The Cyclical Development of Trypanosoma vivax in the Tsetse Fly Involves an Asymmetric Division.

Trypanosoma vivax is the most prevalent trypanosome species in African cattle. It is thought to be transmitted by tsetse flies after cyclical development restricted to the vector mouthparts. Here, we investigated the kinetics of T. vivax development in Glossina morsitans morsitans by serial dissections over 1 week to reveal differentiation and proliferation stages. After 3 days, stable numbers of attached epimastigotes were seen proliferating by symmetric division in the cibarium and proboscis, consistent with colonization and maintenance of a parasite population for the remaining lifespan of the tsetse fly. Strikingly, some asymmetrically dividing cells were also observed in proportions compatible with a continuous production of pre- metacyclic trypomastigotes. The involvement of this asymmetric division in T. vivax metacyclogenesis is discussed and compared to other trypanosomatids.

Genetic engineering of Trypanosoma (Dutonella) vivax and in vitro differentiation under axenic conditions.

Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis, and although this disease is widespread in Africa and Latin America, very few studies have been conducted on the parasite's biology. This is in part due to the fact that no reproducible experimental methods had been developed to maintain the different evolutive forms of this trypanosome under laboratory conditions. Appropriate protocols were developed in the 1990s for the axenic maintenance of three major animal Trypanosoma species: T. b. brucei, T. congolense and T. vivax. These pioneer studies rapidly led to the successful genetic manipulation of T. b. brucei and T. congolense. Advances were made in the understanding of these parasites' biology and virulence, and new drug targets were identified. By contrast, challenging in vitro conditions have been developed for T. vivax in the past, and this per se has contributed to defer both its genetic manipulation and subsequent gene function studies. Here we report on the optimization of non-infective T. vivax epimastigote axenic cultures and on the process of parasite in vitro differentiation into metacyclic infective forms. We have also constructed the first T. vivax specific expression vector that drives constitutive expression of the luciferase reporter gene. This vector was then used to establish and optimize epimastigote transfection. We then developed highly reproducible conditions that can be used to obtain and select stably transfected mutants that continue metacyclogenesis and are infectious in immunocompetent rodents.

Does isometamidium chloride treatment protect tsetse flies from trypanosome infections during SIT campaigns?

African animal trypanosomosis is a major pathological constraint to cattle breeding across 10 million km2 of sub-Saharan West African countries infested by tsetse flies, their cyclic vectors. The release of sterile males (sterile insect technique [SIT]) is a potentially important control technique aimed at eliminating the vectors. Prior to release, tsetse are generally treated with isometamidium chloride, a trypanocide, to prevent them from transmitting parasites. The present study investigated the preventive action of isometamidium chloride (0.5 mg/L) on the subsequent susceptibility of tsetse released into the wild. A total of 1755 Glossina palpalis gambiensis Vanderplank and 744 Glossina tachinoides Westwood were released, of which 50 and 48, respectively, were recaptured 22-43 days after release. Their probosces were analysed by polymerase chain reaction to identify mature infections with three trypanosome species (Trypanosoma vivax, Trypanosoma brucei sensu lato and Trypanosoma congolense savannah type). Two mature infections with T. vivax and four with T. congolense were detected, indicating that the use of this treatment regimen in an SIT campaign would not totally prevent sterile males from transmitting trypanosomes.

Development of an adaptive tsetse population management scheme for the Luke community, Ethiopia.

Since 1996, tsetse (Glossina spp.) control operations, using odor-baited traps, have been carried out in the Luke area of Gurage zone, southwestern Ethiopia. Glossina morsitans submorsitans Newstead was identified as the dominant species in the area, but the presence of Glossina fuscipes Newstead and Glossina pallidipes Austen also was recorded. Here, we refer to the combined number of these three species and report the work undertaken from October 2002 to October 2004 to render the control system more efficient by reducing the number of traps used and maintaining the previously reached levels of tsetse occurrence and trypanosomiasis prevalence. This was done by the design and implementation of an adaptive tsetse population management system. It consists first of an efficient community-participatory monitoring scheme that allowed us to reduce the number of traps used from 216 to 127 (107 monitoring traps and 20 control traps). Geostatistical methods, including kriging and mapping, furthermore allowed identification and monitoring of the spatiotemporal dynamics of patches with increased fly densities, referred to as hot spots. To respond to hot spots, the Luke community was advised and assisted in control trap deployment. Adaptive management was shown to be more efficient than the previously used mass trapping system. In that context, trap numbers could be reduced substantially, at the same time maintaining previously achieved levels of tsetse occurrences and disease prevalence.

Trypanosoma vivax: a simplified protocol for in vivo growth, isolation and cryopreservation.

A rodent adapted clone of Trypanosoma vivax was used to infect cyclophosphamide treated mice and rats. Fresh blood containing trypanosomes, was centrifuged in a density gradient of three Percoll solutions, 1.07, 1.06, 1.05 g/ml, respectively, carefully layered on top of each other. The yields of this simple procedure for trypanosome purification were about six times higher than those obtained with the conventional anion-exchange columns. Cryopreservation of trypanosomes using glycerol yielded 90% viable parasites, whereas using dimethylsulfoxide, a more commonly used cryoprotectant, the viability was only 35%.

Mechanical transmission of Trypanosoma vivax in cattle by the African tabanid Atylotus fuscipes.

An experiment was carried out in Burkina Faso to evaluate the potential for mechanical transmission of Trypanosoma vivax by the African tabanid Atylotus fuscipes. The experiment was carried out in a corral (10 m x 10 m) completely covered by a mosquito net (12 m x 12 m and 2.5m high). Eight heifers (cross-bred Zebu X Baoulé), free of trypanosome infection, were kept together with two heifers experimentally infected with a local stock of T. vivax. An average of 539 A. fuscipes per day, freshly captured with two Nzi traps, were introduced into the mosquito net from Day 1 to 20, to allow mechanical transmission of the parasites among cattle. Daily parasitological examinations (BCM) of cattle blood samples indicated that six of the eight receiver heifers were positive from days 9, 10, 15, 16, 19 and 29. Mechanical transmission of T. vivax by A. fuscipes was demonstrated unequivocally in close to natural conditions, at a high rate (75% incidence over a 20-day period) under a mean challenge of 54 insects per heifer per day. These results, in addition to previous demonstration of mechanical transmission of T. vivax by Atylotus agrestis, confirm that mechanical transmission can be a significant route of infection.

Epidemiological factors that influence time-to-treatment of trypanosomosis in Orma Boran cattle raised at Galana Ranch, Kenya.

Four thousand nine hundred and seventy-one trypanosomosis-surveillance records from an open population of Orma Boran cattle raised under natural trypanosomosis challenge in Galana Ranch, Kenya between the years 1990 and 2000 were analysed. The objective of the analysis was to identify epidemiological factors that influenced time-to-treatment of trypanosomosis cases. Under the surveillance programme, blood was being examined fortnightly for trypanosomosis using buffy coat technique. Infected animals were treated when their packed cell volumes (PCV) fell to 25% or lower. The number of days between the first diagnosis and treatment of trypanosomosis cases was obtained from the difference between diagnosis and treatment dates. Days-to-treatment clustered around the screening periods; therefore, time-to-treatment was represented by a series of time points 0-8 at 14-day intervals. Factors postulated to affect the outcome (time-to-treatment) were age of an animal at time of diagnosis, sex, number of trypanosome infections, trypanosome species and season of the year. Five animal generations were generated from birth dates and treated as nuisance parameters. Conditional logistic regression and Cox proportional hazards models were fitted to the data, the former to analyse factors that influenced treatment after time 0 (outcome dichotomised as time 0 or >0) and the latter to analyse factors that influenced time-to-treatment for cases that were treated after time 0, excluding all cases treated on time 0. The majority of the cases (89.5%) were treated on the same day of diagnosis. Trypanosome infections were more likely to be treated after time 0 in dry than in wet season. Similarly, the rate of treatment was lower in the dry than the wet season. An increase in number of previous trypanosome infections reduced the odds of an animal being treated after time 0. Animals that had been exposed to many infections before had higher rates of treatment than those that had minimal experiences. We offer possible reasons for these observations and conclude that selection of animals for breeding purposes in programmes geared towards improving trypanotolerance should take into consideration the environmental factors that affect classification of an animal as being resistant or susceptible.

The effects of trypanosomosis on sperm morphology in Zebu x Friesian crossbred bulls.

Detailed studies of sperm morphological abnormalities were carried out on 12 Zebu x Friesian crossbred bulls used in a study of the effects of trypanosomosis. Four bulls were infected with T. vivax, another four with T. congolense, while four served as controls. The infected bulls developed chronic trypanosomosis. All the bulls initially had very low sperm morphological abnormalities that were within acceptable limits for fertile animals. After infection there was a rapid and progressive increase in all sperm abnormalities. Spermatozoa of infected bulls were highly deformed with multiple morphological defects. Mean percentage pre-infection baseline values prior to infection for acrosomal, sperm-head, detached heads, proximal cytoplasmic droplets, distal cytoplasmic droplets, sperm-tail, midpiece and total sperm morphological defects ranged between 0.1 +/- 0.1 for acrosomal and 8.3 +/- 3.2 for total morphological abnormalities in the semen of the bulls. All the infected bulls developed sperm morphological abnormalities of more than a mean of 40.0% from the 4th week after infection until the end of the investigation and were considered unfit for breeding. At 7 weeks post-infection (PI) until the end of the study (12 weeks PI), the controls had a mean of less than 5% sperm morphological defects, while the infected bulls had 100%. Mean percentage values of sperm morphological defects throughout the duration of the investigation for control bulls were low and within the normal range for fertile bulls. These values differed significantly (p<0.001) from the elevated values of the infected bulls. The results show that trypanosomosis due to T. vivax or T. congolense infection can render Zebu x Friesian crossbred bulls unfit for breeding within a very short time. The resultant infertility could be of economic importance in trypanosomosis-endemic sub-Saharan Africa where Zebu x Friesian crossbred bulls are kept.

The African trypanosome cyclophilin A homologue contains unusual conserved central and N-terminal domains and is developmentally regulated.

We have cloned and characterized the homologue of cyclophilin A (CypA) from Trypanosoma brucei brucei, Trypanosoma congolense, Trypanosoma evansi and Trypanosoma vivax. The 1-kilobase African trypanosome CypA complementary DNA contains an open reading frame of 531 base pairs, corresponding to 177 amino acids with a calculated molecular weight of 18,700. The CypA gene is present at one copy/haploid genome in T. brucei, T. congolense and T. vivax and is located on large chromosomes (>3 Mb) in T. brucei. CypA is differentially transcribed in African trypanosomes and is localized in the cytosol as well as in the flagellum. It is also detected in the supernatant of in vitro cultivated parasites. The African trypanosome CypA is unique due to a ten amino acid residue N-terminus extension and a block that includes a three amino acid insertion around position 100 that might result in a differently structured surface. Wild-type recombinant CypA and several mutants were over-expressed in Escherichia coli and purified to >98% homogeneity. Antisera from cattle immunized with a trypanosome fraction containing immunosuppressive activity react strongly against CypA. These data indicate that trypanosome CypA might play an important role in the establishment and maintenance of infections in susceptible animals.

The area-wide epidemiology of bovine trypanosomosis and its impact on mixed farming in subhumid West Africa; a case study in Togo.

This paper reports on an area wide study of all major variables determining the expression of trypanosomosis in cattle in the subhumid eco-zone of West Africa, taking Togo as an example. To enable systematic area-wide sampling, the country was divided in 311 grid-squares of 0.125 x 0.125 sides. Cross-sectional surveys were then conducted to generate maps or digital layers on cattle density, herd structure, ownership and breed. These data layers, except for the breed data, were subjected to a cluster analysis in order to define spatial patterns in animal husbandry systems. This analysis revealed two main systems: one is oriented towards integration with crop-agriculture and a second towards investment in cattle. These two systems could be further characterised by incorporating breed data. Zebu cattle and their crossbreeds are more favoured in the second system. The breed distribution map shows the actual situation but also serves to predict the outcome of progressive crossbreeding. An area wide trypanosomosis survey allowed the production of prevalence maps for Trypanosoma congolense, T. vivax and the associated packed cell volume (PCV) values. A simple curvi-linear relationship was established between vector density and disease prevalence. The regression between disease prevalence and PCV for taurine and zebu plus crossbreeds separately, revealed that taurine cattle maintain a comparatively high PCV level particularly in high prevalence scenarios. The relationship between the average herd PCV and cattle density suggests that herd PCV value may provide a mirror for the number of animals not kept because of the prevailing risk. The regression between agricultural intensity and cattle density subsequently in areas with decreasing herd PCV values reveals that the level of integration of cattle in crop production decreases with a decreasing PCV. Thus, despite the presence of taurine animals in Togo, the omnipresence of tsetse in particular Glossina tachinoides, remains a major obstacle to cattle raising and indirectly mixed farming development and intensification. It is argued that only with the present type of wide scale, spatial studies it becomes possible to clarify all the major variables influencing the expression of trypanosomosis. Spatial epidemiological studies at a macro level may form the basis for area wide trypanosomosis control in West Africa.

Hematology of natural bovine trypanosomosis in the Brazilian Pantanal and Bolivian wetlands.

We report hematological changes observed in natural cases of bovine trypanosomosis due to Trypanosoma vivax in beef and dairy cattle from Bolivian wetlands and Pantanal, Brazil. The main hematologic changes produced by T. vivax infections were anemia and severe leucopenia. The cattle presented macrocytic hypochromic anemia. The leukocyte changes were characterized by relative lymphocytosis and monocytosis and decrease in the neutrophil counts. The clinical signs were lachrymation, progressive weakness, marked weight loss, inappetence, diarrhea and abortions during the third trimester of pregnancy.

Health and productivity of traditionally managed Djallonke sheep and West African dwarf goats under high and moderate trypanosomosis risk.

Trypanosome infections, packed red cell volume levels (PCV), body weight and nematode faecal egg counts of village-based small ruminants were monitored in two areas in The Gambia with either moderate or high trypanosomosis risk for 24 and 30 months respectively. Outflows from the flock and new-born animals were recorded and data on housing and management were compiled. Reported mortality rates were higher in goats than in sheep, but for both species highest in the moderate risk area. The peak of trypanosome infections lagged the peak of tsetse densities by 1-3 months in both areas. Trypanosoma vivax was the predominant species found in the infected animals, followed by T. congolense. Trypanosome prevalence was, in general, higher in sheep than in goats but only significantly higher during Year 1 in the moderate risk area. Trypanosome infection reduced the PCV level significantly and seasonal effects indicated significantly lower PCV levels during the rains. Trypanosome infection significantly depressed weight gain in both species at periods where infection rates were highest. In both species considerably lower weight gains were observed during the rainy season. Abortion rates were higher in goats than in sheep in both study sites, and highest in the high-risk site. Trypanosome infection in ewes in the high risk area increased lamb mortality significantly but had no effect on birth weights, nor on growth rates up to 4 months. Offspring mortality up to 4 months was generally high at both sites. Trypanosome infection in the dam between 3.5 to 7 months post parturition significantly increased parturition interval in both species. Peak faecal egg output occurred at the end of the rainy season and was highest for both species in the moderate risk site. Poor grazing management was found responsible for a seasonal nutritional constraint. Based on these results, these breeds of sheep and goats can be considered as trypanotolerant since they are able to remain productive under high and moderate levels of trypanosome challenge. Nevertheless, trypanosomosis affected their health and production level as shown by reduced PCV levels, depressed weight gains, longer parturition intervals and higher lamb mortality. In addition, during the rains, helminth infections and poor management leading to nutritional constraints had also a negative impact on health and production and therefore influenced the innate resilience to trypanosomosis in those indigenous breeds. Adaptations in management may have an equal impact as certain disease control measures to improve biological and economical returns from small ruminants in tsetse infested rural areas.

Study on the sequential tsetse-transmitted Trypanosoma congolense, T. brucei brucei and T. vivax infections to African buffalo, eland, waterbuck, N'Dama and Boran cattle.

Susceptibility of African buffalo, eland, waterbuck, N'Dama and Boran cattle to sequential Glossina morsitans centralis-transmitted infections of Trypanosoma congolense, T. brucei brucei and T. vivax was compared, and their possible role as reservoirs of these parasites for G. moristans centralis, G. pallidipes, G. austeni, G. brevipalpis and G. longipennis determined. The buffalo, eland, waterbuck and N'Dama controlled T. congolense parasitaemias and were able to prevent anaemia. By contrast, one Boran became severely anaemic whilst the other controlled parasitaemia and anaemia. When the above five species of Bovidae were rechallenged with T. brucei brucei they showed persistent parasitaemias but did not develop anaemia. The buffalo died of other causes. When the remaining four bovids were rechallenged with T. vivax they became infected with mixed T. vivax/T. b. brucei parasites. Eland, waterbuck and N'Dama controlled parasitaemias and anaemia whereas the Boran became anaemic. Cyclical development of T. congolense occurred in G. moristans centralis when fed on the bovid hosts, with buffalo being infective for tsetse flies for a much longer period. There was no relationship between the levels of T. congolense parasitaemia in the bovid hosts and the resultant infection rates in tsetse flies. Glossina m. centralis was more susceptible than G. pallidipes to T. brucei brucei whilst G. austeni the least; G. brevipalpis and G. longipennis were refractory to the mature infection. Again there was no relationship between T. brucei brucei parasitaemia levels in the hosts and infection rates in the flies. Glossina m. centralis and G. pallidipes showed mixed T. brucei brucei/T. vivax infections whilst G. austeni, G. brevipalpis and G. longipennis became infected with T. vivax alone. Tsetse flies showed higher T. vivax infection rates when fed on the hosts with high parasitaemias than thosewith low parasitaemias. Thus trypanotolerant African buffalo, eland, waterbuck, N'Dama as well as some trypanosusceptible Boran cattle can serve as reservoirs of single or mixed trypanosome infections for tsetse flies. This study has also shown that the Ag-ELISA on the sera from the five bovid hosts had low sensitivity and species-specificity. Examinations of thin wet blood films and buffy coats with a phase-contrast microscope were not sensitive enough to detect the parasites on all occasions. Xenodiagnosis using mice for T. brucei brucei and T. congolense infections, and tsetse flies for all the three trypanosome species were most sensitive for the detection of trypanosome infections in the bovid hosts.

Differentiation between culture-derived insect stages of T. brucei, T. vivax, T. congolense and T. simiae using a monoclonal antibody-based dot-ELISA.

A sensitive and specific nitrocellulose (NC) membrane-based dot-ELISA, utilizing a panel of monoclonal antibodies (mAbs), was developed for differentiation between in vitro-derived procyclic forms of Trypanosoma brucei, T. congolense and T. simiae, and epimastigotes of T. vivax. Trypanosomes in suspension were applied onto NC membrane in dots and probed with unlabelled trypanosome species-specific mAbs. Bound mAb was revealed by enzyme labelled anti-mouse IgG and precipitable chromogenic substrate. The assay detected the aforementioned trypanosome species in both single and artificially mixed preparations. Ten T. brucei, 4 T. vivax, 7 T. congolense and 3 T. simiae procyclic stocks and clones from different geographical areas were tested and identified using the specific mAbs in the dot-ELISA which had a specificity of 100%. Some of the T. brucei, T. congolense and Nannomonas-specific mAbs could detect as few as 10 trypanosomes/dot, whilst 1 T. vivax mAb was able to detect a minimum of 100 trypanosomes/dot in monospecies preparations. A concentration of 1 x 10(4) trypanosomes/microliters/dot was eventually determined as ideal for testing in the dot-ELISA. Antigen dots stored at 4 degrees C under desiccated conditions did not show any loss in activity for up to 90 days. However, when stored under similar conditions at room temperature (17-26 degrees C), the T. congolense-specific antigen remained unaffected up to 60 days, and then showed decreased activity when tested on day 90.

Evaluation of a short-term in vitro growth-inhibition test to determine susceptibility of Trypanosoma vivax stocks to various trypanocides.

Two Trypanosoma vivax stocks were initiated in culture with tsetse or culture-derived metacyclics. They were propagated axenically as bloodstream trypomastigotes at 35 degrees C in 4% CO2 in air. Populations of trypanosomes were incubated with various concentrations of antitrypanosomal compounds, namely diminazene aceturate, quinapyramine sulphate, DL-alpha-difluoromethylornithine, isometamidium chloride, suramin and melCy. Growth was monitored after 24 h of incubation and the growth inhibition was calculated. All six drugs tested showed little effect upon the growth of the parasite populations. These results indicate that a 24-h growth-inhibition test was not suitable for determining the drug susceptibility of T. vivax stocks in vitro. Neither did the results correlate with those obtained with susceptible or resistant stocks of T.b. brucei, T.b. evansi or T. simiae described in the literature, or with the results of these two T. vivax stocks tested in cattle.

A modified medium for the in vitro cultivation of trypanosomes.

A modified medium (ME-99) for the in vitro cultivation of trypanosomes was developed and evaluated in our laboratory. The medium comprised of Eagle MEM as a base and various components of medium 199 not found in MEM. Trypanosoma brucei brucei, T. b. gambiense and T. vivax were grown in ME-99 and various other media combinations such as MEM/RPMI 1640, MEM/BCM, MEM/199, RPMI 1640/BCM, RPMI 1640/199, BCM/199 for comparison. Both growth and infectivity of these parasites were compared in these media. Parasites grew better and maintained their infectivity for longer periods in ME-99 than in any other medium or combination of media.

Vector competence of Glossina pallidipes and G. morsitans centralis for Trypanosoma vivax, T. congolense and T. b. brucei.

Vector competence of Glossina pallidipes for pathogenic Trypanosoma species was compared to that of G. morsitans centralis. Cattle or goats were the hosts used to infect teneral tsetse, rabbits were used to maintain tsetse which were dissected on day 30. Mean infection rates of G. pallidipes and G. m. centralis by T. vivax isolated from a cow in Kenya were respectively 39.5 +/- 8.9% and 32.1 +/- 10.3% whilst for T. vivax isolated from a cow in Nigeria, they were 30.0 +/- 7.5% and 19.8 +/- 4.3%. Differences were not significant. Differences in infection rates between the sexes of flies were also not significant. Transmission capability to goats by either tsetse species was good for the two T. vivax isolates. Mean infection rates by T. congolense isolated from a lion in Tanzania were significantly lower in G. pallidipes (8.5 +/- 1.8%) than in G. m. centralis (22.5 +/- 2.0%). Males of either tsetse were more susceptible than females. Transmission rates to goats and mice by both tsetse species was 100%. G. pallidipes (3.5%) was less susceptible than G. m. centralis (25.1%) to T. congolense isolated from a cow in Nigeria, but transmission rates to goats and mice by either tsetse was 100%. Also, G. pallidipes (2.7 +/- 0.4%) was significantly less susceptible than G. m. centralis (18.4 +/- 1.1%) to T. b. brucei isolated from a hartebeest in Tanzania. Males of either tsetse species were more susceptible than females. Transmission rates to goats and mice by either tsetse was 100%. G. pallidipes (0%) was not susceptible to T. b. brucei isolated from a pig in Nigeria whilst G. m. centralis showed infection rate of 9.3%. When male G. pallidipes and G. m. centralis were fed every day for 27 days on a goat infected with this T. b. brucei from Nigeria, the infection rates were 8.7% and 20.2%, respectively. Transmission rates to mice by either tsetse species was 100%. In conclusion, G. pallidipes has a vector competence equal to that of G. m. centralis for T. vivax, whilst G. pallidipes has lower vector competence than G. m. centralis for T. congolense and T. b. brucei.

Host parasite relationships in Trypanosoma (duttonella) vivax with special reference to the influence of antigenic variation.

A mouse model system was used to study various aspects of host and parasite relationships in Trypanosoma vivax infections. These included the phenomenon of antigenic variation, the variable parasite antigens responsible for this phenomenon, parasite-host adaption, host immune responses and the role of genes in the major histocompatibility complex in the control of infection. While the mouse model system has allowed investigation of these aspects of host parasite relationships, it is clear that the system is much more limited than those generally used in T. brucei spp and T. congolense infections. This is indicated by the discovery that not all VATs of T. vivax were equally infective for mice, though in some cases infectivity could be improved by bovine serum supplementation and/or immunosuppression of the mouse host. In the case of rats, infection was even restricted to a smaller number of the VATs studied. It was, however, possible to biochemically characterize the variable surface antigen carried by T. vivax and show its similarity to those carried by T. brucei and T. congolense. The H-2 complex was found not to influence acquired resistance of inbred strains. Cyclic transmissions of T. vivax infections to goats combined with chemotherapy were carried out in an attempt to induce protection to subsequent infection as has been shown in T. brucei and T. congolense infections. Such protection could, however, not be obtained, The failure of the metacyclic VATs to induce immunity, was perhaps due to rapid decrease in antibody titres to bloodstream VATs found after treatment and prior to rechallenge. The usefulness of the mouse model system in elucidating the mechanisms responsible for the non-H-2 linked differences in susceptibility to T. vivax infections should be further explored and its relevance to mechanisms of trypanotolerance in domestic ruminants defined.