Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis

Richard Kwizera, Rosalind Parkes-Ratanshi, Iain D Page, Christine Sekaggya-Wiltshire, Joseph Musaazi, Jan Fehr, Barbara Castelnuovo, Andrew Kambugu, David W Denning, Richard Kwizera, Rosalind Parkes-Ratanshi, Iain D Page, Christine Sekaggya-Wiltshire, Joseph Musaazi, Jan Fehr, Barbara Castelnuovo, Andrew Kambugu, David W Denning

Abstract

Background: The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda.

Methods: We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics.

Results: 10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24.

Conclusion: These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis.

Trial registration: The SOUTH trial was registered prospectively. ClinicalTrials.gov Identifier: NCT01782950 ; Registration date: 4th February 2013; Last verified: 13th April 2015.

Keywords: Aspergillosis; Fungal diagnostics; serology; HIV; Tuberculosis.

Conflict of interest statement

Ethics approval and consent to participate

Participants provided written informed consent to participate in the SOUTH study. Ethics approval for this sub-study was received from the Joint Clinical and Research Centre Institutional Review Board, the Uganda National Council for Science and Technology and the Uganda National Drug Authority.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Scatter plots of antibody levels at baseline and week 24. a Shows a significant difference in Aspergillus-specific IgG levels between baseline and week 24 using ImmunoCAP. b Shows no significant difference in Aspergillus-specific IgG levels between baseline and week 24 using Immulite. c Shows a significant difference in total serum IgE levels between baseline and week 24 using Immulite. d Shows distribution of Aspergillus-specific IgE levels at week 24

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