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Introduction Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. Methods A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. Key findings Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. Conclusion Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources– such as upscaled screening– to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

Background. The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data. Methods. All subjects with laboratory‐confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory‐confirmed case of MenC disease occurring ⩾10 days after the subject’s last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease. Results. Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1‐fold higher for SBA titers [P=.03] and 3.2‐fold higher for AIs [P=.001]). Conclusions. The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long‐term protection for MCC vaccines than the ability to generate a booster response on exposure.

Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. Discussion This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored. Trial registration Current Controlled Trial ISRCTN 37666216

Two hundred health care workers in England and Wales were vaccinated with the Lister/Elstree strain of the vaccinia virus, and completed health diaries for 21 days or until the lesion had scabbed over. Pain and temperature were measured daily, and all other symptoms recorded freehand by the vaccinee. One hundred and forty two (71%) vaccinees reported pain, of which 25% considered it to be moderate or severe; 32 vaccinees (16%) recorded a temperature of >37.7 °C, two of which exceeded 39 °C. Other, mainly trivial, adverse events were common; itch was reported in 72%, erythema in 27%, axillary pain or lymphadenopathy in 38%, malaise or flu-like symptoms in 40% and headache in 23%. The incidences of minor adverse events were lower in re-vaccinees, compared with naïve vaccine recipients, significantly so in the case of erythema and general malaise ( p = 0.001 and 0.006, respectively), perhaps reflecting pre-existing immunity. Major adverse events occurred in two vaccinees (hospital admission, one with cellulitis and one with headache and possible encephalitis), and a further five were treated with antibiotics for local cellulitis. This is the first study to report results derived from active follow-up by diaries in recipients of the Lister/Elstree strain of vaccinia, and to document reductions in trivial adverse events in re-vaccinees.

Canine Chagas disease, caused by the protozoan parasite Trypanosoma cruzi , is increasingly recognized as a health concern for dogs in the USA, and infected dogs may signal geographic regions of risk for human disease. Dogs living in multi-dog kennel environments (kennels with more than one dog) where triatomine vectors are endemic may be at high risk for infection. We monitored a cohort of 64 T . cruzi -infected and uninfected dogs across 10 kennels in Texas, USA, to characterize changes in infection status over one year. We used robust diagnostic criteria in which reactivity on multiple independent platforms was required to be considered positive. Among the 30 dogs enrolled as serologically- and/or PCR-positive, all but one dog showed sustained positive T . cruzi diagnostic results over time. Among the 34 dogs enrolled as serologically- and PCR-negative, 10 new T . cruzi infections were recorded over a 12-month period. The resulting incidence rate for dogs initially enrolled as T . cruzi- negative was 30.7 T . cruzi infections per 100 dogs per year. This study highlights the risk of T . cruzi infection to dogs in kennel environments. To protect both dog and human health, there is an urgent need to develop more integrated vector control methods as well as prophylactic and curative antiparasitic treatment options for T . cruzi infection in dogs.

As carnivorans rely heavily on their head and jaws for prey capture and handling, skull morphology and bite force can therefore reflect their ability to take larger or more difficult-to-handle prey. For 568 feral and stray cats (Felis catus), we recorded their demographics (sex and age), source location (feral or stray) and morphological measures (body mass, body condition); we estimated potential bite force from skull measurements for n = 268 of these cats, and quantified diet composition from stomach contents for n = 358. We compared skull measurements to estimate their bite force and determine how it varied with sex, age, body mass, body condition. Body mass had the strongest influence of bite force. In our sample, males were 36.2% heavier and had 20.0% greater estimated bite force (206.2 ± 44.7 Newtons, n = 168) than females (171.9 ± 29.3 Newtons, n = 120). However, cat age was the strongest predictor of the size of prey that they had taken, with older cats taking larger prey. The predictive power of this relationship was poor though (r2 < 0.038, p < 0.003), because even small cats ate large prey and some of the largest cats ate small prey, such as invertebrates. Cats are opportunistic, generalist carnivores taking a broad range of prey. Their ability to handle larger prey increases as the cats grow, increasing their jaw strength, and improving their hunting skills, but even the smallest cats in our sample had tackled and consumed large and potentially ‘dangerous’ prey that would likely have put up a defence.

Background Chagas disease is increasingly recognized in the southern U.S., where triatomine vectors transmit Trypanosoma cruzi among wildlife and domestic dogs with occasional vector spillover to humans. As in humans, clinical outcome in dogs is variable, ranging from acute death to asymptomatic infections or chronic heart disease. In order to characterize cardiac manifestations of T. cruzi infections, we tracked a cohort of naturally-infected dogs and a matched cohort of uninfected dogs. We hypothesized that selected measures of cardiac disease (abnormal rate, abnormal rhythm, and elevated cardiac troponin I (cTnI; a biomarker of cardiac injury)) would occur more commonly in infected than uninfected dogs matched by age, breed, sex and location. In addition to the clearly positive and negative dogs, we specifically tracked dogs with discordant test results across three independent serological assays to gather clinical data that might elucidate the infection status of these animals and inform the utility of the different testing approaches. Results We placed an ambulatory ECG monitor (Holter) on 48 government working dogs and analyzed 39 successful recordings that met length and quality criteria from 17  T. cruzi -infected, 18 uninfected dogs and 4 dogs with discordant results. Overall, 76.5% of positive, 100.0% of discordant, and 11.1% of negative dogs showed >  1 ECG abnormality ( p  < 0.0001), and positive and discordant dogs had a higher mean number of different types of ECG abnormalities than negative dogs ( p < 0.001–0.014). The most common cardiac abnormalities included supraventricular and ventricular arrhythmias and atrioventricular block. Positive dogs had higher serum concentrations of cTnI than both negative dogs ( p = 0.044) and discordant dogs ( p  = 0.06). Based on dog handler reports, nearly all (4/5; 80%) dogs with reported performance decline or fatigue were T. cruzi -infected dogs. Conclusions Further understanding cardiac manifestations in dogs naturally infected with T. cruzi is critical for prognostication, establishing a baseline for drug and vaccine studies, and better understanding of zoonotic risk.