Paul A. M. Michels (editor) - Trypanosomatids: Methods and Protocols (Methods in Molecular Biology (2116), Band 2116)

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Cover illustration: Scanning electron micrograph of Angomonas deanei in early cytokinesis, cleavage furrow indicates two daughter cells ready for division with two externalised flagella. Courtesy of Drs. Carolina Catta-Preta and Cristina Motta (Chapter 26).

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Around the turn of the twentieth century, parasitic protists were identified as causal agents of three groups of serious human diseases in tropical and subtropical countries in different parts of the world: sleeping sicknessor human African trypanosomiasis (HAT)in The Gambia [1], and subsequently in what was then North-East Rhodesia (now Zimbabwe) [2] and elsewhere; Chagas diseaseor American trypanosomiasisfirst in Brazil and then in large parts of Latin-America [3]; and visceral leishmaniasis, in India and then Tunisia [4]. These parasites wereTrypanosoma brucei gambiense,Trypanosoma brucei rhodesiense,Trypanosoma cruzi,Leishmania donovani, andLeishmania infantum. Recognition of otherLeishmaniaspecies responsible for the considerably different manifestations of leishmaniasis seen in many countries of different continents occurred steadily throughout the twentieth century, and novel pathogenicLeishmaniaspecies have continued to be discovered during the first two decades of the twenty-first century [4]. Coincident with the discoveries that apparently related trypanosomatid parasites were responsible for diverse (and serious) tropical diseases, a striking commonality in the mode of disease transmission was also recognized: these parasites were transmitted between people by specific blood-feeding insects.

Large populations wereand still areat risk of sleeping sickness, Chagas disease, or leishmaniasis. However, biological understanding of the parasites that cause these diseases and advances in dealing with the resultant health problems occurred at a slow pace for much of the last century. Some treatments for the diseases were developed (e.g., the antimonials introduced in the 1920s to treat leishmaniasis; suramin and melarsoprol, introduced in 1922 and 1949, respectively, to treat sleeping sickness). However, these and other medicines used to treat trypanosomatid diseases were not adequate: the medicines were little efficacious and often highly toxic. Indeed, there remains no medicine that can be used to treat effectively chronic forms of Chagas disease. Moreover, of the twentieth century pharmaceutical companies that arose and invested in research to develop drugs and vaccines for various human and veterinary infectious diseases, the trypanosomatid-borne diseases remained largely unexplored because they typically affected people living in impoverished regions. Thus, there was little economic incentive for the pharma industry to invest in such research. However, from the 1960s onwards, trypanosomatids started to attract the interest of academic laboratories, both in affluent countries, such as the USA, Japan, or within Europe, and the Global South where trypanosomatid diseases are typically endemic. This new interest was in part due to curiosity for peculiar aspects of the parasites, such as their large mitochondrial DNA content or the antigenic variation ofT. brucei, and in part it related to the wider health burden these parasites posed. Addressing the latter aspect was to a large extent made possible by the Special Programme for Research and Training in Tropical Diseases (TDR), created in 1974 by the World Health Organization (WHO), with cosponsoring by the United Nations Development Programme (UNDP), the World Bank, and UNICEF. TDR set out to conduct research on a defined group of neglected, tropical diseases, including those caused by the three trypanosomatid parasites (TriTryp) aimed at developing new tools to help control them and to train scientists and strengthen institutions from the endemic countries, so that they could play a major role in this endeavor [5, 6]. From the 1980s, research of the parasites and possibilities to combat the diseases was further boosted by support for collaboration between teams from countries in the north and those from countries in the south afflicted by the diseases, enabling multidisciplinary approaches, by organizations like the European Economic Community (later the European Union), the National Institutes of Health (NIH) in the USA, and later also various philanthropic organizations. Crucially, research supported by these and other initiatives has seen the introduction of a few new medicines into the clinic (e.g., eflornithine to treat sleeping sickness; amphotericin B and miltefosine to treat leishmaniasis), often through the repurposing of medicines developed to treat other diseases (for reviews,