RT Journal Article SR 00 ID 10.1016/j.meegid.2018.05.018 A1 Kaboré, Jacques A1 Camara, Oumou A1 Koffi, Mathurin A1 Sanou, Djénéba A1 Ilboudo, Hamidou A1 Sakandé, Hassane A1 Camara, Mamadou A1 De Meeûs, Thierry A1 Ravel, Sophie A1 Belem, Adrien Marie Gaston A1 MacLeod, Annette A1 Bucheton, Bruno A1 Jamonneau, Vincent A1 Thévenon, Sophie T1 Differences in pathogenicity and virulence of Trypanosoma brucei gambiense field isolates in experimentally infected Balb/C mice JF Infection, Genetics and Evolution YR 2018 FD 2018-09 VO 63 SP 269 OP 276 K1 Clinical diversity, host-parasite interaction, human African trypanosomiasis, mouse model, multivariate analysis, pathogenicity, phenotypic diversity, Trypanosoma brucei gambiense, virulence. AB Trypanosoma brucei gambiense (T. b. gambiense) is the major causative agent of human African trypanosomiasis (HAT). A great variety of clinical outcomes have been observed in West African foci, probably due to complex host-parasite interactions. In order to separate the roles of parasite genetic diversity and host variability, we have chosen to precisely characterize the pathogenicity and virulence of T. b. gambiense field isolates in a mouse model. Thirteen T. b. gambiense strains were studied in experimental infections, with 20 Balb/C infected mice per isolate. Mice were monitored for 30 days, in which mortality, parasitemia, anemia, and weight were recorded. Mortality rate, prepatent period, and maximum parasitemia were estimated, and a survival analysis was performed to compare strain pathogenicity. Mixed models were used to assess parasitemia dynamics, weight, and changes in Packed Cell Volume (PCV). Finally, a multivariate analysis was performed to infer relationships between all variables. A large phenotypic diversity was observed. Pathogenicity was highly variable, ranging from strains that kill their host within 9 days to a non-pathogenic strain (no deaths during the experiment). Virulence was also variable, with maximum parasitemia values ranging from 42 million to 1 billion trypanosomes/ml. Reduced PCV and weight occurred in the first two weeks of the infection, with the exception of two strains. Finally, the global analysis highlighted three groups of strains: a first group with highly pathogenic strains showing an early mortality associated with a short prepatent period; a second group of highly virulent strains with intermediate pathogenicity; and a third group of isolates characterized by low pathogenicity and virulence patterns. Such biological differences could be related to the observed clinical diversity in HAT. A better understanding of the biological pathways underlying the observed phenotypic diversity could thus help to clarify the complex nature of the host-parasite interactions that determine the resistance/susceptibility status to T. brucei gambiense. PB Elsevier SN 1567-1348 LK https://eprints.gla.ac.uk/163579/