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Tasnim M Bana, Maia Lesosky, Dominique J Pepper, Helen van der Plas, Charlotte Schutz, Rene Goliath, Chelsea Morroni, Marc Mendelson, Gary Maartens, Robert J Wilkinson, Graeme Meintjes
BACKGROUND: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS...
September 27, 2016: BMC Infectious Diseases
Gopalan Narendran, Dhanasekaran Kavitha, Ramesh Karunaianantham, Leonardo Gil-Santana, Jilson L Almeida-Junior, Sirasanambatti Devarajulu Reddy, Marimuthu Makesh Kumar, Haribabu Hemalatha, Nagesh Nalini Jayanthi, Narayanan Ravichandran, Raja Krishnaraja, Angamuthu Prabhakar, Tamizhselvan Manoharan, Lokeswaran Nithyananthan, Gunasundari Arjunan, Mohan Natrajan, Soumya Swaminathan, Bruno B Andrade
BACKGROUND: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory phenomenon complicating HIV management in coincidental tuberculosis (TB) infection, upon immune reconstitution driven by antiretroviral therapy (ART). Leukotriene A4 hydroxylase (LTA4H), an enzyme which converts LTA4 to LTB4, regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory LTB4, with direct implications in TB-driven inflammation. In humans, a single nucleotide polymorphism (SNP) in the LTA4H promoter which regulates its transcriptional activity (rs17525495) has been identified and described to impact clinical severity of TB presentation and response to corticosteroid therapy...
2016: PloS One
Cari Stek, Charlotte Schutz, Lisette Blumenthal, Friedrich Thienemann, Jozefien Buyze, Christiana Nöstlinger, Raffaella Ravinetto, Edwin Wouters, Robert Colebunders, Gary Maartens, Robert J Wilkinson, Lutgarde Lynen, Graeme Meintjes
BACKGROUND: Early antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS...
August 29, 2016: JMIR Research Protocols
Nicola Wearne, Ikechi G Okpechi
The cause of the human immunodeficiency virus (HIV) epidemic in South Africa (SA) was worsened by the denial by key political players that HIV causes acquired immunodeficiency syndrome (AIDS). South Africa continues to have the highest rate of HIV world-wide, which has had a huge impact on the development of both chronic kidney disease and acute kidney injury. Fortunately, there is now an effective antiretroviral therapy (ART) roll-out program. SA is also dealing with a collision of epidemics of HIV, tuberculosis, and non-communicable disease, particularly hypertension and diabetes...
July 29, 2016: Clinical Nephrology
Eliza Manea, Daniela Munteanu, Raluca Jipa, Ruxandra Moroti, Victoria Arama, Ioan-Alexandru Diaconu, Adriana Hristea
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) related to tuberculosis (TB) is an exacerbation of an inflammatory response that most often occurs in HIV-infected patients but it has also been observed in non-HIV immunocompromised hosts. We describe two cases of TB associated IRIS with CNS involvement, one in a patient diagnosed with HIV infection and the other in a patient with immunosuppression due to anti tumor necrosis factor treatment. CASE REPORT; The first case was a 40-year-old man, newly diagnosed with HIV infection, who developed right hemiplegia and expressive aphasia...
October 2015: Pneumologia: Revista Societății Române de Pneumologie
Violette Dirix, Kinda Schepers, Marguerite Massinga-Loembe, William Worodria, Robert Colebunders, Mahavir Singh, Camille Locht, Luc Kestens, Françoise Mascart
OBJECTIVES: To investigate whether mycobacterial antigen-induced cytokine secretions are helpful in detecting Mycobacterium tuberculosis (Mtb) infection in a cohort of HIV-infected patients living in a country with a high burden of Mtb and HIV infections, and to determine their predictive value for the development of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome. DESIGN: A total of 352 HIV-infected patients (186 with active TB) were prospectively enrolled when initiating antiretroviral therapy (ART)...
July 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
G Narendran, S Swaminathan
The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV-TB patients encounter unique problems like drug-drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non-tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia...
April 2016: Oral Diseases
Hong Yien Tan, Yean Kong Yong, Esaki M Shankar, Geza Paukovics, Rada Ellegård, Marie Larsson, Adeeba Kamarulzaman, Martyn A French, Suzanne M Crowe
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Shruthi Ravimohan, Neo Tamuhla, Shiang-Ju Kung, Kebatshabile Nfanyana, Andrew P Steenhoff, Robert Gross, Drew Weissman, Gregory P Bisson
BACKGROUND: HIV-infected patients with pulmonary TB (pTB) can have worsening of respiratory symptoms as part of TB-immune reconstitution inflammatory syndrome (TB-IRIS) following antiretroviral therapy (ART) initiation. Thus, reconstitution of immune function on ART could drive incident lung damage in HIV/TB. METHODS: We hypothesized that increases in matrix metalloproteinases (MMPs), which can degrade lung matrix, on ART are associated with TB-IRIS among a cohort of advanced, ART naïve, HIV-infected adults with pTB...
January 2016: EBioMedicine
Lucy C K Bell, Gabriele Pollara, Mellissa Pascoe, Gillian S Tomlinson, Rannakoe J Lehloenya, Jennifer Roe, Richard Meldau, Robert F Miller, Alan Ramsay, Benjamin M Chain, Keertan Dheda, Mahdad Noursadeghi
Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis...
March 2016: PLoS Pathogens
Laura W Musselwhite, Bruno B Andrade, Susan S Ellenberg, Ann Tierney, Pablo F Belaunzaran-Zamudio, Adam Rupert, Michael M Lederman, Ian Sanne, Juan G Sierra Madero, Irini Sereti
To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants...
February 2016: EBioMedicine
Efstathios T Detorakis, Nela Stojanovic, Aikaterini Chalkia, Ioannis G Pallikaris
PURPOSE: This study evaluated the feasibility of anterior segment optical coherence tomography (OCT) and ultrasound biomicroscopy (UBM) for the imaging of EX-PRESS(®) implant. MATERIALS AND METHODS: This nonrandomized comparative case series was performed at the Department of Ophthalmology of the University Hospital of Heraklion, Crete, Greece. The Ellex Eye Cubed (40 MHz) UBM and the Zeiss Visante OCT systems were used. The filtering bleb morphology (BL), aqueous outflow (AS), and tube position (TB) were evaluated by two independent observers using a quality scale of 1 (worst) to 4 (best)...
January 2016: Middle East African Journal of Ophthalmology
Violette Dirix, Kinda Schepers, Marguerite Massinga-Loembe, William Worodria, Robert Colebunders, Mahavir Singh, Camille Locht, Luc Kestens, Françoise Mascart
OBJECTIVE(S): To investigate whether mycobacterial antigen-induced cytokine secretions are helpful in detecting Mycobacterium tuberculosis (Mtb) infection in a cohort of HIV-infected patients living in a country with a high burden of Mtb and HIV infections, and to determine their predictive value for the development of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRIS). DESIGN: 352 HIV-infected patients (186 with active TB) were prospectively enrolled when initiating antiretroviral therapy (ART)...
March 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Saša Korom, Eddy Martin, Stefano A Serapian, Carles Bo, Pablo Ballester
We report experimental and theoretical evidence of restrained axial rotation for heteroleptic L2·Ir(I)·1,5-cyclooctadiene (COD) complexes included in the aromatic cavity of Rebek's self-folding octaamide cavitand. At 298 K, the axial spinning motion of the included organometallic guests was slow on the (1)H NMR time scale and produced a proton spectrum for the bound host indicative of C2 symmetry. Signals corresponding to aromatic protons of the bound host coalesced at 323 K, indicating that the spinning process of the included guest became fast on the (1)H NMR time scale and that the complex approached C4 symmetry...
February 24, 2016: Journal of the American Chemical Society
Mariska D DEN Hartogh, Marielle E P Philippens, Iris E VAN Dam, Catharina E Kleynen, Robbert J H A Tersteeg, Alexis N T J Kotte, Marco VAN Vulpen, Bram VAN Asselen, Desirée H J G VAN DEN Bongard
For breast boost radiotherapy or accelerated partial breast irradiation, the tumor bed (TB) is delineated by the radiation oncologist on a planning computed tomography (CT) scan. The aim of the present study was to investigate whether the interobserver variability (IOV) of the TB delineation is reduced by providing the radiation oncologist with additional magnetic resonance imaging (MRI) or CT scans. A total of 14 T1-T2 breast cancer patients underwent a standard planning CT in the supine treatment position following lumpectomy, as well as additional pre- and postoperative imaging in the same position...
November 2015: Oncology Letters
Claire Rivoisy, Florence Tubach, Carine Roy, Nathalie Nicolas, Xavier Mariette, Dominique Salmon, Olivier Lortholary, Anne Bourgarit
OBJECTIVES: Paradoxical tuberculosis (TB) worsening, an example of the immune reconstitution inflammatory syndrome (IRIS), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (TNF) discontinuation during biotherapy-induced TB. To better recognize it, we analyzed the frequency and factors associated with anti-TNF-induced TB-IRIS. METHODS: Case-control study on anti-TNF-associated TB patients. IRIS cases, defined with the following consensus criteria, were matched to two controls (anti-TNF-associated TB without IRIS)...
March 2016: Joint, Bone, Spine: Revue du Rhumatisme
Shruthi Ravimohan, Neo Tamuhla, Kebatshabile Nfanyana, Andrew P Steenhoff, Rona Letlhogile, Ian Frank, Rob Roy MacGregor, Robert Gross, Drew Weissman, Gregory P Bisson
BACKGROUND: The immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART). METHODS: This study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART...
March 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
A Despotovic, B Savic, D Salemovic, J Ranin, Dj Jevtovic
Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB) was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn...
January 2016: International Journal of Infectious Diseases: IJID
Rachel P J Lai, Graeme Meintjes, Robert J Wilkinson
Patients co-infected with HIV-1 and tuberculosis (TB) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) following commencement of antiretroviral therapy (ART). TB-IRIS is characterized by transient but severe localized or systemic inflammatory reactions against Mycobacterium tuberculosis antigens. Here, we review the risk factors and clinical management of TB-IRIS, as well as the roles played by different aspects of the immune response in contributing to TB-IRIS pathogenesis...
March 2016: Seminars in Immunopathology
Susanna K P Lau, Kim-Chung Lee, Shirly O T Curreem, Wang-Ngai Chow, Kelvin K W To, Ivan F N Hung, Deborah T Y Ho, Siddharth Sridhar, Iris W S Li, Vanessa S Y Ding, Eleanor W F Koo, Chi-Fong Wong, Sidney Tam, Ching-Wan Lam, Kwok-Yung Yuen, Patrick C Y Woo
Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS)...
December 2015: Journal of Clinical Microbiology
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