Figure - available from: Mycopathologia
This content is subject to copyright. Terms and conditions apply.
Clinical findings in a young female patient with acute juvenile paracoccidioidomycosis presenting with diffuse crusted skin lesions, cervical lymph node enlargement, and jaundice before (a), and after two years of treatment (b)
Source publication
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 a...
Similar publications
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin American countries. Amphotericin B, sulfonamides, and azoles may be used in the treatment of PCM. However, the high toxicity, prolonged course of treatment, and significant frequency of disease relapse compromise their use. Therefore, there is a need to seek new therapeuti...
Paracoccidioidomycosis (PCM) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae. Thus, the development of alternative therapies is imperative. In the current work, two oxadiazole compounds (LMM5 and LMM11) presented fungicidal activity against Paracoccidioides spp. The minimum inhibitory...
Citations
... Six reports were identified in the medical literature, through a search in the databases of the Pubmed and Scielo platforms, with the following descriptors: "paracoccidioidomycosis" + "portal hypertension". Among these cases, we highlight that one individual was coinfected with schistosomiasis and the other with hepatitis C, diseases classically described as causes of portal hypertension 4,5 . Furthermore, hepatic involvement by PCM is also described in the medical literature as a consequence of perihepatic lymph node obstruction, inflammatory ductal fibrosis or even periampullary obstructive lesion, resulting in jaundice due to cholestatic syndrome 4,5,6,7,8,9,10 . ...
... Among these cases, we highlight that one individual was coinfected with schistosomiasis and the other with hepatitis C, diseases classically described as causes of portal hypertension 4,5 . Furthermore, hepatic involvement by PCM is also described in the medical literature as a consequence of perihepatic lymph node obstruction, inflammatory ductal fibrosis or even periampullary obstructive lesion, resulting in jaundice due to cholestatic syndrome 4,5,6,7,8,9,10 . The rare cases that indicate this clinical manifestation highlight the importance of the differential diagnosis of PCM with proliferative diseases and periampullary tumors. ...
Introduction: Juvenile paracoccidioidomycosis (PCM), a disease caused by fungi of the genus Paracoccidioides, requires high clinical suspicion, as a range of differential diagnoses are possible. Case report: This report describes a patient diagnosed with juvenile PCM who, due to low adherence to treatment, developed a more extensive fungal invasion within eight years, causing portal hypertension due to portal vein thrombosis. This is a rare and serious manifestation. Conclusion: Only six similar reports were identified in the medical literature, through a search in the databases of the Pubmed and Scielo platforms.
... 6,7 In this case, the presence of jaundice was noteworthy, due to the severe hepatobiliary involvement, which is one of the systems most affected by the disease. 8 The main causes of jaundice related to paracoccidioidomycosis are biliary obstruction due to lymph node enlargement, pancreatitis, intraluminal granulomatous lesion, and hepatitis. It should be emphasized that the first two above-mentioned causes were identified in this patient. ...
... 9 In conclusion, in endemic areas, it is important to consider paracoccidioidomycosis among the diagnostic hypotheses for jaundice and other signs and symptoms of cholangitis. 8 Moreover, we must be alert to the emergence of cases in urban areas where environmental changes are taking place, especially with deforestation, which can affect the health-illness relationship. ...
Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.
Keywords:
Paracoccidioidomycosis; Chylothorax; Chylous Ascites
The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidi-oidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of Paracoccidioides spp. This review describes the most relevant biological features of Paracoccidioides spp., including aspects of the phy-logeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.
Introduction
The agents of paracoccidioidomycosis, historically identified as Paracoccidioides brasiliensis, are in fact different phylogenetic species. This study aims to evaluate associations between Paracoccidioides phylogenetic species and corresponding clinical data.
Methods
Paracoccidioides strains from INI/Fiocruz patients (1998–2016) were recovered. Socio-demographic, epidemiological, clinical, serological, therapeutic and prognostic data of the patients were collected to evaluate possible associations of these variables with the fungal species identified through partial sequencing of the ADP-ribosylation factor (arf) and the 43-kDa-glycoprotein (gp43) genes.
Results
Fifty-four fungal strains were recovered from 47 patients, most (72.3%) infected in Rio de Janeiro state, Brazil. Forty-one cases were caused by Paracoccidioides brasiliensis and six by Paracoccidioides americana (former PS2). P. brasiliensis was responsible for severe lymph abdominal forms, whereas patients infected with P. americana presented a high rate of adrenal involvement. However, no statistically significant associations were found for all variables studied. P. americana presented 100% reactivity to immunodiffusion, even when tested against antigens from other species, while negative results were observed in 9 (20%) cases caused by P. brasiliensis, despite being tested against a homologous antigen.
Conclusions
P. brasiliensis and P. americana are sympatric and share similar clinical features and habitat, where they may compete for similar hosts.
Paracoccidioidomycosis (PCM), caused by the Paracoccidioides species, is a systemic mycosis with granulomatous character and a restricted therapeutic arsenal. The aim of this work was to search for new alternatives to treat largely neglected tropical mycosis, such as PCM. In this context, the enzymes of the shikimate pathway constitute excellent drug targets for conferring selective toxicity because this pathway is absent in humans but essential for the fungus. In this work, we have used a homology model of the chorismate synthase (EC 4.2.3.5) from Paracoccidioides brasiliensis ( Pb CS) and performed a combination of virtual screening and molecular dynamics to identify new potential inhibitors. The best hit, CP1, successfully adhered to pharmacologic criteria (adsorption-destribution-metabolism-excretion-toxicity) and was, therefore, used in in vitro experiments. Here, we demonstrate that CP1 binds with a dissociation constant of 64±1 μM to recombinant chorismate synthase from P. brasiliensis and inhibits enzymatic activity with an IC 50 value of 47±5 μM. As expected, CP1 showed no toxicity in three cell lines. On the other hand, CP1 reduced the fungal burden in lungs from treated mice, similar to itraconazole. In addition, the histopathological analysis showed that animals treated with CP1 displayed less lung tissue infiltration, fewer yeast cells, and large areas with preserved architecture. Therefore, CP1 was able to control PCM in mice with less inflammatory response and is, therefore, a promising candidate and lead structure for the development of drugs useful in PCM treatment.
Background:
Paracoccidioidomycosis (PCM) is one of the most important systemic mycoses in Latin America and the leading fungal cause of mortality in non-immunosuppressed individuals in Brazil. However, HIV/PCM co-infection can increase the clinical severity in these co-infected patients. This co-infection is rarely reported in the literature mainly because of the different epidemiological profiles of these infections. Furthermore, PCM is a neglected and non-notifiable disease, which may underestimate the real importance of this disease. The advent of molecular studies on the species of the genus Paracoccidioides has expanded the knowledge regarding the severity and the clinical spectrum in PCM. In this context, the development of studies to describe the association of the Paracoccidioides phylogenetic cryptic species in vulnerable populations, such as HIV-infected patients, appears relevant.
Objective:
To describe the clinical, epidemiological, therapeutic and prognostic aspects in HIV/PCM co-infected patients, along with the molecular identification of the Paracoccidioides species involved in these cases.
Methods:
The investigators performed a molecular and clinical retrospective study involving HIV/PCM co-infected patients, from a reference centre for PCM care in the endemic area of Rio de Janeiro, Brazil, from 1998 to 2015. Molecular identification of the fungal strains was done by amplification of partial sequences of arf and gp43 genes.
Findings:
Of 89 patients diagnosed with PCM by fungal isolation in the culture, a viable isolate was recovered for molecular analysis from 44 patients. Of these 44 patients, 28 (63.6%) had their serum samples submitted for enzyme immunoassay tests for screening of HIV antibodies, and 5 (17.9%) had a positive result. All cases were considered severe, with a variable clinical presentation, including mixed, acute/subacute clinical forms and a high rate of complications, requiring combination therapy. Paracoccidioides brasiliensis S1 was the species identified in all cases.
Conclusions:
HIV/PCM co-infection can change the natural history of this fungal disease. The authors reinforce the need to include HIV screening diagnostic tests routinely for patients with PCM.
