Tuberculosis (TB) remains the single most common infectious disease cause of mortality. We propose to examine the inter- relationships of nutrition, immunology, and epidemiology with respect to TB in Tanzania. Given that TB is so much linked with HIV immunologically, clinically, and epidemiologically, it is essential to examine how these relationships are modified by HIV infection. Published animal and human studies suggest that vitamin deficiency is associated with poor immune response in TB. By modulating immune function, nutritional supplements may be a useful adjunct to anti-TB drugs, and could lead to the development of shorter drug regimens. We propose to enroll 600 patients, half of whom have active TB and are co-infected with HIV, and the other half have TB alone. All patients will be randomized to receive either multivitamins or placebo from the start of their TB therapy, through the 8 months of anti-TB therapy, and for the 12 months following that (i.e. for a total of 20 months). Consenting subjects who present to 2 TB clinics in Dar es Salaam seeking care for respiratory illness will be screened for TB and HIV infection and invited to participate in the study. Patients who are severely debilitated (Karnofsky score of 40 percent or less, basal metabolic index of less than 18 kg/m2, or hemoglobin less than 7 g/dl) will be excluded. All patients will receive standard anti-TB therapy. Follow-up visits will occur every two weeks for the first 2 months and monthly thereafter till the end of the study. The minimum duration of followup is 20 months including 8 months of anti-TB treatment. The endpoints of interest include immune response parameters, bacteriologic cure, and clinical outcomes. Immune parameters (CD4 and CD8 cell counts; ex vivo lymphocyte proliferation; and cytokine production, namely IL-2, INF-g, IL-12, and TNF-alpha will be determined at baseline, 2 months, and 6 monthly thereafter. Bacteriologic cure at 1, 2, and 8 months will be determined by ascertaining conversion of sputum culture to negative. Compliance with therapy will be monitored. Surrogate markers are needed to rapidly evaluate the efficacy of anti-TB treatments or vaccines. Hence, we will examine the utility of the above immune response parameters as surrogate markers for treatment efficacy in TB. Using computer simulation modeling and epidemiological data collected during the follow up in this cohort study, we also propose to assess the effectiveness and cost-effectiveness of different treatment strategies for active TB and the use of INH post-TB treatment in Tanzania.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI045441-04
Application #
6532780
Study Section
Special Emphasis Panel (ZAI1-GSM-M (M1))
Program Officer
Rao, Malla R
Project Start
1999-08-15
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
4
Fiscal Year
2002
Total Cost
$562,158
Indirect Cost
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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Mehta, Saurabh; Mugusi, Ferdinand M; Bosch, Ronald J et al. (2013) Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study. BMJ Open 3:e003703
Isanaka, Sheila; Aboud, Said; Mugusi, Ferdinand et al. (2012) Iron status predicts treatment failure and mortality in tuberculosis patients: a prospective cohort study from Dar es Salaam, Tanzania. PLoS One 7:e37350
Isanaka, Sheila; Mugusi, Ferdinand; Urassa, Willy et al. (2012) Iron deficiency and anemia predict mortality in patients with tuberculosis. J Nutr 142:350-7
Kawai, K; Villamor, E; Mugusi, F M et al. (2011) Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania. Int J Tuberc Lung Dis 15:1380-9
Mehta, Saurabh; Mugusi, Ferdinand M; Bosch, Ronald J et al. (2011) A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania. Nutr J 10:120
Saathoff, E; Villamor, E; Mugusi, F et al. (2011) Anemia in adults with tuberculosis is associated with HIV and anthropometric status in Dar es Salaam, Tanzania. Int J Tuberc Lung Dis 15:925-32
Villamor, Eduardo; Mugusi, Ferdinand; Urassa, Willy et al. (2008) A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis. J Infect Dis 197:1499-505
Villamor, E; Saathoff, E; Mugusi, F et al. (2006) Wasting and body composition of adults with pulmonary tuberculosis in relation to HIV-1 coinfection, socioeconomic status, and severity of tuberculosis. Eur J Clin Nutr 60:163-71
Fawzi, Wafaie; Msamanga, Gernard; Spiegelman, Donna et al. (2005) Studies of vitamins and minerals and HIV transmission and disease progression. J Nutr 135:938-44

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