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Trifluridine/tipiracil (FTD/TPI) is a novel oral formulation of two drugs with promising results in the treatment of metastatic colorectal cancer (mCRC).1 Trifluridine is a thymidine-based nucleoside analogue that, after intracellular phosphorylation, gets incorporated into DNA, causing DNA dysfunction.2 It was first identified by Callahan et al. in 1996 as an active impurity in the herbicide trifluralin, which […]

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Diagnosis of Invasive Fungal Infections – Current Limitations of Classical and New Diagnostic Methods

David W Denning, Alessandro C Pasqualotto
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Published Online: Jun 3rd 2011 European Oncology Review, 2005:1-11 DOI: https://doi.org/10.17925/EOH.2005.0.0.1p
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Article

Despite the availability of new antifungal drugs, the overall survival for immunocompromised patients with invasive fungal infections remains too low, with large variations according to underlying disease.1–15 Although early diagnosis and subsequent early initiation of therapy improves outcome,16–19 diagnosing invasive fungal infections can be difficult. The purpose of this article is to review the available armamentaria for the diagnosis of invasive fungal infections. A brief summary of the main clinical and epidemiological data for these infections is shown in Table 1.3–7,12–15,20–56

Diagnosis of Invasive Fungal Infection
Conventional Methods (Direct Microscopy, Culture and Histopathology)

All fungi obtained from sterile sites should be identified to species level by referral to a specialist laboratory. All bronchoscopy fluids from patients suspected of infection should be examined microscopically for hyphae and cultured on specialised media, and all clinical isolates of Aspergillus should be identified to species level.57
Current ‘conventional methods’ are very limited for the diagnosis of invasive fungal infections. Blood cultures have a low sensitivity for the diagnosis of candidaemia (~50%),58,59 and cultures other than blood are non-specific and can take too long to became positive. Antifungal treatment is recommended following recovery of even one positive blood culture for Candida.5 Identification of Candida spp. by culture requires the presence of viable organisms in blood or body fluids. In addition, several days may be required for blood cultures to become positive and, for non-Albicans spp. of Candida, additional subculturing is required to obtain pure cultures for use in subsequent phenotypic identification systems.59
Although the lungs are frequently involved in disseminated candosis, primary Candida pneumonia is a rare condition,60,61 and benign colonisation of the airway with Candida spp. and/or contamination of the respiratory secretions with oropharyngeal material is much more common than true Candida pneumonia. Thus, diagnoses of Candida pneumonia that are based solely on microbiological data are often incorrect. In addition, debate persists about the significance of the isolation of Candida in the peritoneal fluid,62 and the presence of Candida in the urine usually represents colonisation, despite its presence in 9% of hospitalised patients in the US.63
For the diagnosis of invasive aspergillosis, cultures of the respiratory tract secretions lack sensitivity. Aspergillus is grown from sputum in only 8% to 34%, and from broncho-alveolar lavage (BAL) in 45% to 62% of patients with invasive aspergillosis.64 Aspergillus recovery from the respiratory tract usually represents colonisation in immunocompetent patients but may strongly suggest invasive disease in the immunocompromised host.65,66 While confirmation of the diagnosis of invasive aspergillosis has typically required histopathologic evaluation, profound neutropaenia and thrombocytopaenia often preclude the pursuit of biopsies. Transbronchial biopsy or brushings are too often false negative. Biopsies of endobronchial lesions have been useful when such lesions are encountered. Blood, cerebrospinal fluid (CSF) and bone marrow specimens rarely yield Aspergillus spp.33
In contrast to disseminated aspergillosis, disseminated fusariosis can be diagnosed by blood cultures in 40% of patients.12,15 The rate of positive blood cultures increases to 60% in the presence of disseminated skin lesions.14 Microscopically, the hyphae of Fusarium in tissue resemble those of Aspergillus; the filaments are hyaline, septate and 3–8μm in diameter. They typically branch at acute or right angles. The production of both fusoid macroconidia and microconidia are characteristic of the genus Fusarium.13 Skin lesions should be submitted to biopsy.
The diagnosis of zygomycosis is usually made histologically, and the demonstration of fungal elements from cytologic preparations is complicated by the difficulty of extracting fungal elements from invaded tissues.11 The poor sensitivity of sputum culture (<25%) makes diagnosis of pulmonary zygomycosis challenging.38 The yield of BAL is not higher,38,67 but direct microscopy of BAL together with transbronchial biopsy may increase the yield.43 A positive finding from BAL from a neutropaenic or immunocompromised host would be highly suggestive of infection, and should be treated as such.43 Even though, on microscopy, Mucorales have been classically described as having broad (10 to 50μm), ribbon-like aseptate hyphae with right-angle branching, the hyphae are actually pauciseptate, and the angle of hyphal branching can vary from 45° to 90°, reinforcing the importance of obtaining material for culture.68 About 80% of disseminated infections with S. prolificans are associated with positive blood cultures, but this proportion is much lower with S. apiospermum infections.45
All tissues from patients with suspected infection should be stained with fungal stains in parallel with regular stains. The practice of assessing H&E stains of tissues before deciding whether to use specialised stains for fungi frequently introduces fatal delays for patients. Reporting of specimens containing any fungal elements should always include the presence and absence of yeast forms, hyphae and whether or not they are septate, if it is possible to tell, and whether there is any melanin present.57 However, while the demonstration of Aspergillus in tissue is the reference standard for diagnosis of invasive aspergillosis, a definitive diagnosis is possible only after identification of the fungus cultured from that tissue.69 So, part of the biopsed tissue or other surgical specimen should be sent to the microbiology laboratory (not in formalin), in addition to the pathology laboratory. Immunohistological staining using polyclonal fluorescent antibody reagents can distinguish Aspergillus spp. from Fusarium spp.70 In situ hybridisation may also help to distinguish Fusarium spp. from Aspergillus and Pseudoallescheria in tissue sections.71

New Diagnostic Tool
Galactomannan

Galactomannan is a cell wall polysaccharide released by Aspergillus spp. during fungal growth in tissue.69,72,73 A commercially available sandwich ELISA (Platelia Aspergillus, BioRad) detects galactomannan by use of a rat monoclonal antibody. The test has been validated for serum specimens only and has a detection limit of ~1ng/mL, which is 10 to 15 times lower than the limit of the latex agglutination test used previously (Pastorex Aspergillus, Biorad).73–76 Circulating galactomannan may be detected at a median of five to eight days before clinical manifestation of aspergillosis.72,77–80 The concentration of circulating galactomannan corresponds with the fungal tissue burden81,82 and may therefore be used to monitor the response to treatment.77,78
Studies evaluating the role of galactomannan assay in the diagnosis of invasive aspergillosis have largely been conducted with leukaemia patients or haematopoietic stem-cell transplantation (HSCT) recipients.77,78,82–89 After initial clinical studies suggested a high sensitivity and specificity,73,76,78,79,90,91 further studies revealed high rates of false-positive results among paediatric patients and neonates.81,92,93 In one study, rates of false-positive results as high as 83% were observed93 that may be related to cross-reactivity with Bifidobacterium bifidum, found in large inocula in the guts of breast- and formula-fed infants.94 The presence of a damaged gut endothelium may increase the absorption of dietary galactomannan.95 Specificity was also lower in adult allo-HSCT recipients than in adult auto-HSCT recipients or non-transplant patients.92 The rate of false-positive results is high in the first 30 days following bone marrow transplantation and 10 days after starting cytotoxic chemotherapy.96,97 The use of galactomannan as a surveillance tool in transplant recipients has been associated with a positive predictive value of only 10%.92 The results also suggest that routine ELISA tests are not useful in patients with febrile neutropaenia with no clinical or radiological signs suggestive of a pulmonary infection.92 Otherwise, all high-risk patients with a respiratory tract infection or suspected extrapulmonary aspergillosis should be repeatedly tested with galactomannan ELISA, as the predictive positive value of the assay was highest in these groups.92
Cross-reactivity of Platelia Aspergillus galactomannan with Penicillium spp. has been noted96 but is deemed to be of little clinical relevance since Penicillium spp. are rarely pathogens in humans. In addition, drugs of fungal origin, such as antibiotics, may be associated with a false-positive test, including ampicillin-sulbactam, piperacillin-tazobactam, and amoxicillin-clavulanic acid.98–102 The timing of collection of the sample may influence the test results, with reactivity being less likely in samples collected at trough levels or prior to the administration of the dose.103 ELISA cross-reactivity has been observed with other fungi, including Paecilomyces variotii, and Alternaria spp.92 False-positive reactions have also been seen in bacteraemic patients,96 and in those with autoreactive antibodies.64,88
In a study of 3,924 serum samples in cancer patients, the overall sensitivity of the ELISA galactomannan test was only 29.4% (64.5% when only patients with proven invasive aspergillosis were analysed).92 Low sensitivity for the ELISA assay has also been reported in allo-HSCT recipients (60%), lung transplant recipients (30%),89 liver transplant recipients (56%), and in patients with various other conditions including non-malignant diseases (52%).83,93 While a positive test in a lung transplant recipient with a clinical illness compatible with invasive aspergillosis may be considered highly suggestive of this infection, a negative test does not rule out aspergillosis.64 The sensitivity of the test has been typically lower in non-neutropaenic patients (15% to 30%) and may be related to lower circulating galactomannan levels.64 The use of both prophylactic and empiric antifungals may also lower antigen levels by decreasing the fungal load.64
Overall, the galactomannan test seems to be a highly specific diagnostic tool (94% to 99%), even though sensitivity has ranged from 50% to 93% in patients with haematologic malignancy.72,77,78 In order to improve these results, some authors have suggested that the recommended cut-off value of the test should be reduced from 1,500 to 1,000.72,77 A further reduction to 0.700 was suggested for adults who have not undergone allogeneic transplantation,92 and recent research suggests that an index of 0.5 is a more definitive threshold.104 These modifications may increase the sensitivity of the test, with only a low decrease in specificity. Discussion persists about the best cut-off for galactomannan assays.
Because galactomannan is a water-soluble carbohydrate, it can be detected in other fluids.69 Although the antigen can be detected in the urine,73,74,105–107 little is known about its pharmacokinetics and clearance by the kidney. The effect of renal failure or dialysis on the clearance of galactomannan is also indefinite. Little is known regarding the correlation between galactomannan detection in urine and disease progression, and false-positive results may be an important drawback for this test.69,73,74
Because galactomannan is predominantly released by Aspergillus hyphae during growth and to a much lesser extent by conidia, detection of galactomannan in BAL fluid provides better evidence for aspergillosis than culture108,109 or polymerase chain reactions (PCRs), which do not discriminate between contamination conidia and hyphae.110–112 However, false positive results may occur in patients only colonised with Aspergillus when BAL is tested,69 but this can be improved when one combines this method with the high-resolution computed tomography (CT) scan.34,113
Diagnosis of CNS aspergillosis is very difficult and even brain biopsies do not always result in a clear diagnosis.69 Culture of CSF infrequently yields positive results,94,114 and both chemical findings in the CSF and the CT results are often non-specific.115–117 Galactomannan may also be detected in the CSF, with a sensitivity and specificity of 80% and 100%, respectively, according to a study involving only five patients with proven CNS aspergillosis.117 Galactomannan has been detected in other clinical specimens as well.69

1,3-beta-D-glucan

1,3-beta-D-glucan is a cell wall component of yeast and filamentous fungi, which is detectable in the blood during most invasive fungal infections. Factor G, a coagulation factor, is a sensitive natural detector of this antigen.118 The reported sensitivity and specificity for the assay have ranged from 67% to 100%, and 84% to 100%, respectively.118–122 The test does not detect cryptococcosis, and it is also not positive in cases of oral candidosis or fungal colonisation.121 However, in addition to invasive aspergillosis and candidosis, it detects infections caused by species of Fusarium, Trichosporon, Saccharomyces and Acremonium, which are less common but equally important fungal pathogens, especially in immunocompromised hosts.121 False positive tests have been reported in patients undergoing haemodialysis, patients with cirrhosis, recipients of antitumour polysaccharides, and patients immediately following abdominal surgery.64

PCRn

Although PCR is at lest 19 times more sensitive than culture for A. fumigatus,123 PCR-based molecular diagnostic tests for aspergillosis are not commercially available and remain largely unstandardised. A sensitivity of 79% to 100% and a specificity of 81% to 93% have been documented, depending on the methodology used.124–126 Such assays, when performed on blood or BAL samples, have shown a negative predictive value for invasive aspergillosis ranging from 92% to 99%. However, PCR-based assays performed with BAL samples have shown low positive predictive values that are likely to reflect respiratory tract colonisation.127

Markers for Invasive Candidosis

Mannan is a cell wall surface carbohydrate that circulates during infection with Candida spp.,128 and studies have shown a correlation between detectable mannanemia and tissue invasive in patients with candidaemia.129 However, mannan is rapidly cleared from the blood and occurs in low levels, necessitating frequent sampling for detection.130 In addition, this is a very expensive test. D-arabinitol is a metabolite of certain species of Candida that accumulates in the urine of patients with invasive candidosis. Assay sensitivity for D-arabinitol is only ~50%, and does not detect C. krusei and C. glabrata.131,132 Enolase is perhaps the antigen with the greatest promise for the diagnosis of invasive candidosis.133,134 The sensitivities of assays for enolase have ranged from 54% to 75%, and higher sensitivity may be achieved with serial testing. Furthermore, the enolase antigen is highly specific for Candida spp., and is not present in superficial Candida colonisation.133
Experimental models and clinical studies have shown PCR to be more sensitive than culture for detection of candidaemia. The sensitivity of the Candida PCR assay was 95.0% in one study, compared with a sensitivity of 75.0% for the Candida ELISA aiming to detect mannan (a difference not statistically different).104 The specificities of the Candida PCR and ELISA were the same at 97.0%. In 45% of these patients, the PCR method detected the infection earlier than the ELISA. Newer realtime PCR assays such as TaqMan and the Light Cycler require no post-amplification manipulations and can potentially be automated for all steps from DNA extraction to final PCR amplicon detection and quantitation.59
It should be noted that there have been several headto- head comparisons of the various assays for detection of the Candida antigens discussed earlier. Unfortunately, none of the assays have performed well enough or has good enough predictive value at this point to be able to recommend its routine use in a clinical laboratory. Perhaps a combination of two assays may increase the accuracy of diagnosis of invasive candidosis.130

Markers for Other Invasive Fungal Infections

The amplification of gene sequences unique to fungi is conceptually appealing, offering the potential for rapid and sensitive diagnosis of invasive fungal infections. In general, assays targeting multicopy genes have better detection limits than those targeting single copy genes.135 Although PCR may become a diagnostic modality to identify Mucorales,136–138 Scedosporium,139–141 and several other fungi,142–151 no commercial test is available to date. These techniques hold promise, but they are not yet standardised or readily available in most clinical laboratories. Also, large clinical trials to determine the sensitivity and specificity of such molecular tests are non-existent.

Role of the CT Scan

The ‘halo sign’ refers to a zone of ground-glass attenuation surrounding a pulmonary nodule or mass on computed tomography (CT) images.152 The presence of a halo of ground-glass attenuation is usually associated with haemorrhagic nodules.153 In severely neutropaenic patients, this suggests infection by an angioinvasive fungus, most commonly Aspergillus. The halo sign is documented in 33% to 60% of patients with invasive aspergillosis and is short-lived.154 To be useful for the diagnosis of aspergillosis, the CT scan must be performed within five days of the onset of infection, because ~75% of the initial halo signs disappear within a week.155 The ‘air crescent’ sign does not appear until the third week of the illness, and its appearance may be too delayed to be helpful in the diagnosis of invasive aspergillosis.154
Although usually regarded as an indication of haemorrhagic nodules, the halo sign may also be present when tumour or inflammatory cells infiltrate the lung parenchyma.153,155–159 The halo has been described in patients with eosinophilic pneumonia, bronchiolitis obliterans organising pneumonia,160 and tuberculosis,161 and in patients infected by Mycobacterium avium complex,155 Coxiella burnetti,162 cytomegalovirus, herpes simplex virus,153 and myxovirus.160 Patients with post-transplantation lymphoproliferative disorders163 and Wegener granulomatosis may develop the halo sign,153 as well as some of those who have undergone transbronchial biopsy.155 Although it is less common, the halo sign may also be observed in non-haemorrhagic nodules, in which case either tumour cells or inflammatory infiltration account for the halo of ground-glass attenuation.153 Nonetheless, in the appropriate clinical setting, the halo sign is considered to be early evidence of pulmonary aspergillosis even before serologic tests become positive,164 and it warrants the administration of systemic antifungal therapy.165

Future Perspectives

Invasive fungal infections constitute a major challenge for the management of immuno-compromised patients, mainly haemato-oncology patients, transplant and allo-HSCT recipients. In order to improve the survival for these infections, an early diagnosis is required. As shown in this article, conventional microbiological, histological and radiological techniques remain the cornerstone of diagnosis but are insensitive and have a limited impact on clinical decision-making. There is an urgent need for new and efficient diagnostic methods. These tests should be fast and highly sensitive. In addition, the recognition of the causal agent should be very precise. With the advance of molecular tools, new fungal species and new mechanisms of resistance will be clarified. DNA-and RNA-based methods hold promise for improved sensitivity and specificity, but these methods will require extensive validation in clinical studies. Finally, costs are also very important in selecting an appropriate diagnostic test for invasive fungal infections. ■

1

References

  1. Kullberg B J, Pappas P, Ruhnke M, et al., “Voriconazole compared to a strategy of amphotericin B followed by fluconazole for treatment of candidaemia in non-neutropenic patients”, 14th European Congress of Clinical Microbiology and Infectious Diseases, Prague, 2004, oral presentation 245.
  2. Mora-Duarte J, Betts R, Rotstein C, et al., “Comparison of caspofungin and amphotericin B for invasive candidiasis”, N. Engl. J. Med. (2002);347: pp. 2,020–2,099.
  3. Pasqualotto A C, Nedel W L, Machado T S, Severo L C, “A comparative study of risk factors and outcome among outpatient-acquired and nosocomial candidaemia”, J. Hosp. Infect. (2005);60: pp. 129–134.
  4. Gudlaugsson O, Gillespie S, Lee K, et al., “Attributable mortality of nosocomial candidemia, revisited”, Clin. Infect. Dis. (2003);37, pp. 1,172–1,177.
  5. Pappas P G, Rex J H, Sobel J D, et al., “Guidelines for treatment of candidiasis”, Clin. Infect. Dis. (2004);38: pp. 161–189.
  6. Pasqualotto A C, Nedel W L, Machado T S, Severo L C, “Risk factors and outcome for nosocomial breakthrough candidaemia”, J. Infect. (2005) (in press).
  7. Pasqualotto A C, Bittencourt Severo C, de Mattos Oliveira F, Severo L C, “Cryptococcemia. An analysis of 28 cases with emphasis on the clinical outcome and its etiologic agent”, Rev Iberoam Micol. (2004);21: pp. 143–146.
  8. Herbrecht R, Denning D W, Patterson T F, et al., “Voriconazole versus amphotericin B for primary therapy in invasive aspergillosis”, Clin. Infect. Dis. (1006);23: pp. 608–615.
  9. Maertens J, Raad I, Petrikkos G, et al., “Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy”, Clin. Infect. Dis. (2004);39: pp. 1,563–1,571.
  10. Yeung C K, Cheng V C C, Lie A K W, Yuen K Y, “Invasive disease due to Mucorales: a case report and review of the literature”, HKMJ (2001);7: pp. 180–188.
  11. Pagano L, Offidani M, Fianchi L, et al., “Mucormycosis in hematologic patients”, Haematologica (2004);89: pp. 207–214.
  12. Boutati E I, Anaissie E J, “Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management”, Blood (1997);90: pp. 999–1,008.
  13. Dignani M C, Anaissie E, “Human fusariosis”, Clin. Microbiol. Infect. (2004);10(suppl. 1): pp. 67–75.
  14. Nucci M, Anaissie E, “Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management”, Clin. Infect. Dis. (2002); 35: pp. 909–920.
  15. Hennequin C, Lavarde V, Poirot J L, et al., “Invasive Fusarium infections: a retrospective survey of 31 cases”, J. Med. Vet. Mycol. (1997);35: pp. 107–114.
  16. Denning D W, “Therapeutic outcome in invasive aspergillosis”, Clin. Infect. Dis. (1996);23: pp. 608–615.
  17. Verweij P E, Donnelly J P, de Pauw B E, Meis J E, “Prospects for early diagnosis of invasive aspergillosis in the immunocompromised patient”, Rev. Med. Microbiol. (1996);7: pp. 105–113.
  18. von Eiff M, Ross N, Schulten R, Hesse M, Zuhlsdorf M, van de Loo J, “Pulmonary aspergillosis: early diagnosis improves survival”, Respiration (1995);62: pp. 341–347.
  19. Caillot D, Casasnovas O, Bernard A, et al. “Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery”, J. Clin. Oncol. (1997);15: pp. 139–147.
  20. Antunes A G V, Pasqualotto A C, Diaz M C, d’Azevedo P A, Severo L C, “Candidemia in a Brazilian tertiary care hospital: species distribution and antifungal susceptibility patterns”, Rev. Inst. Med. trop S Paulo (2004);46: 239–241.
  21. Levy I, Rubin L G, Vasishtha S, Tucci V, Sood S K, “Emergence of Candida parapsilosis as the predominant species causing candidemia in children”, Clin. Infect. Dis. (1998);26: pp. 1,086–1,088.
  22. Bross J, Talbot G H, Maislin G, Hurwitz S, Strom B L, “Risk factors for nosocomial candidemia: a case-control study in adults without leukemia”, Am. J. Med. (1989);87: pp. 614–620.
  23. Wey S B, Mori M, Pfaller M A, Woolson R F, Wenzel R P, “Risk factors for hospital-acquired candidemia. A matched case-control study”, Arch. Intern. Med. (1989);149: pp. 2,349–2,353.
  24. Eggimann P, Garbino J, Pittet D, “Epidemiology of Candida species infections in critically ill non-immunosuppressed patients”, Lancet Infect. Dis. (2003);3: pp. 685–702.
  25. Parke D W II, Jones D B, Gentry L O, “Endogenous endophthalmitis among patients with candidemia”, Ophthalmology (1982);89: pp. 789–796.
  26. Pasqualotto A C, Severo L C, “Why don’t we just do what we have to do?”, J. Infect. 2005 (in press).
  27. Pasqualotto A C, Bittar A E, de Quadros M, Severo L C, “Cryptococcal cellulitis in a renal transplant patient”, Nephrol. Dial Transplant (2005);0: pp. 8,011.
  28. Saag M S, Graybill R J, Larsen R A, et al., “Practice guidelines for the management of cryptococcal disease”, Clin. Infect. Dis. (2000);30: pp. 710–718.
  29. Pasqualotto G C, Copetti F A, Meneses C F, Machado A R, Brunetto A L, “Infection by Rhodotorula sp. in children receiving treatment for malignant diseases”, J. Pediatr. Hematol. Oncol. (2005);27: pp. 232–233.
  30. Pasqualotto A C, Sukiennik T C T, Severo L C, de Amorim C S, Colombo A L, “Pichia anomala fungemia outbreak in a Brazilian pediatric intensive care unit”, Infect. Contr. Hosp. Epidemiol. (2005);26: pp. 553–558.
  31. Walsh T J, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E, “Infections due to emerging and uncommon medically important fungal pathogens”, Clin. Microbiol. Infect. (2004);10(suppl. 1): pp. 48–66.
  32. Marr K A, Patterson T, Denning D, “Aspergillosis. Pathogenesis, clinical manifestations, and therapy”, Infect. Dis. Clin. North Am. (2002);16: pp. 875–894.
  33. Stevens D A, Kan V L, Judson M A et al., “Practice guidelines for diseases caused by Aspergillus”, Clin. Infect. Dis. (2000);30: pp. 696–709.
  34. Denning D W, Follansbee S E, Scolaro M et al., “Pulmonary aspergillosis in the acquired immunodeficiency syndrome”, N. Engl. J. Med. (1991);324: pp. 654–662.
  35. Soubani A O, Chandrasekar P H, “The clinical spectrum of pulmonary aspergillosis”, Chest (2002);121: pp. 1,988–1,999.
  36. Young R C, Bennett J E, Vogel C L et al., “Aspergillosis: the spectrum of the disease in 98 patients”, Medicine (Baltimore) (1970);49: pp. 147–173.
  37. Denning D W, “Invasive aspergillosis”, Clin. Infect. Dis. (1998);26: pp. 781–803.
  38. Kontoyiannis D P, Wessel V C, Bodey G P, Rolston V I, “Zygomycosis in the 1990s in a tertiary-care cancer center”, Clin. Infect. Dis. (2000); 30: pp. 851–856.
  39. Eucker J, Sezer O, Graf B, Possinger K, “Mucormycoses”, Mycoses (2001);44: pp. 253–260.
  40. Nosari A, Oreste P, Montillo M et al., “Mucormycosis in hematologic malignancies: an emerging fungal infection”, Haematologica (2000);85: pp. 1,068–1,071.
  41. Prabhu R M, Patel R, “Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment”, Clin. Microbiol. Infect. (2004);10(suppl. 1): pp. 31–47.
  42. Maertens J, Demuynck H, Verbeken E K et al., “Mucormycosis in allogenic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis”, Bone Marrow Transplant. (1999);24: pp. 307–312.
  43. Bigby T D, Serota M L, Tierney L M Jr, Matthay M A, “Clinical spectrum of pulmonary mucormycosis”, Chest (1986);89: pp. 435–439.
  44. Chamilos G, Marom E M, Lewis R E, Lionakis M S, Kontoyiannis D P, “Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer”, Clin. Infect. Dis. (2005);41: pp. 60–66.
  45. Bouza E, Munoz P, “Invasive infections caused by Blastoschizomyces capitatus and Scedosporium spp.”, Clin. Microbiol. Infect. (2004);10(suppl. 1): pp. 76–85.
  46. Idigoras P, Perez-Trallero E, Pineiro L et al., “Disseminated infection and colonization by Scedosporium prolificans: a review of 18 cases 1990–1999”, Clin. Infect. Dis. (2001);32: E158–65.
  47. Lopez L, Gaztelurrutia L, Cuenca-Estrella M et al., “Infection and colonization by Scedosporium prolificans”, Enferm. Infecc. Microbiol. Clin. (2001);19: pp. 308–313.
  48. Boonpasart S, Kasetsuwan N, Puangsricharern V, Pariyakanok L, Jittpoonkusol T, “Infectious keratitis at King Chulalongkorn Memorial Hospital. A 12-year retrospective study of 391 cases”, J. Med. Assoc. Thailand (2002);85: S217–230.
  49. Girmenia C, Arcese W, Micozzi A, Martino P, Bianco P, Morace G, “Onychomycosis as a possible origin of disseminated Fusarium solani infection in a patient with severe aplastic anemia”, Clin. Infectious Dis. (1992);14: p. 1,167.
  50. Sampathkumar P, Paya C V, “Fusarium infection after solid-organ transplantation”, Clin. Infect. Dis. (2001);32: pp. 1,237–1,240.
  51. Revankar S G, Patterson J E, Sutton D A, Pullen R, Rinaldi M G, “Disseminated phaeohyphomycosis: review of an emerging mycosis”, Clin. Infect. Dis. (2002);34: pp. 467–476.
  52. Wheat J, Sarosi G, McKinsey D et al., “Practice guidelines for the management of patients with histoplasmosis”, Clin. Infect. Dis. (2000);30: pp. 688–695.
  53. Blair J E, Smilack J D, Caples S M, “Coccidioidomycosis in patients with hematologic malignancies”, Arch. Intern. Med. (2005);165: pp. 113–117.
  54. Ampel N M, “Combating opportunistic infections: coccidioidomycosis”, Expert Opin. Pharmacother. (2004);5: pp. 255–261.
  55. Restrepo A, Salazar M E, Cano L E et al., “Estrogens inhibit mycelium to yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to paracoccidioidomycosis”, Infect. Immun. (1984);46: pp. 346–353.
  56. Brummer E, Castaneda E, Restrepo A, “Paracoccidioidomycosis: an update”, Clin. Microbiol. Rev. (1993);6: pp. 89–117.
  57. Denning D W, Kibbler C C, Barnes R A, “British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections”, Lancet Infect. Dis. (2003);3: pp. 230–240.
  58. Ascioglu S, Rex J H, de Pauw B et al., “Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus”, Clin. Infect. Dis. (2002);34: pp. 7–14.
  59. Ellepola A N, Morrison C J, “Laboratory diagnosis of invasive candidiasis”, J. Microbiol. (2005);43: pp. 65–84.
  60. Rello J, Esandi M E, Diaz E, Mariscal D, Gallego M, Valles J, “The role of Candida sp. isolated from bronchoscopic samples in nonneutropenic patients”, Chest (1998);114: pp. 146–149.
  61. El-Ebiary M, Torres A, Fabrega N et al., “Significance of the isolation of Candida species from respiratory samples in critically ill, nonneutropenic patients”, Am. J. Respir. Crit. Care Med. (1997);156: pp. 583–590.
    61. El-Ebiary M, Torres A, Fabrega N et al., “Significance of the isolation of Candida species from respiratory samples in critically ill, nonneutropenic patients”, Am. J. Respir. Crit. Care Med. (1997), 156: pp. 583–590.
  62. Dupont H, Bourichon A, Paugam-Burtz C, Mantz J, Desmonts J-M, “Can yeast isolation in peritoneal fluid be predicted in intensive care unit patients with peritonitis?”, Crit. Care Med. (2003);31: pp. 752–757.
  63. Fisher J F, Newman C L, Sobel J D, “Yeast in the urine: solutions for a budding problem”, Clin. Infect. Dis. (1995);20: pp. 183–189.
  64. Paterson D L, Singh N, “Invasive aspergillosis in transplant recipients”, Medicine (1999);78: pp. 123–138.
  65. Horvath J, Dummer S, “The use of respiratory tract cultures in the diagnosis of invasive aspergillosis”, Am. J. Med. (1996);100: pp. 171–178.
  66. Kahn F, Jones J, England D, “The role of bronchoalveolar lavage in the diagnosis of invasive pulmonary aspergillosis”, Am. J. Clin. Path. (1986);86: pp. 518–523.
  67. Glazer M, Nusair S, Breuer R, Lafair J, Sherman Y, Berkman N, “The role of BAL in the diagnosis of pulmonary mucormycosis”, Chest (2000);117: pp. 279–282.
  68. Frater J L, Hall G S, Procop G W, “Histologic features of zygomycosis: emphasis on perineural invasion and fungal morphology”, Arch. Pathol. Lab. Med. (2001);125: pp. 375–378.
  69. Klont R R, Mennink-Kersten M A S H, Verweij P E, “Utility of Aspergillus antigen detection in specimens other than serum specimens”, Clin. Infect. Dis. (2004);39: pp. 1,467–1,474.
  70. Kaufman L, Standard P G, Jalbert M, Kraft D E, “Immunohistologic identification of Aspergillus spp. and other hyaline fungi by using polyclonal fluorescent antibodies”, J. Clin. Microbiol. (1997);35: pp. 2,206–2,209.
  71. Hayden R T, Isotalo P A, Parrett T, et al., “In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section”, Diagnostic. Mol. Pathol. (2003);12: pp. 21–26.
  72. Maertens J, Verhaegen J, Demuynck H, et al., “Autopsy-controlled prospective evaluation of serial screening for circulation galactomannan by a sandwich enzyme-linked immunosorbent assay for haematological patients at risk for invasive aspergillosis”, J. Clin. Microbiol. (1999);37: pp. 3,223–3,228.
  73. Stynen D, Goris A, Sarfati J, Latge J P, “A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis”, J. Clin. Microbiol. (1995);33: pp. 497–500.
  74. Ansorg R, Hintschel von Heinegg E, Rath P M, “Aspergillus antigenuria compared with antigenemia in bone marrow transplant recipients”, Eur. J. Clin. Microbiol. Infect. Dis. (1994);13: pp. 582–589.
  75. Hopwood V, Johnson E M, Cornish J M, Foot A B, Evans E G, Warnock D W, “Use of the Pastorex Aspergillus antigen latex agglutination for the diagnosis of invasive aspergillosis”, J. Clin. Pathol. (1995);48: pp. 210–213.
  76. Verweij P E, Stynen D, Rijs AJMM, DePauw B E, Hoogkamp-Korstanje J A A, Meis J F G M, “Sandwich enzymelinked immunosorbent assay compared with Pastorex latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients”, J. Clin. Microbiol. (1995);33: pp. 1,912–1,914.
  77. Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M, “Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation”, Blood (2001);97: pp. 1,604–1,610.
  78. Sulahian A, Boutboul F, Ribaud P, Leblanc T, Lacroix C, Derouin F, “Value of antigen detection using an enzyme immmnoasay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric haematology units during a 4-year prospective study”, Cancer (2001);91: pp. 311–318.
  79. Verweij P E, Dompeling E C, Donnelly J P, Schattenberg A V, Meis J F, “Serial monitoring of Aspergillus antigen in the early diagnosis of invasive aspergillosis. Preliminary investigations with two examples”, Infection (1997);25: pp. 86–89.
  80. Williamson E C, Oliver D A, Johnson E M, et al., “Aspergillus antigen testing in bone marrow transplant recipients”, J. Clin. Pathol. (2000);53: pp. 362–366.
  81. Rohrlich P, Sarfati J, Mariani P, et al., “Prospective sandwich enzyme-linked immunosorbent assay for serum glactomannan: early predictive value and clinical use in invasive aspergillosis”.
  82. Patterson T F, Miniter P, Ryan J L, Andriole VT , “Effect of immunosuppression and amphotericin B on Aspergillus antigenemia in an experimental model”, J. Infect. Dis. (1988);158: pp. 415–422.
  83. Machetti M, Feasi M, Mordini N, et al., “Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients”, Bone Marrow Transplant (1998);21: pp. 917–921.
  84. Bretagne S, Costa J-M, Bart-Delabesse E, Dhedin N, Rieux C, Cordonnier C, “Comparison of serum galactomannan antigen detection and competitive polymerase chain reaction for diagnosing invasive aspergillosis”, Clin. Infect. Dis. (1998);26: pp. 1,407–1,412.
  85. McLaughlin L, Balajee A, Leisenring W, et al., “Bio-Rad Patelia(r) Aspergillus EIA detection of Aspergillus galactomannan antigen in human serum: performance evaluation in a large bone marrow transplant center”, Focus on Fungal Infections, Phoenix, Ariz., 20–22 March 2002.
  86. Maertens J, van Eldere J, Verhaegen J, Verbeken E, Verschakelen J V, Boogaerts M, “Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients”, J. Infect. Dis. (2002);186: pp. 1,297–1,306.
  87. Fortun J, Martin-Davila P, Alvarez M E, et al., “Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients”, Transplantation (2001);71: pp. 145–149.
  88. Kwak E J, Husain S, Obman A, et al., “Efficacy of galactomannan antigen using Platelia Aspergillus enzyme immunoassay for the diagnosis of invasive aspergillosis in liver transplant recipients”, J. Clin. Microbiol. (2004);42: pp. 435–438.
  89. Husain S, Kwak E J, Obman A, et al., “Propsective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients”, Am. J. Transplant (2004);4: pp. 796–802.
  90. Bretagne S, Marmorat-Khuong A, Kuentz M, et al., “Serum Aspergillus galactomannan antigen testing by sandwich ELISA: Practical use in neutropenic patients”, J. Infect. (1997);35: pp. 7–15.
  91. Sulahian A, Tabouret M, Ribaud P, et al., “Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of aspergillosis”, Eur. J. Clin. Microbiol. Infect. Dis. (1996);15: pp. 139–145.
  92. Herbrecht R, Letscher-Bru V, Oprea C, et al., “Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients”, J. Clin. Oncol. (2002);20: pp. 898–906.
  93. Siemann M, Koch-Dorfler M, Gaude M, “False-positive results in premature infants with the Platelia Aspergillus sandwich enzyme-linked immunosorbent assay”, Mycoses (1998);41: pp. 373–377.
  94. Mennink-Kersten M A S, Klont R R, Warris A, Op Den Camp H J M, Verweij P E, “Bifidobacterium lipoteichoic acid and false ELISA reactivity in Aspergillus antigen detection”, Lancet (2004);363: pp. 325–327.
  95. Lescher-Bru V, Cavalier A, Pernot-Marino E, Koenig H, Eyer D, Waller J, Condolfi E, “Aspergillus galactomannan antigen detection with Platelia(r) Aspergillus: multiple positive antigenemia without Aspegillus infection”, J. Mycol. Med. (1998);8: pp. 112–113.
  96. Swanink C M, Meis J F, Rijs A J, et al., “Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan”, J. Clin. Microbiol. (1997);35: pp. 257–260.
  97. Verweij P E, Latgé J-P, Irijs A J M, et al., “Comparison of antigen detection and PCR assay using bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis in patients receiving treatment for hematological malignancies”, J. Clin. Microbiol. (1995);33: pp. 3,150–3,153.
  98. Ansorg R, van den Boom R, Rath P M, “Detection of Aspergillus galactomannan antigen in foods and antibiotics”, Mycoses (1997);40: pp. 353–357.
  99. Adam O, Auperin A, Wilquin F, Bourhis J.-H, Gachot B, Chachaty F, “Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies”, Clin. Infect. Dis. (2004);38: pp. 917–920.
  100. Mattei D, Rapezzi D, Mordini N, et al., “False-positive Aspergillus galactomannan enzyme-linked immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment”, J. Clin. Microbiol. (2004);42: pp. 5,362≠5,363.
  101. Viscoli C, Machetti M, Cappellano P, et al., “False positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam”, Clin. Infect. Dis. (2004);38: pp. 913–916.
  102. Sulahian A, Touratier S, Ribaud P, “False positive test for Aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam”, N. Engl. J. Med. (2003);349: pp. 2,366–2,367.
  103. Singh N, Obman A, Husain S, Aspinall S, Mietzner S, Stout J, “Reactivity of Platelia Aspergillus galactomannan antigen with piperacillin-tazobactam: clinical implications based on achievable serum concentrations”, Antimicrob. Agents Chemother. (2004);48: pp. 1,989–1,992.
  104. White P L, Archer A E, Barnes R A, “Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections”, J. Clin. Microbiol. (2005);43: pp. 2,181–2,187.
  105. Rogers T R, Haynes K A, Barnes R A, “Value of antigen detection in predicting invasive aspergillosis”, Lancet (1990);336: pp. 1,210–1,213.
  106. Dupont B, Huber M, Kim S J, Bennet J E, “Galactomannan antigenemia and antigenuria in aspergillosis: studies in patients and experimentally infected rabbits”, J. Infect. Dis. (1987);155: pp. 1–11.
  107. Haynes K A, Large J P, Rogers T R, “Detection of Aspergillus antigens associated with invasive aspergillosis”, J. Clin. Microbiol. (1990);28: pp. 2,040–2,044.
  108. Becker M J, de Marie S, Willemse D, Verbrugh H A, “Bakker-Woudenberg IA. Quantitative galactomannan detection is superior to PCR in diagnosing and monitoring invasive pulmonary aspergillosis in an experimental rat model”, J. Clin. Microbiol. (2000);38: pp. 1,434–1,438.
  109. Kaufman H F, Beaumont F, Meurs H, van der Heide S, de Vries K, “Comparison of antibody measurements against Aspergillus fumigatus by means of double-diffusion and enzyme-linked immunosorbent assay (ELISA)”, J. Allergy Clin. Immunol. (1983);72: pp. 255–261.
  110. Raad I, Hanna H, Huaringa A, Sumoza D, Hachem R, Albitar M, “Diagnosis of invasive pulmonary aspergillosis using polymerase chain reaction-based detection of aspergillosis in BAL”, Chest (2002);121: pp. 1,171–1,176.
  111. McWhinney P H, Kibbler C C, Hamon M D, et al., “Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years’ experience”, Clin. Infect. Dis. (1993);17: pp. 397–404.
  112. Bretagne S, Costa J M, Marmorat-Khoung A, et al., “Detection of Aspergillus species DNA in bronchoalveolar lavage samples by competitive PCR”, J. Clin. Microbiol. (1995);33: pp. 1,164–1,168.
  113. Becker M J, Lugtenburg E J, Cornelissen J J, van der Schee C, Hoogsteden H C, de Marie S, “Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis”, Br. J. Haematol. (2003);121: pp. 448–457.
  114. Coates M, Wilson J, “Central nervous system aspergillosis infection complicating renal transplantation”, Australas. Radiol. (2001);45: pp. 338–342.
  115. Verweij P E, Brinkman K, Kremer H P, Kullberg B J, Meis J F, “Aspergillus meningitis: diagnosis by non-culturebased microbiological methods and management”, J. Clin. Microbiol. (1999);37: pp. 1,186–1,189.
  116. Walsh T J, Hier D B, Caplan L R, “Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients”, Ann. Neurol. (1985);18: pp. 574–582.
  117. Kami M, Ogawa S, Kanda Y, et al., “Early diagnosis of central nervous system aspergillosis using polymerase chain reaction, latex agglutination test, and enzyme-linked immunosorbent assay”, Br. J. Haematol. (1999);106: pp. 536–537.
  118. Miyazaki T, Kohno S, Mitsutake K, et al., “Plasma (1,3)-β-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis”, J. Clin. Microbiol. (1995);33: pp. 3,115–3,118.
  119. Yuasa K, Goto H, Iguchi M, Okamura T, Ieki R, “Evaluation of the diagnostic value of the measurement of (1-3)-(- D-glucan in patients with pulmonary aspergillosis”, Respiration (1996);63: pp. 78–83.
  120. Obayashi T, Yoshida M, Mori T, et al., “Plasma (1,3)-b-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes”, Lancet (1995);345: pp. 17–20.
  121. Kohno S, Mitsutake K, Maesaki S, et al., “An evaluation of serodiagnostic tests in patients with candidemia: betaglucan, manna, Candida antigen by Cand-Tec and D-arabinitol”, Microbiol. Immunol. (1993);37: pp. 207–212.
  122. Mori T, Ikemoto H, Matsumura M, et al., “Evaluation of plasma (1_3)-beta-D-glucan measurement by the kinetic turbidimetric Limulus test, for the clinical diagnosis of mycotic infections”, Eur. J. Clin. Chem. Clin. Biochem. (1997);35: pp. 553–560.
  123. Loeffler J, Kloepfer K, Hebart H, et al., “Polymerase chain reaction detection of Aspergillus DNA in experimental models of invasive aspergillosis”, J. Infect. Dis. (2002);158: pp. 1,203–1,206.
  124. Buchheidt D, Baust C, Skladny H, et al., “Detection of Aspergillus species in blood and bronchoalveolar lavage samples from immunocompromised patients by means of 2-step polymerase chain reaction: clinical results”, Clin. Infect. Dis. (2001);33: pp. 428–435.
  125. Hebart H, Bollinger C, Fisch P, et al., “Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individual and patients with hematologic malignancies”, Blood (2003);100: pp. 4,521–4,528.
  126. Kami M, Fukui T, Ogawa S, et al., “Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis”, Clin. Infect. Dis. (2001);33: pp. 1,504–1,512.
  127. Bart-Delabesse E A, Marmorat-Khuon A, Cosa J M, et al., “Detection of Aspergillus DNA in bronchoalveolar lavage fluid of AIDS patients by polymerase chain reaction”, Eur. J. Clin. Microbiol. Infect. (1996);15: pp. 24–25.
  128. Alexander B D, “Diagnosis of fungal infection: new technologies for the mycology laboratory”, Transpl. Infect. Dis. (2002);4(suppl. 3): pp. 32–37.
  129. Girmenia C, Martino P, De Bernardis F, Cassone A, “Assessment of detection of Candida mannoproteinemia as a method to differentiate central venous catheter-related candidemia from invasive disease”, J. Clin. Microbiol. (1997);35: pp. 903–906.
  130. Yeo S F, Wong B, “Current status of non-culture methods for diagnosis of invasive fungal infections”, Clin. Microbiol. Rev. (2002);15: pp. 465–484.
  131. Tokunaga S, Ohkawa M, Takashima M, Hisazumi H, “Clinical significance of measurement of serum D-arabinitol levels in candiduria patients”, Urol. Int. (1992);48: pp. 195–199.
  132. Bernard E M, Christiansen K J, Tsang S F, Kiehn T E, Armstrong D, “Rate of arabinitol production by pathogenic yeast species”, J. Clin. Microbiol. (1981);14: pp. 189–194.
  133. Walsh T J, Hathorn J W, Sobel J D, et al., “Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis”, N. Engl. J. Med. (1991);324: pp. 1,026–1,031.
  134. Franklyn K M, Warmington J R, Ott A K, Ashman R B, “An immunodominant antigen of Candida albicans shows homology to the enzyme enolase”, Immunol. Cell. Biol. (1990);68: pp. 173–178.
  135. McLintock L A, Jones B L, “Advances in the molecular and serological diagnosis of invasive fungal infection in haematooncology patients”, Br. J. Haematol. (2004);126: pp. 289–297.
  136. Einsele H, Hebart H, Roller G, et al., “Detection and identification of fungal pathogens in blood by using molecular probes”, J. Clin. Microbiol. (1997);35: pp. 1,353–1,360.
  137. Rickerts V, Loeffler J, Bohme A, Einsele H, Just-Nubling G, “Diagnosis of disseminated zygomycosis using a polymerase chain reaction assay”, Eur. J. Clin. Microbiol. Infect. Dis. (2001);20: pp. 744–745.
  138. Voigt K, Cigelnik E, O’donnell K, “Phylogeny and PCR identification of clinically important Zygomycetes based on nuclear ribosomal-DNA sequence data”, J. Clin. Microbiol. (1999);37: pp. 3,957–3,964.
  139. Williamson E C, Speers D, Arthur I H, Harnett G, Ryan G, Inglis T J, “Molecular epidemiology of Scedosporium apiospermum infection determined by PCR amplification of ribosomal intergenic spacer sequences in patients with chronic lung disease”, J. Clin. Microbiol. (2001);39: pp. 47–50.
  140. Sole M, Cano J, Rodriguez-Tudela J L, Ponton J, Sutton D A et al., “Molecular typing of clinical and environmental isolates of Scedosporium prolificans by inter-simple-sequence-repeat polymerase chain reaction”, Med. Mycol. (2003);41: pp. 293–300.
  141. Defontaine A, Zouhair R, Cimon B et al., “Genotyping study of Scedosporium apiospermum isolates from patients with cystic fibrosis”, J. Clin. Microbiol. (2002);40: pp. 2,108–2,114.
  142. de Aguirre L, Hurst S F, Choi J S, Shin J H, Hinrikson H P, Morrison C J, “Rapid differentiation of Aspergillus species from other medically important opportunistic molds and yeasts by PCR-enzyme immunoassay”, J. Clin. Microbiol. (2004);42: pp. 3,495–3,504.
  143. Semighini C P, de Camargo Z P, Puccia R, Goldman M H, Goldman G H, “Molecular identification of Paracoccidioides brasiliensis by 5’ nuclease assay”, Diagn. Microbiol. Infect. Dis. (2002);44: pp. 383–386.
  144. Johnson S M, Simmons K A, Pappagianis D, “Amplification of coccidioidal DNA in clinical specimens by PCR”, J. Clin. Microbiol. (2004);42: pp. 1,982–1,985.
  145. Reiss E, Tanaka K, Bruker G et al., “Molecular diagnosis and epidemiology of fungal infections”, Med. Mycol. (1998);36(suppl. 1): pp. 249–257.
  146. Paschoal R C, Hirata M H, Hirata R C, Melhem Mde S, Dias A L, Paula C R, “Neurocryptococcosis: diagnosis by PCR method”, Rev. Inst. Med. Trop. Sao Paulo (2004);46: pp. 203–207.
  147. Bracca A, Tosello M E, Girardini J E, Amigot S L, Gomez C, Serra E, “Molecular detection of Histoplasma capsulatum var. capsulatum in human clinical samples”, J. Clin. Microbiol. (2003);41: pp. 1,753–1,755.
  148. Jana T, Sharma T R, Prasad R D, Arora D K, “Molecular characterization of Macrophomina phaseolina and Fusarium species by a single primer RAPD technique”, Microbiol. Res. (2003);158: pp. 249–257.
  149. Loeffler J, Hebart H, Sepe S, Schumcher U, Klingebiel T, Einsele H, “Detection of PCR-amplified fungal DNA by using a PCR-ELISA system”, Med. Mycol. (1998);36: pp. 275–279.
  150. Hebart H, Loffler J, Reitze H et al., “Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropenia”, Br. J. Haematol. (2000);111: pp. 635–640.
  151. Jordanides N E, Allan E A, Copland M et al., “Real-time PCR is superior to galactomannan and mannan ELISA for the early detection of invasive fungal infection in haematology patients”, Clin. Microbiol. Infect. (2003);9: pp. 72–73.
  152. Kuhlman J E, Fishman E K, Siegelman S S, “Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis”, Radiol. (1985);157: pp. 611–614.
  153. Primack S L, Hartman T E, Lee K S, Muller N L, “Pulmonary nodules and the CT halo sign”, Radiol. (1994);190: pp. 513–515.
  154. Caillot D, Couaillier J F, Bernard A et al., “Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia”, J. Clin. Oncol. (2001);19: pp. 253–259.
  155. Pinto P S, “The CT halo sign”, Radiol. (2004);230: pp. 109–110.
  156. Gaeta M, Volta S, Scribano E, Loria G, Vallone A, Pandolfo I, “Air-space pattern in lung metastasis from adenocarcinoma of the GI tract”, J. Comput. Assist. Tomogr. (1996);20: pp. 300–304.
  157. Gaeta M, Caruso R, Barone M, Volta S, Casablanca G, La Spada F, “Ground-glass attenuation in nodular bronchioloalveolar carcinoma: CT patterns and prognostic value”, J. Comput. Assist. Tomogr. (1998);22: pp. 215–219.
  158. Nara M, Sasaki T, Shimura S et al., “Diffuse alveolar hemorrhage caused by lung metastasis of ovarian angiosarcoma”, Intern. Med. (1996);35: pp. 653–656.
  159. Tomiyama N, Ikezoe J, Miyamoto M, Nakahara K, “CT halo sign in metastasis of osteosarcoma”, AJR Am. J. Roentgenol. (1994);162: pp. 468.
  160. Gaeta M, Blandino A, Scribano E, Minutoli F, Volta S, Pandolfo I, “Computed tomography halo sign in pulmonary nodules: frequency and diagnostic value”, J. Thorac. Imaging (1999);14: pp. 109–113.
  161. Gaeta M, Volta S, Stroscio S, Romeo P, Pandolfo I, “CT ‘halo sign’ in pulmonary tuberculoma”, J. Comput. Assist. Tomogr. (1992);16: pp. 827–828.
  162. Voloudaki A E, Kofteridis D P, Tritou I N, Gourtsoyiannis N C, Tselentis Y J, Gikas A I, “Q fever pneumonia: CT findings”, Radiol. (2000);215: pp. 880–883.
  163. Carignan S, Staples C A, Muller N L, “Intrathoracic lymphoproliferative disorders in the immunocompromised patient: CT findings”, Radiol. (1995);197: pp. 53–58.
  164. Kami M, Tanaka Y, Kanda Y et al., “Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients”, Haematologica (2000);85: pp. 745–752.
  165. Kuhlman J E, Fishman E K, Burch P A, Karp J E, Zerhouni E A, Siegelman S S, “Invasive pulmonary aspergillosis in acute leukemia: the contribution of CT to early diagnosis and aggressive management”, Chest (1987);92: pp. 95–99.
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Mutations of the β-globin gene (HBB) cause sickle cell disease and β-thalassaemia, collectively named the β-haemoglobinopathies. As mankind’s most common severe genetic diseases, where they are most prevalent, public health systems can be stressed.1–3 Asymptomatic heterozygous carriers are protected from severe P. falciparum infection. This has allowed the causative genes to reach polymorphic frequencies in some tropical […]

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