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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 732-734
Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid sample from suspected patients of invasive pulmonary aspergillosis


1 Department of Microbiology, ABVIMS and Dr RML Hospital, New Delhi, India
2 Department of Medicine, ABVIMS and Dr RML Hospital, New Delhi, India

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Date of Submission14-Aug-2020
Date of Decision02-Oct-2020
Date of Acceptance09-Oct-2020
Date of Web Publication20-Oct-2021
 

   Abstract 


Invasive pulmonary aspergillosis (IPA) is mainly caused by Aspergillus fumigatus and other Aspergillus species. Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion; therefore, detection of the GM antigen level can be useful in making an early diagnosis of IPA.

Keywords: Aspergillosis, ELISA, galactomannan, invasive

How to cite this article:
Malhotra S, Kumari R, Chauhan AK, Bhatia NK, Kaur A, Sharma B, Duggal N. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid sample from suspected patients of invasive pulmonary aspergillosis. Indian J Pathol Microbiol 2021;64:732-4

How to cite this URL:
Malhotra S, Kumari R, Chauhan AK, Bhatia NK, Kaur A, Sharma B, Duggal N. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid sample from suspected patients of invasive pulmonary aspergillosis. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 27];64:732-4. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/732/328590





   Introduction Top


Aspergillus is a saprophytic fungus found ubiquitously in the environment and it is responsible for a variety of infections like allergic aspergillosis, invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, CNS aspergillosis etc., depending on the host immune system. Invasive pulmonary aspergillosis (IPA) is reported primarily from the patients with defective immune system and as the number of patients with impaired immune system increases the significance of this infection has also increased. Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus but other species like A. flavus and A. niger can also lead to IPA. Infection Is acquired by the inhalation of the spores of fungus. Aspergillus species can invade the tracheal bronchus and lung directly, resulting in airway colonization, lung inflammatory granuloma, and even more serious sequelae, such as necrotizing pneumonia, and they can also affect other organs through hematogenous spread. Previously, IPA was recognized as occurring mainly in patients with neutrophil deficiencies. These patients generally have serious immunosuppressive conditions, such as malignant hepatopathy, solid organ or hematopoietic stem cell transplants, and human immunodeficiency virus (HIV) infection, or receiving long-term immunosuppressive therapy. However now a days it has increasingly been found in non-neutropenic patients especially those with chronic obstructive pulmonary disease (COPD), bronchiectasis, or previous tuberculosis.[1]

Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion, and the presence of this antigen can be sustained for 1 to 8 weeks.

Therefore, detection of the GM antigen level via enzyme-linked immunosorbent assay (ELISA) can be useful in making an early diagnosis of IPA. Galactomannan assay is included in the microbiological diagnostic criterion for fungus infection, according to the guidelines of 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).[2] With the introduction of new non-invasive tests and more effective antifungal agents, the mortality rates associated with this infection has decreased.

So, the current study was performed to determine the diagnostic value of galactomannan antigen test in early diagnosis of Invasive Pulmonary Aspergillosis.


   Material and Methods Top


The study was carried out on a total of 286 patients with clinically suspected pulmonary aspergillosis. Bronchoalveolar lavage (BAL) and serum samples were obtained from these patients. All BAL samples were processed for fungal microscopy (KOH mount) and culture. Culture was put on SDA (with or without antibiotics) and incubated at 25°C and 37°C for 6 weeks. Identification of fungal isolates was based on morphology as per standard technique.[3] A total of 218 serum samples and 68 BAL samples were received. Both BAL and serum sample were received from 26 patients. Galactomannan detection in Bronchoalveolar lavage fluid and serum samples was performed by enzyme-linked immunosorbent assay (ELISA). Results were read according to the kit used for ELISA assay-

For serum samples- OD index > 0.5 was considered to be positive for Galactomannan antigen.

For BAL samples- OD index > 1 was considered to be positive for Galactomannan antigen.


   Results Top


A total of 286 patients with clinical suspicion of pulmonary aspergillosis were included in the study. Amongst these patients, serum sample were taken from 218 patients and BAL samples from 68 patients. As per diagnostic criteria of IPA European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) Invasive Pulmonary Aspergillosis was clinically confirmed in 137 patients. Amongst these 137 clinically confirmed Invasive pulmonary aspergillosis cases, 96 (65 serum and 31 BAL samples) were found to be positive for galactomannan test. Out of these 96 patients, 24 were female and 72 were male.

A total of 55 (44%) BAL samples were received from 137 patients, out of which 31 were galactomannan positive giving 56% correlation between clinical diagnosis and galactomannan test. However only 18% of these sample were positive by KOH and culture [Figure 1]. Both BAL and Serum samples were received from 26 patients out of which 16 (72.73%) showed positivity for galactomannan in BAL samples and 10 (45.46%) patients showed galactomannan positivity in serum samples.
Figure 1: Comparison of galactomannan, KOH, and Culture of BAL sample

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We check the patients for their immune status and found that out of 286 patients, 160 patients were having some form of immunocompromised state. Amongst these 160 patients, 120 (75%) patients were suffering from IPA. In the remaining 126 immunocompetent patients only 17 (13.49%) patients were found to be suffering with IPA [Figure 2].
Figure 2: Distribution of patients according to immune status

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   Discussion Top


Invasive pulmonary aspergillosis is a severe fungal infection with high morbidity and mortality. If the diagnosis and treatment of IPA is not done at right time or early then the outcome is fatal. Hence early diagnosis of IPA is very important in preventing the mortality from this invasive fungal infection.

In our study we found male preponderance for Invasive pulmonary aspergillosis in comparison to female patients. The reason for same could be much more exposure of males to professional activities predisposing to the fungal infections. A study from Taiwan also showed the male preponderance in case of invasive pulmonary aspergillosis.[4]

We found 70% patients as probable cases of invasive pulmonary aspergillosis while the number of possible invasive pulmonary Aspergillosis were found to be 30% according to European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria (EORTC/MSG).[5] Our results were in concordance to another study by Toienemercier where percentage of probable IPA was 68% and possible IPA was 44%.[6]

The positivity of galactomannan in BAL sample was 56% in comparison to 18% by KOH/Culture. As per literature also the culture positivity for fungi is low that is around 12% in comparison to positivity of galactomannan in BAL 50% shown by Krishtina affolter et al.[7] Another study by Wei Zhou showed that sensitivity of BAL galactomannan was 75% in comparison to culture which was 9%.[8] A similar study conducted by Jorien D Hasse also shows that BAL galactomannan detection has a higher sensitivity (86%).[9] We found 56% galactomannan positivity in BAL which was in accordance to another study performed in Europe.[10] Hence Galactomannan test can serve as a useful tool in the diagnosis of IPA in combination with culture.

Immunocompromised state was observed in 55.94% patients out of the total 286 patients, out of these Immunocompromised patients 75% were diagnosed as IPA. One hundred and twenty-six patients were immunocompetent out of which only 13.49% were suffering with invasive pulmonary aspergillosis. This shows that the incidence of invasive pulmonary aspergillosis is much higher in immunocompromised patients in comparison to immunocompetent patients. But one should not ignore the fact that the disease is not very uncommon in immunocompetent patients as well.[11]


   Conclusions Top


Invasive pulmonary aspergillosis is a life-threatening condition if the diagnosis is delayed. It is difficult to diagnose this disease without performing any invasive procedures. However, galactomannan antigen detection test which is a non-invasive test serve as a useful diagnostic tool for the early detection of invasive aspergillosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Sugui JA, Chung KJK, Juvvadi PR, Paul J, Steinbach WJ. Aspergillus fumigatus and related species. Cold Spring Harb Perspect Med 2015;5:a019786.  Back to cited text no. 1
    
2.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. 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;15;:1813-21.  Back to cited text no. 2
    
3.
Richardson MD. Topley & Wilson. 9th ed. Aspergillosis. p. 3666-710.  Back to cited text no. 3
    
4.
Sun KS, Tsai CF, Chii S, Huang WC. Clinical outcome and prognostic factors associated with invasive pulmonary aspergillosis: An 11-year follow-up report from Taiwan. PLoS One 2017;12:e0186422.  Back to cited text no. 4
    
5.
Blot SI, Taccone FS, Van den Abeele AM, Bulpa P, Meersseman W, Brusselaers N, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically Ill patients. Am J Respir Crit Care Med 2012;186:56-64.  Back to cited text no. 5
    
6.
Mercier T, Schauwvlieghe A, de Kort E, Dunbar A, Reynders M, Guldentops E, et al. Diagnosing invasive pulmonary aspergillosis in hematology patients: A 2 retrospective multicenter evaluation of a novel lateral flow device. J Clin Microbiol 2019;57:e01913-18.  Back to cited text no. 6
    
7.
Affolter K, Tamm M, Jahn K, Halter J, Passweg J, Hirsch HH, et al. Galactomannan in bronchoalveolar lavage for diagnosing invasive fungal disease. Am J Respir Crit Care Med 2014;190:309-17.  Back to cited text no. 7
    
8.
Zhou W, Li H, Zhang Y, Huang M, He Q, Li P, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61.  Back to cited text no. 8
    
9.
Moreno-González G, Ricart de Mesones A, Tazi-Mezalek R, Marron-Moya MT, Rosell A, Mañez R. Invasive pulmonary aspergillosis with disseminated infection in immunocompetent patient. Can Respir J 2016;2016:7984032.  Back to cited text no. 9
    
10.
D'Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: Analytical and clinical validity. J Clin Microbiol 2012;50:1258-63.  Back to cited text no. 10
    
11.
Bergeron A, Belle A, Sulahian A, Lacroix C, Chevret S, Raffoux E, et al. Contribution of galactomannan antigen detection in BAL to the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies. Chest 2010;137:410-5.  Back to cited text no. 11
    

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Correspondence Address:
Shalini Malhotra
Department of Microbiology, ABVIMS and Dr RML Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_985_20

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