Tuberculosis: drug resistance, fitness, and strategies for global control

Directly observed standardized short-course chemotherapy (DOTS) regimes are an effective treatment for drug susceptible tuberculosis disease. Surprisingly, DOTS has been reported to reduce the transmission of multi-drug resistant tuberculosis, and standardized short-course chemotherapy regimens with first-line agents have been found to be adequate treatments for some patients with drug resistant tuberculosis, including multi-drug resistance. These paradoxical observations and the apparent heterogeneity in treatment outcome of multi-drug resistant tuberculosis when using standard regimens may be due in part to limitations of in vitro drug susceptibility testing based on unique but mistakenly used techniques in diagnostic mycobacteriology. Experimental data and mathematical models indicate that the fitness cost conferred by a resistance determinant is the single most important parameter which determines the spread of drug resistance. Chromosomal alterations that result in resistance to first-line antituberculosis agents, e.g. isoniazid, rifampicin, streptomycin, may or may not be associated with a fitness cost. Based on work in experimental models and from observations in clinical drug resistant isolates a picture emerges in which, among the various resistance mutations that appear with similar rates, those associated with the least fitness cost are selected in the population

The (un)heavenly chorus in British politics: Bringing the what, the when and the how questions into the analysis of interest group influence

Increasing attention has been paid to interest group influence in the last decades. Nonetheless, the literature has hitherto theoretically and analytically focused on who exerts influence overlooking on what, when and how influence is exerted. By replicating the analysis in Bernhagen (2009) this works aims to bring the what, when and how questions back into the analysis of interest group influence. In doing so, I provide a more nuanced discussion on politics as being ‘about who gets what, when and how’ (Lasswell, 1936). Aloof from any pretence of conclusiveness, preliminary findings show that not only are those questions worth of investigation per se but also that they potentially have a strong impact on the who question