Early Diagnosis of Invasive Aspergillosis in Neutropenic Patients. Comparison between Serum Galactomannan and Polymerase chain Reaction

Silva, Rodrigo Lopes da; Ribeiro, Patrícia Lisbôa Izetti; Abreu, Natacha; Ferreira, Teresa; Fernandes, Teresa; Monteiro, Alexandra; Costa, Fátima; Caldas, Joana; Silva, Madalena Pereira da; Carande, Luísa; Ferreira, Gilda Aparecida; Conduto, A; Cruz, Ernesto; Sousa, Maria Henrique; Rodrigues, António Silva; Costa, Isabel; Veiga, Joana; Sousa, Aïda Botelho de

doi:10.4137/cmo.s5228

Cited by 13 publications

(5 citation statements)

References 54 publications

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“…Indeed, molecular methods are important alternatives to conventional methods, as they are sensitive and safe and can yield fast results [28]. In a study by Silva et al [29], IA was investigated, using PCR, in 1311 consecutive serum samples from 172 neutropenic patients, and by screening for the GM antigen in 806 consecutive serum samples from 169 neutropenic patients. The authors reported the sensitivity and specificity to be 75.0% and 91.9%, respectively, for PCR and 87.5% and 93.1%, respectively, for GM.…”

Section: Discussionmentioning

confidence: 99%

Investigating the presence of fungal agents in febrile neutropenic patients using different microbiological, serological, and molecular methods

Sönmez

Ekşi

Pehlıvan

et al. 2015

Bosn J of Basic Med Sci

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This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients.

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Section: Discussionmentioning

confidence: 99%

Investigating the presence of fungal agents in febrile neutropenic patients using different microbiological, serological, and molecular methods

Sönmez

Ekşi

Pehlıvan

et al. 2015

Bosn J of Basic Med Sci

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“…1). Twentythree studies provided data for PCR based on the 2002 EORTC/ MSG criteria , and 14 did so by using the revised (2008) criteria (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) (Table 1).…”

Section: Resultsmentioning

confidence: 99%

PCR in Diagnosis of Invasive Aspergillosis: a Meta-Analysis of Diagnostic Performance

et al. 2014

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Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality rate that affects high-risk groups such as patients with neutropenia and hematologic malignancies. We performed a bivariate meta-analysis of diagnostic data for an Aspergillus sp. PCR assay with blood specimens from high-risk hematology patients. We included all studies involving human subjects that assessed the performance of any PCR assay for invasive aspergillosis in whole blood or serum and that used the European Organization for the treatment of Cancer/Mycoses Study Group criteria as a reference standard. Three investigators independently searched the literature for eligible studies and extracted the data. Out of a total of 37 studies, 25 met strict quality criteria and were included in our evidence synthesis. Twenty-five studies with 2,595 patients were analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays was moderate, with a sensitivity and specificity of 84% (95% confidence interval [CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a positive or negative result is unable, on its own, to confirm or exclude a suspected infection. The performance of a PCR assay of serum was not significantly different from that of whole blood. Notably, at least two positive PCR test results were found to have a specificity of 95% and a sensitivity of 64% for invasive infection, achieving a high positive likelihood ratio of 12.8. Importantly, the European Aspergillus PCR Initiative (EAP-CRI) recommendations improved the performance of the PCR even further when at least two positive specimens were used to define PCR positivity. In conclusion, two positive PCR results should be considered highly indicative of an active Aspergillus sp. infection. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance. D espite advances in treatment and supportive care, invasive aspergillosis (IA) is associated with significant morbidity and mortality rates, especially among patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients (1, 2). Systemic antifungal prophylaxis is widely used in this patient population (3, 4), and patients with recurrent or persistent fever and prolonged neutropenia frequently require empirical coverage with antifungal agents (5). Timely and accurate diagnosis of an active infection is needed in order to initiate targeted antifungal therapy and avoid unnecessary antifungal treatment, which is often accompanied by a multitude of side effects and the cumulative risk of resistance.There is a need for the development of newer diagnostic techniques that would ideally be able to identify IA rapidly, noninvasively, and at an early stage. To aid in this endeavor, the European Organization for the treatment of Cancer/Mycoses Study Group (EORTC/MSG) developed specific criteria for the diagnosis of IA in 2002 (6), which were later revised in 2008 (7), in an attempt to provide the elusive "gold standard" to which any newe...

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“…While an accurate diagnosis relies on histopathology, a lung biopsy is seldom performed and even in cases where it is feasible the diagnostic accuracy rarely exceeds 80%, more so in event of false negative results due to failure of the invasive method to reach the area infected by Aspergillus species. [22,23] Additionally, while Aspergillus hyphae can be readily differentiated from the wide, pauciseptate hyphae of mucoraceous moulds, distinguishing them from the narrow, septate hyphae of Fusarium and Scedosporium is often not possible. [11] Culture is time consuming and may delay the diagnosis of IPA.…”

Section: Discussionmentioning

confidence: 99%

Utility of a serum Aspergillusgalactomannan assay in diagnosis of invasive pulmonary Aspergillosis in HIV/AIDS patients: a prospective analysis

Kaur¹,

Mehra²,

Dhakad³

et al. 2017

APALM

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Early Diagnosis of Invasive Aspergillosis in Neutropenic Patients. Comparison between Serum Galactomannan and Polymerase chain Reaction

Cited by 13 publications

References 54 publications

Investigating the presence of fungal agents in febrile neutropenic patients using different microbiological, serological, and molecular methods

Investigating the presence of fungal agents in febrile neutropenic patients using different microbiological, serological, and molecular methods

PCR in Diagnosis of Invasive Aspergillosis: a Meta-Analysis of Diagnostic Performance

Utility of a serum Aspergillusgalactomannan assay in diagnosis of invasive pulmonary Aspergillosis in HIV/AIDS patients: a prospective analysis

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