Timothy Collyns

An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. Parallel investigations were pursued: (1) identification of cardiopulmonary bypass–associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. Eighteen probable cases of cardiopulmonary bypass–associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81–87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and mortality and a rising pressure on health-care systems. However, the development of new antibiotics is an expensive and time-consuming process, urging scientists to seek alternative antimicrobial strategies. Over the past few decades, the concept of therapeutic administration of bacteriophages (also known as phages) has gained popularity worldwide. Although conceptually promising, the widespread implementation of phage therapy in routine clinical practice is restricted by the scarcity of safety and efficacy data obtained according to the strict standards of the applicable clinical trial regulations. In this systematic review, we list clinical data published between Jan 1, 2000 and Aug 14, 2021 on the safety and efficacy of phage therapy for difficult-to-treat bacterial infections, and provide an overview of trials and case studies on the use of phage therapy in several medical disciplines.

Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases.Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation.Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20-39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival.Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

The full British Thoracic Society (BTS) guideline for the use of long-term macrolides in adults with respiratory disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline and online appendices are available on the BTS website. This is the first BTS guideline to use the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach as part of the process of guideline development and the guideline was used to pilot the new methodology.

NICE (National Institute for Health and Clinical Excellence) guidelines for new entrant tuberculosis (TB) screening recommend chest x ray (CXR) for immigrants from countries with TB incidence >40/10(5), and tuberculin skin test (TST) for people with normal CXR from very high TB prevalence countries. A revised screening policy using first-line QuantiFERON-TB Gold (QFT) in high risk immigrants was piloted in 2007. Initially, TST was offered to immigrants from countries with TB incidence 200-339/10(5), and QFT to those from countries with incidence >340/10(5). When increased resources became available, all immigrants from countries with TB incidence >200/10(5) had QFT. Those with positive QFT were invited for CXR. 1336 immigrant were invited for screening, with a 32% attendance rate. 280 patients had QFT, of which 38% were positive, with <2% being indeterminate. Using the NICE approach, the cost of screening these 280 immigrants would be pound 13,346.75 ( pound 47.67 per immigrant) and would identify 83 cases of latent TB infection (LTBI). Using first-line QFT followed by CXR the cost was pound 9781.82 ( pound 34.94 per immigrant) and identified 105 cases of LTBI. The cost to identify one case of LTBI following NICE guidelines would be pound 160.81 and using the present protocol was pound 93.16. For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI.

The full British Thoracic Society (BTS) guideline for the use of long-term macrolides in adults with respiratory disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline and online appendices are available on the BTS website. This is the first BTS guideline to use the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach as part of the process of guideline development and the guideline was used to pilot the new methodology.

ABSTRACT Compared with solid media, broth-based mycobacterial culture systems have increased sensitivity but also have higher false-positive rates due to cross-contamination. Systematic strain typing is rarely undertaken because the techniques are technically demanding and the data are difficult to organize. Variable number tandem repeat (VNTR) analysis by PCR is rapid and reproducible. The digital profile is easily manipulated in a database. We undertook a retrospective study of Mycobacterium tuberculosis isolates collected over an 18-month period following the introduction of the BACTEC MGIT 960 system. VNTR allele profiles were determined with early positive broth cultures and entered into a database with the specimen processing date and other specimen data. We found 36 distinct VNTR profiles in cultures from 144 patients. Three common VNTR profiles accounted for 45% of true-positive cases. By combining VNTR results with specimen data, we identified nine cross-contamination incidents, six of which were previously unsuspected. These nine incidents resulted in 34 false-positive cultures for 29 patients. False-positive cultures were identified for three patients who had previously been culture positive for tuberculosis and were receiving treatment. Identification of cross-contamination incidents requires careful documentation of specimen data and good communication between clinical and laboratory staff. Automated broth culture systems should be supplemented with molecular analysis to identify cross-contamination events. VNTR analysis is reproducible and provides timely results when applied to early positive broth cultures. This method should ensure that patients are not placed on unnecessary tuberculosis therapy or that cases are not falsely identified as treatment failures. In addition, areas where existing procedures may be improved can be identified.

Urinary tract infections are amongst the most common bacterial infections. They can occur in either an uncomplicated host setting, where there is no underlying structural or functional abnormality of the patient's genitourinary tract, or complicated, where there is. For the latter, common predisposing factors are the presence of a foreign body, including urinary catheter, or disruption of normal urinary flow by obstruction or retention. Bacteria vary widely in their ability to successfully invade the urinary tract; the vast majority of such infections being due to a small number of species. The route is usually ascension from the urethra. Certain uropathogenic strains of Escherichia coli are the most proficient as measured by their frequency of being the identified cause. Such strains display a number of virulence factors which enable them to occupy this niche – which with increasing understanding, may promote different methods of treating. Other species are often implicated only in the presence of an underlying urological abnormality. The presence of a urinary catheter, or other urine drainage device, provides a ready scaffold for organisms to develop a biofilm, which in turn shields them from being eradicated successfully. Renal calculi similarly can be linked to biofilm production.

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We report a case of Buruli ulcer in a tourist from the United Kingdom. The disease was almost certainly acquired in Brazil, where only 1 case had previously been reported. The delay in diagnosis highlights the need for physicians to be aware of the disease and its epidemiology.

British Journal of DermatologyVolume 156, Issue 3 p. 586-587 Lichen scrofulosorum caused by Mycobacterium szulgai: a new cause of a tuberculide reaction G.L. Ross, G.L. Ross Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorH. Chong, H. Chong Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorT. Collyns, T. Collyns Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorD.M. Gascoyne-Binzi, D.M. Gascoyne-Binzi Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorR.P.E. Sarkany, R.P.E. Sarkany Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this author G.L. Ross, G.L. Ross Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorH. Chong, H. Chong Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorT. Collyns, T. Collyns Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorD.M. Gascoyne-Binzi, D.M. Gascoyne-Binzi Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this authorR.P.E. Sarkany, R.P.E. Sarkany Skin & Cancer Foundation, 95 Rathdowne Street, Carlton, Vic. 3053, AustraliaDepartments of *Cellular Pathology and‡Dermatology, St George's Hospital, Blackshaw Road, London SW17 0QT, U.K.†Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.Search for more papers by this author First published: 09 January 2007 https://doi.org/10.1111/j.1365-2133.2007.07683.xCitations: 10 Gayle Ross, 37 Union Road, Surrey Hills, Vic. 3127, Australia.E-mail: wiggills@yahoo.com.au Conflicts of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume156, Issue3March 2007Pages 586-587 RelatedInformation

Urinary tract infections are amongst the most common bacterial infections. They can occur in either an uncomplicated host setting, where there is no underlying structural or functional abnormality of the patient’s genitourinary tract, or complicated, where there is. For the latter, common predisposing factors are the presence of a foreign body, including urinary catheter, or disruption of normal urinary flow by obstruction or retention. Bacteria vary widely in their ability to successfully invade the urinary tract; the vast majority of such infections being due to a small number of species. The route is usually ascension from the urethra. Certain uropathogenic strains of Escherichia coli are the most proficient as measured by their frequency of being the identified cause. Such strains display a number of virulence factors which enable them to occupy this niche – which with increasing understanding, may promote different methods of treating. Other species are often implicated only in the presence of an underlying urological abnormality. The presence of a urinary catheter, or other urine drainage device, provides a ready scaffold for organisms to develop a biofilm, which in turn shields them from being eradicated successfully. Renal calculi similarly can be linked to biofilm production.

To the Editors: In October 2008, a sixth form college student in England, UK, who had had a cough for 2 months was diagnosed with sputum smear-positive cavitatory pulmonary tuberculosis. An investigation led to the identification of 19 cases of active tuberculosis among 2,284 students. Here, we describe the outbreak and investigation into the factors associated with active tuberculosis. The study population consisted of students enrolled at the college for daytime courses. All participants were aged >16 yrs. Members of staff who directly taught these students were also screened. Between October 2008 and December 2009, students, friends of the index case and staff at the college were interviewed. The interviews were used to collect demographic and clinical information, including symptoms suggestive of tuberculosis. At the same time, a blood sample was drawn from each participant for interferon-γ release assay (IGRA) testing [1, 2]. Following the screening of household contacts and friends of the index case, the students at the school were assessed in concentric circles of decreasing intensity of exposure in three groups (table 1) [3]. Those with a positive IGRA result from any screening round were recalled for chest radiography and clinical review at a respiratory medicine clinic. Preventative therapy was offered to …

To investigate the use of new gamma-interferon (IFN-gamma)-based blood tests to determine whether or not a higher-than-expected proportion of positive tuberculin skin tests (TSTs) were due to tuberculosis infection.When an unexpectedly high proportion of children in a high school in Leeds were found to have positive TSTs, a cohort study was undertaken based on blood tests and long-term follow-up of the affected children. IFN-gamma-based blood tests are reported to be more specific for tuberculosis infection than TSTs.One hundred and ninety children, aged 13-14 years, were screened and 28 (15%) had a positive TST. None had any known risk factor for tuberculosis infection. Parental consent was requested for testing with QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia). Active cases of tuberculosis with any possible connection to the school or the children were sought through the routine diagnosis and reporting service over the next 36 months.Consent was given for 26 children with Heaf Grade 2 results to be tested using QuantiFERON-TB Gold, and blood was obtained from 24 of these children. All tested negative. None of these children developed active tuberculosis, and no cases of active tuberculosis were identified with any connection to the children or the school.QuantiFERON-TB Gold testing appeared to identify false-positive TSTs correctly in this group. This supports the recent recommendation to use IFN-gamma-based blood tests in people with positive TSTs to confirm or refute the diagnosis of tuberculosis infection.

Abstract Background Respiratory syncytial virus (RSV) is a major cause of acute respiratory illness in young children and elderly people worldwide. It has a complex molecular epidemiology with multiple strains cocirculating during a single epidemic. Whole genome sequencing is a valuable tool for monitoring genetic diversity and providing genomic information essential for antiviral and vaccine development. In the United Arab Emirates (UAE), little is known about the RSV circulating genotypes, their evolution, and transmission dynamics. Using next-generation sequencing, this study aims to identify RSV genotypes circulating among young children with bronchiolitis in Al Ain City, UAE. Methods This cross-sectional study involved 100 children under two years of age who were hospitalized at a tertiary care facility between April and December 2021 with RSV-positive bronchiolitis. Nasopharyngeal samples were obtained, within 24 hours of hospitalization, for RSV genotyping. MinION nanopore sequencer was used to analyze the whole viral genome. We only sequenced samples with cycle threshold (Ct) &amp;lt; 30 (n=70). After sequencing, 7 samples were not analyzed due to long gaps and small lengths. The remaining 63 samples included 59 RSV-A and 4 RSV-B isolates. Results The median age of the studied children was 4.3 months, interquartile range (2.1-10.4), with 56% below the age of 6 months. There was no significant difference in the clinical characteristics of children having RSV-A compared to those infected with RSV-B. Phylogenetic analysis showed that out of the 59 RSV-A sequences, 58 clustered with the NA1 genotype, and 1 sequence clustered with the GA1 genotype. All RSV-B sequences were classified as BA2 genotypes. The amino acid sequence alignment of the G gene revealed that all 58 NA1 genotypes had 24 amino acid duplication regions from 247 to 282 amino acid positions. We also found four substitutional changes at L248I, H258Q, L274P, and P276Q. Conclusion Phylogenetic analysis revealed that the subtype A NA1 genotype was the dominant strain among the studied children in Al Ain, UAE during the 2021 season. As vaccine development advances, further sequencing of RSV is needed to better understand viral origin, transmission, and genetic recombination, particularly in under-studied populations. Disclosures All Authors: No reported disclosures

OBJECTIVE: To compare four vancomycin-containing agar media for the isolation of glycopeptide-resistant enterococci (GRE) from clinical fecal specimens: kanamycin---aesculin---azide (KAA) agar; bile---aesculin---polymixin (BAP) agar; aztreonam---amphotericin blood (CBAA) agar; and neomycin blood (CBN) agar. METHODS: Fecal specimens from 125 patients were inoculated onto each medium. Media were examined for enterococci after incubation for up to 48 h. Enterococci were identified to species level, and glycopeptide phenotypes were determined by measuring minimum inhibitory concentrations of vancomycin and teicoplanin. RESULTS: GRE were isolated from 44/125 samples. Enterococcus faecalis and Enterococcus faecium isolates, expressing glycopeptide resistance of the VanA or VanB phenotypes, were recovered from 27/33 (82%) specimens on BAP medium, 26/33 (79%) on KAA medium, and 21/33 (64%) on CBN and CBAA media. Enterococcus gallinarum and Enterococcus casseliflavus isolates expressing low-level glycopeptide resistance (VanC phenotype) were recovered from 14/15 (93%) specimens on CBAA medium, 7/15 (47%) on KAA and CBN media, and 6/15 (40%) on BAP medium. CONCLUSIONS: The media tested in this study, with the exception of CBN medium, detected at least 75% of patients colonized by GRE. Further development of BAP, CBAA and KAA media is warranted to improve growth and selectivity.

Infective endocarditis (IE) due to multi-drug (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa is rare. MDR P. aeruginosa infections are increasingly reported worldwide, and the choice of effective antimicrobials is limited. Ceftolozane-tazobactam is a new antimicrobial combination with activity against many resistant strains of P. aeruginosa, but there are limited data on its use in complex infections. We present the first reported cases of XDR P. aeruginosa IE and MDR P. aeruginosa intravascular catheter-related bloodstream infection [CRBSI] with possible IE to be treated with ceftolozane-tazobactam in combination with other agents. Patient 1 completed seven weeks treatment with ceftolozane-tazobactam and fosfomycin, in combination with valve replacement, for XDR P. aeruginosa IE and is 2 year post-treatment without signs of relapse. Patient 2 completed 4 weeks treatment with ceftolozane-tazobactam and fosfomycin for MDR P. aeruginosa intravascular CRBSI with possible IE and went 8 months before MDR P. aeruginosa was cultured again from a line culture and tip. These cases highlight the difficulties of managing IE caused by MDR and XDR P. aeruginosa infections and indicate that ceftolozane-tazobactam may be effective when there are no alternative beta-lactams.

Urinary tract infections are amongst the most common bacterial infections. They can occur in either an uncomplicated host setting, where there is no underlying structural or functional abnormality of the patient's genitourinary tract; or complicated, where there is. For the latter, common predisposing factors are the presence of a foreign body, including urinary catheter, or disruption of normal urinary flow by obstruction or retention. Bacteria vary widely in their ability to successfully invade the urinary tract; the vast majority of such infections being due to a small number of species. The route is usually ascension from the urethra. Certain uropathogenic strains of Escherichia coli are the most proficient as measured by their frequency of being the identified cause. Such strains display a number of virulence factors that enable them to occupy this niche – which with increasing understanding, may promote different methods of treating. Other species are often implicated only in the presence of an underlying urological abnormality. The presence of a urinary catheter, or other urine drainage device, provides a ready scaffold for organisms to develop a biofilm, which in turn shields them from being eradicated successfully. Renal calculi similarly can be linked to biofilm production.

Infectious complications are a significant cause of morbidity and mortality in patients with haematological disorders. Relative risks and severity vary with underlying disease. Neutropenic fever is the archetype. After assessment and blood cultures, an anti-pseudomonal β-lactam is the standard first choice coupled with appropriate supportive management. Therapy is reviewed with clinical response and microbiological results. The aetiology, diagnosis and management of respiratory tract and catheter-related infections, which are more common in the critical care setting, are specifically discussed. Finally, some preventative strategies are presented.

Background: IGRA, QuantiFERON®-TB Gold in-tube (QFT-GIT) & T-SPOT.TB®(T-Spot), are widely used to detect LBTI in adults. There is paucity of data regarding their use in children ( Methods: We retrospectively reviewed all the IGRA tests performed in children, for contact & new entrant screening, in our TB service between 2008 & 2010, to look at our indeterminate rates. Results: A total of 188 IGRA tests were performed. T-Spot was undertaken almost exclusively in children under 1 year. None of our cohort had indeterminate IGRA results with QFT-GIT or T-Spot. None of the children were diagnosed with active TB (multiple samples were sent for TB culture from 4 children). Conclusion: A definitive IGRA result is achievable in otherwise healthy children with close liaison between clinical and microbiology staff, prompt transfer of blood samples and incubating QFT-GIT samples within 4 hours of collection. Reference: 1Ling, D.I. et al. Immune-based diagnostics for TB in children:what is the evidence?Paed Resp Reviews. 2011;12(1):9-15.

Aims and Background: Only a limited body of literature exists on how best to investigate suspected Mycobacterium tuberculosis (TB) lymphadenopathy. We aimed to identify if any method of lymph node sampling had greater sensitivity in TB diagnosis. Methods: Records for all adult patients that were treated for extrapulmonary TB lymphadenitis between 2006 and 2010 were examined. The method of lymph node sampling, the rates of culture positivity, and the timescale of culture positivity were documented. Results: 133 patients received treatment for extrapulmonary TB lymphadenitis. Blind fine needle aspiration (FNA) was performed in 61 (46%) of patients, ultrasound guided FNA in 17 (13%), TRUCUT biopsy in 10 (8%) and complete surgical excision in 15 (11%). Overall 39% of these patients were either microscopy or culture positive for TB. The sensitivities of the sampling methods were 61% for blind FNA, 32% for ultrasound guided FNA, 40% for TRUCUT biopsy and 33% for surgical excision. Chi square analysis revealed no significant difference between sampling methods. If a blind FNA sample were to become culture positive this happened by week 2 in 76% of patients and week 3 in 86%. Conclusions: Our data suggests that blind FNA yields results that are of equal diagnostic accuracy to alternative methods. The data suggests that week 3 post sampling might represent a suitable time to consider further sampling methods, as most will be positive by this time, if they are to become positive.

Introduction New immigrant screening is vital for diagnosis of active and latent TB infection (LTBI), enabling treatment and chemoprophylaxis, and reducing risk of transmisison. Since 2007, we have used QuantiFERON-TB Gold (QFT), an Interferon Gamma Release Assay, in new immigrant screening. We are aware that a proportion of patients with positive results do not receive chemoprophylaxis, though reasons for this have not previously been explored. Aims We aimed to examine the reasons for non-treatment in screening recipients with positive QFT, to identify features that would enable us to effectively target this test. Methods We reviewed all positive QFT results in new immigrant screening recipients between 2007 and 2012, and examined patient records to establish reasons for non-treatment. Results 2884 QFT results were identified between 2007 and 2012, of which 684 (23.7%) were positive. Of the positive results, 12 patients (1.8%) were diagnosed with active TB through screening, and 672 (98.2%) were diagnosed with LTBI. Of the LTBI patients, 416 (61.9%) received chemoprophylaxis. The majority (74.3%) of those not treated were aged over 35, in keeping with guidelines. Over 8% were lost to follow-up; 5.4% declined treatment due to pregnancy or breastfeeding, and a similar number declined with no specific reason given. Conclusion The most common reason for non-treatment was age, in keeping with national guidelines. However a significant proportion declined or did not receive chemoprophylaxis due to patient mobility, pregnancy and loss to follow-up. Education about TB and LTBI is crucial during the screening process to improve patient engagement and reduce loss to follow-up.

Using the standards set in the Department of Health's toolkit for Tuberculosis prevention and treatment (2007), we audited whether our current, 5 day a week, service was achieving these standards. The laboratory processes ≈ 7500 samples per year, with "all" receiving continuously monitored liquid culture (Bactec MGIT 960 ®, BD Diagnostic Systems, Sparks, MD). Positive cultures for acid-fast bacilli are sent to the regional mycobacteriology reference laboratory for further identification & sensitivity testing.

Currently, reproducible, discriminatory typing methods for Mycobacterium tuberculosis are predominantly reliant on the presence of repetitive sequences in the bacterial genome. Such sequences include IS 6110, the direct repeat region, and mycobacterial interspersed repetitive sequence units (MIRU). The most established method is IS 6110 restriction fragment length polymorphism (RFLP) but this technique is technically demanding and several polymerase chain reaction-based methods have been developed to overcome its limitations. The molecular typing methods have been widely used to understand the epidemiology of the organism, and help to control its spread. Laboratory contamination can be confirmed, or discovered, on the basis of identical genotypes and suspected institutional or community outbreaks can be corroborated or refuted. Such methods have also greatly assisted in the understanding of the transmission of infection in the wider population, and the pathogenesis of disease in the individual patient. Finally, these techniques have been used to explore the evolutionary emergence and global distribution of this very significant human pathogen.