Rapid in-field malaria diagnosis, prognosis and monitoring using a mobile phone

 描述：疟疾是世界上最致命的传染病之一。在疟疾流行地区，对疟疾疾病的免疫力是逐渐和不规律地获得的，这在诊断和治疗方面造成了两个重大困难：1)感染疟疾的人可能没有症状，相反，感染疟疾的有症状的人可能会因为与疟疾无关的原因患病，以及2)部分患有轻度疟疾的临床护理人员将进展为严重疾病。在这个时间点上，我无法预测哪些患者有恶化的风险，这极大地增加了临床护理的复杂性。申请人和其他人最近的研究表明，定量测量恶性疟原虫富含组氨酸蛋白2(PfHRP2)可用于(A)区分患有脑型疟疾的寄生虫性昏迷儿童(CM)与患有偶发性寄生虫血症和昏迷的非疟疾原因的昏迷儿童，以及(B)确定哪些患有明显不复杂的疟疾的儿童可能进展为更严重的疾病。目前，PfHRP2的定量需要用酶联免疫吸附试验(EL ISA)进行检测，这种方法昂贵、费时、费力。PfHRP2疟疾快速诊断测试是可用的，但这些测试只提供定性结果(“阳性”与“阴性”)，对上述适应症没有用处。长期目标是改善CM的临床诊断和对无并发症疟疾患者的分类。该项目的主要目标是开发和验证一个可现场使用的移动电话平台，用于快速、定量地测量PfHRP2。申请者的初步临床数据，以及将微型检测方案集成到传统移动电话以快速、定量地测量人类血清和血液样本PfHRP2的可行性，支持了拟议研究的基本原理。将开发和验证优化的第二代原型设备，以追求三个具体目标：1)开发一个现场就绪的移动电话平台，用于PfHRP2的定量检测；2)验证和优化设备功能；3)评估设备的有效性，以在现场环境下确定CM患者的CM诊断。这种方法是创新的，因为它将微流控技术与快速、定量的电化学检测方案集成到一个紧凑的移动电话平台上，其重要意义在于它将改善脑型疟疾的预后和治疗，从而有助于降低疟疾相关的发病率和死亡率。

 DESCRIPTION: Malaria is one of the most deadly infectious diseases in the world. Immunity to malaria illness is acquired gradually and irregularly in malaria-endemic areas and this creates two significant difficulties in its diagnosis and treatment: 1) Individuals who are infected with malaria may be asymptomatic, and conversely, symptomatic individuals with malaria infections may be ill for reasons unrelated to malaria, and 2) A proportion of individuals who present for clinical care with a mild malaria illness will progress to severe disease. At this point in time, i is not possible to predict which patients are at risk of deteriorating, and this greatly complicates clinical care. Recent studies by the applicants and others have demonstrated the utility of quantitative Plasmodium falciparum histidine-rich protein 2 (PfHRP2) measurements for (a) distinguishing parasitemic comatose children with cerebral malaria (CM) from comatose children with incidental parasitemia and a non-malarial cause of coma, and (b) identifying which children with apparently uncomplicated malaria are likely to progress to a more serious illness. Currently, PfHRP2 quantification requires an enzyme-linked immunosorbent assay (ELISA) test which is expensive, laborious and time-consuming. Malaria rapid diagnostic tests for PfHRP2 are available, but these assays only provide qualitative results ("positive" vs. "negative") and are no useful for the indications above. The long-term goal is to improve the clinical diagnosis of CM and the triage of patients with uncomplicated malaria. The primary objective of this project is to develop and validate a field-ready mobile phone platform for rapid, quantitative PfHRP2 measurements. The rationale for the proposed research is supported by the applicants' preliminary clinical data, and the feasibility of integrating a miniaturized detection scheme onto conventional mobile phone for rapid, quantitative PfHRP2 measurements of human serum and blood samples. An optimized second-generation prototype device will be developed and validated by pursuing three specific aims: 1) Develop a field-ready, mobile phone platform for quantitative PfHRP2 detection; 2) Validate and optimize device functionality; 3) Evaluate device effectiveness for determining CM diagnosis in patients with CM in field settings. This approach is innovative because it integrates microfluidics with a rapid, quantitative electrochemical detection scheme onto a compact mobile phone platform, and it is significant because is it will improve cerebral malaria prognosis and treatment, and thus, help to reduce malaria-related morbidity and mortality.