Invasive and Subcutaneous Infections Caused by Filamentous Fungi: Report from a Portuguese Multicentric Surveillance Program

Abstract

Invasive fungal infections (IFI) have significantly increased over the past years due to advances in medical care for the at-risk immunocompromised population. IFI are often difficult to diagnose and manage, and can be associated with substantial morbidity and mortality. This study aims to contribute to understanding the etiology of invasive and subcutaneous fungal infections, their associated risk factors, and to perceive the outcome of patients who developed invasive disease, raising awareness of these infections at a local level but also in a global context. A laboratory surveillance approach was conducted over a seven-year period and included: (i) cases of invasive and subcutaneous fungal infections caused by filamentous/dimorphic fungi, confirmed by either microscopy or positive culture from sterile samples, (ii) cases diagnosed as probable IFI according to the criteria established by EORTC/MSG when duly substantiated. Fourteen Portuguese laboratories were enrolled. Cases included in this study were classified according to the new consensus definitions of invasive fungal diseases (IFD) published in 2020 as follows: proven IFI (N = 31), subcutaneous fungal infection (N = 23). Those proven deep fungal infections (N = 54) totalized 71.1% of the total cases, whereas 28.9% were classified as probable IFI (N = 22). It was possible to identify the etiological fungal agent in 73 cases (96%). Aspergillus was the most frequent genera detected, but endemic dimorphic fungi represented 14.47% (N = 11) of the total cases. Despite the small number of cases, a high diversity of species were involved in deep fungal infections. This fact has implications for clinical and laboratory diagnosis, and on the therapeutic management of these infections, since different species, even within the same genus, can present diverse patterns of susceptibility to antifungals.

Clinical mycology capacity and access to antifungal treatment in Portugal

“…among institutions is also in accordance with a previous report from a Portuguese multicentric surveillance program, in which Aspergillus spp. was identified as the most predominant etiological agent in 53 cases of IFD [14]. This change in epidemiology is aligned with the widespread introduction of broad-spectrum antifungal prophylaxis to reduce morbidity and mortality rates associated with invasive candidiasis [35].…”

“…Despite Portugal is not considered an endemic area for dimorphic fungi, the report from the Portuguese multicentric surveillance program surprisingly demonstrated a high frequency of infections caused by these pathogens [14]. Case reports on Portuguese fungal burden have documented the presence of IFD established by other endemic fungi like Paracoccidioides brasiliensis and Histoplasma, endemic in Brazil and in other areas of the Americas and Africa, respectively [14,15]. These occurrences are easily explained by the significant influx of immigrants from Africa and Brazil [42].…”

“…Other vulnerable groups include the elderly population and intensive care unit patients with severely debilitating conditions, namely respiratory viral infections such as Coronavirus disease (COVID-19) and influenza, which underlie the development of COVID-19associated aspergillosis (CAPA) [10,11] and influenza-associated aspergillosis (IAPA) [12]. Traveling to and from endemic regions, whose climate and general conditions are favorable to the development of specific infections, including coccidioidomycosis, histoplasmosis, paracoccidioidomycosis and cryptococcosis (Cryptococcus gatti), further potentiates the dissemination of endemic mycoses to nonendemic areas [13][14][15], which in the case of Portugal, might be due to the high number of South American and African citizens [14].…”

“…reported in Portugal each year [54]. While these numbers may be relatively small compared to other countries, the diversity of fungal species causing these infections is noteworthy[14]. This has important implications for clinical and laboratory diagnosis, and therefore therapeutic management, as different fungal species exhibit diverse patterns of susceptibility to antifungal drugs.In recent years, the emergence of azole-resistant Aspergillus strains has substantially increased in Portugal, with the Portuguese population using more antifungal drugs per capita than other European countries[54][55][56].…”

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal

“…Other vulnerable settings include advanced age and intensive care, and severe debilitating conditions, namely respiratory viral infections, such as COVID-19 and influenza, which underlie the development of COVID-19-associated aspergillosis (CAPA) [ 9 , 10 ] and COVID-19-associated mucormycosis [ 11 ], and influenza-associated aspergillosis (IAPA) [ 12 ], respectively. Traveling to endemic regions further potentiates the dissemination of endemic mycoses to non-endemic areas [ 13 – 15 ], which in the case of Portugal, may be the reflection of the high number of individuals of South American and African origin [ 14 ].…”