233 results found
Nellums LB, Powis J, Jones L, et al., 2021, "It's a life you're playing with": A qualitative study on experiences of NHS maternity services among undocumented migrant women in England, SOCIAL SCIENCE & MEDICINE, Vol: 270, ISSN: 0277-9536
Hayward SE, Rustage K, Nellums LB, et al., 2020, Extrapulmonary tuberculosis among migrants in Europe, 1995 to 2017., Clin Microbiol Infect
OBJECTIVES: The proportion of tuberculosis (TB) cases occurring in migrants in Europe is increasing. Extrapulmonary TB poses challenges in diagnosis and treatment and causes serious morbidity and mortality, yet its extent in migrant populations is unclear. We assessed patterns of extrapulmonary TB in migrants across the European Union (EU)/European Free Trade Association (EFTA). We investigated the proportion of extrapulmonary TB cases among migrants versus non-migrants, and variations by specific site of disease, reporting European region, and migrant region of origin. METHODS: We carried out a cross-sectional secondary database analysis, utilizing 23 years of data collected between 1995 and 2017 from the European Surveillance System of the European Centre for Disease Prevention and Control for 32 EU/EFTA countries. RESULTS: In total, 1 270 896 TB cases were included, comprising 326 987 migrants (25.7%) and 943 909 non-migrants (74.3%). Of TB cases among migrants, 45.2% (n = 147 814) were extrapulmonary compared to 21.7% (n = 204 613) among non-migrants (p < 0.001). Lymphatic, bone/joint and peritoneal/digestive TB were more common among migrant than non-migrant extrapulmonary cases. A lower proportion of extrapulmonary TB was seen in Eastern Europe (17.4%, n = 98 656 of 566 170) and Southern Europe (29.6%, n = 62 481 of 210 828) compared with Western (35.7%, n = 89 498 of 250 517) and Northern Europe (41.8%, n = 101 792 of 243 381). Migrants from South-East Asia and Sub-Saharan Africa were at highest risk of extrapulmonary disease, with 62.0% (n = 55 401 of 89 353) and 54.5% (n = 38 327 of 70 378) of cases, respectively, being extrapulmonary. CONCLUSIONS: Among TB cases in the EU/EFTA, extrapulmonary disease is significantly more common in migrants than in non-migrants. There is
Ong CWM, Migliori GB, Raviglione M, et al., 2020, Epidemic and pandemic viral infections: impact on tuberculosis and the lung, EUROPEAN RESPIRATORY JOURNAL, Vol: 56, ISSN: 0903-1936
Carter J, Friedland JS, Kirwan DE, et al., 2020, Translating scientific discoveries during pandemics: ensuring equity for people affected by COVID-19 and tuberculosis, ERJ OPEN RESEARCH, Vol: 6
Kristensen KL, Ravn P, Petersen JH, et al., 2020, Long-term risk of tuberculosis among migrants according to migrant status: a cohort study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 49, Pages: 776-785, ISSN: 0300-5771
Walker NF, Opondo C, Meintjes GA, et al., 2020, Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis, Clinical Infectious Diseases, Vol: 70, Pages: 1865-1874, ISSN: 1058-4838
RationaleTuberculosis (TB) is the leading cause of mortality and morbidity in people living with HIV infection. HIV-infected patients with TB disease are at risk of the paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) when they commence anti-retroviral therapy. However, the pathophysiology is incompletely understood and specific therapy is lacking.ObjectivesWe investigated the hypothesis that invariant Natural Killer T (iNKT) cells contribute to innate immune dysfunction associated with TB-IRIS.MethodsIn a cross-sectional study of 101 HIV-infected and -uninfected South African patients with active TB and controls, iNKT cells were enumerated using α-galactosylceramide-loaded CD1d tetramers and subsequently functionally characterised by flow cytometry. In a second study of 49 HIV-1-infected TB patients commencing anti-retroviral therapy, iNKT cells in TB-IRIS patients with non-IRIS controls were compared longitudinally.Measurements and main resultsCirculating iNKT cells were reduced in HIV-1 infection, most significantly the CD4+ subset, which was inversely associated with HIV-1 viral load. iNKT cells in HIV-associated TB had increased surface CD107a expression, indicating cytotoxic degranulation. Relatively increased iNKT cell frequency in HIV-infected patients with active TB was associated with development of TB-IRIS following anti-retroviral therapy initiation. iNKT cells in TB-IRIS were CD4+CD8- subset deplete and degranulated around the time of TB-IRIS onset.ConclusionsReduced iNKT cell CD4+ subsets as a result of HIV-1 infection may skew iNKT cell functionality towards cytotoxicity. Increased CD4- cytotoxic iNKT cells may contribute to immunopathology in TB-IRIS.
Tanoglu A, Erdem H, Friedland JS, et al., 2019, Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study, EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, Vol: 39, Pages: 493-500, ISSN: 0934-9723
Hargreaves S, Himmels J, Nellums LB, et al., 2019, Vaccination status of migrant populations in EU/EEA countries and implications for VPD control, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262
Kristensen KL, Lillebaek T, Petersen JH, et al., 2019, Tuberculosis incidence among migrants according to migrant status: a cohort study, Denmark, 1993 to 2015, EUROSURVEILLANCE, Vol: 24, Pages: 14-24, ISSN: 1560-7917
Hargreaves S, Rustage K, Nellums LB, et al., 2019, Occupational health outcomes among international migrant workers: a systematic review and meta-analysis, LANCET GLOBAL HEALTH, Vol: 7, Pages: E872-E882, ISSN: 2214-109X
Osborne W, Chavda A, Katritsis G, et al., 2019, Lesson of the month 1: A rare adverse reaction between flucloxacillin and paracetamol, CLINICAL MEDICINE, Vol: 19, Pages: 127-128, ISSN: 1470-2118
Ravensbergen SJ, Nellums LB, Hargreaves S, et al., 2019, National approaches to the vaccination of recently arrived migrants in Europe: A comparative policy analysis across 32 European countries, TRAVEL MEDICINE AND INFECTIOUS DISEASE, Vol: 27, Pages: 33-38, ISSN: 1477-8939
Sloth LB, Nielsen RT, Ostergaard C, et al., 2019, Antibiotic resistance patterns of Escherichia coli in migrants vs non-migrants: a study of 14 561 urine samples, JOURNAL OF TRAVEL MEDICINE, Vol: 26, ISSN: 1195-1982
Aldridge RW, Nellums LB, Bartlett S, et al., 2018, Global patterns of mortality in international migrants: a systematic review and meta-analysis, LANCET, Vol: 392, Pages: 2553-2566, ISSN: 0140-6736
Hargreaves S, Nellums L, Ravensbergen SJ, et al., 2018, Divergent approaches in the vaccination of recently arrived migrants to Europe: a survey of national experts from 32 countries, 2017, EUROSURVEILLANCE, Vol: 23, Pages: 21-29, ISSN: 1560-7917
Nellums LB, Friedland JS, Hargreaves S, 2018, Antimicrobial resistance among migrants in Europe-Authors' reply (vol 18, pg 945, 2018), LANCET INFECTIOUS DISEASES, Vol: 18, Pages: 1063-1063, ISSN: 1473-3099
Brilha S, Ong CWM, Weksler B, et al., 2018, Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis (vol 7, 16031, 2017), SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
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 Infectious Diseases, Vol: 18, Pages: e259-e271, ISSN: 1473-3099
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
Friedland JS, Hargreaves S, 2018, Antimicrobial resistance among migrants in Europe reply, LANCET INFECTIOUS DISEASES, Vol: 18, Pages: 945-945, ISSN: 1473-3099
Ong C, Fox K, Ettorre A, et al., 2018, Hypoxia increases neutrophil-driven matrix destruction after exposure to mycobacterium tuberculosis, Scientific Reports, Vol: 8, ISSN: 2045-2322
The importance of neutrophils in the pathology of tuberculosis (TB) has been recently established. We demonstrated that TB lesions in man are hypoxic, but how neutrophils in hypoxia influence lung tissue damage is unknown. We investigated the effect of hypoxia on neutrophil-derived enzymes and tissue destruction in TB. Human neutrophils were stimulated with M. tuberculosis (M.tb) or conditioned media from M.tb-infected monocytes (CoMTB). Neutrophil matrix metalloproteinase-8/-9 and elastase secretion were analysed by luminex array and gelatin zymography, gene expression by qPCR and cell viability by flow cytometry. Matrix destruction was investigated by confocal microscopy and functional assays and neutrophil extracellular traps (NETs) by fluorescence assay. In hypoxia, neutrophil MMP-8 secretion and gene expression were up-regulated by CoMTB. MMP-9 activity and neutrophil elastase (NE) secretion were also increased in hypoxia. Hypoxia inhibited NET formation and both neutrophil apoptosis and necrosis after direct stimulation by M.tb. Hypoxia increased TB-dependent neutrophil-mediated matrix destruction of Type I collagen, gelatin and elastin, the main structural proteins of the human lung. Dimethyloxalylglycin (DMOG), which stabilizes hypoxia-inducible factor-1α, increased neutrophil MMP-8 and -9 secretion. Hypoxia in our cellular model of TB up-regulated pathways that increase neutrophil secretion of MMPs that are implicated in matrix destruction.
Fox KA, Kirwan DE, Whittington AM, et al., 2018, Platelets regulate pulmonary inflammation and tissue destruction in tuberculosis, American Journal of Respiratory and Critical Care Medicine, Vol: 198, Pages: 245-255, ISSN: 1073-449X
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 TB patients pre-treatment, and 50 controls. 25 patients were followed longitudinally. Platelet-monocyte interactions were studied in a co-culture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qPCR, Luminex multiplex arrays, matrix degradation assays and colony counts. Immunohistochemistry detected CD41 expression in a pulmonary TB murine model and secreted platelet factors were measured in bronchoalveolar lavage fluid (BALF) from 15 TB patients and matched controls. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of TB patients compared to controls, with concentrations returning to baseline by day 60 of treatment. Gene expression of the monocyte collagenase MMP-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 monocyte-derived chemokine (MDC, 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 BALF, and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a pro-inflammatory, tissue-degrading phenotype in TB.
Knight G, Zimic M, Funk S, et al., 2018, The relative fitness of drug-resistant Mycobacterium tuberculosis: a modelling study of household transmission in Peru, Journal of the Royal Society Interface, Vol: 15, ISSN: 1742-5662
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.
Dos Santos Brilha S, Chong D, Khawaja A, et al., 2018, Integrin α2β1 expression regulates matrix metalloproteinase-1-dependent bronchial epithelial repair in pulmonary tuberculosis, Frontiers in Immunology, 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.
Nellums LB, Thompson H, Holmes A, et al., 2018, Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis, Lancet Infectious Diseases, Vol: 18, Pages: 796-811, 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
Friedland JS, Proano A, Bui D, et al., 2018, Cough frequency during treatment associated with baseline cavitary volume and proximity to the airway in pulmonary tuberculosis, Chest, Vol: 153, Pages: 1358-1367, ISSN: 0012-3692
Background: Cough frequency, and its duration, is a lab-free biomarker that can be used in low-resource settings and has been associated with transmission and treatment response.Radiological characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has never been studied. Methods: We analyzed 41 human immunodeficiency virus-negative adults with culture- confirmed, drug-susceptible pulmonary tuberculosis throughout treatment. Cough recordings were based on the Cayetano Cough Monitor and sputum samples were evaluated using microscopic-observation drug susceptibility broth culture, among culture-positive samples bacillary burden was assessed by time to positivity. Computerized tomography scans were analyzed by a U.S. board-certified radiologist and an automated-computer algorithm. The algorithm evaluates cavity volume and cavitary proximity to the airway. Computerized tomography scans were taken within one month of treatment initiation. We compared small cavities (≤7-mL) versus large cavities (>7-mL) and cavities located closer to (≤10-mm) and farther (>10-mm) from the airway to cough frequency and cough cessation until treatment day 62.Results: Cough frequency during treatment was two-fold higher in participants with large cavity volumes (Rate Ratio [RR]=1.98, p=0.01) and cavities located closer to the airway (RR=2.44, p=0.001). Comparably, cough ceased three times faster in smaller cavities (adjusted hazard ratio [HR]=2.89, p=0.06) and those farther from the airway (adjusted HR=3.61, p=0.02). Similar results are found for bacillary burden and culture conversion during treatment. Conclusions: Cough frequency during treatment is greater and lasts for longer in patients with larger cavities, especially those closer to the airway
Lopez J, Loader M, Smith D, et al., 2018, Exhaled nitric oxide is not a biomarker for pulmonary tuberculosis, American Journal of Tropical Medicine and Hygiene, Vol: 98, Pages: 1637-1639, ISSN: 0002-9637
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, non-invasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multi-drug resistant (MDR)-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) (IQR 8-26), vs. 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 nor as a marker of treatment response.
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
Nakken C, 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
ObjectivesAsylum-seekers to Europe may come from war-torn countries where health systems have broken down, and there is evidence that asylum-seeking children have low coverage of childhood vaccinations, as well as uptake of immunisations in host countries. Such gaps in immunisation have important implications for effective national vaccination programmes. How we approach vaccination in children and adults entering Western Europe, where as a group they face barriers to health services and screening, is a growing debate, however there is limited data on the vaccination status of these hard to reach communities and robust evidence is needed to inform immunisation strategies. The aim of this study was to explore the vaccination status and needs of asylum-seeking children and adolescents in Denmark.Study designWe conducted a retrospective data analysis of anonymised patient records for asylum-seeking children and adolescents extracted from the Danish Red Cross database.MethodsWe retrospectively searched the Danish Red Cross database for children and adolescents (age 3 months to 18 years) with active asylum applications in Denmark as of October 28th, 2015. Data were extracted for demographic characteristics, vaccination status, and vaccinations needed by asylum-seeking children presenting to Red Cross asylum centres for routine statutory health screening. ResultsWe explored the vaccination status and needs of 2,126 asylum-seeking children and adolescents. 64% of the study population was male and 36% was female. Eight nationalities were represented, where 33% of the total of children and adolescents were not immunised in accordance with Danish national guidelines, while 7% were considered partly vaccinated, and 60% were considered adequately vaccinated. Afghan (57% not vaccinated/unknown) and Eritrean (54% not vaccinated/unknown) children were the least likely to be vaccinated of all nationalities represented, as were boys (37% not vaccinated/unknown) compared with girls
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
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in meeting global targets for TB control. In high-income low-TB-incidence countries, a disproportionate number of MDR-TB cases occur in migrant (foreign-born) populations, with concerns about low adherence rates in these patients compared to the host non-migrant population. Tackling MDR-TB in this context may, therefore, require unique approaches. We conducted a systematic review and meta-analysis to identify and synthesise data on MDR-TB treatment adherence in migrant patients to inform evidence-based strategies to improve care pathways and health outcomes in this group. METHODS: This systematic review and meta-analysis was conducted in line with PRISMA guidelines (PROSPERO 42017070756). The databases Embase, MEDLINE, Global Health and PubMed were searched to 24 May 2017 for primary research reporting MDR-TB treatment adherence and outcomes in migrant populations, with no restrictions on dates or language. A meta-analysis was conducted using random-effects models. RESULTS: From 413 papers identified in the database search, 15 studies reporting on MDR-TB treatment outcomes for 258 migrants and 174 non-migrants were included in the systematic review and meta-analysis. The estimated rate of adherence to MDR-TB treatment across migrant patients was 71% [95% confidence interval (CI) = 58-84%], with non-adherence reported among 20% (95% CI = 4-37%) of migrant patients. A key finding was that there were no differences in estimated rates of adherence [risk ratio (RR) = 1.05; 95% CI = 0.82-1.34] or non-adherence (RR = 0.97; 95% CI = 0.79-1.36) between migrants and non-migrants. CONCLUSIONS: MDR-TB treatment adherence rates among migrants in high-income low-TB-incidence countries are approaching global targets for treatment success (75%), and are comparable to rates in non-migrants. The findings highlight that only jus
Singh S, Maniakis-Grivas G, Singh U, et al., 2018, Interleukin-17 regulates matrix metalloproteinase activity in human pulmonary tuberculosis, Journal of Pathology, Vol: 244, Pages: 311-322, ISSN: 0022-3417
Tuberculosis (TB) is characterised by extensive pulmonary matrix breakdown. Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven tissue damage is unknown. We investigated the hypothesis that respiratory stromal cell matrix metalloproteinase (MMP) production in TB is regulated by T helper-17 (TH-17) cytokines. Biopsies of patients with pulmonary TB were analysed by immunohistochemistry (IHC) and patient bronchoalveolar lavage fluid (BALF) MMP and cytokine concentrations measured by Luminex assays. Primary human airway epithelial cells were stimulated with conditioned medium from human monocytes infected with Mycobacterium tuberculosis (Mtb) and TH-17 cytokines. MMP secretion, activity and gene expression were determined by ELISA, Luminex assay, zymography, RT-qPCR and dual luciferase reporter assays. Signalling pathways were examined using phospho-western analysis and siRNA. IL-17 is expressed in TB patient granulomas and MMP-3 is expressed in adjacent pulmonary epithelial cells. IL-17 had a divergent, concentration-dependent effect on MMP secretion, increasing epithelial secretion of MMP-3 (p<0.001) over 72 h whilst decreasing that of MMP-9 (p<0.0001); mRNA levels were similarly affected. Both IL-17 and Interleukin-22 (IL-22) increased fibroblast Mtb-dependent MMP-3 secretion but IL-22 did not modulate epithelial MMP-3 expression. Both IL-17 and IL-22, but not Interleukin-23 (IL-23), were significantly upregulated in BALF from TB patients. IL-17-driven MMP-3 was dependent on p38 MAP kinase and the PI 3-K p110α subunit. In summary, IL-17 drives airway stromal cell-derived MMP-3, a mediator of tissue destruction in TB, alone and with monocyte-dependent networks in TB. This is regulated by p38 MAP kinase and PI3-K pathways.
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