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Review
Non-cultural methods for the diagnosis of invasive fungal disease Expert Rev. Anti Infect. Ther. 13(1), 103–117 (2015)
Małgorzata Mikulska*1,2, Elisa Furfaro2 and Claudio Viscoli1,2 1 Division of Infectious Diseases, IRCCS San Martino University Hospital – IST, L.go R. Benzi, 10 – 16132, Genoa, Italy 2 Department of Health Sciences, University of Genoa, Genoa, Italy *Author for correspondence: Tel.: +39 010 555 4654 Fax: +39 010 3537680 [email protected]
Invasive fungal diseases carry a high mortality risk which can be reduced by early treatment. Diagnosing invasive fungal diseases is challenging, because invasive methods for obtaining histological samples are frequently not feasible in thrombocytopenic immunocompromised patients, while fungal cultures have low sensitivity and a long turn-around time. Non-cultural methods are fundamental for a rapid diagnosis of invasive fungal diseases and they include assays based on the detection of fungal antigens (galactomannan, Aspergillus-lateral flow device, [1,3]-b-D-glucan, mannan), antibodies, such as anti-mannan, and molecular tests. With the exception of some molecular methods for rare fungi, the non-cultural assays are usually applied to the diagnosis of invasive aspergillosis, invasive candidiasis and pneumocystosis. The performance of a single test or a combination of tests will be discussed, with particular focus on choosing the most appropriate marker(s) for every specific patient population. Reasons for potential false-positive or false-negative results will be discussed. KEYWORDS: (1,3)-b-D-glucan • Aspergillus lateral flow device • fungal PCR • galactomannan • invasive aspergillosis • invasive candidiasis • mannan • pneumocystosis
Invasive fungal diseases (IFD) are a major cause of morbidity and mortality in immunocompromised patients. In hematological patients, invasive aspergillosis (IA) and invasive candidiasis (IC) used to be the most frequent fungal diseases until the advent of fluconazole. Nowadays, IA is the main fungal disease during long-lasting neutropenia. Other populations at risk for IA are patients receiving immunosuppressive therapy for prevention or management of graft-versus-host disease following hematopoietic stem cell transplantation (HSCT), solid organ transplant (SOT) recipients (mostly lung) and those with lymphoproliferative diseases [1]. More recently, IA has been also reported in patients with chronic obstructive pulmonary disease or admitted to intensive care units. IC affects predominantly patients who have undergone abdominal surgery, are admitted to ICU, have a central venous catheter placed or receive a broad spectrum antibiotic therapy [2]. Many patients with IC are hospitalized in internal medicine wards. Each of these populations at risk for IFD need an appropriate individualized diagnostic strategy, which should be based on the clinical
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Non-cultural methods for the diagnosis of invasive fungal disease Expert Rev. Anti Infect. Ther. 13(1), 103–117 (2015)
Małgorzata Mikulska*1,2, Elisa Furfaro2 and Claudio Viscoli1,2 1 Division of Infectious Diseases, IRCCS San Martino University Hospital – IST, L.go R. Benzi, 10 – 16132, Genoa, Italy 2 Department of Health Sciences, University of Genoa, Genoa, Italy *Author for correspondence: Tel.: +39 010 555 4654 Fax: +39 010 3537680 [email protected]
Invasive fungal diseases carry a high mortality risk which can be reduced by early treatment. Diagnosing invasive fungal diseases is challenging, because invasive methods for obtaining histological samples are frequently not feasible in thrombocytopenic immunocompromised patients, while fungal cultures have low sensitivity and a long turn-around time. Non-cultural methods are fundamental for a rapid diagnosis of invasive fungal diseases and they include assays based on the detection of fungal antigens (galactomannan, Aspergillus-lateral flow device, [1,3]-b-D-glucan, mannan), antibodies, such as anti-mannan, and molecular tests. With the exception of some molecular methods for rare fungi, the non-cultural assays are usually applied to the diagnosis of invasive aspergillosis, invasive candidiasis and pneumocystosis. The performance of a single test or a combination of tests will be discussed, with particular focus on choosing the most appropriate marker(s) for every specific patient population. Reasons for potential false-positive or false-negative results will be discussed. KEYWORDS: (1,3)-b-D-glucan • Aspergillus lateral flow device • fungal PCR • galactomannan • invasive aspergillosis • invasive candidiasis • mannan • pneumocystosis
Invasive fungal diseases (IFD) are a major cause of morbidity and mortality in immunocompromised patients. In hematological patients, invasive aspergillosis (IA) and invasive candidiasis (IC) used to be the most frequent fungal diseases until the advent of fluconazole. Nowadays, IA is the main fungal disease during long-lasting neutropenia. Other populations at risk for IA are patients receiving immunosuppressive therapy for prevention or management of graft-versus-host disease following hematopoietic stem cell transplantation (HSCT), solid organ transplant (SOT) recipients (mostly lung) and those with lymphoproliferative diseases [1]. More recently, IA has been also reported in patients with chronic obstructive pulmonary disease or admitted to intensive care units. IC affects predominantly patients who have undergone abdominal surgery, are admitted to ICU, have a central venous catheter placed or receive a broad spectrum antibiotic therapy [2]. Many patients with IC are hospitalized in internal medicine wards. Each of these populations at risk for IFD need an appropriate individualized diagnostic strategy, which should be based on the clinical
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