Chronic pulmonary aspergillosis in active pulmonary tuberculosis patients in Jakarta, Indonesia

Objectives: Pulmonary tuberculosis (PTB) is the most common risk factor for chronic pulmonary aspergillosis (CPA). Moreover, these two diseases have the same clinical and radiological manifestations with completely different management approach. Indonesia ranked as the second largest country with tuberculosis burden in the world. There is no single study about CPA in PTB patients in Indonesia. This study aims to estimate the burden of CPA among active PTB patients in Indonesia

Methods: We assessed PTB patients for CPA based on clinical symptoms, chest x-ray (CXR) results and Aspergillus-specific immunoglobulin G (IgG) using Dynamiker immunoassays. During a period of 6 months (from February 2017 to July 2017), we studied 56 PTB patients from five hospitals in Jakarta, Indonesia. There are 27 patients in first 8 weeks (early) PTB therapy and 29 in the final 2 months (late) PTB therapy. Sputum specimens were also analysed by the GeneXpert MTB/RIF test to rule out active PTB as diagnosis.  This is an interim analysis of a large CPA cohort study ongoing in Indonesia. 

Results: Out of 56 patients with TB (32 male, age range: 17-78 years), 10 patients (17.9%) met criteria for CPA. There are 5 CPA patients diagnosed from each group (18.5% from the early PTB therapy group and 17.2% from the late PTB therapy group). Cough (n=2, 40%), hemoptysis (n=2, 40%), fatigue (n=2, 40%) and shortness of breath (n=2, 40%) become the most common symptoms in CPA from the early therapy group. Cough (n=4, 80%) was the most common presenting symptom in the late PTB therapy group.  This compares with the non-CPA PTB patients from the late PTB therapy who described no symptoms (n=17, 70.8%). The key radiological criterion used to diagnose CPA in this study was the presence of cavities. The CXR appearances consist of cavities (n=10, 100%), paracavitary fibrosis (n=8, 80%) and pleural thickening (n=6, 60%). The mean Aspergillus-specific IgG level in CPA patients from early PTB therapy group is 104.8 AU/ml. This level is lower than the mean Aspergillus-specific IgG level in CPA patients from the late PTB therapy group (523.4 AU/ml). Most of the CPA patients (n=4, 80%) from both of the groups showed negative results of both acid-fast bacilli smear (AFB) and/or GeneXpert MTB/RIF. There are 2 patients with positive AFB smears in early therapy become negative 6 months after TB therapy met criteria of CPA. 

Conclusion: CPA is commonly misdiagnosed as PTB in Indonesia where TB is an endemic disease. Most of PTB patients show clinical progression after 6 months therapy unless there is another concomitant disease such as CPA. The combination of clinical presentation, CXR and Aspergillus serology tests may be used as diagnostic tool for CPA.  In the absence of serology in resource-limited settings CPA should be considered if the clinical and radiological findings are in line with those of CPA and there is no evidence of active PTB. There is an urgent need for research in this field to determine the true incidence and prevalence of CPA among PTB patients in Indonesia.

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