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Aspergillus antigen and PCR assays in bone marrow transplanted children
R Bialek1, D Moshous, J-L Casanova
1Institute for Tropical Medicine, University Hospital Tübingen, Germany. ralf.bialek@med.uni-tuebingen.de
Insights
Screening for invasive aspergillosis (IA) in children post-bone marrow transplant using antigen and DNA assays showed low predictive value. Transient fungal presence, not clinical IA, often caused positive results, necessitating further pediatric studies.
Area of Science:
- Mycology
- Pediatric Hematology/Oncology
- Infectious Diseases
Background:
- Invasive aspergillosis (IA) diagnosis in children, especially post-bone marrow transplant (BMT), lacks robust data.
- Current screening methods for IA in adults are antigen and DNA detection, but their utility in pediatric BMT patients is unclear.
Purpose of the Study:
- To evaluate the diagnostic performance of Aspergillus antigen and DNA screening assays in pediatric BMT recipients.
- To correlate assay results with clinical, radiological, and microbiological data for IA diagnosis.
Main Methods:
- Seventeen children (1-108 months) undergoing BMT were prospectively screened for Aspergillus antigenaemia using a commercial assay.
- Seventy-one serum samples were retrospectively analyzed using a novel nested PCR assay for Aspergillus DNA.
- Results were compared against European Organisation for Research and Treatment of Cancer (EORTC) criteria for IA.
Main Results:
- Three cases of probable or possible IA were identified; IA was ruled out in 14 children.
- Aspergillus antigen was detected in 10 children (meeting EORTC microbiological criteria), and specific DNA was found in 8 antigen-positive and 2 antigen-negative sera.
- Both antigen and PCR assays demonstrated a low positive predictive value (20%), indicating frequent detection of transient, non-clinically relevant fungal presence.
Conclusions:
- High rates of positive antigen and PCR results in pediatric BMT patients are often due to transient antigenaemia and fungaemia, not active IA.
- Prospective studies in well-defined pediatric populations are crucial to establish the true value of serial Aspergillus PCR assays for early IA diagnosis.
Abstract:
Screening for Aspergillus antigen and DNA has been introduced for the early diagnosis of invasive aspergillosis (IA) in adults, but data in children at risk are scarce. Seventeen 1-108 month-old children were screened for Aspergillus antigenaemia by a commercial assay before and after bone marrow transplantation (BMT). Seventy-one serum samples were examined retrospectively by a novel nested PCR assay. Results of both assays were correlated with clinical, radiological and microbiological findings used for the definition of invasive aspergillosis by the European Organisation for Research and Treatment of Cancer (EORTC). Three cases of probable or possible IA were defined, and in 14 children invasive aspergillosis was ruled out. In 10 children, Aspergillus antigen was detected in at least two consecutive serum samples, a microbiological EORTC criteria of IA. Specific DNA was detected in 8 antigen-positive and 2 antigen-negative sera. A positive predictive value of 20% was calculated for both assays. Hence, a high rate of positive results of antigen Elisa and PCR assays in BMT children are due to transient antigenaemia and fungaemia without clinical relevance. According to our data, prospective studies in well defined pediatric patients are urgently needed to determine the value of serial Aspergillus PCR assays for the early diagnosis of invasive aspergillosis in children at risk.