Malaria is a major health threat, especially for those in regions of the world without access to advanced health care. But Joseph Conrad ’00, a research assistant professor with the Wright Research Group at Vanderbilt University, is part of an international team using 3D printers to research and develop enhanced rapid diagnostic tests (RDT) for the disease.
Similar in function to a home pregnancy test, malaria RDTs are simple devices used to quickly diagnose infection without sophisticated lab facilities. They are developing technologies that improve the sensitivity of existing rapid tests to provide clear diagnosis of malaria even in the absence of symptomatic infection.
“Existing rapid diagnostic tests are designed to detect the presence of a protein in a small volume of blood,” Conrad explains. “The protein is produced by malaria parasites as they grow, and it’s a specific marker of infection. In individuals with high numbers of parasite in their blood, there is a high concentration of the protein. In individuals with low numbers of parasite in their blood, there isn’t so much protein, and the rapid diagnostic tests have trouble identifying its presence in the small volumes of blood they are designed to assess.
“Our approach and device use magnetic beads to capture the malaria protein from a relatively larger blood specimen than can be used in an RDT alone,” he continues. “The magnetic beads with the protein attached can then be collected using a strong, external magnet and deposited directly onto a commercially available rapid diagnostic test. The test can then be developed normally. Our device facilitates both the chemical and physical steps in this specimen processing routine. It produces positive test results at much lower levels of malaria protein than a rapid test without enhancement.”
Malaria RDTs are often used to quickly screen for malaria infection, and while they are efficient to use in places where microscopes or DNA testing aren’t easily accessible, the rapid tests aren’t sensitive enough to detect very low levels of malaria.
In countries like Zambia where malaria control efforts are advancing, individuals with symptomatic (high-level) malaria infection are being successfully identified and treated for the illness. However, with existing tests, individuals with asymptomatic (low-level) disease may be left undiagnosed and can continue to transmit malaria to others. Conrad and other members of his team at Vanderbilt intend to fill this gap by improving the sensitivity of the tried and true malaria RDTs to identify low-level infections.
Their international team is housed within the Vanderbilt-Zambia Network for Global Health Technologies (VZNIGHT), a post-doctoral research and training program. Conrad works closely with a resident researcher, Priscilla Lumano-Mulenga, a VZNIGHT Fellow and a Zambian physician and infectious diseases specialist. Together, using 3D printer technology, these researchers can fast-track device design in advanced laboratories and deploy designs to rural Zambia where they can perform field trials in realistic conditions.
“We believe we’re one of the first groups to implement device design and field testing in low resource settings using 3D printing technology,” Conrad says. “Because Nashville doesn’t have endemic malaria, our development and field testing teams are separated by long distances and difficult logistical connections. Device design typically uses an iterative ‘design, test, re-design, repeat’ sort of approach. In the case of low resource diagnostic technologies, this often results in devices that work well in nicely appointed laboratories and then fail to perform from the back of a motorcycle in rural areas.
“We don’t aim to revolutionize this design paradigm, but the practicalities of work spaces in different hemispheres means that there could be a ton of time between iterative steps. Using 3D printers in both spaces, we can design and test a device in our Vanderbilt labs as well as print and concurrently test the design in the field in Zambia. Receiving feedback and integrating it into subsequent redesign steps can move at the speed of email rather than the speed of FedEx.”
Malaria isn’t the only disease that can be combated with this technology. With funding from the Fogarty International Center at the National Institutes of Health, Conrad is expanding work on this device to include HIV rapid tests for early infant diagnosis. Others are developing applications for rapid Ebola diagnostics. Their work is also supported by the Bill and Melinda Gates Foundation.
“My global health work began as a Peace Corps Volunteer in Zambia where I contributed to a variety of HIV and AIDS education efforts, and I’ve been fortunate to have opportunities throughout my research training to work in low resource settings from Haiti to China to Zambia. Training in HIV Immunology and epidemiology and global health provide useful context for our ongoing efforts to develop low resource diagnostics. But my academic career in international, biomedical research really has its roots in the Centre College classrooms and offices of Young, Olin and Crounse and the BMB and International Relations courses I took there.”
To see more details of how this diverse team of researchers is addressing the needs of low resource settings with high technology approaches, watch this video produced by Vanderbilt University.
by Cindy Long