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

2020 ◽  
Author(s):  
Kariuki Ndung'u ◽  
Grace Adira Murilla ◽  
John Kibuthu Thuita ◽  
John Maina Kagira ◽  
Paul O. Mireji ◽  
...  
Keyword(s):  
Body Weight ◽  
Trypanosoma Brucei ◽  
Survival Data ◽  
Morphological Characteristics ◽  
Bloodstream Form ◽  
Weight Changes ◽  
Survival Times ◽  
Trypanosoma Brucei Rhodesiense ◽  
Infected Control ◽  
Gross Pathology

Abstract 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.

scholarly journals Differential virulence of Trypanosoma brucei rhodesiense isolates does not influence the outcome of treatment with anti-trypanosomal drugs in the mouse model

2020 ◽  
Author(s):  
Kariuki Ndung’u ◽  
Grace Adira Murilla ◽  
John Kibuthu Thuita ◽  
Geoffrey Njuguna Ngae ◽  
Joanna Eseri Auma ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Post Infection ◽  
Drug Resistant ◽  
Weight Changes ◽  
Trypanosoma Brucei Rhodesiense ◽  
Diminazene Aceturate ◽  
Reference Drug ◽  
Western Kenya ◽  
Biotechnology Research ◽  
Cure Rates

AbstractWe assessed the virulence and anti-trypanosomal drug sensitivity patterns of Trypanosoma brucei rhodesiense (Tbr) isolates in the Kenya Agricultural and Livestock Research Organization-Biotechnology Research Institute (KALRO-BioRI) cryobank. Specifically, the study focused on Tbr clones originally isolated from the western Kenya/eastern Uganda focus of human African Trypanosomiasis (HAT). Twelve (12) Tbr clones were assessed for virulence using groups(n=10) of Swiss White Mice monitored for 60 days post infection (dpi). Based on survival time, four classes of virulence were identified: (a) very-acute: 0-15, (b) acute: 16-30, (c) sub-acute: 31-45 and (d) chronic: 46-60 dpi. Other virulence biomarkers identified included: prepatent period (pp), parasitaemia progression, packed cell volume (PCV) and body weight changes. The test Tbr clones together with KALRO-BioRi reference drug-resistant and drug sensitive isolates were then tested for sensitivity to melarsoprol (mel B) pentamidine, diminazene aceturate and suramin, using mice groups (n= 5) treated with single doses of each drug at 24 hours post infection. Our results showed that the clones were distributed among four classes of virulence as follows: 3/12 (very-acute), 3/12 (acute), 2/12 (sub-acute) and 4/12 (chronic) isolates. Differences in survivorship, parasitaemia progression and PCV were significant (P<0.001) and correlated. The isolate considered to be drug resistant at KALRO-BioRI, KETRI 2538, was confirmed to be resistant to melarsoprol, pentamidine and diminazene aceturate but it was not resistant to suramin. At least 80% cure rates of all the test isolates was achieved with melarsoprol (1mg/Kg and 20 mg/kg), pentamidine (5 and 20 mg/kg), diminazene aceturate (5 mg/kg) and suramin (5 mg/kg) indicating that the isolates were not resistant to any of the drugs despite the differences in virulence. This study provides evidence of variations in virulence of Tbr isolates from a single HAT focus and confirms that these variations are not a significant determinant of isolate sensitivity to anti-trypanosomal drugs.

scholarly journals Virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates in a Swiss white mouse model

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Christopher Kariuki ◽  
John M. Kagira ◽  
Victor Mwadime ◽  
Maina Ngotho
Keyword(s):  
Trypanosoma Brucei ◽  
Late Stage ◽  
Basic Research ◽  
White Mouse ◽  
Primate Research ◽  
Survival Times ◽  
Trypanosoma Brucei Rhodesiense ◽  
Diminazene Aceturate ◽  
Blood Smears ◽  
Peak Parasitaemia

Background: A key objective in basic research on human African trypanosomiasis (HAT) is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.Objective: With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates, labelled as International Livestock Research Institute (ILRI)-2918, ILRI-3953, and Institute of Primate Research (IPR)-001, infected into Swiss white mice.Methods: Swiss white mice were infected intraperitoneally with trypanosomes and observedfor parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stagedisease was undertaken using diminazene aceturate (40 mg/kg, Berenil) with curativetreatment done using melarsoprol (3.6 mg/kg, Arsobal).Results: The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log10 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI) followed by secondary latency in ILRI-2918 (15–17 DPI) and IPR-001 (17–19 DPI). Survival times ranged from six DPI (ILRI-3953) to 86 DPI (IPR-001). Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia) and ILRI-2918 (after relapse parasitaemia). Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.Conclusions: This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.

scholarly journals Computed Tomography Evaluation of Normal Canine Abdominal Lymph Nodes: Retrospective Study of Size and Morphology According to Body Weight and Age in 45 Dogs

2021 ◽  
Vol 8 (3) ◽  
pp. 44
Author(s):  
Simone Teodori ◽  
Giovanni Aste ◽  
Roberto Tamburro ◽  
Antonio Maria Morselli-Labate ◽  
Francesco Simeoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Lymph Nodes ◽  
Lymphatic Vessels ◽  
Morphological Characteristics ◽  
Statistical Correlation ◽  
The Body ◽  
Continuous Variables ◽  
Weight Changes ◽  
Negative Effects ◽  
Volume Measurements

The morphological characteristics of the largest lymphatic vessels and lymph nodes of the body have been described through ultrasonography, although food and gas in the gastrointestinal tract can often have negative effects on the response of small abdominal structures. The aim of the study was to describe the size of normal abdominal lymph nodes (ALs) in dogs affected by disease, not including lymphadenomegaly or lymphadenopathy, and divided according to body weight and age. The ALs studied included the jejunal, medial iliac, portal, gastric, splenic, and pancreaticoduodenal lymph nodes. Statistical correlation considering body weight and age as continuous variables showed that all measurements of the ALs increased according to body weight changes (p < 0.01). The most reliable values were the volume measurements (p < 0.001) compared to the length, thickness, and width. Mixed results emerged from a comparison of weight categories and age; only the jejunal lymph nodes showed a significant correlation (p < 0.05). Other characteristics (shape, attenuation, and enhancement) are subsequently reported. The resulting data can be used to categorize CT measurements of normal ALs displayed based on the body weight and age of the subjects. This study aimed to propose a new parameter of normalcy that may serve as a reference for the evaluation of infectious or neoplastic events.

scholarly journals Differential virulence of Trypanosoma brucei rhodesiense isolates does not influence the outcome of treatment with anti-trypanosomal drugs in the mouse model

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0229060
Author(s):  
Kariuki Ndung’u ◽  
Grace Adira Murilla ◽  
John Kibuthu Thuita ◽  
Geoffrey Njuguna Ngae ◽  
Joanna Eseri Auma ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Post Infection ◽  
Drug Resistant ◽  
Weight Changes ◽  
Cure Rate ◽  
Trypanosoma Brucei Rhodesiense ◽  
Diminazene Aceturate ◽  
Reference Drug ◽  
Western Kenya ◽  
Biotechnology Research

We assessed the virulence and anti-trypanosomal drug sensitivity patterns of Trypanosoma brucei rhodesiense (Tbr) isolates in the Kenya Agricultural and Livestock Research Organization-Biotechnology Research Institute (KALRO-BioRI) cryobank. Specifically, the study focused on Tbr clones originally isolated from the western Kenya/eastern Uganda focus of human African Trypanosomiasis (HAT). Twelve (12) Tbr clones were assessed for virulence using groups(n = 10) of Swiss White Mice monitored for 60 days post infection (dpi). Based on survival time, four classes of virulence were identified: (a) very-acute: 0–15, (b) acute: 16–30, (c) sub-acute: 31–45 and (d) chronic: 46–60 dpi. Other virulence biomarkers identified included: pre-patent period (pp), parasitaemia progression, packed cell volume (PCV) and body weight changes. The test Tbr clones together with KALRO-BioRi reference drug-resistant and drug sensitive isolates were then tested for sensitivity to melarsoprol (mel B), pentamidine, diminazene aceturate and suramin, using mice groups (n = 5) treated with single doses of each drug at 24 hours post infection. Our results showed that the clones were distributed among four classes of virulence as follows: 3/12 (very-acute), 3/12 (acute), 2/12 (sub-acute) and 4/12 (chronic) isolates. Differences in survivorship, parasitaemia progression and PCV were significant (P<0.001) and correlated. The isolate considered to be drug resistant at KALRO-BioRI, KETRI 2538, was confirmed to be resistant to melarsoprol, pentamidine and diminazene aceturate but it was not resistant to suramin. A cure rate of at least 80% was achieved for all test isolates with melarsoprol (1mg/Kg and 20 mg/kg), pentamidine (5 and 20 mg/kg), diminazene aceturate (5 mg/kg) and suramin (5 mg/kg) indicating that the isolates were not resistant to any of the drugs despite the differences in virulence. This study provides evidence of variations in virulence of Tbr clones from a single HAT focus and confirms that this variations is not a significant determinant of isolate sensitivity to anti-trypanosomal drugs.

scholarly journals Computed Tomography Evaluation Of Normal Canine Abdominal Lymph Nodes: Retrospective Study Of Size And Morphology According To Body Weight And Age In 45 Dogs

2020 ◽  
Author(s):  
Simone Teodori ◽  
Giovanni Aste ◽  
Roberto Tamburro ◽  
Antonio Morselli Labate ◽  
Francesco Simeoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Lymph Nodes ◽  
Lymphatic Vessels ◽  
Morphological Characteristics ◽  
The Body ◽  
Weight Changes ◽  
Negative Effects ◽  
Objective Parameter ◽  
Volume Measurements ◽  
Size And Morphology

Abstract BackgroundThe morphological characteristics of the largest lymphatic vessels and lymph nodes of the body have been described through ultrasonography, although food and gas in the gastrointestinal tract can often have negative effects on the response of small abdominal structures. The aim of the study was to describe the size of normal abdominal lymph nodes (ALs) in dogs affected by disease, not including lymphadenomegaly or lymphadenopathy, and divided according to body weight and age. The ALs studied included the jejunal, medial iliac, portal, gastric, splenic, and pancreaticoduodenal lymph nodes.ResultsMultiple statistical analyses among the three groups showed that all measurements of the ALs increased according to body weight changes (P <0.05). The most reliable values were the volume measurements (P <0.001) compared to the length, thickness and width. A single analysis between just two groups showed different values (P>0.1). Mixed results emerged from a comparison of weight categories and age; only the jejunal lymph nodes showed a possible correlation (P<0.1). Other characteristics (shape, attenuation and enhancement) are subsequently reported.Conclusions and Clinical RelevanceThe resulting data can be used to categorize CT measurements of normal ALs displayed based on the body weight and age of the subjects. This study was able to detect an objective parameter of normalcy that can serve as a reference for the evaluation of infectious or neoplastic events.

scholarly journals Prognostic relevance of cellular morphology in multiple myeloma

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1072-1079 ◽  
Author(s):  
E Fritz ◽  
H Ludwig ◽  
M Kundi
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Median Survival ◽  
Survival Data ◽  
Morphological Characteristics ◽  
Risk Groups ◽  
Cellular Morphology ◽  
Regression Equations ◽  
Survival Times ◽  
Bone Marrow Plasma

Abstract Morphological characteristics of tumor cells have been employed in the prognosis of lymphomas and solid tumors. This report documents an attempt to predict survival from the known cytologic heterogeneity in multiple myeloma. Myeloma cells in bone marrow smears from patients at diagnosis were evaluated by assigning them to morphologically defined categories. Cox's multivariate regression model for censored survival data was used to generate optimal weights, which served as coefficients in two regression equations to estimate death risk from cellular morphology. Step-wise procedures excluded redundant parameters. “Myeloma morphology score” (MMS) discriminates significantly (p less than 0.0001) among 3 stages, with median survival times of 42.5, 30.7, and 9.1 mo. For clinical routine application, “myeloma progression scorex201D; (MPS), the weight sum of the proportion of plasmablasts and the extent of bone marrow plasma cell infiltration, is suggested as a simple prognostic tool. Its discriminative power is very high [p less than 10(-9)]. Median survival times of greater than 71.5, 23.4, and 6.1 mo were found for good, moderate, and poor risk groups, respectively. However, staging is not confined to three subgroups, grouping is flexible, and pairs of data can be matched. This fact may prove to be valuable in designing prognosis-controlled clinical trials or theoretical studies on cellular differentiation. Preliminary results suggest changes in morphology due to disease progression and/or the effect of therapy on tumor kinetics. Most importantly, staging according to MPS or MMS may facilitate the adaption of therapy to the current state of the disease in patients with multiple myeloma.

scholarly journals Prognostic relevance of cellular morphology in multiple myeloma

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1072-1079 ◽  
Author(s):  
E Fritz ◽  
H Ludwig ◽  
M Kundi
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Median Survival ◽  
Survival Data ◽  
Morphological Characteristics ◽  
Risk Groups ◽  
Cellular Morphology ◽  
Regression Equations ◽  
Survival Times ◽  
Bone Marrow Plasma

Morphological characteristics of tumor cells have been employed in the prognosis of lymphomas and solid tumors. This report documents an attempt to predict survival from the known cytologic heterogeneity in multiple myeloma. Myeloma cells in bone marrow smears from patients at diagnosis were evaluated by assigning them to morphologically defined categories. Cox's multivariate regression model for censored survival data was used to generate optimal weights, which served as coefficients in two regression equations to estimate death risk from cellular morphology. Step-wise procedures excluded redundant parameters. “Myeloma morphology score” (MMS) discriminates significantly (p less than 0.0001) among 3 stages, with median survival times of 42.5, 30.7, and 9.1 mo. For clinical routine application, “myeloma progression scorex201D; (MPS), the weight sum of the proportion of plasmablasts and the extent of bone marrow plasma cell infiltration, is suggested as a simple prognostic tool. Its discriminative power is very high [p less than 10(-9)]. Median survival times of greater than 71.5, 23.4, and 6.1 mo were found for good, moderate, and poor risk groups, respectively. However, staging is not confined to three subgroups, grouping is flexible, and pairs of data can be matched. This fact may prove to be valuable in designing prognosis-controlled clinical trials or theoretical studies on cellular differentiation. Preliminary results suggest changes in morphology due to disease progression and/or the effect of therapy on tumor kinetics. Most importantly, staging according to MPS or MMS may facilitate the adaption of therapy to the current state of the disease in patients with multiple myeloma.

Sign in / Sign up

Export Citation Format

Share Document