Centre International de Recherche-Développement sur l'Elevage en zone Subhumide (CIRDES), 01 BP 454, Bobo-Dioulasso 01, Burkina Faso; Université NAZI BONI de Bobo-Dioulasso, UFR Sciences et Techniques, 01 BP 1091, Bobo-Dioulasso 01, Burkina Faso.
Programme National de Lutte contre la THA, BP 851, Conakry, Guinea.
Infect Genet Evol. 2018 Sep;63:269-276. doi: 10.1016/j.meegid.2018.05.018. Epub 2018 May 25.
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.
布氏冈比亚锥虫（T. b. gambiense）是引起人类非洲锥虫病（HAT）的主要病原体。在西非流行地区观察到了各种不同的临床结局，这可能是由于复杂的宿主-寄生虫相互作用。为了区分寄生虫遗传多样性和宿主变异性的作用，我们选择在小鼠模型中精确描述 T. b. gambiense 田间分离株的致病性和毒力。在实验感染中研究了 13 株 T. b. gambiense 菌株，每株感染 20 只 Balb/C 小鼠。监测小鼠 30 天，记录死亡率、寄生虫血症、贫血和体重。估计死亡率、潜隐期和最大寄生虫血症，并进行生存分析比较菌株的致病性。混合模型用于评估寄生虫血症动态、体重和红细胞压积（PCV）的变化。最后，进行了多变量分析以推断所有变量之间的关系。观察到表型多样性很大。致病性差异很大，从在 9 天内杀死宿主的菌株到非致病性菌株（实验过程中无死亡）。毒力也不同，最大寄生虫血症值范围从 4200 万到 10 亿个寄生虫/ml。在感染的前两周内，除了两种菌株外，PCV 和体重均下降。最后，全局分析突出了三组菌株：第一组是高致病性菌株，表现出早期死亡率，与潜隐期短有关；第二组是高毒力菌株，具有中等致病性；第三组是具有低致病性和毒力模式的分离株。这种生物学差异可能与 HAT 中观察到的临床多样性有关。因此，更好地了解观察到的表型多样性背后的生物学途径可以帮助阐明决定对布氏冈比亚锥虫抵抗/易感性的宿主-寄生虫相互作用的复杂性。
