Development of Platform Technologies and Sample Preparation Methods to Improve Diagnosis of the “Big Three” Infectious Diseases of Poverty

Abstract

The three diseases most commonly linked to poverty—malaria, tuberculosis (TB), and HIV/AIDS—are the cause of 8.7 million deaths globally each year. Early and accurate diagnosis of these infectious disease is critically important to patient outcome in low-resource settings. It can prevent the transmission of disease and mitigate the indiscriminate use of antibiotics, which contributes greatly to antibiotic resistance. Of the current diagnostic techniques, Lateral flow assays (LFAs) have emerged as the ideal point-of-care (POC) diagnostic because they are rapid, inexpensive, easy to use, and can be deployed to resource-poor settings in mass quantities. However, malaria LFAs are limited by their sensitivity and TB LFAs are limited by their specificity. Further, LFA technology does not lend itself to being able to enumerate CD4 cells to monitor HIV treatment. The focus of my dissertation work was developing strategies to satisfy these diagnostic limitations. We have developed sample preparation tools to improve to the sensitivity of malaria tests to detect an estimated 95% of infectious disease carriers. As part of developing a next generation tuberculosis LFA, we employed a new molecular recognition element to increase TB test specificity, enabling the differentiation between mycobacterium species. Finally, in collaboration with biomedical engineers we developed a prototype low-resource diagnostic instrument that automates a novel self-contained CD4 enumeration assay for use in HIV- endemic areas.