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Project description:Amphotericin B provides improved therapy for visceral leishmaniasis (VL) caused by Leishmania donovani, with single dose liposomal-encapsulated Ambisome providing the best cure rates. The VL elimination program aims to reduce the incidence rate in the Indian subcontinent to <1/10,000 population/year. Ability to predict which asymptomatic individuals (e.g. anti-leishmanial IgG and/or Leishmania-specific modified Quantiferon positive) will progress to clinical VL would help in monitoring disease outbreaks. Here we examined whole blood transcriptional profiles associated with asymptomatic infection, active disease, and in treated cases. Two independent microarray experiments were performed, with analysis focussed primarily on differentially expressed genes (DEGs) concordant across both experiments. No DEGs were identified for IgG or Quantiferon positive asymptomatic groups compared to negative healthy endemic controls. We therefore concentrated on comparing concordant DEGs from active cases with all healthy controls, and in examining differences in the transcriptome following different regimens of drug treatment. In these comparisons 6 major themes emerged: (i) expression of genes and enrichment of gene sets associated with erythrocyte function in active cases; (ii) strong evidence for enrichment of gene sets involved in cell cycle in comparing active cases with healthy controls; (iii) identification of IFNG encoding interferon-γ as the major hub gene in concordant gene expression patterns across experiments comparing active cases with healthy controls or with treated cases; (iv) enrichment for interleukin signalling (IL-1/3/4/6/7/8) and a prominent role for CXCL10/9/11 and chemokine signalling pathways in comparing active cases with treated cases; (v) the novel identification of Aryl Hydrocarbon Receptor signalling as a significant canonical pathway when comparing active cases with healthy controls or with treated cases; and (vi) global expression profiling support for more effective cure at day 30 post-treatment with a single dose of liposomal encapsulated amphotericin B compared to multi-dose non-liposomal amphotericin B treatment over 30 days. (296 words; 300 words allowed).
| S-EPMC6713396 | biostudies-literature
Project description:In this study we set out to determine whole blood transcriptional profiles that might distinguish asymptomatic infection with Leishmania donovani from active disease, as well as to monitor the changes in transcriptional profiles that accompanied drug treatment. Amphotericin B provides improved therapy for visceral leishmaniasis (VL) caused by Leishmania donovani, with single dose liposomal-encapsulated Ambisome providing the best cure rates. The VL elimination program aims to reduce the incidence rate in the Indian subcontinent to <1/10,000 population/year. Ability to predict which asymptomatic individuals (e.g. anti-leishmanial IgG and/or Leishmania-specific modified Quantiferon positive) will progress to clinical VL would help in monitoring disease outbreaks. Here we examined whole blood transcriptional profiles associated with asymptomatic infection, active disease, and in treated cases. Two independent microarray experiments were performed, with analysis focussed primarily on differentially expressed genes (DEGs) concordant across both experiments. No DEGs were identified for IgG or Quantiferon positive asymptomatic groups compared to negative healthy endemic controls. We therefore concentrated on comparing concordant DEGs from active cases with all healthy controls, and in examining differences in the transcriptome following different regimens of drug treatment. In these comparisons 6 major themes emerged: (i) expression of genes and enrichment of gene sets associated with erythrocyte function in active cases; (ii) strong evidence for enrichment of gene sets involved in cell cycle in comparing active cases with healthy controls; (iii) identification of IFNG encoding interferon- as the major hub gene in concordant gene expression patterns across experiments comparing active cases with healthy controls or with treated cases; (iv) enrichment for interleukin signalling (IL-1/3/4/6/7/8) and a prominent role for CXCL10/9/11 and chemokine signalling pathways in comparing active cases with treated cases; (v) the novel identification of Aryl Hydrocarbon Receptor signalling as a significant canonical pathway when comparing active cases with healthy controls, and to a lesser extent with treated cases; and (vi) global expression profiling support for more effective cure at day 30 post-treatment with a single dose of liposomal encapsulated amphotericin B compared to multi-dose non-liposomal amphotericin B treatment over 30 days.
2019-08-05 | GSE125991 | GEO
Project description:In this study we set out to determine whole blood transcriptional profiles that might distinguish asymptomatic infection with Leishmania donovani from active disease, as well as to monitor the changes in transcriptional profiles that accompanied drug treatment. Amphotericin B provides improved therapy for visceral leishmaniasis (VL) caused by Leishmania donovani, with single dose liposomal-encapsulated Ambisome providing the best cure rates. The VL elimination program aims to reduce the incidence rate in the Indian subcontinent to <1/10,000 population/year. Ability to predict which asymptomatic individuals (e.g. anti-leishmanial IgG and/or Leishmania-specific modified Quantiferon positive) will progress to clinical VL would help in monitoring disease outbreaks. Here we examined whole blood transcriptional profiles associated with asymptomatic infection, active disease, and in treated cases. Two independent microarray experiments were performed, with analysis focussed primarily on differentially expressed genes (DEGs) concordant across both experiments. No DEGs were identified for IgG or Quantiferon positive asymptomatic groups compared to negative healthy endemic controls. We therefore concentrated on comparing concordant DEGs from active cases with all healthy controls, and in examining differences in the transcriptome following different regimens of drug treatment. In these comparisons 6 major themes emerged: (i) expression of genes and enrichment of gene sets associated with erythrocyte function in active cases; (ii) strong evidence for enrichment of gene sets involved in cell cycle in comparing active cases with healthy controls; (iii) identification of IFNG encoding interferon- as the major hub gene in concordant gene expression patterns across experiments comparing active cases with healthy controls or with treated cases; (iv) enrichment for interleukin signalling (IL-1/3/4/6/7/8) and a prominent role for CXCL10/9/11 and chemokine signalling pathways in comparing active cases with treated cases; (v) the novel identification of Aryl Hydrocarbon Receptor signalling as a significant canonical pathway when comparing active cases with healthy controls, and to a lesser extent with treated cases; and (vi) global expression profiling support for more effective cure at day 30 post-treatment with a single dose of liposomal encapsulated amphotericin B compared to multi-dose non-liposomal amphotericin B treatment over 30 days.
2019-08-05 | GSE125992 | GEO
Project description:Transcriptional Blood Signatures for Active and Amphotericin B Treated Visceral Leishmaniasis in India
| PRJNA518766 | ENA
Project description:Transcriptional Blood Signatures for Active and Amphotericin B Treated Visceral Leishmaniasis in India [exp2]
| PRJNA518768 | ENA
Project description:Transcriptional Blood Signatures for Active and Amphotericin B Treated Visceral Leishmaniasis in India [exp1]
| PRJNA518767 | ENA
Project description:Transcriptional analysis of complex biological scenarios has been used extensively, even though sometimes the results of such analysis may prove imprecise or difficult to interpret due to an overwhelming amount of information. In this study, a large-scale real-time qPCR experiment was coupled to multivariate statistical analysis in order to describe the main immunological events underlying the early L. infantum infection in livers of BALB/c mice. High-throughput qPCR was used to evaluate the expression of 223 genes related to immunological response and metabolism 1, 3, 5, and 10 days post infection. This integrative analysis showed strikingly different gene signatures at 1 and 10 days post infection, revealing the progression of infection in the experimental model based on the upregulation of particular immunological response patterns and mediators. The gene signature 1 day post infection was not only characterized by the upregulation of mediators involved in interferon signaling and cell chemotaxis, but also the upregulation of some inhibitory markers. In contrast, at 10 days post infection, the upregulation of many inflammatory and Th1 markers characterized a more defined gene signature with the upregulation of mediators in the IL-12 signaling pathway. Our results reveal a significant connection between the expression of innate immune response and metabolic and inhibitory markers in early L. infantum infection of the liver.
| S-EPMC8267970 | biostudies-literature
Project description:BackgroundVisceral leishmaniasis (VL) is a disease caused by a parasite, which can lead to death if untreated. Poor nutritional status hastens the progression of VL infection, and VL worsens malnutrition status. Malnutrition is one of the poor prognostic factors identified for leishmaniasis. However, the effects of nutritional supplementation in people treated for VL are not known.ObjectivesTo assess the effects of oral nutritional supplements in people being treated with anti-leishmanial drug therapy for VL.Search methodsWe searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and two trial registers up to 12 September 2017. We checked conference proceedings and WHO consultative meeting reports, the reference lists of key documents and existing reviews, and contacted experts and nutritional supplement companies.Selection criteriaRandomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (NRCTs) of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL.Data collection and analysisTwo review authors independently screened the literature search results for studies that met the inclusion criteria. We had planned for two review authors to independently extract data and assess the risk of bias of the included studies. We planned to follow the Cochrane standard methodological procedures for assessing risk of bias and analysing the data.Main resultsWe identified no eligible studies for this review, either completed or ongoing.Authors' conclusionsWe found no studies, either completed or ongoing, that assessed the effects of oral nutritional supplements in people with VL who were being treated with anti-leishmanial drug therapy. Thus, we could not draw any conclusions on the impact of these interventions on primary cure of VL, definitive cure of VL, treatment completion, self-reported recovery from illness or resolution of symptoms, weight gain, increased skinfold thickness, other measures of lean or total mass, or growth in children.This absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment. It means that we did not identify research that fulfilled our review inclusion criteria.The effects of oral nutritional supplements in people with VL who are being treated with anti-leishmanial drug therapy have yet to be determined by rigorous experimental studies, such as cluster-randomized trials, that focus on outcomes relevant for patients.
| S-EPMC6494195 | biostudies-literature
Project description:The case of a patient with visceral leishmaniasis showing inadequate response to amphotericin B from a region where leishmaniasis is not endemic is reported, with the Leishmania donovani isolate showing increased tolerance to amphotericin B in vivo. Four single nucleotide polymorphisms (SNPs) detected in the cysteine proteinase B gene resulted in changes to the deduced amino acid sequence: valine→alanine and arginine→leucine. Overexpression and underexpression of proteins were observed in the 65- to 80-kDa range and at 20 kDa, respectively.
| S-EPMC3146580 | biostudies-literature
Project description:Transcriptional analysis of complex biological scenarios has been used extensively, even though sometimes the results of such analysis may prove imprecise or difficult to interpret due to an overwhelming amount of information. In this study, a large-scale real-time qPCR experiment was coupled to multivariate statistical analysis in order to describe the main immunological events underlying the early L. infantum infection in livers of BALB/c mice. High-throughput qPCR was used to evaluate the expression of 223 genes related to immunological response and metabolism 1, 3, 5, and 10 days post infection. This integrative analysis showed strikingly different gene signatures at 1 and 10 days post infection, revealing the progression of infection in the experimental model based on the upregulation of particular immunological response patterns and mediators. The gene signature 1 day post infection was not only characterized by the upregulation of mediators involved in interferon signaling and cell chemotaxis, but also the upregulation of some inhibitory markers. In contrast, at 10 days post infection, the upregulation of many inflammatory and Th1 markers characterized a more defined gene signature with the upregulation of mediators in the IL-12 signaling pathway. Our results reveal a significant connection between the expression of innate immune response and metabolic and inhibitory markers in early L. infantum infection of the liver.
2021-07-12 | GSE159195 | GEO