RESUMO
BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.
Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Meningite , Humanos , HIV , Estudos Retrospectivos , Nova Zelândia/epidemiologia , Austrália/epidemiologia , Criptococose/diagnóstico , Criptococose/epidemiologia , Hospitais , Antígenos de Fungos , Infecções por HIV/complicações , Infecções por HIV/epidemiologiaAssuntos
Infecções por Adenoviridae/diagnóstico , Adenoviridae/isolamento & purificação , Pulmão/patologia , Infecções Oportunistas/diagnóstico , Insuficiência Respiratória/etiologia , Infecções por Adenoviridae/tratamento farmacológico , Adulto , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Cidofovir , Citosina/efeitos adversos , Citosina/análogos & derivados , Citosina/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Pulmão/diagnóstico por imagem , Nasofaringe/virologia , Infecções Oportunistas/tratamento farmacológico , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Radiografia Torácica , Insuficiência Renal/induzido quimicamente , Transplante de Células-Tronco/efeitos adversos , Tomografia Computadorizada por Raios X , Carga ViralAssuntos
Dor Abdominal/etiologia , Anisaquíase/diagnóstico , Gastropatias/diagnóstico , Idoso , Animais , Anisaquíase/patologia , Anisaquíase/transmissão , Diagnóstico Diferencial , Feminino , Peixes/parasitologia , Parasitologia de Alimentos , Mucosa Gástrica/parasitologia , Mucosa Gástrica/patologia , Gastroscopia , Humanos , Gastropatias/patologiaRESUMO
Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important "indirect effects" are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical "indirect effects" in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.