Treatment of human African trypanosomiasis--present situation and needs for research and development.

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.

Temporal analysis of free exploration of an elevated plus-maze in mice.

The elevated plus-maze (EPM) is a very common rodent test of anxiety. It is based on an approach-avoidance conflict between secure closed arms and aversive open arms. However, discrepancies remain on the interpretation of animals' behavior in this assay. The purpose of our study was to get a better understanding of the mouse behavior in the EPM. We applied a minute-by-minute analysis to compare the behavior of mice forcibly exposed to the maze or set free to explore the maze from a familiar box. Three strains of mice (CD1, BALB/c, and C57Bl/6) were tested. The combination of our different conditions of the test with the minute-by-minute analysis showed that mice did not avoid open arms during the first 2 min of the test when they were forcibly exposed to the EPM. Conversely, free exploration of the EPM resulted in a pattern of behavior characterized by open arm avoidance from the outset, demonstrating that open arm avoidance in mice is unconditioned. These findings generalize across the 3 mouse strains. These data suggest that rodents enter the open arms to complete spatial information about the apparatus as a whole before their natural tendency to avoid them is expressed. Our data also indicate that a detailed behavioral analysis is needed whenever BALB/c mice are to be exposed by force to the EPM. Further studies are required to fully understand the behavior of rodents in the EPM and to avoid false interpretations in the fields of psychopharmacology and behavioral neuroscience.

Characterization of sleeping sickness transmission sites in rural and periurban areas of Kinshasa (République Démocratique du Congo).

To characterize the potential transmission sites of sleeping sickness in Kinshasa, two entomologic surveys were carried out during the dry and the rainy seasons in rural and periurban areas of Kinshasa in 2005. About 610 pyramidal traps were set up, and 897 Glossina fuscipes quanzensis were captured. Environmental and biologic factors were reported, and relationships between these factors were evaluated using logistic regression and multiple correspondence analysis. The biologic factors (the presence of tsetse flies, human blood meals, and teneral flies) were progressively accumulated at each capture site to permit the characterization of the sleeping sickness transmission risk. The dry season was found to be a more favorable period for the disease transmission than the rainy season. Moreover, the landscapes characterized by the presence of argillaceous soils, raised ground cover with forest residues and rivers, were identified as types of environments with greater risk of sleeping sickness transmission. Pig breeding appeared as an important factor increasing the disease transmission. If vector control is continuously performed along rivers segments at high risk, the transmission of sleeping sickness in rural and periurban areas of Kinshasa will considerably decrease.

Human African trypanosomiasis transmission, Kinshasa, Democratic Republic of Congo.

To investigate the epidemiology of human African trypanosomiasis (sleeping sickness) in Kinshasa, Democratic Republic of Congo, 2 entomologic surveys were conducted in 2005. Trypanosoma brucei gambiense and human-blood meals were found in tsetse fly midguts, which suggested active disease transmission. Vector control should be used to improve human African trypanosomiasis control efforts.