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.
The proposed research is relevant to public health because it will provide clinicians and healthcare workers with a rapid, quantitative point-of-care malaria tes that will aid them in identifying children with cerebral malaria and triaging patients with apparently uncomplicated malaria, ultimately improving their clinical care. Thus, the proposed research is relevant to both NIAID and NIBIB's missions by advancing malaria research and improving human health through the development and application of a new biomedical technology that bridges the life and physical sciences.
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