The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. I. Analysis of the composition of trypanosome strains.

The sensitivity of strains of polymorphic trypanosomes to human plasma was investigated in mice. By measuring the prepatent period an approximate estimate could be made of how many trypanosomes resisted each of a graded series of doses of plasma and survived to produce infection. In this way the composition of typical strains could be analysed. Three types of strains could be recognized: (i) Strains in which all the individuals composing them were sensitive to full doses of plasma, the response to plasma probably having a "normal" distribution. These are termed "sensitive" strains. (ii) Strains composed mostly of sensitive individuals but containing a small sub-population of resistant individuals (perhaps one in a million). These are termed "subresistant" strains. Most of the strains which have been isolated from animals by previous workers and found to be resistant to human serum and/or infective for volunteers are of this type. (iii) Strains composed mostly of resistant individuals. These are "highly resistant" strains and are the type isolated from man. It is postulated that there are one (or two) genes responsible for resistance to human plasma and that the response of a strain in plasma-sensitivity tests depends upon whether the strain contains no trypanosomes with the R gene (sensitive strain), a few trypanosomes with the R gene (subresistant strain) or a jamority with the R gene (resistant strain). This model of a subresistant strain can be reproduced artificially by mixing a few resistant trypanosomes with a large number of sensitive ones. Passage of three resistant strains through mice for six weeks diminished their plasma resistance slightly to moderately, presumably through overgrowth of sensitive individuals. Passage trrough goats for six weeks diminished plasma resistance markedly but did not convert the strains into "sensitive" ones. Repeated exposure of a subresistant strain to human plasma in mice gradually increases the number of resistant trypanosomes present and so the resistance of a strain as a whole is enhanced.