Trypanosoma vivax: Adaptation of Two East African Stocks to Laboratory Rodents1

Two Trypanosoma vivax stocks from East Africa have been adapted to rats and mice. Adaptation was induced by rapid passage at two- to four-day intervals in sublethally irradiated rats. After 200 such passages, the two stocks gave rise to parasitemias of 10⁹–10¹⁰ trypanosomes/ml in peripheral blood, and the infection was fatal in 90% of the rats. By passaging the rat-adapted T. vivax into normal mice at two- to three-day intervals for over 200 passages, the two stocks also became pathogenic to mice. One of the stocks was also capable of maintenance in non-irradiated rats. The two stocks displayed a marked degree of pleomorphism in irradiated and non-irradiated rats and mice. In the early rising parasitemia, the organisms were predominantly short, with a well formed undulating membrane, a pointed posterior end, and a large terminal kinetoplast. As parasitemia approached its peak, the organisms transformed into long, slender forms with an inconspicuous undulating membrane, an elongated posterior end, and a sub-terminal kinetoplast. The short forms associated with the early, rising parasitemia were more infective for mice than the long forms encountered at peak parasitemia. Although the two rodent-adapted stocks retained their pathogenicity for goats, neither the original stocks nor their corresponding rodent-adapted stocks could be cyclically transmitted by tsetse flies. The availability of these stocks will greatly facilitate investigations on East African T. vivax which would otherwise be difficult to carry out in experimental rodents.     

Differentiation, multiplication and control of bloodstream form Trypanosoma (Duttonella) vivax in mice

The growth and differentiation of Trypanosoma vivax was studied in intact and irradiated C3H/He and C57Bl/6 mice. In irradiated (800 R) or intact C3H/He and irradiated (800 R) C57Bl/6 mice, T. vivax parasitaemia increased rapidly then entered a plateau phase and thereafter declined in an antibody-independent remission phase. Throughout the infection, variations were observed in parasite morphology, density, DNA content, number of organisms with 2 nuclei and 2 kinetoplasts and infectivity of parasites for mice. Parasites in exponential phase had the highest number of members in the S, G2 and M phases of the cell cycle as determined by staining with the interchalating dye Chromomycin A3 and analysis on a flow cytometer. During this phase there were numerous parasites with 2 nuclei and 2 kinetoplasts and infectivity was high for mice. As the parasitaemia approached and entered the plateau phase, the proportion of organisms in the S, G2 and M phases of the cell cycle as well as the number of those with 2 kinetoplasts decreased slightly; the number of organisms with 2 nuclei decreased rapidly; and parasites had a considerably reduced capacity to infect mice. Organisms from the remission phase contained only 1 nucleus and 1 kinetoplast and were not infective for mice. The study suggests that T. vivax organisms transit from dividing to committed non-dividing forms and that some non-diving, non-infective T. vivax organisms remain trapped in the S, G2 and M stages of the cell cycle and die without completing binary fission.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on parasitemia courses and mortality in mice infected with genetically distant Trypanosoma cruzi clonets.

The biological characterization of bloodstream forms of eleven Trypanosoma cruzi cloned stocks, corresponding to two genetically similar clonets (19 and 20) and one distant clonet (39), according to multilocus enzyme electrophoresis analysis, showed dissimilar parasitemia in an experimental isogenic mouse model. While clonet 39 stocks gave low parasitemias, clonets 19 or 20 stocks gave high parasitemias, independently of the inocula (10(2) and 10(4) bloodstream forms) used. High parasitemia did not always associate with greater mortality. Statistical studies on mortality using a low inocula showed significantly higher mortality with clonet 39 stocks when compared to clonets 19 or 20 stocks. Finally, in order to confirm the identity of each stock studied, typing by molecular karyotype was performed before inoculating mice.     

Plasmodium yoelii: induction of attenuated mutants by irradiation

When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number of blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method.     

Molecular and morphological studies of Brazilian Trypanosoma evansi stocks: the total absence of kDNA in trypanosomes from both laboratory stocks and naturally infected domestic and wild mammals

The kinetoplast DNA (kDNA) minicircle molecules of 14 Brazilian stocks of Trypanosoma evansi were studied by morphological approaches (Giemsa and 4'-6'-diamidino-2-phenylindole staining and transmission electron microscopy) and molecular approaches (probing with an oligonucleotide complementary to the minicircle origin of replication and polymerase chain reaction amplification of a minicircle sequence). All methods indicated the absence of both a typical kinetoplast and kDNA minicircles, even in a very small number of parasites of a single stock or in small numbers of copies of molecules per cell. We did not detect any altered kDNA molecules. There were no kDNA molecules in either old or new stocks of T. evansi maintained by successive passages in mice. Similarly, no kDNA minicircles were detected in trypanosomes in blood smears from naturally infected domestic and wild animals. Thus, the total absence of kDNA in Brazilian stocks of T. evansi from both domestic and wild mammals is probably the natural state of Brazilian T. evansi.     

Differentiation, Multiplication and Control of Bloodstream Form Trypanosoma (Duttonella) vivax in Mice

.The growth and differentiation of Trypanosoma vivax was studied in intact and irradiated C3H/He and C57B1/6 mice. In irradiated (800 R) or intact C3H/He and irradiated (800 R) C57B1/6 mice, T. vivax parasitaemia increased rapidly then entered a plateau phase and thereafter declined in an antibody-independent remission phase. Throughout the infection, variations were observed in parasite morphology, density, DNA content, number of organisms with 2 nuclei and 2 kinetoplasts and infectivity of parasites for mice. Parasites in exponential phase had the highest number of members in the S, G₂ and M phases of the cell cycle as determined by staining with the interchalating dye Chromomycin A, and analysis on a flow cytometer. During this phase there were numerous parasites with 2 nuclei and 2 kinetoplasts and infectivity was high for mice. As the parasitaemia approached and entered the plateau phase, the proportion of organisms in the S, G₂ and M phases of the cell cycle as well as the number of those with 2 kinetoplasts decreased slightly; the number of organisms with 2 nuclei decreased rapidly; and parasites had a considerably reduced capacity to infect mice. Organisms from the remission phase contained only 1 nucleus and 1 kinetoplast and were not infective for mice. The study suggests that T. vivax organisms transit from dividing to committed non-dividing forms and that some non-dividing, non-infective T. vivax organisms remain trapped in the S, G₂ and M stages of the cell cycle and die without completing binary fission. In contrast to the above, parasite wave remission occurred in T.vivax-infected intact C57B1/6 mice during exponential growth when there were large numbers of dividing form organisms present in the bloodstream as determined by both DNA content and the proportion of parasites with 2 kinetoplasts and 2 nuclei. Clearance of T. vivax from the bloodstream of infected intact C57B1/6 mice coincided with the production of a parasite-specific antibody response. The studies are discussed with reference to the mode of induction of host protective antibody responses to exponentially growing T. vivax.     

Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole

We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2-10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model. The different T. cruzi stocks obtained from long-term infected dogs showed 50-90% drug resistance right after isolation. However, maintenance of these T. cruzi stocks in mice, by successive blood passages (2.5 years), led to either a decrease or stability of the drug resistance pattern and an increase in parasite virulence. We also demonstrated the effectiveness of the induction of parasitemia reactivation by cyclophosphamide immunosuppression in the evaluation of the response to the specific drug treatment.     

Plasmodium berghei: Isolation and maintenance of an irradiation attenuated strain in the nude mouse

An attenuated strain of malaria causing limited parasitemia in mice was derived from a highly virulent strain of Plasmodium berghei (NK65) which produced 100% lethality in mice. A pool of mouse blood infected with the original highly virulent P. berghei was exposed to 40 Krad irradiation and parasites were inoculated into nude mice as well as into thymus competent normal littermates. Thymus competent mice showed no parasitemia, while one out of the five nude mice inoculated with the irradiated parasites developed a slow and progressive parasitemia. These parasites induced a self-limiting parasitemia in thymus competent mice, even when a large inoculum was administered. Maintenance of the low virulence strain required passage through nude mice. After 50 passages at two weekly intervals, reversion to virulence did not occur. A single vaccination with the attenuated strain induced immunity in mice against a challenge inoculation with the original virulent strain. Specific IgG persisted at high titer for more than 9 weeks in mice receiving a single inoculation of the attenuated strain.     

Trypanosoma vivax: characterization of the spliced-leader gene of a Brazilian stock and species-specific detection by PCR amplification of an intergenic spacer sequence.

The sequence of the spliced-leader gene repeat of a Brazilian Trypanosoma vivax stock from cattle showed high similarity to sequences of West African T. vivax in both intron and intergenic sequences. This is the first evidence based on DNA sequences of close-relatedness between Brazilian and West African T. vivax stocks. A T. vivax-specific diagnostic PCR assay based on spliced-leader gene intergenic sequences was able to amplify DNA from T. vivax stocks from South America (Brazil, Bolivia, and Colombia) and West Africa. Species-specificity of this method was confirmed by results obtained by testing 15 other trypanosomes, including other species and subspecies that can also infect cattle. The PCR assay developed presented high sensitivity, detecting the DNA content of only one parasite and also revealing T. vivax infection in asymptomatic animals without detectable parasitemia by microhematocrit or in Giemsa-stained blood smears. Use of crude preparations from field-blood samples collected on both filter paper and glass slides as DNA template suggested that this method could be useful for the diagnosis of T. vivax in large epidemiological studies.     

Mechanisms of self-cure from Trypanosoma congolense infection in mice

The mechanism(s) of resistance to African trypanosomiasis caused by Trypanosoma congolense was investigated by using the Dinderesso/80/CRTA/3 isolate to which C57B1/6 are resistant (low parasitemia and self-cure) and BALB/c sensitive (high parasitemia and death). The resistance of C57B1/6 is similar to that found in some natural hosts of African trypanosomes such as certain indigenous West African cattle and wild Bovidae. The antibody response to epitopes exposed on the variant surface glycoprotein of a clone obtained from the Dinderesso/80/CRTA/3 isolate was measured by a complement-mediated lysis assay in C57B1/6 and BALB/c. After infections with 10(4), 10(5), or 10(7) motile organisms, antibody appeared in C57B1/6 4 to 8 days earlier than in BALB/c. Peak antibody titers were similar in both strains but were reached about 4 days earlier in C57B1/6. In this strain, antibody appeared during and controlled the first wave of parasitemia, whereas in BALB/c, parasitemia reached a plateau above 10(8) organisms per ml before antibody could be detected, and at this time the animals were dying. At peak antibody response, the proportion of immunoglobulin (Ig) M and IgG antibody was the same in both strains. The antibody response had the same kinetics in C57B1/6 and BALB/c after injection of 10(4), 10(5), and 10(7) lethally irradiated but intact parasites, but the peak titers were 10(3) to 10(4) times lower than after live challenge. The response to nonirradiated trypanosomes appeared to be T cell independent, because the antibody titers were the same in congenitally athymic nu/nu and normal C57B1/6, and no evidence for the induction of T cell activity could be demonstrated in the infected nude mice. A role for trypanolytic serum factors in resistance could not be demonstrated. The extent of immunosuppression after infection with nonirradiated organisms was compared in the two strains by measuring the in vitro response of their splenic lymphocytes to concanavalin A, pokeweed mitogen, and allogeneic cells and their ability to mount an in vivo response to an unrelated trypanosome challenge. Both strains were partially immunosuppressed during rising parasitemia, but as C57B1/6 controlled parasitemia, immunosuppression was gradually reversed, whereas in BALB/c it became worse. Several explanations might account for the resistance of C57B1/6 to the Dinderesso/80/CRTA/3 isolate of T. congolense. It appears that an early immune response is a decisive factor in this resistance.     

Multiplication of Trypanosoma pacifica (Euglenozoa: Kinetoplastea) in English sole, Parophrys vetulus, from Oregon coastal waters

Multiplication of Trypanosoma pacifica was common in the fish host from observations of live flagellates and Giemsa-stained blood smears. Multiplication began with the elongation of the kinetoplast, thickening of the posterior portion of the body, and appearance of a new flagellum near the kinetoplast. The new flagellum was very rigid when less than 3 microm in length, but it became flexible as it elongated. When the new flagellum was approximately 12 microm in length, cell division began and the kinetoplast also began to divide. The timing of nuclear division was variable. Generally, it did not occur until division of the kinetoplast had begun, but occasionally binucleate individuals were observed before cell or kinetoplast division was apparent. As division continued, 1 nucleus migrated past the dividing kinetoplast into the future daughter trypanosome. Finally, the kinetoplast completed division and the trypanosomes separated. Cell division was unequal, with the daughter trypanosome being smaller than the parent and with a more weakly developed undulating membrane.     

Trypanosoma rangeli--in vitro metacyclogenesis and fate of metacyclic trypomastigotes after infection to mice and fibroblast cultures

High metacyclogenesis was induced when freshly-isolated Trypanosoma rangeli from humans were grown in a modified liver-infusion-tryptose medium and transferred into the medium overlaid on mouse fibroblasts at 27 degrees C in a 5% CO2 atmosphere. Such in vitro-generated metacyclic trypomastigotes could induce a significantly high and constant parasitemia in both ICR and SCID mice for a period of about a week but thereafter the parasitemia gradually decreased. Histological examination could not detect any tissue-forms of T. rangeli in various organs of SCID mice. On the other hand, two long-maintained stocks of T. rangeli produced lower metacyclogenesis and only latent parasitemia in both strains of mice. When these populations were incubated in fibroblast cultures at 37 degrees C in a 5% CO2 atmosphere, only trypomastigotes survived for two to three weeks without proliferation, while other forms, mainly epimastigotes, soon began to swell and degenerate. Electron microscopy showed that most surviving trypomastigotes had the basket-like conformation of the kinetoplasts. This is characteristic of the non-dividing trypomastigote stage of T. cruzi, and suggests that T. rangeli trypomastigotes may survive long periods in the blood without proliferation.     

Susceptibility of five strains of mice to Babesia microti of human origin.

One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.     

The axenic cultivation of insect forms of Trypanosoma (Duttonella) vivax and development to the infective metacyclic stage

A method for axenic cultivation of epimastigote and metacyclic forms of Trypanosoma (Duttonella) vivax at 27 degrees C in vitro is described. Iscove's medium was supplemented with specific concentrations of foetal bovine serum, L-proline, L-glutamine hypoxanthine, adenosine, pyruvate, and 2-mercaptoethanol. Bloodstream form parasites rapidly transformed into epimastigote forms that grew as surface-adherent colonies in plastic culture flasks. Transformation of epimastigotes to metacyclic forms was first observed 9-12 days after initiation of cultures. Percentages of metacyclics varied: East African T. vivax ranged up to 40% and West African T. vivax ranged up to 24%. Subcultures were made at two-week intervals and maintained for several months. Transformation of bloodstream forms to epimastigotes depended on initial attachment to the bottom of culture flasks and the presence of L-proline. The number and maturity of metacyclic forms was influenced by the concentrations of foetal bovine serum, L-proline, L-glutamine, and 2-mercaptoethanol. Trypanosomes from cultures were cryopreserved, revived, and used to re-establish fresh axenic cultures. These results represent a significant advance in cultivation of T. vivax insect forms that should enable studies to be accomplished on metabolism, differentiation, and pharmacology of this parasitic protozoan, free from the influence of extraneous cells.     

The Axenic Cultivation of Insect Forms of Trypanosoma (Duttonella) vivax and Development to the Infective Metacyclic Stage

A method for axenic cultivation of epimastigote and metacyclic forms of Trypanosoma (Duttonella) vivax at 27°C in vitro is described. Iscove's medium was supplemented with specific concentrations of foetal bovine serum, L-proline, L-glutamine, hypoxanthine, adenosine, pyruvate, and 2-mercaptoethanol. Bloodstream form parasites rapidly transformed into epimastigote forms that grew as surface-adherent colonies in plastic culture flasks. Transformation of epimastigotes to metacyclic forms was first observed 9–12 days after initiation of cultures. Percentages of metacyclics varied: East African T. vivax ranged up to 40% and West African T. vivax ranged up to 24%. Subcultures were made at two-week intervals and maintained for several months. Transformation of bloodstream forms to epimastigotes depended on initial attachment to the bottom of culture flasks and the presence of L-proline. The number and maturity of metacyclic forms was influenced by the concentrations of foetal bovine serum, L-proline, L-glutamine, and 2-mercaptoethanol. Trypanosomes from cultures were cryopreserved, revived, and used to re-establish fresh axenic cultures. These results represent a significant advance in cultivation of T. vivax insect forms that should enable studies to be accomplished on metabolism, differentiation, and pharmacology of this parasitic protozoan, free from the influence of extraneous cells.     

Trypanosoma congolense: inheritance of susceptibility to infection in inbred strains of mice

Inbred strains of mice have shown marked differences in susceptibility to infection with Trypanosoma congolense, as judged by survival and levels of parasitemia. The underlying genetic basis of the susceptibility was examined with F1 hybrids and backcrosses derived from mouse strains of high and low susceptibility. The influence of H-2 haplotype on susceptibility was studied using H-2 congenic resistant strains of mice. F1 hybrids between the most susceptible strain (A/J) and the least susceptible strain (C57Bl/6) showed similar survival to that of the C57Bl/6 parent. This was reflected in a similar undulating pattern of parasitemia, although the level of parasitemia was consistently higher in the F1 hybrids than in the C57Bl/6. Backcrosses of the F1 hybrids with C57Bl/6 also had a similar pattern of parasitemia although there was a greater scatter in survival times so that a few animals survived longer than either of the parental strains. Backcrosses of F1 hybrids with A/J showed a range of survival times; approximately 25% of these animals died during the period when the A/J mice died, approximately 25% had a similar survival to that of C57Bl/6, while the remaining animals showed an intermediate duration of survival. All these backcrosses had a high initial peak of parasitemia; in about 70% of the mice the early parasitemia showed a distinct undulating pattern. F1 hybrids of A/J and C57Bl/6 with C3H/He mice, which are known to be of intermediate susceptibility, were also examined. The degree of dominance for low susceptibility was much less pronounced in these hybrid combinations than in the A/J × C57Bl/6 hybrids. The H-2 congenic resistant strains, all of which were on a C57Bl/10 genetic background, showed a similar pattern of parasitemia and survival. However, although the majority of all these strains survived for more than 100 days, there was a significant difference in survival between the C57Bl/10 mice and the H-2 congenic resistant strains. It was concluded that susceptibility of mice to T. congolense infection is likely to be under complex genetic control and that, at least in C57Bl/mice, H-2 haplotype has little influence on susceptibility.     

A comparison of the isoenzymes of Trypanosoma (Duttonella) vivax isolates from East and West Africa

The genetic diversity in 13 stocks and clones of Trypanosoma vivax from East and West Africa was compared by isoenzyme analysis. The Ugandan and West African stocks and clones showed a very high degree of genetic similarity to each other but they differed from the Kenyan stocks and clones. Two haemorrhagic stocks, IL 2337 (Galana, Kenya) and IL 3067 (Bamburi, Kenya), showed a high degree of similarity in enzyme banding patterns in electrophoresed preparations. One of the Kenyan stocks, M1D 627, differed in most of its enzyme banding patterns from all the other stocks and clones used.     

Plasmodium berghei: Development of resistance to clindamycin and minocycline in mice

Strains of Plasmodium berghei resistant to clindamycin or minocycline were selected by a procedure in which groups of infected mice were treated with increasing doses of drug during each of a series of subpassages. Groups of five mice, each infected by intravenous inoculation with 10 million parasitized erythrocytes, were treated orally with different doses of drug for four consecutive days beginning on the day of infection. Subpassages were routinely made by Day 7, using donor mice from the group that had been treated with the highest dose of drug that allowed for some development of parasitemia during the preceding passage. Drug doses were increased in each passage as dictated by the development of parasitemia during the previous treated passage.The rate of development of resistance to clindamycin or minocycline was much slower than to conventional antimalarials such as chloroquine, quinine, or pyrimethamine. P. berghei developed total resistance to the latter compounds in nine to 12 treated passages in mice over a period of 60 to 85 days. In contrast, development of total resistance to clindamycin required 42 treated passages over a period of 300 days. Total resistance to minocycline was not attained during 86 successive minocycline-treated passages in mice over a period of 600 days, but a sixfold increase in resistance to minocycline was observed.The clindamycin-resistant strain was normally sensitive to minocycline, chloroquine, quinine, and pyrimethamine. The strain partially resistant to minocycline was normally sensitive to clindamycin, chloroquine, quinine, and pyrimethamine. Resistance to clindamycin was stable during 51 drug-free passages in mice over a period of 1 year. Resistance to minocycline was unstable. During 16 drug-free passages in mice the strain reverted towards normal sensitivity to minocycline. Strains resistant to clindamycin or minocycline showed no difference in rate of development in mice as compared to the parent strain. Likewise, only minor morphological modifications were seen in Giemsa-stained blood smears between the two resistant strains and the parent strain.These results suggest that other species of malaria may develop resistance to clindamycin or minocycline. Should resistance to one of these compounds appear, however, it should not invalidate the use of the other in the treatment of malaria.     

Genetics of resistance to the African trypanosomes. V. Qualitative and quantitative differences in interferon production among susceptible and resistant mouse strains

The induction of interferon (IFN) was examined in different inbred mouse strains infected with Trypanosoma brucei rhodesiense. Relatively susceptible C3HeB/FeJ mice that do not exhibit variant-specific immunity or control parasitemia did not exhibit detectable IFN throughout the infection. Relatively resistant B10.BR mice that exhibit variant-specific immunity and control the first peak of parasitemia exhibited detectable IFN at two intervals. The appearance of IFN in B10.BR serum first coincided with the onset of the parasitemia 4 days after infection and then disappeared; this IFN peak was predominantly IFN-alpha/beta. The second time of appearance coincided with high titers of antibody and remission of the parasitemia. This IFN was predominantly IFN-gamma. Intermediately susceptible CBA/J mice also exhibited two detectable peaks of IFN; the first IFN-alpha/beta peak coincided with the onset of the parasitemia as in B10.BR mice. The second peak of IFN in the serum of CBA mice, however, was delayed in appearance and lower in concentration compared with B10.BR mice. This peak was characterized as being predominantly IFN alpha/beta. BALB/c mice (also intermediately susceptible) did not exhibit a first peak of IFN-alpha/beta production, but the second peak of IFN-alpha/beta production was similar to that seen in CBA mice. In contrast to infected mice, IFN was induced in both susceptible (C3H) and resistant (B10.BR) mice after immunization with glutaraldehyde-fixed trypanosomes or after chemotherapy of infection. We conclude that both the levels of IFN as well as the type of IFN induced during infection with T. b. rhodesiense depend upon the genetic background of the mouse strain infected. The induction of IFN-gamma in mice of the C57BL background may be linked functionally to more effective parasite control and to the presence of an effective immune response to T. b. rhodesiense.