• NECT is next: implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness.

      Yun, O; Priotto, G; Tong, J; Flevaud, L; Chappuis, F; Médecins Sans Frontières/Doctors Without Borders, New York, New York, USA; Epicentre, Paris, France; Médecins Sans Frontières, Geneva, Switzerland; Médecins Sans Frontières, Barcelona, Spain; Geneva University Hospitals, Geneva, Switzerland (2010-05-25)
    • Sleeping sickness

      Malvy, D; Chappuis, F; Travel Clinics and Division of Tropical Medicine and Imported Diseases, Department of Internal Medicine and Tropical Diseases, University Hospital Centre, Bordeaux, France; Universite de Bordeaux, Faculty of Medicine, INSERM U897 and Centre Rene-Labusquiere (Tropical Medicine Branch), Bordeaux, France; Division of International and Humanitarian Medicine, Geneva University Hospital, Switzerland; Medecins Sans Frontieres, Operational Centre, Geneva, Switzerland (Wiley-Blackwell, 2011-04-04)
      Human African trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease that flourishes in impoverished, rural parts of sub-Saharan Africa. It is caused by infection with the protozoan parasite Trypanosoma brucei and is transmitted by tsetse flies of the genus Glossina. The majority of cases are caused by T. b. gambiense, which gives rise to the chronic, anthroponotic endemic disease in Western and Central Africa. Infection with T. b. rhodesiense leads to the acute, zoonotic form of Eastern and Southern Africa. The parasites live and multiply extracellularly in the blood and tissue fluids of their human host. They have elaborated a variety of strategies for invading hosts, to escape the immune system and to take advantage of host growth factors. HAT is a challenging and deadly disease owing to its complex epidemiology and clinical presentation and, if left untreated, can result in high death rates. As one of the most neglected tropical diseases, HAT is characterized by the limited availability of safe and cost-effective control tools. No vaccine against HAT is available, and the toxicity of existing old and cumbersome drugs precludes the adoption of control strategies based on preventive chemotherapy. As a result, the keystones of interventions against sleeping sickness are active and passive case-finding for early detection of cases followed by treatment, vector control and animal reservoir management. New methods to diagnose and treat patients and to control transmission by the tsetse fly are needed to achieve the goal of global elimination of the disease.
    • Treatment of human African trypanosomiasis--present situation and needs for research and development.

      Legros, D; Ollivier, G; Gastellu-Etchegorry, M; Paquet, C; Burri, C; Jannin, J; Büscher, P; Epicentre, Paris, France. dlegros@epicentre.msf.org (Elsevier, 2002-07)
      Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.