A Cross-Sectional Survey to Measure the Prevalence of Chronic Pulmonary Aspergillosis (CPA) Complicating Pulmonary Tuberculosis in Northern Uganda

Abstract

Background. Chronic pulmonary aspergillosis (CPA) complicates pulmonary tuberculosis (TB). It has a 5-year mortality of up to 85%, but is treatable with itraconazole or surgery. The estimated global prevalence of CPA post-TB is 0.8-1.3 million cases. We conducted the first survey to measure the prevalence of CPA secondary to pulmonary TB. Methods. A cross-sectional survey of adults treated for pulmonary TB within the last 7 years in Gulu, Uganda. All underwent clinical assessment, chest X-ray and Aspergillusspecific IgG measurement by Siemens Immulite at a cut-off of 20mg/L, which has a sensitivity of 93% and a specificity of 98% for CPA diagnosis. Patients were resurveyed two years later. CT scan was performed in those with positive serology or chest X-ray signs of CPA. GeneXpert TB PCR testing was performed on those with productive cough. CPA was diagnosed in patients with ALL of the following; (1) >1 month cough or haemoptysis, (2) raised Aspergillus-specific IgG, and (3) paracavitary fibrosis, aspergilloma or progressive cavitation on imaging. Simple aspergilloma was diagnosed in asymptomatic patients with aspergilloma and positive serology. Results. In total, 400 patients were recruited between October 2012 and February 2013. 200 (50%) were HIV positive. Median age was 42 years (range 16-83). Thirtynine percent of patients were female. Median CD4 count in those with HIV was 415 cells/muL (range 0-1400). In total, 284 patients were re-surveyed between October 2014 and February 2015. Twenty-three (7.7%) of those resurveyed had raised Aspergillusspecific IgG levels. Twelve patients (4.2%) had CPA and 1 (0.4%) simple aspergilloma. A further three patients had a fungal ball on CT thorax, but normal levels of Aspergillusspecific IgG. HIV co-infection had no significant impact on the frequency of CPA. Three cases of recurrent pulmonary TB were identified, none in the CPA group. Conclusion. CPA complicates pulmonary tuberculosis. This data suggest the predicted global prevalence is accurate. This is a significant global public health problem, which is currently neglected. The clinical and radiological presentation of CPA is often identical to recurrent TB. In the absence of access to Aspergillus-specific IgG testing most cases of CPA are probably inaccurately diagnosed as recurrent 'smear-negative TB' and subjected to unnecessary and potentially toxic second-line TB therapy.