Fellowship Site: Philanjalo, South Africa
U.S. Institution: Yale University School of Medicine
Project Title: MIF Polymorphisms and TB Disease Risk and Outcome in KwaZulu-Natal, South Africa
M. tuberculosis infects over one-third of the world’s population and tuberculosis (TB) remains a major global health problem in both HIV-positive and negative populations. Global TB control is complicated by the increasing numbers and rates of multiple drug resistant (MDR) TB and extensively drug resistant (XDR) TB, with extremely high disease severity and mortality. KwaZulu-Natal, South Africa has a high burden of TB/HIV co infection, particularly with MDR and XDR TB. A striking feature of these epidemics is differential treatment success and mortality associated with drug susceptible (DS), MDR, and XDR TB. While these are in part related to clinical features, it is additionally important to document the role of the immune system in these differences.
The cytokine macrophage migratory inhibition factor (MIF) is an upstream regulator of the host immune response. The MIF gene has several polymorphisms in humans that code for high, medium, and low MIF production. Varied MIF production has been associated with severity of infectious diseases including TB (Das, PNAS, 2013). Dr. Bucala’s laboratory at Yale has recently shown that low expressers of MIF were 2.4 times more frequently identified among patients with TB bacteremia than those without in a Ugandan cohort (Das, JID, 2013).
My study is a cross-sectional study designed to quantify the MIF gene polymorphisms and MIF cytokine levels in patients who present with active pulmonary TB and compare them to controls with no active TB disease. We will enroll patients presenting with TB symptoms at three clinics in KwaZulu-Natal, obtain blood draws, and sequence DNA and quantify the levels of MIF cytokines.