Nonmolecular Methods for the Diagnosis of Respiratory Fungal Infections

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Key points

  • •

    Nonmolecular fungal biomarkers are part of the diagnostic workup of invasive fungal pneumonia in conjunction with other clinical, radiologic, and microbiological criteria.

  • •

    Good evidence supports the use of the galactomannan (GM) test in serum or bronchoalveolar lavage fluid for the diagnosis and follow-up of invasive aspergillosis in patients who have hematologic cancer.

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    The 1,3-β-d-glucan (BG) test in serum can detect a broad spectrum of invasive fungal pathogens, including Pneumocystis jirovecii

Microbiology/Epidemiology

Pneumonia is the leading infectious cause of death in developed countries.1 Among the broad variety of respiratory pathogens, fungi account for only a small proportion of community-acquired and nosocomial pneumonias.2, 3 However, fungal respiratory infections are of particular concern in the expanding population of immunosuppressed patients, and the spectrum of opportunistic fungi causing infections in predisposed individuals is constantly increasing, as shown in Table 2. Aspergillus represents

Clinical presentation

Signs and symptoms of fungal pneumonia are not specific and are indistinguishable from those associated with respiratory infections of other origins. Fever is often the only sign of infection in neutropenic patients, who are not able to mount an effective immune response. Albeit not specific, pulmonary nodules are present in most cases of fungal pneumonia. A ground-glass opacity surrounding a macronodule is referred to as the halo sign and is present in about 60% of cases of invasive

Pathogenesis

Fungi may simply colonize body sites without overt disease or they may invade, producing a variety of clinical syndromes. Development of disease is based on the susceptibility of the host and virulence of the pathogen. For example, Aspergillus fumigatus conidia are continuously inhaled by humans but rarely result in disease, because they are eliminated efficiently by the innate immune response. Pulmonary alveolar macrophages ingest inhaled A fumigatus conidia and inhibit germination. If

Diagnosis

The mortality of fungal respiratory infections has remained high despite the advent of new antifungal therapies.14, 15 The lack of specific signs of infection and the low sensitivity of conventional culture-based methods for diagnosis of fungal diseases result in delayed initiation of antifungal therapy. The early recognition and treatment of these infections are crucial for optimal outcome and represent a major challenge for the clinicians. A consensus group of the European Organization for

Treatment

Although the performance of nonmolecular fungal markers for the diagnosis of IFI has been evaluated in multiple analyses, few studies have focused on their role in triggering therapeutic decisions. Overall, it is estimated that the GM and BG test anticipate the diagnosis of IFI by approximately 1 week (2–10 days) compared with conventional clinical, radiologic, and microbiological criteria,29, 30, 32, 33, 122 which supports their usefulness as screening tests for the early initiation of

Discussion/Summary

Non–culture-based diagnostic tools represent an attractive alternative approach for the diagnosis of fungal pneumonia. Because these infections are life threatening and have a low prevalence, a valuable diagnostic test should be both highly sensitive and specific. Although the cryptococcal antigen has been admitted as a conventional test in the diagnostic workup of cryptococcosis, the role of the GM and BG tests for diagnosis of IFIs is still controversial. Many studies have reported data on

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