Comparative pathogenicity of Trypanosoma brucei rhodesiense strains in Swiss white mice and Mastomys natalensis rats

Muchiri, Margaret Wanjiku; Ndung’u, Kariuki; Kibugu, James Karuku; Thuita, John K.; Ngae, G. N.; Mdachi, Raymond; Kagira, John

doi:10.1016/j.actatropica.2015.06.010

Cited by 5 publications

(7 citation statements)

References 16 publications

(29 reference statements)

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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%

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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%

“…The difference we observed in our study could be attributed to the severity of CNS over BSF infected mice. In a study by Muchiri [51], the authors observed pronounced splenomegaly and hepatomegaly in T.b. rhodesiense isolates causing severe as compared to those causing less severe infection.…”

Section: Discussionmentioning

confidence: 97%

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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“…The density at which long slender trypanosomes cease to proliferate, and become stumpy, differs according to the environment [ 8 ]. In rodents, maximal densities of fully pleomorphic parasites are 1–5 x 10 8 /ml [ 16 – 18 ] for the initial parasitaemia, with differentiation initiating above 5 x 10 7 /ml. In contrast, differentiation-competent trypanosomes in liquid culture arrest at 1–2 x 10 6 /ml [ 8 ]).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, differentiation-competent trypanosomes in liquid culture arrest at 1–2 x 10 6 /ml [ 8 ]). In experimentally infected cattle [ 19 ] or Mastomys natalensis rats (but not Swiss mice) [ 18 ], parasitaemias are lower during chronic infection than in the initial wave. Humans who present for sleeping sickness diagnosis, have usually been infected for some time, and rarely show T .…”

Section: Introductionmentioning

confidence: 99%

Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods

Mulindwa

Leiss

Ibberson³

et al. 2018

PLoS Negl Trop Dis

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All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of human patients with those of trypanosomes from culture and rodents. The data were aligned and analysed using new user-friendly applications designed for Kinetoplastid RNA-Seq data. The transcriptomes of trypanosomes from human blood and cerebrospinal fluid did not predict major metabolic differences that might affect drug susceptibility. Usefully, there were relatively few differences between the transcriptomes of trypanosomes from patients and those of similar trypanosomes grown in rats. Transcriptomes of monomorphic laboratory-adapted parasites grown in in vitro culture closely resembled those of the human parasites, but some differences were seen. In poly(A)-selected mRNA transcriptomes, mRNAs encoding some protein kinases and RNA-binding proteins were under-represented relative to mRNA that had not been poly(A) selected; further investigation revealed that the selection tends to result in loss of longer mRNAs.

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“…Differences in the severity and progression of trypanosome-caused diseases (virulence and pathogenicity, as defined in this study) have been described for infections of T. bruceigambiense ( Holzmuller et al, 2008 , Kaboré et al, 2018 ), T. bruceirhodesiense ( Maclean et al, 2007 , Muchiri et al, 2015 ), T. congolense ( Bengaly et al, 2002a , Bengaly et al, 2002b , Grébaut et al, 2009 , Masumu et al, 2006 ), T. evansi ( Perrone et al, 2018 , Verdillo et al, 2012 ) and T. cruzi ( Andrade et al, 1985 , Belew et al, 2017 , Henrique et al, 2016 , Lauria-Pires and Teixeira, 1996 ). Similarly, differences in virulence and pathogenicity have been recognized between East and West African strains of T. vivax , the West African strains being generally more pathogenic to cattle ( Gardiner, 1989 ).…”

Section: Discussionmentioning

confidence: 76%

Trypanosoma vivax infection in sheep: Different patterns of virulence and pathogenicity associated with differentially expressed proteomes

Ramirez-Barrios

Reyna-Bello

Parra

et al. 2019

Veterinary Parasitology

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Highlights Trypanosoma vivax strains exhibit different virulence and pathogenicity patterns. TvMT1 strain showed low virulence and high pathogenicity. TvLIEM176 strain showed high virulence and moderate pathogenicity. Protein expression varies in high virulence/moderate pathogenicity strain vs low virulence/high pathogenicity strain.

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Comparative pathogenicity of Trypanosoma brucei rhodesiense strains in Swiss white mice and Mastomys natalensis rats

Cited by 5 publications

References 16 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.

Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods

Trypanosoma vivax infection in sheep: Different patterns of virulence and pathogenicity associated with differentially expressed proteomes

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