In Sub-Saharan Africa, deaths occur in 5-10% of people living with HIV during the first year after initiating antiretroviral therapy (ART), and the causes for these early deaths are not clear. Matthew Painschab, MD, member of the Institute for Global Health and Infectious Diseases, and an assistant professor of hematology, is a clinician and researcher who treats patients with hematologic malignancies in Chapel Hill and UNC Project Malawi, focusing on HIV-associated cancers. His new five-year NIH Director’s Pioneer Award will fund a multi-dimensional study to identify the barriers to pathologic diagnosis of lymphadenopathy in Malawi, which is treatable and curable if diagnosed appropriately. The study will also introduce a novel diagnostic device to detect viral DNA. A CFAR Developmental Award served as the seed money for his earlier research.
What will this funding allow you to do?
The primary focus of this study is to understand the causes of lymph node swelling and the barriers to diagnosis in people living with HIV in outlying HIV clinics in Malawi. We plan to collect basic clinical and laboratory information as well as test for tuberculosis and perform lymph node biopsies.
We then aim to use this basic clinical information to predict which patients are more likely to have tuberculosis versus lymphoma or multicentric Castleman disease, two cancers that are common in people living with HIV and have very similar symptoms to tuberculosis. Finally, and most interestingly, we are testing a novel diagnostic device, the TINY machine (Tiny Isothermal Nucleic acid quantification sYstem), which can detect viral DNA, namely from Epstein-Barr Virus and Kaposi Sarcoma-associated Herpesvirus, that is associated with lymphoma and multicentric Castleman disease. The TINY machine was developed by engineers at Cornell University and has been validated for use in Kaposi sarcoma diagnosis in sub-Saharan Africa including at UNC Project Malawi, but has not been tested previously in lymph nodes.
This device is especially exciting because it does not require electricity to run, instead it can be run using solar power or Bunsen burner, among other power sources, allowing it to reach areas with inconsistent electricity. We therefore hope to find a pattern of viruses among these patients which might allow us to more identify patients with lymphoma or multicentric Castleman disease at the point-of-care without having to wait for relatively expensive, difficult, risky, and slow diagnostic methods currently used.
How will this award impact patient care in Malawi?
Currently, 50% or more of our patients with lymphoma or multicentric Castleman disease come from the capital city, Lilongwe, despite making up only 10% of the population of the Northern and Central regions where our samples come from. We therefore believe that we are likely significantly underdiagnosing these diseases. Currently, due to the overlap in symptoms, most of these patients are assumed to have tuberculosis in a setting where tuberculosis is heartbreakingly common.
It is critical to rapidly diagnose patients with lymphoma or multicentric Castleman disease because, as we have shown in a number of previous publications, these are disease that can be treated and cured in Malawi. However, if not diagnosed and treated in a relatively rapid manner, these diseases are almost universally fatal. We therefore hope to develop an algorithm that will identify patients who are likely to have tuberculosis and those that are likely to have cancer using the point-of-care TINY system and clinical characteristics.
Why is this receiving this award so important to your research?
This is a unique and exciting grant that I am extremely privileged to receive. This award advances a research focus that is distinct from my previous work, and this will be my first time studying diagnostics and implementation science, and the first time working in peripheral health centers. It specifically supports early career investigators like myself who are focused on innovative research in comorbidities in people living with HIV, and it provides flexibility from year to year to pivot your research plan and budget based on the findings of the early years of the award. It is the first independent research award I have received and therefore marks an important milestone in my career that I can only attribute to the incredible research infrastructure and remarkable mentorship I have received over the years at UNC and at UNC Project Malawi.