WP4: Reducing the daily dose of doxycycline to successfully treat filarial LE – a multinational, randomized, controlled non-inferiority trial.

This task is a clinical trial and it seeks to investigate whether a dose reduction of doxycycline to 100mg/day, which could be safely self-medicated, will show equivalent beneficial effects on LE pathology as the standard dosage of 200 mg/day which requires medical supervision. In previous LF trials, treatment with doxycycline resulted in a high macrofilaricidal (adult worm killing) effect with a much better efficacy than the mass drug administration (MDA) combination used in Africa (ivermectin plus albendazole), which does not show macrofilaricidal effects. A recent study by members of this consortium, which compared doxycycline treatment in LE patients with and without active worm infection showed an improvement of LE stages in both patients with ongoing infection (CFA-positive) and thus, harboring Wolbachia as targets for doxycycline, as well as in patients without ongoing infection. The study, which used the standard doxycycline regimen of 200 mg/day, suggested that the off-target drug effects of doxycycline such as direct anti-inflammatory effects on mammalian cells, including anti-proliferative effects on the lymph endothelium contribute significantly to the improvement seen in LE patients. This significant finding from the study showed for the first time a medical treatment and prevention for people suffering from filarial LE. However, in African rural health settings where LF is endemic, there are not enough medical personnel to carry out supervision after treatment with 200 mg/day doxycycline, hence the need for a dose reduction which can safely be self-medicated. This task will be led by Prof. Achim Hoerauf and all the PIs.