New Chemotherapy Against Trypanosomiasis and Leishmaniasis
Pp. 454-530 (77)
Jair L. de Siqueira-Neto
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi
affecting mostly the American continent eventually leading to chronic cardiomyopathy
or digestive syndromes. Human African Trypanosomiasis is caused by the related
parasite T. brucei, endemic in the African continent and being characterized by
invasion and damage in the central nervous system. Leishmaniasis is caused by a
number of species from the genera Leishmania and can manifest with different clinical
outcomes including skin ulcers and visceral organ damage, being endemic in 88
countries in tropical areas of the globe. Despite having different geographical
distribution and unique clinical symptoms, these diseases are all caused by related
protozoan parasites from the order Kinetoplastida. Another aspect shared by these
diseases is related to the treatment options currently available, unfortunately, all
inadequate. Serious problems are toxicity and inefficacy due parasite acquired
resistance or lack of natural susceptibility. The population affected by these three
diseases does not represent an attractive economic market, reflecting on little
pharmaceutical industry interest in developing better chemotherapies. However, in the
last decade, the situation has dramatically improved, with the active engagement of
philanthropic financial support, national government organizations, research centers,
the pharmaceutical industry and the Drugs for Neglected Diseases Initiative (DNDi).
After the development of screening assays, millions of molecules have been tested, and
some have reached Clinical Trials stage. A milestone has been set for the year 2020, by
the London Declaration: control of Chagas disease and leishmaniasis, and elimination of Human African Trypanosomiasis. Advances and progress to achieve these goals are
presented in this chapter.
African Trypanosomiasis, Chagas Disease, Chemotherapy, Drug
development, High-throughput hit selection, Lead optimization, Leishmaniasis,
Medicinal chemistry, Neglected Diseases, Pharmacokinetics.
Skaggs School of Pharmacy and Pharmaceutical Sciences / Center for Discovery and Innovation in Parasitic Diseases, University of California San Diego, La Jolla, CA 92093, USA.