COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.

BACKGROUND: Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection. OBJECTIVES: To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023. METHODS: We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test. RESULTS: A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%. CONCLUSIONS: Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.

Antagonism between co-infecting gastrointestinal nematodes: A meta-analysis of experimental infections in Sheep.

Gastrointestinal nematodes (GIN) have enormous global impacts in humans, wildlife and grazing livestock. Within grazing livestock, sheep are of particular global importance and the economics and sustainability of sheep production are greatly constrained by GIN infections. Natural infections are composed of co-infections with multiple species, and while some past work suggests species can interact negatively with one another within the same host, there is wide variation in reported patterns. Here, we undertook a systematic literature search and meta-analysis of experimental GIN co-infections of sheep to determine whether these experimental studies support the hypothesis of antagonistic interactions between different co-infecting GIN, and test whether aspects of parasite biology or experimental design influence the observed effects. A systematic search of the literature yielded 4848 studies, within which, we identified 19 experimental sheep studies comparing post-mortem worm counts across two co-infecting GIN species. Meta-analysis of 67 effects obtained from these studies provides strong evidence for interactions between GIN species. There was wide variation in the strength and direction of these interactions, but the global effect was significantly antagonistic. On average, there was a decrease in the number of worms of one species when a co-infecting species was also present, relative to a mono-infection with that species alone. This effect was dependent on the infectious dose and was rapidly lost after anthelmintic treatment, suggesting that live worms are required for the effect to occur. Individual parasite species varied in the extent to which they both exerted, and were subject to, these interspecies interactions, and these differences are more complex than simply co-localisation within the gastrointestinal tract. Antagonistic interactions between co-infecting GIN may feedback into their epidemiology as well as potentially affecting the clinical impacts of infection. Furthermore, the consequences of these interactions may be heightened when clinical interventions affect only one species within the co-infecting network. Whilst it was not possible to identify the causes of variation between GIN species in the impact of co-infection, these findings point to new avenues for epidemiological, clinical and mechanistic research on GIN co-infections.

Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

Outcomes of a residential respite service for homeless people with tuberculosis in London, UK: a cross-sectional study.

BACKGROUND: Many countries are seeking to eliminate tuberculosis (TB), but incidence remains high in socially excluded groups such as people experiencing homelessness. There is limited research into the effectiveness of residential respite services (RRS), which provide accomodation and social and clinical support for homeless people with active TB. METHODS: We used a register of all cases of TB diagnosed in London between 1 January 2010 and 3 October 2019 to compare characteristics and outcomes of patients treated in an RRS with patients receiving standard care. The primary outcome was successful treatment completion. We used logistic regression to compare likelihood of completing treatment, and simulation to estimate the absolute change in treatment completion resulting from this service. RESULTS: A total of 78 homeless patients finished an episode of TB treatment at the RRS. Patients treated in the RRS were more likely than patients treated in standard care to have clinical and social risk factors including drug resistance, history of homelessness, drug or alcohol use, and need for directly observed therapy. After adjusting for these factors, patients treated in the RRS had 2.97 times the odds of completing treatment (95% CI = 1.44-6.96). Treatment ended in failure for 8/78 patients treated in the RRS (10%, 95% CI = 5%-20%). We estimated that in the absence of the RRS, treatment would have ended in failure for 17/78 patients (95% CI = 11-25). CONCLUSION: The residential respite service for homeless TB patients with complex social needs was associated with better treatment outcomes.

Liver fluke in beef cattle - Impact on production efficiency and associated greenhouse gas emissions estimated using causal inference methods.

We aimed to estimate 1) the marginal effect of liver fluke (Fasciola hepatica) infection on productivity of Scottish beef cattle, and 2) the associated greenhouse gas emissions intensity (GHG EI). Data comprised 240,065 abattoir records from NE Scotland from 2014 to 2017, including the presence or absence of lesions typical of liver fluke in the liver at the time of slaughter, from which we inferred liver fluke infection status. The retrospective analysis of abattoir records to estimate marginal effects of an exposure is complicated by the multi-dimensional, clustered nature of the datasets, which result in confounding of potential causal factors with the exposure. Causal inference methods are required to identify and correct for variation in background exposure. We constructed directed acyclic graphs (DAGs) of observed variables, including the potential confounders, breed, sex, breeder, finisher, season of birth and year of birth. We then applied inverse probability weighting (IPW) to adjust for variation among exposure risk and applied a doubly robust generalized linear model (DRGLM) to the weighted observations to estimate the marginal effect of fluke on the growth rate of animals and total days from birth until slaughter. We compared these estimates with the results of linear mixed effects (LME) models with the same variables, treating breeder and producer as random effects. To estimate GHG EI, we applied IPCC tier-2 type GHG calculations to the marginal effects estimated from IPW with DRGLM. The IPW with DRGLM model estimated that animals with active fluke lesions (adult fluke seen on postmortem inspection) gained 17 (95 % CI 12-22) g/d less saleable beef than animals with no lesions and no visible fluke. Animals with active fluke lesions were 11 (95 % CI 6.5-15) d older at slaughter weight than animals with no lesions. Animals with historic lesions in which there was scarring of the liver but in which no adult fluke were seen showed a wide variation in effect estimates, consistent with some misclassification. The effect estimates from LME models suggested slightly lower effects of fluke on growth rate and days to slaughter but with overlapping 95 % confidence intervals. Calculation of the associated GHG emissions suggest the EI of meat from a herd with no fluke is approximately 1.5 % lower than the same herd with fluke. Sustainably controlling liver fluke would have additional production benefits not included in this estimate and could therefore have a much greater impact on GHG EI in practice than demonstrated here.

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records.

BACKGROUND: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians' prescribing. But much of the information needed could be sourced from electronic health records (EHRs). OBJECTIVES: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. METHODS: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017-August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (n = 61679 admissions). RESULTS: We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4-3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison. CONCLUSIONS: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.

Tolerance of liver fluke infection varies between breeds and producers in beef cattle.

Liver flukes (Fasciola spp.) are important helminth parasites of livestock globally and cause substantial reductions in health and productivity of beef cattle. Attempts to control fluke have been thwarted by the difficulty of vaccine design, the evolution of flukicide resistance and the need to control the intermediate snail host. Mechanisms to reduce the impact of parasites on animal performance have typically focused on promoting host resistance - defined as the ability of the host to kill and remove the parasite from its system - and such strategies include improving protein nutrition or selective breeding for resistance. Organisms, however, have another broad mechanism for mitigating the impact of parasites: they can show tolerance, defined as the ability to maintain health or performance under increasing parasite burden. Tolerance has been studied in the plant literature for over a century, but there are very few empirical studies of parasite tolerance in livestock. In this study, we used data collected from >90 000 beef cattle to estimate the impact of the severity of liver fluke infection on performance and variation in tolerance of fluke. Severity of liver fluke infection was estimated using liver "fibrosis score" on a scale of 0-3 and performance estimated as (1) age at slaughter and (2) daily dead weight gain. Animals with higher fibrosis scores were slaughtered around 2 weeks later than animals with no fluke and gained around 10 g less weight per day. There was also considerable variation in these effects of fibrosis score, such that animals from different producers and breeds varied in their tolerance of fluke infection. While breeds did not vary in the association between fibrosis and age at slaughter, there was considerable variation among producers: high fibrosis score delayed slaughter by up to 50 days in some producers, but not at all in others. Meanwhile, there was support for variation in the slope of daily dead weight gain on fibrosis score among both breeds and producers, with some unaffected by high fluke scores and some breeds and producers experiencing a 20 g/day lower weight gain under high fluke scores. Our results point to the potential for both environmental and genetic variation in tolerance of liver fluke in cattle, paving the way for quantitative genetic and nutritional research into the feasibility of promoting tolerance as a disease mitigation strategy.

Precision worm control in grazing lambs by targeting group treatment based on performance of sentinels.

Given the economic impact of gastrointestinal nematode infection on livestock farming worldwide, and increasing anthelmintic resistance, it is imperative to develop practical, efficient and sustainable control strategies. Targeted selective treatment (TST), whereby anthelmintic treatments are administered to animals individually, based on selection criteria such as weight gain, has been shown to successfully maintain animal productivity whilst reducing the selection pressure for anthelmintic resistance and the economic cost of treatment in experimental and commercial settings. Despite the benefits of the TST approach, the equipment and time required to monitor animals individually make this strategy unsuitable for some farming enterprises. The sentinel group approach aims to maintain the benefits observed using TST whilst reducing these requirements. The study involved two experiments, each following a group of 80 lambs through their first grazing season. Anthelmintic treatment of the whole group was determined by monitoring the weight gain of identified sentinel lambs within it every 2 weeks: when 40% of the sentinel lambs failed to reach their weight gain targets, the whole group was treated. The sentinel lambs consisted of 45% of the group (n = 36) in experiment one and 20% (n = 16) in experiment two. A control group of 20 lambs was co-grazed with the main group during both experiments; in experiment one, the sentinel approach was compared with a TST approach, in which control lambs were treated on an individual basis in response to weight gain. In experiment two, the sentinel approach was compared with conventional prophylaxis, where all lambs in the control group were treated at strategic time points throughout the season (= strategic prophylactic treatment). The sentinel lambs were found to be representative of overall group performance regardless of the proportion of sentinels within the group: they recorded similar growth rates and reached weight gain targets simultaneously at each time point and overall. Live-weight gain was also similar between sentinel and control animals in both experiments. The findings of the current study suggest that monitoring sentinel lambs comprising 20% of a group of grazing lambs is sufficient to determine the need for anthelmintic treatment within the whole group, and that this approach maintains production in line with conventional or TST treatment regimes.

The relationship between clinical outcomes and empirical antibiotic therapy in patients with community-onset Gram-negative bloodstream infections: a cohort study from a large teaching hospital.

Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73-5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.

Lifetime prevalence of homelessness in housed people aged 55-79 years in England: its childhood correlates and association with mortality over 10 years of follow-up.

OBJECTIVES: Since 2010, the number of homeless people in the UK has increased, and homelessness in its different types has become a major public health problem. Housed older people with past experience of homelessness are an understudied population that can provide valuable insight into this problem. For this reason, we examined the lifetime prevalence of homelessness and its associations with childhood adversity and mortality in a national sample of older people. STUDY DESIGN: This is a longitudinal cohort study. METHODS: We studied 6649 housed individuals aged 55-79 years in 2007 from the English Longitudinal Study of Ageing (ELSA). We used logistic regression to model the association between adverse childhood experiences (ACE) and lifetime experience of homelessness (ever been homeless for ≥1 months) and Cox proportional hazards regression to model the prospective association between lifetime experience of homelessness and mortality. RESULTS: We identified 107 participants with lifetime experience of homelessness. We found a strong graded association between the number of ACE and lifetime experience of homelessness; participants with two ACE had 5.35 (95% confidence interval [CI]: 3.17-9.05) times greater odds of having experienced homelessness than those reporting none. Most ACE were individually associated with lifetime homelessness, but fewer remained so in the mutually adjusted model. Participants with lifetime experience of homelessness had 1.55 (95% CI: 1.01-2.37) times greater risk of mortality over a 10-year follow-up and after adjustment for covariates. CONCLUSIONS: Exposure to childhood adversity is associated with increased risk of experiencing homelessness. Older housed people with past experience of homelessness are at increased risk of mortality.

Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era.

Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research.

Accuracy of an automated system for tuberculosis detection on chest radiographs in high-risk screening.

SETTING: Tuberculosis (TB) screening programmes can be optimised by reducing the number of chest radiographs (CXRs) requiring interpretation by human experts. OBJECTIVE: To evaluate the performance of computerised detection software in triaging CXRs in a high-throughput digital mobile TB screening programme. DESIGN: A retrospective evaluation of the software was performed on a database of 38 961 postero-anterior CXRs from unique individuals seen between 2005 and 2010, 87 of whom were diagnosed with TB. The software generated a TB likelihood score for each CXR. This score was compared with a reference standard for notified active pulmonary TB using receiver operating characteristic (ROC) curve and localisation ROC (LROC) curve analyses. RESULTS: On ROC curve analysis, software specificity was 55.71% (95%CI 55.21-56.20) and negative predictive value was 99.98% (95%CI 99.95-99.99), at a sensitivity of 95%. The area under the ROC curve was 0.90 (95%CI 0.86-0.93). Results of the LROC curve analysis were similar. CONCLUSION: The software could identify more than half of the normal images in a TB screening setting while maintaining high sensitivity, and may therefore be used for triage.

Assessing hepatitis C spontaneous clearance and understanding associated factors-A systematic review and meta-analysis.

New advances in the treatment of hepatitis C provide high levels of sustained viral response but their expense limits availability in publicly funded health systems. The aim of this review was to estimate the proportion of patients who will spontaneously clear HCV, to identify factors that are associated with clearance and to support better targeting of directly acting antivirals. We searched Ovid EMBASE, Ovid MEDLINE and PubMed from 1 January 1994 to 30 June 2015 for studies reporting hepatitis C spontaneous clearance and/or demographic, clinical and behavioural factors associated with clearance. We undertook meta-analyses to estimate the odds of clearance for each predictor. Forty-three studies met the inclusion criteria, representing 20 110 individuals, and 6 of these studies included sufficient data to estimate spontaneous clearance. The proportion achieving clearance within 3, 6, 12 and 24 months following infection were, respectively, 19.8% (95% CI: 2.6%-47.5%), 27.9% (95% CI: 17.2%-41.8%), 36.1% (95% CI: 23.5%-50.9%) and 37.1% (95% CI: 23.7%-52.8%). Individuals who had not spontaneously cleared by 12 months were unlikely to do so. The likelihood of spontaneous clearance was lower in males and individuals with HIV co-infection, the absence of HBV co-infection, asymptomatic infection, black or nonindigenous race, nongenotype 1 infection, older age and alcohol or drug problems. This study suggests that patients continue to spontaneously clear HCV for at least 12 months following initial infection. However, injecting drug users are comparatively less likely to achieve clearance; thus, they should be considered a priority for early treatment given the continuing risks that these individuals pose for onwards transmission.

Seasonality of urinary tract infections in the United Kingdom in different age groups: longitudinal analysis of The Health Improvement Network (THIN).

Evidence regarding the seasonality of urinary tract infection (UTI) consultations in primary care is conflicting and methodologically poor. To our knowledge, this is the first study to determine whether this seasonality exists in the UK, identify the peak months and describe seasonality by age. The monthly number of UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions (N = 1 719 416) during 2008-2015 was extracted from The Health Improvement Network (THIN), a large nationally representative UK dataset of electronic patient records. Negative binomial regression models were fitted to these data to investigate seasonal fluctuations by age group (14-17, 18-24, 25-45, 46-69, 70-84, 85+) and by sex, accounting for a change in the rate of UTI over the study period. A September to November peak in UTI consultation incidence was observed for ages 14-69. This seasonality progressively faded in older age groups and no seasonality was found in individuals aged 85+, in whom UTIs were most common. UTIs were rare in males but followed a similar seasonal pattern than in females. We show strong evidence of an autumnal seasonality for UTIs in individuals under 70 years of age and a lack of seasonality in the very old. These findings should provide helpful information when interpreting surveillance reports and the results of interventions against UTI.

Evolutionary associations between host traits and parasite load: insights from Lake Tanganyika cichlids.

Parasite diversity and abundance (parasite load) vary greatly among host species. However, the influence of host traits on variation in parasitism remains poorly understood. Comparative studies of parasite load have largely examined measures of parasite species richness and are predominantly based on records obtained from published data. Consequently, little is known about the relationships between host traits and other aspects of parasite load, such as parasite abundance, prevalence and aggregation. Meanwhile, understanding of parasite species richness may be clouded by limitations associated with data collation from multiple independent sources. We conducted a field study of Lake Tanganyika cichlid fishes and their helminth parasites. Using a Bayesian phylogenetic comparative framework, we tested evolutionary associations between five key host traits (body size, gut length, diet breadth, habitat complexity and number of sympatric hosts) predicted to influence parasitism, together with multiple measures of parasite load. We find that the number of host species that a particular host may encounter due to its habitat preferences emerges as a factor of general importance for parasite diversity, abundance and prevalence, but not parasite aggregation. In contrast, body size and gut size are positively related to aspects of parasite load within, but not between species. The influence of host phylogeny varies considerably among measures of parasite load, with the greatest influence exerted on parasite diversity. These results reveal that both host morphology and biotic interactions are key determinants of host-parasite associations and that consideration of multiple aspects of parasite load is required to fully understand patterns in parasitism.

Evidence for increasing severity of community-onset boils and abscesses in UK General Practice.

In England, hospital admissions for severe staphylococcal boils and abscesses trebled between 1989 and 2004. We investigated this trend using routine data from primary and secondary care. We used The Health Improvement Network (THIN), a large primary-care database and national data on hospital admissions from Hospital Episode Statistics (HES). Time trends in the incidence of primary-care consultations for boils and abscesses were estimated for 1995-2010. HES data were used to calculate age-standardized hospital admission rates for boils, abscesses and cellulitis. The incidence of boil or abscess was 450 [95% confidence interval (CI) 447-452] per 100 000 person-years and increased slightly over the study period (incidence rate ratio 1·005, 95% CI 1·004-1·007). The rate of repeat consultation for a boil or abscess increased from 66 (95% CI 59-73) per 100 000 person-years in 1995 to peak at 97 (95% CI 94-101) per 100 000 person-years in 2006, remaining stable thereafter. Hospital admissions for abscesses, carbuncles, furuncles and cellulitis almost doubled, from 123 admissions per 100 000 in 1998/1999 to 236 admissions per 100 000 in 2010/2011. Rising hospitalization and recurrence rates set against a background of stable community incidence suggests increased disease severity. Patients may be experiencing more severe and recurrent staphylococcal skin disease with limited treatment options.

Early reproductive investment, senescence and lifetime reproductive success in female Asian elephants.

The evolutionary theory of senescence posits that as the probability of extrinsic mortality increases with age, selection should favour early-life over late-life reproduction. Studies on natural vertebrate populations show early reproduction may impair later-life performance, but the consequences for lifetime fitness have rarely been determined, and little is known of whether similar patterns apply to mammals which typically live for several decades. We used a longitudinal dataset on Asian elephants (Elephas maximus) to investigate associations between early-life reproduction and female age-specific survival, fecundity and offspring survival to independence, as well as lifetime breeding success (lifetime number of calves produced). Females showed low fecundity following sexual maturity, followed by a rapid increase to a peak at age 19 and a subsequent decline. High early life reproductive output (before the peak of performance) was positively associated with subsequent age-specific fecundity and offspring survival, but significantly impaired a female's own later-life survival. Despite the negative effects of early reproduction on late-life survival, early reproduction is under positive selection through a positive association with lifetime breeding success. Our results suggest a trade-off between early reproduction and later survival which is maintained by strong selection for high early fecundity, and thus support the prediction from life history theory that high investment in reproductive success in early life is favoured by selection through lifetime fitness despite costs to later-life survival. That maternal survival in elephants depends on previous reproductive investment also has implications for the success of (semi-)captive breeding programmes of this endangered species.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.