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Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Mercedes Pérez-Bonilla, Daniel Oves-Costales, Mercedes de la Cruz, Maria Kokkini, Jesús Martín, Francisca Vicente, Olga Genilloud, Fernando Reyes
Phocoenamicins B and C ( 1 and 2 ), together with the known spirotetronate phocoenamicin ( 3 ), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, displayed activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis . Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds 1 and 2 belonging to the spirotetronate class of polyketides...
March 16, 2018: Marine Drugs
Stefanie Kroeze, Pascale Ondoa, Cissy M Kityo, Margaret Siwale, Sulaimon Akanmu, Maureen Wellington, Marleen de Jager, Prudence Ive, Kishor Mandaliya, Wendy Stevens, T Sonia Boender, Marieke E de Pundert, Kim C E Sigaloff, Peter Reiss, Ferdinand W Wit, Tobias F Rinke de Wit, Raph L Hamers
OBJECTIVE: To assess incidence, determinants and clinical consequences of suboptimal immune recovery in HIV-1 infected adults in sub-Saharan Africa with sustained viral suppression on antiretroviral therapy (ART). DESIGN: Multi-country prospective cohort. METHODS: Suboptimal immune recovery was defined as proportions of participants who failed to attain clinically relevant CD4 cell count thresholds (>200, >350 and >500 cells/μL) despite sustained viral suppression on continuous first-line ART...
March 15, 2018: AIDS
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Ramani Baddam, Narender Kumar, Lothar H Wieler, Aditya Kumar Lankapalli, Niyaz Ahmed, Sharon J Peacock, Torsten Semmler
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, resistance to which occurs primarily due to mutations in pncA (Rv2043c) that encodes the pyrazinamidase enzyme responsible for conversion of pro-drug PZA into its active form. Previous studies have reported numerous resistance-conferring mutations distributed across the entire length of pncA without any hotspot regions. As different lineages of Mycobacterium tuberculosis display a strong geographic association, we sought to understand whether the genetic background influenced the distribution of mutations in pncA...
March 15, 2018: Scientific Reports
Eulogio J Llorent-Martínez, Lucía Molina-García, Gema M Durán, Antonio Ruiz-Medina, Ángel Ríos
Graphene quantum dots (GQD) were determined in water samples using terbium-sensitized luminescence (TSL). Terbium ions complex with GQD due to the carboxylic groups that are usually present in these nanomaterials, increasing the luminescence signal of terbium. In Tb(III)-GQD complexes, GQD absorb energy at their characteristic excitation wavelength and transfer it to terbium ion, which emits at its particular emission wavelength. The analytical signal, measured at λexc =257nm and λem =545nm, increases proportionally to GQD concentration between 50 and 500μgL-1 ...
March 7, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Urmi Bajpai, Abhishek Kumar Mehta, Kandasamy Eniyan, Avni Sinha, Ankita Ray, Simran Virdi, Shazeb Ahmad, Aridni Shah, Deepanksha Arora, Devyani Marwaha, Gunjan Chauhan, Prarthna Saraswat, Punita Bathla, Ruchi Singh
Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide spread occurrence of drug-resistance amongst the clinical isolates of M. tuberculosis. However, there isn't much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using M. smegmatis as the bacterial host where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophage (PDRPv)...
March 15, 2018: Canadian Journal of Microbiology
Nomakorinte Gcebe, Victor P M G Rutten, Nicolaas Gey van Pittius, Brendon Naicker, Anita L Michel
Some species of non-tuberculous mycobacteria (NTM) have been reported to be opportunistic pathogens of animals and humans. Recently there has been an upsurge in the number of cases of NTM infections, such that some NTM species are now recognized as pathogens of humans and animals. From a veterinary point of view, the major significance of NTM is the cross-reactive immune response they elicit against Mycobacterium bovis antigens, leading to misdiagnosis of bovine tuberculosis. Four NTM isolates were detected from a bovine nasal swab, soil and water, during an NTM survey in South Africa...
March 15, 2018: International Journal of Systematic and Evolutionary Microbiology
Florian Glaus, Darija Dedic, Priyanka Tare, Valakunja Nagaraja, Liliana Rodrigues, Jose A Ainsa, Jens Kunze, Gisbert Schneider, Ruben C Hartkoorn, Stewart T Cole, Karl-Heinz Altmann
Described is the total synthesis of the myxobacterial natural product ripostatin B and of a small number of analogs. Ripostatin B is a polyketide-derived 14-membered macrolide that acts as an inhibitor of bacterial RNA-polymerase, but is mechanistically distinct from rifamycin-derived RNA-polymerase inhibitors that are in use for tuberculosis treatment. The macrolactone ring of ripostatin B features two stereocenters and a synthetically challenging doubly skipped triene motif, with one of the double bonds being in conjugation with the ester carbonyl...
March 15, 2018: Journal of Organic Chemistry
Prakash Shrestha, Hemanta Khanal, Prasanna Dahal, Pranita Dongol
Background: In Nepal, introduction of GeneXpert MTB/RIF assay (Xpert assay) as an initial confirmation test for tuberculosis (TB) has been considered to have impact as a significant decrease in number of clinically diagnosed pulmonary tuberculosis (PTB) cases than previous years. This study aims to find out the distribution profile of suspected tuberculosis cases according to patients age, gender, treatment history and HIV status as well as to evaluate the utility of the Xpert assay over conventional acid-fast bacilli (AFB) staining method for the proper diagnosis of M...
2018: Open Microbiology Journal
Wendy E Whatney, Neel R Gandhi, Cecilia S Lindestam Arlehamn, Azhar Nizam, Hao Wu, Melanie J Quezada, Angela Campbell, Salim Allana, Mbuyi Madeleine Kabongo, Jeremiah Khayumbi, Benson Muchiri, Joshua Ongalo, Joan Tonui, Loren E Sasser, Tawania J Fergus, Gregory Sadat Ouma, Samuel Gurrion Ouma, Allison A Beck, Mark J Mulligan, Alawode Oladele, Deepak Kaushal, Kevin P Cain, Lance Waller, Henry M Blumberg, John D Altman, Joel D Ernst, Jyothi Rengarajan, Cheryl L Day
Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis -specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Paolo Miotto, Andrea M Cabibbe, Emanuele Borroni, Massimo Degano, Daniela M Cirillo
Low-level rifampicin resistance associated with specific rpoB mutations (referred as "disputed") in Mycobacterium tuberculosis is easily missed by some phenotypic methods. To understand the mechanism by which some mutations are systematically missed by MGIT phenotypic testing we performed an in silico analysis of their effect on the structural interaction between the RpoB protein and rifampicin. We also characterized 24 representative clinical isolates by determining minimum inhibitory concentrations (MICs) on 7H10 agar, and testing them by an extended MGIT protocol...
March 14, 2018: Journal of Clinical Microbiology
A Alaga, Y X Yew, M K Razul
A 47-year-old female, with multiple comorbidities, presented with a cough of two months, loss of weight and appetite. She was treated for pneumonia. A chest X-ray showed bilateral reticulonodular opacities. She was noted to have a vague central abdominal mass and a systolic murmur over the mitral region. Ultrasonography and computed tomography of the abdomen showed an omental mass and loculated ascites. Oesophagoduedenoscopy showed antral gastritis and during colonoscopy the surgical team was unable to advance the scope beyond 40 cm due to external compression...
December 2017: Journal of the Royal College of Physicians of Edinburgh
D Cano-Terriza, M A Risalde, S Jiménez-Ruiz, J Vicente, J Isla, J Paniagua, I Moreno, C Gortázar, J A Infantes-Lorenzo, I García-Bocanegra
In recent decades, habitat change and the intensive management of wild ungulates for hunting have led to an increase in their populations in south-central Spain. This implies a higher generation of hunting waste, which can favour the transmission of infectious diseases, including tuberculosis (TB). The aim of this study was to assess the usefulness of the proper disposal of hunting waste as TB control measure in wild boar (Sus scrofa) and red deer (Cervus elaphus) during the 2008/2009 to 2016/2017 hunting seasons...
March 13, 2018: Transboundary and Emerging Diseases
Maopeng Tian, Zijie Zhou, Songwei Tan, Xionglin Fan, Longmeng Li, Nadeem Ullah
Despite the vaccine Mycobacterium bovis Bacillus Calmette-Guérin is used worldwide, tuberculosis (TB) remains the first killer among infectious diseases. An effective vaccine is urgently required. DNA vaccine has shown prophylactic as well as therapeutic effects against TB, while its weak immunogenicity hinders the application. As a strong inducer of Th1-biased immune response, DMT, consisting of dimethyldioctadecylammonium (DDA) and two pattern recognition receptor agonists monophosphoryl lipid A and trehalose 6,6'-dibehenate (TDB), was a newly developed liposomal adjuvant...
2018: Frontiers in Immunology
Mariateresa Coppola, Susan J F van den Eeden, Naoko Robbins, Louis Wilson, Kees L M C Franken, Linda B Adams, Tom P Gillis, Tom H M Ottenhoff, Annemieke Geluk
Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines...
2018: Frontiers in Immunology
Francles Blanco-Guillot, M Lucía Castañeda-Cediel, Pablo Cruz-Hervert, Leticia Ferreyra-Reyes, Guadalupe Delgado-Sánchez, Elizabeth Ferreira-Guerrero, Rogelio Montero-Campos, Miriam Bobadilla-Del-Valle, Rosa Areli Martínez-Gamboa, Pedro Torres-González, Norma Téllez-Vazquez, Sergio Canizales-Quintero, Mercedes Yanes-Lane, Norma Mongua-Rodríguez, Alfredo Ponce-de-León, José Sifuentes-Osornio, Lourdes García-García
BACKGROUND: Genotyping and georeferencing in tuberculosis (TB) have been used to characterize the distribution of the disease and occurrence of transmission within specific groups and communities. OBJECTIVE: The objective of this study was to test the hypothesis that diabetes mellitus (DM) and pulmonary TB may occur in spatial and molecular aggregations. MATERIAL AND METHODS: Retrospective cohort study of patients with pulmonary TB. The study area included 12 municipalities in the Sanitary Jurisdiction of Orizaba, Veracruz, México...
2018: PloS One
N T de Siqueira Filha, M de Fatima Pessoa Militao de Albuquerque, R Legood, L Rodrigues, A C Santos
OBJECTIVE: The objective of this study was to evaluate the direct and indirect costs of tuberculosis (TB) (active and latent TB [LTB]) and HIV co-infection from the patient perspective. STUDY DESIGN: Costing study conducted alongside a pragmatic clinical trial. METHODS: The study was conducted in Brazil in a referral service for HIV/AIDS. We applied a standardised questionnaire to collect data about out-of-pocket expenses and indirect cost...
March 10, 2018: Public Health
Vinod K Bhutani, M Jeffrey Maisels, David L Schutzman, Martin E Castillo Cuadrado, Janelle L Aby, Debra L Bogen, Robert D Christensen, Jon F Watchko, Ronald J Wong, David K Stevenson
AIM: To identify neonates at risk for haemolytic hyperbilirubinaemia through near-concurrrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis. METHODS: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n=283) at 20 to <60h of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk using the Bhutani hour-specific nomogram...
March 13, 2018: Acta Paediatrica
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