Detection of infectious diseases in febrile patients in field studies in Gabon using molecular assays including next generation diagnostics

Lead Research Organisation: St George's University of London
Department Name: Institute of Infection & Immunity

Abstract

Acute febrile illness is characterised by a rapid on-set fever, which is defined as an abnormally high-body temperature, accompanied by headache, chills, and muscle pain. It is caused by a variety of different organisms, which contribute to a substantial rate of morbidity and mortality in tropical regions. A current, unmet need exists in diagnosing febrile patients with diseases such as malaria and dengue due to extensive overlapping of clinical signs and symptoms. This makes it difficult for clinicians to diagnose the problem and often results in delayed treatment, and many preventable deaths occur due to patients not receiving the right therapy. In malaria and dengue endemic areas, patients admitted with fever will generally be administered with anti-malarial drugs or antibiotics until a definitive diagnosis is obtained. Not only is this detrimental to the patient but the incorrect and overuse of these drugs has a major impact to the global problem were facing with resistance.

The current tools demonstrating the greatest diagnostic reliability are currently not suitable for developing countries as they are costly, complex, require a constant power supply, and cannot be used at point-of-care. Rapid diagnostic tests (RDTs) are cheap and easy to use at point-of-care. Though they often lack sensitivity and the ability to diagnose more than one pathogen, RDTs can ensure that patients receive the correct treatment in a timely manner. A malaria RDT currently available has contributed to a drastic reduction in malaria related deaths. Despite this, overdiagnosis of malaria is still recognised along with the overtreatment of acute febrile illnesses. This necessitates the need for a test that can accurately diagnose fever causing pathogens and treat accordingly.

With this in mind, the project proposes the use of modern molecular techniques to help develop a test that can accurately diagnose patients with acute febrile illness in the Gabon region. Thanks to a collaboration between St. Georges, University of London and a close industrial partner this can be made possible. Using their diagnostic platform, a point of care assay can be developed which detects DNA in the blood specific for a range of pathogens within 15 minutes. This DNA detection cartridge will be optimised to accurately diagnose a range of different febrile related pathogens such as malaria and other arboviruses to ensure the patient receives the correct treatment.

This project will involve the following MRC core skills:
-Quantitative: epidemiological analysis of fever related diseases in the Gabon region, statistical and bioinformatical analysis of data. I have previous experience in bioinformatics, and I am currently undertaking training in epidemiology and statistics for public health to further develop my skills in these areas.
-Interdisciplinary: As this project has the potential to provide a real health benefit, it will require collaborations with translational research groups, non-governmental groups and biotechnology companies to provide the foundations to administer this tool in a clinical setting. My previous experience working in industry will benefit greatly here and am currently in the process of converting to an iCASE studentship which will involve a three-month placement working with our diagnostic partner to help make this assay compatible with their handheld diagnostic platform.

This project is of crucial importance due to the urgent demand for a cheap, easy to use and rapid diagnostic test applicable in a resource-limited setting. A test that is able to accurately differentiate between the organisms responsible for fever would not only have a significant impact on the clinical outcome of those affected but will also help to combat drug resistance as it means patients are receiving the correct treatment.

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