Mantar enfeksiyonlarının serolojik tanısı

Yıl 2016, Cilt: 73 Sayı: 2, 175 - 182, 01.06.2016

Asuman Birinci Yeliz Tanrıverdi Çaycı

Öz

İnvaziv mantar hastalıklarının tanısında, günümüzde kullanılan yöntemlerin duyarlılık ve özgüllüğündeki yetersizlikler veya klinik olarak yararlı olabilecek bir sonucun elde edilmesinin çok zaman alması nedeniyle zorluklar yaşanmaktadır. Hasta sonuçlarında, hızlı tanı anahtar noktadır. Kültür testleri dışında, konaktaki özgül antikor yanıtının ölçülmesine dayalı serolojik testlerin, hızlı uygulanabilmesi ve invaziv örnek alım yöntemleri gerektirmemesi bu testleri çekici kılmaktadır. Ancak özellikle immünosupressif durumlar nedeniyle, özgül antikor yanıtı oluşturamayan hastalarda bu testler her zaman invaziv hastalık göstergesi olmamaktadır. Mikrobiyal antijenlerin tespitinin ise genellikle daha fazla miktarda mikrobiyal yük gerektirmesi duyarlılığını kısıtlamaktadır. Yine de çok sayıda başarıyla çalışan antijen tespit sistemleri geliştirilmiştir ve bunların bazıları halen yaygın olarak kullanılmaktadır. Dolaşımdaki Aspergillus galaktomannanlarını tespit için sıçan monoklonal EBA2’leri kullanan emzim immünoassay yöntemi Platelia ticari olarak kullanımdadır. Bu test 0,5-1,0 ng/ml düzeyindeki galaktomannanı tespit edebilmektedir. Ayrıca, galaktomannan klinik belirti ve semptomlar oluşmadan invaziv aspergillozun erken safhalarında serumda tespit edilebilmektedir. Ancak, bu testin yanlış pozitif veya negatif sonuçlar gibi dezavantajları bulunmaktadır. -β-D-glukan Zygomycetes’ler hariç mantar hücre duvarının karakteristik bir birleşenidir. İnvaziv enfeksiyonlar sırasında Aspergillus, Candida, Fusarium, Trichosporon, Saccharomyces, Acremonium ve Pneumocyctis jirovecii içeren birçok mantar tarafından -β-D-glukan kana salınmaktadır. -β-D-glukan konsantrasyonunun belirlenmesinde kullanılan yöntem, atnalı horsecrab shoe yengecinin

Anahtar Kelimeler

Mantar enfeksiyonları, galaktomannan, -β-D-glukan, mannan

Serological diagnosis of fungal infections

Öz

Difficulties are being faced in the diagnosis of invasive fungal diseases due to the lack of sensitivity and specificity of the current diagnostic methods or taking too long time to get a result having clinical importance. Rapid diagnosis is the key point in patient outcomes. Excluding the culture tests, because of its rapid application and no need for invasive sampling, was making the serological tests based on the measurement of response of specific host antibody became attractive. However especially due to immunosuppressive conditions, these tests are not always the indicator of invasive disease in the patients who have no ability to produce specific antibody response. Detection of microbial antigens generally requiring a relatively large microbial burden, limits the assay sensitivity. Nonetheless, several examples of successful antigen detection systems have been developed, and some of these are widely used. To detect circulating Aspergillus galactomannans enyzme immunoassay Platelia method utilizing the rat monoclonal antibody EB-A2 is commercially in use. This test is able to detect galactomannan in the level of 0.5-1.0 ng/ml. Furthermore, galactomannan could be detected in the serum at a early stage of invasive aspergillosis before clinical signs and symptoms occured. However, this test has some disavantages like false positive or negative results. -β-D-glucan is a characteristic cell-wall component of fungi except for Zygomycetes. A broad range of fungi including Aspergillus, During invasive infections -β-D-glucan is released to the blood by some fungi containing Aspergillus, Candida, Fusarium, Trichosporon, Saccharomyces, -β-D-glukan konsantrasyonunun belirlenmesinde kullanılan yöntem, atnalı horsecrab shoe yengecinin

Anahtar Kelimeler

Fungal infections, galactomannan, -β-D-glucan, mannan

Kaynakça

• Yeo SF, Wong B. Current status of non culture methods for diagnostics of invasive fungal infetions. Clin Microbiol Rev, 2002; 15: 465-83.
• McLintock LA, Jones BL. Advances in the molecular and serological diagnosis of invasive fungal infection in haemato-oncology patients. Brith J Hematol, 2004;126: 289-97.
• Kozel TH, Wickes B. Fungal Diagnostics. Cold Spring Harb Perspect Med, 2014; doi: 10.1101/ cshperspect.a019299.
• Verweij PE, Meis JFGM. Microbiological diagnosis of invasive fungal infections in transplant recipients. Transpl Infect Dis, 2000: 2: 80–7.
• Stynen D, Goris A, Sarfati J, Latge JP. A new sensitive sandwich enzyme-linked immünosorbent assay to detect galactofuran in patients with invasive aspergillosis. J Clin Microbiol, 1995; 33: 497–500.
• Mennik-Kersten M, Donnelly JP, Verweij P. Detection of circulating galactomannan for the diagnosis and management of invasive aspergilllosis. Lancet, 2004; 4(6): 349-57.
• Herbrecht R, Letscher-Bru V, Oprea C, Lioure B, Waller J, Campos F et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncology, 2002; 20: 1898–906.
• Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. Detection of galactomannan antigenemia by Enzyme Immunoassay for the Diagnosis of invasive Aspergillosis: variables that affect performance. J Infect Dis, 2004; 190(3): 641- 9.
• Aubry A, Porcher R, Bottero J, Touratier S, Leblanc T, Brethon B 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 Microb, 2006; 44: 389- 4.
• Mattei D, Rapezzi D, Mordini N, Cuda F, Nigro C, Musso M et al. False-Positive Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Results In Vivo during Amoxicillin-Clavulanic Acid Treatment. J Clin Microb, 2004; 42: 5362-3.
• Ağca H, Ener B, Yılmaz E, Ursavas A, Kazak E, Özkocaman V et al. Comparative evaluation of galactomannan optical density indices and culture results in bronchoscopic specimens obtained from neutropenic and non-neutropenic patients. Mycoses, 2014; 57: 169-75.
• Clancy CJ, Jaber RA, Leather HC, Wingard JR, Staley B, Wheat LJ et al. Bronchoalveolar Lavage Galactomannan in Diagnosis of Invasive Pulmonary Aspergillosis among Solid-Organ Transplant Recipients. J Clin Microbiol, 2007; 45(6): 1759-65.
• Fisher CE, Stevens AM, Leisenring W, Pergam SA, Boeckh M, Hohl TM. Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis. Transpl Infect Dis, 2014; 16: 505–10.
• Cuenca-Estrella M, Bassetti M, Lass-Flörl C, Racil Z, Richardson M, Rogers TR. Detection and investigation invasive mold disease. J Antimicrob Chemother, 2011; 66: 15-24.
• Miyazaki T, Kohno S, Mitsutake K, Maesaki S, Tanaka K, Ishikawa N et al. Plasma (1,3)-β-D-Glucan and Fungal Antigenemia in Patients with Candidemia, Aspergillosis, and Cryptococcosis. J Clin Microbiol, 1995; 33(12): 3115-8.
• Sulahian A, Porcher R, Bergeron A, Touratier S, Raffoux E, Menotti J et al. Use and Limits of (1,3)-β-D-Glucan Assay (Fungitell), Compared to Aspergillus), for Diagnosis of Invasive Aspergillosis. J Clin Microbiol, 2014; 52(7): 3228-33. (Platelia
• Ener B. İnvazif fungal infeksiyonlarda tanısal yaklaşım. Ankem Derg, 2013; 27(Ek2): 141-3.
• Stevens DA. Diagnosis of fungal infectons: current status. J Antimicrob Chemother, 2002; 49: 11-4.
• Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ et al. Β-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, 2004; 39: 199-205.
• Metan G, Koç AN, Kaynar LG, Atalay A, Öztürk A, Eser B et al. What is the role of the (1,3)-b-D- glucan assay in the screening of patients undergoing autologous haematopoietic stem-cell transplantation? Mycoses, 2013; 56: 34-8.
• Koo S, Bryar J, Page JH, Baden LR, Marty FM. Clinical utility of the (1,3)-B-D-glucan assay (BG) in the diagnosis of invasive fungal infections (IFI). Program and abstracts of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 27-30, 2006; San Francisco, California. Abstract M-1600.
• Held J, Kohlberger I, Rappold E, Grawitz AB, Häcker G. Comparison of (1,3)-β-D-Glucan, Mannan/anti- Mannan-antibodies and Cand-Tec Candida-Antigen as Serum Biomarkers for Candidemia. J Clin Microbiol, 2013;45(6):1158- 64.
• Sendid B, Poiret JL, Tabouret M, Bonnin A, Caillot D, Camus D, et al. Combined detection of mannanaemia and anti-mannan antibodies as a strategy for the diagnosis of systemic infections caused by pathogenic Candida species. J Med Microbiol, 2002; 51: 433– 42.
• Martínez JP, Gil ML, López-Ribot JL, Chaffin WLJ. Serologic Response to Cell Wall Mannoproteins and Proteins of Candida albicans. Clin Microbiol Rev, 1998; 11(1):121- 41.
• Lopez-Ribot JL, Casanova M, Murgui A, Martinez JP. Antibody response to Candida albicans cell wall antigen. FEMS Immunology and Medical Microbiology, 2004; 41: 187–96.
• Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C, The Third European Conference on Infections in Leukomia Group. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukomia Group. Critical Care, 2010;14 (R222): 2-14.
• Wang H, Yuan X, Zhang L. Latex agglutination: Diagnose the early Cryptococcus neoformans test of capsular polysaccharide antigen. Pak J Pharm Sci, 2015; 28 (Suppl): 307-11.
• Jaye DL, Waites KB, Parker B, Bragg SL, Moser SA. Comparison of two rapid latex agglutination tests for polysaccharide. Am J Clin Pathol, 1999; 109: 634–41. capsular
• Gade W, Hinnefeld SW, Babcock LS, Gilligan P, Kelly W, Wait K, et al. Comparison of the PREMIER cryptococcal antigen enzyme immüno assay and the latex agglutination assay for detection of cryptococcal antigens. J Clin Microbiol, 1991; 29: 1616–9.
• Quindós G, Moragues MD, Pontón J. Is there a role for antibody testing in the diagnosis of invasive candidiasis? Rev Iberoam Micol, 2004; 21: 10-4.
• Ellepola NBA, Morrison CJ. Laboratory Diagnosis of Invasive Candidiasis. The J of Microbiol, 2005;43: 65-84.
• Burnie JP, Williams JD. Evaluation of the Rameo latex agglutination test in the early diagnosis of systemic candidiasis. Eur J Clin Microbiol, 1998; 5(4): 98–101.