Antiprotozoal Drug Discovery: A Challenge That Remains

This chapter focuses on the effect that five parasitic diseases, produced by five protozoa, have on human health, namely: malaria, toxoplasmosis, Chagas disease, leishmaniasis and trichomoniasis. Our approach is the following: An analysis of the epidemiological components of these diseases in the context of the parasite’s life cycle; an analysis of the modifications in the natural history of these diseases introduced by human activities such as: migration, iatrogenesis and increased human mobility due to technological advances in the transportation of merchandise and persons; an analysis of how immune suppression produced by other living agents and chemotherapy affects these diseases, and their dispersion by tissue grafts; an analysis of the impact that these diseases have on the society, communities and family economies of countries affected by them, as well as what is being done to prevent them. In conclusion we find that research on new drugs is absolutely necessary to alleviate suffering, but given that these diseases are inextricably linked to poverty, we have to think of poverty as a disease, and as such we have an obligation to prevent it and eradicate it, as in the many other diseases and ills that befall mankind.

For many years, one of the driving forces for the development of drugs has been, and still is, the pharmaceutical industry, but the need for therapeutic agents regarding unprofitable diseases makes necessary a change in this situation. Parasitic diseases are a good example since the quantity and safety of many drugs currently in use are inadequate, and the development of new agents is insufficient. In the paper herein, we discuss the main methodologies used for the development and discovery of antiparasitics, the new trends and prospects, as well as the first results achieved by supranational programs and consortia created for such purposes.

Chagas’ disease, or American trypanosomiasis, is a potentially mortal disease caused by the protozoan Trypanosoma cruzi. It is included in the list of neglected diseases or poverty-linked diseases. An estimate of 5.7 million people in the endemic areas are infected, resulting in 7000 yearly deaths. The disease is distributed in Central and South America, Mexico, and the southern United States. Due to rural-urban migration, the parasite is transmitted by blood transfusion, by vertical transmission from mother to child, or by organ transplantation; on the other side, some cases have been detected in non-endemic zones both in America and in Europe. Chagas’ disease is among the 17 neglected diseases; it is a complex zoonosis, involving interaction of vectors species with wild, peridomestic, and domestic mammals, showing several clinical pictures and transmission modes. It poses the highest economic burden among parasitic diseases in Latin America due to its long chronicity. The clinical manifestations and epidemiologic traits of the disease vary from region to region. The current medication against T. cruzi, nifurtimox and benznidazole, has adverse effects. Aiming to make new treatment alternatives known, the activity of plant-isolated compounds from Central America, South America, and Mexico is herein discussed, along with their action against different stages of Trypanosoma cruzi.

Malaria is still a grave public health problem in tropical areas of the world. The greater genetic diversity of Plasmodium vivax at geographic sites with less control over infection reveals the importance of genetic studies of these parasites. Plasmodium vivax is the main cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The search for vaccine development remains an issue of global concern.

Malaria remains one of the major infectious diseases with high morbidity and mortality in developing and under-developed countries of the world. Although readily curable, the development of resistance by the malaria parasite especially Plasmodium falciparum, to existing antimalarials necessitates the need for continuous search for new antimalarial drugs. Several approaches have been adopted in this search including those based on natural products, particularly medicinal plants and herbs. As exemplified in the discovery of quinine and artemisinin, there has been intensified effort in the search of safe and efficacious plant-based antimalarial compounds. This search has yielded moderate success. The current chapter highlights the most promising plant-based drug discovery success with particular emphasis on studies that have reached some advanced clinical stages. With many plant-based compounds exerting antimalarial activities through multiple mechanisms, it is expected that further studies will complement current research efforts towards successful antimalarial drug discovery and development.

Protozoa infections are a worldwide health problem that preferentially affects populations in underdeveloped countries. Plasmodium, Leishmania, Trypanosoma, Toxoplasma, Neospora, Entamoeba and Trichomonas are some of the most important genuses of protozoan parasites that infect and invade cells, tissues and organs. These parasites proliferate, migrate and mutate to evade the chemotherapeutic effects of drugs that were previously effective for their treatment. The use of metals and metals complexes to control and treat these parasites, seems a very prominent alternative. Palladium, platinum, ruthenium, antimonium, gold, iron and vanadium are some of the metals that have been evaluated as antiprotozoal treatments with favorable results. A review of the experimental effects of metal complexes on these parasites follows, along with commentary.