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

急性发热病的特征是在片场迅速发烧，定义为异常高的体温，伴有头痛、寒战和肌肉疼痛。它是由各种不同的生物体引起的，这些生物体在热带地区造成了相当大的发病率和死亡率。由于临床体征和症状的广泛重叠，目前在诊断患有疟疾和登革热等疾病的发烧患者方面存在未得到满足的需求。这使得临床医生很难诊断出这个问题，并经常导致延迟治疗，许多可预防的死亡是由于患者没有接受正确的治疗而发生的。在疟疾和登革热流行地区，入院的发烧患者通常会接受抗疟疾药物或抗生素治疗，直到得到明确诊断。这不仅对患者有害，而且这些药物的不正确和过度使用对面临耐药性的全球问题有重大影响。目前显示出最高诊断可靠性的工具目前不适合发展中国家，因为它们昂贵、复杂、需要持续的电力供应，并且不能在护理点使用。快速诊断测试(RDT)价格便宜，易于在医疗保健地点使用。尽管RDT往往缺乏敏感性和诊断不止一种病原体的能力，但它们可以确保患者得到及时正确的治疗。现有的疟疾RDT大大减少了与疟疾有关的死亡。尽管如此，疟疾的过度诊断仍然与急性发热性疾病的过度治疗一起被认识到。这就需要一种能够准确诊断发热病原体并进行相应治疗的检测方法。考虑到这一点，该项目建议使用现代分子技术来帮助开发一种可以准确诊断加蓬地区急性发热病患者的检测方法。由于圣乔治大学、伦敦大学和一个密切的工业合作伙伴之间的合作，这一点得以实现。使用他们的诊断平台，可以开发出一种护理点分析，在15分钟内检测血液中针对一系列病原体的DNA。这种DNA检测盒将经过优化，以准确诊断一系列不同的与发热有关的病原体，如疟疾和其他虫媒病毒，以确保患者得到正确的治疗。该项目将涉及以下MRC核心技能：定量：加蓬地区与发热有关的疾病的流行病学分析、数据的统计和生物信息分析。我以前在生物信息学方面有经验，目前正在接受流行病学和公共卫生统计学方面的培训，以进一步发展我在这些领域的技能。-跨学科：由于这个项目有可能提供真正的健康益处，它将需要与翻译研究小组、非政府组织和生物技术公司合作，为在临床环境中管理这一工具提供基础。我之前在工业领域的工作经验将使我在这里受益匪浅，目前我正在转换为iCASE学生，这将包括与我们的诊断合作伙伴一起进行为期三个月的实习，以帮助使该检测与他们的手持诊断平台兼容。由于对适用于资源有限的廉价、易用和快速诊断测试的迫切需求，该项目至关重要。一种能够准确区分引起发烧的微生物的检测方法，不仅将对患者的临床结果产生重大影响，还将有助于对抗耐药性，因为这意味着患者正在接受正确的治疗。

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.