Early invasion of brain parenchyma by african trypanosomes

Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.     

The activity of nifluridide on reduviids and rodent and human trypanosomes

The ability of nifluridide to kill reduviids was assayed in mice fed 7 ppm in diet and on cattle injected subcutaneously at 5 mg/kg body weight. Nifluridide was systemically active against Triatoma infestans on mice and Rhodnius prolixus on cattle. No effects on Trypanosoma (Schizotrypanum) cruzi could be detected in the intestinal contents of Triatoma infestans killed by the compound. In vitro and in vivo studies were conducted to determine the effects of nifluridide on trypanosomes growing in medium and in experimentally infected mice. Culture forms of Trypanosoma cruzi grown at 27 degrees C that are morphologically similar to epimastigotes found in infected bugs were affected by 2.5 to 10 ppm in the medium. Mice fed nifluridide in the diet simultaneous with infection of Trypanosoma cruzi or Trypanosoma (Herpetosoma) musculi exhibited parasitemias and tissue infections similar to nontreated infected mice. At the concentration tested, bloodstream trypomastigotes and culture epimastigotes of Trypanosoma musculi were unaffected by nifluridide. Only the culture epimastigotes of Trypanosoma cruzi were affected by the drug but not the bloodstream and tissue forms.     

The life cycle of Paraquimperia tenerrima: a parasite of the European eel Anguilla anguilla

Previous studies on the life history of the nematode eel specialist Paraquimperia tenerrima (Nematoda: Quimperiidae) have failed to determine whether an intermediate host is required in the life cycle. In the laboratory, eggs failed to hatch below 10 degrees C, hatching occurring only at temperatures between 11 and 30 degrees C. Survival of the free-living second stage larvae (L2) was also temperature dependent, with maximal survival between 10 and 20 degrees C. Total survival of the free-living stages (eggs and L2) is unlikely to exceed a month at normal summer water temperatures, confirming that parasite could not survive the 6 month gap between shedding of eggs in spring and infection of eels in early winter outside of a host. Eels could not be infected directly with L2, nor could a range of common freshwater invertebrate species. Third stage larvae (L3) resembling P. tenerrima were found frequently and abundantly in the swimbladder of minnows Phoxinus phoxinus from several localities throughout the year and were able to survive in this host in the laboratory for at least 6 months. Third stage larvae identical to these larvae were recovered from minnows experimentally fed L2 of P. tenerrima, and eels infected experimentally with naturally and experimentally infected minnows were found to harbour fourth stage larvae (L4) and juvenile P. tenerrima in their intestines. Finally, the whole life cycle from eggs to adult was completed in the laboratory, confirming that minnows are an obligate intermediate host for P. tenerrima.     

Trypanosoma rhodesiense: variant specificity of immunity induced by irradiated parasites.

Rats immunized with irradiated Trypanosoma rhodesiense resisted infection with the homologous strain. When similarly immunized rats were challenged with parasites obtained from rhesus monkeys infected with the same strain, resistance depended on when parasites were obtained from the donor monkeys. Immunized rats challenged with trypanosomes obtained from a monkey during the first peak of parasitemia were solidly immune; immunized rats challenged with trypanosomes obtained from monkeys after their initial peak of parasitemia all succumbed to the challenging infection. These observations indicate that parasites of a variant antigenic specificity arose during the course of the monkey infections. Neutralization tests performed on the various isolates from rats and monkeys using antiserum obtained from immunized rats confirmed that the immunity produced by irradiated trypanosomes was variant specific.     

Effect of Haemoproteus belopolskyi (Haemosporida: Haemoproteidae) on body mass of the blackcap Sylvia atricapilla

The effect of initial Haemoproteus belopolskyi infection on the weight of its natural host, the blackcap Sylvia atricapilla, was investigated. Fourteen blackcap nestlings were taken at the age of 4-5 days and raised by hand in the laboratory. They were free of blood parasites. Seven 20- to 21-day-old nestlings were infected experimentally by inoculation in their pectoral muscle with approximately 45 sporozoites, which had developed in the experimentally infected biting midge Culicoides impunctatus. Seven nestlings were used as negative controls. Parasitemia developed in 6 inoculated nestlings, with a prepatent period of 11-12 days. No infections were detected in the controls during this study. The weight of experimentally infected and control birds was measured 2 days before parasitemia became patent and for a 45-day period after patency. Blood smears were prepared from all birds on the days when they were weighed. When compared with controls, there was a significant weight loss of experimentally infected blackcaps during 6 days after the decline of parasitemia at 10-16 days of patency, indicating a short-term influence of the infection on the birds' body mass. Clinical symptoms of the infection were not recorded. All birds from both groups survived until the end of the experiment.     

In Vivo Imaging of Trypanosome-Brain Interactions and Development of a Rapid Screening Test for Drugs against CNS Stage Trypanosomiasis

Human African trypanosomiasis (HAT) manifests in two stages of disease: firstly, haemolymphatic, and secondly, an encephalitic phase involving the central nervous system (CNS). New drugs to treat the second-stage disease are urgently needed, yet testing of novel drug candidates is a slow process because the established animal model relies on detecting parasitemia in the blood as late as 180 days after treatment. To expedite compound screening, we have modified the GVR35 strain of Trypanosoma brucei brucei to express luciferase, and have monitored parasite distribution in infected mice following treatment with trypanocidal compounds using serial, non-invasive, bioluminescence imaging. Parasites were detected in the brains of infected mice following treatment with diminazene, a drug which cures stage 1 but not stage 2 disease. Intravital multi-photon microscopy revealed that trypanosomes enter the brain meninges as early as day 5 post-infection but can be killed by diminazene, whereas those that cross the blood-brain barrier and enter the parenchyma by day 21 survived treatment and later caused bloodstream recrudescence. In contrast, all bioluminescent parasites were permanently eliminated by treatment with melarsoprol and DB829, compounds known to cure stage 2 disease. We show that this use of imaging reduces by two thirds the time taken to assess drug efficacy and provides a dual-modal imaging platform for monitoring trypanosome infection in different areas of the brain.     

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.     

Trypanosoma rhodesiense: variable effects of cyclophosphamide on antibody production, survival, and parasitemia in infected mice

Mice of the CBA/CaJ strain, infected with Trypanosoma rhodesiense, were injected with a single high dose (approximately 200 mg/kg) of the immunosuppressive drug cyclophosphamide to determine if an induced, transient inability to make antibody affected survival or parasitemia. When given on the day of infection, the drug had no significant effect on survival. It delayed, but did not prevent, the appearance of specific antibodies and the clearance of the infecting trypanosome variants. When cyclophosphamide was injected 1 week after infection, survival mass significantly decreased. Antibody production to specific variant antigens and to common trypanosome antigens were terminated, but the mice were able to eliminate the infecting trypanosomes. These findings suggest that a temporary inability to make antibody to trypanosomes does not result in more rapid death when only the infecting trypanosome variant is present. However, immunosuppression may accelerate death if it occurs when there are many different types of trypanosomes present.     

Trypanosoma lewisi Infections in Normal Rats and in Rats Treated with Dexamethasone

SYNOPSIS. Administration of dexamethasone to rats infected with Trypanosoma lewisi resulted in the development of exceedingly large populations of trypanosomes which were fatal to their hosts. The elevated levels of parasitemia in treated rats early in infections were thought not to be a result of an increased reproductive rate. However, trypanosomes in treated rats 2 days postinfection did have a higher coefficient of variation in total length and a greater percentage of dividing forms than those observed from infected rats which were not given the drug. The course of infection may be markedly altered not only in intensity but also in length by this corticosteroid. It is suggested that dexamethasone administered at the levels recorded to rats infected with T. lewisi inhibits the production of ablastin and trypanocidal antibodies.     

The Biology of Trypanosoma diemyctyli, Tobey. III. Factors influencing the cycle of Trypanosoma diemyctyli in the vertebrate host Triturus v. viridescens.

SYNOPSIS. The effects of some environmental influences on the cycle of Trypanosoma diemyctyli in Triturus v. viridescens are described. Bleeding of the host produced a reduction in the number of trypanosomes but did not affect their growth rate. The temperature at which the host was maintained affected the cycle of the trypanosomes. The length of the post-inoculation latent stage increased from 24 hours at 25°C. to an indefinitely long time at 5°C. The trypanosomes were found to be dimorphic. Adult parasites of the short form had a range of 45–75 μ and those of the long form of 76–116 μ. Growth rate of the trypanosomes was inhibited or greatly retarded at temperatures of 10°C. or lower and was greatest at 25°C. The size attained by the parasites and the number of parasites were greatest at 15°C. At this temperature the infection was pathogenic and the dimorphic parasites were in their long form. At the higher temperatures (20–25°C.) the infection was non-pathogenic with the trypanosomes in their short form.
The infection is primarily one of adult newts. Experiments indicated that the larvae were resistant to the trypanosomes at all temperatures while the red efts were not. The latter are usually free from the trypanosomes because they are not exposed to them. Attempts to infect other newts and to locate any cryptic stages by the injection of blood and tissues from infected newts gave negative results.
Starvation, sodium salicylate, and treatments used to control fungus infection of the newts had no detectable effects on the trypanosomes.     

The Life Cycle of Trypanoplasma bullocki (Zoomastigophorea: Kinetoplastida)1

The leech Calliobdella vivida (Verrill) is the vector of Trypanoplasma bullocki. At 10°C, infective-stage flagellates were first present in the leech's proboscis sheath five days after feeding. At 5°C, infective-stage flagellates were not present in the leech's proboscis sheath until 10 days after feeding, but at 20°C, flagellates were located there as early as 24 h after feeding. Infected leeches retained flagellates through three subsequent feeds on uninfected fish. When flagellates were first observed in hogchoker, Trinectes maculatus (Bloch & Schneider), they were much larger than infective stages from the leech. Average flagellate length then decreased during early acute phase, but gradually increased thereafter. Peak parasitemia was greater in a hogchoker inoculated by only one leech but held at colder temperature than in a hogchoker inoculated by 45 leeches, suggesting that temperature may be more important than inoculum in determining peak parasitemia. Cell division in the fish host is described. SEM studies of fish blood flagellates revealed a pre-oral ridge and a cytostome.     

Lymphocyte function in experimental African trypanosomiasis. V. Role of antibody and the mononuclear phagocyte system in variant-specific immunity

The role of parasite-specific antibody and the mononuclear phagocyte system (MPS) in immunity to the African trypanosomes was examined. For this study C57BL/10SnJ mice were infected with Trypanosoma rhodesiense clone LouTat 1.0. Infected mice were injected with 75Se-labeled LouTat 1.0 trypanosomes, and clearance from the blood upon reexposure was measured throughout the course of infection. Clearance of labeled organisms occurred only on or after day 5, which was the day of natural elimination of LouTat 1.0 from the blood. Clearance was dependent on a functional immune system and correlated with the appearance of antibody to the variant-specific surface antigen (VSSA) of the trypanosomes. The ability to clear trypanosomes was transferred to normal, uninfected mice by immune serum. Both the IgM and IgG fractions of immune serum mediated the clearance, and VSSA-specific IgM fractions were as efficient in clearing LouTat 1.0 as the IgG fractions. Normal levels of complement (C3) were not required for clearance. The liver was the primary organ of clearance, and the ability of the liver to sequester radiolabeled trypanosomes was not impaired in the terminal phase of the disease or by large numbers of circulating trypanosomes present representing different variant antigenic types (VAT). We conclude that in African trypanosomiasis the MPS is not depressed in its ability to clear trypanosomes of the infecting VAT at any time during the course of infection. The observed clearance function requires parasite-specific antibody but normal levels of C3.     

Trypanosoma brucei: Antigenic analysis of bloodstream,vector, and culture stages by the quantitative fluorescent antibody methods

Quantitative direct fluorescent antibody methods were used in antigenic analysis of developmental stages of Trypanosoma brucei brucei strains, most of them having the same variant antigen B, which were derived from a cyclically transmissible stabilate. Antigen-B trypanosomes were used for initiation of cultures in modified Tobie's (Tm) medium and in Glossina morsitans morsitans organ cultures, and for the infective feed of G. m. morsitans. Antisera against antigen-B bloodstream forms and against Tm-grown culture forms were developed in rabbits by inoculations of disrupted organisms mixed (1:1) with complete Freund's adjuvant. The globulin fractions of the antisera were conjugated with fluorescein isothiocyanate, and processed on Sephadex G-25 and DEAE-cellulose columns. The DEAE fractions with 2.0 and 4.7 or 4.8 molar fluorescein:protein ratios were pooled and concentrated twofold.Examination of 109 flies at 30 or 31 days after the infective feed revealed about 18.3% midgut, about 10.1% proventricular, and about 3.7% salivary-gland infections. A salivary gland suspension from one of the infected flies gave rise to a parasitemia in a mouse, and trypanosomes from the first parasitemia were transferred by two 3-day syringe passages into another mouse. Smears were prepared of trypanosomes (antigens B-164, B-167) from the first parasitemias from these two mice, of intact B-antigen trypanosomes, of culture forms (CT) from Tm medium, and of procyclics (CG) from Glossina cultures as well as of midgut (GM), proventricular (GP), and salivary-gland (GS) forms from tsetse flies. All these forms were fixed by one or more of the three following methods: complete fixation (CoFix) by the formalin-NH₄OH-Tween 80 procedure; fixation before affixation to slides (F+); fixation after affixation to slides (F?). The best results with regard to fluorescence intensity and specificity were obtained by using the CoFix technique.Statistical analyses of the fluorescence means of the antigens subjected to direct and inhibition staining gave the following results: (1) CT, CG, GM, and GP forms were antigenically the same. (2) GM and GP trypanosomes from different flies were antigenically indistinguishable. (3) The surface antigen of the variant-B bloodstream trypanosomes was different from these antigens of culture, midgut, and proventricular forms. It differed also from those of metacyclics from two flies and of B-164 and B-167 bloodstream forms. (4) No antigenic differences were found, in preparations fixed by the F? method, between B-164 and B-167 bloodstream trypanosomes and the metacyclics from two flies, one of which served as the source of the salivary-gland trypomastigotes (GS-98) that gave rise to these two bloodstream form antigens. (5) Closer antigenic relationships were noted between B forms and B-164 and B-167 trypanosomes than between B and CT organisms in smears fixed by the F+ technique, but no such differences were discernible in preparations fixed by the F? procedure.     

Trypanosoma lewisi: termination of pregnancy in the infected rat

Trypanosoma lewisi has previously been described as a nonpathogenic parasite of the rat, but these experiments demonstrate that both embryonal and maternal death may occur in the pregnant rat after infection with this parasite.Rats infected early in the first week of pregnancy resorbed their young with little apparent difficulty, and exhibited parasitemia curves typical of nonpregnant infected females of similar age.Rats infected late in the first week of pregnancy experienced greater difficulty resorbing the young, with half of the females dying shortly before parturition. The parasitemia counts were also similar to those of nonpregnant infected rats.The majority of rats infected during the midterm of pregnancy died at the time of parturition, without giving birth to their young. The number of parasites in these animals was abnormally high compared to nonpregnant infected females. Unusually large numbers of dividing trypanosomes were present in the placentae of these animals, many of them containing 8–16 nuclei and kinetoplasts.Animals infected during the last week of pregnancy gave birth to litters of normal size with little apparent difficulty, and had extremely low parasite counts.The hematocrits of all groups of infected animals showed a decrease at the time of peak parasitemia, and the hematocrits of all groups of pregnant rats showed a decrease at the time of birth, except for those infected when day 2 pregnant. These animals completely resorbed their young. The weight losses of rats infected on day 2 and day 6 of pregnancy reflected a termination of pregnancy.     

Macrophage activation and histopathological findings in Calomys callosus and Swiss mice infected with several strains of Trypanosoma cruzi.

Peritoneal macrophage activation as measured by H2O2 release and histopathology was compared between Swiss mice and Calomys callosus, a wild rodent, reservoir of Trypanosoma cruzi, during the course of infection with four strains of this parasite. In mice F and Y strain infections result in high parasitemia and mortality while with silvatic strains Costalimai and M226 parasitemia is sub-patent, with very low mortality. H2O2 release peaked at 33.6 and 59 nM/2 x 10(6) cells for strains Y and F, respectively, 48 and 50 nM/2 x 10(6) for strains Costalimai and M226, at different days after infection. Histopathological findings of myositis, myocarditis, necrotizing arteritis and absence of macrophage parasitism were found for strains F and Costalimai. Y strain infection presented moderate myocarditis and myositis, with parasites multiplying within macrophages. In C. callosus all four strains resulted in patent parasitemia which was eventually overcome, with scarce mortality. H2O2 release for strains Y and F was comparable to that of mice-peaks of 27 and 53 nM/2 x 10(6) cells, with lower values for strains Costalimai and M226-16.5 and 4.6 nM/2 x 10(6) cells, respectively. Histopathological lesions with Y and F strain injected animals were comparable to those of mice at the onset of infections; they subsided completely at the later stages with Y strain and partially with F strain infected C. callosus. In Costalimai infected C. callosus practically no histopathological alterations were observed.     

In vitro production of metacyclic forms of Trypanosoma musculi and their infectivity in CBA mice

Bloodstream forms of Trypanosoma musculi, cultured in Schneider's drosophila medium at room temperature, multiply and differentiate through a series of developmental stages into infective metacyclic trypomastigotes in 10 days. Oral inoculation with these culture forms into CBA mice produced a parasitemia similar to that produced by intraperitoneal infection with bloodstream forms except for a three-day longer prepatent period. Attempts to induce parasitemia with bloodstream forms given orally were unsuccessful.     

Endogenous IFN-gamma is required for resistance to acute Trypanosoma cruzi infection in mice

In order to study the role of endogenous IFN-gamma in Trypanosoma cruzi infection in mice, a potent murine IFN-gamma-specific mAb was injected i.p. on days -1, 7, and 14, relative to infection. Irrespective of the parasite inocula (100 or 25,000), groups of antibody-treated mice had significantly greater cumulative mortality rates than did appropriate controls. In antibody-treated mice, mean survival times were also significantly shorter, and maximum mean parasitemia levels were significantly higher, than in controls. Moreover, the number of amastigote nests in tissues was higher than in control mice and attained a maximum at the same time as parasitemia. As evident from kinetic studies of neutralizing activity, injected mAb were rapidly consumed in infected, but not in noninfected, mice, which is suggestive of massive IFN-gamma production during the early parasitemic phase of the disease. Nevertheless, IFN-gamma remained undetectable in the sera of infected but untreated mice. Unexpectedly, however, a peak of IFN-like antiviral activity, characterizable as a mixture of IFN-gamma and IFN-beta, appeared in mAb-treated mice that survived to infection at a time when neutralizing activity of injected mAb had drastically decreased in the circulation. We hypothesize that this high level of artificially induced endogenous IFN-gamma, not neutralized by the amounts of injected mAb, was due to the more intense parasite multiplication occurring in mAb-treated mice, which in turn may have induced an increased amount of various cytokines. TNF-alpha was not found in the serum of our mice. The humoral immune response entered its exponential phase at a time point later than that when protection by endogenous IFN-gamma was evident. Treatment with IFN-gamma-specific antibody, as applied in our study, failed to affect the level of different Ig isotypes or of T. cruzi-specific antibodies. Our study clearly indicates that IFN-gamma is produced early in acute T. cruzi infection and exerts a protective effect that is probably independent from the humoral immune response.     

A revised arithmetic model of long slender to short stumpy transformation in the African trypanosomes

An arithmetic model that closely approximates an African trypanosome infection in immunosuppressed mice is presented. The final model was based on an examination of the following parameters: the rate of long slender to short stumpy transition, the maximum percentage of long slender to short stumpy stages that can be induced, the survival time or half life of the short stumpy stage in vivo, and the rate (%) of long slender to short stumpy stage transition following the peak in transformation. The model is based on the assumption that the long slender to short stumpy transition is parasite population dependent and that in mice the long slender to short stumpy transition only begins when the trypanosome population reaches a density of 1 x 10(7) trypanosomes/ml. The model predicts that the parasitemia during the first several days of an infection is controlled solely by the kinetics of the transition of the dividing long slender stage to the nondividing short stumpy stage. It was not necessary to include in the model the host's immune response in order to simulate the early growth kinetics of pleomorphic trypanosomes in infected mice.     

Trypanosoma vivax: adaptation of two East African stocks to laboratory rodents

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 10(9)-10(10) 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.