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Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients. Author summary: Visceral leishmaniasis (VL) is a neglected vector-borne infectious disease with a systemic and chronic involvement that is lethal when untreated. Para-kala-azar dermal leishmaniasis (para-KDL) is a complication of VL, in which the patient presents with dermatological and visceral manifestations simultaneously. Para-KDL cases are of significant epidemiological importance, as humans act as a source of infection in parasite transmission. In the Americas, Brazil accounts for over 90% of VL cases. Nevertheless, reports of para-KDL remain scarce. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The three cases exhibit similarities in terms of signs and symptoms, diagnostic criteria for AIDS, and the presence of active VL with skin lesions. The study contributes to the understanding of the epidemiological profile of para-PKDL cases in Brazil. It highlights the significance of multidisciplinary follow-up and secondary prophylaxis for patients with VL and emphasizes the need for more effective clinical management strategies for these patients. [ABSTRACT FROM AUTHOR] more...

Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available. [ABSTRACT FROM AUTHOR] more...

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition. [ABSTRACT FROM AUTHOR] more...

Paracoccidioidomycosis (PCM) is a systemic mycosis with high incidence in Latin America, caused by species of the genus Paracoccidioides spp. Brazil is considered to be the endemic center of this disease, which is identified as the eighth cause of mortality from chronic infectious disease in the country. There are several specific diagnostic methods in PCM, such as microbiological, immunological, histopathological, and molecular. However, the standard laboratory diagnosis depends mostly on fungus direct observation - the gold standard of PCM diagnosis. The implementation of new technologies, such as Fourier Transform Infrared (FTIR), can contribute to the clinical diagnosis trial of this disease. Here, we evaluated a new strategy for the diagnosis of PCM by using blood serum FTIR spectra from 20 patients with PCM and 20 healthy individuals. Machine learning algorithms were able to provide an overall accuracy of 91.67% by using Cubic SVM in the PCA data from FTIR results., (Copyright © 2022. Published by Elsevier B.V.) more...