Low Cost Multiplexed DNA Diagnostic Sensors for Infectious Diseases

用于传染病的低成本多重 DNA 诊断传感器

• 批准号: 2292681
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2292681
• 关键词: Low; Cost; Multiplexed; DNA; Diagnostic

Nearly 260m people are infected with schistosomiasis, with >90% ofinfections found in sub-Saharan Africa. Worldwide ~3.2b people areat risk of malaria, many also in Sub-Saharan Africa. Both diseasesare endemic in the same rural locations and there is difficulty indifferentiating symptoms and informing correct diagnosis andtreatment. Incorrect diagnosis is known to lead to unnecessarydispensation of drugs leading to increased probability of drugresistance.Professor Cooper has developed a paper-based multiplexed DNAmalaria diagnostic device that exploits novel hot wax printing tointegrate sample preparation and microfluidic flows. The device candifferentiate between three species of malaria causing plasmodiumand has now been tested using whole patient blood samples in thelaboratory.The aim of this project is to develop a novel blood-based multiplextest that can, from a single drop of blood, distinguish between malariaand schistosomiasis and identify drug resistant microbes. This newhighly sensitive diagnostic device will enable field workers to monitortreatment outcomes, with the specific aims of(i) providing correct diagnosis;(ii) preventing re-emergence of infections following localtreatment;(iii) reducing resistance by ensuring effective and appropriatetreatment.Field-testing will be carried out operator double-blind field-testing inEast Africa. The samples will also be characterised using(i) the paper based test;(ii) through microscopy in-the-field(iii) will also be stored (as dried blood spots) for retrospectivelaboratory based molecular testing in Glasgow.Ethics permissions will be obtained.Additional Information: The schistosoma live in the hepatic portal veinand shed cells into the blood. Malaria parasites (Plasmodium sp.) livewith red blood cells as part of their lifecycle. We will therefore alsodevelop a blood based assay, where DNA will be detected from afingerpick of blood. The assay will again be configured as a low cost,paper based assay and will be developed as a duplex, enabling bothmalaria and bliharzia (schistosomiasis) to be detected at the sametime. This will guide appropriate treatment for febrile patientspresenting themselves at field clinics.Benefits:This project is also aligned with the Health priority of the GlobalChallenge Fund, which aims 'to tackle diseases, strengthen healthsystems and reach the worlds' most vulnerable'. Indeed, according tothe latest WHO estimates, at least 258 million people have requiredtreatment for schistosomiasis in 2014, with 61.6 million peoplereported to be treated. 90% of those requiring treatment live in Africa.In children, schistosomiasis causes anaemia, stunted growth andreduced ability to learn. Treatment usually reverses these effects, butits efficacy needs to be monitored to establish cure and adapttherapy. If untreated, chronic disease affects people's ability to workand can result in death. The disease burden has been estimated toaccount for 4.5 million DALYs (disability affected life years).Mass drug administration of praziquantel has been delivered throughNational Control Programmes, e.g. in Uganda for over a decade.Hotspots of infection have been detected, where prevalence,intensity and associated morbidity are now higher than they were atbaseline.

近2.6亿人感染血吸虫病，其中超过90%的感染发生在撒哈拉以南非洲。全世界约有32亿人面临疟疾风险，其中许多人也在撒哈拉以南非洲。这两种疾病都在同一农村地区流行，很难区分症状并提供正确的诊断和治疗。众所周知，不正确的诊断会导致不必要的药物分配，从而增加耐药的可能性。库珀教授开发了一种基于纸张的多路复用DNA疟疾诊断设备，该设备利用新颖的热蜡印刷来整合样品制备和微流体流动。该设备可以区分三种引起疟原虫的疟疾，现在已经在实验室用病人的全血样本进行了测试。该项目的目的是开发一种新的基于血液的多重测试，可以从一滴血中区分疟疾和血吸虫病，并识别耐药微生物。这一新的高灵敏度诊断设备将使现场工作人员能够监测治疗结果，其具体目标是：（i）提供正确的诊断;（ii）防止当地治疗后再次出现感染;（iii）通过确保有效和适当的治疗减少耐药性。这些样本也将通过（i）纸基检测;（ii）现场显微镜检查进行表征;（iii）还将储存（作为干血斑），用于格拉斯哥的回顾性实验室分子检测。将获得伦理许可。附加信息：肝细胞瘤生活在肝门静脉中，并将细胞脱落到血液中。疟原虫（Plasmodium sp.）与红细胞一起生活作为其生命周期的一部分。因此，我们还将开发一种基于血液的检测方法，从一次采集的血液中检测DNA。该检测试剂盒将再次被配置为低成本、基于纸的检测试剂盒，并将被开发为双链体，使疟疾和血吸虫病（血吸虫病）能够同时检测。这将指导在现场诊所就诊的发热患者进行适当的治疗。好处：该项目也与全球挑战基金的健康优先事项保持一致，该基金旨在“应对疾病，加强卫生系统，并覆盖世界上”最脆弱的人“。事实上，根据世卫组织的最新估计，2014年至少有2.58亿人需要血吸虫病治疗，据报道有6160万人接受了治疗。90%需要治疗的人生活在非洲。血吸虫病会导致儿童贫血、发育迟缓和学习能力下降。治疗通常会逆转这些效应，但需要监测其疗效以确定治愈和适应性治疗。如果不治疗，慢性病会影响人们的工作能力，并可能导致死亡。据估计，疾病负担达450万残疾影响生命年，通过国家控制方案提供大规模吡喹酮药物管理，例如在乌干达已有十多年，发现了感染热点，其流行率、严重程度和相关发病率现在高于基线。