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Search Results: 1 - 10 of 219504 matches for " C Lienhardt "
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What Research Is Needed to Stop TB? Introducing the TB Research Movement
Christian Lienhardt ,Marcos Espinal,Madhukar Pai,Dermot Maher,Mario C. Raviglione
PLOS Medicine , 2011, DOI: 10.1371/journal.pmed.1001135
Risk factors for pulmonary tuberculosis: a clinic-based case control study in The Gambia
Philip C Hill, Dolly Jackson-Sillah, Simon A Donkor, Jacob Otu, Richard A Adegbola, Christian Lienhardt
BMC Public Health , 2006, DOI: 10.1186/1471-2458-6-156
Abstract: We conducted a case control study at the Medical Research Council Outpatients' clinic in The Gambia. Pulmonary TB cases were at least 15 years old, controls were age and sex matched clinic attendees. Participants were interviewed using a structured questionnaire.100 sputum smear positive TB cases and 200 clinic controls were recruited. HIV prevalence was 6.1% in cases and 3.3% in controls. Multivariable assessment of host factors showed that risk of TB was increased among the Jola ethnic group and smokers, and decreased in those in a professional occupation. Assessment of environmental factors showed an increased risk with household crowding, history of household exposure to a known TB case, and absence of a ceiling in the house. In a combined multivariable host-environment model, the risk of TB increased with crowding, exposure to a known TB case, as well as amongst the Jola ethnic group.In The Gambia, household crowding and past household exposure to a known TB case are the standout risk factors for TB disease. Further research is needed to identify why risk of TB seems to differ according to ethnicity.Tuberculosis (TB) causes approximately 2 million deaths per year globally [1]; 98% occur in low-income countries [2]. In Africa, in contrast to many other parts of the world, the incidence rate is rising by approximately 6% per year [3] High rates of HIV infection have been a key driving factor in this [4]. However, even in African countries with relatively low HIV prevalence, the TB case notification has been rising: in The Gambia (where community HIV seroprevalence is approximately 2%[5]) TB case notification rose from 82/100,000 in 1994 to 140/100,000 in 2004 [6]. New ways to tackle the epidemic are urgently needed.Studies investigating the risk factors for TB have been conducted in a variety of settings, but very few in Africa [7]. Recently, we published a community-based case control study of host and environmental risk factors for TB from 3 West African countr
Diagnosis of tuberculosis in Ghana: The role of laboratory training
KK Addo, D Yeboah-Manu, M Dan-Dzide, K Owusu-darko, P Caulley, GI Mensah, M Minamikawa, C Lienhardt, FA Bonsu, D Ofori-Adjei
Ghana Medical Journal , 2010,
Abstract: Objectives: The laboratory is considered the cornerstone of tuberculosis (TB) control programme. International review of Ghana’s programme in the late nineties identified the laboratory services as the weakest component. Sputum smear microscopy (SSM) being the main method of diagnosing pulmonary TB in Ghana, the training objectives were to: (i) strengthen the knowledge and skills of laboratory personnel on SSM (ii) impart necessary techniques in biosafety and (iii) introduce a Quality Assurance (QA) system in order to strengthen SSM services. Methods: Personnel were selected for training during a nationwide situation analysis of SSM centres in 2000/2001. Four training sessions on SSM/QA were held between 2001/2004. Results: A total of 80 personnel were trained: 10 regional TB coordinators and 70 laboratory personnel. The participants upon return to their respective regions also organized training within their districts. This approach resulted in another 100 district TB coordinators and 200 laboratory personnel being trained. Improvement in smear preparation, staining and reading ability of the participants were observed during the post-test and subsequent visit to their respective laboratories. The training has led to strengthening of TB laboratory services in the country and has contributed to increase in case detection from 10,745 in 2000 to 11,827 in 2004 and 14,022 in 2008. It was observed during the post-training follow-up and quarterly supervision visits that morale of the personnel was high. Conclusion: Continuous training and re-training of laboratory personnel on SSM and QA at regular intervals do play an important role for effective and efficient TB control programme.
Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research
Sculier Delphine,Getahun Haileyesus,Lienhardt Christian
Journal of the International AIDS Society , 2011, DOI: 10.1186/1758-2652-14-s1-s5
Abstract: Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.
A framework for deadlock detection in core ABS
Elena Giachino,Cosimo Laneve,Michael Lienhardt
Computer Science , 2015, DOI: 10.1007/s10270-014-0444-y
Abstract: We present a framework for statically detecting deadlocks in a concurrent object-oriented language with asynchronous method calls and cooperative scheduling of method activations. Since this language features recursion and dynamic resource creation, deadlock detection is extremely complex and state-of-the-art solutions either give imprecise answers or do not scale. In order to augment precision and scalability we propose a modular framework that allows several techniques to be combined. The basic component of the framework is a front-end inference algorithm that extracts abstract behavioural descriptions of methods, called contracts, which retain resource dependency information. This component is integrated with a number of possible different back-ends that analyse contracts and derive deadlock information. As a proof-of-concept, we discuss two such back-ends: (i) an evaluator that computes a fixpoint semantics and (ii) an evaluator using abstract model checking.
Safety and Immunogenicity of the Candidate Tuberculosis Vaccine MVA85A in West Africa
Roger H. Brookes, Philip C. Hill, Patrick K. Owiafe, Hannah B. Ibanga, David J. Jeffries, Simon A. Donkor, Helen A. Fletcher, Abdulrahman S. Hammond, Christian Lienhardt, Richard A. Adegbola, Helen McShane, Adrian V. S. Hill
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002921
Abstract: Background Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers. Methods and Findings We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-na?ve Gambians than previously studied BCG-na?ve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis. Conclusions These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis. Trial Registration ClinicalTrials.gov NCT00423839
Building Clinical Trials Capacity for Tuberculosis Drugs in High-Burden Countries
Neil Schluger,Unni Karunakara ,Christian Lienhardt,Thomas Nyirenda,Richard Chaisson
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040302
Research Questions and Priorities for Tuberculosis: A Survey of Published Systematic Reviews and Meta-Analyses
Ioana Nicolau, Daphne Ling, Lulu Tian, Christian Lienhardt, Madhukar Pai
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042479
Abstract: Background Systematic reviews are increasingly informing policies in tuberculosis (TB) care and control. They may also be a source of questions for future research. As part of the process of developing the International Roadmap for TB Research, we did a systematic review of published systematic reviews on TB, to identify research priorities that are most frequently suggested in reviews. Methodology/Principal Findings We searched EMBASE, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect of TB published between 2005 and 2010. One reviewer extracted data and a second reviewer independently extracted data from a random subset of included studies. In total, 137 systematic reviews, with 141 research questions, were included in this review. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. The three most common research topics were in the area of detection, screening and diagnosis of TB (32.6%), development and evaluation of treatments and therapeutic interventions (23.4%), and TB aetiology and risk factors (19.9%). The research priorities determined were mainly focused on the discovery and evaluation of bacteriological TB tests and drug-resistant TB tests and immunological tests. Other important topics of future research were genetic susceptibility linked to TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments for TB, drug-resistant TB and HIV/TB were also frequently proposed research topics. Conclusions Systematic reviews are a good source of key research priorities. Findings from our survey have informed the development of the International Roadmap for TB Research by the TB Research Movement.
CD209 Genetic Polymorphism and Tuberculosis Disease
Fredrik O. Vannberg, Stephen J. Chapman, Chiea C. Khor, Kerrie Tosh, Sian Floyd, Dolly Jackson-Sillah, Amelia Crampin, Lifted Sichali, Boubacar Bah, Per Gustafson, Peter Aaby, Keith P. W. J. McAdam, Oumou Bah-Sow, Christian Lienhardt, Giorgio Sirugo, Paul Fine, Adrian V. S. Hill
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001388
Abstract: Background Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. Methods and Findings A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2x2 χ2 = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77–0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2×2 χ2 = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27–0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. Conclusion This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.
Standardized Treatment of Active Tuberculosis in Patients with Previous Treatment and/or with Mono-resistance to Isoniazid: A Systematic Review and Meta-analysis
Dick Menzies ,Andrea Benedetti,Anita Paydar,Sarah Royce,Madhukar Pai,William Burman,Andrew Vernon,Christian Lienhardt
PLOS Medicine , 2009, DOI: 10.1371/journal.pmed.1000150
Abstract: Background A standardized regimen recommended by the World Health Organization for retreatment of active tuberculosis (TB) is widely used, but treatment outcomes are suspected to be poor. We conducted a systematic review of published evidence of treatment of patients with a history of previous treatment or documented isoniazid mono-resistance. Methods and Findings PubMed, EMBASE, and the Cochrane Central database for clinical trials were searched for randomized trials in previously treated patients and/or those with with mono-resistance to isoniazid, published in English, French, or Spanish between 1965 and June 2008. The first two sources were also searched for cohort studies evaluating specifically the current retreatment regimen. In studies selected for inclusion, rifampin-containing regimens were used to treat patients with bacteriologically confirmed pulmonary TB, in whom bacteriologically confirmed failure and/or relapse had been reported. Pooled cumulative incidences and 95% CIs of treatment outcomes were computed with random effects meta-analyses and negative binomial regression. No randomized trials of the currently recommended retreatment regimen were identified. Only six cohort studies were identified, in which failure rates were 18%–44% in those with isoniazid resistance. In nine trials, using very different regimens in previously treated patients with mono-resistance to isoniazid, the combined failure and relapse rates ranged from 0% to over 75%. From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid, lower failure, relapse, and acquired drug resistance rates were associated with longer duration of rifampin, use of streptomycin, daily therapy initially, and treatment with a greater number of effective drugs. Conclusions There are few published studies to support use of the current standardized retreatment regimen. Randomized trials of treatment of persons with isoniazid mono-resistance and/or a history of previous TB treatment are urgently needed. Please see later in the article for the Editors' Summary
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