Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

ABSTRACT: Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts.

SUBMITTER: Young BC

PROVIDER: S-EPMC9472670 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

Young Bernadette C BC Bush Stephen J SJ Lipworth Sam S George Sophie S Dingle Kate E KE Sanderson Nick N Brankin Alice A Walker Timothy T Sharma Srilakshmi S Leong James J Plaha Puneet P Hofer Monika M Chiodini Peter P Gottstein B B Furrer Lavinia L Crook Derrick D Brent Andrew A

Open forum infectious diseases 20220823 9

Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts. ...[more]

PMID: 36119959

Similar Datasets

T-cell regulation in lepromatous leprosy.

Project description:Regulatory T (Treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25+ cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients' skin lesions. Depletion of CD25+ cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25+ cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25+ cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25+ T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25+ cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25+ cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3+ CD8+CD25+ T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68+CD163+ as well as FoxP3+ cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25+ Treg cells play a role in M. leprae-Th1 unresponsiveness in LL.

| S-EPMC3983090 | biostudies-literature

Late-onset ulnar neuritis following treatment of lepromatous leprosy infection.

Project description:Neuritis is a frequent complication of Myocobacteria leprae infection and treatment due to the variety of mechanisms through which it can occur. Not only can mycobacterial invasion into peripheral nerves directly cause damage and inflammation, but immune-mediated inflammatory episodes (termed leprosy reactions) can also manifest as neuritis at any point during infection. Treatment of leprosy reactions with thalidomide can also lead to neuritis due to an adverse drug effect. Neuritis can emerge years after initial diagnosis and treatment, although it is most frequently found at time of diagnosis or early into the treatment course. Treatment of neuritis is dependent on high-dose corticosteroid therapy as well as therapy for suspected underlying etiology. Here, we present a case of ulnar neuritis presenting in a patient with lepromatous leprosy four years after treatment of initial infection, with subsequent improvement after corticosteroid burst while maintained on thalidomide therapy.

| S-EPMC6715229 | biostudies-literature

Diffuse Lepromatous Leprosy Due to Mycobacterium lepromatosis in Quintana Roo, Mexico.

Project description:A 43-year-old woman of Mayan origin from Quintana Roo, Mexico, was diagnosed with diffuse lepromatous leprosy. The etiologic bacillus was determined to be Mycobacterium lepromatosis instead of Mycobacterium leprae. This case likely represents the first report of this leprosy form and its agent in the southeastern tip of Mexico.

| S-EPMC4609715 | biostudies-literature

Transcription profiling of human skin samples from borderline tuberculoid leprosy and lepromatous leprosy patients

Project description:Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

2007-12-12 | E-GEOD-443 | biostudies-arrayexpress

Differential dermal expression of CCL17 and CCL18 in tuberculoid and lepromatous leprosy.

Project description:BackgroundLeprosy is characterized by polar clinical, histologic and immunological presentations. Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time.MethodologyWe used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions. mRNA from 24 chemokines and cytokines, and 6 immune cell type markers were measured from 85 Nepalese leprosy subjects. Selected findings were confirmed with immunohistochemistry.Principal resultsExpression of three soluble mediators (CCL18, CCL17 and IL-10) and one macrophage cell type marker (CD14) was significantly elevated in lepromatous (CCL18, IL-10 and CD14) or tuberculoid (CCL17) lesions. Higher CCL18 protein expression by immunohistochemistry and a trend in increased serum CCL18 in lepromatous lesions was observed. No cytokines were associated with erythema nodosum leprosum or Type I reversal reaction following multiple comparison correction. Hierarchical clustering suggested that CCL18 was correlated with cell markers CD209 and CD14, while neither CCL17 nor CCL18 were highly correlated with classical TH1 and TH2 cytokines.ConclusionsOur findings suggest that CCL17 and CCL18 dermal expression is associated with leprosy polarity.

| S-EPMC4238987 | biostudies-literature

Mycobacterium lepromatosis Lepromatous Leprosy in US Citizen Who Traveled to Disease-Endemic Areas.

Project description:We report Mycobacterium lepromatosis infection in a US-born person with an extensive international travel history. Clinical symptoms, histopathology, and management are similar to those of infections caused by M. leprae. Clinicians should consider this pathogen in the diagnosis of patients with symptoms of leprosy who have traveled to endemic areas.

| S-EPMC5652441 | biostudies-literature

The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing.

Project description:Lepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a pro-inflammatory and anti-microbial cytokine, in the subset of macrophages exhibiting a high expression level of LIPA. The exhaustion of CD8+ T cells featured by the high expression of TIGIT and LAG3 in L-LEP lesions was demonstrated. Moreover, remarkable enhancement of inhibitory immune receptors mediated crosstalk between skin immune cells was observed in L-LEP lesions. For PBMCs, a high expression level of APOE in the HLA-DRhighFBP1high monocyte subset and the expansion of regulatory T cells were found to be associated with L-LEP. These findings revealed the primary suppressive landscape in the L-LEP patients, providing potential targets for the intervention of intracellular bacteria caused persistent infections.

| S-EPMC8748782 | biostudies-literature

Osteological, biomolecular and geochemical examination of an early anglo-saxon case of lepromatous leprosy.

Project description:We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21-35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America.

| S-EPMC4430215 | biostudies-literature

Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

Project description:Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN- and IL-1. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.

2021-05-04 | GSE167889 | GEO

Concurrent pulmonary tuberculosis and lepromatous leprosy in a newly diagnosed HIV positive patient: a case report.

Project description:BackgroundThe leprosy-tuberculosis (TB) co-infection is rarely reported in recent times. However, this dual comorbidity is associated with high mortality and major morbidity. Unrecognised leprosy-TB co-infection may predispose affected patients to rifampicin monotherapy and subsequent drug resistance.Case presentationA 35 year old migrant, human immunodeficiency virus (HIV) positive male worker presented with 6 month history of symmetric infiltrative nodular plaques of the face and distal, upper extremities. A few days after initial dermatology presentation, a sputum positive pulmonary tuberculosis diagnosis was made at his base hospital. Subsequent dermatology investigations revealed histology confirmed lepromatous leprosy and a weakly reactive rapid plasma reagin test. The presenting clinical features and laboratory results were suggestive of lepromatous leprosy coexisting with pulmonary tuberculosis in an HIV positive patient.ConclusionsThis case illustrates the occurrence of leprosy with pulmonary tuberculosis in an HIV infected patient and the difficulties in interpreting non-treponemal syphilis tests in these patients. This case also highlights the need for a high index of suspicion for co-infection and the need to exclude PTB prior to initiation of rifampicin containing multi-drug therapy (MDT). Interdisciplinary management and social support are crucial in these patients.

| S-EPMC8247149 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data