Impact of COVID-19 on paracoccidioidomycosis. Which was the most influential: The pandemic or the virus?

The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the pandemic declaration, 285 proven PCM patients were registered. No association between both diseases was documented. PCM frequency decreased to extremely low levels in 2020. Mandatory social isolation and the emotional and psychological effects generated under pandemic circumstances led to delays in diagnosis, severe disseminated cases, and other challenges for diagnosis in subsequent years. Probable underdiagnosis should be considered due to the overlap of clinical manifestations, the low index of suspicion and the lack of sensitive diagnostic tools.

Clinical and Demographic Features of Paracoccidioidomycosis in Argentina: A Multicenter Study Analysis of 466 Cases.

Information on paracoccidioidomycosis (PCM) in Argentina is fragmented and has historically been based on estimates, supported only by a series of a few reported cases. Considering the lack of global information, a national multicentric study in order to carry out a more comprehensive analysis was warranted. We present a data analysis including demographic and clinical aspects of a historical series of 466 cases recorded over 10 years (2012-2021). Patients were aged from 1 to 89 years. The general male: female (M:F) ratio was 9.5:1 with significant variation according to the age group. Interestingly, the age range 21-30 shows an M:F ratio of 2:1. Most of the cases (86%) were registered in northeast Argentina (NEA), showing hyperendemic areas in Chaco province with more than 2 cases per 10,000 inhabitants. The chronic clinical form occurred in 85.6% of cases and the acute/subacute form occurred in 14.4% of cases, but most of these juvenile type cases occurred in northwestern Argentina (NWA). In NEA, the incidence of the chronic form was 90.6%; in NWA, the acute/subacute form exceeded 37%. Diagnosis by microscopy showed 96% positivity but antibody detection displays 17% of false negatives. Tuberculosis was the most frequent comorbidity, but a diverse spectrum of bacterial, fungal, viral, parasitic, and other non-infectious comorbidities was recorded. This national multicenter registry was launched in order to better understand the current status of PCM in Argentina and shows the two endemic zones with a highly diverse epidemiology.

Genomic diversity of the human pathogen Paracoccidioides across the South American continent.

Paracoccidioidomycosis (PCM) is a life-threatening systemic mycosis widely reported in the Gran Chaco ecosystem. The disease is caused by different species from the genus Paracoccidioides, which are all endemic to South and Central America. Here, we sequenced and analyzed 31 isolates of Paracoccidioides across South America, with particular focus on isolates from Argentina and Paraguay. The de novo sequenced isolates were compared with publicly available genomes. Phylogenetics and population genomics revealed that PCM in Argentina and Paraguay is caused by three distinct Paracoccidioides genotypes, P. brasiliensis (S1a and S1b) and P. restrepiensis (PS3). P. brasiliensis S1a isolates from Argentina are frequently associated with chronic forms of the disease. Our results suggest the existence of extensive molecular polymorphism among Paracoccidioides species, and provide a framework to begin to dissect the connection between genotypic differences in the pathogen and the clinical outcomes of the disease.

Características clínicas y epidemiológicas de pacientes con paracoccidioidomicosis diagnosticados en un hospital de Resistencia, Chaco / Clinical and epidemiological characteristics of patients with paracoccidioidomycosis diagnosed in a hospital of Resistencia, Chaco

Con el objetivo de describir las características clínico-epidemiológicas de la paracoccidioidomicosis, se realizó un estudio descriptivo de los casos diagnosticados por el Servicio de Microbiología Clínica del hospital de adultos Dr. Julio C. Perrando, de la ciudad de Resistencia (Chaco, Argentina). Entre 2011 y 2014 se detectaron 46 casos. En 2013 y 2014 se constató un incremento de la tasa de incidencia de alrededor de 4 veces con respecto a los anos anteriores. La forma crónica fue la predominante, con una media de edad de los pacientes de 53 anos. Del total de ellos, a 39 se les realizaron pruebas serológicas. En 15 de 39 casos, las pruebas serológicas fueron la única herramienta diagnóstica, mientras que en 4 de estos casos con diagnóstico microbiológico, la prueba resultó no reactiva. La inclusión de la paracoccidioidomicosis en el diagnóstico diferencial de pacientes de áreas endémicas que presentan un síndrome infeccioso inespecífico y la aplicación de las herramientas diagnósticas disponibles contribuyen al diagnóstico oportuno, así como a disminuir las secuelas de esta afección y su impacto socioeconómico.

In order to describe the clinical and epidemiological characteristics of paracoccidioidomycosis, a descriptive study of all the cases diagnosed by the Clinical Microbiology Service at Dr. Julio C. Perrando hospital in the city of Resistencia (Chaco Province, Argentina) was conducted. Between 2011 and 2014, 46 cases were detected. In the period 2013-2014, an almost 4-fold increase in the incidence rate was detected. The chronic form of the disease was predominant with an average age of 53 years. Serological tests in 39 out of 46 patients were performed. In 15 of 39 patients, serological tests were the only diagnostic tool while in 4 patients with a microbiological diagnosis serological tests were non-reactive. In patients from endemic areas with non-specific infectious syndrome it is important to include paracoccidioidomycosis in the differential diagnosis and to apply all available diagnostic tools to reach a timely diagnosis and to reduce the long-term sequelae and their socio-economic impact.

Emergence of acute/subacute infant-juvenile paracoccidioidomycosis in Northeast Argentina: Effect of climatic and anthropogenic changes?

Argentina has two endemic areas of paracoccidioidomycosis (PCM). Bordering Paraguay and Brazil, Northeast Argentina (NEA) comprises the area with the highest incidence where the chronic adult clinical form has historically been reported. Juvenile form in children and adolescents is rare in this area since only one case was reported in the last 10 years. Despite this, between 2010 and 2012, several cases of acute/subacute clinical forms in children aged 10 to 16 (median 12) were detected. In the last decade, the NEA region has been exposed to ecological variations as consequences of certain climatic and anthropogenic changes, including El Niño-Southern Oscillation phenomenon during 2009, and deforestation. The region has also suffered from the significant ecological effects of the construction of one of the biggest hydroelectric dams of South America. This study aims to describe clinical and epidemiological aspects of acute/subacute PCM cases detected in children from NEA and to discuss climatic and anthropogenic changes as possible contributing factors in the emergence of this disease in children. This acute/subacute PCM cluster was characterized by severe disseminated and aggressive presentations to localized form, with a high spectrum of clinical manifestations uncommonly observed. Due to the lack of experience in acute/subacute PCM in children in the studied area and the atypical clinical manifestations observed, the diagnosis was delayed. In order to avoid misdiagnosis, a higher level of suspicion is now required in NEA and countries bordering the southern part of the endemic area, which are affected by the changes discussed in this article.

[Clinical and epidemiological characteristics of patients with paracoccidioidomycosis diagnosed in a hospital of Resistencia, Chaco]. / Características clínicas y epidemiológicas de pacientes con paracoccidioidomicosis diagnosticados en un hospital de Resistencia, Chaco.

In order to describe the clinical and epidemiological characteristics of paracoccidioidomycosis, a descriptive study of all the cases diagnosed by the Clinical Microbiology Service at Dr. Julio C. Perrando hospital in the city of Resistencia (Chaco Province, Argentina) was conducted. Between 2011 and 2014, 46 cases were detected. In the period 2013-2014, an almost 4-fold increase in the incidence rate was detected. The chronic form of the disease was predominant with an average age of 53 years. Serological tests in 39 out of 46 patients were performed. In 15 of 39 patients, serological tests were the only diagnostic tool while in 4 patients with a microbiological diagnosis serological tests were non-reactive. In patients from endemic areas with non-specific infectious syndrome it is important to include paracoccidioidomycosis in the differential diagnosis and to apply all available diagnostic tools to reach a timely diagnosis and to reduce the long-term sequelae and their socio-economic impact.

Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review.

A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement caused by Sporothrix schenckii is reported in a sexagenarian woman with a long smoking history. The patient was hospitalized for septic shock with multiorgan failure from a respiratory focus. The diagnosis was delayed due to the fungal etiological agent was not initially considered in the differential diagnosis. A good clinical and radiological evolution was obtained with the antifungal therapy. Occasional cases of primary pulmonary sporotrichosis have been reported in the literature. Due to its low incidence, this is a less-known and underestimated clinical form. Both clinical suspicion and microbiological studies are needed to reach pulmonary sporotrichosis diagnosis.

Identification of Candida parapsilosis Sensu Lato in Pediatric Patients and Antifungal Susceptibility Testing.

A total of 59 Candida parapsilosis sensu stricto and 1 Candida orthopsilosis recovered from catheters and blood cultures of pediatric patients from the northeastern region of Argentina were studied. Susceptibility to azoles, amphotericin B, and echinocandins was tested by the broth microdilution method. According to CLSI clinical breakpoints, >91% of the strains were azole susceptible, whereas 15% showed high amphotericin B MICs.

Protothecosis in a patient with T cell lymphocytic leukemia.

Human protothecosis is a rare infection caused by algae of the genus Prototheca. Prototheca wickerhamii has been recognized as the main species that causes infection in immunocompromised hosts with deficits in innate or cellular immunity. We report a case of persisting subcutaneous protothecosis in a patient with T-cell large granular lymphocyte leukemia, who also presented a history of disseminated histoplasmosis.

Biodiversity of species of Aspergillus section Fumigati in semi-desert soils in Argentina.

The distribution of Aspergillus species in soil has been widely studied all over the world. The aim of this study was the phenotypic and genotypic characterization of species Aspergillus belonging to section Fumigati present in soils from two Argentinian semi-desert areas having different geological conditions. Altogether, 23 isolates belonging to Aspergillus section Fumigati were recovered and identified using a polyphasic approach including phenotypic and molecular identifications. Aspergillus fumigatus sensu stricto and Aspergillus fumigatiaffinis had the highest frequency, of occurrence while isolates closely related to Aspergillus udagawae and Aspergillus felis were rarely observed. A. fumigatiaffinis and isolates closer to A. udagawae were isolated for the first time from Argentinian soils and this is the first report on the occurrence of species belonging to the A. felis clade in South America. Recent scientific interests in biodiversity, as well as the increasing importance of aspergilli as causative agents of human and animal diseases increase the need to understand the diversity and occurrence of these fungi in nature.

In Vivo Paracoccidioides sp. Biofilm on Vascular Prosthesis.

Paracoccidioidomycosis is an endemic mycosis caused by Paracoccidioides species limited to Latin America arising with the chronic form in 90% of cases. The capacity of microorganisms to form biofilms is considered of great importance medical since can contribute to the persistence and to the chronic state of the diseases. The ability of Paracoccidioides to form biofilm has been demonstrated in vitro. In our study, for the first time we have observed this capability in vivo on a vascular prosthesis using scanning electron microscope showing a dense network of Paracoccidioides yeasts covered by an extracellular matrix.

Antifungal susceptibility testing of Malassezia yeast: comparison of two different methodologies.

All Malassezia species are lipophilic; thus, modifications are required in susceptibility testing methods to ensure their growth. Antifungal susceptibility of Malassezia species using agar and broth dilution methods has been studied. Currently, few tests using disc diffusion methods are being performed. The aim was to evaluate the in vitro susceptibility of Malassezia yeast against antifungal agents using broth microdilution and disc diffusion methods, then to compare both methodologies. Fifty Malassezia isolates were studied. Microdilution method was performed as described in reference document and agar diffusion test was performed using antifungal tablets and discs. To support growth, culture media were supplemented. To correlate methods, linear regression analysis and categorical agreement was determined. The strongest linear association was observed for fluconazole and miconazole. The highest agreement between both methods was observed for itraconazole and voriconazole and the lowest for amphotericin B and fluconazole. Although modifications made to disc diffusion method allowed to obtain susceptibility data for Malassezia yeast, variables cannot be associated through a linear correlation model, indicating that inhibition zone values cannot predict MIC value. According to the results, disc diffusion assay may not represent an alternative to determine antifungal susceptibility of Malassezia yeast.

In vitro activities of amphotericin B, terbinafine, and azole drugs against clinical and environmental isolates of Aspergillus terreus sensu stricto.

The antifungal susceptibilities of 40 clinical and environmental isolates of A. terreus sensu stricto to amphotericin B, terbinafine, itraconazole, and voriconazole were determined in accordance with CLSI document M38-A2. All isolates had itraconazole and voriconazole MICs lower than epidemiologic cutoff values, and 5% of the isolates had amphotericin B MICs higher than epidemiologic cutoff values. Terbinafine showed the lowest MICs. No significant differences were found when MICs of clinical and environmental isolates were compared.

Especies de Aspergillus en ambientes hospitalarios con pacientes pediátricos en estado crítico / Aspergillus species in hospital environments with pediatric patients in critical condition

Antecedentes. Aspergillus es un hongo oportunista que provoca infecciones con alta morbimortalidad en pacientes inmunosuprimidos. Aspergillus fumigatus causa frecuentemente infecciones nosocomiales, pero la incidencia de otras especies ha aumentado en los últimos años. Objetivos. Evaluar la carga fúngica aérea y la diversidad de especies de Aspergillus en ambientes hospitalarios con pacientes pediátricos en estado crítico. Métodos. Durante otoño y primavera, cada 15 días, se muestrearon aire y superficies de la Unidad de Terapia Intensiva y la Unidad de Quemados de un hospital pediátrico. Las muestras de aire se tomaron con el SAS Super 100®, y las de superficies, con el método del hisopo. Resultados. Los recuentos de UFC/m3 superaron los niveles admisibles. En la Unidad de Terapia Intensiva se encontró mayor cantidad de UFC/m3 y mayor diversidad de especies de Aspergillus que en la Unidad de Quemados. La carga fúngica y la diversidad de especies dentro de las salas fueron mayores que en los ambientes control. La aplicación conjunta del método del hisopo y del SAS permitió encontrar mayor diversidad de especies. Se aislaron 96 cepas de Aspergillus, de las cuales se identificaron 12 especies. Destacaron por su alta frecuencia Aspergillus sydowii, Aspergillus niger, Aspergillus flavus, Aspergillus terreus y Aspergillus parasiticus. Se aisló Aspergillus fumigatus de ambas salas, especie considerada inaceptable en ambientes internos. Conclusiones. Aspergillus se aisló con una alta frecuencia en estas salas. Muchas de estas especies son de interés en salud pública por ser potenciales patógenos. El control y muestreo del aire es el eje en la prevención de estas infecciones (AU)

Background. Aspergillus is a group of opportunistic fungi that cause infections, with high morbimortality in immunosuppressed patients. Aspergillus fumigatus is the most frequent species in these infections, although the incidence of other species has increased in the last few years. Aims. To evaluate the air fungal load and the diversity of Aspergillus species in hospitals with pediatric patients in critical condition. Methods. The Intensive Care Unit and Burns Unit of a pediatric hospital were sampled every 15 days during the autumn and spring seasons. The air samples were collected with SAS Super 100® and the surface samples were collected by swab method. Results. The UFC/m3 counts found exceeded the acceptable levels. The UFC/m3 and the diversity of Aspergillus species found in the Intensive Care Unit were higher than those found in the Burns Unit. The fungal load and the diversity of species within the units were higher than those in control environments. The use of both methods -SAS and swab- allowed the detection of a higher diversity of species, with 96 strains of Aspergillus being isolated and 12 species identified. The outstanding findings were Aspergillus sydowii, Aspergillus niger, Aspergillus flavus, Aspergillus terreus and Aspergillus parasiticus, due to their high frequency. Aspergillus fumigatus, considered unacceptable in indoor environments, was isolated in both units. Conclusions. Aspergillus was present with high frequency in these units. Several species are of interest in public health for being potential pathogenic agents. Air control and monitoring are essential in the prevention of these infections (AU)

Native trees of the Northeast Argentine: natural hosts of the Cryptococcus neoformans-Cryptococcus gattii species complex / Árboles autóctonos del nordeste argentino. Huéspedes naturales de las especies del complejo Cryptococcus neoformans-Cryptococcus gattii

Background. In Argentina, information about epidemiology and environmental distribution of Cryptococcus is scarce. The city of Resistencia borders with Brazil and Paraguay where this fungus is endemic. All these supported the need to investigate the ecology of the genus and the epidemiology of cryptococcosis in this area. Aims. The aim was to investigate the presence of species of Cryptococcus neoformans-Cryptococcus gattii complex and their genotypes in trees of the city of Resistencia. Methods. One hundred and five trees were sampled by swabbing technique. The isolates were identified using conventional and commercial methods and genotyped by PCR-RFLP (Restriction Fragment Length Polymorphism). Results. Cryptococcus was found in 7 out of the total trees. 6 out of 7 Cryptococcus isolates were identified as C. neoformans and one as C. gattii. C. gattii was isolated from Grevillea robusta. C. neoformans strains were isolated from Tabebuia avellanedae and Peltophorum dubium. Genotyping showed that all C. neoformans belonged to the VNI type and C. gattii belonged to the VGI type. Conclusions. This represents the first study on the ecology of Cryptococcus spp. associated to trees from northeastern Argentina, and the first report describing Grevillea robusta as a host of members of this fungal genus. Another finding is the isolation of C. neoformans from Tabebuia avellanedae and Peltophorum dubium, both tree species native to northeastern Argentina (AU)

Antecedentes. En Argentina la información sobre la epidemiología y la distribución ambiental de Cryptococcus es escasa.. Resistencia es una ciudad que limita con Brasil y Paraguay, donde este hongo es endémico. Esto apoya la necesidad de investigar la ecología de este género y la epidemiología de la criptococosis en la región. Objetivos. El objetivo del presente estudio fue investigar la presencia de especies del complejo Cryptococcus neoformans - Cryptococcus gattii y sus genotipos en árboles de la ciudad de Resistencia, situada en el nordeste argentino. Métodos. Mediante la técnica del hisopo se tomaron muestras de 105 árboles. Los aislamientos se identificaron utilizando métodos convencionales y comerciales, y se genotipificaron mediante la prueba PCR-RFLP (Restriction Fragment Length Polimorphism). Resultados. Se aisló Cryptococcus en 7 árboles. Se identificaron 6 aislamientos como Cryptococcus neoformans y uno como Cryptococcus gattii. Este último se aisló de Grevillea robusta. Cryptococcus neoformans se aisló de Tabebuia avellanedae y Peltophorum dubium. La genotipificación mostró que todos los aislamientos de C. neoformans pertenecían al tipo molecular VNI, y C. gattii al tipo molecular VGI. Conclusiones. El presente estudio es la primera investigación sobre la ecología del género Cryptococcus asociado a árboles del nordeste argentino, y la primera que describe Grevillea robusta como nicho ecológico de este género fúngico. Otro hallazgo es el aislamiento de C. neoformans de Tabebuia avellanedae y Peltophorum dubium, ambas especies de árboles originarias del nordeste argentino (AU)

Antifungal susceptibility of Malassezia furfur, Malassezia sympodialis, and Malassezia globosa to azole drugs and amphotericin B evaluated using a broth microdilution method.

We studied the in vitro activity of fluconazole (FCZ), ketoconazole (KTZ), miconazole (MCZ), voriconazole (VCZ), itraconazole (ITZ) and amphotericin B (AMB) against the three major pathogenic Malassezia species, M. globosa, M. sympodialis, and M. furfur. Antifungal susceptibilities were determined using the broth microdilution method in accordance with Clinical and Laboratory Standards Institute reference document M27-A3. To support lipid-dependent yeast development, glucose, peptone, ox bile, malt extract, glycerol, and Tween supplements were added to Roswell Park Memorial Institute RPMI 1640 medium. The supplemented medium allowed good growth of all three species studied. The minimal inhibitory concentrations (MICs) were recorded after 72 h of incubation at 32ºC. The three species showed different susceptibility profiles for the drugs tested. Malassezia sympodialis was the most susceptible and M. furfur the least susceptible species. KTZ, ITZ, and VCZ were the most active drugs, showing low variability among isolates of the same species. FCZ, MCZ, and AMB showed high MICs and wide MIC ranges. Differences observed emphasize the need to accurately identify and evaluate antifungal susceptibility of Malassezia species. Further investigations and collaborative studies are essential for correlating in vitro results with clinical outcomes since the existing limited data do not allow definitive conclusions.