RESUMO
Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.
Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Animais , Antifúngicos/uso terapêutico , Argentina/epidemiologia , Fluconazol , Itraconazol , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/veterináriaRESUMO
Fungal infections have increased in the last years, particularly associated to an increment in the number of immunocompromised individuals and the emergence of known or new resistant species, despite the difficulties in the often time-consuming diagnosis. The controversial efficacy of the currently available strategies for their clinical management, apart from their high toxicity and severe side effects, has renewed the interest in the research and development of new broad antifungal alternatives. These encompass vaccines and passive immunization strategies with monoclonal antibodies (mAbs), recognizing ubiquitous fungal targets, such as fungal cell wall ß-1,3-glucan polysaccharides, which could be used in early therapeutic intervention without the need for the diagnosis at species level. As additional alternatives, based on the Dectin-1 great affinity to ß-1,3-glucan, our group developed broad antibody-like Dectin1-Fc(IgG)(s) from distinct subclasses (IgG2a and IgG2b) and compared their antifungal in vitro and passive immunizations in vivo performances. Dectin1-Fc(IgG2a) and Dectin1-Fc(IgG2b) demonstrated high affinity to laminarin and the fungal cell wall by ELISA, flow cytometry, and microscopy. Both Dectin-1-Fc(IgG)(s) inhibited Histoplasma capsulatum and Cryptococcus neoformans growth in a dose-dependent fashion. For Candida albicans, such inhibitory effect was observed with concentrations as low as 0.098 and 0.049 µg/ml, respectively, which correlated with the impairment of the kinetics and lengths of germ tubes in comparison to controls. Previous opsonization with Dectin-1-Fc(IgG)(s) enhanced considerably the macrophage antifungal effector functions, increasing the fungi macrophages interactions and significantly reducing the intraphagosome fungal survival, as lower CFUs were observed. The administration of both Dectin1-Fc(IgG)(s) reduced the fungal burden and mortality in murine histoplasmosis and candidiasis models, in accordance with previous evaluations in aspergillosis model. These results altogether strongly suggested that therapeutic interventions with Dectin-1-Fc(IgG)(s) fusion proteins could directly impact the innate immunity and disease outcome in favor of the host, by direct neutralization, opsonization, phagocytosis, and fungal elimination, providing interesting information on the potential of these new strategies for the control of invasive fungal infections. LAY SUMMARY: Mycoses have increased worldwide, and new efficient therapeutics are needed. Passive immunizations targeting universally the fungal cell would allow early interventions without the species-level diagnosis. Lectins with affinity to carbohydrates could be used to engineer 'antibody-like' strategies.
Assuntos
Infecções Fúngicas Invasivas , Micoses , Animais , Antifúngicos/farmacologia , Modelos Animais de Doenças , Imunoglobulina G , Infecções Fúngicas Invasivas/veterinária , Lectinas Tipo C/metabolismo , CamundongosRESUMO
Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.
Assuntos
Neoplasias Hematológicas , Infecções Fúngicas Invasivas , Infecções Respiratórias , Animais , Antifúngicos/uso terapêutico , Geotrichum , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/veterinária , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/veterinária , Masculino , México/epidemiologia , Encaminhamento e Consulta , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/veterináriaRESUMO
A criptococose é a micose profunda mais comum em gatos, mas raramente diagnosticada na clínica médica de pequenos animais. O agente infeccioso da doença é o Cryptococcus sp., um fungo oportunista que pode disseminar-se por todo o organismo. Uma gata com aproximadamente dois anos de idade, 3 kg e sem raça definida foi atendida em uma clínica particular na cidade de São Paulo. O exame físico revelou lesões cutâneas piogranulomatosas invasivas, principalmente em plano nasal e no segundo dígito do membro torácico esquerdo. O animal não apresentava sinais neurológicos ou respiratórios. A resposta ao antifúngico nas lesões cutâneas foi favorável, porém o animal não resistiu a uma segunda sedação e veio a óbito vinte e oito dias após início do tratamento. Este relato apresenta um caso atípico de criptococose, devido à inexistência de imunodeficiência.(AU)
Cryptococcosis is the most common deep mycosis in cats, despite its rarity in the medical practice of small animals. The infectious agent of the disease is Cryptococcus sp, an opportunistic fungus that can spread throughout the body. An approximately two-year-old mixed breed cat, weighing 3 kg was presented to a private practice in the city of São Paulo, Brazil. Physical examination revealed pyogranulomatous skin lesions, mainly on the nasal planum and the second digit of the left thoracic limb. The animal presented no neurological or respiratory signs.The response to antifungal on cutaneous lesions was favorable, but the animal did not resist a second sedation and died within twenty-eight days after starting treatment. This report shows an atypical case of cryptococcosis due to the lack of immunodeficiency.(AU)
La criptococosis es la micosis profunda más común en los gatos, aunque es muy raro su diagnóstico en la clínica de pequeños animales. El agente infeccioso de esta enfermedad es el Cryptococcus sp., un hongo oportunista que se puede diseminar por todo el organismo. Una gata mestiza de aproximadamente dos años de edad y 3 kg de peso fue atendida en una clínica particular de la ciudad de São Paulo (Brasil). Durante el examen físico se comprobó la presencia de lesiones cutáneas piogranulomatosas invasivas, principalmente en la región nasal, y también en la segunda falange del miembro anterior izquierdo. El animal no presentaba signos neurológicos o respiratorios. A pesar de que la respuesta al antifúngico en las lesiones cutáneas fue favorable, el paciente no resistió a un segunda sedación y murió 28 días después de iniciado el tratamiento. El presente relato muestra un caso atípico de criptococosis en el que no existía un cuadro previo de inmunodeficiencia.(AU)
Assuntos
Animais , Feminino , Gatos , Criptococose/veterinária , Dermatomicoses/veterinária , Cryptococcus neoformans , Infecções Fúngicas Invasivas/veterinária , FungosRESUMO
A criptococose é a micose profunda mais comum em gatos, mas raramente diagnosticada na clínica médica de pequenos animais. O agente infeccioso da doença é o Cryptococcus sp., um fungo oportunista que pode disseminar-se por todo o organismo. Uma gata com aproximadamente dois anos de idade, 3 kg e sem raça definida foi atendida em uma clínica particular na cidade de São Paulo. O exame físico revelou lesões cutâneas piogranulomatosas invasivas, principalmente em plano nasal e no segundo dígito do membro torácico esquerdo. O animal não apresentava sinais neurológicos ou respiratórios. A resposta ao antifúngico nas lesões cutâneas foi favorável, porém o animal não resistiu a uma segunda sedação e veio a óbito vinte e oito dias após início do tratamento. Este relato apresenta um caso atípico de criptococose, devido à inexistência de imunodeficiência.
Cryptococcosis is the most common deep mycosis in cats, despite its rarity in the medical practice of small animals. The infectious agent of the disease is Cryptococcus sp, an opportunistic fungus that can spread throughout the body. An approximately two-year-old mixed breed cat, weighing 3 kg was presented to a private practice in the city of São Paulo, Brazil. Physical examination revealed pyogranulomatous skin lesions, mainly on the nasal planum and the second digit of the left thoracic limb. The animal presented no neurological or respiratory signs.The response to antifungal on cutaneous lesions was favorable, but the animal did not resist a second sedation and died within twenty-eight days after starting treatment. This report shows an atypical case of cryptococcosis due to the lack of immunodeficiency.
La criptococosis es la micosis profunda más común en los gatos, aunque es muy raro su diagnóstico en la clínica de pequeños animales. El agente infeccioso de esta enfermedad es el Cryptococcus sp., un hongo oportunista que se puede diseminar por todo el organismo. Una gata mestiza de aproximadamente dos años de edad y 3 kg de peso fue atendida en una clínica particular de la ciudad de São Paulo (Brasil). Durante el examen físico se comprobó la presencia de lesiones cutáneas piogranulomatosas invasivas, principalmente en la región nasal, y también en la segunda falange del miembro anterior izquierdo. El animal no presentaba signos neurológicos o respiratorios. A pesar de que la respuesta al antifúngico en las lesiones cutáneas fue favorable, el paciente no resistió a un segunda sedación y murió 28 días después de iniciado el tratamiento. El presente relato muestra un caso atípico de criptococosis en el que no existía un cuadro previo de inmunodeficiencia.