RNA-seq of blood taken from patients suffering from sleeping sickness and infected with Trypanosoma brucei rhodesiense
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB27207 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Shotgun sequencing of sleeping sickness patient blood. WARNING: these results cannot be compared with those from trypanosome poly(A)+ mRNA, because the poly(A) selection introduces substantial bias, including loss of long mRNAs. Details will appear in the publication. These are additional sequencing runs that match some from E-MTAB-5293
2018-06-18 | E-MTAB-5614 | biostudies-arrayexpress
Project description:The host central nervous system (CNS) response to infection with Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense parasites, the causing agent of human African trypanosomiasis (HAT), is a poorly explored area. The two parasites are responsible for respectively a chronic and an acute form of HAT. In both cases, however, the disease progresses from a haemolymphatic first stage (S1) to a meningo-encephalitic second stage (S2) due to the penetration of parasites into the CNS. In the present study, we investigated and compared the cerebrospinal fluid (CSF) from S2 patients affected by either T. b. gambiense or T. b. rhodesiense HAT, using a mass spectrometry quantitative proteomics approach. Gene ontology and pathway analyses on the 222 quantified proteins, revealed a predominant activation of the innate immune and the acute phase responses in rhodesiense HAT. These results were further confirmed through the verification of the over-expression of two proteins involved in these mechanisms, C-reactive protein (CRP) and orosomucoid 1 (ORM1), in 126 S2 HAT patients suffering from either the chronic or the acute form of HAT. Both proteins were significantly increased (p<0.0001) in the CSF of rhodesiense HAT patients. These findings contribute in better understanding the pathophysiological mechanisms of late stage HAT caused by T. b. gambiense or T. b. rhodesiense and pave the way for further investigations on the clinical significance of CRP and ORM1. See article: <a href="http://www.sciencedirect.com/science/article/pii/S2212963414000126">Increased acute immune response during the meningo-encephalitic stage of Trypanosoma brucei rhodesiense sleeping sickness compared to Trypanosoma brucei gambiense</a>
2015-01-23 | PXD001082 | Pride
Project description:Background: Human African trypanosomiasis (HAT), also called sleeping sickness, is one of 20 in WHO’s list of ‘Neglected Tropical Diseases’, for which, less than 3,500 cases are reported each year. The disease is caused by the parasite Trypanosoma brucei. Even though the clinical symptoms are well described, physiological aspects of the disease remain unclear. Diagnosis of the disease is difficult, requiring a lumbar puncture to determine the disease stage and guide treatment. Identifying new markers for disease stage has been a challenge for many years. Methods and Findings: In our study, a liquid chromatography coupled with tandem mass spectrometry tandem approach (LC-MS/MS) provides a new way to establish the proteomic profile of patients in stages 1 and 2 of the disease. The biological fluids (serum, cerebrospinal fluid, urine and saliva) of three uninfected controls, three patients with stage 1 disease, and four patients with stage 2 disease, are analyzed. In addition, quantification of samples from 14 controls, 23 patients with stage 1 disease and 43 patients with stage 2 disease by ELISA completes this analysis, and highlights two potential new markers, neuroserpin and moesin, with the latter present in urine — an easily accessed fluid. Conclusion: These result suggest that quantifying proteins present in biological fluids by LC-MS/MS) could provide new biomarkers for the diagnosis and stage discrimination of HAT.
2018-11-15 | PXD007842 | Pride
Project description:Rats (four per isolate) were infected with Trypansooma rhodesiense taken from the CNS of two different patients from Lwala. Blood was taken at parasitaemias ranging from 3-20 E7. The results can be compared with those from human patient samples.
2017-12-30 | E-MTAB-6125 | biostudies-arrayexpress
Project description:Accurate stage determination is crucial in the choice of treatment for patients suffering from sleeping sickness, also known as human African trypanosomiasis (HAT). Current staging methods, based on the counting of white blood cells (WBC) and the detection of parasites in the cerebrospinal fluid (CSF) have limited accuracy. We hypothesized that immune mediators reliable for staging T. b. gambiense HAT could also be used to stratify T. b. rhodesiense patients, the less common form of HAT.A population comprising 85 T. b. rhodesiense patients, 14 stage 1 (S1) and 71 stage 2 (S2) enrolled in Malawi and Uganda, was investigated. The CSF levels of IgM, MMP-9, CXCL13, CXCL10, ICAM-1, VCAM-1, neopterin and B2MG were measured and their staging performances evaluated using receiver operating characteristic (ROC) analyses.IgM, MMP-9 and CXCL13 were the most accurate markers for stage determination (partial AUC 88%, 86% and 85%, respectively). The combination in panels of three molecules comprising CXCL13-CXCL10-MMP-9 or CXCL13-CXCL10-IgM significantly increased their staging ability to partial AUC 94% (p value < 0.01).The present study highlighted new potential markers for stage determination of T. b. rhodesiense patients. Further investigations are needed to better evaluate these molecules, alone or in panels, as alternatives to WBC to make reliable choice of treatment.
| S-EPMC3561069 | biostudies-literature
Project description:Recent blood transcriptomic analysis of rhodesiense sleeping sickness patients has revealed that neutrophil signature genes and activation markers constitute the top indicators of trypanosomiasis-associated inflammation. Here, we used single cell RNA sequencing (scRNA-seq) to analyze the diversity of neutrophils in the spleen. We show that Trypanosoma brucei infection results in expansion and differentiation of four splenic neutrophil subpopulations, including Mki67+Birc5+Gfi1+Cebpe+ proliferation-competent precursors, two intermediate immature subpopulations and Cebpb+Spi1+Irf7+Mcl1+Csf3r+ inflammation reprogrammed mature neutrophils. Transcriptomic scRNA-seq profiling identified the largest immature subpopulation by Mmp8/9 positive tertiary granule markers.
2023-08-10 | GSE222784 | GEO
Project description:BackgroundThe acute form of Human African Trypanosomiasis (HAT, also known as Sleeping sickness) caused by Trypanosoma brucei rhodesiense has been shown to have a wide spectrum of focus specific clinical presentation and severity in East and Southern Africa. Indeed HAT occurs in regions endemic for other tropical diseases, however data on how these co-morbidities might complicate the clinical picture and affect disease outcome remains largely scanty. We here describe the clinical presentation, presence of co-infections, and how the latter impact on HAT prognosis.Methods and findingsWe carried out a retrospective analysis of clinical data from 258 sleeping sickness patients reporting to Lwala hospital between 2005 and 2012. The mean patient age was 28.6 years with a significant number of cases below 18 years (p< 0.0001). About 93.4% of the cases were diagnosed as late stage (p< 0.0001). The case fatality rate was 10.5% with post treatment reactive encephalopathys reported in 7.9% of the cases, of whom 36.8% eventually died. Fever was significantly (p = 0.045) higher in patients under 18 years. Of the early stage patients, 26.7% and 6.7% presented with late stage signs of sleep disorder and mental confusion respectively. Among the co-infections, malaria was significantly more prevalent (28.9%; p< 0.0001) followed by urinary tract infections (4.2%). Co-infections were present in 14.3% of in-hospital deaths, 38.5% of which were recorded as Malaria. Malaria was significantly more common in patients under 18 years (45.5%; p< 0.02), and was reported in 60% of the fatal cases in this age group.ConclusionsWe show a wide spectrum of sleeping sickness clinical presentation and disease outcome that was apparently not significantly influenced by concurrent infections. It would thus be interesting to determine the host and/or parasite factors that might be responsible for the observed diverse clinical presentation.
| S-EPMC4342333 | biostudies-literature
Project description:We carried out a baseline survey of cattle in Kaberamaido district, in the context of controlling the domestic animal reservoir of Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) towards elimination. Cattle blood was subjected to capillary tube centrifugation followed by measurement of the packed cell volume (PCV) and examination of the buffy coat area for motile trypanosomes. Trypanosomes were detected in 561 (21.4%) out of 2621 cattle screened by microscopy. These 561 in addition to 724 apparently trypanosome negative samples with low PCVs (?25%) were transported to the laboratory and tested by PCR targeting the trypanosomal Internal Transcribed Spacer (ITS-1) as well as suspect Tick-Borne Diseases (TBDs) including Anaplasmamosis, Babesiosis, and Theileriosis. PCR for Anaplasma sp yielded the highest number of positive animals (45.2%), followed by Trypanosoma sp (44%), Theileria sp (42.4%) and Babesia (26.3%); multiple infections were a common occurrence. Interestingly, 373 (29%) of these cattle with low PCVs were negative by PCR, pointing to other possible causes of aneamia, such as helminthiasis. Among the trypanosome infections classified as T. brucei by ITS-PCR, 5.5% were positive by SRA PCR, and were, therefore, confirmed as T. b. rhodesiense. Efforts against HAT should therefore consider packages that address a range of conditions. This may enhance acceptability and participation of livestock keepers in programs to eliminate this important but neglected tropical disease. In addition, we demonstrated that cattle remain an eminent reservoir for T. b. rhodesiense in eastern Uganda, which must be addressed to sustain HAT elimination.
| S-EPMC7157584 | biostudies-literature
Project description:ObjectiveHuman African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes.ResultsTrypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.
| S-EPMC5658916 | biostudies-literature
Project description:Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a 'deep-mining" proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification.
| S-EPMC3738533 | biostudies-literature