Immune response profile in patients with active tuberculosis in a BCG vaccinated area.

Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin test responses to PPD and lymphocyte proliferative responses to crude mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens (tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in patients with pulmonary disease compared to endemic controls. However, mitogen (phytohemagglutinin)-stimulated responses were comparable in patients and controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE responses which are considered to be surrogate markers for Th2 responses were significantly higher in patients with pulmonary disease compared to healthy endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node disease showed strong Th1 responses but did not show significant responses for either polyclonal or antigen specific IgE. Thus overall suppression of T cell memory response was observed only in patients with pulmonary disease but not in patients with lymph node disease suggesting that sequestration of antigen in different compartments leads to differential activation of Th1 and Th2 responses. PPD skin test responses were highly positive in endemic controls (47% positive) and household contacts (86% positive). Furthermore, PPD positivity decreased with disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area cannot be used as a diagnostic marker for active tuberculosis particularly in advanced disease.

Pulmonary tuberculosis in a BCG vaccinated area: relationship of disease severity with immunological and hematological parameters and drug resistance patterns.

Clinical hematological and immunological parameters were studied in a group of 145 pulmonary patients with active tuberculosis, from a defined area of Karachi (Kharadar) belonging to the lower socioeconomic strata. Although clinical symptomatology could not differentiate the extent of lung involvement, a majority (69.6%) of the patients were diagnosed radiologically as having moderately advanced pulmonary disease. The peak number of patients were in their second decade of life. No differences were observed in the extent of disease based on age or gender. All hematological parameters for the group were in the normal ranges except for low levels of hemoglobin (9.58 +/- 1.55 SD; normal range 12-14 mg/dl) and a high ESR (90 +/- 31 SD; normal range 0-13 mm/hour). A negative correlation of PPD skin test induration (r = 0.21, p = 0.02), and a positive correlation of total white blood cell (r = 0.20; p = 0.015) was observed with the amount of lung tissue involved. The resistance amongst the strains for the four first line anti-tuberculosis agents was found to be: isoniazid = 27.4%; ethambutol = 14.5%; rifampicin = 11.29% and streptomycin = 12.9%. Multi-drug resistance to the most commonly prescribed combination (rifampicin and ethambutol) was 8.06%. Drug resistance patterns to individual drugs were comparable with resistance patterns observed in strains from greater Karachi at The Aga Khan Hospital during the same period. Such studies should provide improved rationale for patients diagnosis and treatment.