First experience of implementing Candida auris real-time PCR for surveillance in the UK: detection of multiple introductions with two international clades and improved patient outcomes.

BACKGROUND: Candida auris has been associated with rapid transmission and high mortality. A novel PCR-based surveillance programme was initiated at a London teaching hospital from January 2018. The results of this implementation until March 2019 are presented along with the clinical, transmission and phylogenetic characteristics encountered in that setting. METHODS: A real-time PCR assay for C. auris was developed, validated, and implemented for direct use on skin swabs and urine. Environmental swabs were also tested by PCR as an emergency outbreak-control measure. Clinical risk factors and outcomes of patients were determined. Environmental dispersal was assessed using 24 h settle plate cultures around nine colonized patients followed by air sampling around one colonized patient during high- and low-turbulence activities. Sequencing was performed using Illumina HiSeq and maximum likelihood phylogenies were constructed using rapid bootstrap analysis. RESULTS: Twenty-one C. auris colonized patients were identified. Median turnaround time of colonization detection reduced from 141 h (5.8 days) to approximately 24 h enabling rapid infection-control precautions. Settle plates detected 70-600 cfu/m2 around colonized patients over 24 h and air sampling suggested dispersal during turbulent activities. C. auris DNA was detected from 35.7% environmental swabs. Despite being in a high-risk setting, no patients developed invasive infection. Sequencing analysis of isolates from this centre identified two introductions of the South Asian (Clade I) and one of the South African (Clade III) strain. CONCLUSION: The PCR offers a rapid, scalable method of screening and supports clinical risk reduction in settings likely to encounter multiple introductions.

Source space reduction for eLORETA.

Objective.We introduce Sparse exact low resolution electromagnetic tomography (eLORETA), a novel method for estimating a nonparametric solution to the source localization problem. Its goal is to generate a sparser solution compared to other source localization methods including eLORETA while benefitting from the latter's superior source localization accuracy.Approach.Sparse eLORETA starts by reducing the source space of the Lead Field Matrix using structured sparse Bayesian learning from which a Reduced Lead Field Matrix is constructed, which is used as input to eLORETA.Main results.With Sparse eLORETA, source sparsity can be traded against signal fidelity; the proposed optimum is shown to yield a much sparser solution than eLORETA's with only a slight loss in signal fidelity.Significance.When pursuing a data-driven approach, for cases where it is difficult to choose specific regions of interest, or when subsequently a connectivity analysis is performed, source space reduction could prove beneficial.

Bronchoalveolar lavage fluid IMMY Sona Aspergillus lateral-flow assay for the diagnosis of invasive pulmonary aspergillosis: a prospective, real life evaluation.

Prompt and reliable diagnosis of invasive pulmonary aspergillosis (IPA) is essential for early initiation of antifungal therapy. We evaluated bronchoalveolar lavage (BAL) fluid IMMY Sona Aspergillus lateral-flow assay (IMMY LFA) in 92 individuals with suspected pulmonary infection. Sensitivity and specificity (vs. host factor but no IPA) of BAL IMMY LFA for diagnosis of IPA in individuals with any European Organisation for Research and Treatment of Cancer-defied "host factor" were 67% and 85%, respectively. Performance appeared better in individuals with renal transplantation (100%, 100%), compared to those with hematological malignancy and/or allogenic stem cell transplantation (70%, 78%). We found BAL IMMY LFA to be a convenient and useful addition to our diagnostic armory for IPA. LAY ABSTRACT: We evaluated a new test for diagnosing invasive pulmonary aspergillosis from bronchoscopy samples. We tested 92 people and found that it was 67% sensitive and 85% specific (compared to diagnosis according to a set of internationally recognised criteria). We found this test convenient and useful.

Cataract management in children: a review of the literature and current practice across five large UK centres.

Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK 'state of play' in the management of paediatric cataracts.

Yeasticidal activity of chemical disinfectants and antiseptics against Candida auris.

Candida auris appears to be transmitted readily between patients, yet information regarding the efficacy of environmental disinfection and skin decolonization is lacking. A quantitative suspension test (EN 13624:2013) was used to evaluate the yeasticidal activity of different chemical disinfectants and antiseptics against C. auris and Candida albicans. When tested in suspension, both a chlorine-based disinfectant and iodine-based skin antiseptic were effective against C. auris, suggesting that their use could reduce environmental contamination and skin colonization, respectively, if applied appropriately. Chlorhexidine-based products may also be effective. However, in this study, activity depended on formulation, specifically the presence of isopropyl alcohol.

The effects of ryanodine receptor (RYR1) mutation on natural killer cell cytotoxicity, plasma cytokines and stress hormones during acute intermittent exercise in pigs.

Stress susceptibility has been mapped to a single recessive gene, the ryanodine receptor 1 (RYR1) gene or halothane (Hal) gene. Homozygous (Hal(nn)), mutated pigs are sensitive to halothane and susceptible to Porcine Stress Syndrome (PSS). Previous studies have shown that stress-susceptible RYR1 gene mutated homozygotes in response to restraint stress showed an increase in natural killer cell cytotoxicity (NKCC) accompanied by more pronounced stress-related hormone and anti-inflammatory cytokine changes. In order to determine the relationship of a RYR1 gene mutation with NKCC, plasma cytokines and stress-related hormones following a different stress model - exercise - 36 male pigs (representing different genotypes according to RYR1 gene mutation: NN, homozygous dominant; Nn, heterozygous; nn, homozygous recessive) were submitted to an intermittent treadmill walking. During the entire experiment the greatest level of NKCC and the greatest concentrations of interleukin (IL-) 6, IL-10, IL-12, interferon (IFN-)γ and tumor necrosis factor-α and stress-related hormones (adrenaline, prolactin, beta-endorphin) were observed in nn pigs, and the greatest concentration of IL-1 and growth hormone in NN pigs. Immunostimulatory effects of intermittent exercise on NKCC in nn pigs were concomitant with increases in IL-2, IL-12 and IFN-γ, the potent NKCC activators. Our findings suggest that stress-susceptible pigs RYR1 gene mutated pigs develop a greater level of NKCC and cytokine production in response to exercise stress. These results suggest that the heterogeneity of immunological and neuroendocrine response to exercise stress in pigs could be influenced by RYR1 gene mutation.

Pseudotumoral presentation of fungating mycetoma caused by Phaeoacremonium fuscum in a renal transplant patient.

Eumycetoma is an unusual infection in immunocompromised patients outside the tropics, caused by a variety of fungal pathogens. We describe the case of a 51-year-old renal transplant recipient who presented with a large pseudotumoral foot lesion necessitating complete surgical excision of the lesion. Cultures and molecular diagnosis confirmed Phaeoacremonium fuscum. This is the first case, to our knowledge, of fungating mycetoma caused by this fungal species in a solid organ transplant recipient.

First confirmation of Pseudogymnoascus destructans in British bats and hibernacula.

White-nose syndrome (WNS) is a fatal fungal infection of bats in North America caused by Pseudogymnoascus destructans. P. destructans has been confirmed in Continental Europe but not associated with mass mortality. Its presence in Great Britain was unknown. Opportunistic sampling of bats in GB began during the winter of 2009. Any dead bats or samples from live bats with visible fungal growths were submitted to the Animal Health and Veterinary Laboratories Agency for culture. Active surveillance by targeted environmental sampling of hibernacula was carried out during the winter of 2012/2013. Six hibernacula were selected by their proximity to Continental Europe. Five samples, a combination of surface swabs or sediment samples, were collected. These were sent to the Center for Microbial Genetics and Genomics, Northern Arizona University, for P. destructans PCR. Forty-eight incidents were investigated between March 2009 and July 2013. They consisted of 46 bat carcases and 31 other samples. A suspected P. destructans isolate was cultured from a live Daubenton's bat (Myotis daubentonii) sampled in February 2013. This isolate was confirmed by the Mycology Reference Laboratory, Bristol (Public Health England), as P. destructans. A variety of fungi were isolated from the rest but all were considered to be saprophytic or incidental. P. destructans was also confirmed by the Center for Microbial Genetics and Genomics in five of the six sites surveyed.

Natural killer cell cytotoxicity, cytokine and neuroendocrine responses to opioid receptor blockade during prolonged restraint in pigs.

This study evaluated porcine natural killer cell cytotoxicity (NKCC), plasma cytokines including interleukin (IL) 1ß, IL-6, IL-10, IL-12 and tumor necrosis factor-α and plasma stress-related hormones including prolactin (PRL), growth hormone (GH), ß-endorphin (BEND), ACTH and cortisol (COR) during a 4h restraint and recovery phase after saline or naloxone (1mg/kg BW) administration. The restraint preceded with saline altered NKCC and IL-12 concentration (an early from 15 to 60 min increase followed by a decrease) and increased other measured cytokines and hormones concentrations. Naloxone pretreatment blocked the suppressive effects of the restraint on NKCC and IL-12 and altered IL-10, IL-6, TNF-α, PRL and ACTH concentrations. Furthermore, in naloxone-injected pigs, a positive correlation was found between NKCC and all measured cytokines (with the exception of IL-6) and BEND, ACTH and COR. Results suggest that naloxone-sensitive opioid pathways could influence the mechanisms underlying the immune system (including NKCC) response during stress.

Isolation of the fungus Geosmithia argillacea in sputum of people with cystic fibrosis.

We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.

Can a community optometrist-based referral refinement scheme reduce false-positive glaucoma hospital referrals without compromising quality of care? The community and hospital allied network glaucoma evaluation scheme (CHANGES).

BACKGROUND/AIMS: To describe the design, activity, and quality of the referral refinement phase of a novel glaucoma shared-care scheme. METHODS: Eight Optometrists with a Specialist Interest in glaucoma (OSI) were trained to perform a community-based comprehensive glaucoma evaluation of low-risk glaucoma hospital referrals (only one/none of the following factors noted for either eye: abnormal optic disc, abnormal visual field, abnormal intraocular pressure (IOP; 22-28 mmHg or IOP asymmetry)) using equipment standardized to that of the hospital glaucoma service. RESULTS: One hundred and thirty-eight (27%) of a total of 512 glaucoma-related referrals were deemed 'low risk'. Their choice of OSI discharged 40 (35%). The consultant agreed (virtually) with the decision to discharge with 28 (70%) and disagreed with 12 (30%). Comparing findings between OSI and consultant for 99 referred patients, sensitivity, specificity, and negative predictive values for a suspicious optic disc were 78, 61, and 79%, respectively. For an IOP of >21 mmHg, they were 74, 85, and 90%, respectively. For an occludable anterior chamber angle (Van Herick's versus gonioscopy), they were 69, 88, and 94%, respectively. CONCLUSION: This referral refinement process can reduce numbers of false-positive referrals attending the hospital glaucoma service while retaining a relatively high level of examination quality.

Adiaspiromycosis mimicking widespread malignancy in a patient with pulmonary adenocarcinoma.

Adiaspiromycosis, a mycotic disease of small animals, has rarely been reported in humans. The principle causative organism in Europe is Emmonsia crescens. Inhaled, dust-borne spores of E crescens fail to germinate in host tissue, instead increasing in size dramatically to become thick-walled, round adiapsores, which induce a granulomatous response. The pathological effects depend on the spore burden and host immunocompetence, and range from asymptomatic infection through to necrogranulomatous pneumonia, respiratory failure and, rarely, death. Diagnosis is principally made through histological examination. This report describes a case of a patient with low-grade, localised pulmonary adenocarcinoma with occult adiaspiromycosis that radiologically mimicked widespread malignancy. It is believed to be the first reported human case of adiaspiromycosis in the UK.