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

Abstract

ObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary 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.MethodsIn 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 categorised as proven, probable and possible.ResultsOf 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 rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two 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.ConclusionCPA 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.

Serious fungal disease incidence and prevalence in Indonesia

“…Indonesia ranks third on the number of TB which is an important factor related to the incidence of chronic pulmonary aspergillosis. In an abstract presented in 2017, we estimated ~83,030 treated pulmonary TB patient will suffer CPA and here we estimate a prevalence of 378,700, based on recently completed studies 24,25,64 . Due to the similarity of clinical signs, usually, these patients are treated as recurrent TB.…”

“…Chronic pulmonary aspergillosis (CPA) estimation is partly based on data from Indonesia and partly international. At the end of 6 months therapy for pulmonary TB, 8% of patients had CPA 24 . Pulmonary cavitation is present in 32% of those on completion of TB therapy and we assumed that 22% are at risk of CPA (ie 32%−10%) after having completed TB therapy.…”

“…Tertiary medical service facilities are also available in capital cities of the provinces such as Makassar in South Sulawesi, Manado in North Sulawesi, Denpasar in Bali and others. Twenty-seven percent of the population was less than 15 years old (70,486,700) and 9.3% are over 60 (24,754,500).…”

“…At the end of 6 months therapy for pulmonary TB, 8% of patients had CPA. 24 Pulmonary cavitation is present in 32% of those on completion of TB therapy and we assumed that 22% are at risk of CPA (ie 32%−10%) after having completed TB therapy. Using data from Uganda where 6.5% of survivors from TB who had cavitation developed CPA each year, 25 we calculated the annual incidence and 7-year period prevalence, assuming a 15% annual mortality of surgical resection rate.…”

Serological Changes in Anti-Aspergillus IgG Antibody and Development of Chronic Pulmonary Aspergillosis in Patients Treated for Pulmonary Tuberculosis

“…Another study, conducted in Indonesia, reported that 8% of patients had CPA at the completion of PTB treatment. This same study also provided evidence of serological changes in anti-Aspergillus IgG from baseline to treatment completion [26].…”