210 results found
Brilha S, Chong DLW, Khawaja AA, et al., 2018, Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis., Front Immunol, Vol: 9, ISSN: 1664-3224
Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.
Fox KA, Kirwan DE, Whittington AM, et al., 2018, Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis., Am J Respir Crit Care Med, Vol: 198, Pages: 245-255
RATIONALE: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a proinflammatory, tissue-degrading phenotype in TB.
Hargreaves S, Nellums LB, Ramsay M, et al., 2018, Who is responsible for the vaccination of migrants in Europe?, LANCET, Vol: 391, Pages: 1752-1754, ISSN: 0140-6736
Knight GM, Zimic M, Funk S, et al., 2018, The relative fitness of drug-resistant Mycobacterium tuberculosis: a modelling study of household transmission in Peru., J R Soc Interface, Vol: 15
The relative fitness of drug-resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous and mostly derived from in vitro experiments. Measuring fitness in the field allows us to determine how the environment influences the spread of resistance. We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multidrug resistance (MDR) carriage in Mtb in Lima, Peru during 2010-2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts, we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtb to be 0.32 (95% credible interval: 0.15-0.62) or 0.38 (0.24-0.61), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR-Mtb increased to 0.56 (0.42-0.72) when the fitness cost influenced both transmission and progression to disease equally. We found the average relative fitness of MDR-Mtb circulating within households in Lima, Peru during 2010-2013 to be significantly lower than concurrent susceptible Mtb If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.
López JW, Loader M-CI, Smith D, et al., 2018, Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis., Am J Trop Med Hyg, Vol: 98, Pages: 1637-1639
To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.
Nakken CS, Skovdal M, Nellums LB, et al., 2018, Vaccination status and needs of asylum-seeking children in Denmark: a retrospective data analysis, PUBLIC HEALTH, Vol: 158, Pages: 110-116, ISSN: 0033-3506
Nellums LB, Rustage K, Hargreaves S, et al., 2018, Multidrug-resistant tuberculosis treatment adherence in migrants: a systematic review and meta-analysis, BMC MEDICINE, Vol: 16, ISSN: 1741-7015
Nellums LB, Thompson H, Holmes A, et al., 2018, Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis, Lancet Infectious Diseases, ISSN: 1473-3099
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus
Proano A, Bui DP, Lopez JW, et al., 2018, Cough Frequency During Treatment Associated With Baseline Cavitary Volume and Proximity to the Airway in Pulmonary TB, CHEST, Vol: 153, Pages: 1358-1367, ISSN: 0012-3692
Seedat F, Hargreaves S, Nellums LB, et al., 2018, How effective are approaches to migrant screening for infectious diseases in Europe? A systematic review., Lancet Infect Dis
Rates of migration to Europe, and within Europe, have increased in recent years, with considerable implications for health systems. Migrants in Europe face a disproportionate burden of tuberculosis, HIV, and hepatitis B and C, yet experience a large number of barriers to accessing statutory health care on arrival. A better understanding of how to deliver effective and cost-effective screening, vaccination, and health services to this group is now crucial. We did a systematic review to document and assess the effectiveness and cost-effectiveness of approaches used for infectious diseases screening, and to explore facilitators and barriers experienced by migrants to accessing screening programmes. Following PRISMA guidelines, we searched Embase, PubMed, PsychINFO, the Cochrane Library, and Web of Science (1989 to July 1, 2015, updated on Jan 1, 2018), with no language restrictions, and systematically approached experts across the European Union (EU) for grey literature. Inclusion criteria were primary research studies assessing screening interventions for any infectious disease in the migrant (foreign-born) population residing in EU or European Economic Area (EEA) countries. Primary outcomes were the following effectiveness indicators: uptake of screening, coverage, infections detected, and treatment outcomes. Of 4112 unique records, 47 studies met our inclusion criteria, from ten European countries (Belgium, Denmark, France, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the UK) encompassing 248 402 migrants. We found that most European countries screening migrants focus on single diseases only-predominantly active or latent tuberculosis infection-and specifically target asylum seekers and refugees, with 22 studies reporting on other infections (including HIV and hepatitis B and C). An infection was detected in 3·74% (range 0·00-95·16) of migrants. Latent tuberculosis had the highest prevalence across all infections (median 15&mi
Singh S, Maniakis-Grivas G, Singh UK, et al., 2018, Interleukin-17 regulates matrix metalloproteinase activity in human pulmonary tuberculosis, JOURNAL OF PATHOLOGY, Vol: 244, Pages: 311-322, ISSN: 0022-3417
Brace PT, Tezera LB, Bielecka MK, et al., 2017, Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology, PLOS PATHOGENS, Vol: 13, ISSN: 1553-7366
Brilha S, Ong CWM, Weksler B, et al., 2017, Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Brilha S, Sathyamoorthy T, Stuttaford LH, et al., 2017, Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 56, Pages: 223-232, ISSN: 1044-1549
Brilha S, Wysoczanski R, Whittington AM, et al., 2017, Monocyte Adhesion, Migration, and Extracellular Matrix Breakdown Are Regulated by Integrin alpha V beta 3 in Mycobacterium tuberculosis Infection, JOURNAL OF IMMUNOLOGY, Vol: 199, Pages: 982-991, ISSN: 0022-1767
Hargreaves S, Duarte R, Friedland JS, 2017, The role of pre-migration medical screening in high TB burden countries, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 21, Pages: 718-719, ISSN: 1027-3719
Hargreaves S, Lonnroth K, Nellums LB, et al., 2017, Multidrug-resistant tuberculosis and migration to Europe, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 23, Pages: 141-146, ISSN: 1198-743X
Kirwan DE, Ugarte-Gil C, Gilman RH, et al., 2017, Histological Examination in Obtaining a Diagnosis in Patients with Lymphadenopathy in Lima, Peru, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 97, Pages: 1271-1276, ISSN: 0002-9637
Moores RC, Brilha S, Schutgens F, et al., 2017, Epigenetic Regulation of Matrix Metalloproteinase-1 and-3 Expression in Mycobacterium tuberculosis Infection, FRONTIERS IN IMMUNOLOGY, Vol: 8, ISSN: 1664-3224
Ong CWM, Pabisiak PJ, Brilha S, et al., 2017, Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis, JOURNAL OF NEUROINFLAMMATION, Vol: 14, ISSN: 1742-2094
Proano A, Bravard MA, Lopez JW, et al., 2017, Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis, CLINICAL INFECTIOUS DISEASES, Vol: 64, Pages: 1174-1181, ISSN: 1058-4838
Saunders MJ, Wingfield T, Tovar MA, et al., 2017, A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study, LANCET INFECTIOUS DISEASES, Vol: 17, Pages: 1190-1199, ISSN: 1473-3099
Walker NF, Wilkinson KA, Meintjes G, et al., 2017, Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: 121-132, ISSN: 1058-4838
Dudley MZ, Sheen P, Gilman RH, et al., 2016, Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 95, Pages: 1239-1246
Hargreaves S, Nellums L, Friedland JS, 2016, Time to rethink approaches to migrant health screening, LANCET, Vol: 388, Pages: 2456-2457, ISSN: 0140-6736
Hargreaves S, Nellums L, Friedland JS, et al., 2016, Extending migrant charging into emergency services, BMJ-BRITISH MEDICAL JOURNAL, Vol: 352, ISSN: 1756-1833
Kubler A, Larsson C, Luna B, et al., 2016, Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis, JOURNAL OF INFECTIOUS DISEASES, Vol: 213, Pages: 618-627, ISSN: 0022-1899
Martin LJ, Roper MH, Grandjean L, et al., 2016, Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?, BMC MEDICINE, Vol: 14, ISSN: 1741-7015
Proano A, Bravard MA, Tracey BH, et al., 2016, Protocol for studying cough frequency in people with pulmonary tuberculosis, BMJ OPEN, Vol: 6, ISSN: 2044-6055
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