Utility of a serum Aspergillus galactomannan assay in diagnosis of invasive pulmonary Aspergillosis in HIV/AIDS patients: a prospective analysis
Keywords:
galactomannan, HIV/AIDS, invasive pulmonary aspergillosis, serumAbstract
Background: Invasive pulmonary aspergillosis (IPA) is a life threatening infection among immunocompromised patients. A timely and precise diagnosis of this condition is often precluded by lack of sensitive and specific noninvasive diagnostic tools. Detection of galactomannan has emerged as a promising tool in this regard. While the analytical performance of serum galactomannan assay has been extensively evaluated in various high risk groups, its possible utility in HIV/AIDS patients is yet to be explored. The present study was undertaken to evaluate the yield of a serum galactomannan assay for diagnosis of IPA in a cohort of HIV/AIDS patients.
Methods: 49 febrile HIV reactive patients with co-existent symptomatic AIDS were prospectively enrolled for the evaluation. Blood samples were drawn from each patient and serum galactomannan screening was performed employing the commercially available serum galactomannan assay, Plateliaâ„¢ Aspergillus EIA. An optical density index >0.5 for at least two serum samples was considered the defining criteria for a positive result. Furthermore, sputum samples were collected and direct microscopic examination (10% potassium hydroxide wet mount) and fungal cultures were performed.
Result: In accordance with the definitions laid down under EORTC/MSG (European Organization for Research and Treatment of Cancer / Mycoses Study Group) criteria, ten cases of probable and 23 cases of possible IPA were diagnosed. The sensitivity, specificity, and positive and negative predictive values of Plateliaâ„¢ Aspergillus EIA for patients with probable IPA were 90%, 100%, 100% and 94.12 % respectively.
Conclusion: Serum galactomannan assay has a high sensitivity and specificity and when complemented with relevant lower respiratory tract symptomatology and imaging findings, can serve as a useful adjunct to conventional modalities for the diagnosis of IPA in HIV/AIDS patients.
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DOI:Â 10.21276/APALM.1439
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25. De Pauw B, Walsh TJ, Donnelly JP, et al; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46:1813-21.
26. Guinea J, Jensen J, Peláez T, et al. Value of a single galactomannan determination (Platelia) for the diagnosis of invasive aspergillosis in non-hematological patients with clinical isolation of Aspergillus spp. Med Mycol 2008; 46:575-9.
27. Husain S, Paterson DL, Studer SM, et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation 2007; 83:1330-6.
28. Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis 2007; 45:205-16.
29. Maertens J, Verhaegen J, Demuynck H, et al. Autopsy-controlled prospective evaluation of serial screening for circulating galactomannan by a sandwich enzyme-linked immunosorbent assay for hematological patients at risk for invasive Aspergillosis. J Clin Microbiol 1999; 37:3223-8.
30. Aubry A, Porcher R, Bottero J, et al. Occurrence and kinetics of false-positive Aspergillus galactomannan test results following treatment with beta-lactam antibiotics in patients with hematological disorders. J Clin Microbiol 2006; 44:389-94.
31. Maertens J, Theunissen K, Lodewyck T, Lagrou K, Van Eldere J. Advances in the serological diagnosis of invasive Aspergillus infections in patients with haematological disorders. Mycoses 2007; 50 Suppl 1:2-17.
32. Viscoli C, Machetti M, Cappellano P, et al. False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. Clin Infect Dis 2004; 38:913-6.
33. Racil Z, Kocmanova I, Lengerova M, Winterova J, Mayer J. Intravenous PLASMA-LYTE as a major cause of false-positive results of platelia Aspergillus test for galactomannan detection in serum. J Clin Microbiol 2007; 45:3141-2.
34. Mikulska M, Furfaro E, Del Bono V, et al. Galactomannan testing might be useful for early diagnosis of fusariosis. Diagn Microbiol Infect Dis 2012; 72:367-9.
35. Huang YT, Hung CC, Hsueh PR. Aspergillus galactomannan antigenemia in penicilliosis marneffei. AIDS 2007; 21:1990-1.
36. Dalle F, Charles PE, Blanc K, et al. Cryptococcus neoformans Galactoxylomannan contains an epitope(s) that is cross-reactive with Aspergillus Galactomannan. J Clin Microbiol 2005; 43:2929-31.
37. Bonini A, Capatti C, Parmeggiani M, et al. Galactomannan detection in Geotrichum capitatum invasive infections: report of 2 new cases and review of diagnostic options. Diagn Microbiol Infect Dis 2008; 62:450-2.
38. He H, Ding L, Sun B, Li F, Zhan Q. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Crit Care 2012; 16:R138.
2. Min Z, Baddley JW, Rodriguez JM, Moser SA, Patel M. Cross-reactivity of Aspergillus galactomannan in an HIV-infected patient with histoplasmosis. Med Mycol Case Rep 2012; 1: 119-22.
3. Holding KJ, Dworkin MS, Wan PC, et al. Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Adult and Adolescent Spectrum of HIV Disease Project. Clin Infect Dis 2000; 31: 1253-7.
4. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006; 42:1417-27.
5. Klont RR, Mennink-Kersten MA, Verweij PE. Utility of Aspergillus antigen detection in specimens other than serum specimens. Clin Infect Dis 2004; 39: 1467-74.
6. Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R. Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. J Thorac Imaging 2007; 22:160-5.
7. Li XS, Zhu HX, Fan HX, Zhu L, Wang HX, Song YL. Pulmonary fungal infections after bone marrow transplantation: the value of high-resolution computed tomography in predicting their etiology. Chin Med J (Engl) 2011; 124:3249-54.
8. Walsh TJ, Anaissie EJ, Denning DW, et al; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46:327-60.
9. Hope WW, Walsh TJ, Denning DW. The invasive and saprophytic syndromes due to Aspergillus spp. Med Mycol 2005; 43 Suppl 1:S207-38.
10. Ascioglu S, Rex JH, de Pauw B, et al; Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34: 7-14.
11. Barton RC. Laboratory diagnosis of invasive aspergillosis: from diagnosis to prediction of outcome. Scientifica (Cairo) 2013; 2013:459405.
12. Steinbach WJ, Addison RM, McLaughlin L, et al. Prospective Aspergillus galactomannan antigen testing in pediatric hematopoietic stem cell transplant recipients. Pediatr Infect Dis J 2007; 26:558-64.
13. Patterson TF. Clinical utility and development of biomarkers in invasive aspergillosis. Trans Am Clin Climatol Assoc 2011; 122: 174-83.
14. Donnelly JP. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin Infect Dis 2006; 42:487-9.
15. Hope WW, Kruhlak MJ, Lyman CA, et al. Pathogenesis of Aspergillus fumigatus and the kinetics of galactomannan in an in vitro model of early invasive pulmonary aspergillosis: implications for antifungal therapy. J Infect Dis 2007; 195:455-66.
16. Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis 2004; 4:349-57.
17. Khanna S, Oberoi J K, Datta S, Aggarwal S, Wattal C. Variables affecting the performance of galactomannan assay in high-risk patients at a tertiary care centre in India. Indian J Med Microbiol 2013;31:34-9
18. Ghosh I, Raina V, Kumar L, Sharma A, Bakhshi S, Iqbal S. Serum galactomannan assay for diagnosis of probable invasive Aspergillosis in acute leukemia and hematopoietic stem cell transplantation. Indian J Med Paediatr Oncol 2013; 34:74-9.
19. Moore GS, Jaciow DM (1979) Mycology for the Clinical Laboratory. Reston, VA: Prentice-Hall, USA.
20. Guinea J, Torres-Narbona M, Gijón P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16: 870-7.
21. Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med 2004; 170: 621-5.
22. Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011; 24: 247-80.
23. Lopes da Silva R, Ribeiro P, Abreu N, et al. Early diagnosis of invasive aspergillosis in neutropenic patients. Comparison between serum galactomannan and polymerase chain reaction Clinical Medicine Insights: Oncology 2010; 4:81-8.
24. Tarrand JJ, Lichterfeld M, Warraich I, et al. Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol 2003; 119:854-8.
25. De Pauw B, Walsh TJ, Donnelly JP, et al; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46:1813-21.
26. Guinea J, Jensen J, Peláez T, et al. Value of a single galactomannan determination (Platelia) for the diagnosis of invasive aspergillosis in non-hematological patients with clinical isolation of Aspergillus spp. Med Mycol 2008; 46:575-9.
27. Husain S, Paterson DL, Studer SM, et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation 2007; 83:1330-6.
28. Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis 2007; 45:205-16.
29. Maertens J, Verhaegen J, Demuynck H, et al. Autopsy-controlled prospective evaluation of serial screening for circulating galactomannan by a sandwich enzyme-linked immunosorbent assay for hematological patients at risk for invasive Aspergillosis. J Clin Microbiol 1999; 37:3223-8.
30. Aubry A, Porcher R, Bottero J, et al. Occurrence and kinetics of false-positive Aspergillus galactomannan test results following treatment with beta-lactam antibiotics in patients with hematological disorders. J Clin Microbiol 2006; 44:389-94.
31. Maertens J, Theunissen K, Lodewyck T, Lagrou K, Van Eldere J. Advances in the serological diagnosis of invasive Aspergillus infections in patients with haematological disorders. Mycoses 2007; 50 Suppl 1:2-17.
32. Viscoli C, Machetti M, Cappellano P, et al. False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. Clin Infect Dis 2004; 38:913-6.
33. Racil Z, Kocmanova I, Lengerova M, Winterova J, Mayer J. Intravenous PLASMA-LYTE as a major cause of false-positive results of platelia Aspergillus test for galactomannan detection in serum. J Clin Microbiol 2007; 45:3141-2.
34. Mikulska M, Furfaro E, Del Bono V, et al. Galactomannan testing might be useful for early diagnosis of fusariosis. Diagn Microbiol Infect Dis 2012; 72:367-9.
35. Huang YT, Hung CC, Hsueh PR. Aspergillus galactomannan antigenemia in penicilliosis marneffei. AIDS 2007; 21:1990-1.
36. Dalle F, Charles PE, Blanc K, et al. Cryptococcus neoformans Galactoxylomannan contains an epitope(s) that is cross-reactive with Aspergillus Galactomannan. J Clin Microbiol 2005; 43:2929-31.
37. Bonini A, Capatti C, Parmeggiani M, et al. Galactomannan detection in Geotrichum capitatum invasive infections: report of 2 new cases and review of diagnostic options. Diagn Microbiol Infect Dis 2008; 62:450-2.
38. He H, Ding L, Sun B, Li F, Zhan Q. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Crit Care 2012; 16:R138.
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Kaur R, Mehra B, Dhakad MS, Goyal R, Bhalla P, Dewan R. Utility of a serum Aspergillus galactomannan assay in diagnosis of invasive pulmonary Aspergillosis in HIV/AIDS patients: a prospective analysis. Ann of Pathol and Lab Med [Internet]. 2017 Oct. 24 [cited 2024 Nov. 19];4(5):A515-521. Available from: https://pacificejournals.com/journal/index.php/apalm/article/view/apalm1439
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Copyright (c) 2017 Ravinder Kaur, Bhanu Mehra, Megh Singh Dhakad, Ritu Goyal, Preena Bhalla, Richa Dewan
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