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A 45-year-old man (Case 1) from a rural area in the state of Rio de Janeiro, Brazil presented with a 2-year history of dry cough and an extensive ulcerated genital lesion. Chest radiography showed a bilateral perihilar infiltrate. A 56-year-old man (Case 2) from the countryside of Rio de Janeiro presented with a 14-month history of an ulcerated tongue, dysphagia, and weight loss. In both cases, clinical samples were collected for histologic examination using hematoxylin-eosin and Grocott methenamine silver stains.

Neuroparacoccidioidomycosis (NPCM) is a rare and severe clinical presentation of paracoccidioidomycosis (PCM). We performed a retrospective cohort study at the Evandro Chagas National Institute of Infectious Diseases (INI/Fiocruz), a reference center for PCM in the state of Rio de Janeiro, Brazil. All cases of PCM admitted to the INI/Fiocruz from January 2007 to December 2019 were reviewed. Eight (3.9%) among 207 patients met the diagnostic criteria for NPCM. The mean age was 44.6 years and the male:female ratio was 7:1. All cases presented multifocal disease, 5 (62.5%) the chronic form and 3 (37.5%) the acute/subacute form. All patients presented the pseudotumoral pattern and 6 (75.0%) had multiple lesions in the cerebral hemispheres. Seizures and motor symptoms were the most frequent clinical manifestations (50.0%, each). The treatment of choice was sulfamethoxazole/trimethoprim (SMZ-TMP) and fluconazole, in association (87.5%). Most patients responded well to the treatment. Sequela and death occurred in one (12.5%) patient, each.

Background Cryptococcosis is a neglected and predominantly opportunistic mycosis that, in Brazil, poses an important public health problem, due to its late diagnosis and high lethality. Methods The present study analysed cryptococcosis mortality in Brazil from January 2000 to December 2012, based on secondary data (Mortality Information System/SIM-DATASUS and IBGE). Results Out of 5,755 recorded deaths in which cryptococcosis was mentioned as one of the morbid states that contributed to death, two distinct groups emerged: 1,121 (19.5%) registered cryptococcosis as the basic cause of death, and 4,634 (80.5%) registered cryptococcosis associated with risk factors, mainly AIDS (75%), followed by other host risks (5.5%). The mortality rate by cryptococcosis as the basic cause was 6.19/million inhabitants, whereas the mortality rate by cryptococcosis as an associated cause was 25.19/million inhabitants. Meningitis was the predominant clinical form (80%), males were the more affected (69%), and 39.5 years old was the mean age. The highest mortality rate due to cryptococcosis as basic cause occurred in the state of Mato Grosso (10.96/million inhabitants). Mortality rates due to cryptococcosis as associated cause were highest in the states of Santa Catarina (70.41/million inhabitants) and Rio Grande do Sul (64.40/million inhabitants), both in the South Region. Southeast, Northeast and South showed significant time trends in mortality rates. Conclusions This study is relevant because it shows the magnitude of cryptococcosis mortality linked to AIDS and removes the invisibility of a particular non-AIDS-related disease, accounting for almost 20% of all cryptococcosis deaths. It can also contribute to control and surveillance programs, beyond highlighting the urgent prioritization of early diagnosis and proper treatment to reduce the unacceptable mortality rate of this neglected mycosis in Brazil., Author summary Cryptococcosis is an invasive, global, and neglected mycosis. Species of the Cryptococcus neoformans complex cause opportunistic infections in immunosuppressed hosts, particularly AIDS patients, while infections by species of the C. gattii complex predominate as a primary endemic mycosis in tropical and subtropical areas. In Brazil, it is an important and hidden public health problem, mainly in its meningitis form, whose lethality ranges from 45 to 65%, but remains as a not-notifiable disease. Brazilian studies placed it as the first cause of mortality among all AIDS-associated systemic mycoses and the second cause of mortality among systemic mycoses in general. This national study used data from the Brazilian Mortality Information System (SIM) in which all mentioned causes were considered, allowing the analysis of the associated causes of deaths and showing two different patterns of infections: a primary and an opportunistic cryptococcosis. Primary cryptococcosis presented a peculiar epidemiological regional profile and the opportunistic cryptococcosis was hidden by several immunosuppressive conditions. The authors expect that this study can support a better understanding of this infection and encourage more research and public health initiatives to prevent and control the cryptococcosis, both primary and opportunistic.

Objective To analyse hospital morbidity records due to paracoccidioidomycosis in Brazil, including its nationwide distribution in time and space, as well as key epidemiological and sociodemographic characteristics. Methods Descriptive analysis of hospital morbidity records due to paracoccidioidomycosis covering the period January 1998 to December 2006. Hospital records were obtained from the Hospital Information System of the Brazilian Unified Health System (SIH/SUS). Results There were 6732 hospitalisations (82% male) due to paracoccidioidomycosis in the period, representing 4.3 per 1.0 million inhabitants. Admissions due to this mycosis were recorded in 27% of the 5560 Brazilian municipalities, covering 35% of the country. Ten municipalities concentrated 52% of all admissions. The temporal distribution of admissions for paracoccidioidomycosis showed a slight increase. The geographical analysis showed two distinct patterns of the disease: (i) traditional areas of southern and south-eastern regions, covering 60% of admissions, and (ii) a second pattern in northern Brazil revealed a transverse band of higher concentration with about 27% of admissions, particularly along the southern border of the Amazon region. Conclusion This first nationwide analysis of hospitalisation due to paracoccidioidomycosis in Brazil shows that it is the most prevalent systemic mycosis in Brazil. Despite its importance, there are major deficits in its proper registry, diagnostics and treatment. The particular epidemiological and medical challenges of paracoccidioidomycosis will not be met while the disease continues to be perceived as an isolated infectious entity restricted to a few faraway regions of the globe. Objectif Analyser les registres hospitaliers sur la morbidite due a la paracoccidioidomycose au Bresil, y compris sa distribution temporelle et spatiale a l’echelle nationale, ainsi que les caracteristiques epidemiologiques et sociodemographiques cles. Methodes Analyse descriptive des registres hospitaliers sur la morbidite due a la paracoccidioidomycose couvrant la periode de janvier 1998 a decembre 2006. Les registres des hopitaux ont ete obtenus a partir du Systeme d'Information Hospitalier du Systeme de sante unifie bresilien (SIH/SUS). Resultats Il y avait 6732 hospitalisations (82% d'hommes) pour la paracoccidioidomycose dans la periode, ce qui represente 4,3 cas pour 1,0 millions d'habitants. Les admissions dues a cette mycose ont ete enregistrees dans 27% des 5 560 municipalites bresiliennes, couvrant 35% du pays. Dix municipalites concentraient 52% de toutes les admissions. La repartition temporelle des admissions pour la paracoccidioidomycose a montre une legere augmentation. L'analyse geographique montre deux modeles distincts de la maladie: (1) les zones traditionnelles des regions du sud et du sud-est, couvrant 60% des admissions et (2) un second model dans le nord du Bresil a revele une bande transversale de concentration plus elevee avec environ 27% des admissions, particulierement le long de la frontiere sud de la region amazonienne. Conclusion Cette premiere analyse nationale des hospitalisations pour la paracoccidioidomycose au Bresil montre que c'est la mycose systemique la plus repandue au Bresil. Malgre son importance, il y a des lacunes importantes pour une bonne documentation, pour le diagnostic et le traitement. Les defis epidemiologiques et medicaux particuliers de la paracoccidioidomycose ne seront pas vaincus quand la maladie continue d’etre percue comme une entite infectieuse isolee, limitee a quelques regions eloignees du globe. Objetivo Analizar los registros de morbilidad hospitalaria por paracoccidioidomicosis en Brasil, incluyendo su distribucion a nivel nacional en tiempo y espacio, al igual que sus principales caracteristicas epidemiologicas y sociodemograficas. Metodos Analisis descriptivo de los registros de morbilidad hospitalaria por paracoccidioidomicosis durante el periodo comprendido entre Enero de 1998 y Diciembre del 2006. Los registros hospitalarios se obtenian del Sistema de Informacion Hospitalaria del Sistema Sanitario Unificado del Brasil (SIH/ SSU). Resultados Hubo 6,732 hospitalizaciones (82% hombres) debido a paracoccidioidomicosis durante el periodo de estudio, representando un 4.3 por 1.0 millon de habitantes. Las admisiones debido a esta micosis se registraron en un 27% de las 5,560 municipalidades brasileras, abarcando un 35% del pais. Diez municipios concentraban el 52% de todas las admisiones. La distribucion temporal de las admisiones por paracoccidioidomicosis mostraron un leve aumento. El analisis geografico mostro dos patrones distintivos de la enfermedad: (1) Areas tradicionales de las regiones del sur y sudeste, cubriendo un 60% de las admisiones; y (2) un segundo patron al norte del Brasil, revelo una banda transversal de mayor concentracion con cerca del 27% de las admisiones, particularmente a lo largo de borde meridional de la region Amazonica. Conclusion Este primer analisis nacional de hospitalizaciones por paracoccidioidomicosis demuestra que es la micosis sistemica mas prevalente en Brasil. A pesar de su importancia, hay grandes deficits en su registro, diagnostico y tratamiento adecuados. Los retos epidemiologicos y medicos particulares de la paracoccidioidomicosis no se resolveran mientras que la enfermedad continue siendo percibida como una entidad infecciosa aislada, restringida a unas pocas regiones remotas del planeta.

Background Paracoccidioidomycosis (PCM) is a systemic mycosis caused by pathogenic dimorphic fungi of the genus Paracoccidioides. It is the most important systemic mycosis in Latin America and the leading cause of hospitalizations and death among them in Brazil. Acute PCM is less frequent but relevant because vulnerable young patients are affected and the severity is usually higher than that of the chronic type. Methods The authors performed a retrospective cohort study from 2001 to 2009 including acute juvenile PCM patients from a reference center in Rio de Janeiro, Brazil. Clinical, epidemiological, diagnostic, therapeutic, and prognostic data were reported. Results Twenty-nine patients were included. The average age was 23 years old and the male to female ratio was 1:1.07. All cases were referred from 3 of 9 existing health areas in the state of Rio de Janeiro, predominantly from urban areas (96.5%). Lymph nodes were the most affected organs (100%), followed by the skin and the spleen (31% each). Twenty-eight patients completed treatment (median 25 months) and progressed to clinical and serological cure; 1 death occurred. Twenty-four patients completed 48-month median follow-up. Four patients abandoned follow-up after the end of treatment. The most frequent sequela was low adrenal reserve. Paracoccidioides brasiliensis S1 was identified by partial sequencing of the arf and gp43 genes from 4 patients who presented a viable fungal culture. Conclusion Acute juvenile PCM is a severe disease with a high rate of complications. There are few cohort clinical studies of acute PCM in the literature. More studies should be developed to promote improvement in patients’ healthcare., Author summary Paracoccidioidomycosis (PCM) is a neglected systemic mycosis caused by fungi of the genus Paracoccidioides present in the soil and is endemic to Latin America. The acute clinical form of this disease is less frequent than the chronic type of presentation. However, it is a more severe clinical condition, potentially life-threatening, affecting many important organs of the immune defense such as the lymph nodes, liver, and spleen. It can lead to serious complications as well as many sequelae in young vulnerable patients and children. There are few works published in the literature concerning clinical, epidemiological, prognostic and therapeutic features of acute juvenile PCM. This study aims to describe a 9-year cohort study of patients with acute juvenile PCM from a reference center in the endemic area of Rio de Janeiro, Brazil. Results demonstrate that early diagnosis can prevent poor outcomes and that a specialized medical structure is required to promote proper healthcare for these patients. Severe outcomes such as low adrenal reserve and a death occurred in 4 and 1 patients, respectively. The authors expect that these results can contribute to a better understanding of this severe fungal disease.

The paracoccidioidomycosis mortality rate in the State of Paraná, Brazil (1980/1998) was analyzed using the death registry data from the Brazilian Mortality Information System and the estimated population from the Brazilian Institute of Geography and Statistics. To qualify the deaths, we deployed ICD-9 for 1980/1995 and ICD-10 for the more recent years. During this period there were 551 deaths from paracoccidioidomycosis in the State of Paraná. Most of the deaths were in male in the 30-59-year age group. The average annual mortality rate was 3.48 per million inhabitants, showing a tendency to stabilize during the study period. Paracoccidioidomycosis was the fifth cause of mortality among the predominantly chronic infectious diseases and had the highest mortality rate among the systemic mycoses. Paracoccidioidomycosis was observed in 184 counties in the State of Paraná. Most deaths were recorded in the North-Central meso-region, and the highest mortality rate occurred in the West meso-region.

An atypical case of acquired immunodeficiency syndrome-associated mucocutaneous lesions due to Leishmania braziliensis is described. Many vacuolated macrophages laden with amastigote forms of the parasite were found in the lesions. Leishmanin skin test and serology for leishmaniasis were both negative. The patient was resistant to therapy with conventional drugs (antimonial and amphotericin B). Interestingly, remission of lesions was achieved after an alternative combined therapy of antimonial associated with immunotherapy (whole promastigote antigens). Peripheral blood mononuclear cells were separated and stimulated in vitro with Leishmania antigens to test the lymphoproliferative responses (LPR). Before the combined immunochemotherapy, the LPR to leishmanial antigens was negligible (stimulation index - SI=1.4). After the first course of combined therapy it became positive (SI=4.17). The antigen responding cells were predominantly T-cells (47.5%) most of them with CD8+ phenotype (33%). Very low CD4+ cells (2.2%) percentages were detected. The increased T-cell responsiveness to leishmanial antigens after combined therapy was accompanied by interferon-g (IFN-g) production as observed in the cell culture supernatants. In this patient, healing of the leishmaniasis lesions was associated with the induction of a specific T-cell immune response, characterized by the production of IFN-g and the predominance of the CD8+ phenotype among the Leishmania-reactive T-cells.

This study analyzes 3,181 deaths from paracoccidioidomycosis in Brazil, based on 16 years of sequential data (from 1980 to 1995). During this period paracoccidioidomycosis showed considerable magnitude and low visibility, representing the eighth most common cause of death from predominantly chronic or recurrent types of infectious and parasitic diseases. It also had the highest mortality rate among the systemic mycoses. The mean annual mortality rate was 1.45 per million inhabitants, indicating a downward long-term trend (reduction of 31.28%), while spatial distribution among the different regions and States of Brazil was non-homogenous. The South (with the highest regional rate) and the Southeast showed a downward trend, while the Central West had the second highest rate in the country. At least one-fifth of Brazilian municipalities (or 22.71% of the country's total area) reported deaths from paracoccidioidomycosis. Overall nationwide mortality per area was 3.73/10,000km². The disease was endemic in non-metropolitan areas. The majority of deaths occurred in males (84.75%), and there was a sex ratio of 562 men/100 women. The 30-59-year and over-60-year age groups were the most affected. The study showed that the mortality rate justifies classifying this disease as a major health problem in Brazil. Foram estudados 3.181 óbitos por paracoccidioidomicose no Brasil, a partir de séries temporais de 16 anos (1980-1995). No período, esta micose mostrou grande magnitude e baixa visibilidade, destacando-se como oitava causa de mortalidade por doença predominantemente crônica ou repetitiva, entre as infecciosas e parasitárias, e a mais elevada taxa de mortalidade entre as micoses sistêmicas. A taxa de mortalidade média anual foi de 1,45/milhão de habitantes, com tendência secular em queda (redução de 31,28%), a distribuição espacial não foi homogênea entre as diferentes regiões e Estados. O Sul, com a maior taxa regional, e o Sudeste apresentaram tendência a queda. A Região Centro-Oeste teve o segundo coeficiente mais alto do País, com tendência a ascensão. Houve registro de óbitos pela endemia em cerca de um quarto dos municípios brasileiros, estendendo-se por 22,71% de sua área. A densidade geral de óbitos foi de 3,73 óbitos/10.000km². A doença prevaleceu como endemia nas áreas não metropolitanas. A taxa de mortalidade predominou em indivíduos do sexo masculino, com 84,75% dos óbitos e razão de masculinidade de 562 homens/100 mulheres. O grupo etário entre 30-59 anos foi o mais atingido, seguido dos indivíduos com 60 anos ou mais. O estudo mostrou que a taxa de mortalidade pode ser considerada como indicador para definir a doença como importante agravo de saúde no Brasil.