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

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

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Division of Nutritional Sciences, Cornell University, Ithaca, New York.
Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.



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.


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).


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).


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.


hemoglobin; hepcidin; inflammation; iron; tuberculosis

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