Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections.

Natural scrapie in sheep occurs in classical and atypical forms, which may be distinguished on the basis of the associated neuropathology and properties of the disease-associated prion protein on Western blots. First detected in 1998, atypical scrapie is known to have occurred in UK sheep since the 1980s. However, its aetiology remains unclear and it is often considered as a sporadic, non-contagious disease unlike classical scrapie which is naturally transmissible. Although atypical scrapie tends to occur in sheep of prion protein (PRNP) genotypes that are different from those found predominantly in classical scrapie, there is some overlap so that there are genotypes in which both scrapie forms can occur. In this search for early atypical scrapie cases, we made use of an archive of fixed and frozen sheep samples, from both scrapie-affected and healthy animals (∼1850 individuals), dating back to the 1960s. Using a selection process based primarily on PRNP genotyping, but also on contemporaneous records of unusual clinical signs or pathology, candidate sheep samples were screened by Western blot, immunohistochemistry and strain-typing methods using tg338 mice. We identified, from early time points in the archive, three atypical scrapie cases, including one sheep which died in 1972 and two which showed evidence of mixed infection with classical scrapie. Cases with both forms of scrapie in the same animal as recognizable entities suggest that mixed infections have been around for a long time and may potentially contribute to the variety of scrapie strains.

Hepatitis E virus in blood components: a prevalence and transmission study in southeast England.

BACKGROUND: The prevalence of hepatitis E virus (HEV) genotype 3 infections in the English population (including blood donors) is unknown, but is probably widespread, and the virus has been detected in pooled plasma products. HEV-infected donors have been retrospectively identified through investigation of reported cases of possible transfusion-transmitted hepatitis E. The frequency of HEV transmission by transfusion and its outcome remains unknown. We report the prevalence of HEV RNA in blood donations, the transmission of the virus through a range of blood components, and describe the resulting morbidity in the recipients. METHODS: From Oct 8, 2012, to Sept 30, 2013, 225,000 blood donations that were collected in southeast England were screened retrospectively for HEV RNA. Donations containing HEV were characterised by use of serology and genomic phylogeny. Recipients, who received any blood components from these donations, were identified and the outcome of exposure was ascertained. FINDINGS: 79 donors were viraemic with genotype 3 HEV, giving an RNA prevalence of one in 2848. Most viraemic donors were seronegative at the time of donation. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused before identification of the infected donation. Follow-up of 43 recipients showed 18 (42%) had evidence of infection. Absence of detectable antibody and high viral load in the donation rendered infection more likely. Recipient immunosuppression delayed or prevented seroconversion and extended the duration of viraemia. Three recipients cleared longstanding infection after intervention with ribavirin or alteration in immunosuppressive therapy. Ten recipients developed prolonged or persistent infection. Transaminitis was common, but short-term morbidity was rare; only one recipient developed apparent but clinically mild post-transfusion hepatitis. INTERPRETATION: Our findings suggest that HEV genotype 3 infections are widespread in the English population and in blood donors. Transfusion-transmitted infections rarely caused acute morbidity, but in some immunosuppressed patients became persistent. Although at present blood donations are not screened, an agreed policy is needed for the identification of patients with persistent HEV infection, irrespective of origin, so that they can be offered antiviral therapy. FUNDING: Public Health England and National Health Service Blood and Transplant.

Colonisation with toxigenic Corynebacterium diphtheriae in a Scottish burns patient, June 2015.

On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae.

Susceptibility of young sheep to oral infection with bovine spongiform encephalopathy decreases significantly after weaning.

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) (or prion disease) that is readily transmissible to sheep by experimental infection and has the shortest incubation period in animals with the ARQ/ARQ PRNP genotype (at codons 136, 154, and 171). Because it is possible that sheep in the United Kingdom could have been infected with BSE by being fed contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection; however, this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (~24 h, 2 to 3 weeks, 3 months, and 6 months) and adult sheep. The incidence of clinical BSE disease after inoculation was high in unweaned lambs (~24 h and 2 to 3 weeks old) but much lower in older weaned animals The incubation period was also found to be influenced by the genotype at codon 141 of the PRNP gene, as lambs that were LF heterozygotes had a longer mean incubation period than those that were homozygotes of either type. The results suggest that sheep in the United Kingdom would have been at high risk of BSE infection only if neonatal animals had inadvertently ingested contaminated supplementary foodstuffs.

Pilot Project for a Web-Based Dynamic Nomogram to Predict Survival 1 Year After Hip Fracture Surgery: Retrospective Observational Study.

BACKGROUND: Hip fracture is associated with high mortality. Identification of individual risk informs anesthetic and surgical decision-making and can reduce the risk of death. However, interpreting mathematical models and applying them in clinical practice can be difficult. There is a need to simplify risk indices for clinicians and laypeople alike. OBJECTIVE: Our primary objective was to develop a web-based nomogram for prediction of survival up to 365 days after hip fracture surgery. METHODS: We collected data from 329 patients. Our variables included sex; age; BMI; white cell count; levels of lactate, creatinine, hemoglobin, and C-reactive protein; physical status according to the American Society of Anesthesiologists Physical Status Classification System; socioeconomic status; duration of surgery; total time in the operating room; side of surgery; and procedure urgency. Thereafter, we internally calibrated and validated a Cox proportional hazards model of survival 365 days after hip fracture surgery; logistic regression models of survival 30, 120, and 365 days after surgery; and a binomial model. To present the models on a laptop, tablet, or mobile phone in a user-friendly way, we built an app using Shiny (RStudio). The app showed a drop-down box for model selection and horizontal sliders for data entry, model summaries, and prediction and survival plots. A slider represented patient follow-up over 365 days. RESULTS: Of the 329 patients, 24 (7.3%) died within 30 days of surgery, 65 (19.8%) within 120 days, and 94 (28.6%) within 365 days. In all models, the independent predictors of mortality were age, BMI, creatinine level, and lactate level. The logistic model also incorporated white cell count as a predictor. The Cox proportional hazards model showed that mortality differed as follows: age 80 vs 60 years had a hazard ratio (HR) of 0.6 (95% CI 0.3-1.1), a plasma lactate level of 2 vs 1 mmol/L had an HR of 2.4 (95% CI 1.5-3.9), and a plasma creatinine level of 60 vs 90 mol/L had an HR of 2.3 (95% CI 1.3-3.9). CONCLUSIONS: In conclusion, we provide an easy-to-read web-based nomogram that predicts survival up to 365 days after hip fracture. The Cox proportional hazards model and logistic models showed good discrimination, with concordance index values of 0.732 and 0.781, respectively.

The impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission of HIV on the uptake of maternal antiretroviral therapy among HIV-seropositive pregnant women in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVES: To identify the approaches that are used in improving on male partner involvement in the prevention of mother-to-child transmission (PMTCT) of HIV and their impact on the uptake maternal antiretroviral therapy (ART) in sub-Saharan Africa (SSA). SETTING: This was a systematic review and meta-analysis of published studies carried out in SSA at all levels of healthcare (primary, secondary, tertiary and community). PARTICIPANTS: The participants of the studies included were HIV-positive pregnant women and breastfeeding mothers with their male partners. Studies were included if they were conducted in SSA and mentioned an approach used in improving male partner involvement with data on the impact on the uptake of maternal ART uptake. OUTCOMES: In the protocol, maternal ART uptake, infant prophylaxis, safe infant feeding options, condom use and family planning were envisaged. However, only maternal ART has been reported here due to limitations on the word count. RESULTS: From an initial 2316 non-duplicate articles, 17 articles were included in the systematic review and meta-analysis. In the combined model, the ORs for complex community interventions, enhanced psychosocial interventions, verbal encouragement and invitation letters were 4.22 (95% CI 2.27 to 7.77), 2.29 (95% CI 1.42 to 7.69), 2.39 (95% CI 1.26 to 4.53) and 1.21 (95% CI 0.89 to 1.63), respectively, whereas in the model using adjusted ORs, enhanced psychosocial interventions had a higher effect than any other intervention. The heterogeneity was moderate using adjusted ORs. CONCLUSION: Enhanced psychosocial interventions and complex community interventions increase male partner involvement and the uptake of PMTCT services more than any other intervention. Invitation letters had no effect. More randomised trials and observational studies (that have adjusted for potential confounders) are needed in the future. PROSPERO REGISTRATION NUMBER: 42016032673.

Short-term changes in the health state of children with group B meningococcal disease: A prospective, national cohort study.

OBJECTIVES: The short-term impact of childhood invasive meningococcal disease (IMD) on quality-of-life (QoL) remains largely unquantified. This study aimed to quantify QoL loss at the point when illness was at its worst, and assess health state recovery in the months following illness. METHODS: Parents of children aged <16 years with laboratory-confirmed meningococcal group B (MenB) disease in England, with onset dates from November 2012 to May 2013 were asked to complete a short questionnaire, which included EQ-5DY, a version of EQ-5D for 8-15 year-olds. The parents, or child if able, were asked to complete the questionnaires while considering the child's health on the worst day of illness and on the date the questionnaires were completed. RESULTS: The overall response rate was 43% (109/254 children), with no significant differences between respondents and non-respondents. The median time from disease onset to questionnaire completion was 134 days (interquartile range (IQR), 92 to 156 days). After imputation, the median health index was -0.056 (IQR, -0.073 to 0.102) on the worst day of illness, and 1 (IQR 0.866 to 1.000) on the date of questionnaire completion. The respective Visual Analogue Scores (VAS) were 6.5/100.0 (IQR, 0.0 to 20.0) and 95.0/100.0 (IQR, 90.0 to 100.0). The health state of cases with long-term sequelae (n = 41) was significantly worse at follow-up than those who recovered uneventfully (n = 64; 90.0 vs. 98.0; p<0.001), although there was no significant difference on the worst day of illness (5.0 vs. 10.0; p = 0.671). CONCLUSIONS: This work has provided, for the first time, a quantitative estimate of QoL loss at the peak of illness and in the months after MenB disease in children. The magnitude of QoL loss is staggering, with the reported health state being at, or close to, the worst possible outcome imaginable. This study highlights the difficulties in measuring the impact of illness in young children, who often have the highest burden of potentially preventable infectious diseases.

Impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission (PMTCT) of HIV on the uptake of PMTCT services in sub-Saharan Africa: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Several studies have reported approaches used in improving the delivery of prevention of mother-to-child transmission (PMTCT) of HIV services through the involvement of male partners, but evidence from a systematic review is limited. We aim at determining the impact of male partner involvement on PMTCT in sub-Saharan Africa. METHODS AND ANALYSIS: This will be a systematic review of published literature. Interventional and observational studies on male involvement in PMTCT carried out in sub-Saharan Africa will be included irrespective of the year and language of publication. OVID Medline, Embase, PschINFO, and Cochrane database of controlled trials will be searched. After manual searching of articles, authors shall be contacted for further information. 2 authors (NFT and CJ) will independently screen potential articles for eligibility using defined inclusion and exclusion criteria. Critical Appraisal Skills Programme (CASP) tools, Jadad scale and the STROBE checklist will be used for critical appraisal, and the 2 authors will independently assess the quality of articles. Authors will independently extract data from studies using a pre-established data collection form, and any discrepancies will be sorted by a third author (TRK). Outcomes will be analysed using STATA V.12.0. The random effect model will be used to produce forest plots. The heterogeneity χ(2) statistics and I(2) will be used to assess for heterogeneity. Publication bias will be assessed using funnel plots. This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines. ETHICS AND DISSEMINATION: No ethical approval since included studies will be published studies that had already obtained ethical approvals. The findings will guide HIV programmes on the best approaches towards involving male partners in PMTCT with a view to improving PMTCT services in sub-Saharan Africa. PROSPERO REGISTRATION NUMBER: 42016032673.

A systematic review of the health impacts of mass Earth movements (landslides).

Background. Mass ground movements (commonly referred to as 'landslides') are common natural hazards that can have significant economic, social and health impacts. They occur as single events, or as clusters, and are often part of 'disaster' chains, occurring secondary to, or acting as the precursor of other disaster events. Whilst there is a large body of literature on the engineering and geological aspects of landslides, the mortality and morbidity caused by landslides is less well documented. As far as we are aware, this is the first systematic review to examine the health impacts of landslides. Methods. The MEDLINE, EMBASE, CINAHL, SCOPUS databases and the Cochrane library were systematically searched to identify articles which considered the health impacts of landslides. Case studies, case series, primary research and systematic reviews were included. News reports, editorials and non-systematic reviews were excluded. Only articles in English were considered. The references of retrieved papers were searched to identify additional articles. Findings. 913 abstracts were reviewed and 143 full text articles selected for review. A total of 27 papers reporting research studies were included in the review (25 from initial search, 1 from review of references and 1 from personal correspondence). We found a limited number of studies on the physical health consequences of landslides. Only one study provided detail of the causes of mortality and morbidity in relation a landslide event. Landslides cause significant mental health impacts, in particular the prevalence of PTSD may be higher after landslides than other types of disaster, though these studies tend to be older with only 3 papers published in the last 5 years, with 2 being published 20 years ago, and diagnostic criteria have changed since they were produced. Discussion. We were disappointed at the small number of relevant studies, and the generally poor documentation of the health impacts of landslides. Mental health impacts were better documented, though some of the studies are now quite old. Further research on the health impacts of landslides needs to be undertaken to support those responding to landslide disasters and to aid disaster risk mitigation advocacy.

A semi-quantitative and thematic analysis of medical student attitudes towards M-Learning.

RATIONALE, AIMS AND OBJECTIVES: Smartphone and mobile application technology have in recent years furthered the development of novel learning and assessment resources. 'MBChB Mobile' is a pioneering mobile learning (M-Learning) programme at University of Leeds, United Kingdom and provides all senior medical students with iPhone handsets complete with academic applications, assessment software and a virtual reflective environment. This study aimed to evaluate the impact of MBChB Mobile on student learning. METHODS: Ethical approval was granted to invite fourth and fifth year medical students to participate in a semi-quantitative questionnaire: data were collected anonymously with informed consent and analysed where appropriate using chi-squared test of association. Qualitative data generated through focus group participation were subjected to both content and thematic analysis. RESULTS: A total of 278 of 519 (53.6%) invited participants responded. Overall, 72.6% of students agreed that MBChB Mobile enhanced their learning experience; however, this was significantly related to overall usage (P < 0.001) and self-reported mobile technology proficiency (P < 0.001). Qualitative data revealed barriers to efficacy including technical software issues, non-transferability to different mobile devices, and perceived patient acceptability. CONCLUSIONS: As one of the largest evaluative and only quantitative study of smartphone-assisted M-Learning in undergraduate medical education, MBChB Mobile suggests that smartphone and application technology enhances students' learning experience. Barriers to implementation may be addressed through the provision of tailored learning resources, along with user-defined support systems, and appropriate means of ensuring acceptability to patients.

Screening for gonorrhoea using samples collected through the English national chlamydia screening programme and risk of false positives: a national survey of local authorities.

OBJECTIVES: To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England. DESIGN AND SETTING: During May-July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15-24 years. MAIN OUTCOME MEASURES: (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%. RESULTS: 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450-4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17-67%. CONCLUSIONS: Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed.