Progress Towards New Treatments for Human African Trypanosomiasis
The treatment of African trypanosomiasis has essentially remained unchanged for decades. A mountain of excellent work has been produced on many aspects of trypanosome biochemistry, biology, genetics, etc., but this has not translated into new therapies, a
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Progress Towards New Treatments for Human African Trypanosomiasis Jose A. Garcia-Salcedo, Jane C. Munday, Juan D. Unciti-Broceta, and Harry P. de Koning
Abstract
The treatment of African trypanosomiasis has essentially remained unchanged for decades. A mountain of excellent work has been produced on many aspects of trypanosome biochemistry, biology, genetics, etc., but this has not translated into new therapies, although the disease burden has steadily increased through the latter half of the twentieth century. The only new drug to be introduced in the last 50 years or so is eflornithine, in the late 1970s, for the treatment of late-stage gambiense sleeping sickness only. However, this was in many ways unsatisfactory and melarsoprol remained the first-line treatment for late-stage sleeping sickness until an alarming increase in treatment failures necessitated change. Since the emerging sleeping sickness epidemic became widely recognised, around the year 2000, needs-driven development of new drugs, and the preservation of the production of old drugs, has been the result of dedicated work by organisations such as the World Health Organisation, the Drugs for Neglected Diseases initiative (DNDi), the Access to Essential Medicines campaign, and the Consortium for Parasitic Drug Development (CPDD) among others, much of it in partnership with academia and the pharmaceutical industry. This has already
J.A. Garcia-Salcedo • J.D. Unciti-Broceta Infectious Diseases Unit, San Cecilio University Hospital, Biosanitary Research Institute of Granada, Av. Dr. Oloriz 16, 18012 Granada, Spain J.C. Munday Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK H.P. de Koning (*) Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK e-mail: [email protected] S. Magez and M. Radwanska (eds.), Trypanosomes and Trypanosomiasis, DOI 10.1007/978-3-7091-1556-5_9, # Springer-Verlag Wien 2014
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resulted in milestones such as the donations of free treatments by producers; improved drug distribution, case finding and clinical care; an improved 10-day melarsoprol treatment; the first clinical trial for an oral sleeping sickness drug— pafuramidine and the introduction of eflornithine–nifurtimox combination therapy to begin replacing melarsoprol. While these efforts have undoubtedly contributed to reducing the disease burden in central Africa, newer treatments are still very necessary, especially as most current treatments are threatened by drug resistance. Here, we review recent advances in understanding drug resistance mechanisms, progress towards new drugs, and new delivery systems to improve efficacy.
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Introduction
Chemotherapy of human African trypanosomiasis (HAT) started as early as 1905 with the introduction of the arsenic compound atoxyl, the name o
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