Analysis of virulence in monomorphic African Trypanosomiasis

Date

1989-05

Journal Title

Journal ISSN

Volume Title

Publisher

Texas Tech University

Abstract

The protozoan hermoflagellate parasites o£ the genus Trypanosoma infect both humans and other animals. In humans the disease African sleeping sickness is caused by Trvpanosoma brucei gambiense and T. b. rhodesiense. A T. b. gambiense infection generally causes a chronic disease with slow onset, while a T. b. rhodesiense infection often takes a fulminating clinical course. These two organisms, which are morphologically indistinguishable, can only be recognized as separate subspecies by serological analysis. Mechanisms responsible £or the virulence differences have been studied, and correlations have been found £or several different £actors.

One isolate o£ T. b. gambiense at low inocula causes immunologically controlled, low grade and limited infections in mice (Diffley & Scott, 1984). The purposes o£ this study were to derive a virulent organism from this avirulent primary ("parental") isolate and to define trypanosomal virulence factors by coroparative analyses.

Virulence was enhanced by rapid serial transfer of infections in mice. After the thirtieth passage, the virulent trypanosomes were cloned and cryopreserved. In a comparison o£ lethal (first peak) challenge inoculations, the virulent isolate had LD100 and LD50 values o£ 10^5 and 10^4 organisms, respectively. The avirulent population required nearly a one-hundred £old increase in organism numbers to achieve the same LD100 and LD50 values.

Both virulent and avirulent organisms were monomorphic, as indicated by microscopic examination (light and SEM) o£ bloodstream forms and by their inability to transform into procyclic forms in culture. Both appeared to have the same variant specific surface-coat glycoprotein, as determined by cross-protection and agglutination assays. Both appeared to have similar immunogenicity and vulnerability to immune lysis.

0f the four virulence mechanisms investigated and discussed in this thesis, only one emerged that had been associated with virulence: population doubling time. The avirulent parasite doubled its population in the bloodstream every 11.0 hours, while the virulent organism doubled every 8.5 hours. The significance of these findings is the possible establishment of a model system £or the genus Trypanosoma with population doubling time (the "base-line" o£ virulence mechanisms) as the only operating mechanism. Further, this report introduces a new approach within Trypanosoma spp. research for establishing this "base-line" of virulence.

Description

Keywords

African trypanosomiasis

Citation