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Introduction: immunity, diagnosis, vector, and beneficial uses of neurotropic viruses
W. Robert Finberg, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA,
Shenghua Zhou, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA,
Evelyn A. Kurt-Jones, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Toll-like receptors (TLRs) are pattern recognition proteins found both on cell surfaces as well as within intracellular compartments. Originally defined on the basis of their homology to the Drosophila protein Toll, which is important in the fruit fly defense against fungal infections , mammalian TLRs were first demonstrated to be critical in determining whether animals develop shock after challenge with bacterial lipopolysaccharide (LPS). The interaction between E.coli LPS and TLR4 leads to a series of events resulting in the production of cytokines and inflammatory mediators that affect vascular permeability and that ultimately cause a decrease in blood pressure and death of the animal. Subsequent studies have revealed a role for TLRs in the immune responses not only to bacteria but also to fungi, parasites, and viruses.
TLRs are a family of proteins with a structure including an N-terminal pattern recognition domain composed of leucine-rich repeats which form a molecular scaffold and a cytosolic C-terminal Toll-interleukin-1 receptor (TIR) domain that interacts with a series of adapter proteins. Engagement of TLR adapters ultimately leads to intracellular signaling events that induce the production of chemokines and cytokines (Figure 15.1). The human genome encodes 10 different TLR proteins, all of which are homologous to the interleukin-1 receptor (IL-1R) protein in their TIR domain. While TLRs are pattern recognition proteins (recognizing viruses and bacteria predominantly through their leucine-rich repeat regions), they initiate the production of cytokines and chemokines that directly (through activation of other cells) or indirectly (through stimulating migration of immune cells) result in the initial host response to infection.
To compare a surveillance definition of nosocomial bloodstream infections requiring only microbiology data to the Centers for Disease Control and Prevention's (CDC) current definition.
Six teaching hospitals.
We classified a representative sample of 73 positive blood cultures from six hospitals growing common skin contaminant isolates using a definition for bacteremia requiring only microbiology data and the CDC definition for primary bloodstream infection (National Nosocomial Infections Surveillance [NNIS] System review method). The classifications assigned during routine prospective surveillance also were noted, and the time required to classify isolates by the two methods was compared.
Among 65 blood cultures growing common skin contaminant isolates obtained from adults, the agreement rate between the microbiology data method and the NNIS review method was 91%. Agreement was significantly poorer for the eight blood cultures growing common skin contaminant isolates obtained from pediatric patients. The microbiology data method requires approximately 20 minutes less time per isolate than does routine surveillance.
A definition based on microbiology data alone yields the same result as the CDC's definition in the large majority of instances. It is more resource-efficient than the CDC's current definition
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