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MICROBIAL IMMUNOLOGY

High Levels of β-d-Glucan in Immunocompromised Children with Proven Invasive Fungal Disease

Alessandra Mularoni, Elisa Furfaro, Maura Faraci, Alessia Franceschi, Paola Mezzano, Roberto Bandettini, Claudio Viscoli, Elio Castagnola
Alessandra Mularoni
1Infectious Diseases Unit
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Elisa Furfaro
6Infectious Diseases Department, University of Genoa, Genoa, Italy
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Maura Faraci
2Hemopoietic Stem Cell Transplant Unit
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Alessia Franceschi
3Pediatric Intensive Care Unit
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Paola Mezzano
4Neonatal Intensive Care Unit
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Roberto Bandettini
5Laboratory of Clinical Microbiology, G. Gaslini Children's Hospital, Genoa, Italy
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Claudio Viscoli
6Infectious Diseases Department, University of Genoa, Genoa, Italy
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Elio Castagnola
1Infectious Diseases Unit
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  • For correspondence: eliocastagnola@ospedale-gaslini.ge.it
DOI: 10.1128/CVI.00038-10
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ABSTRACT

The plasmatic levels of 1,3-β-d-glucan (BDG) were >523 pg/ml in 4 children, 2 low-birth-weight neonates and 2 stem cell transplant recipients, with the following invasive fungal diseases (IFD) proven apart from this BDG test: 3 cases of Candida parapsilosis candidemias and 1 case of disseminated aspergillosis. The BDG test may be useful for identification of IFD in pediatrics.

Invasive fungal diseases (IFD) may represent severe complications in immunocompromised children or low-birth-weight neonates. The definitions of proven and probable IFD implemented for adults (7) may also be applied successfully to immunocompromised children (4). However, while there is enough evidence of the reliability of the galactomannan antigen test for the diagnosis of invasive aspergillosis in pediatrics (5, 16, 17), no data are available for the use of 1,3-β-d-glucan (BDG) to define a diagnosis of “probable” IFD either in immunocompromised children or in low-birth-weight neonates, which represent another group at high risk of IFD (2, 3). At present, the only pediatric study available was performed with normal children using the Fungitell assay (Associates of Cape Cod, Inc., Falmouth, MA) and showed the presence of some false-positive results (15).

With the aim of evaluating the performance of the BDG test in children with proven IFD, we checked for the presence of this antigen in blood samples obtained from 4 pediatric patients with IFD already proven by positive culture from a sterile site and/or the demonstration of fungal elements in diseased tissues (7). The test was performed using the Fungitell assay (Associates of Cape Cod, Inc., Falmouth, MA), with a positive cutoff of 60 pg/ml, according to the manufacturer's recommendations. In all cases, the first positive test had to be confirmed by a second positive test performed with a sample taken more than 24 h after the first one.

Two cases were represented by low-birth-weight neonates (12 and 20 days old) with Candida parapsilosis candidemia, who presented values of BDG of >523 pg/ml in the presence of persistently positive blood cultures, and another case of C. parapsilosis candidemia with a BDG value of >523 pg/ml was observed in an 11-year-old girl receiving an allogeneic hematopoietic stem cell transplant (HSCT). The fourth case was a complex clinical condition observed in a 14-year-old boy with chronic graft-versus-host disease (GvHD), following an allogeneic HSCT. The patient was admitted into the intensive care unit for septic shock and pneumonia initially treated empirically with piperacillin-tazobactam and liposomal amphotericin B. In the following days, Pseudomonas aeruginosa was documented in blood and sputum cultures. The serum galactomannan antigen test initially had an index of 0.3, which increased to 0.9 in the following days, but this low positive value was attributed to piperacillin-tazobactam (12). Anyway, antibacterial treatment was shifted to meropenem for better monitoring of the risk of invasive aspergillosis, considering the possibility of concomitant infections by P. aeruginosa and Aspergillus in patients with chronic GvHD (1). In the meantime, the BDG test was also performed, and it resulted in a BDG level of 222 pg/ml. Although the blood cultures were negative, the BDG result was positive. This result was considered with suspicion because of the possibility of false-positive results in the presence of P. aeruginosa bacteremia (8). However, 2 days later, the patient presented a dramatic worsening of pulmonary disease, associated with the appearance of disseminated nodular skin lesions. At this time, the galactomannan antigen test had an index of 5.8, and the BDG level was >523 pg/ml. A biopsy specimen of the skin lesions showed the presence of filamentous fungi infiltrating blood vessels. Unfortunately, no pathogen grew from skin or blood cultures, and therefore, the diagnosis was that of an IFD due to a filamentous fungus, probably Aspergillus. Clinical data regarding all 4 patients are summarized in Table 1.

In spite of the use of different diagnostic assays, studies in neutropenic and nonneutropenic adults demonstrated that the monitoring of BDG levels might be a useful noninvasive method for the early diagnosis of IFD (6, 10, 11, 13, 14). The only pediatric data available derive from a study of normal children without IFD showing that mean glucan levels were higher in children than in adults, with a small number of false-positive results (15). Unfortunately, this study did not report any data showing the performance of BDG testing in children with IFD. Even if derived from a small number of cases, our experience shows that BDG levels may be very high in children with proven IFD. The BDG test has many causes for false-positive results, including antibiotics (amoxicillin-clavulanate) and bacterial infections (Alcaligenes faecalis, Streptococcus pneumoniae, and P. aeruginosa) (8, 9). We considered these possibilities, and retrospectively, this consideration led to a delay in the diagnosis for one case. We evaluated the BDG test in children with already proven IFD for exploratory purposes only; therefore, any first test (that resulted in very high levels in any case) had to be confirmed by a second one in spite of the fact that the IFD was already documented. With these assumptions, our results suggest the utility of the BDG test for immunocompromised children or low-birth-weight neonates with IFD. However, further prospective studies are needed to evaluate the right cutoff and the timing of positivity of BDG, as well as its sensitivity, specificity, and predictive values as a predictor of IFD in children at risk.

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TABLE 1.

Demographics, underlying conditions, types and etiology, and values and timing of positive levels of 1,3-β-d-glucan in four children with documented IFD

FOOTNOTES

    • Received 28 January 2010.
    • Returned for modification 25 February 2010.
    • Accepted 16 March 2010.
  • Copyright © 2010 American Society for Microbiology

REFERENCES

  1. 1.↵
    Alangaden, G. J., M. Wahiduzzaman, and P. H. Chandrasekar. 2002. Aspergillosis: the most common community-acquired pneumonia with gram-negative bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease. Clin. Infect. Dis.35:659-664.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    Benjamin, D. K., Jr., B. J. Stoll, A. A. Fanaroff, S. A. McDonald, W. Oh, R. D. Higgins, S. Duara, K. Poole, A. Laptook, and R. Goldberg. 2006. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics117:84-92.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    Castagnola, E., and S. Buratti. 2009. Clinical aspects of invasive candidiasis in paediatric patients. Drugs69(Suppl. 1):45-50.
    OpenUrlCrossRefPubMed
  4. 4.↵
    Castagnola, E., S. Cesaro, M. Giacchino, S. Livadiotti, F. Tucci, G. Zanazzo, D. Caselli, I. Caviglia, S. Parodi, R. Rondelli, P. E. Cornelli, R. Mura, N. Santoro, G. Russo, R. De Santis, S. Buffardi, C. Viscoli, R. Haupt, and M. R. Rossi. 2006. Fungal infections in children with cancer: a prospective, multicenter surveillance study. Pediatr. Infect. Dis. J.25:634-639.
    OpenUrlCrossRefPubMedWeb of Science
  5. 5.↵
    Castagnola, E., E. Furfaro, I. Caviglia, M. Licciardello, M. Faraci, F. Fioredda, P. Tomà, R. Bandettini, M. Machetti, and C. Viscoli. 11 February 2010, posting date. Performance of galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing hemopoietic stem cell transplant. Clin. Microbiol. Infect. doi:10.1111/j.1469-0691.2009.03065.x.
    OpenUrlCrossRef
  6. 6.↵
    Del Bono, V., A. Mularoni, E. Furfaro, E. Delfino, L. Rosasco, F. Miletich, and C. Viscoli. 2009. Clinical evaluation of a (1,3)-beta-d-glucan assay for presumptive diagnosis of Pneumocystis jiroveci pneumonia in immunocompromised patients. Clin. Vaccine Immunol.16:1524-1526.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    De Pauw, B., T. J. Walsh, J. P. Donnelly, D. A. Stevens, J. E. Edwards, T. Calandra, P. G. Pappas, J. Maertens, O. Lortholary, C. A. Kauffman, D. W. Denning, T. F. Patterson, G. Maschmeyer, J. Bille, W. E. Dismukes, R. Herbrecht, W. W. Hope, C. C. Kibbler, B. J. Kullberg, K. A. Marr, P. Munoz, F. C. Odds, J. R. Perfect, A. Restrepo, M. Ruhnke, B. H. Segal, J. D. Sobel, T. C. Sorrell, C. Viscoli, J. R. Wingard, T. Zaoutis, and J. E. Bennett. 2008. 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.46:1813-1821.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    Mennink-Kersten, M. A., D. Ruegebrink, and P. E. Verweij. 2008. Pseudomonas aeruginosa as a cause of 1,3-beta-D-glucan assay reactivity. Clin. Infect. Dis.46:1930-1931.
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    Mennink-Kersten, M. A., and P. E. Verweij. 2006. Non-culture-based diagnostics for opportunistic fungi. Infect. Dis. Clin. North Am.20:711-727.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    Odabasi, Z., G. Mattiuzzi, E. Estey, H. Kantarjian, F. Saeki, R. J. Ridge, P. A. Ketchum, M. A. Finkelman, J. H. Rex, and L. Ostrosky-Zeichner. 2004. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin. Infect. Dis.39:199-205.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    Ostrosky-Zeichner, L., B. D. Alexander, D. H. Kett, J. Vazquez, P. G. Pappas, F. Saeki, P. A. Ketchum, J. Wingard, R. Schiff, H. Tamura, M. A. Finkelman, and J. H. Rex. 2005. Multicenter clinical evaluation of the (1→3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin. Infect. Dis.41:654-659.
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    Pfeiffer, C. D., J. P. Fine, and N. Safdar. 2006. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin. Infect. Dis.42:1417-1427.
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    Pisculli, M. L., and P. E. Sax. 2008. Use of a serum beta-glucan assay for diagnosis of HIV-related Pneumocystis jiroveci pneumonia in patients with negative microscopic examination results. Clin. Infect. Dis.46:1928-1930.
    OpenUrlCrossRefPubMedWeb of Science
  14. 14.↵
    Senn, L., J. O. Robinson, S. Schmidt, M. Knaup, N. Asahi, S. Satomura, S. Matsuura, B. Duvoisin, J. Bille, T. Calandra, and O. Marchetti. 2008. 1,3-Beta-D-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clin. Infect. Dis.46:878-885.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    Smith, P.-B., D. K. Benjamin, Jr., B. D. Alexander, M. D. Johnson, M. A. Finkelman, and W. J. Steinbach. 2007. Quantification of 1,3-beta-d-glucan levels in children: preliminary data for diagnostic use of the beta-glucan assay in a pediatric setting. Clin. Vaccine Immunol.14:924-925.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    Steinbach, W. J., R. M. Addison, L. McLaughlin, Q. Gerrald, P. L. Martin, T. Driscoll, C. Bentsen, J. R. Perfect, and B. D. Alexander. 2007. Prospective Aspergillus galactomannan antigen testing in pediatric hematopoietic stem cell transplant recipients. Pediatr. Infect. Dis. J.26:558-564.
    OpenUrlCrossRefPubMed
  17. 17.↵
    Sulahian, A., F. Boutboul, P. Ribaud, T. Leblanc, C. Lacroix, and F. Derouin. 2001. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer91:311-318.
    OpenUrlCrossRefPubMedWeb of Science
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High Levels of β-d-Glucan in Immunocompromised Children with Proven Invasive Fungal Disease
Alessandra Mularoni, Elisa Furfaro, Maura Faraci, Alessia Franceschi, Paola Mezzano, Roberto Bandettini, Claudio Viscoli, Elio Castagnola
Clinical and Vaccine Immunology May 2010, 17 (5) 882-883; DOI: 10.1128/CVI.00038-10

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High Levels of β-d-Glucan in Immunocompromised Children with Proven Invasive Fungal Disease
Alessandra Mularoni, Elisa Furfaro, Maura Faraci, Alessia Franceschi, Paola Mezzano, Roberto Bandettini, Claudio Viscoli, Elio Castagnola
Clinical and Vaccine Immunology May 2010, 17 (5) 882-883; DOI: 10.1128/CVI.00038-10
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KEYWORDS

Aspergillosis
Candidiasis
Fungemia
Immunocompromised Host
beta-Glucans

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