title: Complex anemia in tuberculosis: the need to consider causes and timing when designing interventions.
abstract: 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.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Minchella
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Simon
authors.initials: S
authors.lastname: Donkor
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Olumuyiwa
authors.initials: O
authors.lastname: Owolabi
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Sutherland
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York.
authors.forename: Joann M
authors.initials: JM
authors.lastname: McDermid
mesh_terms: D000328:Adult; D000740:Anemia / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*; D015415:Biomarkers / Q000097:blood*; D001774:Blood Chemical Analysis; D005260:Female; D005293:Ferritins / Q000097:blood; D005714:Gambia / Q000453:epidemiology; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood; D014168:Transferrin / Q000032:analysis; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D033862:Iron-Binding Proteins; D011956:Receptors, Cell Surface; D014168:Transferrin; C027293:ferritin receptor; D005293:Ferritins; D007501:Iron
keywords: hemoglobin; hepcidin; inflammation; iron; tuberculosis