The mechanisms which affect the periodic cycle of Pacific Wuchereria bancrofti microfilariae.

1. Investigations were made of the effect of various procedures in raising or lowering the microfilaria count of Pacific type Wuchereria bancrofti in the peripheral blood. 2. Raising the body temperature in the early morning was followed by a moderate fall in the counts. Breathing increased oxygen, or reduced oxygen (hypoxia) or increased carbon dioxide, or the ingestion of sodium bicarbonate produced no consistent and significant change in the count. Ingestion of glucose (in one volunteer) was followed by a small rise in the count. Muscular exercise was followed by a fall in the count, which is interpreted as probably being a response to a lower concentration of oxygen in the venous blood returning to the lung. 3. It has not been possible to identify the physiological components on the circadian rhythm of the human body which entrain the cycle of these microfilariae. Attempts to obtain evidence incriminating the stimuli described above have been unsuccessful.

The resistance of Trypanosoma congolense, T. vivax and T. evansi to human plasma.

Tests were made in mice on the resistance of cattle trypanosomes to human plasma. 12 stocks of Trypanosoma, congolense were tested' three were fully resistant, eight were moderately or highly resistant, and one was fully sensitive. Four stocks of T. vivax were tested; two were fully resistant, one was somewhat resistant, and one was highly sensitive. Two stocks of T. evansi were tested; both fully sensitive. The possibility is discussed that T. congolense and T. vivax might produce transient infections in man.

The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense: III. Clones of two plasma-resistant strains.

Tests for resistance to human plasma were made on six clones of a stabilate of Trypanosoma rhodesiense (LUMP 10) which was calculated to contain about 3,000 resistant trypanosomes per million. Two of the clones were not resistant and four were only subresistant. Tests were also made on 12 lines (clones) of a stabilate of polymorphic trypanosomes isolated from tsetse flies. One of them, ETAT 10, had infected a laboratory worker and was found to be fully resistant to human plasma; the other lines showed only low or moderate resistance. Resistance of a strain to human plasma often depends upon a small minority of resistant trypanosomes. Strains of polymorphic trypanosomes may be classified as fully resistant, moderately resistant, subresistant, or sensitive to human plasma, if they contain respectively, all, some (e.g. one per hundred), very few (e.g. one per million) or no individuals which are resistant.

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.

The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. II. Survey of strains from East Africa and Nigeria.

Tests were made in vivo of the sensitivity or resistance to human plasma of many strains of polymorphic trypanosomes. Five strains of T. gambiense from Nigeria were tested and all were highly resistant. Fifteen strains of T. rhodesiense (isolated from man in East Africa) were tested and they showed great variation in their degree of resistance from high resistance (five strains) to only subresistance (two strains). Forty strains of T. brucei (isolated from animals or tsetse flies) were tested; 20 were sensitive, nine were doubtful (probably sensitive) and 10 were subresistant (i.e., probably only one of a million trypanosomes in them was resistant). One strain (ETAT 10, isolated from tsetse flies) was highly resistant. During this work, tests were made on 14 stains of T. brucei (isolated from animals or fly) which were recorded as having been tested on human volunteers. Six of these strains were sensitive to human plasma and none had infected volunteers. Seven strains were subresistant, and three had infected volunteers. One strain was highly resistant and had infected a laboratory worker. For practical purposes it is advisable to consider that if a strain of polymorphic trypanosomes is plasmasensitive, it is probably not infective for man; if a strain is at all plasma-resistant it is potentially infective for man; and if a strain is highly resistant then it is almost certainly infective for man.