Inhibition of growth of Trypanosoma brucei parasites in chronic infections.

The growth of Trypanosoma brucei parasites in chronic infections was investigated by superimposing upon chronic infections, secondary infections in which all parasites expressed the same variable antigen type (VAT). The fate of trypanosomes in secondary infections could then be monitored using the VAT as a marker to discriminate cells in primary and secondary infections and thus enable growth to be observed separately from its interactions with antigenic variation on the part of the parasite and specific immune responses of the host. Our results show that as an infection proceeds, the growth rate is progressively inhibited in mice and sheep, suggesting that inhibition is a general feature of chronic infections. Inhibition was not specific to either the stock or the VAT of the trypanosome, but the degree of inhibition did vary between stocks. Inhibition appeared to be mediated by a lowering of the rate of replication of 'slender'-form parasites rather than by an increase in either the rate of differentiation from dividing slender to non-dividing 'stumpy' forms or the mortality caused by non-specific immune mechanisms. Evidence indicated that the development of specific immune responses to non-variant parasite antigens was also unlikely. These data constitute, we believe, the first evidence for negative regulation of growth in vivo, which may be an important determinant of the virulence of trypanosome infections.