DEVELOPMENT OF ENHANCED SURVEILLANCE TOOLS FOR LOW-RESOURCE MALARIA CONTROL AND ELIMINATION

Malaria is a lethal infectious disease which is estimated to cause 229,000,000 cases worldwide, with 409,000 deaths. In this work, two methods are explored to enhance the efficacy and utility of malaria control and elimination efforts directly at the point of care. In the first, a paper-based immobilized metal separation system is functionalized and optimized for use in malaria sample preparation. The paper membrane is used to enhance the sensitivity of rapid diagnostic tests (RDTs) specific for the two primary malarial biomarkers: histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (PLDH). The immobilized metal-enhanced cellulose was found to improve HRP2-specific tests by 15.8-fold, decreasing the limit of detection for these tests from 108.6 parasites/μL of blood to 6.88 parasites/μL. For non-histidine-rich biomarkers such as PLDH, commercial tests were found to be only moderately enhanced, with a 1.81-fold enhancement determined based on the slope of the linear regression for each method (e.g. enhanced versus unenhanced). The second method consists of a mobile phone application designed to enhance data collection for RDTs. This mobile health and treatment application, or mHAT, was found to perform well compared to both the field and the laboratory gold standards for RDT evaluation. The application was observed to have a limit of detection of 23.2 parasites/μL using iOS hardware, and 20.9 parasites/μL using Android hardware, which was comparable to the calculated limit of detection for a commercially-available benchtop test reader. Furthermore, the mHAT app was found to perform with 94.6% sensitivity and 88.6% specificity when compared to visual analysis by a trained professional in the field. The projects presented in this work look to solve the problems presented by disease surveillance and control in highly endemic areas, with a focus on providing tools that will be the most usable and useful to the communities and healthcare systems most significantly affected by malaria. These tools have the potential to increase the accuracy and efficacy of malaria surveillance efforts, thus ending a years-long plateau of progress.