Following the end of universal testing in the UK, hospital admissions are a key measure of COVID-19 pandemic pressure. Understanding leading indicators of admissions at the National Health Service (NHS) Trust, regional and national geographies help health services plan for ongoing pressures. We explored the spatio-temporal relationships of leading indicators of hospitalisations across SARS-CoV-2 waves in England. This analysis includes an evaluation of internet search volumes from Google Trends, NHS triage calls and online queries, the NHS COVID-19 app, lateral flow devices (LFDs), and the ZOE app. Data sources were analysed for their feasibility as leading indicators using Granger causality, cross-correlation, and dynamic time warping at fine spatial scales. Google Trends and NHS triages consistently temporally led admissions in most locations, with lead times ranging from 5 to 20 days, whereas an inconsistent relationship was found for the ZOE app, NHS COVID-19 app, and LFD testing, which diminished with spatial resolution, showing cross-correlation of leads between –7 and 7 days. The results indicate that novel surveillance sources can be used effectively to understand the expected healthcare burden within hospital administrative areas though the temporal and spatial heterogeneity of these relationships is a key determinant of their operational public health utility.

Haematopoietic stem cell transplant (HSCT) recipients lose immune memory of exposure to infectious agents and vaccines accumulated throughout their lifetime and therefore need to be revaccinated. We aimed to evaluate the influence of different factors on hepatitis A virus (HAV) immunity in both child and adult HSCT recipients living in an intermediate endemic region, Turkey. Eighty patients (age range 2·5–57 years) who had HAV serology prior to HSCT were evaluated. The prevalence of HAV seropositivity was 85% (n=68) before HSCT. There was no history of HAV vaccination before HSCT in children and HAV vaccine was not available in Turkey 10 years ago, so it was assumed that all seropositive patients reflected natural immunity. After the exclusion of six patients with autologous HSCT, the remaining 62 seropositive and allogeneic patients were included in this retrospective study. The duration of HAV seropositivity was estimated using the Kaplan–Meier method, log-rank analysis and Cox regression models. Estimated mean time to loss of HAV seropositivity was 48·6 months after transplantation. Patients who were older (⩾18 years) at transplantation and who had older (⩾18 years) donors became seronegative later (P<0·05). Cox backward-stepwise regression confirmed that older age of recipient at transplantation was the only significant parameter for HAV seropositivity (P<0·05). HAV-inactivated vaccine might be recommended later to older HSCT recipients in intermediate endemic regions.

The impact of hepatitis B virus (HBV) infection on clinical outcomes of coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study is to explore this impact. For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (VIP), and Wan Fang database for articles between 1 January 2020 and 1 February 2023. We used the Newcastle–Ottawa Quality Assessment to evaluate the study’s quality. A random-effects meta-analysis was performed utilising the rates of severe/critical illness and death in COVID-19 patients with and without HBV infection. Eighteen studies with a total of 40,502 participants met the inclusion criteria. The meta-analysis showed that compared to those without HBV infection, COVID-19 patients with HBV were at increased risk of mortality (OR = 1.65, I2 = 58%, and 95% CI 1.08–2.53) and severity (OR = 1.90, I2 = 44%, and 95% CI 1.62–2.24). The region and gender may influence the outcomes of COVID-19 patients with HBV infection, but it requires more global data to confirm. In conclusion, HBV infection is significantly linked to an increased risk of severity and mortality in COVID-19.

Despite high exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), the predictors for seropositivity in the context of husbandry practices for camels in Eastern Africa are not well understood. We conducted a cross-sectional survey to describe the camel herd profile and determine the factors associated with MERS-CoV seropositivity in Northern Kenya. We enrolled 29 camel-owning households and administered questionnaires to collect herd and household data. Serum samples collected from 493 randomly selected camels were tested for anti-MERS-CoV antibodies using a microneutralisation assay, and regression analysis used to correlate herd and household characteristics with camel seropositivity. Households reared camels (median = 23 camels and IQR 16–56), and at least one other livestock species in two distinct herds; a home herd kept near homesteads, and a range/fora herd that resided far from the homestead. The overall MERS-CoV IgG seropositivity was 76.3%, with no statistically significant difference between home and fora herds. Significant predictors for seropositivity (P ⩽ 0.05) included camels 6–10 years old (aOR 2.3, 95% CI 1.0–5.2), herds with ⩾25 camels (aOR 2.0, 95% CI 1.2–3.4) and camels from Gabra community (aOR 2.3, 95% CI 1.2–4.2). These results suggest high levels of virus transmission among camels, with potential for human infection.

This paper describes a solid-phase microtitre plate enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to equine influenza viruses. Using egg-grown influenza viruses as the antigens attached to the solid phase, crossreactions were observed between an H7N7 equine virus (designated A1) and an H3N8 equine influenza virus (designated A2) when untreated antisera were tested. Absorption of antisera with egg-grown A/Porcine/Shope/1/33 influenza virus eliminated cross-reactive antibodies so that specific detection of anti-equine influenza A1 or A2 antibodies was possible.

Examination of horse sera following vaccination with A1 and/or A2 isolates showed that antibodies were produced against antigen associated with egg allantoic fluid as well as against virus. Such antibodies were eliminated following the absorption of antisera with porcine influenza virus. Results using sera from horses with known vaccination histories confirmed that the ELISA preferentially detected antibodies homologous to the antigen attached to the solid phase and methods to evaluate the current serological state of individual horses by relating the titres of specific antibodies against equine influenza A1 and A2 isolates are shown. This ELISA provides a simple and rapid method of assessing specific antibodies from horse sera and offers advantages over the ‘routine’ HI and SRH assessments since it gives high precision, is economical of reagents and has the capacity to handle large numbers of serum samples.

Outbreaks of epidemic keratoconjunctivitis have occurred among workers in shipyards and other industrial concerns in the West of Scotland in 1956, 1967 and 1971–72. In the most recent episode 220 persons were known to be affected and those mainly involved were shipyard personnel working on the open decks of ships under construction; only a few non-industrial workers were affected. As in previous outbreaks adenovirus type 8 was shown to be the causal organism. It is likely that spread of the virus was probably facilitated in some of the patients by such procedures as first aid measures to remove foreign bodies from the eye. A survey of the family contacts of those affected in 1971–72 revealed that only 2% were secondarily infected. This was probably due to propaganda measures to discourage the use of communal face towels, etc.

Despite close virological surveillance over a period of 6 years of patients attending opthalmic clinics in the West of Scotland, there is as yet no clue to the whereabouts of adenovirus type 8 during interepidemic periods. It is suggested that travellers might be responsible for the introduction of the infection into an area.

To examine evidence of positive antibodies against immunogenic proteins of Anaplasma phagocytophilum in patients with other tick-borne infections and to diagnose possible co-infections, 412 serum specimens were tested by immunoblotting using three specific Anaplasma antigens: surface proteins p44 and Asp62 and outer membrane protein A (OmpA). In total, 284 serum samples from children with Lyme borreliosis and 12 serum samples from children with tick-borne encephalitis were tested. Sera from patients with viral aseptic meningitis (n = 47) and from blood donors (n = 69) were used as controls. Among all serum specimens from patients with tick-borne infections submitted for this study, six samples (2·0%) showed positive IgM reactions and seven samples (2·4%) were IgG positive for A. phagocytophilum by immunoblot. Borderline reactivity was found in 30 samples (10·14%) for IgM and 36 samples (12·2%) for IgG. The difference between patients and blood donors was statistically significant for IgM (P = 0·006) and for IgG (P = 0·0007) antibodies. A statistically significant result was obtained for IgG (P = 0·02) but not for IgM between patients and children with aseptic meningitis. Immunoblot using three specific antigens provides novel information about the positivity of antibodies to A. phagocytophilum in children with other tick-borne infections. Taking into account clinical and laboratory findings of children despite antibody positivity, no case of human granulocytic anaplasmosis was demonstrated.

A simple method, applicable in routine work, for simultaneous air sampling of total bacteria, on serum agar, and Str. salivarius and Bact. coli on specific media, is described.

Simultaneous air sampling including, in addition to detection of total bacteria, Str. salivarius and Bact. coli as indicators of buccal and faecal air-borne bacteria, respectively, reveals the kind and source of air-borne pollution much better than the simple total bacterial count.

The air in various medical and public institutions was examined; the results are presented and discussed. The air pollution of the premises examined was relatively high, especially in the operating theatres. The air of infants' wards was found to be heavily polluted with Bact. coli as a result of poor nursing technique and this might have had bearing on the epidemic of infant diarrhoea.

Tuberculosis (TB) remains a global public health threat. Misdiagnosis and delayed therapy of sputum smear-negative TB can affect the treatment outcomes and promote pathogen transmission. The application of Xpert MTB/RIF assay in bronchoalveolar lavage fluid (BALF) has been recommended but needs clinical evidence. We carried out a prospective study in the Nanjing Public Health Medical Center from September 2018 to August 2019. Pulmonary tuberculosis (PTB) patients were enrolled in the study if they had negative results of sputum smear. We compared the performance of Xpert MTB/RIF assay in sputum and BALF using sputum culture as the reference. In addition to this, we applied parallel tests using sputum culture, sputum-based Xpert MTB/RIF assay and BALF-based Xpert MTB/RIF assay to jointly detect smear-negative PTB using clinical diagnosis as the reference. With mycobacterial culture as the reference standard, Xpert MTB/RIF of BALF showed a higher sensitivity (14/16, 87.5%), but a relatively lower specificity (57/92, 62.0%). Xpert MTB/RIF of sputum showed relatively lower sensitivity (6/10, 60.0%) and higher specificity (63/88, 71.6%). Compared with sputum culture, Xpert MTB /RIF assay reduced the median detection time of MTB from 30 to 0 days, which significantly shortened the diagnosis time of the smear-negative TB patients. Among the combined detections, the positive detection proportion was improved with significant differences comparing with sputum culture only, from 11.1% (10/90) to 46.7% (42/90) (P < 0.05). Our study showed Xpert MTB/RIF in BALF had a better performance in detecting MTB of smear-negative patients.

Nucleos(t)ide analogues (NAs) are widely used for antiviral therapy in patients with chronic hepatitis B (CHB), but real-world data on treatment patterns and long-term clinical outcomes are not always available. Using data from electronic medical records between January 2011 and December 2016 in Shanghai, China, we evaluated patient characteristics, treatment patterns and clinical outcomes in patients with CHB. There were 6688 patients in the study cohort. The incidences of cirrhosis and hepatocellular carcinoma (HCC) were 41.0‰ and 6.8‰ person-years, respectively. There were more cirrhosis and HCC cases among patients who had shorter NA treatment duration (<365 days), or who were less compliant (<80%). In addition, increased risk of cirrhosis and HCC was observed in patients who did not achieve hepatitis B surface antigen (HBsAg) loss/seroconversion. Moreover, patients with cirrhosis developed after antiviral treatments had a higher incidence of HCC (adjusted hazard ratio 15.86, 95% confidence interval 7.35–34.24). Good compliance with treatment and longer treatment duration significantly decreased the risk of developing cirrhosis and HCC. HBsAg loss seemed to be a protective factor for cirrhosis/HCC in NAs-treated patients with CHB, and cirrhosis was a confirmed risk factor for HCC development as expected.

We conducted a case-control study based on 884 laboratory-confirmed sporadic Salmonella cases reported to the German infectious disease notification system. For controls, we recruited 510 rotavirus cases via the same system. Univariable and multivariable logistic regression analyses were performed separately for children aged 0–3 years and 4–14 years. In both age groups, the highest odds ratios (OR) were found for raw ground pork consumption [0–3 years: OR 8·6, 95% confidence interval (CI) 2·4–30·8; 4–14 years: OR 4·5, 95% CI 1·1–19]. Further risk factors were exposure to animals (OR 1·6, 95% CI 1·1–2·1), consumption of poultry (OR 1·5, 95% CI 1·1–2·1), food items containing eggs (OR 1·5, 95% CI 1·1–2) and black pepper (OR 1·7, 95% CI 1·1–3·5) in children aged 0–3 years, and consumption of uncooked pork sausage (OR 3·6, 95% CI 1·4–9·3) in children aged 4–14 years. This study highlights the significance of raw pork products (‘Mett’ in German) as risk factors for sporadic salmonellosis in children in Germany.

The time to positivity (TTP) of blood cultures has been considered a predictor of clinical outcomes for bacteremia. This retrospective study aimed to determine the clinical value of TTP for the prognostic assessment of patients with Escherichia coli bacteremia. A total of 167 adult patients with E.coli bacteremia identified over a 22-month period in a 3500-bed university teaching hospital in China were studied. The standard cut-off TTP was 11 h in the patient cohort. The septic shock occurred in 27.9% of patients with early TTP (⩽11 h) and in 7.1% of those with a prolonged TTP (>11 h) (P = 0.003). The mortality rate was significantly higher for patients in the early than in the late group (17.7% vs. 4.0%, P < 0.001). Multivariate analysis showed that an early TTP (OR 4.50, 95% CI 1.70–11.93), intensive care unit admission (OR 8.39, 95% CI 2.01–35.14) and neutropenia (OR 4.20, 95% CI 1.55–11.40) were independently associated with septic shock. Likewise, the independent risk factors for mortality of patients were an early TTP (OR 3.80, 95% CI 1.04–12.90), intensive care unit admission (OR 6.45; 95% CI 1.14–36.53), a Pittsburgh bacteremia score ⩾2 (OR 4.34, 95% CI 1.22–15.47) and a Charlson Comorbidity Index ⩾3 (OR 11.29, 95% CI 2.81–45.39). Overall, a TTP for blood cultures within 11 h appears to be associated with worse outcomes for patients with E.coli bacteremia.

1. An outbreak of ‘Winter Vomiting Disease’ is described involving women at a University Hall of Residence. Of the 165 women exposed, 74 vomited in the first 24 hr., and 17 more over the next 4 days.

2. Public health investigations were negative.

3. On the hypothesis that the vomiting was at least partly hysterical it was predicted that the affected would have higher N scores than the unaffected on the Eysenck Personality Inventory; that they would have a higher frequency of past attendance at the University Health Centre; and that they would be non-randomly distributed through the Hall and its annexes. All these predictions proved to be incorrect.

4. There is some slight but consistent evidence to suggest that there is a neurotic component in the small group of 28 who felt nauseated but did not vomit.

5. The histogram of time of vomiting has two peaks. It is shown that 71 out of the first 74 cases can be accounted for on the hypothesis of contamination of the food at both lunch and dinner on the first day of the outbreak, with the mean response coming 7 hr. after eating.

6. It is suggested that these results make a food-borne agent a more likely explanation of ‘Winter Vomiting Disease’ than the currently favoured airborne virus acting via the central nervous system.

The costs involved in the psychiatric side of this investigation were defrayed by a grant from the Clinical Research Committee of the Middlesex Hospital. We would like to thank the Chairman and members of the Committee for making these funds available and for their interest and confidence. We would also like to thank Dr A. W. Beard, Consultant Physician at the Middlesex Hospital for his advice and support.

Evidence for influenza-associated excess mortality in the three centuries before the 20th has been sought from parish burial registers in Cumbria, Devon, Dyfed, East Anglia, Gloucestershire and Northumbria, compared with inter-epidemic years. Most of the registers showed excess of burials concordant with eight historic influenza epidemics.

Comparison of the dates of these epidemics, deduced from the burials data in different areas, showed a rate of spread difficult to reconcile with direct personto-person spread of influenza from the sick. An alternative explanation based on development of latency of the virus in the sick person and subsequent seasonal reactivation is discussed.

The high rate of chronic hepatitis C (CHC) was one of the key issues of global public health concern. Interferon (IFN)-λ relevant genes were in the antiviral treatment pathway, not only influenced hepatitis C virus (HCV) spontaneous clearance, but also affected the IFN-mediated viral clearance. The aim of this study was to identify the association of interleukin 28B (IL28B), myxovirus resistance A (MxA) gene polymorphisms with HCV spontaneous clearance and therapeutic response in Chinese CHC patients. IL28B and MxA gene genotypes were detected among 231 CHC carriers, 428 subjects with HCV spontaneous clearance and 662 CHC patients with pegylated IFN-α and ribavirin (pegIFN-α/RBV) treatment. Patients with MxA rs2071430 TT genotype were more likely to develop HCV infection chronicity (additive model: odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.48, P = 0.042). IL28B rs1298075 variant genotypes (additive model: OR 0.58, 95% CI 0.34–0.98, P = 0.040) and MxA rs17000900 variant genotypes (additive model: OR 0.54, 95% CI 0.30–0.99, P = 0.048) were less likely to achieve a sustained virological response. The life table indicated that patients with IL28B rs1298075 AG genotype were slower to achieve a viral load <500 copies/ml (P = 0.018). During the treatment, the downward trend in viral load was different among each IL28B rs1298075 genotype, especially in subgroup with a baseline HCV-RNA >106 copies/ml (all P < 0.05). This study illustrated that the carriage of IL28B rs12980275 AA had a positive effect on treatment response to pegIFN-α/RBV among Chinese CHC patients.

The objectives of this study were to characterize methicillin-resistant Staphylococcus aureus (MRSA) blood culture isolates and to determine their relative importance in both nosocomial and community-acquired infections. A total of 535 MRSA blood culture isolates were analysed. In vitro susceptibility to 14 agents was determined. The genes nuc, mecA and coding for PVL toxin were identified by PCR. All isolates were characterized by PFGE or spa typing to assess their genomic relationships. Most MRSA isolates were retrieved from nosocomial bloodstream infections (474, 89%) and were of the CMRSA2 genotype. Healthcare-associated (HA)-MRSA bloodstream infections were associated with older age (70–89 years, P = 0·002) and most often secondary to central line infections (P = 0·005). Among MRSA strains associated with community-acquired (CA)-MRSA, 28·8% were isolated in intravenous drug users. CA-MRSA genotypes were more frequently found in young adults (20–39 years, P < 0·0001) with skin/soft tissue as the primary sources of infection (P = 0·006). CMRSA10 genotype was the predominant CA-MRSA strain. All MRSA isolates were susceptible to doxycycline, tigecycline, trimethoprim/sulfamethoxazole and vancomycin. Both the presence of the genes coding for PVL toxin (89·8%) and susceptibility to clindamycin (86·5%) were predictive of CA-MRSA genotypes. Whereas in the USA, HA-MRSA have been replaced by USA300 (CMRSA10) clone as the predominant MRSA strain type in positive blood cultures from hospitalized patients, this phenomenon has not been observed in the province of Quebec.

1. The history of a typical sanguineus-borne human case of typhus is given, together with the results of intraperitoneal inoculation of material from the initial lesion into guinea-pigs.

2. This material in the earlier inoculations caused a high mortality rate among guinea-pigs, and is characterized from the other material obtained from rats and fleas by the swing of temperatures between morning and evening.

3. Three cases of non-lesion typhus occurred in a brewery heavily infested with rats and fleas, the patients affirming they had been bitten only by fleas.

A high rat infestation was noted and a Xenopsylla index of 15·0 per rat.

4. Inoculation into guinea-pigs of emulsified brain and testicle material from Rattus rattus trapped at this typhus focus, and of emulsified fleas from the rats, resulted in the establishment of a strain of virus which produced a typhus-like syndrome in guinea-pigs.

5. Infection of guinea-pigs with strains of virus from rats, ticks and fleas, has been secured without any difficulty in Kenya, and it has not been found necessary to keep guinea-pigs on vitamin-deficient diets.

6. Typical scrotal reaction has been observed in the majority of guinea-pigs inoculated. The onset is generally sudden and coincides with the rise in temperature. Subsidence of the swelling and inflammation is gradual over about 3 days.

7. Loss in weight is not a marked feature of the forms of virus encountered in Kenya.

8. Post-mortem appearances in the rat-and flea-forms differ from those of the tick-type mainly in less ascites and slight enlargement of the spleen.

The main objective of this paper is to address the following question: are the containment measures imposed by most of the world governments effective and sufficient to stop the epidemic of COVID-19 beyond the lock-down period? In this paper, we propose a mathematical model which allows us to investigate and analyse this problem. We show by means of the reproductive number, ${\cal R}_0$ that the containment measures appear to have slowed the growth of the outbreak. Nevertheless, these measures remain only effective as long as a very large fraction of population, p, greater than the critical value $1-1/{\cal R}_0$ remains confined. Using French current data, we give some simulation experiments with five scenarios including: (i) the validation of model with p estimated to 93%, (ii) the study of the effectiveness of containment measures, (iii) the study of the effectiveness of the large-scale testing, (iv) the study of the social distancing and wearing masks measures and (v) the study taking into account the combination of the large-scale test of detection of infected individuals and the social distancing with linear progressive easing of restrictions. The latter scenario was shown to be effective at overcoming the outbreak if the transmission rate decreases to 75% and the number of tests of detection is multiplied by three. We also noticed that if the measures studied in our five scenarios are taken separately then the second wave might occur at least as far as the parameter values remain unchanged.

The molecular properties of the circulating causative agents of hand, foot and mouth disease (HFMD) in Wuxi remain unclear, posing diagnostic and prevention challenges. Additionally, in several regions of mainland China, the EV71 immunisation drastically reduced related cases and altered the HFMD pathogen spectrum, while the precise situation in Wuxi remained unknown. To address these issues, paediatric HFMD cases diagnosed in the clinic were enrolled and anal swabs were acquired in the spring of 2019. The 5′-UTR and VP1 genes were interpreted using RT-nPCR with degenerate primers to confirm their genotypes. Following that, the entire genome sequences of each viral type were recovered, allowing for the interpretation of several molecular properties. A total of 249 clinically confirmed HFMD cases had their anal swabs taken for viral identification, from which the genome sequences of seven genotypes were recovered. Coxsackievirus A16 is the most prevalent type, followed by Coxsackievirus A6, A10, A2, A4, A5 and Echovirus 11, all of which were genetically determined for the first time in Wuxi. Phylogenetic and recombination analyses were used to evaluate their evolutionary relationships with other strains found in other regions. Noticeably, a CVA16 subtype, responsible for a large proportion of the observed cases, phylogenetically clustered within clade B1a along with some strains from other countries, was the first one to be reported in China. Furthermore, some recombination events were inferred from strains detected in sporadic cases, particularly the recombination between CVA2 and CVA5 strains. Our investigation elucidated the multiple molecular characteristics of the HFMD causal enterovirus strains in Wuxi, underlining the potential hazards associated with these circulating viral types in the population and aiding in future surveillance and prevention of this disease.

Two fatal drumming-related inhalational anthrax incidents occurred in 2006 and 2008 in the UK. One individual was a drum maker and drummer from the Scottish Borders, most likely infected whilst playing a goat-skin drum contaminated with Bacillus anthracis spores; the second, a drummer and drum maker from East London, likely became infected whilst working with contaminated animal hides.

We have collated epidemiological and environmental data from these incidents and reviewed them alongside three similar contemporaneous incidents in the USA. Sampling operations recovered the causative agent from drums and drum skins and from residences and communal buildings at low levels. From these data, we have considered the nature of the exposures and the number of other individuals likely to have been exposed, either to the primary infection events or to subsequent prolonged environmental contamination (or both).

Despite many individual exposures to widespread low-level spore contamination in private residences and in work spaces for extended periods of time (at least 1 year in one instance), only one other individual acquired an infection (cutaneous). Whilst recognising the difficulty in making definitive inferences from these incidents to specific residual contamination levels, and by extending the risk to public health, we believe it may be useful to reflect on these findings when considering future incident management risk assessments and decisions in similar incidents that result in low-level indoor contamination.