Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (485 page)

Core laboratory
: Laboratory tests related to specific organ systems infected by NTM. HIV serology or other diagnostic testing should be considered in any patient who is diagnosed with significant or severe infection with these mycobacteria.

Suggested Readings

Brown-Elliott BA, Brown JM, Conville PS, et al. Clinical and laboratory features of the
Nocardia
spp. based on current molecular taxonomy.
Clin Microbiol Rev.
2006;19:259–282.

Lederman ER, Crum NF. A case series and focused review of nocardiosis, Clinical and microbiologic aspects.
Medicine (Baltimore).
2004;83:300–313.

   
DISEASES CAUSED BY FUNGAL PATHOGENS

Fungi are eukaryotic organisms widely distributed in the environment; specific pathogens, like
Coccidioides
, may show a restricted geographic distribution. The fungal pathogens in this section may be initially characterized as yeasts (e.g., reproduce by binary fission with minimal cellular differentiation) or molds (e.g., formation of multicellular mycelia with differentiation of cells within the mycelial structure: vegetative hyphae, aerial hyphae, reproductive structures).

Direct examination of patient specimens (e.g., histopathology, KOH wet mount, staining) may provide initial presumptive evidence of infection. Detection of specific (e.g., cryptococcal antigen) or nonspecific (e.g., galactomannan) fungal antigens also supports a diagnosis of fungal disease. Definitive diagnosis of fungal infections, however, is primarily based on isolation of a pathogen in culture. Serologic testing may be useful for epidemiologic studies but are rarely used for the diagnosis of acute infection. See Chapter
17
, Infectious Disease Assays for additional information related to diagnostic testing for fungal infection.

   
Molds
: A huge variety of mold species are ubiquitous in nature, with a global distribution; humans are exposed on a daily basis. In immunocompetent individuals, infection is rare. A number of common mold species have emerged as significant opportunistic pathogens in immunocompromised patients. In these patients, infection is usually acquired by inhalation or direct inoculation. Disseminated or locally invasive disease may ensue.

A definitive diagnosis of infection is most reliably established by some combination of histopathology, imaging studies, and isolation of the pathogen by culture. Although septate hyphae may be distinguished from aseptate hyphae histologically, identification of different pathogens within these groups cannot be reliably established by standard histologic staining techniques alone. Definitive species identification is usually based on examination of culture isolates. Opportunistic mold species usually grow well and rapidly on nonselective fungal media. Some species may be inhibited by cycloheximide. Serology does not play a significant role in the diagnosis of opportunistic invasive fungal infections.

   Laboratory findings are consistent with dysfunction of organ systems affected by fungal infection as well as predisposing diseases (e.g., diabetes, neoplasms, IV drug use, and malnutrition).

   
Yeasts
: Yeasts behave more like bacteria than mold in the clinical laboratory; they are often isolated on bacterial culture media. Infection is usually based on microscopic morphology and biochemical testing. Antigen detection may support the diagnosis. Standardized susceptibility testing methods are available for common pathogens.

   
Dimorphic fungi
: This group of fungi includes species with intrinsic pathogenicity. Most exhibit different forms depending on their growth conditions. In the environment, the spore-forming mold form predominates. In the patient, organisms differentiate into a tissue (usually yeast) form. These organisms may be widely distributed in the environment, but the geographic distribution varies by species. Most infection is transmitted by inhalation of spores, but direct inoculation is well described.

ASPERGILLOSIS

   Definition

Species of the genus
Aspergillus
cause a variety of diseases referred to as aspergillosis. These fungi are nonpigmented, septate mold species. Humans are frequently exposed to hyphal fragments or spores, usually by inhalation. Such exposure may result in disease by invasive proliferation (infection), colonization of aerated spaces (fungus ball, otomycosis), or by immunologic response to
Aspergillus
antigens.

   Who Should Be Suspected?

   Risk factors for invasive aspergillosis include advanced AIDS, allogeneic hematopoietic stem cell and solid organ transplantation, chronic granulomatous disease, glucocorticoid therapy, graft versus host disease, hematologic malignancy, and/or prolonged profound neutropenia. Infection has been associated with exposure to construction sites, presumably due to increased dispersal of spores.

   The respiratory tract is the common portal of entry and disease most commonly involves the lungs or pararespiratory tissues. Secondary infection may be seen in any organ system, although the CNS, kidney, liver, and spleen are most commonly affected.