RESUMO
Infrastructure, processes of care and outcome measurements are the cornerstone of quality care for pediatric trauma. This review aims to evaluate current evidence on system organization and concentration of pediatric expertise in the delivery of pediatric trauma care. It discusses key quality indicators for all phases of care, from pre-hospital to post-discharge recovery. In particular, it highlights the importance of measuring quality of life and psychosocial recovery for the injured child.
RESUMO
Most invasive bacterial infections are caused by species that more commonly colonize the human host with minimal symptoms. Although phenotypic or genetic correlates underlying a bacterium's shift to enhanced virulence have been studied, the in vivo selection pressures governing such shifts are poorly understood. The globally disseminated M1T1 clone of group A Streptococcus (GAS) is linked with the rare but life-threatening syndromes of necrotizing fasciitis and toxic shock syndrome. Mutations in the GAS control of virulence regulatory sensor kinase (covRS) operon are associated with severe invasive disease, abolishing expression of a broad-spectrum cysteine protease (SpeB) and allowing the recruitment and activation of host plasminogen on the bacterial surface. Here we describe how bacteriophage-encoded GAS DNase (Sda1), which facilitates the pathogen's escape from neutrophil extracellular traps, serves as a selective force for covRS mutation. The results provide a paradigm whereby natural selection exerted by the innate immune system generates hypervirulent bacterial variants with increased risk of systemic dissemination.
Assuntos
Desoxirribonuclease I/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/enzimologia , Streptococcus pyogenes/patogenicidade , Animais , Sobrevivência Celular , Desoxirribonuclease I/genética , Humanos , Imunidade Inata , Camundongos , Neutrófilos/citologia , Neutrófilos/microbiologia , Fenótipo , Seleção Genética , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/genética , VirulênciaRESUMO
The innate immune response plays a crucial role in satisfactory host resolution of bacterial infection. In response to chemotactic signals, neutrophils are early responding cells that migrate in large numbers to sites of infection. The recent discovery of secreted neutrophil extracellular traps (NETs) composed of DNA and histones opened a novel dimension in our understanding of the microbial killing capacity of these specialized leukocytes. M1 serotype strains of the pathogen Group A Streptococcus (GAS) are associated with invasive infections including necrotizing fasciitis (NF) and express a potent DNase (Sda1). Here we apply a molecular genetic approach of allelic replacement mutagenesis, single gene complementation, and heterologous expression to demonstrate that DNase Sda1 is both necessary and sufficient to promote GAS neutrophil resistance and virulence in a murine model of NF. Live fluorescent microscopic cell imaging and histopathological analysis are used to establish for the first time a direct linkage between NET degradation and bacterial pathogenicity. Inhibition of GAS DNase activity with G-actin enhanced neutrophil clearance of the pathogen in vitro and reduced virulence in vivo. The results demonstrate a significant role for NETs in neutrophil-mediated innate immunity, and at the same time identify a novel therapeutic target against invasive GAS infection.