BackgroundThe incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency.Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level.MethodsAll individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included.ResultsBetween 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001).The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old.ConclusionUsing a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change.We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required.

We have assessed tracheal intubating conditions in 60 ASA I or II patients after induction of anaesthesia with propofol 2.5 mg kg-1 and alfentanil 10 or 20 micrograms kg-1 with or without i.v. lignocaine 1 mg kg-1. No neuromuscular blocking agents were administered. Patients were allocated randomly to four groups: group 1 = propofol-alfentanil 10 micrograms kg-1; group 2 = propofol-alfentanil 10 micrograms kg-1-lignocaine 1 mg kg-1; group 3 = propofol-alfentanil 20 micrograms kg-1; group 4 = propofol-alfentanil 20 micrograms kg-1-lignocaine 1 mg kg-1. Intubating conditions were assessed as acceptable or unacceptable on the basis of a scoring system dependent on ease of laryngoscopy, vocal cord position and coughing on insertion of the tracheal tube. Intubating conditions were acceptable in 20%, 73%, 73% and 93% of patients in groups 1-4, respectively. Intubating conditions were better and there was less coughing in the lignocaine group.

The Effective Blood Concentration (EC) of propofol required to prevent response to surgical incision was determined in 65 ASA I or II female patients breathing either 100% oxygen or 67% N2O in oxygen. Propofol was administered via a microcomputer-controlled infusion system programmed to maintain the blood propofol concentration at predetermined target values. The blood propofol concentrations predicted by the micro-computer were validated by measurement of whole blood propofol concentration. Predicted and measured concentrations differed during infusion of propofol, but became similar after discontinuing the infusion for at least 90 s, suggesting that equilibration within the central compartment was incomplete during infusion. The response to the initial incision was observed and probit analysis used to determine the predicted blood concentration at which 50% of patients responded. The predicted EC50 for propofol/N2O/O2 and propofol/O2 was 4.5 micrograms ml-1 and 6.0 micrograms ml-1 respectively, and the measured EC50 propofol/N2O/O2 and propofol/O2 was 5.36 micrograms ml-1 and 8.1 micrograms ml-1, 67% nitrous oxide in oxygen reducing the predicted EC50 by 25% and the measured EC50 of propofol by 33%. The predicted EC may be more representative of the equilibrated concentration in the central compartment and thus reflective of tissue propofol concentrations.

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BackgroundMycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries to determine Mycobacterium tuberculosis relatedness. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken.MethodsWe studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data for the relevant patients were extracted from the Enhanced Tuberculosis Surveillance system run by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, to samples from individuals with shared epidemiological risk factors, and to those with both characteristics.Findings1999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only co-residence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4.InterpretationIn the setting studied, this molecular epidemiological study shows MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage.FundingPublic Health England, Health Innovation Challenge Fund, NIHR Health Protection Research Unit Oxford, NIHR Oxford Biomedical Research Centre.

Initial resistance of bacterial infection is mediated primarily by polymorphonuclear leucocytes (PMN). Anaesthetic agents have been reported to impair various aspects of PMN function. It is possible that the use of these agents to sedate critically ill patients may further compromise an already depressed host defence mechanism. A flow cytometric technique with fresh whole blood from 10 healthy volunteers was used. Phagocytic and respiratory burst activity of PMN incubated for 1 h with either propofol, thiopentone, midazolam or ketamine at both clinical plasma concentrations and 100 times this concentration were determined. Thiopentone at the higher concentration reduced both respiratory burst activity (mean peak channel 50.7 compared with control value of 77.6 (P < 0.0001)) and phagocytosis (mean peak channel 47.5 compared with 79.9 (P < 0.0001)). Ketamine at 100 times the clinical plasma concentration also reduced respiratory burst and phagocytosis, but this failed to reach statistical significance (P = 0.10 and P = 0.053, respectively). No significant depression occurred in the other groups. The results suggest that these i.v. anaesthetic agents, at clinically relevant concentrations, have minimal effects on PMN phagocytosis and oxygen free radical production. At higher concentrations thiopentone and ketamine may affect phagocytic function and thiopentone may impair intracellular cytolysis.

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We used whole-genome sequencing (WGS) to delineate transmission networks and investigate the benefits of WGS during cluster investigation.We included clustered cases of multidrug-resistant (MDR) tuberculosis (TB)/extensively drug-resistant (XDR) TB linked by mycobacterial interspersed repetitive unit variable tandem repeat (MIRU-VNTR) strain typing or epidemiological information in the national cluster B1006, notified between 2007 and 2013 in the UK. We excluded from further investigation cases whose isolates differed by greater than 12 single nucleotide polymorphisms (SNPs). Data relating to patients' social networks were collected.27 cases were investigated and 22 had WGS, eight of which (36%) were excluded as their isolates differed by more than 12 SNPs to other cases. 18 cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in seven out of 18 cases (39%) in the transmission network following WGS and epidemiological investigation.This investigation of a drug-resistant TB cluster illustrates the opportunities and limitations of WGS in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However, not every cluster will be solvable, regardless of the quality of genomic data.