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Mycobacterium tuberculosis, which grows within phagosomes among these populations has been attributed solely to ingestion
of macrophages, has an elaborate system of mycobactin sidero- of high levels of dietary iron in a traditional fermented beverage,
phores for acquiring and storing iron [1, 2]. The growth of M. recent studies indicate that a genetic predisposition may also
tuberculosis in serum [3] and in mice [4] is enhanced by the be a factor [8]. Iron loading of macrophages could, conceivably,
addition of iron. On the other hand, the addition of iron inhibits enhance the growth of M. tuberculosis and impair the ability
experimental infection with M. tuberculosis in monocytes under of macrophages to suppress invading microorganisms. A recent
certain conditions [5]. Furthermore, the addition of monocytes statistical analysis of an autopsy series collected in South Africa
to cultures of M. tuberculosis in serum is inhibitory, with or in the 1920s found an association between high macrophage
without iron supplementation [6]. iron stores and death from tuberculosis [9]. Also, in a retro-
Dietary iron overload, which affects ⭓10% of some rural spective study of bone marrow iron stores, a history of tuber-
African populations, causes heavy iron deposits within both culosis was more common in human immunodeficiency virus
macrophages and parenchymal cells [7]. Although the condition (HIV)–infected patients with elevated iron levels [10]. In the
present study, we explored a potential relationship between a
history of dietary iron and tuberculosis in a setting where HIV
Received 25 September 2000; revised 24 May 2001; electronically pub-
lished 17 August 2001. infection is common.
Presented in part: 2d International Conference on HIV and Iron, Brugge,
Belgium, 31 March to 2 April 2000.
Written informed consent was obtained from all study participants. Human
experimentation guidelines of the Medical Research Council of Zimbabwe and Subjects and Methods
the US Department of Health and Human Services were followed.
Financial support: Office of Minority Health to the Cell Biology and Study subjects. We studied 98 patients with pulmonary tuber-
Metabolism Branch of the National Institute of Child Health and Human culosis from Nyadire Mission Hospital, Mutoko District, Zim-
Development (NICHD); Cell Biology and Metabolism Branch of NICHD babwe, and 98 community control subjects matched by age, sex,
(HD 3-3196); J. F. Kapnek Charitable Trust (Harare, Zimbabwe).
and area of residence. A preliminary analysis of haptoglobin poly-
Reprints or correspondence: Dr. I. T. Gangaidzo, Dept. of Medicine,
University of Zimbabwe School of Medicine, Box A178, Avondale, Harare, morphisms in these subjects has been published elsewhere [11].
Zimbabwe (gangaidz@ecoweb.co.zw). History of increased dietary iron. We estimated the amount of
traditional beer, which is prepared at home from local grains in
The Journal of Infectious Diseases 2001; 184:936–9
䉷 2001 by the Infectious Diseases Society of America. All rights reserved. nongalvanized steel containers, consumed over each subject’s life-
0022-1899/2001/18407-0020$02.00 time as an indicator of exposure to increased dietary iron. The
JID 2001;184 (1 October) Tuberculosis and Dietary Iron 937
beverage has a high ferrous iron level and a low alcohol content, patients with pulmonary tuberculosis, with adjustment for age and
and consumption is associated with increased iron stores, as as- serum AST level.
sessed directly by examination of liver tissue and indirectly by mea-
suring serum ferritin concentration and transferrin saturation [7].
The estimate of traditional beer consumption was based on inter- Results
views conducted before blood samples were obtained by researchers
who were fluent in the local languages and knowledgeable of the Patients with tuberculosis and control subjects. Demographic
local culture. The number of liters of traditional beer consumed in and clinical characteristics for patients and control subjects are
a typical beer-drinking day was multiplied by the number of days summarized and compared in table 1. For patients with pul-
the individual usually drank per month, and this monthly total monary tuberculosis, the laboratory measurements of hemato-
was then multiplied by 12 times the number of years during which logic and iron status presented in table 1 were done during weeks
the individual had drunk traditional beer. This estimate provides 1–3 of treatment. HIV seropositivity was more common in the
a broad approximation of lifetime traditional beer consumption,
patients with tuberculosis than in control subjects, whereas high
because consumption may not be uniform over time and because
levels of dietary iron in the form of traditional beer was com-
information was obtained by recollection. Increased dietary iron
Table 2. Chronological summary of measurements of iron status in Iron status according to dietary iron content. To confirm re-
patients with tuberculosis at Nyadire Mission Hospital, Zimbabwe, sults from other studies demonstrating higher iron status with
according to human immunodeficiency virus (HIV) infection status.
increased dietary iron, we compared indirect measures of iron
HIV-negative patients HIV-positive patients
status in control subjects, according to the presence or absence
Measurement, time Value n Value n P of increased dietary iron. After adjustment for age and sex, the
Serum ferritin geometric mean serum ferritin concentration was 115 mg/L (SE
concentration, range, 90–148 mg/L) in 20 control subjects with a history of in-
a
ng/mL
Weeks creased dietary iron, compared with 62 mg/L (SE range, 56–70
1–3 411 (145–1169) 24 514 (155–1706) 52 .5 mg/L) in 78 subjects without increased dietary iron (P p .038).
4–6 317 (92–1094) 25 321 (100–1030) 40 1.0 Similarly, the ratio of serum ferritin concentration to AST level
7–9 232 (63–861) 21 236 (56–989) 35 1.0
Months was 4.9 mg/U (SE range, 3.8–6.5 mg/U) in control subjects with
3 161 (48–542) 16 138 (33–577) 37 .7 increased dietary iron, compared with 2.1 mg/U (SE range, 1.9–2.4
4–6 126 (39–338) 21 91 (26–318) 41 .3 mg/U) in those without increased dietary iron (P p .009). The
7–9 87 (19–401) 10 47 (18–119) 11 .3
adjusted mean Ⳳ SE transferrin saturation was 39% Ⳳ 4% in
transferrin saturation [13], in this study, we chose to gauge iron and tuberculosis are common, the possible association of high
status by exposure to increased dietary iron in the form of levels of dietary iron with tuberculosis has potential public
traditional beer. Estimated traditional beer consumption has health implications. Of note, iron overload may be found in
been shown to correlate with iron status in both community urban areas where consumption of traditional beer is less com-
and hospitalized rural African subjects [7, 8], and we observed mon [15]. Further studies to examine the relationship between
serum ferritin concentrations to be significantly higher in con- iron status and tuberculosis seem to be warranted.
trol subjects with increased dietary iron, even after adjustment
for liver dysfunction, as reflected in serum AST level. We found References
a significant association between exposure to high levels of di-
1. De Voss JJ, Rutter K, Schroeder BG, Barry CE. Iron acquisition and meta-
etary iron and the presence of pulmonary tuberculosis. We also
bolism by mycobacteria. J Bacteriol 1999; 181:4443–51.
found a trend toward higher mortality in the patients with 2. De Voss JJ, Rutter K, Schroeder BJ, Su H, Zhu Y, Barry CE. The salicylate-
tuberculosis who had exposure to high levels of dietary iron, derived mycobactin siderophores of Mycobacterium tuberculosis are essential
but the trend was not statistically significant. for growth in macrophages. Proc Natl Acad Sci USA 2000;97:1252–7.