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，对疟疾的免疫力是逐渐和不定期获得的，这给诊断和治疗带来了两个重大困难：1）感染疟疾的个体可能没有症状，相反，有症状的疟疾感染个体可能因与疟疾无关的原因而患病，和2）一部分患有轻度疟疾疾病的人在接受临床护理时将发展为严重疾病。在这个时间点，不可能预测哪些患者有恶化的风险，这极大地使临床护理复杂化。 本申请人和其他人最近的研究已经证明了定量的恶性疟原虫富组氨酸蛋白2（PfHRP 2）测量用于（a）区分患有脑型疟疾（CM）的寄生虫血症昏迷儿童与具有偶然寄生虫血症和非疟疾原因的昏迷的昏迷儿童，和（B）鉴定哪些患有明显无并发症的疟疾的儿童可能进展为更严重的疾病的效用。目前，PfHRP 2定量需要酶联免疫吸附测定（ELISA）测试，其昂贵、费力且耗时。PfHRP 2的疟疾快速诊断测试是可用的，但这些测定仅提供定性结果（“阳性”与“阴性”），并且对于上述适应症没有用处。 长期目标是改善CM的临床诊断和无并发症疟疾患者的分诊。该项目的主要目标是开发和验证一个现场准备的移动的手机平台，用于快速，定量PfHRP 2测量。申请人的初步临床数据以及将小型化检测方案集成到传统移动的电话上以快速定量测量人血清和血液样本的PfHRP 2的可行性支持了所提出的研究的基本原理。 将通过追求三个具体目标开发和验证优化的第二代原型器械：1）开发用于定量PfHRP 2检测的现场就绪的移动的电话平台; 2）验证和优化器械功能; 3）评价器械在现场环境中确定CM患者的CM诊断的有效性。这种方法是创新的，因为它将微流体与快速定量电化学检测方案集成到紧凑的移动的电话平台上，并且它是重要的，因为它将改善脑疟疾预后和治疗，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.