Decreased plasma granulysin and increased interferon-gamma concentrations in patients with newly diagnosed and relapsed tuberculosis.

Granulysin and interferon-gamma (IFN-γ) have broad antimicrobial activity which controls Mycobacterium tuberculosis (M. tuberculosis) infection. Circulating granulysin and IFN-γ concentrations were measured and correlated with clinical disease in Thai patients with newly diagnosed, relapsed and chronic tuberculosis (TB). Compared to controls, patients with newly diagnosed, relapsed and chronic TB had lower circulating granulysin concentrations, these differences being significant only in newly diagnosed and relapsed TB (P < 0.001 and 0.004, respectively). Granulysin concentrations in patients with newly diagnosed and relapsed TB were significantly lower than in those with chronic TB (P= 0.003 and P= 0.022, respectively). In contrast, significantly higher circulating IFN-γ concentrations were found in patients with newly diagnosed and relapsed TB compared to controls (P < 0.001). The IFN-γ concentrations in newly diagnosed and relapsed patients were not significantly different from those of patients with chronic TB. However, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with newly diagnosed, relapsed and chronic TB with purified protein derivative (PPD) or heat killed M. tuberculosis (H37Ra) enhanced production of granulysin by PBMCs. In vitro, stimulation of PBMCs of newly diagnosed TB patients with PPD produced greater amounts of IFN-γ than did controls, while those stimulated with H37Ra did not. The results demonstrate that patients with active pulmonary TB have low circulating granulysin but high IFN-γ concentrations, suggesting possible roles in host defense against M. tuberculosis for these agents.

Time of highest tuberculosis death risk and associated factors: an observation of 12 years in Northern Thailand.

PURPOSE: Northern Thailand is a tuberculosis (TB) endemic area with a high TB death rate. We aimed to establish the time of highest death risk during TB treatment, and to identify the risk factors taking place during that period of high risk. PATIENTS AND METHODS: We explored the TB surveillance data of the Chiang Rai province, Northern Thailand, retrospectively for 12 years. A total of 19,174 TB patients (including 5,009 deaths) were investigated from 1997 to 2008, and the proportion of deaths in each month of TB treatment was compared. Furthermore, multiple logistic regression analysis was performed to identify the characteristics of patients who died in the first month of TB treatment. A total of 5,626 TB patients from 2005 to 2008 were included in this regression analysis. RESULT: The numbers of deaths in the first month of TB treatment were 38%, 39%, and 46% in the years 1997-2000, 2001-2004, and 2005-2008, respectively. The first month of TB treatment is the time of the maximum number of deaths. Moreover, advancing age, HIV infection, and being a Thai citizen were significant factors contributing to these earlier deaths in the course of TB treatment. CONCLUSION: Our findings have pointed to the specific time period and patients at higher risk for TB death. These findings would be useful for prioritizing interventions in order to diminish TB-related deaths globally. Studies based on these findings are necessary for the introduction of newer intervention strategies.