Development of a nanozyme-based immunoassay for rapid and sensitive detection of malaria transmission competency
File(s)
Author(s)
Haghighi, Tabasom
Type
Thesis
Abstract
Malaria is the most significant parasitic disease in humans and it claims the lives of more children worldwide than any other infectious disease. A device for the quick and accurate detection of individuals capable of transmitting malaria, including asymptomatic parasite carriers, would be a key new technology to help revive prevention, control and elimination strategies for malaria. This thesis presents the development of such a novel rapid diagnostic test for identifying malaria transmission competent individuals. Gametocytes are the sexual stages of the parasite’s life cycle and they are solely responsible for malaria transmission from humans back to the mosquito vector. Once activated after mosquito uptake, gametocytes turn into gametes, which is accompanied by outer membrane rupture and protein release. Two of these proteins, G377 and MTRAP, were selected in this thesis to serve as novel biomarkers of malaria transmission potential. By incorporating enzyme-mimicking platinum-nanocatalysts (PtNCs) as the signal-generating labels, highly sensitive and robust nanozyme-linked immunosorbent assays (NLISA) were fabricated in a plate-based format. The performance, including the sensitivity and specificity of the developed assays, was assessed in vitro through the analysis of parasite culture samples. The preliminary clinical trial validation of the designed assays further revealed the suitability of the assays in distinguishing malaria-positive from malaria-negative individuals. The assay was then translated into a multiplexed immunochromatographic assay format for the detection of both the G377 protein and a well-known malaria disease biomarker called HRP2, in a single test strip. By facilitating the detection of both the symptom-causing stages of the parasite (asexual forms via HRP2) as well as the transmission potential of an individual (gametocyte activation via G377), this multiplexed rapid diagnostic test has the potential to aid in achieving a malaria-free world.
Version
Open Access
Date Issued
2023-03-13
Date Awarded
01/06/2023
License URL
Advisor
Stevens, Molly
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)