Transmission of multidrug-resistant tuberculosis in the UK: a cross-sectional molecular and epidemiological study of clustering and contact tracing

BACKGROUND: Between 2000 and 2012 the number of multidrug-resistant (MDR) tuberculosis cases in the UK increased from 28 per year to 81 per year. We investigated the proportion of MDR tuberculosis cases arising from transmission in the UK and associated risk factors. METHOD: We identified patients with MDR tuberculosis notified in England, Wales, and Northern Ireland between Jan 1, 2004, and Dec 31, 2007, by linking national laboratory and surveillance data. Data for laboratory isolates, including drug sensitivities and 24-mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing were obtained routinely from the National Tuberculosis Reference laboratories as part of national tuberculosis surveillance. We investigated clusters of cases with indistinguishable MIRU-VNTR profiles to identify epidemiological links. We calculated transmission using the n-1 method and established associated risk factors by logistic regression. We also assessed the likelihood of transmission to additional secondary active tuberculosis cases, identified through conventional contact tracing. FINDINGS: 204 patients were diagnosed with MDR tuberculosis in the study period; 189 (92·6%) had an MIRU-VNTR profile. We identified 12 clusters containing 40 individuals and 149 unique strains. The proportion of cases attributable to recent transmission, on the basis of molecular data, was 15% (40 cases clustered-12 clusters/189 with a strain type). The proportion of cases attributable to recent transmission (ie, transmission within the UK) after adjustment for epidemiological links was 8·5% (22 cases with epidemiological links-six clusters/189 cases with a strain type). Being UK born (odds ratio 4·81; 95% CI 2·03-11·36, p=0·0005) and illicit drug use (4·75; 1·19-18·96, p=0·026) were significantly associated with clustering. The most common transmission setting was the household but 21 of 22 of epidemiological links were missed by conventional contact tracing. 13 secondary active tuberculosis cases identified by conventional contact tracing were mostly contacts of patients with MDR tuberculosis from countries of high tuberculosis burden. 11 (85%) of 13 shared the same country of birth as the index case, of whom ten did not share a strain type or drug resistance pattern. INTERPRETATION: Transmission of MDR tuberculosis in the UK is low and associated with being UK born or illicit drug use. MIRU-VNTR typing with cluster investigation was more successful at identifying transmission events than conventional contact tracing. Individuals with tuberculosis who have had contact with a known MDR tuberculosis source case from a country of high tuberculosis burden should have drug-sensitivity testing on isolates to ensure appropriate treatment is given. FUNDING: Public Health England

Comparative analysis of the impacts of marketing instruments on the organic market in Austria, the United Kingdom and Germany

Conclusions: This paper provides a comparative analysis of the impacts of the marketing instruments: The price-level can be identified as an important factor for further development. To promote sustained consumer demand, the premium price-level should be closer to the conventional price, although consumers are willing to pay some premium. Organic produce is associated with healthy food, which may appeal to consumers interested in healthy nutrition. Nevertheless, producers, processors and retailers of organic food should bear in mind general trends in food consumption and create organic food with lifestyle-oriented design. In future, supermarkets will become the main retail outlets for organic produce. In order to compete with larger, mainstream retailers, outlets like organic food shops or direct marketing channels should concentrate on offering special and added values e.g. by offering locally/regionally produced food or by creating an environment which provides the consumer with a unique shopping experience. Promotion activities are extremely important in influencing consumer behaviour, therefore all those involved should invest in further promotion activities. (ZENNER, S., FOSTER, C., PADEL, S. und B. WIRTHGEN (2000): Comparative analysis of the impacts of marketing instruments on the organic market in Austria, the United Kingdom and Germany. In: ALFLÖDI, Th., LOCKERETZ, W. und U. NIGLI: Proceedings 13th International IFOAM Scientific Conference. Zürich, S. 523

Oxygen superstructures throughout the phase diagram of (Y,Ca)Ba2Cu3O6+x\bf (Y,Ca)Ba_2 Cu_3 O_{6+x}

Short-range lattice superstructures have been studied with high-energy x-ray diffuse scattering in underdoped, optimally doped, and overdoped $\rm (Y,Ca)Ba_2 Cu_3 O_{6+x}$. A new four-unit-cell superstructure was observed in compounds with $x\sim 0.95$. Its temperature, doping, and material dependence was used to attribute its origin to short-range oxygen vacancy ordering, rather than electronic instabilities in the $\rm CuO_2$ layers. No significant diffuse scattering is observed in YBa$_2$Cu$_4$O$_{8}$. The oxygen superstructures must be taken into account when interpreting spectral anomalies in $\rm (Y,Ca)Ba_2 Cu_3 O_{6+x}$

Neutrino Spin Transitions and the Violation of the Equivalence Principle

The violation of the equivalence principle (VEP) causing neutrino oscillations is of current interest. We study here the possibility of not only flavor oscillation but spin flavor oscillation of ultra high energy ($\sim$ 1 PeV) neutrinos emanating from AGN due to VEP and due to the presence of a large magnetic field ($\sim$ 1 Tesla) in AGN. In particular we look at the resonance spin flavor conversion driven by the AGN potential. Interesting bounds on the transition magnetic moment of neutrinos may therefore be obtained.Comment: Latex, 12 pages, no figures. To appear in Journal of Physics G: Nuclear and Particle Physics. Two references adde

The Compact Nucleus of the Deep Silicate Absorption Galaxy NGC 4418

High resolution, Hubble Space Telescope (HST) near-infrared and Keck mid-infrared images of the heavily extinguished, infrared luminous galaxy NGC 4418 are presented. These data make it possible to observe the imbedded near-infrared structure on scales of 10-20 pc, and to constrain the size of the mid-infrared emitting region. The 1.1-2.2 um data of NGC 4418 show no clear evidence of nuclear star clusters or of a reddened active galactic nucleus. Instead, the nucleus of the galaxy consists of a ~100-200 pc linear structure with fainter structures extending radially outward. The near-infrared colors of the linear feature are consistent with a 10-300 Myr starburst suffering moderate levels (few magnitudes) of visual extinction. At 7.9-24.5 um, NGC 4418 has estimated size upper limits in the range of 30-80 pc. These dimensions are consistent with the highest resolution radio observations obtained to date of NGC 4418, as well as the size of 50-70 pc expected for a blackbody with a temperature derived from the 25 um, 60 um, and 100 um flux densities of the galaxy. Further, a spectral energy distribution constructed from the multi-wavelength mid-infrared observations show the strong silicate absorption feature at 10 um, consistent with previous mid-infrared observations of NGC 4418. An infrared surface brightness of 2.1x10^13 L_sun kpc^-2 is derived for NGC 4418. Such a value, though consistent with the surface brightness of warm ultraluminous infrared galaxies (ULIGs: L_IR [8-1000 um] >~ 10^12 L_sun) such as IRAS 05189-2524 and IRAS 08572+3915, is not large enough to distinguish NGC 4418 as a galaxy powered by an Active Galactic Nucleus (AGN), as opposed to a lower surface brightness starburst.Comment: LaTex, 7 pages, including 2 jpg figures and 3 postscript figures, AJ, in press (May, 2003

Nutritional profile of Syrian refugee children before resettlement

Background The year 2015 marked the highest number of refugees globally and included record numbers of Syrians moving to neighboring countries. Half of the Syrians were children aged ≤18 years. Our study sought to examine undernutrition and overnutrition among a group of Syrian refugee children who underwent medical screening by IOM for resettlement. Methods This is a retrospective review of Syrian refugee children aged 6 to 59 months from January 1, 2015 to December 31, 2016. The World Health Organization (WHO) Stata package computed Z-scores based on available weight and height data. Prevalence estimates of undernutrition (wasting and stunting) and overnutrition (overweight and obesity) were made using WHO standards. Multivariate analysis was used to determine the factors associated with wasting, stunting, and overnutrition, adjusting for age, sex, family size, and country of health assessment. Results A total of 14,552 Syrian refugee children aged 6 to 59 months underwent health assessments in Jordan (43·1%), Lebanon (38·8%), Turkey (7·0%), Greece (6·7%), Egypt (2·4%), and Iraq (2·1%). Overall, this group of Syrian refugee children had a low prevalence of wasting (< 5%) and stunting (< 10%), and high prevalence of overweight or obese (10.6%). Differences were observed in the prevalence of wasting by country of health assessment. In the multiple regression analysis, the prevalence of stunting and overnutrition decreased with increasing age, and being male was associated with overnutrition but not wasting and stunting. Conclusions Findings revealed an overall low prevalence of undernutrition among this group of Syrian children assessed, although prevalence varied by age group. This low prevalence may reflect the effectiveness, as well as expose possible gaps, of refugee nutrition programs or interventions in countries of asylum. Further studies are recommended to evaluate other possible contributors to malnutrition in this refugee group

Nutritional profile of Syrian refugee children before resettlement.

Background: The year 2015 marked the highest number of refugees globally and included record numbers of Syrians moving to neighboring countries. Half of the Syrians were children aged ≤18 years. Our study sought to examine undernutrition and overnutrition among a group of Syrian refugee children who underwent medical screening by IOM for resettlement. Methods: This is a retrospective review of Syrian refugee children aged 6 to 59 months from January 1, 2015 to December 31, 2016. The World Health Organization (WHO) Stata package computed Z-scores based on available weight and height data. Prevalence estimates of undernutrition (wasting and stunting) and overnutrition (overweight and obesity) were made using WHO standards. Multivariate analysis was used to determine the factors associated with wasting, stunting, and overnutrition, adjusting for age, sex, family size, and country of health assessment. Results: A total of 14,552 Syrian refugee children aged 6 to 59 months underwent health assessments in Jordan (43·1%), Lebanon (38·8%), Turkey (7·0%), Greece (6·7%), Egypt (2·4%), and Iraq (2·1%). Overall, this group of Syrian refugee children had a low prevalence of wasting (< 5%) and stunting (< 10%), and high prevalence of overweight or obese (10.6%). Differences were observed in the prevalence of wasting by country of health assessment. In the multiple regression analysis, the prevalence of stunting and overnutrition decreased with increasing age, and being male was associated with overnutrition but not wasting and stunting. Conclusions: Findings revealed an overall low prevalence of undernutrition among this group of Syrian children assessed, although prevalence varied by age group. This low prevalence may reflect the effectiveness, as well as expose possible gaps, of refugee nutrition programs or interventions in countries of asylum. Further studies are recommended to evaluate other possible contributors to malnutrition in this refugee group

Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: Observational study using the Enhanced Tuberculosis Surveillance system.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is one of the most widely-used vaccines worldwide. BCG primarily reduces the progression from infection to disease, however there is evidence that BCG may provide additional benefits. We aimed to investigate whether there is evidence in routinely-collected surveillance data that BCG vaccination impacts outcomes for tuberculosis (TB) cases in England. METHODS: We obtained all TB notifications for 2009-2015 in England from the Enhanced Tuberculosis surveillance system. We considered five outcomes: All-cause mortality, death due to TB (in those who died), recurrent TB, pulmonary disease, and sputum smear status. We used logistic regression, with complete case analysis, to investigate each outcome with BCG vaccination, years since vaccination and age at vaccination, adjusting for potential confounders. All analyses were repeated using multiply imputed data. RESULTS: We found evidence of an association between BCG vaccination and reduced all-cause mortality (aOR:0.76 (95%CI 0.64-0.89), P:0.001) and weak evidence of an association with reduced recurrent TB (aOR:0.90 (95%CI 0.81-1.00), P:0.056). Analyses using multiple imputation suggested that the benefits of vaccination for all-cause mortality were reduced after 10 years. CONCLUSIONS: We found that BCG vaccination was associated with reduced all-cause mortality in people with TB although this benefit was less pronounced more than 10 years after vaccination. There was weak evidence of an association with reduced recurrent TB

A feasibility study evaluating the uptake, effectiveness and acceptability of routine screening of pregnant migrants for latent tuberculosis infection in antenatal care: a research protocol

INTRODUCTION: Globally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI. METHODS AND ANALYSIS: This is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16-35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers. ETHICS AND DISSEMINATION: The study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals. TRIAL REGISTRATION NUMBER: NCT04098341

Private-key Symbolic Encryption

Symbolic encryption, in the style of Dolev-Yao models, is ubiquitous in formal security analysis aiming at the automated verification of network protocols. The naive use of symbolic encryption, however, may unnecessarily require an expensive construction: an arbitrary-length encryption scheme that is private and non-malleable in an adaptive CCA-CPA setting. Most of the time, such assumptions remain hidden and rather symbolic encryption is instantiated with a seemingly ``good\u27\u27 cryptographic encryption, such as AES in the CBC configuration. As an illustration of this problem, we first report new attacks on ECB and CBC based implementations of the well-known Needham-Schroeder and Denning-Sacco protocols. We then present a few symbolic encryption schemes along with their cryptographic semantics, and prove the hierarchical relations between the proposed schemes from both cryptographic and formal perspectives. These symbolic schemes can be seamlessly used in many existing formal security models