Iron homeostasis and progression to pulmonary tuberculosis disease among household contacts

Early identification of individuals at risk for progressing to active tuberculosis (TB) disease may limit new transmission and improve clinical outcomes. Evidence indicates altered iron homeostasis may identify those at greater risk of disease progression in HIV co-infection. We aimed to investigate iron homeostasis biomarkers as risk factors for progression to TB. Archived plasma samples were analyzed from household contacts of pulmonary TB index cases in The Gambia. Contacts were classified as asymptomatic non-progressors (n = 17) or TB-progressors (n = 10), which included two HIV-infected participants. Iron homeostasis (hemoglobin, ferritin, hepcidin, soluble transferrin receptor, transferrin) was assessed in all contacts at study recruitment. Plasma was collected a median of 910 days prior to TB diagnosis. Low transferrin around the time of known exposure to infectious TB was a disease progression risk factor among all TB-progressors (Poisson incidence rate ratio: 0.55; 95% CI: 0.35-0.89). Iron homeostasis also differed between early and delayed TB-progressors, with higher ferritin and hepcidin concentrations observed among early TB-progressors (mean ferritin 50.2 vs. 26.2 ng/ml; P = 0.027; mean hepcidin 37.7 vs. 5.6 ng/ml; P = 0.036). Iron homeostasis is associated with progression to TB among household contacts. Further studies are needed to elucidate mechanisms and determine the clinical utility of monitoring iron homeostasis biomarkers.