Diagnostic Usefulness of Galactomannan Assay for Invasive Aspergillosis

Kyoung-Ho Song; Shinwon Lee; Hee-Chang Jang; Jae Hyun Jeon; Wan Beom Park; Kyoung Un Park; Sang-Won Park; Myoung-don Oh; Kang Won Choe

doi:10.3947/ic.2009.41.2.82

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Song, Lee, Jang, Jeon, Park, Park, Park, Oh, and Choe: Diagnostic Usefulness of Galactomannan Assay for Invasive Aspergillosis

Original Article

Infection and Chemotherapy

Infection and Chemotherapy 2009; 41(2): 82-89.

Published online: 30 April 2009

DOI: https://doi.org/10.3947/ic.2009.41.2.82

Diagnostic Usefulness of Galactomannan Assay for Invasive Aspergillosis

Kyoung-Ho Song, M.D.¹, Shinwon Lee, M.D.¹, Hee-Chang Jang, M.D.¹, Jae Hyun Jeon, M.D.¹, Wan Beom Park, M.D.¹, Kyoung Un Park, M.D.², Sang-Won Park, M.D.¹, Myoung-don Oh, M.D.¹, Kang Won Choe, M.D.¹

¹Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

²Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Correspondence: Myoung-don Oh, M.D. Department of Internal Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongro-gu, Seoul, Republic of Korea. 110-744. Tel: +82-2-2072-2945, Fax: +82-2-762-9662, mdohmd@snu.ac.kr

Received 17 October 2008 Accepted 31 December 2008

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. However, IA is difficult to diagnose, especially in the aforementioned patient group. Recently, galactomannan assay (GMA) using enzyme immunoassay has been introduced in Korea. We evaluated its diagnostic usefulness in the diagnosis of IA and we analyzed the results according to the underlying diseases.

Materials and Methods

All patients who underwent GMA during the period from October 2007 to June 2008 were evaluated retrospectively. According to the criteria of European Organization for Research and Treatment of Cancer/Mycoses Study Group, IA was classified into four clinical categories: 'proven', 'probable', 'possible', and 'non' IA. Patients with 'proven' and 'probable' IA were used as the reference standards for IA. GMA was performed using Platelia Aspergillus EIA (Bio-Rad, Hercules, CA, USA). Optical density index ≥0.5 was considered positive.

Results

Of the 144 patients who underwent GMA, two patients were classificed as 'proven' IA and sixteen patients were 'probable' IA. Overall sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 50% (95% confidence interval [CI95], 26-74%), 88% (CI95, 81-93%), 38% (CI95, 19-59%), and 93% (CI95, 86-97%), respectively. Among the 99 patients with underlying hematologic diseases, GMA showed 67% (CI95, 35-90%) sensitivity and 89% (CI95, 80-94%) specificity, whereas in 45 patients with underlying diseases other than hematologic diseases, sensitivity and specificity of the assay were 17% (CI95, 0-64%) and 87% (CI95, 73-96%), respectively.

Conclusion

GMA showed high specificity, irrespective of the patient population. However, sensitivity of GMA was low and the assay was less sensitive in patients with underlying diseases other than hematologic diseases than in patients with hematologic diseases.

Keywords: Aspergillosis, Diagnosis, Galactomannan, Antigen

Figures and Tables

Table 1

Characteristics of 144 Patients who Underwent Galactomannan Assay for the Diagnosis of Invasive Aspergillosis (IA)

Of the 18 patients with invasive aspergillosis (IA), 2 patients were diagnosed with 'proven' IA and 16 patients with 'probable' IA, according to the EORTC/MSG (European Organization of the Research and Treatment of Cancer/Mycoses Study Group) criteria (11).

^*Liver transplantation (2 patients)

^†Heart transplantation (5 patients), liver transplantation (3), kidney transplantation (2), liver-kidney co-transplantation (2) and lung transplantation (1).

^‡Polyarteritis nodosa (1), interstitial lung disease (1) and diabetes mellitus only (1).

^§Neutropenia was defined as an absolute neutrophil count below 500/mm3 over 10 days.

^∥2 patients were co-infected with Aspergillus fumigatus and Aspergillus flavus.

^¶Aspergillus versicolor (1) and Aspergillus spp.(1).

Table 2

Diagnostic Performances of Galactomannan Assay for Proven and Probable Invasive Aspergillosis in 144 Patients

TP, no. of cases with true-positive result; TN, no. of cases with true-negative result; FP, no. of cases with false-positive result; FN, no. of cases with false-negative result; PPV, positive predictive value; NPV, negative predictive value; LR+, likelihood ratio for positive test; LR-, likelihood ratio for negative test; CI95, 95% confidence interval

Table 3

Clinical Characteristics of 9 Patients with False-negative Result of Galactomannan Assay (GMA) for the Diagnosis of Invasive Aspergillosis (IA)

EORTC/MSG, European Organization of the Research and Treatment of Cancer/Mycoses Study Group; ILD, interstitial lung disease; DM, diabetes mellitus; TBLB, transbronchial lung biopsy; AML, acute myelocytic leukemia; BMT, bone marrow transplantation; ALL, acute lymphocytic leukemia; NHL, non-Hodgkins lymphoma; TPL, transplantation; PAN, polyarteritis nodosa; BAL, bronchoalveolar lavage.

^*As risk factors for invasive aspergillosis, "neutropenia" was defined as an absolute neutrophil count below 500/mm³ over 10 days and steroid was defined as prolonged (>3 weeks) use of corticosteroids in previous 60 days

^†Antifungal therapy active against mold infection.

^‡Optical density index ≥0.5 was considered as positive result.

Table 4

Clinical Characteristics of 15 Patients with False-positive Result of Galactomannan Assay (GMA) for the Diagnosis of Invasive Aspergillosis (IA)

There was no patient who had received amoxicillin/clavulanate and no patient with graft-versus-host disease and renal failure. EORTC/MSG, European Organization of the Research and Treatment of Cancer/Mycoses Study Group; Pip/Taz, piperacillin-tazobactam; AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; MDS, myelodysplastic syndrome; MM, multiple myeloma; TPL, transplantation; ILD, interstitial lung disease; DM, diabetes mellitus; NA, not available.

^*As risk factors for invasive aspergillosis, "neutropenia" was defined as an absolute neutrophil count below 500/mm3 over 10 days and "steroid" was defined as prolonged (>3 weeks) use of corticosteroids in previous 60 days

^†If the attending physician requested, additional galactomannan assay was performed within a week after the first test.

^‡Treatment outcome was evaluated at least 3 months after the first galactomannan assay.

^§Penicillium marneffei was isolated in sputum.

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