Diagnostics research at the Center for Infectious Disease Research uses advanced analytical technologies and mathematical analysis to develop tools that can answer basic questions about AIDS, tuberculosis, and malaria:
(1) Among people that have been exposed to a pathogen, who will develop disease? Diagnostics that can answer this question will allow people to be treated before they get sick and can help stop the spread of the infection. These diagnostics can also reveal immune system differences between people that control their infections and people that develop disease. Understanding these differences can guide the development of new therapies.
(2) Among people that have been treated for a given disease, who will be cured? Diagnostics that can answer this question will help identify people who may need extra monitoring or need alternative treatments in order to be made healthy. These diagnostics can also identify the immune response differences between people that are cured or not cured by a given treatment. Understanding these differences can guide the development of new therapies.
(3) Among people that have been given an experimental vaccine, who will be protected? Current experimental vaccines for AIDS, tuberculosis, and malaria are not perfect; they only protect a fraction of the people that receive them - and we don’t yet know what is different about the immune responses of the protected people. Diagnostics that can answer this question will identify the immune responses the next generation of vaccines will need to activate in order to protect everyone. In the field, these diagnostics also may be used to identify people with weaker immune responses that would need additional monitoring or treatments in order to keep them from becoming infected.
WHY are diagnostics for AIDS, tuberculosis, and malaria so challenging?
The pathogens that cause AIDS (HIV), tuberculosis (Mycobacterium tuberculosis), and malaria (Plasmodium) are experts at hiding out in the body. While it is comparatively easy to directly detect these pathogens during full-blown disease, they are very hard to find during early or dormant infection stages that come before symptoms and illness.
What are the Center for Infectious Disease Research scientists measuring?
The human immune system has an extraordinary ability to sense invaders, even if these invaders sometimes outsmart the immune system and establish an infection. Immune cells constantly travel all over the body and become activated if they find something awry. These activated immune cells then travel into the blood where they become accessible for analysis. Diagnostics research at the Center for Infectious Disease Research takes advantage of these wandering sentinel cells, analyzing the state of the immune system itself when the pathogens are inaccessible. This work involves evaluating many immune parameters that can be measured in the blood, including gene activities (RNA levels), protein levels, metabolite levels, and many other factors.
How are the Center for Infectious Disease Research scientists developing these diagnostics?
The analyses combine advanced genomic and immune measurements with cutting-edge mathematical analysis. In fact, we use the same type of computer-based analyses that are now widespread in advertising and social media. Instead of mining big data to target ads to people, we are mining big clinical datasets to find the unique signatures that predict who is at risk of developing disease, who will be cured by disease treatment, and who will be protected by an experimental vaccine.
Who do the Center for Infectious Disease Research scientists collaborate with to do this work?
These problems are challenging; the diseases are global; and the answers can only be found through collaboration. The Center for Infectious Disease Research teams up with top-notch scientists from Africa, Asia, Europe, and the Americas to do this work. Collaborating scientists are biologists, immunologists, and statisticians who work side-by-side with the Center for Infectious Disease Research to ensure the maximum information is gleaned from every sample, as well as doctors and clinicians who do the extremely difficult job of running the trials and collecting precious clinical samples from the field.