26 results found
White R, Basu Roy R, 2020, Projections of pregnancy: art as the voice for the unheard., Lancet Child Adolesc Health
Noguera-Julian A, Calzada-HernÁndez J, Brinkmann F, et al., 2019, Tuberculosis disease in children and adolescents on therapy with anti-tumor necrosis factor-alpha agents: a collaborative, multi-centre ptbnet study., Clin Infect Dis
BACKGROUND: In adults, anti-tumor-necrosis-factor (TNF)-α therapy is associated with progression of latent tuberculosis infection (LTBI) to tuberculosis (TB) disease. The existing paediatric data are very limited. METHODS: Retrospective multi-centre study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy. RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified; Crohn´s disease (n=8;42%) and juvenile idiopathic arthritis (n=6;32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-gamma release assay) was performed in 15 patients before commencing anti-TNF-α therapy, but only identified one LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR:7.1-20.3) months. All cases presented with severe disease, predominately miliary TB (n=14;78%). One case was diagnosed post-mortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR:46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. CONCLUSIONS: The data indicate that LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease, and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low TB prevalence settings.
Cresswell F, Davis A, Sharma K, et al., 2019, Recent developments in tuberculous meningitis pathogenesis and diagnostics [version 1; peer review: awaiting peer review], Wellcome Open Research, Vol: 4, Pages: 1-13, ISSN: 2398-502X
The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of <150 cells/μL) having higher CSF neutrophils, greater CSF cytokine concentrations and higher mortality than those with CD4+ T-cell counts > 150 cells/μL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a “one-size-fits-all” approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens.
Roy RB, 2019, A prescription for cinematic lenses on child and adolescent health, LANCET CHILD & ADOLESCENT HEALTH, Vol: 3, Pages: 681-682, ISSN: 2352-4642
Darboe S, Dobreniecki S, Jarju S, et al., 2019, Prevalence of Panton-Valentine Leukocidin (PVL) and Antimicrobial Resistance in Community-Acquired Clinical Staphylococcus aureus in an Urban Gambian Hospital: A 11-Year Period Retrospective Pilot, FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol: 9, ISSN: 2235-2988
Roy RB, Sambou B, Uhia I, et al., 2019, An auto-luminescent fluorescent BCG whole blood assay to enable evaluation of paediatric mycobacterial responses using minimal blood volumes, Frontiers in Pediatrics, Vol: 7, ISSN: 2296-2360
Introduction: Understanding protective human immunity against mycobacteria is critical to developing and evaluating new vaccines against tuberculosis. Children are the most susceptible population to infection, disease, and death from tuberculosis, but also have the strongest evidence of BCG-inducible protection. Limited amounts of blood can be obtained for research purposes in paediatrics and therefore there is a need for high-yield, low-volume, human immunology assays.Methods: We transformed BCG Danish with plasmids encoding luciferase full operon derived from Photorhabdus luminescens together with Green Fluorescent Protein and antibiotic selection markers. We characterised the luminescent and fluorescent properties of this recombinant BCG strain (BCG-GFP-LuxFO) using a luminometer and flow cytometry and developed a paediatric whole blood in vitro infection model.Results: Luminescence of BCG-GFP-LuxFO correlated with optical density (Spearman Rank Correlation coefficient r = 0.985, p < 0.0001) and colony forming units (CFUs) in liquid culture medium (r = 0.971, p < 0.0001). Fluorescence of BCG-GFP-LuxFO in paediatric whole blood was confirmed by flow cytometry in granulocytes and monocytes 1 h following infection. Luminescence of BCG-GFP-LuxFO in whole blood corresponded with CFUs (r = 0.7123, p < 0.0001).Conclusion: The BCG-GFP-LuxFO assay requires 225 μL whole blood per sample, from which serial luminescence measurements can be obtained, together with biochemical analysis of supernatants and cellular assay applications using its fluorescent properties. This offers the opportunity to study human-mycobacterial interactions using multiple experimental modalities with only minimal blood volumes. It is therefore a valuable method for investigating paediatric immunity to tuberculosis.
Basu Roy R, Whittaker E, Seddon JA, et al., 2019, Tuberculosis susceptibility and protection in children, Lancet Infectious Diseases, Vol: 19, Pages: e96-e108, ISSN: 1473-3099
Children represent both a clinically important population susceptible to tuberculosis and a key group in whom to study intrinsic and vaccine-induced mechanisms of protection. After exposure to Mycobacterium tuberculosis, children aged under 5 years are at high risk of progressing first to tuberculosis infection, then to tuberculosis disease and possibly disseminated forms of tuberculosis, with accompanying high risks of morbidity and mortality. Children aged 5–10 years are somewhat protected, until risk increases again in adolescence. Furthermore, neonatal BCG programmes show the clearest proven benefit of vaccination against tuberculosis. Case-control comparisons from key cohorts, which recruited more than 15 000 children and adolescents in total, have identified that the ratio of monocytes to lymphocytes, activated CD4 T cell count, and a blood RNA signature could be correlates of risk for developing tuberculosis. Further studies of protected and susceptible populations are necessary to guide development of novel tuberculosis vaccines that could facilitate the achievement of WHO's goal to eliminate deaths from tuberculosis in childhood.
Antolin LF, Kadambari S, Braccio S, et al., 2018, Increased detection of human parechovirus infection in infants in England during 2016: epidemiology and clinical characteristics, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 103, Pages: 1061-1066, ISSN: 0003-9888
Kampmann B, Seddon JA, Paton J, et al., 2018, Evaluating UK National Guidance for Screening of Children for TB: A prospective multi-centre study, American Journal of Respiratory and Critical Care Medicine, Vol: 197, Pages: 1058-1064, ISSN: 1073-449X
Rationale and Objective In order to identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of interferon-gamma release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children screened TST-positive but IGRA-negative. We carried out a cohort study to evaluate the risk of TB disease in this group. Methods Children exposed to an infectious case of TB in their household were recruited from 11 paediatric TB clinics. TST and IGRA were carried out at baseline, IGRA repeated at 8 weeks and TST repeated if initially negative. Children were treated according to 2006 NICE guidelines and followed for 24 months. Measurements and Main Results Of 431 recruited children 392 completed the study. We diagnosed 48 (12.2%) cases of prevalent TB disease, 105 (26.8%) with TB infection and 239 (60.9%) without TB infection or disease. 18 children aged two years and above had a positive TST but persistently negative IGRA. None received TB infection treatment and none developed TB disease. 90 (26.1%) children qualified for TB infection treatment according to 2006 NICE guidelines. In contrast, 147 (42.7%) children would have qualified under revised NICE guidance, issued in 2016. Conclusions In this low prevalence setting we saw no incident cases of TB disease in children who were TST-positive but IGRA-negative and did not receive treatment for TB infection. Following the latest NICE guidance, significantly more children will require medication.
Basu Roy R, Seddon JA, 2017, Linezolid for children with tuberculous meningitis: more evidence required, Pediatric Infectious Disease Journal, Vol: 36, Pages: 439-439, ISSN: 1532-0987
Broger T, Basu Roy R, Filomena A, et al., 2017, Diagnostic performance of tuberculosis-specific IgG antibody profiles in patients with presumptive tuberculosis from two continents, Clinical Infectious Diseases, Vol: 64, Pages: 947-955, ISSN: 1537-6591
Background. Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identifiedMycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World HealthOrganization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens.Methods. Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at atuberculosis reference center in Vietnam were recruited. We tested blood samples from 755 HIV–uninfected adults with presumptivepulmonary tuberculosis to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serologicalassay and a 132-antigen bead-based reference assay. We evaluated single antigen performance and models of all possible 3-antigencombinations and multiantigen combinations.Results. Three-antigen and multiantigen models performed similarly and were superior to single antigens. With specificityset at 90% for a detection test, the best sensitivity of a 3-antigen model was 35% (95% confidence interval [CI], 31–40). Withsensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34% (95% CI, 29–40). The reference assayalso did not meet study targets. Antigen performance differed significantly between the study sites for 7/22 of the best-performingantigens.Conclusions. Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen ormultiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosisin high-volume, urban settings in tuberculosis-endemic countries.
Basu Roy R, Brandt N, Moodie N, et al., 2016, Why the Convention on the Rights of the Child must become a guiding framework for the realization of the rights of children affected by tuberculosis, BMC International Health and Human Rights, Vol: 16, ISSN: 1472-698X
BackgroundUntil recently, paediatric tuberculosis (TB) has been relatively neglected by the broader TB and the maternal and child health communities. Human rights-based approaches to children affected by TB could be powerful; however, awareness and application of such strategies is not widespread. DiscussionWe summarize the current challenges faced by children affected by TB, including: consideration of their family context; the limitations of preventive, diagnostic and treatment options; paucity of paediatric-specific research; failure in implementation of interventions; and stigma. We examine the articles of the Convention on the Rights of the Child (CRC) and relate them to childhood TB. Specifically, we focus on the five core principles of the CRC: children’s inherent right to life and States’ duties towards their survival and development; children’s right to enjoyment of the highest attainable standard of health; non-discrimination; best interests of the child; and respect for the views of the child. We highlight where children’s rights are violated and how a human rights-based approach should be used as a tool to help children affected by TB, particularly in light of the Sustainable Development Goals and their focus on universality and leaving no one behind. SummaryThe article aims to bridge the gap between those providing paediatric TB clinical care and conducting research, and those working in the fields of human rights policy and advocacy to promote a human rights-based approach for children affected by TB based upon the Convention on the Rights of the Child.
Long J, Basu Roy R, Zhang YJ, et al., 2016, Plasma Membrane Profiling Reveals Upregulation of ABCA1 by Infected Macrophages Leading to Restriction of Mycobacterial Growth, Frontiers in Microbiology, Vol: 7, ISSN: 1664-302X
The plasma membrane represents a critical interface between the internal and extracellular environments, and harbors multiple proteins key receptors and transporters that play important roles in restriction of intracellular infection. We applied plasma membrane profiling, a technique that combines quantitative mass spectrometry with selective cell surface aminooxy-biotinylation, to Bacille Calmette–Guérin (BCG)-infected THP-1 macrophages. We quantified 559 PM proteins in BCG-infected THP-1 cells. One significantly upregulated cell-surface protein was the cholesterol transporter ABCA1. We showed that ABCA1 was upregulated on the macrophage cell-surface following infection with pathogenic mycobacteria and knockdown of ABCA1 resulted in increased mycobacterial survival within macrophages, suggesting that it may be a novel mycobacterial host-restriction factor.
Fullerton L, Norrish G, Wedderburn CJ, et al., 2015, Nosocomial Neonatal Listeria monocytogenes Transmission by Stethoscope, Pediatric Infectious Disease Journal, Vol: 34, Pages: 1042-1043, ISSN: 1532-0987
Williams B, Ramroop S, Shah P, et al., 2013, Multidrug-resistant tuberculosis in UK children: presentation, management and outcome, EUROPEAN RESPIRATORY JOURNAL, Vol: 41, Pages: 1456-1458, ISSN: 0903-1936
Amer K, Roy RB, Parslow R, et al., 2013, GENDER MORTALITY DIFFERENCES OF INFANTS ON PICU, 24th Annual Meeting of the European-Society-of-Paediatric-and-Neonatal-Intensive-Care, Publisher: SPRINGER, Pages: S76-S76, ISSN: 0342-4642
Pollock L, Basu Roy R, Kampmann B, 2013, How to use: interferon γ release assays for tuberculosis, Arch Dis Child Educ Pract Ed
Basu Roy R, Rubin EJ, 2013, Tuberculosis, The Prokaryotes, Editors: Rosenberg, DeLong, Lory, Stackebrandt, Thompson, Publisher: Springer Berlin Heidelberg, Pages: 133-133, ISBN: 978-3-642-30144-5
Mycobacterium tuberculosis is an obligate human pathogen of immense importance, infecting up to one third of the human population and causing 1.4 million deaths per year. Despite a long-established vaccine and initially effective antibiotics, M. tuberculosis continues to be a scourge of mankind through a combination of factors: related to the organism, host, their interaction, co-infections such as with HIV, and societal issues. The hallmark of M. tuberculosis as a pathogen is its intracellular growth and ability to evade killing by macrophages, including latent infection for many years. Here we consider distinctive characteristics of the organism, pathogenesis, epidemiology, clinical syndrome, diagnosis, treatment, and prevention of tuberculosis. Pressing challenges include combating drug resistance, designing better vaccines, improved diagnostics, and simplified treatment regimes. Molecular techniques are increasingly being transferred from bench to bedside and the coordinated efforts of microbiologists, immunologists, epidemiologists, clinicians, and policy-makers are required to turn the tide against tuberculosis.
Basu Roy R, McMahon GT, 2012, High fidelity and fun: but fallow ground for learning?, Med Educ, Vol: 46, Pages: 1022-1023, ISSN: 0308-0110
Roy RB, Sotgiu G, Altet-Gomez N, et al., 2012, Identifying Predictors of Interferon-gamma Release Assay Results in Pediatric Latent Tuberculosis: A Protective Role of Bacillus Calmette-Guerin? A pTB-NET Collaborative Study, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 186, Pages: 378-384, ISSN: 1073-449X
Roy RB, Whittaker E, Kampmann B, 2012, Current understanding of the immune response to tuberculosis in children, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 25, Pages: 250-257, ISSN: 0951-7375
Roy RB, McMahon GT, 2012, Video-based cases disrupt deep critical thinking in problem-based learning, MEDICAL EDUCATION, Vol: 46, Pages: 426-435, ISSN: 0308-0110
Giehl C, Roy RB, Knellwolf AL, 2011, The situation of HIV/M. tuberculosis co-infection in Europe, Open Infectious Diseases Journal, Vol: 5, Pages: 21-35
This article provides an overview of the situation of HIV/AIDS, tuberculosis (TB), and HIV/MTB co-infection in the 27 member states of the European Union (EU27), prepared in the context of the FP7 project EUCO-Net (European Network for global cooperation in the field of AIDS & TB). Information contained herein, together with similar reports compiled for the four other EUCO-Net partner regions Africa, India, Russia, and South America provided the basis for the development of the EUCO-Net AIDS/TB Roadmap, a document which was compiled to support and facilitate the development of national, regional, and global research priorities and health policies, and to help boost international cooperation aimed at combating the scourge of HIV/AIDS, TB, and their deadly combination. A comprehensive overview of the national situation in all 27 EU member states is a prerequisite for effective disease management and adequate priority setting in research and development (R&D) activities in Europe. Therefore, results presented here include demographic and epidemiological data on HIV and MTB infection, both separately and combined, as well as information concerning disease management such as diagnostics, resistance testing, treatment, and associated economic costs. Results of the primary data collection were presented at the "AIDS/TB workshop on research challenges and opportunities for future collaboration" at the University of Stellenbosch, South Africa, in July 2009, which brought together more than 60 scientists from Europe and all EUCO-Net target regions to discuss future joint AIDS/TB research. In this context, intercultural aspects that may hamper cross-national cooperation and research in these fields such as language barriers, different ethical regulations, or operational challenges were also taken into account. The article concludes by summarizing the jointly identified key areas to improve disease management within the EU and by recommending priority areas fo
Giehl C, Roy RB, Knellwolf A-L, 2011, The Situation of HIV/M. tuberculosis Co-Infection in Europe, The Open Infectious Diseases Journal, Vol: 5, Pages: 21-35, ISSN: 1874-2793
Roy RB, Newbould C, Monrose C, et al., 2010, Does adherence to antiretroviral therapy run in families?, HIV MEDICINE, Vol: 11, Pages: 72-73, ISSN: 1464-2662
Roy RB, 2009, The sea and poison, BMJ (Online), Vol: 338
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