Sandra Z Mwebe, Christina Yoon, Lucy Asege, Martha Nakaye, Jane Katende, Alfred Andama, Adithya Cattamanchi, Fred C Semitala
Point-of-care C-reactive protein (POC CRP) testing is a potential tuberculosis (TB) screening tool for people living with HIV (PLHIV). Unlike lab-based assays, POC assays do not routinely adjust CRP levels for hematocrit, potentially resulting in TB screening status misclassification. We compared the diagnostic accuracy of unadjusted and hematocrit-adjusted POC CRP for culture-confirmed TB among PLHIV with CD4 cell-count ≤350 cells/uL initiating antiretroviral therapy (ART) in Uganda. We prospectively enrolled consecutive adults, measured POC CRP (Boditech; normal <8 mg/L), collected two spot sputum specimens for comprehensive TB testing, and extracted pre-ART hematocrit from clinic records...
November 26, 2020: Diagnostic Microbiology and Infectious Disease
Saptarshi Ghosh, Karishma Berta Cotta, Aniket A Hande, Moneesha Fernandes, Sarika Mehra
The emergence of antibiotic-resistant strains of Mycobacterium tuberculosis and the decelerating development of new and effective antibiotics has impaired the treatment of tuberculosis (TB). Efflux pump inhibitors (EPIs) have the potential to improve the efficacy of existing anti-TB drugs although with toxicity limitations. Peptide nucleic acids (PNAs), oligonucleotide mimics, by virtue of their high nucleic acid binding specificity have the capability to overcome this drawback. We, therefore, investigated the efflux pump inhibitory properties of a PNA designed against an efflux pump of Mycobacterium smegmatis...
January 13, 2021: Microbial Pathogenesis
Tania Regina Tozetto-Mendoza, Kelly Aparecida Kanunfre, Lucy Santos Vilas-Boas, Evelyn Patricia Sanchez Espinoza, Heuder Gustavo Oliveira Paião, Mussya Cisotto Rocha, Anderson Vicente de Paula, Maura Salaroli de Oliveira, Daniella Bosco Zampelli, José Mauro Vieira, Lewis Buss, Silvia Figueiredo Costa, Ester Cerdeira Sabino, Steven S Witkin, Thelma Suely Okay, Maria Cassia Mendes-Correa
OBJECTIVES: We evaluated the performance of a nucleoprotein-based enzyme-linked immunosorbent assay (ELISA) for detection of IgG antibodies to SARS-CoV-2. METHODS: The ELISA was based on serum IgG reactivity to a 46-kDa protein derived from the recombinant SARS-CoV2 nucleoprotein. Assay sensitivity was assessed using serum samples from 134 COVID-19 confirmed cases obtained > 15 days after symptom onset. Specificity was determined by testing sera from 94 healthy controls...
January 13, 2021: Journal of Virological Methods
Farheen Qureshi, Vijay Viswanathan, Sudhir Sane
No abstract text is available yet for this article.
January 15, 2021: Indian Pediatrics
Hasan Tükenmez, Souvik Sarkar, Saber Anoosheh, Anastasiia Kruchanova, Isabel Edström, Gregory A Harrison, Christina L Stallings, Fredrik Almqvist, Christer Larsson
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a major health threat listed among the top 10 causes of death worldwide. Treatment of multidrug-resistant Mtb requires use of additional second-line drugs that prolong the treatment process and result in higher death rates. Our team previously identified a 2-pyridone molecule (C10) that blocks tolerance to the first-line drug isoniazid at C10 concentrations that do not inhibit bacterial growth. Here, we discovered that the genes rv3160c and rv3161c are highly induced by C10, which led us to investigate them as potential targets...
January 15, 2021: Scientific Reports
Uday Tak, Terje Dokland, Michael Niederweis
Mycobacterium tuberculosis secretes the tuberculosis necrotizing toxin (TNT) to kill host cells. Here, we show that the WXG100 proteins EsxE and EsxF are essential for TNT secretion. EsxE and EsxF form a water-soluble heterodimer (EsxEF) that assembles into oligomers and long filaments, binds to membranes, and forms stable membrane-spanning channels. Electron microscopy of EsxEF reveals mainly pentameric structures with a central pore. Mutations of both WXG motifs and of a GXW motif do not affect dimerization, but abolish pore formation, membrane deformation and TNT secretion...
January 15, 2021: Nature Communications
Keith D Kauffman, Shunsuke Sakai, Nickiana E Lora, Sivaranjani Namasivayam, Paul J Baker, Olena Kamenyeva, Taylor W Foreman, Christine E Nelson, Deivide Oliveira-de-Souza, Caian L Vinhaes, Ziv Yaniv, Cecilia S Lindestam Arleham, Alessandro Sette, Gordon J Freeman, Rashida Moore, Alan Sher, Katrin D Mayer-Barber, Bruno B Andrade, Juraj Kabat, Laura E Via, Daniel L Barber
Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti-PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control-treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti-PD-1-treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies...
January 15, 2021: Science Immunology
Seanantha S Baros, Jonathan M Blackburn, Nelson C Soares
Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive...
February 2020: Molecular & Cellular Proteomics: MCP
Anna Allué-Guardia, Rajagopalan Saranathan, John Chan, Jordi B Torrelles
The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens...
January 13, 2021: International Journal of Molecular Sciences
S Kluge, U Janssens, T Welte, S Weber-Carstens, G Schälte, C D Spinner, J J Malin, P Gastmeier, F Langer, M Wepler, M Westhoff, M Pfeifer, K F Rabe, F Hoffmann, B W Böttiger, J Weinmann-Menke, A Kersten, P Berlit, R Haase, G Marx, C Karagiannidis
Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic...
January 15, 2021: Pneumologie
Manaswini Jagadeb, Kali Prasad Pattanaik, Surya Narayan Rath, Avinash Sonawane
Due to several limitations of the only available BCG vaccine, to generate adequate protective immune responses, it is important to develop potent and cost-effective vaccines against tuberculosis (TB). In this study, we have used an immune-informatics approach to identify potential peptide based vaccine targets against TB. The proteome of Mycobacterium tuberculosis (Mtb), the causative agent of TB, was analyzed for secretory or surface localized antigenic proteins as potential vaccine candidates. The T- and B-cell epitopes as well as MHC molecule binding efficiency were identified and mapped in the modelled structures of the selected proteins...
December 29, 2020: Computers in Biology and Medicine
Priti Kambli, Kanchan Ajbani, Mubin Kazi, Meeta Sadani, Swapna Naik, Anjali Shetty, Jeffrey A Tornheim, Harpreet Singh, Camilla Rodrigues
BACKGROUND: Timely drug resistance detection is essential to global tuberculosis management. Unfortunately, rapid molecular tests assess resistance to only a few drugs, with culture required for comprehensive susceptibility test results. METHODS: We evaluated targeted next generation sequencing (tNGS) for tuberculosis on 40 uncultured sputum samples. Resistance profiles from tNGS were compared with profiles from Xpert MTB/RIF, line probe assay (LPA), pyrosequencing (PSQ), and phenotypic testing...
January 8, 2021: Tuberculosis
Pauline Texier, Patricia Bordes, Jyotsna Nagpal, Ambre Julie Sala, Moise Mansour, Anne-Marie Cirinesi, Xibing Xu, David Andrew Dougan, Pierre Genevaux
Bacterial toxin-antitoxin (TA) systems are composed of a deleterious toxin and its antagonistic antitoxin. They are widespread in bacterial genomes and mobile genetic elements, and their functions remain largely unknown. Some TA systems, known as TAC modules, include a cognate SecB-like chaperone that assists the antitoxin in toxin inhibition. Here, we have investigated the involvement of proteases in the activation cycle of the TAC system of the human pathogen Mycobacterium tuberculosis. We show that the deletion of endogenous AAA+ proteases significantly bypasses the need for a dedicated chaperone and identify the mycobacterial ClpXP1P2 complex as the main protease involved in TAC antitoxin degradation...
January 12, 2021: Journal of Molecular Biology
Shintaro Sagami, Kiyohiro Nishikawa, Fumika Yamada, Yasuo Suzuki, Mamoru Watanabe, Toshifumi Hibi
BACKGROUND AND AIM: CT-P13, an infliximab (IFX) biosimilar, was approved for treatment of inflammatory bowel disease. However, no comparison with the originator IFX in this indication has been conducted in Japan where endemic levels of tuberculosis and hepatitis virus infection are not low. We evaluated the safety and efficacy in real-world data of CT-P13 and compared with originator IFX data in Japan. METHODS: In a prospective post-marketing surveillance (PMS) study, patients who received CT-P13 in a 28-month period from January 2015 were followed up for 2 years...
January 15, 2021: Journal of Gastroenterology and Hepatology
Kenneth S Gunasekera, Elisabetta Walters, Marieke M van der Zalm, Megan Palmer, Joshua L Warren, Anneke C Hesseling, Ted Cohen, James A Seddon
BACKGROUND: Limitations in the sensitivity and accessibility of diagnostic tools for childhood tuberculosis contribute to the substantial gap between estimated cases and cases notified to national tuberculosis programs. Thus, tools to make accurate and rapid clinical diagnoses are necessary to initiate more children on antituberculosis treatment. METHODS: We analyzed data from a prospective cohort of children <13 years being routinely evaluated for pulmonary tuberculosis in Cape Town, South Africa from March 2012 to November 2017...
January 15, 2021: Clinical Infectious Diseases
Mulusew Andualem Asemahagn, Getu Degu Alene, Solomon Abebe Yimer
BACKGROUND: Tuberculosis (TB) remains a key health menace in Ethiopia and its districts. This study aimed to assess the spatial-temporal clustering of notified pulmonary TB (PTB) cases in East Gojjam Zone, Northwest Ethiopia. METHODS: A retrospective study was conducted among all PTB cases reported from 2013-2019. Case notification rates (CNRs) of PTB cases at Kebele (the lowest administrative unit), woreda, and zone levels were estimated. The PTB clustering was done using global Moran's I statistics on Arc GIS 10...
2021: PloS One
Timothy H M Fung, Archana Pradeep
No abstract text is available yet for this article.
January 11, 2021: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Ajay D Patil
No abstract text is available yet for this article.
January 11, 2021: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Yali Yu, Yiyi Kong, Jing Ye, Aiguo Wang, Wenteng Si
Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce. Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection. Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI...
January 15, 2021: Journal of Medical Microbiology
Mediha Türktan, Antonio Esquinas
No abstract text is available yet for this article.
December 2020: Tüberküloz Ve Toraks
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