Although African horse sickness (AHS) can cause up to 95% mortality in horses, naïve animals can be protected by vaccination against the homologous AHSV serotype. Genome segment 2 (Seg-2) encodes ...outer capsid protein VP2, the most variable of the AHSV proteins. VP2 is also a primary target for AHSV specific neutralising antibodies, and consequently determines the identity of the nine AHSV serotypes. In contrast VP1 (the viral polymerase) and VP3 (the sub-core shell protein), encoded by Seg-1 and Seg-3 respectively, are highly conserved, representing virus species/orbivirus-serogroup-specific antigens. We report development and evaluation of real-time RT-PCR assays targeting AHSV Seg-1 or Seg-3, that can detect any AHSV type (virus species/serogroup-specific assays), as well as type-specific assays targeting Seg-2 of the nine AHSV serotypes. These assays were evaluated using isolates of different AHSV serotypes and other closely related orbiviruses, from the 'Orbivirus Reference Collection' (ORC) at The Pirbright Institute. The assays were shown to be AHSV virus-species-specific, or type-specific (as designed) and can be used for rapid, sensitive and reliable detection and identification (typing) of AHSV RNA in infected blood, tissue samples, homogenised Culicoides, or tissue culture supernatant. None of the assays amplified cDNAs from closely related heterologous orbiviruses, or from uninfected host animals or cell cultures.
Objective To verify or refute the value of hospital episode statistics (HES) in determining 30 day mortality after open congenital cardiac surgery in infants nationally in comparison with central ...cardiac audit database (CCAD) information.Design External review of paediatric cardiac surgical outcomes in England (HES) and all UK units (CCAD), as derived from each database.Setting Congenital heart surgery centres in the United Kingdom.Data sources HES for congenital heart surgery and corresponding information from CCAD for the period 1 April 2000 to 31 March 2002. HES was restricted to the 11 English centres; CCAD covered all 13 UK centres.Main outcome measure Mortality within 30 days of open heart surgery in infants aged under 12 months.Results In a direct comparison for the years when data from the 11 English centres were available from both databases, HES omitted between 5% and 38% of infants operated on in each centre. A median 40% (range 0-73%) shortfall occurred in identification of deaths by HES. As a result, mean 30 day mortality was underestimated at 4% by HES as compared with 8% for CCAD. In CCAD, between 1% and 23% of outcomes were missing in nine of 11 English centres used in the comparison (predominantly those for overseas patients). Accordingly, CCAD mortality could also be underestimated. Oxford provided the most complete dataset to HES, including all deaths recorded by CCAD. From three years of CCAD, Oxford's infant mortality from open cardiac surgery (10%) was not statistically different from the mean for all 13 UK centres (8%), in marked contrast to the conclusions drawn from HES for two of those years.Conclusions Hospital episode statistics are unsatisfactory for the assessment of activity and outcomes in congenital heart surgery. The central cardiac audit database is more accurate and complete, but further work is needed to achieve fully comprehensive risk stratified mortality data. Given unresolved limitations in data quality, commercial organisations should reconsider placing centre specific or surgeon specific mortality data in the public domain.
Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an ...age-appropriate influenza vaccine.
In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248.
Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos −1·29%, 95% CI −14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, −6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, −34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, −13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, −5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, −11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected.
Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need.
National Institute for Health Research Policy Research Programme
Honeybees1 and bumblebees2 perform learning flights when leaving a newly discovered flower. During these flights, bees spend a portion of the time turning back to face the flower when they can ...memorize views of the flower and its surroundings. In honeybees, learning flights become longer when the reward offered by a flower is increased.3 We show here that bumblebees behave in a similar way, and we add that bumblebees face an artificial flower more when the concentration of the sucrose solution that the flower provides is higher. The surprising finding is that a bee’s size determines what a bumblebee regards as a “low” or “high” concentration and so affects its learning behavior. The larger bees in a sample of foragers only enhance their flower facing when the sucrose concentration is in the upper range of the flowers that are naturally available to bees.4 In contrast, smaller bees invest the same effort in facing flowers whether the concentration is high or low, but their effort is less than that of larger bees. The way in which different-sized bees distribute their effort when learning about flowers parallels the foraging behavior of a colony. Large bumblebees5,6 are able to carry larger loads and explore further from the nest than smaller ones.7 Small ones with a smaller flight range and carrying capacity cannot afford to be as selective and so accept a wider range of flowers.
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•Bees leaving flowers perform flights to memorize a flower’s looks and surroundings•Large bees prefer to learn about richly rewarding flowers and do so thoroughly•Small bees are less selective in flower learning and spend less effort doing so•These size differences in learning mirror the foraging of small and large bees
Frasnelli et al. find that a bee’s size sets what it memorizes on learning flights after drinking from flowers. Large bees only perform effective learning flights from flowers with rich rewards. Small bees spend less effort and memorize equally flowers with high or low rewards. This effect of size mirrors the foraging ranges of these bees.
Abstract African horse sickness is a lethal viral disease of equids transmitted by biting midges of the Genus Culicoides . The disease is endemic to sub-Saharan Africa but outbreaks of high mortality ...and economic impact have occurred in the past in non-endemic regions of Africa, Asia and Southern Europe. Vaccination is critical for the control of this disease but only live attenuated vaccines are currently available. However, there are bio-safety concerns over the use of this type of vaccines, especially in non-endemic countries, and live attenuated vaccines do not have DIVA (Differentiation of Infected from Vaccinated Animals) capacity. In addition, large scale manufacturing of live attenuated vaccines of AHSV represents a significant environmental and health risk and level 3 bio-safety containment facilities are required for their production. A variety of different technologies have been investigated over the years to develop alternative AHSV vaccines, including the use of viral vaccine vectors such Modified Vaccinia Ankara virus (MVA). In previous studies we demonstrated that recombinant MVA expressing outer capsid protein AHSV-VP2 induced virus neutralising antibodies and protection against virulent challenge both in a mouse model and in the horse. However, AHSV-VP2 is antigenically variable and determines the existence of 9 different AHSV serotypes. Immunity against AHSV is serotype-specific and there is limited cross-reactivity between certain AHSV serotypes: 1 and 2, 3 and 7, 5 and 8, 6 and 9. In Africa, multiple serotypes circulate simultaneously and a polyvalent attenuated vaccine comprising different AHSV serotypes is used. We investigated the potential of a polyvalent AHSV vaccination strategy based on combinations of MVA-VP2 viruses each expressing a single VP2 antigen from a specific serotype. We showed that administration of 2 different recombinant MVA viruses, each expressing a single VP2 protein from AHSV serotype 4 or 9, denoted respectively as MVA-VP2(4) and MVA-VP2(9), induced virus neutralising antibodies against the homologous AHSV serotypes. Vaccination was more efficient when vaccines were administered simultaneously than when they were administered sequentially. A third and fourth dose of a different MVA expressing VP2 of AHSV serotype 5, given 4 months later to ponies previously vaccinated with MVA-VP2(4) and MVA-VP2(9), resulted in the induction of VNAb against serotypes 4, 5, 6, 8 and 9. The anamnestic antibody response against AHSV 9 and AHSV 4 following the MVA-VP2(5) boost suggests that it is possible some shared epitopes exist between different serotypes. In conclusion this study showed that it is feasible to develop a polyvalent AHSV vaccination regime based on the use of combinations of MVA-VP2 viruses.
There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of ...disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity.
A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection.
Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 Relative Risk (RR) = 0.42 (95%CI: 0.34–0.52), P < 0.001, WHO outcome score >5 RR = 0.33 (95%CI: 0.21–0.50), P < 0.001, and to have had a LOS > 3 days RR = 0.84 (95%CI: 0.76–0.92), P < 0.001. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity.
We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease.
AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
Aims and Objectives
To determine whether a low‐dose intravenous insulin regimen reduces blood glucose levels at a timely rate and associated side effects among patients with Acute Coronary Syndrome ...and Left Ventricular Failure.
Background
Induced hypoglycaemia and the associated risks have questioned the benefits of intensive insulin therapy in patients presenting with raised blood glucose levels and Acute Coronary Syndromes. Local audit data identified that patients with Acute Coronary Syndrome and Left Ventricular Failure experienced more hypoglycaemic episodes than those with Acute Coronary Syndrome alone. Consequently, a new regimen of low‐dose insulin for this group was implemented and audited over 12 months.
Design
Audit.
Methods
Thirty‐six consecutive patient notes with a diagnosis of Acute Coronary Syndrome and blood glucose of ≥10 mmol/l treated with a new insulin therapy regimen were analysed. Data were extracted using a standardised form and entered into an Excel spreadsheet for analysis.
Results
The mean age of the sample was 70 years with 66% of subjects being men and 50% presenting with Acute Coronary Syndrome and Left Ventricular Failure. The low‐dose regimen was effective in achieving normoglycaemia, (range 4–8 mmol/l) for a consecutive six‐hour period. This was achieved in 72% of patients and within a median time of 13 hours.
Conclusion
The audit suggests that a low‐dose insulin regimen can effectively stabilise blood glucose in patients presenting with both Acute Coronary Syndrome and Left Ventricular Failure. The importance of regularly monitoring blood sugar levels is vital and highlights the role of nurses in minimising patient risk and promoting safety.
Relevance to practice
Nurses are instrumental in the safe implementation of intensive insulin guidelines. Close monitoring of patients is essential, enabling timely adjustments to treatments and ensuring patient safety. Regular audits allow nurses to evaluate care provision and continue to drive practice forward.
Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic ...(symptom-based) case ascertainment in older (greater than or equal to 65y) as compared to younger adults (< 65y). We included adults (greater than or equal to 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age greater than or equal to 65y reduced the probability of meeting syndromic LRTI case definitions, using patients' symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.
Hospitalisations relating to acute respiratory deteriorations (ARD) in Interstitial Lung Disease (ILD) have poor outcomes. Factors predicting adverse outcomes are not fully understood and data ...addressing the use of illness severity scores in prognostication are limited.
To investigate the use of CURB-65 and NEWS-2 severity scores in the prediction of mortality following ARD-ILD hospitalisation, using prospective methodology and to validate previously determined cut-offs, derived from a retrospective study cohort.
A dual-centre prospective observational cohort study of all adults (≥18y) hospitalised with ARD-ILD in Bristol, UK (n = 179). Gender-Age-Physiology (GAP), CURB-65 and NEWS-2 scores were calculated for each eligible admission.
Receiver operating characteristics (ROC) curve analysis was used to quantify the strength of discrimination for NEWS-2 and CURB-65 scores. Univariable and multivariable logistic regression analyses were performed to explore the relationship between baseline severity scores and mortality.
GAP showed some merit at predicting 30-day mortality (AUC = 0.64, P = 0.015); whereas CURB-65 showed modest predictive value for in-hospital (AUC = 0.72, P < 0.001) and 90-day mortality (AUC = 0.67, P < 0.001). NEWS-2 showed higher predictive value for in-hospital (AUC = 0.80, P < 0.001) and 90-day mortality (AUC = 0.75, P < 0.001), with an optimal derived cut-off ≥6.5 found to be sensitive and specific for predicting in-hospital (83% and 63%) and 90-day (73% and 72%) mortality. In exploratory analyses, GAP score addition improved the predictive ability of NEWS-2 against 30-day mortality and CURB-65 across all time-periods.
NEWS-2 has good discriminatory value for predicting in-hospital mortality and moderate discriminatory value for predicting 90-day mortality. The optimal NEWS-2 cut-off value determined was the same as in a previous retrospective cohort, confirming the NEWS-2 score shows promise in predicting mortality following ARD-ILD hospitalisation.
•ARD-ILD is associated with high in-hospital, 30- and 90- day mortality, irrespective of cause.•NEWS-2 has high sensitivity and specificity in predicting 90d & in-hospital mortality in ARD-ILD.•CURB-65 showed high sensitivity for predicting mortality but low specificity.•CURB-65 did not add value to the NEWS-2 predictive ability.•Simple illness severity scores may support refinement of ARD-ILD management pathways.
African Horse Sickness (AHS) is a highly lethal arboviral disease of equines. The lack of treatment makes vaccination essential. However, there are nine AHSV serotypes and AHSV immunity is ...serotype-specific; therefore AHSV vaccines must protect against all serotypes circulating in the field. A commercial polyvalent live-attenuated vaccine has been used for decades. However, bio-safety risks associated with its use, derived from gene segment re-assortment between vaccine and field strains, prompted the development of safer alternatives. These include the use of recombinant Modified Vaccinia Ankara virus (MVA). Previous studies showed that recombinant MVA vaccines expressing the AHSV outer-capsid VP2 protein successfully induced homologous protection and that a polyvalent MVA-VP2 vaccine could be developed (Manning et al., 2017). MVA vaccines expressing full length VP2 or fragments thereof, including a truncated-VP2 lacking the central VP2 immunodominant region, indicated that the structural integrity of VP2 was critical for preservation of neutralising epitopes. Further studies aimed at enhancing MVA-VP2 immunogenicity showed that monovalent MVA-VP2, expressing full-length VP2 from 'immediate-early' vaccinia promoters, could be used in a multivalent vaccination regime inducing homologous protection. To improve the design of polyvalent MVA-VP2 vaccines, a novel strategy based on using bivalent MVA-VP2, expressing two VP2 proteins from different serotypes, was proven successful. Homologous protection conferred by a bivalent MVA-VP2 for AHSV-4 and -9 was comparable to its monovalent counterpart. Previous studies showed MVA-VP2 immunogenicity depends on levels of VP2 protein presented to the immune system at the time of vaccination, since purified MVA-VP2 failed to induce virus neutralising antibodies (VNAb). Further studies described in this thesis, showed the addition of carbopol adjuvant improved immunogenicity of purified MVA-VP2 vaccines. MVA recombinants were produced expressing conserved AHSV capsid proteins, including VP5, VP7 and VP3, and immunogenicity of MVA-VP3 was tested which did not confer any protection against challenge. Various single and dual-expression MVA viruses were generated which will enable generating virus-like-particle AHSV vaccines by MVA expression, which has not been reported previously.
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