Failure of fluconazole in treating cutaneous leishmaniasis caused by Leishmania guyanensis in the Brazilian Amazon: An open, nonrandomized phase 2 trial

BackgroundThe treatment of Leishmaniasis caused by Leishmania (Viannia) guyanensis is based on a weak strength of evidence from very few clinical trials and some case series reports. Current treatment guidelines recommend pentamidine isethionate or meglumine antimoniate (Glucantime) as the first-line choices. Both are parenteral drugs with a low therapeutic indexes leading to a high risk of undesired effects. Imidazole derivatives interfere with the production of leishmanial ergosterol, an essential component of their membrane structure. One drug that has been studied in different clinical presentations of Leishmania is fluconazole, a hydrophilic bis-triazole, which is easily absorbed through the oral route with a low toxicity profile and is considered safe for children. This drug is readily available in poor countries with a reasonable cost making it a potential option for treating leishmaniasis.Methods and findingsAn adaptive nonrandomized clinical trial with sequential groups with dose escalation of oral fluconazole was designed to treat adult men with localized cutaneous leishmaniasis (LCL) in Manaus, Brazil. Eligible participants were patients with LCL with confirmed Leishmania guyanensis infection.ResultsTwenty adult male patients were treated with 450 mg of fluconazole daily for 30 days. One patient (5%) was cured within 30 days of treatment. Of the 19 failures (95%), 13 developed a worsening of ulcers and six evolved lymphatic spreading of the disease. Planned dose escalation was suspended after the disappointing failure rate during the first stage of the trial.Conclusion/SignificanceOral fluconazole, at the dose of 450mg per day, was not efficacious against LCL caused by Leishmania guyanensis in adult men.Trial registrationBrazilian Clinical Trial Registration (ReBec)—RBR-8w292w; UTN number—1158-2421</div

Spatiotemporal Characterization of a Fibrin Clot Using Quantitative Phase Imaging

Studying the dynamics of fibrin clot formation and its morphology is an important problem in biology and has significant impact for several scientific and clinical applications. We present a label-free technique based on quantitative phase imaging to address this problem. Using quantitative phase information, we characterized fibrin polymerization in real-time and present a mathematical model describing the transition from liquid to gel state. By exploiting the inherent optical sectioning capability of our instrument, we measured the three-dimensional structure of the fibrin clot. From this data, we evaluated the fractal nature of the fibrin network and extracted the fractal dimension. Our non-invasive and speckle-free approach analyzes the clotting process without the need for external contrast agents