galactomannan and Neuroaspergillosis

Invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. Although there is a great number of Aspergillus species, Aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. The increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent years. Galactomannan detection and radiological diagnostic images complement the limitations of microbiology cultures in these patients. Voriconazole and liposomal amphotericin B are the gold standard in patients requiring therapy, and posaconazole, itraconazole, caspofungin and other echinocandins are effective alternatives. The prognosis depends of clinical forms and characteristics of the host, but it is particularly poor in the disseminated invasive forms.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; Cross Infection; Drug Resistance, Multiple, Fungal; Endocarditis; Endophthalmitis; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Neuroaspergillosis; Postoperative Complications; Pulmonary Aspergillosis; Radiography; Risk Factors; Salvage Therapy; Species Specificity; Vulnerable Populations

Invasive aspergillosis is extremely rare in immunocompetent children. Here we describe the clinical, radiologic, and laboratory course of fatal invasive pulmonary and central nervous system aspergillosis in a previously healthy child after a near-drowning incident with submersion in a pond. Findings were compared with data from the literature, which is reviewed. Serum Aspergillus galactomannan levels were determined retrospectively and were compared with the results of routine microbiological and radiologic examinations, showing a significant diagnostic and therapeutic delay of the routine diagnostic approach in comparison with the use of the Aspergillus galactomannan assay. This delay may have contributed to the fatal course. Serial determination of serum Aspergillus galactomannan may be helpful in diagnosing invasive aspergillosis early in case of pulmonary disease after near-drowning and may contribute to an early appropriate treatment. Currently voriconazole, eventually in combination with caspofungin, should be considered as the drug of choice in the management of invasive aspergillosis after near-drowning.

Topics: Aspergillosis; Aspergillus fumigatus; Disease Susceptibility; Early Diagnosis; Epilepsy; Fatal Outcome; Female; Fresh Water; Galactose; Gram-Negative Bacterial Infections; Humans; Infant; Lung Diseases, Fungal; Mannans; Near Drowning; Neuroaspergillosis; Paraplegia; Pneumonia, Aspiration; Pneumonia, Bacterial; Respiratory Distress Syndrome; Respiratory Insufficiency; Stenotrophomonas maltophilia; Water Microbiology

Testing cerebrospinal fluid (CSF) for the presence of galactomannan (GM) antigen may help in diagnosing cerebral aspergillosis (CA). However, the use of the CSF GM test as a diagnostic test has been little studied. We evaluated its diagnostic performance by comparing the CSF GM optical density indexes (ODI) at different cutoffs in patients with probable and proven CA to those in patients without CA. Patients from 2 tertiary referral hospitals with suspected CA between 2004 and 2014 and in whom CSF GM ODI had been determined were selected. European Organization for Research and Treatment of Cancer/Invasive Infectious Diseases Study Mycoses Group (EORTC/MSG) definitions of invasive aspergillosis and CA were used, but with the exclusion of the test to be validated (i.e., the CSF GM test) as a microbiological EORTC/MSG criterion. The study population consisted of 44 patients (4 with proven CA, 13 with probable CA, and 27 with no CA). Of the 17 patients with CA, 15 had a CSF GM ODI of ≥2.0. Of 27 patients without CA, 26 had a CSF GM ODI of <0.5 and 1 had a CSF GM ODI of 8.2. When a GM CSF ODI cutoff of 1.0 was used, the sensitivity, specificity, and positive and negative predictive values were 88.2%, 96.3%, 93.8%, and 92.9%, respectively. The same results were found when a CSF GM ODI cutoff of 0.5 or 2.0 was used. Testing GM in CSF has a high diagnostic performance for diagnosing CA and may be useful to diagnose or virtually rule out the infection without the need for a cerebral biopsy.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Child; Child, Preschool; Female; Galactose; Humans; Male; Mannans; Middle Aged; Neuroaspergillosis; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Young Adult

The central nervous system (CNS) is the most common site of dissemination during Aspergillus infection. PCR has the potential to facilitate early diagnosis of CNS aspergillosis, which could assist in reducing disease mortality. In two experiments, neutropenic CD-1 male mice were infected intracranially with 5×10⁶ conidia of Aspergillus fumigatus. At time points up to 120 h after infection, mice were euthanized and samples of blood, brain, spinal cord and cerebrospinal fluid (CSF) were taken. The brain fungal burden was determined by quantitative culture, and fungal DNA was detected by quantitative PCR. Plating for A. fumigatus from the brain confirmed that all mice had burdens of log₁₀>3 from 4 to 120 h after infection. A. fumigatus DNA was detected in blood (88 %), brain (96 %), CSF (52 %) and spinal cord (92 %) samples. The brain and spinal cord contained the highest concentrations of fungal DNA. Adapting the extraction protocol to maximize yield from small sample volumes (10 µl CSF or 200 µl blood) allowed PCR detection of A. fumigatus in infected mice, suggesting the use of CSF and blood as diagnostic clinical samples for CNS aspergillosis.

Topics: Animals; Aspergillus fumigatus; Brain; DNA, Fungal; Galactose; Male; Mannans; Mice; Neuroaspergillosis; Neutropenia; Polymerase Chain Reaction; Sensitivity and Specificity; Stem Cells

Invasive aspergillosis is a life-threatening infectious complication in hematological patients undergoing immunosuppressive chemotherapy.. We report 29 cases of invasive aspergillosis diagnosed in the Sousse Farhat Hached hospital Hematology unit, Tunisia, between 2002 and 2010.. The most frequent disease (65.5%) was acute myeloid leukemia. All patients were severely neutropenic (<500/mm(3), mean duration=27 days). Pulmonary invasive aspergillosis was suggested in 28 (96.5%) cases. The most frequent respiratory signs were cough (64.3%), chest pain (53.6%), and hemoptysis (50%). The chest X-ray showed suggestive lesions in 60.7% of cases. CT scans revealed nodules with cavitation in 65% of cases, a halo sign in 20% of cases, and nodules in 15% of cases. Galactomannan antigenemia was positive in 88%, mycological examination positive in 51.6%, and seroconversion was noted in 35.7% of the cases. Invasive pulmonary aspergillosis was classified, according to EORTC/MSG criteria, as probable in 26 cases, possible in one case, and proven in one case. Aspergillus flavus was the dominant species in pulmonary invasive aspergillosis accounting for 73.7% of isolates. Extrapulmonary involvement was suggested in 39.3% of cases, the most frequent were sinusitis and brain abscess. Primary cutaneous aspergillosis was observed in one case. The overall mortality rate was 64.2%; the 12-week survival rate was 71.4%.. Our results are correlated to published data. A. flavus was the most frequent species in our region.

Topics: Adolescent; Adult; Aged; Antigens, Fungal; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Brain Abscess; Child; Child, Preschool; Dermatomycoses; Enzyme-Linked Immunosorbent Assay; Female; Fungemia; Galactose; Hematologic Neoplasms; Humans; Induction Chemotherapy; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Neuroaspergillosis; Neutropenia; Sinusitis; Survival Rate; Tomography, X-Ray Computed; Tunisia; Young Adult

The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 patients with probable cerebral aspergillosis and from 16 control patients. Cerebrospinal fluid galactomannan levels were significantly higher in aspergillosis patients, and most galactomannan was produced intrathecally. Comparison of serum galactomannan values in pulmonary and cerebral aspergillosis patients showed significant overlapping. Detection of Aspergillus galactomannan in cerebrospinal fluid may be diagnostic of cerebral aspergillosis.

Topics: Antigens, Fungal; Aspergillus; Bone Marrow Transplantation; Cerebral Cortex; Cerebrospinal Fluid; Enzyme-Linked Immunosorbent Assay; Galactose; Humans; Mannans; Neuroaspergillosis