential infection hazard. The extent of cream contamination was analysed by emulsifying it in 1 % peptone broth with 1 % Tween-80 added as a wetting agent, and culturing quantitatively for bacteria and fungi by membrane filtration. Twenty-three per cent of cream samples and 35 % of swabs taken from outside the tube beneath the screw cap demonstrated microbial contamination. Isolates included potential pathogens such as enterococci, staphylococci, Proteus mirabilis, Pseudomonas aeruginosa, opportunists like Moraxella spp. and diphtheroids, and contaminants such as Bacillus spp., micrococci, and a mould of the genus Cladosporium. Contamination of cream with a particular bacterial strain was found to precede urinary tract infection with the same microbe. We recommend that chlorhexidine cream for this use be dispensed in single dose units to ensure sterility.

Prevalence of vancomycin-resistant enterococci (VRE) and use of daptomycin are increasing in Asia. To determine the prevalence of daptomycin non-susceptible enterococci (DNSE) and understand factors associated with reduced daptomycin susceptibility in VRE, we conducted a case-control study in a 1600-bed adult tertiary hospital in Singapore. All VRE isolates from inpatients in 2012 were tested for daptomycin susceptibility. Patients with VRE isolates of daptomycin minimum inhibitory concentration (MIC) ⩾3 µg/ml were classified as daptomycin-reduced susceptible VRE (DRS-VRE) and those with daptomycin MIC <3 µg/ml classified as daptomycin-susceptible VRE (DS-VRE). Medical records were reviewed for clinical and epidemiological data. None of 243 VRE isolates had MIC >4 µg/ml (DNSE). About half (135, 55%) had reduced susceptibility to daptomycin (MIC 3–4 µg/ml). None in the DS-VRE group had prior exposure to daptomycin. After adjusting for age, gender, comorbidity, hospitalization duration, surgical history, indwelling device use, and duration of antibiotic exposure in the prior 3 months, >1 movement between wards [odds ratio (OR) 0·35, 95% confidence interval (CI) 0·16–0·74, P = 0·006] and minocycline resistance (OR 0·45, 95% CI 0·25–0·84, P = 0·011) were independently associated with DRS-VRE. Our study suggests that daptomycin exposure, >1 movement between wards, and resistance to minocycline, were associated with reduced daptomycin susceptibility in VRE.

Using multivariable models, we compared whether there were significant differences between reported outbreak and sporadic cases in terms of their sex, age, and mode and site of disease transmission. We also determined the potential role of administrative, temporal, and spatial factors within these models. We compared a variety of approaches to account for clustering of cases in outbreaks including weighted logistic regression, random effects models, general estimating equations, robust variance estimates, and the random selection of one case from each outbreak. Age and mode of transmission were the only epidemiologically and statistically significant covariates in our final models using the above approaches. Weighing observations in a logistic regression model by the inverse of their outbreak size appeared to be a relatively robust and valid means for modelling these data. Some analytical techniques, designed to account for clustering, had difficulty converging or producing realistic measures of association.

In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan – a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.

The Cambridge University Health Service started work in October 1948. So far it has been restricted to preventive measures and has been confined to new entrants to the University on an entirely voluntary basis. The Service provides a clinical examination and a chest X-ray. A general survey of the scope of the Service and the results obtained have been given in the annual reports of the Senior Health Service Officer, Sir Alan Rook (1950, 1951). In addition to the original clinical records a Hollerith punched-card record system has been used since the inception of the Service to facilitate detailed investigations. In Appendix I to the first annual report mentioned above (Rook, 1950) I gave a few preliminary results on various physical measurements for the first 900 men examined. It has now been possible to complete a much more extensive investigation, the results of which are given in the present paper. In some cases this has been based on the completed records for the year 1948–9, while in others the records for the two years 1948–50 have been utilized. I have already given a brief summary of the contents of this paper in Appendix I to the second annual report (Rook, 1951).

A total of 160 consecutive isolates of Neisseria gonorrhoeae was collected over a 3-month period. They were tested for their susceptibility to penicillin, erythromycin and spectinomycin and the auxotype and the serotype determined. We have evaluated two sampling methods, the collection of every fifth isolate and the first 20 isolates (10 male and 10 female) each month, to determine whether either is representative of the total population. There was no significant difference between either method of sampling and the total for detecting the predominant auxotypes and serovars or the distributions in antibiotic susceptibility. It is possible to monitor major changes in a gonococcal population, particularly susceptibility to antibiotics, using a sample of the total population.

To assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and related parameters to the severity of coronavirus disease 2019 (COVID-19) symptoms. Clinical data from 38 COVID-19 patients who were diagnosed, treated and discharged from the Qishan Hospital in Yantai over the period from January to February 2020 were analysed. NLR and procalcitonin (PCT) were determined in the first and fourth weeks after their admission, along with the clinical characteristics and laboratory test results of these patients. Based on results as obtained on the first and fourth weeks after admission, five indices consisting of NLR, white blood cells, neutrophils, lymphocytes (LY) and monocytes (MON) were selected to generate receiver operating characteristic curves, while optimal cutoff values, sensitivities and specificities were obtained according to the Yuden index. Statistically significant differences in neutrophils, LY and the NLR were present in the severe vs. moderate COVID-19 group from the first to the fourth week of their hospitalisation. The cut-off value of NLR for predicting the severity of COVID-19 was 4.425, with a sensitivity of 0.855 and a specificity of 0.979. A statistically significant positive correlation was present between PCT and NLR in the severe group as determined within the first week of admission. NLR can serve as a predictor of COVID-19 disease severity as patients' progress from the first to the fourth week of their hospitalisation. The statistically significant positive correlation between levels of NLR and PCT in severe patients indicated that increases in NLR were accompanied with gradual increases in PCT.

1. The virulence of a given strain of B. aertrycke was tested on 54 occasions during the 3-year period, October 1926–October 1929. Each test was made by inoculating intra-peritoneally about 100 viable organisms into 20 parti-coloured mice, usually of 17–23 grm. in weight, drawn at random from the general laboratory stock. The average number of specific deaths caused by this procedure was 12·71 ± 3·39, but very marked deviations were noticeable, varying from a minimum of 5 to a maximum of 20. These deviations occurred without any observable regularity, and appeared to have no definite seasonal relationship. Evidence is brought to suggest that they were chiefly determined not by variations in the dosage or in the virulence of the strain, but by fluctuations in the resistance of the mice.

2. The meaning of the term “resistance” is discussed, and it is suggested that the term “fluctuating immunity” should be used to denote those variations in resistance which occur from time to time, and which are due to alterations in the physiological behaviour of the animal dependent on changing environmental conditions. This fluctuating immunity should be distinguished from innate, inherited, orgenetic immunity on the one hand and from acquired immunity on the other.

3. It is pointed out that the existence of fluctuations from time to time in the susceptibility of animals to infection renders fruitless any attempt to obtain an absolute measure of virulence. The most that can be done is to compare the relative virulence of two or more strains injected simultaneously.

In January 1940 British Ministry of Health circular 1307 proposed the introduction of mass childhood diphtheria immunization. This was a policy reversal after a decade during which opportunities for diphtheria prophylaxis were ignored, or resisted on grounds of cost. Diphtheria toxoid was to be the first of many centrally funded childhood immunizations in the UK and it set a pattern that has now held good for over 70 years. The circumstances in 1940 were particularly fortuitous, and diphtheria toxoid has since given successive generations of children a lifetime's protection from the disease; but difficulties have been experienced in introducing and evaluating some of the more recent immunizations, and in maintaining and justifying them in the face of parental scepticism and academic or pressure-group opposition, however ill-founded this may have been. The task of decision-making with regard to new candidate vaccines demands a careful balancing against the costs of the expected benefits during the recipient's lifespan.

The objective of the study was to assess whether genotypic characterization by means of DNA-fingerprinting pattern (DFP) and multilocus enzyme electrophoresis (MEE) profile as compared to phenotypic characterization would improve the differentiation of Neisseria meningitidis strains associated with outbreaks from strains associated with sporadic cases of meningococcal disease. In addition, the differentiation of serogroup C carrier strains from those associated with an outbreak of serogroup C meningococcal disease was investigated.

A total of 118 N. meningitidis strains were available for the study: 59 from patients involved in outbreaks of meningococcal disease (2 serogroup B and 2 serogroup C), 37 from patients considered to be sporadic cases and 22 serogroup C carrier strains.

Among the 59 strains from patients involved in outbreaks the 4 strains isolated from the patient registered as the first in each outbreak were designated the index strains. Among the remaining 55 outbreak strains 52 were either DFP-identical or DFP-indistinguishable when compared with the one relevant out of the 4 index strains. This was only the case for 17 of the 37 strains isolated from sporadic cases caused by the same serogroup of meningococci during the outbreak periods, and 5 of the 22 meningococcal strains isolated from healthy carriers. Among the 56 (52 + 4) DFP-identical or DFP-indistinguishable outbreak strains 5 different electrophoretic types were identified by MEE.

Among 59 assumed outbreak strains a total of 4 were identified as genotypically distinct. Among the 37 mainly DFP-indistinguishable or DFP-different strains from sporadic cases 17 different ETs were identified, and among the 22 mainly DFP-different carrier strains 13 different ETs were identified. Two strains among those selected from sporadic cases were identical to the outbreak strain. None of the local serogroup C carrier strains isolated during the outbreak of serogroup C disease were identical to the outbreak strain.

Both DNA-fingerprinting and MEE improved the differentiation of meningococci when compared with phenotypic characterization. The results indicate that tracing a virulent strain within an open group of contacts is irrelevant.