Virulence and pathogenicity of three &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; stabilates in a Swiss white mouse model

Kariuki, Christopher; Kagira, John; Mwadime, Victor; Ngotho, Maina

doi:10.4102/ajlm.v4i1.137

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…The present study recorded tissue inflammation in mice infected with the two forms and was in consistent with previous observations [27,51]. Trypanosome-induced inflammation lesions were more intense in CNS than in BSF derived trypanosomes infected mice which could be informed by the enhanced tissue invasion in CNS infected mice.…”

Section: Discussionsupporting

confidence: 92%

“…Indeed, our results showed that at the end of experiment the spleen and liver organs of BSF and CNS infected mice were heavier when compared with the non-infected control. Our findings showed short survival times for mice infected with EATRO 2291 and KETRI 2656 demonstrating the two isolates as the most virulent among isolates used in this study [27,38].…”

Section: Discussionmentioning

confidence: 47%

“…The shortest survival time was observed in mice infected with EATRO 2291 at 13.7 ± 2.0 and 12.7 ± 1.5 for BSF or CNS infected mice, respectively determined after which the mouse was euthanized, dissected and the brain, spleen, kidneys, liver, lungs and heart collected and weighed using a weighing balance (Mettler Toledo PB 302 ®, Switzerland). These organs were preserved in 10% formalin and thereafter processed for histopathology as previously described [27]..…”

Section: Survivalmentioning

confidence: 99%

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Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

Ndung'u¹,

Ga²,

Jk³

et al. 2020

Preprint

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Background: Phenotypic and morphological characteristics distinguishing from bloodstream form (BSF) and central nervous system (CNS) of Trypanosoma brucei rhodesiense (Tbr) are poorly understood. Method: To identify these distinguishing characteristics, we separately infected four donor mice with each of five Tbr isolates (KETRI 2537/3537/2656/3459 and EATRO 2291). At 21 days post infection (DPI), donor mice were euthanized, BSF or CNS derived trypanosomes recovered and used for the following studies: 1) determination of morphological characteristics 2) pathogenicity studies using groups of 10 mice per isolate form. We then assessed differences in their lengths and morphology) and other characteristics including pre-patent period (PP), parasitaemia progression, packed cell volume (PCV), body weight, survival times, gross pathology, and histopathology. All analyses of data were conducted using GenStat, UK where p ⩽ 0.05 were considered statistically significant. Differences between and within the means were analyzed using one-way ANOVA. General Linear Model was used to analyze data on the length of the trypanosome. Survival data analysis was carried out employing the Kaplan–Meier method. Results: Morphologically, the CNS forms were predominantly long slender (LS) while BSF forms consisted of a mixture of short stumpy and intermediate forms. The mean length of CNS trypanosomes was 0.6 micrometer longer than their counterpart BSF derived trypanosomes. The PP was significantly (p<0.05) shorter and progression to peak parasitaemia faster (7 vs 9 days) in CNS than BSF derived trypanosomes. PCV declined by 21.6% and 26.9% in BSF and CNS infected mice respectively whereas non-infected control increased by 3.8% at 14 DPI. Body weight changes in BSF and CNS infected mice were (12.7% and 9.2% respectively) and significantly (p <0.05) lower than in non-infected control (27.6%) at 14 DPI. Gross pathology changes (splenomegaly and hepatomegaly) and histopathology changes were pronounced in mice infected with CNS relative to BSF trypanosome forms. Changes in histopathology included congestion, infiltration with inflammatory cells, hemolysis and necrosis, all indicators of differential virulence of the forms. Conclusion: Our study identified higher pathogenicity in CNS relative to BFS derived trypanosome forms in the mouse model. We also identified KETRI 2656 as a suitable isolate for acute menigo- encephalitic studies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 47%

Section: Survivalmentioning

confidence: 99%

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Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

Ndung'u¹,

Ga²,

Jk³

et al. 2020

Preprint

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“…brucei) , the donor mice were anaesthetized using carbon dioxide, the parasites collected through cardiac puncture in tubes containing 10% EDTA and quantified using improved Neubauer chamber method of [23] The parasites (in blood) were subsequently diluted to 1.0 x 10 4 trypanosomes/mL with Phosphate-buffered-Saline-Glucose (PSG) (44 mM NaCl, 57 mM Na 2 HPO 4 , 3 mM KH 2 PO 4 , 55 mM glucose) pH 8.0 solution. Subsequently, five groups of six mice [5,24,25]each were intraperitoneally, subcutaneously, intramuscularly, intradermaly or intravenously inoculated with 0.1mL (1.0 x 10 4 trypanosomes) of the T . brucei or T .…”

Section: Methodsmentioning

confidence: 99%

Route of inoculation influences Trypanosoma congolense and Trypanosoma brucei brucei virulence in Swiss white mice

et al. 2019

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Experiments on infections caused by trypanosomes are widely performed in Swiss white mice through various inoculation routes. To better understand the effect of route of trypanosome inoculation on disease outcomes in this model, we characterised the virulence of two isolates, Trypanosoma bruce i KETRI 2710 and T . congolense KETRI 2765 in Swiss white mice. For each of the isolates, five routes of parasite inoculation, namely intraperitoneal (IP), subcutaneous (SC), intramuscular (IM) intradermal (ID) and intravenous (IV) were compared using groups (n = 6) of mice, with each mouse receiving 1x10 4 trypanosomes. We subsequently assessed impact of the routes on disease indices that included pre-patent period (PP), parasitaemia levels, Packed Cell Volume (PCV), bodyweight changes and survival time. Pre-patent period for IP inoculated mice was a mean ± SE of 3.8 ± 0.2 and 6.5 ± 0.0 for the T brucei and T . congolense isolates respectively; the PP for mice groups inoculated using other routes were not significantly different(p> 0.05) irrespective of route of inoculation and species of trypanosomes. With ID and IP routes, parasitaemia was significantly higher in T . brucei and significantly lower in T . congolense infected mice and the progression to peak parasitaemia routes showed no significant different between the routes of either species of trypanosome. The IM and ID routes in T . congolense inoculations, and IP and IV in T . b . brucei induced the fastest and slowest parasitaemia progressions respectively. There were significant differences in rates of reduction of PCV with time post infection in mice infected by the two species and which was more pronounced in sc and ip injected mice. No significant differences in mice body weight changes and survivorship was observed between the routes of inoculation. Inoculation route therefore appears to be a critical determinant of pathogenicity of Trypanosoma congolense and Trypanosoma brucei brucei in murine mouse model of African trypanosomiasis.

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“…Gating strategies are given in S4 and S5 Figs. of motor dysfunction are often present in HAT and were reported in mice infected with T. b. gambiense or with T. b. rhodesiense [41,42]. Although we have not directly analyzed parasite penetration in the brain nor the extension of neuroinflammation, the appearance of the motor disorders in the infected mice can be considered an indirect sign of neurodegeneration, and therefore, helped to assess the contribution of TbISP2 to pathogenicity.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 97%

Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host

et al. 2021

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Trypanosoma brucei rhodesiense is one of the causative agents of Human African Trypanosomiasis (HAT), known as sleeping sickness. The parasite invades the central nervous system and causes severe encephalitis that is fatal if left untreated. We have previously identified ecotin-like inhibitors of serine peptidases, named ISPs, in trypanosomatid parasitic protozoa. Here, we investigated the role of ISP2 in bloodstream form T. b. rhodesiense. We generated gene-deficient mutants lacking ISP2 (Δisp2), which displayed a growth profile in vitro similar to that of wild-type (WT) parasites. C57BL/6 mice infected with Δisp2 displayed lower blood parasitemia, a delayed hind leg pathological phenotype and survived longer. The immune response was examined at two time-points that corresponded with two peaks of parasitemia. At 4 days, the spleens of Δisp2-infected mice had a greater percentage of NOS2+ myeloid cells, IFN-γ+-NK cells and increased TNF-α compared to those infected with WT and parasites re-expressing ISP2 (Δisp2:ISP2). By 13 days the increased NOS2+ population was sustained in Δisp2-infected mice, along with increased percentages of monocyte-derived dendritic cells, as well as CD19+ B lymphocytes, and CD8+ and CD4+ T lymphocytes. Taken together, these findings indicate that ISP2 contributes to T. b. rhodesiense virulence in mice and attenuates the inflammatory response during early infection.

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Virulence and pathogenicity of three <i>Trypanosoma brucei rhodesiense</i> stabilates in a Swiss white mouse model

Cited by 7 publications

References 30 publications

Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

Route of inoculation influences Trypanosoma congolense and Trypanosoma brucei brucei virulence in Swiss white mice

Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host

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