Flying DaF. Der Beitrag des Fachs DaF für die internationale Deutschlehrerausbildung und Germanistik

Riemer C. Flying DaF. Der Beitrag des Fachs DaF für die internationale Deutschlehrerausbildung und Germanistik. In: Böcker J, Stauch A, eds. Konzepte aus der Sprachlehrforschung – Impulse für die Praxis. Festschrift für Karin Kleppin. Fremdsprachen lebenslang lernen. Vol 4. Frankfurt a.M. u.a.: Peter Lang; 2015: 333-344

Treatment of Visceral Leishmaniasis: Model-Based Analyses on the Spread of Antimony-Resistant <em>L. donovani</em> in Bihar, India

<div><h3>Background</h3><p>Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment.</p> <h3>Methods and Findings</h3><p>We use simulation studies based on a mathematical <em>L. donovani</em> transmission model to identify parameters which can explain why treatment failure rates under antimonial treatment increased up to 65% in Bihar between 1980 and 1997. Model analyses suggest that resistance to treatment alone cannot explain the observed treatment failure rates. We explore two hypotheses referring to an increased fitness of antimony-resistant parasites: the additional fitness is (i) disease-related, by causing more clinical cases (higher pathogenicity) or more severe disease (higher virulence), or (ii) is transmission-related, by increasing the transmissibility from sand flies to humans or vice versa.</p> <h3>Conclusions</h3><p>Both hypotheses can potentially explain the Bihar observations. However, increased transmissibility as an explanation appears more plausible because it can occur in the background of asymptomatically transmitted infection whereas disease-related factors would most probably be observable. Irrespective of the cause of fitness, parasites with a higher fitness will finally replace sensitive parasites, even if antimonials are replaced by another drug.</p> </div

Data.

<p>Twenty treatment groups taken from 12 clinical studies involving antimonial treatment in Bihar, India, between 1980 and 1997 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001973#pntd.0001973-Olliaro1" target="_blank">[42]</a>. Points and bars show observed treatment failure rates with 95% confidence intervals.</p

Analyses on the effects of parameter variations on the treatment failure rates observed in Bihar.

<p>Two hypotheses on increased fitness in resistant parasites are compared in three panels A, B, C. Panel A) the distributions of and correlations between <i>T</i> (the year when first resistance has emerged), <i>TFR_res</i> (the treatment failure rate of patients infected with the resistant strain) and <i>f_FS</i> (the disease-related fitness factor) or <i>f_FA</i> (the transmission-related fitness factor). Panel B) the simulated overall TFR predicted by the model together with the data based observed TFR and their 95% confidence intervals. Panel C) the predicted proportions of resistant infections among all infections. In panel B and C, distributions of the hypothesis-specific predictions are represented by the minimum, by quantiles 2.5%, 25%, 50%, 75%, and 97.5%, and by the maximum. Model predictions are extrapolated until 2020 under the assumption of an unchanged antimonial treatment schedule.</p

Model-Based Investigations of Different Vector-Related Intervention Strategies to Eliminate Visceral Leishmaniasis on the Indian Subcontinent

<div><p>The elimination of infectious diseases requires reducing transmission below a certain threshold. The Visceral Leishmaniasis (VL) Elimination Initiative in Southeast Asia aims to reduce the annual VL incidence rate below 1 case per 10,000 inhabitants in endemic areas by 2015 via a combination of case management and vector control. Using a previously developed VL transmission model, we investigated transmission thresholds dependent on measures reducing the sand fly density either by killing sand flies (e.g., indoor residual spraying and long-lasting insecticidal nets) or by destroying breeding sites (e.g., environmental management).</p><p>Model simulations suggest that elimination of VL is possible if the sand fly density can be reduced by 67% through killing sand flies, or if the number of breeding sites can be reduced by more than 79% through measures of environmental management.</p><p>These results were compared to data from two recent cluster randomised controlled trials conducted in India, Nepal and Bangladesh showing a 72% reduction in sand fly density after indoor residual spraying, a 44% and 25% reduction through the use of long-lasting insecticidal nets and a 42% reduction after environmental management.</p><p>Based on model predictions, we identified the parameters within the transmission cycle of VL that predominantly determine the prospects of intervention success. We suggest further research to refine model-based predictions into the elimination of VL.</p></div