Iron Absorption and Utilization During Tuberculosis and After Treatment
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Observational

Summary: 
      Background: The disease burden of tuberculosis (TB), second only to HIV/AIDS among infectious
      diseases, is a major public health problem in developing countries. Accumulating evidence
      suggests that iron status is a primary determinant of TB progression. Anaemia is prevalent in
      patients with TB, particularly in sub-Saharan Africa, and associated with increased
      mortality. Anaemia in TB may be due to inflammation, dietary iron deficiency, or both, and
      distinguishing among these aetiologies is difficult. Iron supplementation is commonly used to
      treat anaemia in TB patients, but may be unnecessary if inflammation is the cause. Body iron
      sequestered by TB inflammation can be mobilized during treatment and used to correct the
      anaemia. Moreover, supplemental iron may be retained within macrophages, potentially
      increasing susceptibility to TB and leading to a poorer clinical outcome. Thus, better
      understanding of iron metabolism during TB and the aetiology of TB-related anaemia would
      clarify the potential role of iron in pathogenesis and optimal management of the disease.

      The investigators hypothesize that: a) TB will increase circulating hepcidin and thereby
      impair dietary iron absorption and systemic utilization of iron, resulting in iron
      sequestration and anaemia; b) TB treatment and resolution of inflammation over 6 months will
      decrease circulating hepcidin, correcting these impairments and improving iron status and
      hemoglobin; c) the majority of iron utilized to replenish hemoglobin during recovery from TB
      will come from mobilization of sequestered iron stores rather than from iron absorption.

      Objectives: Use iron stable isotopes to characterize iron balance over six months of TB
      treatment, and specifically to: a) quantify oral and intravenous iron incorporation (oral
      absorption and systemic iron utilization) at three time points during TB treatment (acute
      disease, after the intensive treatment phase and at completion of the continuation treatment
      phase); and b) determine the effect of treatment on iron mobilization from stores to
      replenish hemoglobin.

      Methods/Subjects: Using a triple stable-isotope technique, iron absorption from labelled test
      meals (57Fe) and systemic iron utilization after labelled intravenous doses (54Fe, 58Fe) will
      be determined in 18 Tanzanian subjects with newly diagnosed pulmonary TB. The subjects will
      be studied at three time points (i) the day after TB diagnosis while infected, (ii) after 8
      weeks of intensive phase treatment, and (iii) after another 16 weeks of continuation phase
      treatment. Iron status, hemoglobin, hepcidin and inflammation indexes will be measured at
      each time point. Isotope enrichment during the two treatment phases will be measured to
      estimate the relative rates of iron absorption and mobilization from stores during the
      intensive and continuation phases to determine the relative contributions of iron absorption
      and iron mobilization from stores during TB treatment and recovery.

      Outcome: These studies will provide important new insights into the aetiology of anaemia and
      iron metabolism in TB patients. The results will provide essential data for evidence-based
      recommendations on the timing, administration route and efficacy of iron therapy in patients
      with TB, making possible, a safer and more effective treatment of anaemia in TB while
      decreasing morbidity and mortality from the disease.
    


Intervention name(s): Stable iron isotopes, non-drug intervention
Intervention type(s): Other
Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        18 tuberculosis cases recruited at the Bagamoyo District Hospital and surrounding TB
        diagnostic centres.