Trends in Parasitology
Volume 26, Issue 8, August 2010, Pages 395-403
Journal home page for Trends in Parasitology

Review
Collaborative actions in anti-trypanosomatid chemotherapy with partners from disease endemic areas

https://doi.org/10.1016/j.pt.2010.04.012Get rights and content

The protozoan diseases leishmaniasis, human African trypanosomiasis and Chagas disease are responsible for substantial global morbidity, mortality and economic adversity in tropical and subtropical regions. In most countries, existing strategies for control and treatment are either failing or under serious threat. Environmental changes, drug resistance and immunosuppression contribute to the emergence and spread of these diseases. In the absence of safe and efficient vaccines, chemotherapy, together with vector control, remains the most important measures to control trypanosomatid diseases. Here, we review current limitations of anti-trypanosomatid chemotherapy and describe new efforts to safeguard existing treatments and to identify novel drug leads through the three multinational and interdisciplinary European Union Framework Programmes for Research and Technological Development (FP7) funded consortia KALADRUG-R, TRYPOBASE, and LEISHDRUG.

Section snippets

Trypanosomatid diseases are a major global health problem

Trypanosomatids are parasitic kinetoplastid protozoa that cause major diseases in humans [1], including human African trypanosomiasis (HAT or sleeping sickness) caused by Trypanosoma brucei sspp., Chagas disease caused by Trypanosoma cruzi, and various forms of leishmaniasis caused by species of the Leishmania genus (Table 1). The leishmaniases are characterized by a spectrum of clinical manifestations, including visceral, cutaneous and mucocutaneous infections. In this review, we will focus on

Current limitations of anti-trypanosomatid chemotherapy

Chemotherapy, together with vector control, remains one of the most important elements in the control of trypanosomatid disease as there are currently no vaccines to prevent either Leishmania or Trypanosoma infection [6]. The arsenal of available drugs is limited, and all current treatments suffer from significant drawbacks (Table 2) (i.e. parenteral route of administration, length of treatment, toxicity, and/or cost, which limits their utilization in disease endemic areas).

Novel efforts to confront limitations in anti-trypanosomatid chemotherapy

The European Commission (EC) has supported research in parasitic diseases over the past 25 years through the successive Framework Programmes for Research and Technological Development (FP). Prior to the launch of the most recent Framework Programme (FP7, 2007-2013), the political support to increase European research in neglected infectious diseases mounted as a result of advocacy by the scientific community, international humanitarian organisations and stakeholders in disease-endemic

Future perspectives for a global trypanosomatid network

The establishment of the three consortia, LEISHDRUG, KALADRUG-R and TRYPOBASE, is the first important step in a new, concerted attempt to establish a global initiative to safeguard existing drugs and discover, develop and deliver new and improved drugs for neglected protozoal diseases. The three consortia presented in this review provide three distinct ways to tackle and overcome the challenges associated with discovery, development, delivery and guarding of new drug candidates for three

Acknowledgements

We express our gratitude to our partners from Europe and Developing Countries. Activities presented in this review are funded by EC (Grant agreements n°223414, n°222895, and n°223238). The Genome and Metabolome Integrated Initiative (GeMInI) is funded by secondary research funding of the Institute of Tropical Medicine, Antwerp. The authors would like to thank all members of the LEISHDRUG, KALADRUG-R and TRYPOBASE consortia for their contributions and critical reading of the manuscript.

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