Immunotherapy for Fungal Infections

Opportunistic fungal infections are a major health problem being appointed by some studies as the fourth main cause of hospital-acquired infection in susceptible populations. The constantly growing incidences of these diseases are associated with the growing number of susceptible individuals, such as immunocompromised individuals (leukemia, AIDS, etc) and treatment-induced immunodeficiency (hematopoietic stem cell, solid organ transplant, anticancer therapy). Furthermore, other advances in medical care, patient’s long-term hospitalization and antimicrobial therapies have created several vulnerable populations to fungal infections. Currently, antifungal drug therapies are several times inefficient, and the poor outcomes are linked to difficulties in the early diagnosis of fungal infections and drug resistance among fungal pathogens. In this context, novel therapeutic approaches are welcome to stimulate efficiently the host immune response to eliminate the fungal pathogen. This chapter is intended to review advances in immunotherapy strategies for fungal infections

Perfil epidemiológico e terapêutico de pacientes com criptococose atendidos em hospital escola de Santa Maria/RS

Cryptococcosis is a fungal disease caused by yeasts of the complex Cryptococcus neoformans and Cryptococcus gattii. The infection usually occurs by inhaling the basidiospores of the fungus present in the environment. Severe cases occur due to infection of the central nervous system. The disease has a worldwide distribution, mainly associated to the immunocompromised individuals with human immunodeficiency virus (HIV). This study aimed to verify the epidemiological profile and therapeutic protocols of patients diagnosed with cryptococcosis at the Hospital Universitário de Santa Maria (Santa Maria, RS), from March 2010 to March 2017. A total of 46 clinical records were evaluated, the profile of the patients was predominantly Caucasian, aged between 31 and 50 years, with HIV, presenting a CD4 + cell count <100 cells / μL and with a prevalent clinical form neurocryptococcosis. The combination of amphotericin B and fluconazole was the therapeutic protocol adopted in the majority of patients studied.Criptococose é uma doença fúngica causada por leveduras do complexo Cryptococcus neoformans e Cryptococcus gattii. A infecção geralmente ocorre através da inalação dos basidiósporos do fungo presente no ambiente. Casos graves ocorrem devido à infecção do sistema nervoso central. A enfermidade possui distribuição mundial, associada principalmente aos indivíduos imunocomprometidos, portadores do vírus da imunodeficiência humana (HIV). Este estudo objetivou verificar o perfil epidemiológico e os protocolos terapêuticos dos pacientes diagnosticados com criptococose no Hospital Universitário de Santa Maria (Santa Maria, RS), no período de março de 2010 a março de 2017. Avaliaram-se 46 prontuários clínicos, sendo que o perfil dos pacientes observados foi predominantemente do sexo masculino, etnia branca, faixa etária de 31 a 50 anos, portadores de HIV, apresentando taxa de células CD4+<100 células/µL e com forma clínica prevalente, a neurocriptococose. A associação de anfotericina B e fluconazol foi o protocolo terapêutico adotado na maioria dos pacientes estudados

Survival rates of uninfected immunocompetent (Control, <i>n</i> = 5), infected immunocompetent (PI, <i>n</i> = 5) and immunosuppressed mice with one dose of 200 mg/Kg cyclophosphamide plus one dose of 250 mg/Kg hydrocortisone acetate at 72 h and 24 h, respectively, before infection (PI+CYP+HCA, <i>n</i> = 20).

<p>Mice were infected by the subcutaneous route with 2 x 10⁴ <i>P</i>. <i>insidiosum</i> zoospores. The 14-day survival rate was 100% for Control and PI groups and 40.0% for the CYP+HCA group (<i>p</i> < 0.001; log-rank test). Control and PI groups are superimposed on the first line.</p

Histological lesions and immunohistochemistry of pythiosis in the kidneys, liver and lungs of BALB/c mice from the immunosuppressed (PI+CYP+HCA) group that was subcutaneously infected with <i>P</i>. <i>insidiosum</i>.

<p>A) Histological sections of kidney from a healthy control mouse (hematoxylin-eosin [HE, Bar = 20μm]). B) Kidney sections from the infected mouse with thrombosis (arrow) and tubular necrosis (arrowheads) (HE, Bar = 20μm). C) Positively stained hyphae are observed in the arterial small thrombus and vessel wall and surrounding the kidney (arrowheads) (immunohistochemistry [IHC] anti-<i>P</i>. <i>insidiosum</i>, peroxidase-polymer method, Bar = 20 μm). D) Histological sections of liver from a healthy control mouse (HE, Bar = 20 μm). E) Liver of the infected mouse with thrombus (arrow) containing negative profiles of hyphae (arrowheads) (HE, Bar = 20 μm). F) Positively stained hyphae are observed in the arterial thrombus and vessel wall and surrounding the liver (arrowheads) (IHC anti-<i>P</i>. <i>insidiosum</i>, Bar = 20 μm). G) Histological sections of the lung from a healthy control mouse (HE, Bar = 50 μm). H) Lung with severe congestion in septal capillaries and multifocal hemorrhage (arrowhead) in alveoli with mild edema (arrow) and fibrin (HE Bar = 20 μm). I) Lung with fibrinoid necrosis (arrow) and thrombosis (arrowhead) in one arteriole (HE, Bar = 20 μm).</p

Evolution of subcutaneous lesions of immunocompetent BALB/c mice experimentally infected by the subcutaneous route with 2 x 10⁴ <i>P</i>. <i>insidiosum</i> zoospores (PI group).

<p>A) ulcerative lesions eight days after infection (the lesion was humidified with sterile water for better visualization); B) the same mouse from Fig 1A with spontaneous resolution of the ulcerative lesion 10 days after infection.</p