Iron Status Predicts Treatment Failure and Mortality in Tuberculosis Patients: A Prospective Cohort Study from Dar es Salaam, Tanzania

Abstract

BackgroundExperimental data suggest a role for iron in the course of tuberculosis (TB) infection, but there is limited evidence on the potential effects of iron deficiency or iron overload on the progression of TB disease in humans. The aim of the present analysis was to examine the association of iron status with the risk of TB progression and death.Methodology/Principal FindingsWe analyzed plasma samples and data collected as part a randomized micronutrient supplementation trial (not including iron) among HIV-infected and HIV-uninfected TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV-uninfected) to the risk of treatment failure at one month after initiation, TB recurrence and death using binomial and Cox regression analyses. Overall, low (plasma ferritin<30 µg/L) and high (plasma ferritin>150 µg/L for women and>200 µg/L for men) iron status were seen in 9% and 48% of patients, respectively. Compared with normal levels, low plasma ferritin predicted an independent increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to 3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95% CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein concentrations, was associated with an increased risk of overall mortality (adjusted RR = 3.02, 95% CI: 1.95 to 4.67).Conclusions/SignificanceBoth iron deficiency and overload exist in TB patients and may contribute to disease progression and poor clinical outcomes. Strategies to maintain normal iron status in TB patients could be helpful to reduce TB morbidity and mortality.

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

“…These findings should also be considered in light of numerous reports that associate high serum iron levels and transferrin-iron saturation with an increased mortality and morbidity due to tuberculosis [16][17][18][19][20] . It is possible that extracellular M.tb present in a transferrin-rich environment utilize this pathway for immediate access to iron.…”

“…Other studies have demonstrated that ironsaturated transferrin promotes the replication of M. avium within the phagosome 15 . Elevated serum iron and high levels of ironsaturated transferrin are known to have a strong correlation with the exacerbation of tuberculosis in both mouse models and patient studies 3,[16][17][18][19][20] .…”

Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

“…There is considerable evidence of the contribution of iron availability to mycobacterial growth in vitro as well as in experimental animal models [13,14], but reports on host iron status in response to anti-mycobacterial treatment are scarce. Among pulmonary TB (PTB) patients, high ferritin levels have been reported [15–18], but few studies evaluated if ferritin levels reflect treatment outcomes [7,19–21]. On the other hand, circulating levels of C-reactive protein (CRP), an established biomarker of systemic inflammation, have been described to reflect both TB disease severity and radiographic improvement after 2 months of ATT [22,23].…”

Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke

“…More than 36 million people died from NCDs in 2008 with 48% of these deaths caused by CVD [1]. Despite advances in medical therapy, the prognosis following a vascular event remains poor [2].…”