Diagnosis of invasive aspergillosis in bone marrow transplant recipients by polymerase chain reaction

Williamson, Emma; Leeming, J.P.; Palmer, Helen; Steward, Colin G.; Warnock, David W.; Marks, David I.; Millar, Michael

doi:10.1046/j.1365-2141.2000.01795.x

Cited by 121 publications

(93 citation statements)

References 30 publications

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“…Quantitative PCR was performed using a real-time PCR protocol with Aspergillus specific primers ASF1 and ADR1 (Table S3) targeting the 28S rRNA gene [49]. Relative fungal DNA content was quantified by the 2 −ΔΔCT method using mouse GAPDH as the reference.…”

Section: Methodsmentioning

confidence: 99%

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Liu

Solis

et al. 2018

Virulence

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Gliotoxin contributes to the virulence of the fungus Aspergillus fumigatus in non-neutropenic mice that are immunosuppressed with corticosteroids. To investigate how the absence of gliotoxin affects both the fungus and the host, we used a nanoString nCounter to analyze their transcriptional responses during pulmonary infection of a non-neutropenic host with a gliotoxin-deficient ΔgliP mutant. We found that the ΔgliP mutation led to increased expression of aspf1, which specifies a secreted ribotoxin. Prior studies have shown that aspf1, like gliP, is not required for virulence in a neutropenic infection model, but its role in a non-neutropenic infection model has not been fully investigated. To investigate the functional significance of this up-regulation of aspf1, a Δaspf1 single mutant and a Δaspf1 ΔgliP double mutant were constructed. Both Δaspf1 and ΔgliP single mutants had reduced lethality in non-neutropenic mice, and a Δaspf1 ΔgliP double mutant had a greater reduction in lethality than either single mutant. Analysis of mice infected with these mutants indicated that the presence of gliP is associated with massive apoptosis of leukocytes at the foci of infection and inhibition of chemokine production. Also, the combination of gliP and aspf1 is associated with suppression of CXCL1 chemokine expression. Thus, aspf1 contributes to A. fumigatus pathogenicity in non-neutropenic mice and its up-regulation in the ΔgliP mutant may partially compensate for the absence of gliotoxin.Abbreviations:PAS: periodic acid-Schiff; PBS: phosphate buffered saline; ROS: reactive oxygen species; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling

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Section: Methodsmentioning

confidence: 99%

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Liu

Solis

et al. 2018

Virulence

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“…The first clinical data in BMT patients indicate that this method has very high sensitivity and specificity. 15,16 Therefore, use of PCR in early detection of fungus infection seems to be extremely useful.…”

Section: Discussionmentioning

confidence: 99%

Skin involvement as the first manifestation of systemic aspergillosis in patients after allogeneic hematopoietic cell transplantation

Schimmelpfennig

Naumann

Zuberbier

et al. 2001

Bone Marrow Transplant

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Summary:Skin involvement due to a systemic infection with Aspergillus species in the course of allogeneic hematopoietic cell transplantation is extremely rare. We report the clinical course of two patients with hematologic malignancies who underwent allogeneic hematopoietic cell transplantation (HCT) and developed disseminated skin involvement as the first clinical symptom of a proven systemic Aspergillus infection. Bone Marrow Transplantation (2001) 27, 753-755. Keywords: cutaneous Aspergillus infection; HCT; BMT; STX; skin infection Aspergillus species are increasingly recognized as major fungal pathogens in severely immunosuppressed or neutropenic patients, particularly after allogeneic hematopoietic cell transplantation (HCT). 1 The risk of developing systemic Aspergillus infection increases with the duration of immunosuppression. The most common manifestation of an Aspergillus infection in these patients is invasive pulmonary aspergillosis characterized by hyphal invasion and destruction of pulmonary tissue. 2,3 Hematogenous dissemination as a secondary event occurs in 20-50% of these patients and most commonly involves the central nervous system and the gastrointestinal tract. 4 The overall mortality is up to 82% and reflects the clinical importance of Aspergillus infection in immunosuppressed or neutropenic patients. 5 Solitary extrapulmonary Aspergillus infection occurs most frequently in the maxillary sinuses 6,7 and colonization of the nasal sinuses can lead to endogenous spread to the lungs causing invasive pulmonary aspergillosis. The skin is a rare site of infection, 8 and cutaneous infections are most often found at the entry site of Hickman catheters. 4,7,9,10 Cutaneous aspergillosis is a poorly described entity Case report No. 1A 50-year-old male with Philadelphia-positive chronic myeloid leukemia in accelerated phase received a non-T cell-depleted bone marrow graft (1.2 × 10 8 MNC/kg BW) from his HLA-identical, MLC-negative brother. He was conditioned with busulfan (10 mg/kg), thiotepa (750 mg/kg) and cyclophosphamide (120 mg/kg) and received methotrexate and cyclosporine as GVHD prophylaxis. On day −1 twice daily prophylactic aerosol inhalation of 10 mg amphotericin B was started. On day +2 he developed fever of unknown origin and was empirically treated with a combination of cefotaxim, piperacillin and vancomycin. Because there was no resolution of the fever, intravenous (i.v.) amphotericin B was started at a dose of 0.8 mg/kg/day on day +4. On day +9 a round warm red swelling resembling a small furuncle appeared on the right thigh. This lesion grew rapidly and was extremely painful. On day +13 this lesion measured approximately 5 cm in diameter and in the centre a circular area of necrosis, 2 cm in diameter, had developed (Figure 1). Until that time microbiological examination of multiple blood cultures had yielded no positive result. Necrotic tissue from the lesion on the right thigh was sent for microbiological culture and histological examination. Both microbiological and histological exa...

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“…Polymerase chain reaction (PCR) methods are being developed, which may permit early detection by analyzing several different types of samples. Despite the variety of strategies being developed, some have shown limited applicability for routine use in a clinical setting, and so far, most studies were performed in limited numbers of patients [18,19].…”

Section: Introductionmentioning

confidence: 99%