The Tuberculosis Network European Trials group (TBnet) ERS Clinical Research Collaboration: addressing drug-resistant tuberculosis through European cooperation

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The Use of Case Study Competitions to Prepare Students for the World of Work

As we continue into the new millennium, it is imperative that educational institutions equip graduates with the knowledge and skills that are increasingly needed and valued by business and industry. In this article, the authors argue that the case study approach and, specifically, case study competitions constitute an ideal pedagogical strategy for achieving this objective in an effective and efficient manner, with resulting benefits for both students and employers

Increasing Drug Resistance in Extensively Drug-Resistant Tuberculosis, South Africa

We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008–April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa

Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. METHODS: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. RESULTS: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). DISCUSSION: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB

Treatment Outcomes of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

BACKGROUND:Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis (MDRTB) are generally poor compared to drug sensitive disease. We sought to estimate treatment outcomes and identify risk factors associated with poor outcomes in patients with MDRTB. METHODOLOGY/PRINCIPAL FINDINGS:We performed a systematic search (to December 2008) to identify trials describing outcomes of patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined outcomes at the end of treatment and follow-up. Where appropriate, pooled covariates were analyzed to identify factors associated with worse outcomes. Among articles identified, 36 met our inclusion criteria, representing 31 treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57-67] of patients had successful outcomes, while 13% [9]-[17] defaulted, 11% [9]-[13] died, and 2% [1]-[4] were transferred out. Factors associated with worse outcome included male gender 0.61 (OR for successful outcome) [0.46-0.82], alcohol abuse 0.49 [0.39-0.63], low BMI 0.41[0.23-0.72], smear positivity at diagnosis 0.53 [0.31-0.91], fluoroquinolone resistance 0.45 [0.22-0.91] and the presence of an XDR resistance pattern 0.57 [0.41-0.80]. Factors associated with successful outcome were surgical intervention 1.91 [1.44-2.53], no previous treatment 1.42 [1.05-1.94], and fluoroquinolone use 2.20 [1.19-4.09]. CONCLUSIONS/SIGNIFICANCE:We have identified several factors associated with poor outcomes where interventions may be targeted. In addition, we have identified high rates of default, which likely contributes to the development and spread of MDRTB

GeneXpert—A Game-Changer for Tuberculosis Control?

Carlton Evans considers whether the new tuberculosis diagnostic test, GeneXpert, is the solution for TB control that it's said to be

A genealogy of hacking

Hacking is now a widely discussed and known phenomenon, but remains difficult to define and empirically identify because it has come to refer to many different, sometimes incompatible, material practices. This paper proposes genealogy as a framework for understanding hacking by briefly revisiting Foucault’s concept of genealogy and interpreting its perspectival stance through the feminist materialist concept of the situated observer. Using genealogy as a theoretical frame a history of hacking will be proposed in four phases. The first phase is the ‘pre-history’ of hacking in which four core practices were developed. The second phase is the ‘golden age of cracking’ in which hacking becomes a self-conscious identity and community and is for many identified with breaking into computers, even while non-cracking practices such as free software mature. The third phase sees hacking divide into a number of new practices even while old practices continue, including the rise of serious cybercrime, hacktivism, the division of Open Source and Free Software and hacking as an ethic of business and work. The final phase sees broad consciousness of state-sponsored hacking, the re-rise of hardware hacking in maker labs and hack spaces and the diffusion of hacking into a broad ‘clever’ practice. In conclusion it will be argued that hacking consists across all the practices surveyed of an interrogation of the rationality of information techno-cultures enacted by each hacker practice situating itself within a particular techno-culture and then using that techno-culture to change itself, both in changing potential actions that can be taken and changing the nature of the techno-culture itself

Negative incentive steering in a policy network

In this article the process of developing a policy for the recent comprehensive retrenchment operation in the Dutch university system is analysed from a theoretical point of view on decisionmaking. The article especially addresses the question whether some empirical evidence can be found for the rationalist view of collective decision-making, which states that a process of social communication should eventually lead to a unanimous and rational consensus concerning the selection of the optimal policy.\ud \ud The actual analysis concerns the way a retrenchment policy has been developed in a process of social communication between the most important actors: the Minister of Education and Science and the thirteen Dutch universities. It is assumed that the various communicative linkages between these actors can be interpreted as a policy network in which both governmental and non-governmental actors operate.\ud \ud The article concludes that in the Dutch university policy-network a complicated balance of interdependencies exists and that several sub-networks can be distinguished. It is also concluded that the Minister, while recognizing the interdependencies in the network, was able to use a special kind of (negative) incentive, inducing the universities to act as he wished.\ud \ud This negative incentive steering, however, also persuaded the universities to go to the utmost in their consultation efforts, thus trying to reach the rationalist ideal of collective decision-making. The final conclusion therefore is that the rationalist view of collective decision-making does not appear to be unrealistic. The article ends with a warning against a common mistake made regarding the normative appearance of the rationalist perspective

Transmission of MDR and XDR Tuberculosis in Shanghai, China

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are global health problems. We sought to determine the characteristics, prevalence, and relative frequency of transmission of MDR and XDR TB in Shanghai, one of the largest cities in Asia. Methods: TB is diagnosed in district TB hospitals in Shanghai, China. Drug susceptibility testing for first-line drugs was performed for all culture positive TB cases, and tests for second-line drugs were performed for MDR cases. VNTR-7 and VNTR-16 were used to genotype the strains, and prior treatment history and treatment outcomes were determined for each patient. Results: There were 4,379 culture positive TB cases diagnosed with drug susceptibility test results available during March 2004 through November 2007. 247 (5.6%) were infected with a MDR strain of M. tuberculosis and 11 (6.3%) of the 175 MDR patients whose isolate was tested for susceptibility to second-line drugs, were XDR. More than half of the patients with MDR and XDR were newly diagnosed and had no prior history of TB treatment. Nearly 57 % of the patients with MDR were successfully treated. Discussion: Transmission of MDR and XDR strains is a serious problem in Shanghai. While a history of prior anti-TB treatment indicates which individuals may have acquired MDR or XDR TB, it does not accurately predict which TB patients have disease caused by transmission of MDR and XDR strains. Therefore, universal drug susceptibility testing i

Heightened Vulnerability to MDR-TB Epidemics after Controlling Drug-Susceptible TB

Prior infection with one strain TB has been linked with diminished likelihood of re-infection by a new strain. This paper attempts to determine the role of declining prevalence of drug-susceptible TB in enabling future epidemics of MDR-TB.A computer simulation of MDR-TB epidemics was developed using an agent-based model platform programmed in NetLogo (See http://mdr.tbtools.org/). Eighty-one scenarios were created, varying levels of treatment quality, diagnostic accuracy, microbial fitness cost, and the degree of immunogenicity elicited by drug-susceptible TB. Outcome measures were the number of independent MDR-TB cases per trial and the proportion of trials resulting in MDR-TB epidemics for a 500 year period after drug therapy for TB is introduced.MDR-TB epidemics propagated more extensively after TB prevalence had fallen. At a case detection rate of 75%, improving therapeutic compliance from 50% to 75% can reduce the probability of an epidemic from 45% to 15%. Paradoxically, improving the case-detection rate from 50% to 75% when compliance with DOT is constant at 75% increases the probability of MDR-TB epidemics from 3% to 45%.The ability of MDR-TB to spread depends on the prevalence of drug-susceptible TB. Immunologic protection conferred by exposure to drug-susceptible TB can be a crucial factor that prevents MDR-TB epidemics when TB treatment is poor. Any single population that successfully reduces its burden of drug-susceptible TB will have reduced herd immunity to externally or internally introduced strains of MDR-TB and can experience heightened vulnerability to an epidemic. Since countries with good TB control may be more vulnerable, their self interest dictates greater promotion of case detection and DOTS implementation in countries with poor control to control their risk of MDR-TB