The rate of proliferation among African trypanosomes is a stable trait that is directly related to virulence.

The relationship between the growth rate of Trypanosoma brucei gambiense and its virulence was investigated. A cloned, monomorphic, slow growing, and relatively avirulent line of T. b. gambiense was serially passaged at 3- to 5-day intervals through immunosuppressed mice. The growth rate measured within the first 2 patent days of infection did not vary significantly through the first 25 passages but by passage 50 had decreased significantly from 11.9 +/- 1.1 hr to 9.0 +/- 0.7 hr. A clone from passage 50 and three different second peak heterologous variants all had statistically similar growth rates, indicating that the rate of proliferation was a stable trait. With the faster rate of proliferation there was a corresponding increase in virulence. The inoculum necessary to kill 50% of normal outbred mice in the first peak of parasitemia (LD50) dropped significantly from 3 X 10(6) first passage parasites to 4 X 10(5) passage 50 parasites. The lethal load for both fast and slow growing organisms was the same (greater than 2 X 10(9) trypanosomes/ml of blood). To further link virulence and growth rate, a strong correlation (r = 0.89) was measured when generation times of 10 closely related lines of T. b. gambiense, and 2 lines of pleomorphic T. b. rhodesiense were compared to their LD50 values. While the rate of trypanosomal proliferation was similar between the day of inoculation through the second patent day, it slowed to 64% of that level once parasitemias exceeded 3 X 10(8) organisms/ml of host blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological control of chronic Trypanosoma brucei gambiense in outbred rodents.

Recent human isolates of Trypanosoma brucei gambiense generally fail to become or remain patent in laboratory rodents. The purpose of this study was to determine if this was due to acquired immunity and if so which immunosuppressive method was the most efficient in raising parasitemia levels. Prior to infection, rats and mice were immunosuppressed by treatments with cobra venom factor, anti-lymphocyte sera, hydrocortisone acetate, cyclophosphamide; by splenectomy; or by lethal X-irradiation. While no parasites were detected in the blood of most of the untreated rodents for 30 days postinfection, all immunosuppressive procedures resulted in patent parasitemias in at least fifty percent of the treated animals. The most effective method, lethal X-irradiation, consistently caused fulminating infections typical of acute African trypanosomiasis. Cyclophosphamide had the same effect as X-irradiation in rats but was less effective in mice. Splenectomy allowed fulminating first peak parasitemias in two-thirds of the rodents while cobra venom factor and anti-lymphocyte sera in general allowed only low first peaks of parasitemia that were resolved within 10 days of infection. Hydrocortisone acetate allowed low grade and sporadically patent infections throughout the 30-day study. To determine if in untreated rodents, the parasites were eliminated or maintained in a subpatent state, rodents infected for 30-45 days were immunosuppressed with cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS)