Micronutrient status and risk of Mycobacterium tuberculosis infection in Indonesian tuberculosis case contacts

TL;DR

High ferritin levels in Indonesian TB case contacts are linked to a higher risk of Mycobacterium tuberculosis infection.

Contribution

This study identifies elevated ferritin as a novel risk factor for TB infection in case contacts.

Findings

Ferritin concentration was positively associated with IGRA conversion (adjusted IRR=1.17; 95% CI 1.01 to 1.35).

The association remained significant in the final multivariable model (IRR=1.27; 95% CI 1.09 to 1.47).

Abstract

Certain micronutrient levels have been associated with the risk of developing TB disease. We explored the possible association of selected at-risk micronutrient levels with the development of Mycobacterium tuberculosis (M.tb) infection.

This cohort study in Bandung, Indonesia, followed Interferon Gamma Release Assay (IGRA) negative TB case contacts with a repeat IGRA test at 3 mo. At baseline, blood was analysed for haemoglobin, 25-hydroxyvitamin D, retinol-binding protein, C-reactive protein, alpha-1-acid glycoprotein, serum transferrin receptor (sTfR), ferritin, zinc and selenium. Total body iron was calculated using ferritin and sTfR status. Associations between case contact micronutrient concentration and IGRA conversion were estimated using Poisson regression.

Of 430 contacts, 115 (27%) underwent IGRA conversion. Ferritin concentration (adjusted for inflammation) was positively associated with risk of IGRA conversion (incidence rate ratio [IRR] for ferritin=1.17; 95% CI 1.01 to 1.35; p=0.03), but other select micronutrients were not. This association held for ferritin in the final multivariable model (IRR=1.27; 95% CI 1.09 to 1.47; p=0.002).

The risk of developing M.tb infection, as defined by IGRA conversion, is associated with increasing ferritin. Interventions in TB case contacts to temporarily reduce iron levels, including considering withholding any iron supplementation, may be worthy of evaluation.