Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease

Abstract

Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment.

Endemic Mycoses and Cryptococcus in Solid Organ Transplant Recipients

“…A proven diagnosis of paracoccidioidomycosis can be made when the characteristic yeast form is found in clinical specimens under direct microscopy [78]. Microscopically, the yeast form has a characteristic multiple budding formation, referred to as a pilot's wheel, characterized by large yeast cells surrounded by multipolar budding daughter cells [73,78]. At 35-37C the fungus will grow in about 10 days, however culture can take up to one month to grow, and the ideal means of diagnosis should always be through direct observation of the organism in a tissue sample.…”

“…Serological methods are available in endemic regions, but there are no standardized serological assays and results may vary between different laboratories. There are no validated serologic assays for the diagnosis of P. lutzii [78]. Serological tests may also not be reliable in diagnosis of acute disease in the solid organ transplant population due to a delayed immune response in the setting of immunosuppression.…”

Living Within the Macrophage: Dimorphic Fungal Pathogen Intracellular Metabolism

“…Disease results from inhalation of aerosolized fungal conidia from the environmental mold form. Severity of disease ranges from subclinical to acute, and is largely a function of the dose inhaled and the immunological defenses of the host (Kauffman, 2009 ; Queiroz-Telles and Escuissato, 2011 ; Salzer et al, 2018 ). In immunocompromised individuals (e.g., HIV patients), infection can result in life-threatening disseminated disease.…”

Endemic pulmonary fungal diseases in immunocompetent patients: an emphasis on thoracic imaging

“…Diagnosis of pulmonary disease related to systemic endemic mycoses is challenging, especially in low-prevalence settings where physicians may not be familiar with the clinical manifestations. Moreover, pulmonary manifestations may mimic other granulomatous diseases such as tuberculosis and sarcoidosis, as well as bacterial or viral pneumonia and lung cancer [6]. Accurate diagnosis remains difficult despite improvements in imaging studies, serologic/microbiologic testing and interventional bronchoscopic/radiologic procedures [7].…”