New formulations and therapeutic switching of the established drugs, amphotericin
B and paromomycin, together with the discovery of miltefosine, have significantly
improved the opportunities for treatment of visceral leishmaniasis (VL) chemotherapy.
However, for human African trypanosomiasis (HAT), Chagas disease and cutaneous leishmaniases
there has been limited progress. For HAT, a novel diamidine, parfuramidine, is in
phase III clinical trial for early-stage disease, but for the treatment of late-stage
disease there are no new drugs and combinations of eflornithine with melarsoprol or
nifurtimox have been the focus of clinical studies. For Chagas disease, different
classes of compounds that have validated biochemical targets, sterol biosynthesis
methylases and cysteine proteases, are in various stages of development. The genome
sequences that are now available for the pathogens that cause the leishmaniases and
trypanosomiases, and new methods for rapid validation of targets, are part of the
solution to discover new drugs. The integration of medicinal chemistry, pharmacokinetics,
project planning and interaction with the pharma/biotech sector are essential if progress
is to be made. Although there are financial constraints, the appearance of new funding
sources and not-for-profit product development partnerships offers hope for drug development.