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

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.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0500-9) contains supplementary material, which is available to authorized users.

Seroprevalence of Aspergillus IgG and disease prevalence of chronic pulmonary aspergillosis in a country with intermediate burden of tuberculosis: a prospective observational study

“…In our study, even using the highest cut-off level ever proposed in the literature (50 mgA/L), there would be a 15.4% false-positive rate among old TB cases. Furthermore, a previous study conducted in Ugandan human immunodeficiency virus-infected pulmonary TB patients revealed a median Aspergillus IgG level of 4.4 mgA/L and 4% IgG positivity (cutoff 40 mgA/L) [22]. Our active TB patients received a median followup for 2.5 years and only one (0.2%) developed CPA during followup (71 events per 100 000 person-years).…”

“…In present study, A. fumigatus-specific IgG positivity was defined as A. fumigatus IgG above 27 mgA/L (milligrams of antigen-specific antibodies per liter) [19e21]. While 50, 40 and 20 mgA/L have also been proposed, this cut-off was made because it has been used in the majority of publications [8,9,21,22]. The definition of rural or urban residency followed a previous local Taiwan study [23].…”

Identification of Mycoses in Developing Countries

“…Elevated serum levels of Aspergillus-specific IgG and IgE are indicative of chronic pulmonary aspergillosis and allergic aspergillosis, which may be complicated by pulmonary tuberculosis resulting in death [51,52]. Importantly, serum levels of A. fumigatus-specific IgG and GM-specific IgG decrease inconsistently during the treatment of chronic pulmonary aspergillosis and may not be useful indicators for monitoring patient response [53].…”

Algorithm-aided diagnosis of chronic pulmonary aspergillosis in low- and middle-income countries by use of a lateral flow device

“…CPA affects immunocompetent or subtly immunocompromised patients with underlying structural lung diseases [2] and is estimated to affect approximately three million people per year worldwide [3]. It can co-exist with pulmonary tuberculosis (PTB), has both pulmonary and systemic symptoms that are clinically indistinguishable from that of PTB, and is often misdiagnosed and managed as smearnegative PTB [4]. According to the Infectious Diseases Society of America (IDSA), the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Confederation of Medical Mycology (ECMM), and the European Respiratory Society (ERS) Guidelines, the diagnosis of CPA should be based on characteristic symptoms and radiologic features present or presumed to have been present for at least 3 months in a patient with no or minimal immunosuppression and a prior or current lung condition with microbiological or immunological evidence of Aspergillus spp.…”