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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases
Ana Burgos1, Theoklis E Zaoutis, Christopher C Dvorak
1Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Insights
Pediatric invasive aspergillosis has a high mortality rate, with surgery being the only independent predictor of survival. Immune reconstitution, not specific antifungal therapy, improved outcomes in children.
Area of Science:
- Pediatric Infectious Diseases
- Mycology
- Hematology-Oncology
Background:
- Invasive aspergillosis (IA) is a significant cause of mortality in immunocompromised children.
- While IA is characterized in adults, pediatric IA lacks comprehensive data on risk factors, diagnostics, treatments, and outcomes.
Purpose of the Study:
- To analyze the incidence, risk factors, diagnostic methods, treatments, and outcomes of IA in a large pediatric cohort.
- To compare pediatric IA findings with those in adult populations.
Main Methods:
- Retrospective review of proven and probable pediatric IA cases from January 1, 2000, to July 1, 2005.
- Data collected from 6 major medical centers, analyzing 139 pediatric patients.
Main Results:
- Aspergillus fumigatus was the most common species (52.8%).
- Immunosuppressive therapies and allogeneic stem cell transplant were significant risk factors for mortality.
- Surgery was the sole independent predictor of survival; immune reconstitution was also key.
- Radiologic findings like nodules were common, but air crescent and halo signs were infrequent in children compared to adults.
Conclusions:
- Pediatric IA shares similarities with adult IA but differs in radiologic diagnostic signs.
- Children often lack classic signs (cavitation, air crescent, halo), complicating diagnosis.
- Immune reconstitution, rather than specific antifungal agents, emerged as the strongest predictor of survival in pediatric IA.
Objective:
Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients.
Methods:
We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005).
Results:
Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received > or = 3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival.
Conclusions:
Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival.
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