Rising rates of paracoccidioidomycosis-related hospitalizations and in-hospital deaths, Rio de Janeiro, Brazil (2010-2019).

The epidemiological dynamics of paracoccidioidomycosis (PCM) has been changing over the years. We analyzed secondary public data from the Hospital Information System of the Brazilian Unified Health System (SIH/SUS), focusing on PCM-related hospitalizations and in-hospital deaths. In the period between 2010 and 2019, 396 hospitalizations and 30 deaths were related to PCM among 7 073 334 hospitalizations registered in Rio de Janeiro. We highlight the rising rates, reflecting the increase in the number of acute forms previously reported. Urgent public health policies are essential to prevent poor outcomes related to this neglected mycosis.

Epidemiology of paracoccidioidomycosis has been changing in endemic areas. We analyzed secondary data on hospitalizations in Rio de Janeiro, an important endemic area. There is a trend on increasing rates of hospitalizations and in-hospital deaths mainly in the Metropolitan belt.

Acute-subacute paracoccidioidomycosis: A paediatric cohort of 141 patients, exploring clinical characteristics, laboratorial analysis and developing a non-survival predictor.

The acute-subacute form of paracoccidioidomycosis (PCM) is a severe systemic mycosis that affects children and adolescents from endemic regions, leading to generalised lymphadenopathy, fever, weight loss, anaemia, eosinophilia, hypoalbuminemia and hypergammaglobulinemia. The objective of this study is to describe the clinical and laboratorial characteristics of acute-subacute PCM, to determine a mortality risk factor and to propose a test for non-survival hazard related to the disease. Children and adolescents diagnosed with PCM, under 15 years were included in the study. Their epidemiological, clinical and laboratorial data were obtained from the hospital records. Descriptive analysis, comparison of means, univariate logistic regression, multivariate logistic regression and a ROC curve were performed in order to identify significant information (P < .05). Through a period of 38 years, 141 children and adolescents were diagnosed with acute-subacute PCM. The main antifungal agent used for the treatment was sulfamethoxazole-trimethoprim (SMX-TMP). The complication rate was 17%, the relapse rate was 7.8% and the mortality rate was 5.7%. A low albumin dosage was identified as a predictor factor for mortality. The cut-off for serum albumin was 2.18 g/dL, above which, the survival rate is 99.1%. Thus, simple clinical and laboratorial examinations may lead to the diagnosis of acute-subacute PCM, and the beginning of the treatment is encouraged even before the isolation of the fungus in biological samples, preventing unfavourable outcomes. Patients with an albumin dosage ≤ 2.18g/dL must receive special attention, preferably hospitalised, during the first four weeks of treatment for presenting an elevated mortality hazard.

Autopsy and biopsy study of paracoccidioidomycosis and neuroparacoccidioidomycosis with and without HIV co-infection.

Paracoccidioidomycosis (PCM) is a systemic mycosis prevalent among immunocompetent patients in Latin America. This study aimed to describe the frequency, demographics and clinical characteristics of central nervous system PCM (NPCM) and PCM in an endemic region, and the impact of human immunosuppression virus (HIV) co-infection. This was a retrospective study of autopsy and biopsy reports from the Medical Pathology Section of the Hospital de Clinicas, UFPR, Curitiba, Southern Brazil, between 1951 and 2014. PCM was present in 0.1% of 378,323 cases examined, with 5.7% being NPCM. Infection was prevalent in working-age men, agricultural workers and rural residents. Numbers of HIV autopsy cases increased over time, while those of PCM cases decreased. Prevalence of co-infection of HIV/PCM and HIV/NPCM was 1.6%, and 0.4%, respectively. Adrenals were affected more frequently in the NPCM group compared with the PCM group. Mortality was higher on NPCM group. The clinical course of PCM in HIV patients resembles an acute/sub-acute infection. Association of NPCM and HIV is rare, while diagnosis of NPCM is difficult, it should be considered a differential diagnosis in HIV patients who live in, or have visited, endemic areas and present with neurological symptoms.

Can passage in Galleria mellonella activate virulence factors of Paracoccidioides brasiliensis as in the murine model?

Paracoccidioidomycosis (PCM) is a fungal disease restricted to Latin countries, and its etiologic agents derive from the Paracoccidioides genus. Attenuation or loss of virulence in Paracoccidioides spp. following successive subculturing has been described. However, virulence can be recovered by passage in mammalian host. In this study, the recovery of adhesion of P. brasiliensis through passage in mice was compared to that in the insect Galleria mellonella. Analysis of in vitro fungal-host cell interaction, gene expression of adhesins, and analysis of the survival curves revealed that Galleria mellonella is useful for the reactivation of P. brasiliensis adhesion.

Paracoccidioidomycosis Mimicking Sarcoidosis: A Review of 8 Cases.

Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with this disease. The diagnosis is based on exhaustive exclusion of differential diagnoses, particularly granulomatous infections. We report data on eight patients with paracoccidioidomycosis mimicking sarcoidosis. Five patients presented with a chronic pulmonary type infection and three had a disseminated form after immunosuppressive treatment. The mycological diagnosis in noncaseating granulomas is emphasized and reviewed.

Paracoccidioidomycosis in a western Brazilian Amazon State: clinical-epidemiologic profile and spatial distribution of the disease.

INTRODUCTION: Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus Paracoccidioides brasiliensis. PCM is considered one of the most important systemic mycoses in Latin America. METHODS: This is a clinical, epidemiological, retrospective, quantitative study of PCM cases in patients attending the National Health Service in the State of Rondônia in 1997-2012. The examined variables included sex, age group, year of diagnosis, education level, profession, place of residence, diagnostic test, prior treatment, medication used, comorbidities and case progress. RESULTS: During the study period, 2,163 PCM cases were registered in Rondônia, and the mean annual incidence was 9.4/100,000 people. The municipalities with the highest rates were located in the southeastern region of Rondônia, and the towns of Pimenteiras do Oeste and Espigão do Oeste had the highest rates in the state, which were 39.1/100,000 and 37.4/100,000 people, respectively. Among all cases, 90.2% and 9.8% were observed in men and women, respectively, and most cases (58.2%) were observed in patients aged between 40 and 59 years. Itraconazole was used to treat 91.6% (1,771) of cases, followed by sulfamethoxazole in combination with trimethoprim (4.4% [85] of cases). One hundred thirty-one (6%) patients died. CONCLUSIONS: The State of Rondônia has a high incidence of PCM, and the municipalities in the southeastern region of the state were found to have the highest incidence rates of this disease. Our findings suggest that Rondônia is the state in the northern region with the highest mortality rate for PCM.

Paracoccidioidomycosis in a western Brazilian Amazon State: Clinical-epidemiologic profile and spatial distribution of the disease

Introduction: Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus Paracoccidioides brasiliensis. PCM is considered one of the most important systemic mycoses in Latin America. Methods: This is a clinical, epidemiological, retrospective, quantitative study of PCM cases in patients attending the National Health Service in the State of Rondônia in 1997-2012. The examined variables included sex, age group, year of diagnosis, education level, profession, place of residence, diagnostic test, prior treatment, medication used, comorbidities and case progress. Results: During the study period, 2,163 PCM cases were registered in Rondônia, and the mean annual incidence was 9.4/100,000 people. The municipalities with the highest rates were located in the southeastern region of Rondônia, and the towns of Pimenteiras do Oeste and Espigão do Oeste had the highest rates in the state, which were 39.1/100,000 and 37.4/100,000 people, respectively. Among all cases, 90.2% and 9.8% were observed in men and women, respectively, and most cases (58.2%) were observed in patients aged between 40 and 59 years. Itraconazole was used to treat 91.6% (1,771) of cases, followed by sulfamethoxazole in combination with trimethoprim (4.4% [85] of cases). One hundred thirty-one (6%) patients died. Conclusions: The State of Rondônia has a high incidence of PCM, and the municipalities in the southeastern region of the state were found to have the highest incidence rates of this disease. Our findings suggest that Rondônia is the state in the northern region with the highest mortality rate for PCM. .

5-Lipoxygenase activity increases susceptibility to experimental Paracoccidioides brasiliensis infection.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermodimorphic fungus Paracoccidioides brasiliensis. Leukotrienes and lipoxins are lipid mediators produced after 5-lipoxygenase (5-LO) activation that exhibit pro- and anti-inflammatory roles, respectively. Here, we have investigated the contribution of 5-LO enzymatic activity in PCM using an experimental model of P. brasiliensis infection. B6.129 wild-type (B6.129) and 5-LO-deficient (5-LO(-/-)) mice were intravenously inoculated with a virulent strain of P. brasiliensis (Pb18), and the survival rate of the infected mice was investigated on different days after yeast infection. 5-LO(-/-) mice exhibited an increased survival rate associated with a decreased number of CFU. The resistance of 5-LO(-/-) during PCM was associated with augmented nitric oxide (NO) production and the formation of compact granulomas. In addition, the absence of 5-LO was associated with a diminished number of CD4(+) CD25(+) regulatory T cells, higher levels of gamma interferon and interleukin-12, and increased T-bet (a T-box transcription factor that directs Th1 lineage commitment) mRNA levels in the lungs. Taken together, our results show for the first time that 5-LO enzymatic activity increases susceptibility to P. brasiliensis, suggesting that this pathway may be a potential target for therapeutic intervention during PCM.

Paracoccidioidomicosis crónica multifocal de tipo adulto en paciente inmunocompetente / Chronic Multifocal Paracoccidioidomycosis in an Immunocompetent Adult

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Occurrence of 102 cases of paracoccidioidomycosis in 18 months in the Itaipu Lake region, Western Paraná.

INTRODUCTION: The study investigated the incidence of disease and death events among patients with paracoccidioidomycosis who were residents in the Itaipu Lake region from 2008 to 2009. METHODS: A review of patient records was conducted at the Department of Tuberculosis of the Epidemiology Center of the City of Foz do Iguaçu, Paraná. RESULTS: The results identified 102 new cases of paracoccidioidomycosis in the period described, 72 men and 30 women, and 15 deaths were recorded during the study. CONCLUSIONS: It can be concluded that the Itaipu Lake region is an endemic region.

Occurrence of 102 cases of paracoccidioidomycosis in 18 months in the Itaipu Lake region, Western Paraná / Ocorrência de 102 casos de paracoccidioidomicose em 18 meses na região do Lago de Itaipu, Oeste do Paraná

INTRODUCTION: The study investigated the incidence of disease and death events among patients with paracoccidioidomycosis who were residents in the Itaipu Lake region from 2008 to 2009. METHODS: A review of patient records was conducted at the Department of Tuberculosis of the Epidemiology Center of the City of Foz do Iguaçu, Paraná. RESULTS: The results identified 102 new cases of paracoccidioidomycosis in the period described, 72 men and 30 women, and 15 deaths were recorded during the study. CONCLUSIONS: It can be concluded that the Itaipu Lake region is an endemic region.

INTRODUÇÃO: O estudo investigou a incidência da doença e eventos de morte entre os portadores de paracoccidiodomicose residentes na região do Lago de Itaipu, no período de 2008 a 2009. MÉTODOS: Foi realizado levantamento em registros de pacientes do Setor de Tuberculose do Centro de Epidemiologia da Cidade de Foz do Iguaçu, Paraná, entre o período de janeiro de 2008 e julho de 2009. RESULTADOS: Os resultados apontam 102 novos casos de paracoccidiodomicose, 72 homens e 30 mulheres, foram registrados 15 óbitos durante o estudo. CONCLUSÕES: Conclui-se que a região do Lago de Itaipu é uma região endêmica.

Morbimortalidade por paracoccidioidomicose no Brasil: 1998 -2006 / Morbidity and mortality from paracoccidioidomycosis in Brazil: 1998 -2006

Morbimortalidade por paracoccidioidomicose no Brasil. 1998-2006. INTRODUÇÃO: A paracoccidioidomicose (PCM) é micose sistêmica exclusiva do continente americano. O Brasil detém cerca de 80 por cento dos casos da doença. OBJETIVO: A presente pesquisa analisa, pela primeira vez, a morbidade hospitalar da paracoccidioidomicose no Brasil avaliando-a conjuntamente com a mortalidade pela endemia. METODOLOGIA: Realizou-se um estudo descritivo da morbidade hospitalar e mortalidade por paracoccidioidomicose, no período de janeiro de 1998 a dezembro de 2006. Analisou-se sua distribuição no tempo e no espaço e as características epidemiológicas, sociodemográficas e administrativas. As variáveis analisadas foram: frequência dos eventos segundo local de residência e de ocorrência, sexo e idade, óbito hospitalar e ocupação. A fonte dos dados para internações foi o Sistema de Informações Hospitalares (SIH/SUS), e para os óbitos, o Sistema de Informações de Mortalidade (SIM/SUS) do Sistema Único de Saúde. Selecionaram-se as internações e óbitos que tiveram como diagnóstico principal e causa básica, respectivamente, a paracoccidioidomicose (categoria B41) e a blastomicose (B40). O diagnóstico de blastomicose foi considerado equivalente a paracoccidioidomicose. RESULTADOS: No período estudado, ocorreram 6.732 internações e 1523 óbitos, representando, respectivamente, uma taxa de internação de 4,3 e uma taxa de mortalidade por paracoccidioidomicose de 1,0 por milhão de habitantes. A paracoccidioidomicose, com aproximadamente 50 por cento, das internações e dos óbitos, foi a micose sistêmica mais prevalente, figurando entre as dez principais causas de mortalidade por doença infecciosa e parasitária de natureza crônica e recorrente. A maioria dos casos era do sexo masculino, com 82 por cento das internações e 88 por cento dos óbitos. Entre as ocupações bem definidas, 60 por cento dos óbitos ocorreram em trabalhadores rurais...

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to the American continent. Brazil holds about 80% of cases of the disease.OBJECTIVE: This study aims, first, to analyze, for the first time, the hospital morbidity together with the mortality due to this endemic in Brazil.METHODS: A descriptive study of hospital morbidity and mortality due to paracoccidioidomycosis, was performed from January 1998 to December 2006. Their distribution in time and space, their epidemiological, socio-demographic and administrative characteristics were analyzed. The variables included: frequency of events by place of residence and occurrence, sex and age, in-hospital death and occupation. The source of data for admissions was the Hospital Information System (SIH / SUS), and deaths, the Information System of Mortality (SIM / SUS) of the Unified Health System. All hospital admissions and deaths were selected, respectively, either as primary diagnosis and underlying cause, paracoccidioidomycosis (Category B41) and/or blastomycosis (B40). The diagnosis of blastomycosis was considered equivalent to paracoccidioidomycosis. CONCLUSION: The study demonstrated that during the analyzed period paracoccidioidomycosis, with approximately 50 percent of all hospital admissions and deaths, was the most prevalent systemic mycosis in Brazil and showed a new spatial distribution of the disease in face of recent trends in the economic, environmental and migration that occur in the Brazilian territory...

CD28 exerts protective and detrimental effects in a pulmonary model of paracoccidioidomycosis.

T-cell immunity has been claimed as the main immunoprotective mechanism against Paracoccidioides brasiliensis infection, the most important fungal infection in Latin America. As the initial events that control T-cell activation in paracoccidioidomycosis (PCM) are not well established, we decided to investigate the role of CD28, an important costimulatory molecule for the activation of effector and regulatory T cells, in the immunity against this pulmonary pathogen. Using CD28-deficient (CD28(-/-)) and normal wild-type (WT) C57BL/6 mice, we were able to demonstrate that CD28 costimulation determines in pulmonary paracoccidioidomycosis an early immunoprotection but a late deleterious effect associated with impaired immunity and uncontrolled fungal growth. Up to week 10 postinfection, CD28(-/-) mice presented increased pulmonary and hepatic fungal loads allied with diminished production of antibodies and pro- and anti-inflammatory cytokines besides impaired activation and migration of effector and regulatory T (Treg) cells to the lungs. Unexpectedly, CD28-sufficient mice progressively lost the control of fungal growth, resulting in an increased mortality associated with persistent presence of Treg cells, deactivation of inflammatory macrophages and T cells, prevalent presence of anti-inflammatory cytokines, elevated fungal burdens, and extensive hepatic lesions. As a whole, our findings suggest that CD28 is required for the early protective T-cell responses to P. brasiliensis infection, but it also induces the expansion of regulatory circuits that lately impair adaptive immunity, allowing uncontrolled fungal growth and overwhelming infection, which leads to precocious mortality of mice.

Micoses sistêmicas: fatores associados ao óbito em pacientes com infecção pelo vírus da imunodeficiência humana, Cuiabá, Estado de Mato Grosso, 2005-2008 / Systemic mycosis: factors associated with death among patients infected with the human immunodeficiency virus, Cuiabá, State of Mato Grosso, Brazil, 2005-2008

A prevalência de micose sistêmica entre 1.300 pacientes portadores de HIV/Aids de Cuiabá, Mato Grosso foi de 4,6 por cento, no período de 2005-2008. As espécies de fungos isoladas foram o Cryptococcus neoformans (50 por cento), Cryptococcus gattii (1,6 por cento), Cryptococcus spp (6,6 por cento), Histoplasma capsulatum (38,3 por cento) e Paracoccidioides brasiliensis (3,3 por cento). Óbito foi registrado em 32 (53,3 por cento) pacientes, sendo a criptococose a principal causa. A contagem de linfócitos T CD4+ foi baixa e semelhante entre os pacientes que sobreviveram ou faleceram por micose sistêmica. O etilismo (OR:8,2; IC95 por cento: 1,4-62,1; p=0,005) e o nível médio de desidrogenase lática [758 (182) U/L vs 416 (268) U/L; p<0,001] foram as características independentemente associadas ao óbito dos pacientes do estudo. Os resultados mostram alta letalidade por micoses sistêmicas em pacientes portadores de HIV/Aids de Cuiabá e sugerem que características clínico-laboratoriais tais como o etilismo e a elevação precoce da desidrogenase lática podem ser fatores relacionados ao pior prognóstico nessas condições.

Between 2005 and 2008, the prevalence of systemic mycosis among 1,300 HIV/AIDS patients in Cuiabá, Mato Grosso, was 4.6 percent. The fungus species isolated were Cryptococcus neoformans in 50 percent, Cryptococcus gattii in 1.6 percent, Cryptococcus spp in 6.6 percent, Histoplasma capsulatum in 38.3 percent and Paracoccidioides brasiliensis in 3.3 percent. Death was recorded in the cases of 32 patients (53.3 percent), and cryptococcosis was the main cause. The CD4+ T lymphocyte count was low and similar among patients who survived or died due to systemic mycosis. The factors independently associated with the deaths of these patients were alcoholism (OR: 8.2; 95 percent CI: 1.4-62.1; p = 0005) and the mean level of lactate dehydrogenase [758 (182) U/l vs. 416 (268) U/l; p < 0001]. The findings showed that systemic mycosis was highly lethal among the patients with HIV/AIDS in Cuiabá and suggested that clinical-laboratory characteristics such as alcoholism and early elevation of lactate dehydrogenase may be factors relating to worse prognosis under these conditions.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006.

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (approximately 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2 percent). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9 percent) appeared at the top of the list, followed by candidiasis (30.2 percent), histoplasmosis (10.1 percent) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

[Systemic mycosis: factors associated with death among patients infected with the human immunodeficiency virus, Cuiabá, State of Mato Grosso, Brazil, 2005-2008]. / Micoses sistêmicas: fatores associados ao óbito em pacientes com infecção pelo vírus da imunodeficiência humana, Cuiabá, Estado de Mato Grosso, 2005-2008.

Between 2005 and 2008, the prevalence of systemic mycosis among 1,300 HIV/AIDS patients in Cuiabá, Mato Grosso, was 4.6%. The fungus species isolated were Cryptococcus neoformans in 50%, Cryptococcus gattii in 1.6%, Cryptococcus spp in 6.6%, Histoplasma capsulatum in 38.3% and Paracoccidioides brasiliensis in 3.3%. Death was recorded in the cases of 32 patients (53.3%), and cryptococcosis was the main cause. The CD4+ T lymphocyte count was low and similar among patients who survived or died due to systemic mycosis. The factors independently associated with the deaths of these patients were alcoholism (OR: 8.2; 95% CI: 1.4-62.1; p = 0005) and the mean level of lactate dehydrogenase [758 (182) U/l vs. 416 (268) U/l; p < 0001]. The findings showed that systemic mycosis was highly lethal among the patients with HIV/AIDS in Cuiabá and suggested that clinical-laboratory characteristics such as alcoholism and early elevation of lactate dehydrogenase may be factors relating to worse prognosis under these conditions.

Deficiency of IL-12p40 subunit determines severe paracoccidioidomycosis in mice.

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. To investigate the role of interleukin (IL)-12 in this disease, IL-12p40-/- deficient mice (IL-12p40-/-) and wild type mice (WT) were infected intravenously with viable yeast cells of P. brasiliensis 18 isolate. We found that, unlike WT mice, IL-12p40-/- mice did not control fungal proliferation and dissemination and succumbed to infection by day 21 after inoculation. Additionally, IL-12p40-/- mice presented a higher number of granulomas/mm2 in lung tissue than WT mice, and showed unorganized granulomas containing high numbers of yeast cells. Moreover, IL-12p40-/- mice did not release detectable levels of IFN-gamma, but they produced high levels of IL-10, as well as IgG1 antibody. Additionally, splenocytes from both infected IL-12p40-/- and WT mice exhibited a suppressed Con-A-induced T cell proliferative response. Our findings suggest that the IL-12p40 subunit mediates resistance in paracoccidioidomycosis by inducting IFN-gamma production and a Th1 immune response.