A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL)

Abstract

Objectives: Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary tuberculosis (TB). CPA may also be misdiagnosed as bacteriologically-negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia; a country with a high incidence of TB. Methods: In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (>3 months), characteristic radiological features and positive Aspergillus serology, and categorized as proven, probable and possible. Results: Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence of proven and probable CPA at baseline was 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (2 with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. Conclusion: CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.