ID Page, W Worodria, A Andama, I Ayakaka, R Kwizera, L Davis, L Huang, M Richardson, DW Denning


CPA is estimated to affect 3 million people globally. The most common underlying condition in CPA is treated pulmonary tuberculosis. Our recent cross-sectional survey identified CPA in 8.2% of 400 Ugandan adults with previously treated pulmonary tuberculosis (Union Lung Conference 2015, abstract PC-957-05).
CPA diagnosis is often made years after completing tuberculosis treatment, but no prospective surveys have defined the natural history. Co-infection with atypical mycobacteria frequently occurs in CPA. Co-infection with Mycobacterium tuberculosis and Aspergillus has been described in several case reports. Subacute invasive aspergillosis (SAIA) has been documented in 3-11% of autopsies of patients who died of AIDS, in the absence of pulmonary tuberculosis. This raises the possibility that onset of CPA may occur during active pulmonary tuberculosis, especially in patients with AIDS. We aimed to estimate the prevalence of aspergillosis in patients with active pulmonary tuberculosis.
Stored sera were available from 57 adult patients admitted to Mulago Hospital, Kampala between March 2010 and March 2011. All patients had between 2 weeks and 6 months cough and were diagnosed with pulmonary tuberculosis based on culture or GeneXpert PCR testing of sputum and/or broncho-alveolar fluid. We measured Aspergillus-specific IgG in these samples using the Siemens Immulite assay, which has a specificity of 98% and sensitivity of 96% for the diagnosis of chronic pulmonary aspergillosis (Journal of Infection, in press).
46 (81%) patients and 2% controls were HIV positive. Mean CD4 count in patients with HIV was 99 cells/mL (range 2 - 581 cells/mL). 35 (61%) patients had CD4 count <100 cells/mL and 24 (42%) patients had CD4 count <50 cells/mL.
Mean Aspergillus-specific IgG levels were 5 mg/L in healthy controls and 11mg/L in pulmonary tuberculosis cases (p – 0.000). Raised levels were found in 2 (2%) of healthy controls and 27 (47%) pulmonary tuberculosis patients (p – 0.000). There was no significant difference in 2-month mortality in tuberculosis patients with normal or raised levels of Aspergillus-specific IgG.
These results cannot differentiate Aspergillus colonization from active disease. This is a select group of tuberculosis patients requiring emergency hospital admission and results may not be generalisable to other patients with tuberculosis. However, given the diagnostic accuracy of the Siemens Immulite assay active Aspergillus co-infection is probably present in many of those with positive results. This possibility should be considered in patients who fail to improve or clinically relapse in spite of appropriate tuberculosis therapy.
The frequency of raised Aspergillus-specific IgG levels is four times higher in these patients with active pulmonary tuberculosis than the rate of CPA found in patients with treated tuberculosis in our earlier survey. It is possible that many patients develop Aspergillus colonization during active pulmonary tuberculosis, which then resolves as the tuberculosis is cured. Alternatively, our earlier survey may have failed to identify those who died of CPA soon after completing tuberculosis treatment and so underestimated the frequency of CPA complicating pulmonary tuberculosis. Prospective studies are now needed to record the outcome of patients with pulmonary tuberculosis and raised Aspergillus-specific IgG and define the natural history of CPA secondary to pulmonary tuberculosis.


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7th Advances Against Aspergillosis Conference