title: Population genetics of Trypanosoma brucei gambiense in sleeping sickness patients with treatment failures in the focus of Mbuji-Mayi, Democratic Republic of the Congo.
abstract: Human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) is caused by the protozoan Trypanosoma brucei gambiense. Until recently, all patients in the second or neurological stage of the disease were treated with melarsoprol. At the end of the past and the beginning of the present century, alarmingly high relapse rates in patients treated with melarsoprol were reported in isolated HAT foci. In the Mbuji-Mayi focus of DRC, a particular mutation that confers cross resistance for pentamidine and melarsoprol was recently found for all strains studied. Nevertheless, treatment successfully cured a significant proportion of patients. To check for the existence of other possible genetic factors of the parasites, we genotyped trypanosomes isolated from patients before and after treatment (relapsing patients) with eight microsatellite markers. We found no evidence of any genetic correlation between parasite genotype and treatment outcome and we concluded that relapse or cure probably depend more on patients' factors such as disease progression, nutritional or immunological status or co-infections with other pathogens. The existence of a melarsoprol and pentamidine resistance associated mutation at such high rates highlights an increasing problem, even for other drugs, especially those using the same transporters as melarsoprol and pentamidine.
authors.affiliation: Département de Parasitologie, Institut National de Recherche Biomédicale, Av. de la Démocratie, BP 1197, Kinshasa Gombe, Congo.
authors.forename: Patient Pati
authors.initials: PP
authors.lastname: Pyana
authors.affiliation: Centre International de Recherche-Développement sur l'Élevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Modou
authors.initials: M
authors.lastname: Sere
authors.affiliation: Centre International de Recherche-Développement sur l'Élevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso; Université Polytechnique de Bobo-Dioulasso, 01 BP 1091 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Jacques
authors.initials: J
authors.lastname: Kaboré
authors.affiliation: Centre International de Recherche-Développement sur l'Élevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso; Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, TA A-17/G, Campus International de Baillarguet, F-34398 Montpellier, France. Electronic address: thierry.demeeus@ird.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: De Meeûs
authors.affiliation: Wellcome Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom.
authors.forename: Annette
authors.initials: A
authors.lastname: MacLeod
authors.affiliation: Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry BP 851, Guinea; Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, TA A-17/G, Campus International de Baillarguet, F-34398 Montpellier, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bucheton
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Van Reet
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Büscher
authors.affiliation: Université Polytechnique de Bobo-Dioulasso, 01 BP 1091 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Adrien Marie Gaston
authors.initials: AMG
authors.lastname: Belem
authors.affiliation: Centre International de Recherche-Développement sur l'Élevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso; Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, TA A-17/G, Campus International de Baillarguet, F-34398 Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jamonneau
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D051379:Mice; D010802:Phylogeny; D017211:Treatment Failure; D014347:Trypanosoma brucei gambiense / Q000145:classification / Q000187:drug effects / Q000235:genetics; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*
chemical_list: D000981:Antiprotozoal Agents
keywords: Democratic Republic of the Congo; Population genetics; Sleeping sickness; Treatment failure; Trypanosoma brucei gambiense