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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.3-3 | Award Amount: 3.85M | Year: 2010

Over the last years, large outbreaks of Crimean Congo Hemorrhagic fever virus (CCHFV) in several European countries and neighbouring areas are on the rise. This disease poses a great threat to public health due to its high mortality rate, modes of transmission and geographical distribution. Climate changes and observation of the CCHFV vector in central Europe alarm the European community as we cannot exclude that future outbreaks will take place in non-endemic area of Europe. To date, there is no vaccine available and no selective antiviral drug for the management of the disease. The general knowledge of migration, epidemiology, re-assortment and recombination of the virus is very limited. To fill these gaps, the CCH Fever project proposes to create a multidisciplinary collaborative research environment by bringing together selected competitive advantages such as: operative capacity with appropriate high security research facilities, reference centers and clinical samples from endemic areas and an international network of experienced researchers. This multidisciplinary research consortium will facilitate the progress in several key research areas of the field. This program will mainly focus on (i) developing sensitive and biosafe state-of-art diagnostic tools for CCHFV, (ii) gathering the forces and resources in Europe to build a Biobank of clinical samples, (iii) building a comprehensive database consisting in clinical, laboratory and surveillance data, (iv) taking advantage of unique and state-of art tools to progress towards vaccine candidates and specific antivirals against this bio-threat and (v) disseminating the appropriate knowledge to the health care workers in endemic regions and contributing to capacity building. These achievements will provide tools for local and European public health authorities to prevent or counter future outbreaks and monitor the spread of the disease thanks to the established novel and unique tools and resources.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 12.17M | Year: 2015

The overall objective will be to create and mobilise an International network of high calibre centres around a strong European group of institutes selected for their appropriate expertises, to collect, amplify, characterise, standardise, authenticate, distribute and track, mammalian and other exotic viruses. The network of EVAg laboratories including 25 institutions represents an extensive range of virological disciplines. The architecture of the consortium is based on the association of capacities accessible to the partners but also to any end-users through the EVAg web-based catalogue. This concept has been elaborated and tested for its efficiency during the successful EVA project (FP7). The project will integrate more facilities dedicated to high risk pathogen (HRP) manipulation (1 in EVA, 13 in EVAg) The access to products derived from those HRP will be enhanced and for instance the production of diagnostic reagents will be facilitated. The new project will also provide access to high containment biosafety facilities to carry out in vivo studies of infectious disease using natural or models hosts, to look at prophylactic or therapeutic control measures and to develop materials for the evaluation of diagnostic tests, meaning an extensive capacity to service and to training. EVAg will also link up with other network-based virus-associated programmes that exist globally. However, looking further ahead, EVAg is conceived ultimately to be an open entity aiming at developing synergies and complementarity capabilities in such a way as to offer an improved access to researchers. This project will generate the largest collection of mammalian viruses in the world and move beyond the current state-of-the-art to provide an increasingly valuable resource and service to the worlds scientific community, including government health departments, higher education institutes, industry and, through information systems, the general public.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: KBBE-2007-1-3-06 | Award Amount: 1.12M | Year: 2008

West Nile Fever (WNF), Rift Valley Fever (RVF) and Crimean-Congo Haemorrhagic Fever (CCHF) are arthropod-borne diseases of different domestic and wild animals and can also affect humans, posing a great threat to public health because of their epidemic and zoonotic potential. Their geographical distribution has expanded in recent decades. WNF outbreaks have already occurred in Europe, CCHF is endemic in many countries including Europe. In 2000, RVF, was reported the first time outside of the African continent, cases being confirmed in Saudi Arabia and Yemen. This virgin-soil epidemic raises the threat of expansion into other parts of Asia and Europe. There is a general public concern regarding emerging zoonotic diseases which has gained new relevance in the light of global warming. This is especially true regarding the spread of vector-borne diseases such as CCHF, RVF and WNF. It is imperative to work out integrated control measures which include vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions. The anticipated project will address these areas specifically aiming at: 1) creating common knowledge on the diseases, sharing and exchanging data, expertise, experiences and scientific information; 2) maintaining and expanding surveillance systems, monitoring disease occurrence, and vaccine use; 3) introducing, distributing and harmonizing disease detection and control tools; 4) disseminating knowledge and training staff of relevant third countries; 5) interlinking different scientific disciplines which look at the problem from differrent angles. A coordinated research programme including key laboratories in Europe and neighbouring countries can address scientific questions of joint interest enabling the development of effective control measures, aimed at improving the EUs response to outbreaks of diseases.


The main objective of this research proposal is to identify and elaborate those characteristics of ENM that determine their biological hazard potential. This potential includes the ability of ENM to induce damage at the cellular, tissue, or organism levels by interacting with cellular structures leading to impairment of key cellular functions. These adverse effects may be mediated by ENM-induced alterations in gene expression and translation, but may involve also epigenetic transformation of genetic functions. We believe that it will be possible to create a set of biomarkers of ENM toxicity that are relevant in assessing and predicting the safety and toxicity of ENM across species. The ENM-organism interaction is complex and depends, not simply on the composition of ENM core, but particularly on its physico-chemical properties. In fact, important physico-chemical properties are largely governed by their surface properties. All of these factors determine the binding of different biomolecules on the surface of the ENM, the formation of a corona around the ENM core. Thus, any positive or negative biological effect of ENM in organisms may be dynamically modulated by the bio-molecule corona associated with or substituted into the ENM surface rather than the ENM on its own. The bio-molecule corona of seemingly identical ENM cores may undergo dynamic changes during their passage through different biological compartments; in other words, their biological effects are governed by this complex surface chemistry. We propose that understanding the fundamental characteristics of ENM underpinning their biological effects will provide a sound foundation with which to classify ENM according to their safety. Therefore, the overarching objective of this research is to provide a means to develop a safety classification of ENM based on an understanding of their interactions with living organisms at the molecular, cellular, and organism levels based on their material characteristics.


Lowman W.,University of Witwatersrand | Lowman W.,National Health Laboratory Services | Aithma N.,National Health Laboratory Services
Journal of Clinical Microbiology | Year: 2010

Nocardiosis is an underrecognized clinical entity in South Africa, for which interspecies epidemiological and clinical differences are poorly understood. The taxonomical state of flux and the lack of a simple antimicrobial susceptibility testing method are partly responsible. Definitive identification is molecularly based, which further complicates the study of this ubiquitous organism, as this methodology is beyond the scope of most routine diagnostic laboratories. The Etest methodology has been proposed as an alternative to the reference broth microdilution method, although there have been a limited number of comparative studies. We profiled 51 clinical isolates of aerobic actinomycetes, including 39 Nocardia species, using sequence-based (16S rRNA) identification. Broth microdilution and Etests were done concurrently on all isolates. The overall level of categorical and essential agreement for broth microdilution and Etest for the Nocardia isolates ranged from 67.5 to 100% and 46.2 to 81.6%, respectively. Very major errors were seen with amikacin, amoxicillin-clavulanate, ciprofloxacin, clarithromycin, and imipenem. For Nocardia species, uniform susceptibility to co-trimoxazole, amikacin, and linezolid was demonstrated, with a 48.8% susceptibility rate to imipenem. Nocardia farcinica (20.5%) and Nocardia cyriacigeorgica (15.4%) were the most commonly identified species among the 82% of isolates identified to species level using 16S rRNA sequences. Furthermore, drug susceptibility patterns demonstrated limited concordance with species identification. Our results suggest that, in a routine diagnostic setting, the Etest is not an acceptable alternative to the reference method of broth microdilution for antimicrobial susceptibility testing. Given the diversity and limited understanding of this group of organisms, further widespread evaluation of clinical isolates, from both clinical and diagnostic perspectives, is warranted. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Scott L.,University of Witwatersrand | Gous N.,University of Witwatersrand | Carmona S.,University of Witwatersrand | Carmona S.,National Health Laboratory Services | And 2 more authors.
Journal of Clinical Microbiology | Year: 2015

Point-of-care (POC) HIV viral load (VL) testing offers the potential to reduce turnaround times for antiretroviral therapy monitoring, offer near-patient acute HIV diagnosis in adults, extend existing centralized VL services, screen women in labor, and prompt pediatrics to early treatment. The Liat HIV Quant plasma and whole-blood assays, prerelease version, were evaluated in South Africa. The precision, accuracy, linearity, and agreement of the Liat HIV Quant whole-blood and plasma assays were compared to those of reference technologies (Roche CAP CTMv2.0 and Abbott RealTime HIV-1) on an HIV verification plasma panel (n=42) and HIV clinical specimens (n=163). HIV Quant plasma assay showed good performance, with a 2.7% similarity coefficient of variation (CV) compared to the Abbott assay and a 1.8% similarity CV compared to the Roche test on the verification panel, and 100% specificity. HIV Quant plasma had substantial agreement (pc [concordance correlation]=0.96) with Roche on clinical specimens and increased variability (pc=0.73) in the range of<3.0 log copies/ml range with the HIV Quant wholeblood assay. HIV Quant plasma assay had good linearity (2.0 to 5.0 log copies/ml; R2=0.99). Clinical sensitivity at a viral load of 1,000 copies/ml of the HIV Quant plasma and whole-blood assays compared to that of the Roche assay (n=94) was 100% (confidence interval [CI], 95.3% to 100%). The specificity of HIV Quant plasma was 88.2% (CI, 63.6% to 98.5%), and that for whole blood was 41.2% (CI, 18.4% to 67.1%). No virological failure (downward misclassification) was missed. Liat HIV Quant plasma assay can be interchanged with existing VL technology in South Africa. Liat HIV Quant whole-blood assay would be advantageous for POC early infant diagnosis at birth and adult adherence monitoring and needs to be evaluated further in this clinical context. LIAT cartridges currently require cold storage, but the technology is user-friendly and robust. Clinical cost and implementation modeling is required. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


Sherman G.G.,University of Witwatersrand | Sherman G.G.,National Health Laboratory Services | Sherman G.G.,Wits Health Consortium | Lilian R.R.,Wits Health Consortium | Coovadia A.H.,University of Witwatersrand
Pediatric Infectious Disease Journal | Year: 2012

BACKGROUND: Rapid tests have the potential to improve the identification of HIV-infected children in resource-limited settings. However, they remain underutilized because of a lack of data on their performance in the field using whole blood specimens. This study aimed to assess the accuracy of rapid tests for detecting HIV exposure, excluding HIV infection in HIV-exposed infants, and diagnosing HIV infection in children older than 18 months of age. METHODS: Five rapid tests (First Response, Pareekshak, Determine, Smart Check, and Insti) were performed using whole blood from children enrolled in a multisite, cross-sectional study in South Africa. HIV enzyme-linked immunosorbent assay and DNA polymerase chain reaction results defined HIV exposure and infection, respectively, and were the standards used for comparison. RESULTS: Of the 851 children enrolled, 186 (21.9%) were infected with HIV. For detecting HIV exposure, Determine demonstrated the highest sensitivity of 99.3% (95% confidence interval, 98.0-99.8) in early infancy, but sensitivity declined with age as seroreversion occurred. After 8 months of age, all tests except First Response excluded HIV infection in 82% to 100% of HIV-uninfected infants and, in conjunction with a clinical assessment, did not miss any HIV-infected children. Insti was the only test that detected all HIV-infected infants, albeit on the smallest number of samples. The performance of all rapid tests in children older than 18 months of age was similar to that in adults. CONCLUSIONS: Determine was the only rapid test that had a high enough sensitivity for detecting HIV exposure in early infancy, but it identified seroreversion later in life than the other tests. Insti warrants further investigation for both indications. Copyright © 2012 by Lippincott Williams & Wilkins.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NMP-30-2015 | Award Amount: 9.83M | Year: 2016

The objective of the caLIBRAte project is to establish a state-of-the-art versatile Risk Governance framework for assessment and management of human and environmental risks of MN and MN-enabled products. The framework will be a web-based system-of-systems linking different models and methods for: 1) screening of apparent and perceived risks and trends in nanotechnology, 2) control banding, qualitative and fully integrated predictive quantitative risk assessment operational at different information levels, 3) safety-by-design and multi-criteria decision support methods, 4) risk surveillance, -management and -guidance documents. The risk management framework will support assessments of emerging and existing MN and MN-enabled products following the recent ISO31000 risk governance framework, as well as safety in innovation by matching models to the principle innovation steps in the Cooper Stage-Gate product innovation model Control banding tools and quantitative models will be subject to sensitivity analysis and performance testing followed by a revision as needed. After revision the models will again be analyzed by sensitivity testing, calibration, performance tested to establish the uncertainties. After calibration, the models will be part of the framework, which will be demonstrated by case studies. Stakeholders will be involved for defining the user requirements of the framework and will receive training in the framework at the end. The caLIBRAte project proposal answers to the call of NMP30-2015: Next generation tools for risk governance of MNs. The project is specifically designed to address the key challenges defined in the scope of the call text. There is particular focus on model revision, calibration and demonstration of existing models and methods that support the risk governance framework in regards to safe innovation and already implemented nanomaterials. Next generation computational exposure assessment and -toxicology is anticipated in the framework


Mans J.,University of Pretoria | Netshikweta R.,University of Pretoria | Magwalivha M.,University of Pretoria | Van Zyl W.B.,University of Pretoria | And 2 more authors.
Epidemiology and Infection | Year: 2013

This study aimed to assess norovirus (NoV) contamination and genotype diversity in surface water in Gauteng, South Africa. Between January 2008 and December 2010, three rivers, namely Klip, Suikerbosrant, and Rietspruit were monitored for NoV genogroup (G)I and GII. Viruses were recovered using the glass wool adsorption-elution technique and detected by real-time reverse transcription-polymerase chain reaction. From 2008 to 2010, NoVs were detected in 66% (70/106) of Klip river samples. The Rietspruit and Suikerbosrant rivers were contaminated with NoV in 95% (20/21) and 21% (5/24) of samples, respectively. NoV-positive samples comprised of 33% GI, 29% GII and 38% of both GI and GII strains. Based on partial capsid gene analysis (region C), 16 NoV genotypes (6 GI, 10 GII) were identified. The major genotypes detected were GI.4, GI.5 and GII.4. These rivers could be a potential source of NoV infection for communities using the water for domestic or recreational purposes. © 2012 Cambridge University Press.


Osman M.,City Health | Simpson J.A.,National Health Laboratory Services | Simpson J.A.,University of Cape Town | Caldwell J.,City Health | And 3 more authors.
Journal of Clinical Microbiology | Year: 2014

A recent Cochrane review estimated GeneXpert MTB/RIF specificity for rifampin resistance as 98% (95% confidence interval [CI], 97 to 99), based on results from earlier test versions. The measured positive predictive value of the new generation test from programmatic implementation in Cape Town, South Africa, was 99.5% (95% CI, 98.5 to 100), confirming excellent specificity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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