Association of Pulmonary Tuberculosis with Increased Dietary Iron

To determine whether increased dietary iron could be a risk factor for active TB, dietary iron history and HIV status were studied in 98 patients with pulmonary TB and in 98 control subjects from rural Zimbabwe. Dietary iron overload, which affects 10 percent or more of some rural African populations, causes heavy iron deposits within both macrophages and parenchymal cells. A recent statistical analysis of an autopsy series collected in South Africa in the 1920s found an association between high macrophage iron stores and death from TB. Also, in a retrospective study of bone marrow iron stores, a history of TB was more common in HIV-infected patients with elevated iron levels.

In the present study, researchers explored a potential relationship between a history of dietary iron and TB in a setting where HIV infection is common. Researchers studied 98 patients with pulmonary TB from Nyadire Mission Hospital, Mutoko District, Zimbabwe, and 98 community control subjects matched by age, sex, and area of residence. HIV seropositivity was more common in the patients with TB than in control subjects, whereas high levels of dietary iron in the form of traditional beer was comparable. The researchers estimated the amount of traditional beer, which is prepared at home from local grains in non-galvanized steel containers, consumed over each subject's lifetime as an indicator of exposure to increased dietary iron. The beverage has a high ferrous iron level and a low alcohol content. Consumption is associated with increased iron stores, as assessed directly by examination of liver tissue and indirectly by measuring serum ferritin concentration and transferrin saturation.

Among 84 subjects who were both HIV seronegative and negative for increased dietary iron, 17 (20.2 percent) had TB. Among 29 subjects who were HIV seronegative but were positive for increased dietary iron, 13 (44.8 percent) had TB. Among 69 subjects who were HIV seropositive but were negative for increased dietary iron, 58 (84.1 percent) had TB. Among 14 subjects who were both HIV seropositive and positive for increased dietary iron, 10 (71.4 percent) had TB. Logistic regression modeling indicated that, after adjustment for the degree of dietary iron and liver function, as assessed by serum AST level, HIV seropositivity was associated with a 17.3-fold increase in the estimated odds of developing active TB.

In this study, because inflammation associated with active TB tends to increase serum ferritin concentration and decrease transferrin saturation, researchers chose to gauge iron status by exposure to increased dietary iron in the form of traditional beer. They found a significant association between exposure to high levels of dietary iron and the presence of pulmonary TB. In addition, they also found a trend toward higher mortality in the patients with TB who had exposure to high levels of dietary iron, but the trend was not statistically significant.

Although findings seem to be consistent with the hypothesis that macrophage iron-loading in African iron overload may be associated with impaired macrophage function and increased risk for active TB, there are alternative interpretations. In view of in vitro work indicating that added iron may inhibit the growth of M. tuberculosis in macrophages, under certain circumstances it is possible that the increased transferrin saturation in patients with high levels of dietary iron might open up the extracellular space as an additional niche for M. tuberculosis replication. Also, if any of the subjects with high levels of dietary iron had cirrhosis, then the general immunocompromised status associated with cirrhosis could represent a risk for TB independent of iron status. In sub-Saharan Africa, where iron overload, HIV infection, and TB are common, the possible association of high levels of dietary iron with TB has potential public health implications. Of note, iron overload may be found in urban areas where consumption of traditional beer is less common. Further studies to examine the relationship between iron status and TB seem to be warranted.

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