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Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer-DNDi partnership is an outstanding example of "One World Health," in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area., Competing Interests: I have read the journal’s policy and want to declare the following conflicts of interest. The authors DK, SH, AH were employees of Bayer Animal Health GmbH, Germany. Bayer Animal Health GmbH was a company that developed and commercialized veterinary medicines including anthelmintics. The remaining authors of this manuscript have declared no competing interests.

Introduction: American trypanosomiasis, better known as Chagas disease, is a global public health issue. Current treatments targeting the causative parasite, Trypanosoma cruzi , are limited to two old nitroheterocyclic compounds; new, safer drugs are needed. New tools to identify compounds suitable for parasitological cure in humans have emerged through efforts in drug discovery., Areas Covered: Animal disease models are an integral part of the drug discovery process. There are numerous experimental models of Chagas disease described and in use; rather than going through each of these and their specific features, the authors focus on developments in recent years, in particular the imaging technologies that have dramatically changed the Chagas R&D landscape, and provide a critical view on their value and limitations for moving compounds forward into further development., Expert Opinion: The application of new technological advances to the field of drug development for Chagas disease has led to the implementation of new and robust/standardized in vivo models that contributed to a better understanding of host/parasite interactions. These new models should also build confidence in their translational value for moving compounds forward into clinical development.

Juan Carlos Gabaldón-Figueira,1 Nieves Martinez-Peinado,1 Elisa Escabia,1 Albert Ros-Lucas,1,2 Eric Chatelain,3 Ivan Scandale,3 Joaquim Gascon,1,2 María-Jesús Pinazo,2,3 Julio Alonso-Padilla1,2 1Barcelona Institute for Global Health (ISGlobal), Hospital Clínic—University of Barcelona, Barcelona, Spain; 2CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Madrid, Spain; 3Drugs for Neglected Diseases Initiative (DNDi), Geneva, SwitzerlandCorrespondence: Julio Alonso-Padilla, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic—University of Barcelona. Carrer Rosselló 149, Barcelona, 08036, Spain, Tel +34 932275400 – ext. 4284, Email julio.a.padilla@isglobal.orgAbstract: Chagas disease is the most important protozoan infection in the Americas, and constitutes a significant public health concern throughout the world. Development of new medications against its etiologic agent, Trypanosoma cruzi, has been traditionally slow and difficult, lagging in comparison with diseases caused by other kinetoplastid parasites. Among the factors that explain this are the incompletely understood mechanisms of pathogenesis of T. cruzi infection and its complex set of interactions with the host in the chronic stage of the disease. These demand the performance of a variety of in vitro and in vivo assays as part of any drug development effort. In this review, we discuss recent breakthroughs in the understanding of the parasite’s life cycle and their implications in the search for new chemotherapeutics. For this, we present a framework to guide drug discovery efforts against Chagas disease, considering state-of-the-art preclinical models and recently developed tools for the identification and validation of molecular targets.Keywords: Chagas disease, Trypanosoma cruzi, drug development, screenings, target, animal models