Investigation of pulmonary fungal diseases in Indonesia with a focus on aspergillosis

UoM administered thesis: Phd

  • Authors:
  • Findra Setianingrum Sudradjat

Abstract

It is estimated that fungal diseases affect over a billion people and kill more than 1.5 million people annually. Pulmonary fungal infections (PFIs) such as chronic pulmonary aspergillosis (CPA) and pulmonary cryptococcosis are a major cause of morbidity and mortality globally. However, PFIs are still under-diagnosed particularly in resource-limited settings despite risk factors for PFIs being common in the population. The aim of this research was to estimate the burden of disease for CPA and pulmonary cryptococcosis in Indonesia and to evaluate the outcomes of CPA surgery in a cohort of patients in the UK. The first study aimed to establish the cutoffs for two serological assays for the diagnosis of CPA. Patients (n=203) finishing their treatment for pulmonary tuberculosis (TB) and healthy controls (n=90) were recruited and serum from 100 diseased controls were also used as controls. The recommended cutoff for Aspergillus-specific IgG and anti-galactomannan IgG was established to be 11.5 mg/l (sensitivity: 88.5%, specificity: 87.8%) and 106.8 AU/ml (sensitivity: 82.6%, specificity: 68.9%), respectively. The second study was a prospective multi-centre cohort study aiming to establish the prevalence of CPA in patients undergoing treatment for TB in Indonesia. We applied the cutoffs from the first study to 216 patients at the start of TB therapy (0-8 weeks, baseline), 128 patients at the end of TB therapy (5-6 months), and 67 patients post TB therapy (12-14 months). At baseline, probable CPA was diagnosed in 6% (n=12) patients, 8% (n=10) patients at the end of therapy, 10% (n=7) patients at post TB therapy. The mean total St. George's Respiratory Questionnaire score in CPA patients was significantly higher than in non-CPA patients in all aspects (23.3 vs 3, p=0.002) indicating that the symptoms were persistent in CPA patients but resolved in those with TB only. Two patients were diagnosed with concomitant CPA and TB. The third study retrospectively evaluated the surgical outcomes of 61 CPA patients in the National Aspergillosis Centre, UK. Relapse occurred in 25 patients (41%) at mean 26 months after surgery. In 12 patients with data available at the end of follow-up time, the median Aspergillus-IgG level was lower than at the time of relapse (67 mg/L vs 126 mg/L) (p=0.016). Antifungal therapy before or after surgery were found to be protective against relapse (p≤0.005). The fourth study aimed to survey the prevalence of pulmonary cryptococcosis in patients presenting with community-acquired pneumonia (CAP) in Indonesia. Of the 17 patients recruited, 5 (29%) had findings suggestive of pulmonary cryptococcosis. The mean duration of cough in pulmonary cryptococcosis was significantly longer (12 vs 5 weeks) in pulmonary cryptococcosis patients than in non-pulmonary cryptococcosis (p=0.015). The latex agglutination tests were more sensitive than the lateral-flow device in the antigen detection for the diagnosis of cryptococcal pneumonia. In conclusion, CPA and pulmonary cryptococcosis were diagnosed at a considerable rate among risk populations in Indonesia. Most pulmonary TB patients show clinical progression after 6 months of therapy unless there is another concomitant disease such as CPA. Monitoring for CPA is required also after surgery, as the relapse rate is high.

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Original languageEnglish
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Award date1 Aug 2020