A newly identified cause of false-positive galactomannan antigen test
Galactomannan (GM) is a component of the fungal cell wall and an exoantigen of
Aspergillus. Detection of GM antigen in serum by the ELISA-based kit "Platelia
Aspergillus EIA" (Bio-Rad Lab.) is now one of the adjunctive methods used in diagnosis of invasive aspergillosis (IA). GM antigen positivity is among the microbiological diagnostic criteria proposed by European Organization for Research and Treatment of Cancer (EORTC) and Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) for diagnosis of IA.
While the GM antigen test is now commonly used as a screening test in patients at high risk of developing IA, there are still challenges in interpretation of the test results. One of these difficulties is the positivity of the GM antigen test due to causes other than IA.
Several causes have so far been identified for false-positive GM antigen test results. These include true antigenic cross-reactivity with other fungi such as
Penicillium chrysogenum,
Penicillium digitatum, and
Paecilomyces variotii; false-positive antigenemia due probably to translocation of the antigen found in various foodstuffs (unsalted bread, macaroni, corn flakes, salted rice, dry cake, turkey slices, grilled sausage, fried potatoes, etc.) through the damaged intestinal mucosa; translocation of
Bifidobacterium from the intestinal tract particularly in neonates; and drugs such as piperacillin-tazobactam, amoxicillin-clavulanic acid, and cytotoxic chemotherapeutics.
A new cause of false-positive GM antigen test has now been determined. The story started with the detection by Wheat and colleagues at Mira Vista Laboratories of false-positive GM test results in bronchoalveolar lavage fluid samples over a period of few months. The cause of this false positivity turned out to be an intravenous hydration fluid, Plasmalyte, which was used for lavage. Upon testing, several lots of Plasmalyte yielded strongly positive results when tested for GM. GM was presumably carried through the purification process while preparing sodium gluconate, one of the components of Plasmalyte which is produced by fermentation in cultures of
Aspergillus.
Whether the intravenous administration of Plasmalyte will yield false-positive results for GM still remains unknown. In the interim, the potential of Plasmalyte to cause false-positive GM antigen test results should be kept in mind. It is not known whether similar electrolyte solutions (e.g., Pedialyte) will similarly generate false-positive results.
The readers are kindly referred to our related Mycology Newsletter (July, 2003) from the archive for detailed information about GM antigen test.
Related reading
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Wheat LJ. New cause for false-positive Aspergillus galactomannan antigen tests. Mira Vista e-newsletter, May 2006.
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Mennink-Kersten MA et al. Bifidobacterial lipoglycan as a new cause for false-positive Platelia Aspergillus enzyme-linked immunosorbent assay reactivity. J Clin Microbiol 2005;43:3925-31.
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Aubry 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.
