Chronic Pulmonary Aspergillosis in Post Tuberculosis Patients in Indonesia and the Role of LDBio Aspergillus ICT as Part of the Diagnosis Scheme

Abstract

Chronic pulmonary aspergillosis (CPA) is a common sequela of pulmonary tuberculosis (TB). The diagnosis of CPA is difficult and often misdiagnosed as smear-negative TB in endemic settings. Aspergillus IgG detection is the cornerstone of CPA diagnosis. There are a lack of studies on the prevalence of CPA in GeneXpert/smear-negative TB patients in Indonesia, despite a high number of TB cases. This study aims to determine the CPA rate in HIV-negative, GeneXpert-negative patients presenting with symptoms following completion of TB therapy and to evaluate the performance of LDBio Aspergillus immunochromatographic technology (ICT) lateral flow assay in the diagnosis of CPA. CPA was diagnosed on the basis of symptoms for ≥3 months, characteristic chest imaging and positive Aspergillus culture. Twenty (22%) out of 90 patients met the criteria for CPA. The LDBio test was positive in 16 (80%) CPA patients and in 21 (30%) non-CPA patients (p < 0.001) with 80% sensitivity and 70% specificity. Logistic regression revealed a positive LDBio Aspergillus ICT result, smoking history and diabetes to be important predictors of CPA diagnosis. Although CPA is an unrecognised disease in Indonesia, this study suggests that more than one in five GeneXpert negative patients with persistent symptoms following completion of TB therapy may have CPA.

Performance of LDBio Aspergillus WB and ICT Antibody Detection in Chronic Pulmonary Aspergillosis

“…The sensitivity and specificity rate of both assays were comparable. In other studies of CPA, the sensitivity ranged from 86.7% to 93.4% for WB and from 80% to 89.8% for ICT [ 8 , 9 , 10 ]. Combination of both assays appeared to increase specificity (80.9%) and achieved the best AUC (0.804).…”

“…Sera from 70 post-TB patients collected from April 2019 to February 2020 were tested at the Mycology Laboratory, Faculty of Medicine, Universitas Indonesia in Jakarta by ICT as previously described [ 10 ] followed by WB. The patients were adults (>18 years) who presented to a respiratory clinic (Persahabatan National Respiratory Referral Hospital, Jakarta, Indonesia) with symptoms following TB therapy.…”

“…Fisher exact test, chi-square and student t -test were use for the descriptive statistics. We utilised pre-existing data from our previous study [ 10 ] to perform statistical analyses of clinical, radiological and laboratory variables. The agreement between ICT and WB was evaluated using Cohen’s Kappa coefficient.…”

“…However, there is no study of WB in a population with high risk of CPA such as post-tuberculosis patients. We recently reported the use of ICT in post-tuberculosis patients with 80% sensitivity and 70% specificity [ 10 ]. Unlike ICT, which is a qualitative method, the WB is a semi-quantitative antibody detection assay which might help in quantifying Aspergillus IgG where automated ELISA is not available.…”

Evaluation of an Aspergillus IgG/IgM lateral flow assay for serodiagnosis of fungal asthma in Uganda

“…Similar, among a cohort of 154 patients with CPA at the National Aspergillosis Centre in Manchester, UK, the reported sensitivity and specificity of the kit was 91.6% and 98.0%, respectively [ 33 ]. In Indonesian patients with proven CPA, LDBio LFD had a sensitivity of 80% and a specificity of 70% [ 34 ]. From these studies, LDBio kit has been demonstrated to meet the ASSURED (“affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end users”) criteria outlined by the WHO [ 35 ].…”