Dataset Information

Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus-1.

ABSTRACT:

Background

The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1-infected individuals are likely to progress to active disease is unknown.

Methods

Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1-infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations.

Results

Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1?, transforming growth factor-? (TGF-?). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-? were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly.

Conclusions

Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.

SUBMITTER: Lesosky M

PROVIDER: S-EPMC6603269 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus-1.

Lesosky Maia M Rangaka Molebogeng X MX Pienaar Cara C Coussens Anna K AK Goliath Rene R Mathee Shaheed S Mwansa-Kambafwile Judith J Maartens Gary G Wilkinson Robert J RJ Wilkinson Katalin Andrea KA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190701 2

<h4>Background</h4>The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1-infected individuals are likely to progress to active disease is unknown.<h4>Methods</h4>Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1-infected persons recruited within the screening and enrollmen ...[more]

PMID: 30256919

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Project description:BACKGROUND:Due to the similar clinical, lung imaging, and pathological characteristics, talaromycosis is most commonly misdiagnosed as tuberculosis. This study aimed to identify the characteristics of talaromycosis pleural effusion (TMPE) and to distinguish TMPE from tuberculosis pleural effusion (TPE). METHODS:We enrolled 19 cases each of TMPE and TPE from Guangxi, China. Patients' clinical records, pleural effusion tests, biomarker test results, and receiver operating characteristic curves were analyzed. RESULTS:In total, 39.8% (65/163) of patients exhibited serous effusion, of whom 61 were non-human immunodeficiency virus (HIV)-infected patients; 68.85% of the non-HIV-infected patients (42/61) had TMPE. Thoracentesis was performed only in 19 patients, all of whom were misdiagnosed with tuberculosis and received long-term anti-tuberculosis treatment. In four of these patients, interleukin (IL)-23, IL-27, and interferon-gamma (IFN-γ) measurements were not performed since pleural effusion samples could not be collected because the effusion had been drained prior to the study. In the remaining 15 patients, pleural effusion samples were collected. Talaromyces marneffei was isolated from the pleural effusion and pleural nodules. Most TMPEs were characterized by yellowish fluid, with marked elevation of protein content and nucleated cell counts. However, neutrophils were predominantly found in TMPEs, and lymphocytes were predominantly found in TPEs (both p < 0.05). Adenosine deaminase (ADA) and IFN-γ levels in TMPEs were significantly lower than those in TPEs (all p < 0.05) and provided similar accuracies for distinguishing TMPEs from TPEs. IL-23 concentration in TMPEs was significantly higher than that in TPEs (p < 0.05), and it provided similar accuracy for diagnosing TMPEs. IL-27 concentrations in TMPEs were significantly lower than those in TPEs (all p < 0.05) but was not useful for distinguishing TMPE from TPE. CONCLUSIONS:Talaromycosis can infringe on the pleural cavity via the translocation of T. marneffei into the pleural space. Nonetheless, this phenomenon is still commonly neglected by clinicians. TMPE is a yellowish fluid with exudative PEs and predominant neutrophils. Higher neutrophil counts and IL-23 may suggest talaromycosis. Higher lymphocyte counts, ADA activity, and IFN-γ concentration may suggest tuberculosis.

Project description:IntroductionThe association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature.Patient concernsWe present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission).DiagnosisA LyCD4 count of 38/μL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis.InterventionsHighly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection.OutcomeBurkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis.ConclusionsThe association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands.

Dataset Information

Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus-1.

Background

Methods

Results

Conclusions

Publications

Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus-1.

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