Aspergillus sensitisation and asthma in Uganda

Abstract

Background: Asthma is one of the neglected diseases in Africa and occurs at a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. Aspergillus fumigatus is the most common causative agent. However, data on prevalence of Aspergillus sensitisation in asthma and whether this is associated with severe asthma phenotypes remain limited in Uganda. Furthermore, knowledge about the factors associated with fungal asthma due to Aspergillus among asthmatic Ugandans is not known. Objectives: The main objective of the study was to investigate the burden of A. fumigatus sensitisation, allergic bronchial pulmonary aspergillosis (ABPA), severe asthma with fungal sensitisation (SAFS) and allergic bronchial pulmonary mycosis (ABPM) among Ugandan asthmatics, exploring the factors associated with fungal asthma in this population. We also aimed to evaluate the diagnostic performance of a point of care test for fungal asthma caused by A. fumigatus in the same population. In addition, we aimed to assess the background prevalence of A. fumigatus skin prick positivity in apparently healthy adults without known atopic disease in Uganda. Methods: In this thesis, we first estimated the burden of fungal asthma among adults and children in Africa using a systematic review. In addition, we estimated the baseline prevalence of A. fumigatus skin positivity among a healthy non-atopic population in Uganda. We then estimated the prevalence of A. fumigatus sensitisation, ABPA, SAFS, and ABPM among adult Ugandan asthmatics enrolled into a prospective cohort study. Using baseline characteristics, we investigated the clinical and socio-demographic factors associated with fungal asthma in this population. We then evaluated the diagnostic performance of an Aspergillus-specific IgG/IgM lateral flow device (LFD) for the detection of immune reactivity to A. fumigatus in the same population. This study had ethics approval from the School of Biomedical Sciences Research and Ethics Committee and the Uganda National Council for Science and Technology. Results: The systematic review on the burden of fungal asthma in Africa revealed a high prevalence of fungal sensitisation among African asthmatics with a pooled estimate of 23%, mostly due to Aspergillus species. Prevalence of ABPA was estimated at 1.6–21.2% and SAFS at 3.3%. Diagnosis of fungal sensitisation was mostly made by skin prick tests. There were no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children. The prevalence of A. fumigatus skin positivity in apparently healthy adults without known atopic disease was 60%. Healthy participants with a positive A. fumigatus SPT were significantly younger than those with a negative result. In the cross-sectional study, we observed a high prevalence of A. fumigatus sensitisation at 42.0%, ABPA 3.2%, SAFS 16.0% and ABPM 2.9%. Older age, sensitisation to at least one allergen and hypertension were significantly associated with A. fumigatus sensitisation. High occupational exposure to Aspergillus and contact with moulds were significantly associated with ABPA. Palpitations, uncontrolled asthma, eczema/dermatitis, poor lung function and frequent exacerbations were significantly associated with SAFS. Eczema/dermatitis was significantly associated with ABPM. The sensitivity, specificity, positive predictive value and negative predictive values for the Aspergillus LFD for the diagnosis of ABPA were 0.0%, 96.4%, 0.0% and 96.7% respectively, and for SAFS 6.7%, 97.1%, 30.8% and 84.5% respectively. False positive and negative rates were 3.5% and 3.2% for ABPA and 2.4% and 14.9% for SAFS, respectively. Patients with a positive LFD had a higher median A. fumigatus-specific IgE levels compared to those with negative LFD. Conclusions: From the systematic review, we concluded that fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. We found a high prevalence of A. fumigatus skin positivity in adults without an apparent/known atopic disease in Uganda. From the cross-sectional study, we similarly observed that fungal asthma is a significant problem among Ugandans with asthma. The Aspergillus LFD demonstrated a poor diagnostic performance for the diagnosis of both ABPA and SAFS. Key recommendations: We recommend an urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa. Fungal asthma should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy. Since fungal asthma is associated with worse outcomes, we need routine screening in the asthma clinics to place those diagnosed in the hands of specialists for better monitoring to improve outcomes. There is need to develop an affordable Aspergillus point-of-care test that detects Aspergillus IgE. This could improve on the diagnostic performance and be more useful in resource limited settings like Africa. There is also a need to advocate for translational research into developing more fungal diagnostics to address the local disease burden. There is an urgent need to establish a normal wheal cut off with clinical value in both asthmatics and apparently healthy non-atopic individuals for diagnostic purposes. The skin prick test alone may be an unreliable test for the diagnosis of A. fumigatus associated allergic syndromes. More studies are needed to define the prevalence of A. fumigatus skin positivity among non-atopic healthy population in Africa.