Malaria is a deadly disease transmitted by mosquito bites. Every year, many millions of people in developing areas are affected by this disease. Children under 5 are most vulnerable to malaria. Great strides have been made to develop vaccines and medicines to prevent and treat malaria. The number of annual malaria deaths has decreased by about 85% in the past 100 years. This said, malaria is still endemic in 78 countries. One of the great challenges to further eradication of this disease is detection of subclinical/asymptomatic infections, especially in large rural areas in the developing world. Molecular methods such as PCR or LAMP assays can detect these infections, but they require equipment and expertise which are best suited to the laboratory environment. Portable rapid antigen tests are generally well suited for use in remote areas, but they lack the required sensitivity to detect many low-level infections. Recent reports indicate that rapid antigen tests miss up to 98% of the subclinical cases identified using a LAMP assay on the same samples. Also, many malaria tests require extensive sample prep which is very difficult to perform in remote locations. The overall goal of this project is to create a rugged, portable lateral flow assay to detect malaria. These types of assays are well suited for field use because they do not require equipment and have a simple visual readout. Our test will use specially-engineered sample pads and cassette design to process blood samples within the device - this feature eliminates the need for complicated sample prep in the field. Unlike current rapid diagnostics based on antibody/antigen interactions, our assay utilizes a malarial biomarker (called hemozoin) to create a visual signal. Our test uses the iron atoms within the hemozoin to catalyze the labeling of gold nanoparticles. Our catalytic reaction scheme can generate many labeled particles from each analyte, thereby creating strong signal amplification. The signal amplification will greatly improve the detection sensitivity of our device compared other rapid diagnostic tests and permit detection of low-level subclinical infections in the field. We believe that our unique lateral flow assay device will be an important tool in the ongoing fight to eradicate malaria. Specific Aim #1: Construct a lateral flow test to detect hemozoin. Specific Aim #2: Develop an integrated lateral flow assay device to process blood samples and perform the test. Specific Aim #3: Detect infected cells in whole blood using a novel hemozoin-based lateral flow assay.
Public Health Relevance Statement: Narrative Malaria is a deadly disease caused by mosquitos which kills many thousands of children every year. A great deal of progress has been made in the last century in the fight against malaria, but many people in the developing world are still at risk. Existing rapid diagnostic tests are not sensitive enough to detect infected people who are asymptomatic. In Phase I, we will develop a new kind lateral flow diagnostic test to detect asymptomatic malaria infections. Terms:
