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.

Antibody Isotype and Subclass Responses in Human Patients With Different Clinical Presentations of Sporotrichosis.

Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition.

The present and future research agenda of sporotrichosis on the silver anniversary of zoonotic sporotrichosis in Rio de Janeiro, Brazil.

Twenty-five years have passed since the initial observation of endemic zoonotic sporotrichosis in Rio de Janeiro, Brazil. Since then, this disease has spread throughout South America. Accompanying the emergence of this mycosis, some progress has been made, including the expansion of a research network in this field and higher visibility of sporotrichosis within government authorities and funding agencies. However, there are still some challenges to curbing the expansion of this disease in the coming years. These include the development of rapid and accurate diagnostic tests, new antifungal drugs, particularly for the treatment of extracutaneous manifestations of sporotrichosis, and more comprehensive care for cats with sporotrichosis. Including these actions in the sporotrichosis research agenda is required so as to change the development of this disease in the years to come.

Sporotrichosis After Tattooing Caused by Sporothrix brasiliensis.

Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the genus Sporothrix. Since 1998, the number of cases of sporotrichosis due to Sporothrix brasiliensis has grown significantly in Rio de Janeiro, Brazil. Nearly all cases are related to cats as the main source of fungal infection. We report two cases of sporotrichosis following tattoos, a transmission form of S. brasiliensis not yet reported. The first patient, a 22-year-old female, had cutaneous sporotrichosis, fixed form, over a tattoo in her lumbar region. The lesion appeared 12 weeks after she was tattooed. The second patient, a 27-year-old female, had a lymphocutaneous sporotrichosis over a forearm tattoo. The lesion appeared two weeks after she was tattooed. In both cases there was no history of contact with cats or other plausible source of infection. The present study highlights that other non-zoonotic forms of transmission of S. brasiliensis may occur in endemic areas.

Zoonotic sporotrichosis with greater severity in Rio de Janeiro, Brazil: 118 hospitalizations and 11 deaths in the last 2 decades in a reference institution.

Since 1998, there has been an increase in the number of cat-transmitted cases of human sporotrichosis in Rio de Janeiro state, and severe forms are observed especially when associated with human immunodeficiency virus (HIV). A retrospective search of the INI/ Fiocruz database was conducted to identify sporotrichosis cases, hospitalized and deceased patients, between 1999 and 2015. There were 3917 adult patients diagnosed, 75 of them hospitalized, and 11 died. We conclude there is still a progression toward hyperendemic levels and greater severity has been demonstrated mainly in a socially excluded population.

Paracoccidioides brasiliensis habitat: far beyond armadillo burrows?

Paracoccidioides spp. isolation from environmental samples is rare and hardly reproducible. Molecular techniques have facilitated the fungal detection. However, it can be still difficult. Some strategies to enhance the capacity of DNA detection have been adopted, including the analysis of soil samples belonging to the habitat of animals from which Paracoccidioides spp. have already been isolated, notably armadillo burrows. To date, the detection of Paracoccidioides spp. has not yet been reported from outbreak hotspots. Clusters and outbreaks of acute paracoccidioidomycosis (PCM), usually a more severe clinical form, have currently occurred in urban areas being associated to climate changes, deforestation, and great constructions. These occurrences potentially signalise the fungus' environmental niche, a riddle not yet solved. The authors performed an environmental investigation in a deeply disturbed area, after a highway construction in Rio de Janeiro, Brazil, where a recent outbreak of acute PCM occurred. Specific DNA sequences of Paracoccidioides brasiliensis were detected in shallow soil samples around the highway, reinforcing the association between the road construction and this PCM outbreak.

A case of sporotrichosis caused by different Sporothrix brasiliensis strains: mycological, molecular, and virulence analyses.

BACKGROUND: Sporotrichosis is a subcutaneous mycosis caused by dimorphic pathogenic fungi belonging to the Sporothrix genus. Pathogenic Sporothrix species typically produce melanin, which is known to be a virulence factor. OBJECTIVES: The aim of this study was to perform phenotypic, genotypic, and virulence analyses of two distinct Sporothrix brasiliensis strains isolated from the same lesion on a patient from Rio de Janeiro. METHODS AND FINDINGS: Genotypic analyses by partial sequencing of the calmodulin, ß-tubulin, and chitin synthase genes, as well as polymerase chain reaction (PCR)-fingerprinting by T3B, M13, and GACA, showed that the isolates were very similar but not identical. Both isolates had similar phenotypic characteristics and effectively produced melanin in their yeast forms, accounting for their ability of causing disease in a murine sporotrichosis model. Remarkably, isolate B was albino in its environmental form but caused more severe disease than the pigmented A isolate. CONCLUSIONS: These findings indicate that the patient was infected by two genetically and biologically distinct S. brasiliensis that vary in their production of melanin in their environmental forms. The results underscore the importance of characterizing phenotypically different isolates found in the same clinical specimen or patient.

Hepatic Disease with Portal Hypertension and Acute Juvenile Paracoccidioidomycosis: A Report of Two Cases and Literature Review.

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole-trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.

Paracoccidioides brasiliensis PS2: First Autochthonous Paracoccidioidomycosis Case Report in Rio de Janeiro, Brazil, and Literature Review.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by pathogenic dimorphic fungi of the Paracoccidioides brasiliensis complex. It is the most important systemic mycosis in Latin America, mainly in Brazil. Despite its severity and high mortality rates, it is considered a neglected disease. Species within the genus Paracoccidioides present genetics and morphological variations with probable clinical, diagnostic and therapeutic consequences. In fact, there are a very small number of detailed case reports with molecular identification of these fungal agents. Here, it is reported a case of PCM due to Paracoccidioides brasiliensis PS2. Molecular identification of the isolate was performed by amplification and sequencing of the arf and gp43 genes. Clinical cases and strain reports with molecular identification in the literature are also reviewed. The case herein presented is the first autochthonous report of PCM due to Paracoccidioides brasiliensis PS2 species in the state of Rio de Janeiro, Brazil, an important endemic area. The patient presented a chronic pulmonary form of PCM and had a satisfactory response to sulfamethoxazole/trimethoprim although sequelae such as adrenal insufficiency and dysphonia were observed. This study may contribute to improve the knowledge about this severe disease, its causative cryptic species and their consequences to patients.

Histoplasma capsulatum urinary antigen detection in a kidney transplant recipient with acute paracoccidioidomycosis: Case study and literature review.

BACKGROUND: Paracoccidioidomycosis (PCM) and histoplasmosis are endemic fungal diseases in South America. Both can lead to lung involvement with fungal dissemination progressing to systemic and severe clinical manifestations, especially in immunosuppressed hosts. As the population of immunosuppressed individuals has been rising, a higher occurrence of fungal infections is predicted in this setting. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of cases. OBJECTIVES: In this study, the authors discuss the occurrence of a false-positive Histoplasma urinary antigen detection in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided. METHODS: A comprehensive literature search was conducted to investigate previous studies that found cross-reactivity between Histoplasma urinary antigen assays in human patients with confirmed diagnosis of PCM. Additionally, an update of PCM in transplant recipients is provided. FINDINGS: The included studies reported 120 samples from patients with PCM tested for Histoplasma antigen, presenting an overall cross-reactivity of 51.67% and 17 cases of PCM in transplant recipients. CONCLUSIONS: The galactomannan urinary antigen developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap.

Non-Zoonotic Transmission of Sporotrichosis: A Translational Study of Forty-Three Cases in a Zoonotic Hyperendemic Area.

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii. In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle.

COVID-19 in patients with paracoccidioidomycosis.

INTRODUCTION: In 2020, we reported the first patient with concomitant COVID-19 and paracoccidioidomycosis (PCM). Since then, no other cases have been recorded in the literature. We aim to update information on the occurrence of COVID-19 in patients with PCM followed at a reference center for infectious diseases at Rio de Janeiro, Brazil. METHODS: We reviewed the medical records from patients diagnosed with PCM who presented with clinical symptoms, radiological findings, and/or laboratory diagnosis of COVID-19 at any time during their acute or follow-up care. The clinical profiles of these patients were described. RESULTS: Between March 2020 and September 2022, we identified six individuals with COVID-19 among the 117 patients with PCM evaluated. The median age was 38 years and the male to female ratio 2:1. Most patients (n = 5) presented for evaluation due to acute PCM. The severity of COVID-19 ranged from mild to severe in acute PCM and only the single patient with chronic PCM died. CONCLUSIONS: There is a range of disease severity in COVID-19 and PCM co-infection and concomitant disease may represent a severe association, especially in the chronic type of the mycosis with pulmonary involvement. As COVID-19 and chronic PCM share similar clinical aspects and PCM is neglected, it is probable that COVID-19 has been hampering simultaneous PCM diagnosis, which can explain the absence of new co-infection reports. With the continued persistence of COVID-19 globally, these findings further suggest that more attention by providers is necessary to identify co-infections with Paracoccidioides.

Trends in the Epidemiological and Clinical Profile of Paracoccidioidomycosis in the Endemic Area of Rio de Janeiro, Brazil.

Paracoccidioidomycosis (PCM) is a neglected endemic mycosis in Latin America. Most cases occur in Brazil. It is classified as PCM infection and PCM disease and is subdivided into chronic (adult type) or acute (juvenile type) disease, with the latter being less frequent and more severe. In 2016, we reported an increase in the numbers of patients diagnosed with acute PCM after a highway's construction. We conducted a study at INI-Fiocruz, a reference center for infectious diseases, including endemic mycoses, in Rio de Janeiro, Brazil, aiming to deepen the analysis of this new clinical and epidemiological profile of PCM. The authors developed a retrospective study including 170 patients diagnosed with PCM between 2010 and 2019. There was an increase in the number of atypical and severe forms, starting in 2014. In subsequent years, we detected a higher incidence of adverse outcomes with patients requiring more hospitalizations and an increased mortality rate. We estimate that PCM has become more severe throughout the Rio de Janeiro state, affecting a greater number of young individuals and leading to a greater number of and longer hospitalizations. Surveillance measures and close monitoring of future notification data in the state, with emphasis on children, adolescents, and young adults are necessary for a better understanding of the perpetuation of this public health challenge.

Acute paracoccidioidomycosis worsened by immunosuppressive therapy due to a misdiagnosis of Crohn's disease.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, mostly in Brazil. The involvement of the gastrointestinal tract is uncommon and usually associated with the acute form. Recently, a cluster of acute PCM cases has been described in Rio de Janeiro, Brazil. We report a 42-year-old male, resident of Rio de Janeiro, presenting chronic diarrhea and abdominal pain in the past 3 years, previously diagnosed as Chron´s disease. When immunosuppressive therapy was prescribed, the patient evolved with worsening of the previous symptoms in addition to odynophagia, 20 kg-weight loss, disseminated skin lesions, diffuse lymphadenopathy and adrenal insufficiency. Histopathological and mycological examination of a skin lesion were compatible with PCM. Itraconazole was prescribed in high doses (400 mg/day). After seven months of treatment, the patient presented with acute abdominal pain which led to an emergent appendectomy, revealing the presence of the fungus. After 24 months, the patient reached clinical cure and recovered from adrenal insufficiency. We emphasize the importance of PCM as a differential diagnosis in patients with chronic diarrhea. The risk of fungal infections should be considered prior to initiating immunosupressive therapies, particularly in endemic areas.

Sporotrichosis in Older Adults: A Cohort Study of 911 Patients from a Hyperendemic Area of Zoonotic Transmission in Rio de Janeiro, Brazil.

Generally, older people tend to suffer from more severe infections than younger adults. In addition, there are accumulations of comorbidities and immune senescence in some cases. This cohort study evaluated the clinical and epidemiological characteristics of older adults (≥60 years old) with sporotrichosis. The cohort consisted of 911 patients with a median age of 67 years, most of whom were female (72.6%), white (62.1%), and afflicted with comorbidities (64.5%). The lymphocutaneous form occurred in 62% of the patients, followed by the fixed form (25.7%), cutaneous disseminated form (8.9%), and extracutaneous/disseminated forms (3.3%). In this study, we draw attention to the frequency of osteoarticular involvement (2.1%) secondary to skin lesions such as osteomyelitis and/or tenosynovitis. A clinical cure was achieved in 87.3% of cases. Itraconazole was used in 81.1% of cases, while terbinafine was used in 22.7% of cases, usually in low doses. Survival analysis showed that the median treatment time was 119 days, and the multiple Cox model demonstrated that the presentation of a black coloration and diabetes was associated with a longer treatment time required to establish a cure. Therefore, these subgroups should be monitored more closely to reduce possible difficulties during treatment. It would be interesting to conduct more studies analyzing older adults with sporotrichosis from different geographic areas to better comprehend the disease in this group.

Paracoccidioidomycosis and pregnancy: A 40-year single-center cohort study in the endemic area of Rio de Janeiro, Brazil.

The occurrence of acute paracoccidioidomycosis (PCM) in urban areas of the Rio de Janeiro state, Brazil, has emerged in recent years. Therefore, young populations, including pregnant women, are at a higher risk of infection. Furthermore, young women undergoing itraconazole treatment for PCM have increased chances to get pregnant because this medication may reduce the effectiveness of contraceptives. Acute PCM is invasive, reaching abdominal organs, posing a maternal-fetal risk. PCM treatment in pregnant women is also challenging due to the teratogenicity associated with the currently available oral drugs. There are scarce studies on PCM and pregnancy, mainly consisting of case reports and experimental murine models that highlight the severity of this association. We conducted a database research at a PCM reference center in Rio de Janeiro state from 1980 to 2020. We included patients diagnosed with PCM who were pregnant shortly before, at admission, or at any moment of their PCM follow-up care. Data related to pregnancy, childbirth, and the newborn were obtained from the Brazilian official public databases. We also reviewed the epidemiological and clinical features of these patients. During the study period, we identified 18 pregnant patients, with a median age of 26 years (range: 16-38). Among these cases, six (33.3%) were detected in the last 5 years, and 14 (77.8%) presented acute PCM, supporting the recent shift in the epidemiological profile towards acute PCM. Most pregnancies occurred during PCM treatment (n = 11, 61.1%), which led to challenges in the therapeutic management. Maternal-fetal complications occurred in some of these cases, including vaginal bleeding (n = 1), preeclampsia (n = 1), prematurity (n = 2), low birth weight (n = 4), and fetal deaths (n = 2). PCM during pregnancy presents a significant public health concern in the context of the emergence of acute PCM in urban areas.

Sporotrichosis in HIV-infected patients: report of 21 cases of endemic sporotrichosis in Rio de Janeiro, Brazil.

Sporotrichosis is endemic in Rio de Janeiro, Brazil, and cases have been reported to be associated with HIV. This article describes the clinical manifestations and evolution of sporotrichosis in HIV-positive patients and constitutes the largest case series reported to date. There were 21 HIV-positive patients with sporotrichosis diagnosed by the recovery of the etiologic agent from 1999-2009. Sixteen patients (76.2%) were men and five (23.8%) were women, with a mean age of 41.2 years. Seven of these individuals were previously unaware of their HIV infection. Mean CD4 count was 346.4 cells/µl. The most frequent clinical presentations of sporotrichosis in these patients were the lymphocutaneous and disseminated form (seven patients each, 33.3%), followed by the widespread cutaneous form in five (23.8%), and fixed form in the remaining two (9.5%). In patients with the disseminated forms, clinical manifestations involved the skin in six, mucosa (nasal, oral, or conjunctival) in four, bone in two, and meninges in two. Eleven (52.4%) patients received itraconazole and eight (38.1%) amphotericin B contributing to an overall cure rate of 81%. Spontaneous cure was observed in one patient. The clinical forms of sporotrichosis varied according to the patients' immune status. The results demonstrate the importance of sporotrichosis as an opportunistic infection associated with AIDS in countries where the mycosis occurs.

A Spatial Analysis of the Spread of Hyperendemic Sporotrichosis in the State of Rio de Janeiro, Brazil.

Sporotrichosis is a subacute/chronic subcutaneous mycosis. Since the late 1990s, there has been a hyperendemic zoonotic transmission in the state of Rio de Janeiro, involving Sporothrix brasiliensis, the most virulent causative species, and a "belt" was described along the limits between the capital and its outskirts ("Baixada Fluminense"). This study analyzes the distribution of sporotrichosis using secondary data from the Notifiable Diseases Information System (Sinan) of the Rio de Janeiro State Health Department (SES/RJ) from 2011 to 2015 and from the INI Electronic Patient Record System (Sipec) from 2008 to 2015. Cases diagnosed since the onset of the hyperendemic exceed all previously reported case series of the disease and there is a progressive expansion in the state of Rio de Janeiro. The study suggests the spread of the mycosis to all regions of the state and the expansion of the previously described "belt", despite public health measures and changes in its profile over the years, with great social impact.