Human African trypanosomiasis: connecting parasite and host genetics Andre ´ Garcia 1 , David Courtin 1, 2 , Philippe Solano 2, 3 , Mathurin Koffi 2, 3 and Vincent Jamonneau 2 1 Institut de Recherche pour le De ´ veloppement, Unite ´ de Recherche 010, Faculte ´ de Pharmacie, 4 Avenue de l’Observatoire, 75270 Paris, France 2 Institut de Recherche pour le De ´ veloppement, Unite ´ Mixte de Recherche IRD-CIRAD 177, Laboratoire de Recherche et de Coordination sur les Trypanosomoses, TA 207/G, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France 3 Institut Pierre Richet, s/c INSP, Abidjan BP V47, Co ˆ te d’Ivoire In West and Central Africa, the protozoan parasite Trypanosoma brucei (T. b.) gambiense causes a chronic form of Human African trypanosomiasis (HAT) that might last several years, whereas T. b. rhodesiense refers to an acute form in East Africa that lasts weeks to months. Without treatment, both forms can cause death. Diagnosis relies on detecting parasites in blood, lymph or cerebrospinal fluid. HAT was no longer con- sidered a public health problem in the 1960s, but it returned to alarming levels in the 1990s. After intensify- ing case detection and treatment, WHO recently declared the situation is under control. However, research based on host and trypanosome interactions should be encouraged to help develop innovative tools for HAT diagnosis and treatment to prevent re-emergence. Human African trypanosomiasis control: let the past be a lesson Human African trypanosomiasis (HAT) is caused by pro- tozoan parasites. Classically, infection with Trypanosoma brucei gambiense (T. b. gambiense) gives rise to a chronic form in West and Central Africa that might last several years, whereas T. b. rhodesiense refers to an acute form in East Africa that might last from weeks to months. After a first hemolymphatic stage, with no specific clinical symp- toms, the chronic form evolves progressively into a central nervous system syndrome (chronic encephalopathy, headache, mental changes and terminal somnolence state), whereas the acute form is characterized by an early severe infectious syndrome. Without treatment, both forms cause death. After an epidemic from 1900 to 1940, HAT was largely eradicated in the 1960s [1]. However, in the past two decades the disease has re-emerged and returned to levels comparable with those in the early 20th century. In 1998 and 1999, some 45 000 new cases were reported every year [2], and in 2000 it was estimated that 300 000 individuals were infected. However, only 10–15% of the 60 million people living in risk areas were under surveillance [3]. Faced with this alarming situation, the National Control Programs of the more endemic countries, notably in Central Africa, intensified active case detection and treatment with substantial financial support (from the French and Belgian governments and from WHO). The results seem promising. WHO have recently indicated a decline in the number of new reported cases and declared that we might now have returned to an elimination pro- cess, defined as the control of the disease by means of case detection and treatment, and by the development of epidemiologic surveillance systems [3,4]. Re-emergence in the past two decades can be explained partly by the relaxation of control and, to a lesser extent, by a decrease in the financial support for research. To avoid a new dramatic re-emergence, we remain convinced that the elimination process has to be linked with substantial research developments in various areas, such as the study of host–parasite interactions. The aim of the present paper is to report our opinion on the role of the interactions between host and parasite genetic polymorphisms on the variability of responses to infection. Programs focusing on these interactions will help clarify the mechanisms involved in the re-emergence phenomenon, and will parti- cipate in the development of innovative and better adapted control tools (for diagnosis, treatment and vaccine strategies) to prevent future re-emergence. HAT diagnosis and the variability of responses to infection Despite the classical dichotomy between the chronic form of HAT caused by T. b. gambiense and the acute form attributable to T. b. rhodesiense, a diversity of clinical progression has been observed for T. b. gambiense, from asymptomatic forms [5] to acute forms [6,7]. In East Africa, there is a longstanding belief that the disease is chronic in southern countries and increases in severity towards the north. Some chronic forms caused by T. b. rhodesiense have also been mentioned [8]. This diversity of clinical progres- sion, together with the diversity of symptoms encountered in HAT, renders accurate clinical diagnosis of HAT impossible. Nevertheless, control of HAT has been based principally on case detection and treatment, which are highly depen- dent on the strain and the stage of the disease. This strategy assumes that the population at risk can be easily divided into healthy subjects and HAT cases, although the Opinion TRENDS in Parasitology Vol.22 No.9 Corresponding author: Garcia, A. (andre.garcia@ird.fr) Available online 11 July 2006. www.sciencedirect.com 1471-4922/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2006.06.011