The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus

[摘要] Mycobacterium tuberculosis (M. tuberculosis) accounts for more adult deaths thanany other infectious agents. The present study included 162 patients with tuberculouspericarditis; 50% of the tuberculous pericarditis patients studied were humanimmunodeficiency virus (HIV) positive, compared to only 4.2% of patients whopresented with non-tuberculous pericardial effusions. A steady year-to-year rise inHIV prevalence was observed in this 6-year study. Although the prognosis ofpericardial tuberculosis (TB) is excellent with appropriate medical treatment,untreated pericardial TB has a mortality of 80-85%. It is thus important to diagnosetuberculous pericarditis efficiently. Traditionally, the diagnosis of pericardial TB isestablished by positive mycobacterial culture and/or histological evidence ofnecrotising granulomatous inflammation of the pericardium. Our study confirmed theinsensitivity of pericardial fluid culture and pericardial biopsy in the diagnosis ofpericardial TB, and at the time of clinical decision-making, results were usually notavailable. To overcome these difficulties, we explored various alternative strategiesand this resulted in two diagnostic tools, namely a diagnostic rule and a diagnosticalgorithm or classification tree.By means of classification and regression tree analysis, we allocated a weighteddiagnostic index to each of five independently predictive features (fever, night sweats,weight loss, serum globulin >40 g/L and peripheral blood leukocyte count<10x109/L). A total diagnostic index of 6 or more corresponded to 82-86% sensitivityand 76-87% specificity for a diagnosis of tuberculous pericarditis. When possible, pericardial fluid should be aspirated to determine adenosinedeaminase (ADA) levels and pericardial differential leukocyte counts. Fluid shouldalso be sent for Gram stain and culture. The proposed diagnostic classification treeutilises the independently predictive attributes of pericardial adenosine deaminaselevels, pericardial fluid lymphocyte/neutrophil ratios, peripheral leukocyte counts andthe HIV status. Applying this prediction model to our entire data set of 233 patientsresulted in 96% sensitivity and 97% specificity for the correct diagnosis oftuberculous pericarditis.Generally, patients were critically ill at the time of enrolment; 90% of tuberculouspericarditis presented with echocardiographic features of cardiac tamponade. Echoguidedpercutaneous pericardiocentesis with an indwelling catheter and intermittentdaily aspiration was highly effective and safe. It is likely that the combination of thisdrainage technique and the early initiation of anti-tuberculous chemotherapycontributed to the almost complete absence of constriction in the patients studied, andour data do not support the routine use of adjunctive corticosteroids in patients withtuberculous pericarditis.Tuberculous exudates result from a Th1 mediated immune response characterised bylymphocyte dominance, significantly elevated levels of gamma-interferon (IFN-γ) andundetectable levels of interleukin-4 (IL-4). IFN-γ levels were not influenced by HIVstatus in spite of the severely diminished pericardial CD4+ lymphocyte countsobserved in this study. It is thus likely that in HIV positive patients IFN-γ productionis partly maintained by activated CD8+ T cells, which were significantly elevated inHIV positive patients compared to HIV negative tuberculous pericarditis patients. This finding underlines the importance of IFN-γ in the human immune responseagainst M. tuberculosis. We also demonstrated that the presence of ADA inpericardial fluids reflects the activity of the cellular immune response. Both IFN-γ andADA can be utilised as sensitive and specific diagnostic tools for pericardial TB.

[发布机构] Stellenbosch University