Okeke I.N.,Haverford College |
Peeling R.W.,London School of Hygiene and Tropical Medicine |
Goossens H.,University of Antwerp |
Auckenthaler R.,Unilabs SA |
And 5 more authors.
Drug Resistance Updates | Year: 2011
Antibacterial drugs are overused and often inappropriately selected. This exacerbates drug resistance and exacts a high burden from acute respiratory tract, bloodstream, sexually-transmitted, diarrheal and other infections. Appropriate use of existing diagnostic tests, and developing better ones, could avert these costs and would avoid selective pressure from unnecessary antibacterial use. Product profiles of resistance-averting tests would specify WHO 'ASSURED' (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free and Deliverable) criteria and request susceptibility as well as etiological information. Advances in genomics, nanoscience, microfluidics and bioengineering, as well as innovative funding paradigms can help to overcome research and development barriers for such diagnostics if they are deliberately and forcefully applied. Rapid uptake of new tests requires timely translation of research on cost-benefit analyses into policy, value-based subsidies and reimbursements, as well as behavioral change of health care providers and users. © 2011 Elsevier Ltd. All Rights Reserved.
Wallis R.S.,Pfizer |
Pai M.,McGill University |
Pai M.,Montreal Chest Institute |
Menzies D.,McGill University |
And 5 more authors.
The Lancet | Year: 2010
Human infection with Mycobacterium tuberculosis can progress to active disease, be contained as latent infection, or be eradicated by the host response. Tuberculosis diagnostics classify a patient into one of these categories. These are not fixed distinct states, but rather are continua along which patients can move, and are affected by HIV infection, immunosuppressive therapies, antituberculosis treatments, and other poorly understood factors. Tuberculosis biomarkers-host or pathogen-specific-provide prognostic information, either for individual patients or study cohorts, about these outcomes. Tuberculosis case detection remains difficult, partly because of inaccurate diagnostic methods. Investments have yielded some progress in development of new diagnostics, although the existing pipeline is limited for tests for sputum-smear-negative cases, childhood tuberculosis, and accurate prediction of reactivation of latent tuberculosis. Despite new, sensitive, automated molecular platforms for detection of tuberculosis and drug resistance, a simple, inexpensive point-of-care test is still not available. The effect of any new tests will depend on the method and extent of their introduction, the strength of the laboratories, and the degree to which access to appropriate therapy follows access to diagnosis. Translation of scientific progress in biomarkers and diagnostics into clinical and public health programmes is possible-with political commitment, increased funding, and engagement of all stakeholders. © 2010 Elsevier Ltd. All rights reserved.
Denkinger C.M.,Beth Israel Deaconess Medical Center |
Denkinger C.M.,McGill University |
Schumacher S.G.,McGill University |
Boehme C.C.,Foundation for Innovative New Diagnostics |
And 4 more authors.
European Respiratory Journal | Year: 2014
Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is endorsed for the detection of pulmonary tuberculosis (TB). We performed a systematic review and meta-analysis to assess the accuracy of Xpert for the detection of extrapulmonary TB. We searched multiple databases to October 15, 2013. We determined the accuracy of Xpert compared with culture and a composite reference standard (CRS). We grouped data by sample type and performed meta-analyses using a bivariate random-effects model. We assessed sources of heterogeneity using meta-regression for predefined covariates. We identified 18 studies involving 4461 samples. Sample processing varied greatly among the studies. Xpert sensitivity differed substantially between sample types. In lymph node tissues or aspirates, Xpert pooled sensitivity was 83.1% (95% CI 71.4-90.7%) versus culture and 81.2% (95% CI 72.4-87.7%) versus CRS. In cerebrospinal fluid, Xpert pooled sensitivity was 80.5% (95% CI 59.0-92.2%) against culture and 62.8% (95% CI 47.7-75.8%) against CRS. In pleural fluid, pooled sensitivity was 46.4% (95% CI 26.3-67.8%) against culture and 21.4% (95% CI 8.8-33.9%) against CRS. Xpert pooled specificity was consistently >98.7% against CRS across different sample types. Based on this systematic review, the World Health Organization now recommends Xpert over conventional tests for diagnosis of TB in lymph nodes and other tissues, and as the preferred initial test for diagnosis of TB meningitis. Copyright ©ERS 2014.
Agency: Cordis | Branch: FP7 | Program: CP-SICA | Phase: HEALTH-2007-2.3.4-1 | Award Amount: 3.41M | Year: 2009
African trypanosomiasis is in need of new diagnostic detection tools and new treatment methods. To date the widely used card agglutination test for trypanosomiasis is not very specific as the test is based on the screening for cross-reactive host antibodies. The availability of treatment for Trypanosmiasis on the other hand is limited due to the fact that only very few drugs are registered for use, and all can cause serious side effects in treated patients or animals. Hence, this project will focus on the development of new and innovative diagnosis and treatment tools, using the nanobody technology that has been developed by the coordinating partner of this network. Nanobodies are small single domain antibody fragments that have unique properties that include their capacity to recognize particular epitopes (not recognized by conventional antibodies) and their improved stability. In addition, they can be used as molecular target- or transport devices of other biological active components. As such they are excellent tools to support this project. Despite the fact that the coordinating laboratory has been a pioneer in differential molecular characterization of African trypanosomes and were involved in the initial release of diagnostic PCR methods that have now been adopted by many other research groups, this project will deliberately adopt a different approach. Indeed, in comparison to nanobody technology, PCR based diagnostics are much more costly and require an infrastructure that is hard to sustain over prolonged periods of time in African field situations. The simplicity of the nanobody technology on the other hand makes it an excellent topic for knowledge transfer. Despite its high-technology approach, the technique it will be relatively easy to be adopted by laboratories of participating African partner groups.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.2-3 | Award Amount: 4.07M | Year: 2008
Recent developments in molecular tools combined with updated epidemiological data provide novel challenges to the development of modern molecular diagnostics. The increasing threat of infections due to Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections poses important questions that call for development of integrated tools for rapid diagnosis. In the specific case of tuberculosis (TB), an integrated rapid diagnostic approach should be able to allow at the same time species identification, drug susceptibility testing and molecular typing. We propose to develop and validate a silicon-based platform for molecular biology testing consisting in a single disposable device (biochip) and on associated specific instruments (reader). This technology is able to simultaneously serve as a platform for high specificity amplification and hybridisation of selected targets, and to provide the diagnostic report within few hours. Main advancement over existing technology (i.e. Real-Time PCR) consists in the possibility to perform the test at competitive costs, using an higher number of genetic probes by integrating multiple, separate PCR chambers and medium density array (50-200 probes), with faster and more stable amplification and hybridisation reactions through optimised and controlled thermal ramps and profile. In addition to the technology development, special focus will be put on the feasibility and cost-effectiveness of such a novel tool with high technological content for application in countries with high TB, MDR- and XDR-TB incidence. In parallel to the development and validation of the chip-based diagnostic platform for TB, a feasibility study on its applicability to other poverty related diseases such as malaria, will be carried out. In summary, the present proposal aims at developing an affordable, high-tech platform for rapid molecular diagnosis applicable to TB and other infectious and poverty-related diseases