Paracoccidioidomycosis: What We Know and What Is New in Epidemiology, Diagnosis, and Treatment

Abstract

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America caused by thermodimorphic fungi of the genus Paracoccidioides. In the last two decades, enhanced understanding of the phylogenetic species concept and molecular variations has led to changes in this genus’ taxonomic classification. Although the impact of the new species on clinical presentation and treatment remains unclear, they can influence diagnosis when serological methods are employed. Further, although the infection is usually acquired in rural areas, the symptoms may manifest years or decades later when the patient might be living in the city or even in another country outside the endemic region. Brazil accounts for 80% of PCM cases worldwide, and its incidence is rising in the northern part of the country (Amazon region), owing to new settlements and deforestation, whereas it is decreasing in the south, owing to agriculture mechanization and urbanization. Clusters of the acute/subacute form are also emerging in areas with major human intervention and climate change. Advances in diagnostic methods (molecular and immunological techniques and biomarkers) remain scarce, and even the reference center’s diagnostics are based mainly on direct microscopic examination. Classical imaging findings in the lungs include interstitial bilateral infiltrates, and eventually, enlargement or calcification of adrenals and intraparenchymal central nervous system lesions are also present. Besides itraconazole, cotrimoxazole, and amphotericin B, new azoles may be an alternative when the previous ones are not tolerated, although few studies have investigated their use in treating PCM.

Overview of invasive fungal infections in children in South America – the threat of resistant Candida species and the role of climate change in the new geographic distribution of endemic systemic mycosis

“…Paracoccidioidomycosis (PCM) is a severe neglected tropical mycosis of great importance in Latin American countries [48 ▪▪ ,49], especially in Brazil with 80% of cases, followed by Colombia, Venezuela, Ecuador, and Argentina, associated with rural environments and agricultural activities [50,54 ▪▪ ]. The incidence of paracoccidioidomycosis can be altered by climate phenomena, by human migration and occupation of poorly explored territories [50].…”

Diagnosis and Treatment of Pulmonary Coccidioidomycosis and Paracoccidioidomycosis

“…Skin lesions may also be found in 25% to 30% of patients, with a considerable polymorphism of manifestations, including papulonodular, ulcer-crusted, molluscoid, or acneiform lesions [ 85 , 86 , 128 ]. Notably, these lesions may facilitate laboratory diagnosis by direct mycological or histopathological examination of exudates or tissues [ 129 ]. When only pulmonary abnormalities are present, epidemiological inquiry and imaging findings represent the main red flags that trigger laboratory investigations of fungal infections.…”

“…in culture, as well as microscopic visualization of typical yeast cells by direct mycological examination (DME) or histopathology [ 55 , 56 ] ( Table 1 ). Direct mycological examination of exudates may be performed using 20–40% KOH solution, depending on the clinical sample, with or without Parker ink, by placing the sample between a slide and a coverslip [ 60 , 129 ]. Clinical samples for DME may be collected from skin or mucous membranes, sputum, bronchoalveolar lavage, and some difficult-to-access samples, such as biopsies from the lungs, the larynx, lymph nodes, central nervous system, and adrenals [ 135 , 136 ].…”

“…Typical fungal elements of Paracoccidioides spp. are represented by mother cells measuring 10–40 µm in diameter surrounded by multiple buds (blastoconidia) 2–6 µm in diameter, resembling the aspect of “pilot’s wheel” (multiple buds) or “Mickey Mouse” (two buds) [ 55 , 56 , 129 ]. Grocott’s methenamine silver and PAS stains provide better sensitivity when identifying fungal elements in tissue than HE [ 57 , 137 ].…”

“…identification is still considered to be DNA sequencing followed by phylogenetic analysis. Considering that there is no commercially available molecular method for this identification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) is a reliable and more suitable alternative for the accurate identification of P. brasiliensis complex and P. Lutzii in routine laboratories [ 55 , 129 , 140 ].…”