In this study, we aimed to assess whether or not the resistance of T. congolense strain to trypanocides affects the development of infection in susceptible hosts. The slightly shorter prepatent period of drug-resistant T. congolense Mbagala in mice and steer relates with the observations of Tesfaye and co-workers [26] where resistant and sensitive isolates of T. congolense were compared in goats. Unlike these two studies, however, most reports revealed shorter prepatent period in drug sensitive strains [27]. This theory coincides with the proliferation and differentiation phenomenon of actively dividing slender form of trypanosomes, T. brucei in particular [27]. Findings of the present study therefore portray greater ability of the drug-resistant T. congolense Mbagala to multiply and establish in new hosts as relative to drug-sensitive T. congolense Mikese. This is the reason why parasitemia in mice and cattle infected with resistant strain appeared relatively faster compared to the sensitive strain. This unpopular short prepatent period and high rate of parasitemia observed in T. congolense Mbagala strain could be emanating from selection pressure created by extensive syringe passage, which often tend to select for parasite with higher replication rates. Similar scenario may be happening to the field population of trypanosomes in cases of intense selection pressure; thus emphasizing the need for collecting and testing fresh resistant isolate from the field where the current one was originally collected. Furthermore, the high multiplication rate in the drug resistant strain could also be explained by the ability of resistant trypanosomes to survive a die-off phenomenon owing to host’s immunological responses and possible rapid expression of variable surface glycoprotein (VSG) [28].
Although done definitely for the purpose of re-examining whether or not the test strains were still retaining their original drug sensitivity status, our results emphasize maintenance of such traits despite undergoing serial passage in laboratory white mice [29]. This observation, however, warrants further studies to ascertain how long such traits are retained particularly in cases of short cycles of repeated serial passages.
Worth noting, the initially high level of parasitaemia observed in cattle infected with resistant strain, declined over time post infection. Similar pattern was also observed in the trend of packed cell volume (PCV), which was measured as a proxy for anaemia. Such patterns varied prominently with observations made when mice were infected with such strain; suggesting the role of host immune response in limiting the increase of parasitaemia and anaemia. This phenomenon is among other factors that benefit trypanotolerant breeds of cattle. Naessens [30] defined trypanotolerance in bovine as the better capacity to control anaemia throughout the infection and eventually control parasite numbers in the blood during the later stages of infection. Low parasitaemia, moderate anaemia and non-disease state was also observed in this study in steer infected with resistant strain of T. congolense. Marcotty et al. [31] explained more parasite detection at early stages of infection even before anaemia development but low parasitaemia with marked anaemia at later stages of infections. The decline of parasitaemia and anaemia in cattle with resistant strain was associated with low rate of switching of variant surface glycoprotein (VSG) coat of trypanosomes attributed to serial syringe passaged infection [32].
Moreover, the mean PCV steer infected with the sensitive strain were significantly lower than that of steer infected with the resistant stock (p=0.04). This observation affirmed that there was a difference in the level of anaemia exerted by either strain; and emphasized anaemia is one of the major clinical manifestations of Trypanosoma infections. In this case anaemia is caused by mechanical injury of erythrocytes due to lashing movement of trypanosomes during parasitaemia [33]. Mbaya et al. [34] observed severe anaemia which was associated with high parasitaemia in gazelles concurrently infected with T. congolense and Haemonchus contortus. As expected, this and other similar findings corroborate with findings of the present studies in that the severity of anaemia and its correlation with parasitemia.
Scanty or absence of parasitaemia has been a characteristic feature in chronic form of T. congolense infections in cattle. This is normally accompanied by severe illness and death. Contrary was observed in this study, that parasitaemia in steer infected with T. congolense resistant strain declined over time resulting into asymptomatic host. However, the situation was different in steer infected with T. congolense-sensitive strain which demonstrated significantly low PCV, relatively higher parasitaemia, which resulted into development of the disease and eventually death of the steer within 31 days of monitoring. The animal died in the course of treatment. Mortalities in cattle after 4-7 weeks after infection with T. congolense strains were also reported elsewhere [20]. Based on the results of this study, the T. congolense-sensitive strain in cattle seemed more pathogenic that the resistant strain due to the fact that it eventually caused more severe anaemia, clinical manifestation and finally killed the animal.
The characteristic fluctuation in the rectal body temperature was also observed in the present study. There was increase in rectal body temperature in both groups in the second and third day post infection for sensitive and resistant strains infected mice. Despite both groups showing rise in rectal temperature, the rise was significantly higher (P=0.049) in mice infected with sensitive strains. The fluctuation in rectal temperature was observed throughout the parasitaemic phase and these observations were consistent with those reported by Mbaya et al. [35] following T. brucei infection in gazelles.
In the course of this study it was observed that mice infected with T. congolense-resistant strain appeared dull with reduced activities in a way that made them easy to handle as compared to those infected with T. congolense-sensitive strain. Mortalities were observed in T. congolense-resistant strain as early as nine days post-infection and hardly struggled to survive for 30 days since inoculation. In view of the observations mentioned above, T. congolense-resistant and sensitive strain were categorized as highly pathogenic and moderately pathogenic in mice; and this was in accordance to the categorization by Bengaly et al. [19]. These observed signs and animal death could be owing to the facts that highly virulent parasites tends to cause a severe damage as they multiply rapidly and reach a peak of parasitaemia within a short time after their introduction to a host.
The two strains of T. congolense behave contrariwise in cattle and mice. This could be due to variations of these hosts in terms of species, their body size, daily and metabolic activities and their immunological response. However, the observed high and low transmissibility and pathogenicity of T. congolense-resistant strain in mice and cattle respectively could also be attributed to pathogen defense against the hosts reactions and transmission cycle between hosts as this involved serial syringe passage of the stocks in mice prior to infection in cattle. Van Den Bossche et al. [5] suggested that susceptible host infected by highly virulent trypanosome strains will display a severe disease and leading to either treatment and/or death, leading therefore to a decrease in dispersion of highly virulent trypanosome as compared to its' less pathogenic competitor resulting in a relatively low fitness. This complements the observed difference in pathogenicity of resistant strain in mice and cattle in this study.
Variation in the ability of mice and cattle in handling infection of these two trypanosome strains suggest variation in pathogenicity of the two strains attributed to a number of hosts-related factors. Neither parasite antigen switching nor developmental progression to transmission stages is driven by host, instead host contribute to the infection dynamics [27]. The level at which primary peak of parasitaemia is reached is host specific [36]. Also, host’s immunity to most variants cause drop in antigenic switching rate as infection progresses [37]. In consistence with our findings, a number of studies correlated the ability of controlling anaemia with maintenance of low level of parasitaemia and thus signify trypanotolerance in cattle [30,38]. In contrast, trypanotolerance in mice associated with parasitaemia control as well as maintaining longer survival time [39]. As true this may be, results obtained in mice should cautiously be extrapolated in cattle, as may not be a true reflection of the same stock characteristics in cattle [40].