Complex anemia in tuberculosis: the need to consider causes and timing when designing interventions

Clin Infect Dis. 2015 Mar 1;60(5):764-72. doi: 10.1093/cid/ciu945. Epub 2014 Nov 26.


Background: Anemia is common in tuberculosis, and multiple etiologies necessitate targeted interventions. The proportion of iron-responsive anemia due to iron deficiency compared with iron-unresponsive anemia due to impaired iron absorption/redistribution from tuberculosis-associated immune activation or inflammation is unknown. This impedes selection of safe and effective treatment and appropriate intervention timing.

Methods: Baseline hemoglobin, ferritin, hepcidin, soluble transferrin receptor (sTfR), and transferrin were measured in 45 patients with confirmed pulmonary tuberculosis (cases), 47 tuberculin skin test (TST)-positive controls, and 39 TST-negative controls in The Gambia. Tuberculosis cases were additionally followed 2 and 6 months after tuberculosis treatment initiation. Mutually exclusive anemia categories based on iron biomarker concentrations were iron deficiency anemia (IDA), anemia of inflammation (AI), and multifactorial anemia (IDA+AI).

Results: Anemia was more frequent in tuberculosis cases (67%) than in TST-positive (36%) or TST-negative (21%) controls. AI was the predominant anemia at tuberculosis diagnosis, declining from 36% to 8% after 6 months of treatment; however, a corresponding reduction was not evident for anemia with iron-responsive components (IDA, IDA+AI). Iron biomarkers discriminated between active tuberculosis and TST-positive or TST-negative controls, as well as between active untreated and treated tuberculosis. This was most noticeable for hepcidin, which decreased from a median of 84.0 ng/mL at diagnosis to 9.7 ng/mL after 2 months (P < .001).

Conclusions: Tuberculosis chemotherapy is associated with significant reductions in AI, but IDA and IDA+AI remain unresolved. Iron-based interventions are needed for IDA and IDA+AI, and monitoring of iron biomarkers reveals a window for intervention opening as early as 2 months into tuberculosis treatment.

Keywords: hemoglobin; hepcidin; inflammation; iron; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia / diagnosis
  • Anemia / drug therapy
  • Anemia / epidemiology*
  • Anemia / etiology*
  • Biomarkers / blood*
  • Blood Chemical Analysis
  • Female
  • Ferritins / blood
  • Gambia / epidemiology
  • Hepcidins / blood
  • Humans
  • Iron / metabolism
  • Iron-Binding Proteins / blood
  • Male
  • Middle Aged
  • Receptors, Cell Surface / blood
  • Transferrin / analysis
  • Tuberculosis / complications*
  • Tuberculosis / drug therapy*
  • Young Adult


  • Biomarkers
  • Hepcidins
  • Iron-Binding Proteins
  • Receptors, Cell Surface
  • Transferrin
  • ferritin receptor
  • Ferritins
  • Iron