Abstract
BackgroundTuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness.MethodsWe enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.50 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model.ConclusionIncreasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness.
Highlights
The global plan for tuberculosis (TB) by the Stop TB Partnership is to halve the prevalence and mortality caused by TB by 2015, followed by eliminating TB as a public health problem by 2050. [1] Tuberculosis is an infection spread through the air
We observed that increasing release of IL-4 and IL12p40 by bronchoalveolar lavage (BAL) cells were risk factors for being Acid-fast bacillus (AFB) smear positive. These results suggest immune pathways that are Th2-like with increased IL-4 and IL-12 p40 release are associated with increased infectiousness
Study Subjects: Patients with pulmonary tuberculosis were recruited from April 2005 to December 2006 in the Division of Pulmonology at the University of Cape Town with the following inclusion criteria [7]: All patients had Mycobacterium tuberculosis (Mtb) cultured from their sputum, were drug-sensitive and had extensive infiltrates
Summary
The global plan for tuberculosis (TB) by the Stop TB Partnership is to halve the prevalence and mortality caused by TB by 2015, followed by eliminating TB as a public health problem by 2050. [1] Tuberculosis is an infection spread through the air. TB patients frequently cough and generate aerosols of Mycobacterium tuberculosis (Mtb) that dry and produce suspended fomites. A TB specific Th1 immune response develops, preventing active tuberculosis but failing to eradicate all viable Mtb, producing latent tuberculosis infection (LTBI). 10% of HIV negative LTBI patients develop active TB over the course of their lives. With HIV co-infection, a large majority of those with LTBI will develop active disease [2]. In high TB burden countries like South Africa, approximately 40–50% of the population has LTBI and 1% of the population of South Africa developed active TB in 2009 producing an annual incidence of 480,000 cases [3]. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness
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