Abstract

BackgroundThe 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.MethodsWe 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.Results10% 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.ConclusionThese 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 registrationThe SOUTH trial was registered prospectively. ClinicalTrials.gov Identifier: NCT01782950; Registration date: 4th February 2013; Last verified: 13th April 2015.

Highlights

  • The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans

  • Study design and population This was a nested cohort study under the “Study on Outcomes related to Tuberculosis and HIV drug concentrations in Uganda” (SOUTH) (ClinicalTrials.gov: NCT01782950)

  • There was no record of these three conditions in our participants, and we argue that Aspergillus sensitisation is the explanation for these high immunoglobulin E (IgE) results, which could represent a strong T-helper 2 (Th2) response

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Summary

Introduction

The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. More results from this work showed Aspergillus-specific IgG antibody levels were raised in 26% of patients with “smear negative TB” and suggested that previously unrecognized CPA might be responsible for significant mortality in patients treated for TB in Uganda [6,7,8]. Beyond this limited data, little is known about the epidemiology of fungal colonisation and sensitisation, and their contribution to TB disease progress and treatment outcomes in Uganda where pulmonary TB is very common, in part driven by the high prevalence of HIV [9]

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