Survival of drug resistant tuberculosis patients in Lithuania: retrospective national cohort study

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement FP7-223681.

Variability in interpretation of chest radiographs among Russian clinicians and implications for screening programmes: observational study.

OBJECTIVE: To determine variability in interpretation of chest radiographs among tuberculosis specialists, radiologists, and respiratory specialists. DESIGN: Observational study. SETTING: Tuberculosis and respiratory disease services, Samara region, Russian Federation. PARTICIPANTS: 101 clinicians involved in the diagnosis and management of pulmonary tuberculosis and respiratory diseases. MAIN OUTCOME MEASURES: Interobserver and intraobserver agreement on the interpretation of 50 digital chest radiographs, using a scale of poor to very good agreement (kappa coefficient: < or = 0.20 poor, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 good, and 0.81-1.00 very good). RESULTS: Agreement on the presence or absence of an abnormality was fair only (kappa = 0.380, 95% confidence interval 0.376 to 0.384), moderate for localisation of the abnormality (0.448, 0.444 to 0.452), and fair for a diagnosis of tuberculosis (0.387, 0.382 to 0.391). The highest levels of agreement were among radiologists. Level of experience (years of work in the specialty) influenced agreement on presence of abnormalities and cavities. Levels of intraobserver agreement were fair. CONCLUSIONS: Population screening for tuberculosis in Russia may be less than optimal owing to limited agreement on interpretation of chest radiographs, and may have implications for radiological screening programmes in other countries

BRICS' role in global health and the promotion of universal health coverage: the debate continues.

The acronym BRIC was coined by Jim O’Neill, a senior executive at Goldman Sachs, to denote four emerging national economies: Brazil, the Russian Federation, India and China. Although BRICS and other multinational groupings may be useful to policy-makers involved in the development of some foreign policies, it remains unclear if such groupings have a role in the study and development of global health policy. We examine the debate around this issue and focus on BRICS’ potential role in the promotion of universal health coverage – an “umbrella” goal for health in the post-2015 development framework. We do not argue that BRICS has no value as a grouping. The constituent nations do have some things in common: they are all large, populous, diverse countries with many different ethnic, social and – in some cases – religious divisions. They share these characteristics with some other countries, such as Indonesia, Nigeria, Indonesia and Pakistan, that have made less progress toward universal health coverage but may be able to learn from BRICS’ experiences. There is no doubt that, in the promotion of universal health coverage, there is a need for collaboration and shared learning. However, a grouping of countries that may make sense in the coordination of global macroeconomic policy cannot be assumed to be relevant in the development of any global health policy

Microevolution of extensively drug-resistant tuberculosis in Russia.

Extensively drug-resistant (XDR) tuberculosis (TB), which is resistant to both first- and second-line antibiotics, is an escalating problem, particularly in the Russian Federation. Molecular fingerprinting of 2348 Mycobacterium tuberculosis isolates collected in Samara Oblast, Russia, revealed that 72%belonged to the Beijing lineage, a genotype associated with enhanced acquisition of drug resistance and increased virulence. Whole-genome sequencing of 34 Samaran isolates, plus 25 isolates representing global M. tuberculosis complex diversity, revealed that Beijing isolates originating in Eastern Europe formed a monophyletic group. Homoplasic polymorphisms within this clade were almost invariably associated with antibiotic resistance, indicating that the evolution of this population is primarily driven by drug therapy. Resistance genotypes showed a strong correlation with drug susceptibility phenotypes. A novel homoplasic mutation in rpoC, found only in isolates carrying a common rpoB rifampicin-resistance mutation, may play a role in fitness compensation. Most multidrug-resistant (MDR) isolates also had mutations in the promoter of a virulence gene, eis, which increase its expression and confer kanamycin resistance. Kanamycin therapy may thus select for mutants with increased virulence, helping preserve bacterial fitness and promoting transmission of drug-resistant TB strains. The East European clade was dominated by two MDR clusters, each disseminated across Samara. Polymorphisms conferring fluoroquinolone resistance were independently acquired multiple times within each cluster, indicating that XDR TB is currently not widely transmitted. © 2012 by Cold Spring Harbor Laboratory Press

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Ethics, politics and migration: Public debates on the free movement of Romanians and Bulgarians in the UK, 2006–2013

Public debates on immigration have become the subject of much concern, particularly in the UK. This article applies an ethical lens to assess changes in public debates over intra-EU migration in six UK national newspapers during 2006 and 2013. It finds an almost complete dominance of communitarian justifications, mainly based on welfare chauvinism, but a notable increase in security-related arguments and a decrease in economic nationalist ideas. Alternative cosmopolitan arguments about immigration go from rare to virtually absent. The discussion links these shifts to a failure of the UK centre-left to overcome historic difficulties in presenting a coherent narrative on immigration policy

Methodological aspects of assessing regional publication activity and citations: the case of the RF central federal District Universities

The article focuses on calculations to assess contribution made by University publication activity and citations indicators to the regional integral indicator of publication activity and citations for Voronezh Region, Ivanovo Region, and Ryazan Region. It shows that relative indicators are more significant in calculations of this kind therefore regions with a large number of Universities have no advantage. The article offers a triangular matrix of ratios expressing how much one regional integral indicator of publication activity and citations exceeds the other, which was calculated for the RF Central Federal District regions. Ratios range up to 3.47. It is concluded that the offered triangular matrix of ratios can be useful for arbitrary rankings of items by values of some indicator.Key words: publication activity, citations, regional integral indicator of publication activity and citations, RSCI, RF Central Federal District, a triangular matrix of ratios for arbitrary rankings

The Directly Observed Therapy Short-Course (DOTS) strategy in Samara Oblast, Russian Federation

BACKGROUND: The World Health Organisation (WHO) defines Russia as one of the 22 highest-burden countries for tuberculosis (TB). The WHO Directly Observed Treatment Short Course (DOTS) strategy employing a standardised treatment for 6 months produces the highest cure rates for drug sensitive TB. The Russian TB service traditionally employed individualised treatment. The purpose of this study was to implement a DOTS programme in the civilian and prison sectors of Samara Region of Russia, describe the clinical features and outcomes of recruited patients, determine the proportion of individuals in the cohorts who were infected with drug resistant TB, the degree to which resistance was attributed to the Beijing TB strain family and establish risk factors for drug resistance. METHODS: prospective study RESULTS: 2,099 patients were recruited overall. Treatment outcomes were analysed for patients recruited up to the third quarter of 2003 (n = 920). 75.3% of patients were successfully treated. Unsuccessful outcomes occurred in 7.3% of cases; 3.6% of patients died during treatment, with a significantly higher proportion of smear-positive cases dying compared to smear-negative cases. 14.0% were lost and transferred out. A high proportion of new cases (948 sequential culture-proven TB cases) had tuberculosis that was resistant to first-line drugs; (24.9% isoniazid resistant; 20.3% rifampicin resistant; 17.3% multidrug resistant tuberculosis). Molecular epidemiological analysis demonstrated that half of all isolated strains (50.7%; 375/740) belonged to the Beijing family. Drug resistance including MDR TB was strongly associated with infection with the Beijing strain (for MDR TB, 35.2% in Beijing strains versus 9.5% in non-Beijing strains, OR-5.2. Risk factors for multidrug resistant tuberculosis were: being a prisoner (OR 4.4), having a relapse of tuberculosis (OR 3.5), being infected with a Beijing family TB strain (OR 6.5) and having an unsuccessful outcome from treatment (OR 5.0). CONCLUSION: The implementation of DOTS in Samara, Russia, was feasible and successful. Drug resistant tuberculosis rates in new cases were high and challenge successful outcomes from a conventional DOTS programme alone

Tuberculosis control in Samara Oblast, Russia: institutional and regulatory environment.

SETTING: Tuberculosis control programme in Samara Oblast, Russia, funded in part by the government of the United Kingdom. OBJECTIVE: To identify and evaluate institutional and regulatory influences as well as incentives and disincentives that might be amenable to change in the promotion of the DOTS strategy. DESIGN: Multidisciplinary situational analysis through in-depth interviews of stakeholders and review of official federal and oblast documents. RESULTS: Interpretation of traditional notification data is complex because classification and reporting systems differ from World Health Organization principles. Regulations governing financing encourage lengthy hospitalisations and interventions, and provide few incentives to shift policy to ambulatory care. CONCLUSION: Accurate comparability of epidemiological trends and programmatic successes requires equivalent classification and reporting systems. If the DOTS strategy is to be sustainable, changes to financing systems will be needed