Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients

Background. We report the temporal-spatial spread of severe acute respiratory syndrome (SARS) among inpatients in a hospital ward during a major nosocomial outbreak and discuss possible mechanisms for the outbreak. Methods. All inpatients who had stayed in the same ward as the initial index case patient for any duration before isolation were recruited into a cohort and followed up to document the occurrence of SARS. The normalized concentration of virus-laden aerosols at different locations of the ward was estimated by use of computational fluid dynamics modeling. The attack rates in the various subgroups stratified by bed location were calculated. Multivariate Cox proportional hazards regression was used to document important risk factors. Results. The overall attack rate of SARS was 41% (30 of 74 subjects). It was 65%, 52%, and 18% in the same bay, adjacent bay, and distant bays, respectively (P = .001). Computation fluid dynamics modeling indicated that the normalized concentration of virus-laden aerosols was highest in the same bay and lowest in the distant bays. Cox regression indicated that staying in the ward on 6 or 10 March entailed higher risk, as well as staying in the same or adjacent bays. The epidemic curve showed 2 peaks, and stratified analyses by bed location suggested >1 generation of spread. Conclusions. The temporal-spatial spread of SARS in the ward was consistent with airborne transmission, as modeled by use of computational fluid dynamics. Infected health care workers likely acted as secondary sources in the latter phase of the outbreak. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

AMPK in Pathogens

During host–pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host–pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.CIHR -Canadian Institutes of Health Researc

Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37

The extensive world-wide morbidity and mortality caused by influenza A viruses highlights the need for new insights into the host immune response and novel treatment approaches. Cationic Host Defense Peptides (CHDP, also known as antimicrobial peptides), which include cathelicidins and defensins, are key components of the innate immune system that are upregulated during infection and inflammation. Cathelicidins have immunomodulatory and anti-viral effects, but their impact on influenza virus infection has not been previously assessed. We therefore evaluated the effect of cathelicidin peptides on disease caused by influenza A virus in mice. The human cathelicidin, LL-37, and the murine cathelicidin, mCRAMP, demonstrated significant anti-viral activity in vivo, reducing disease severity and viral replication in infected mice to a similar extent as the well-characterized influenza virus-specific antiviral drug zanamivir. In vitro and in vivo experiments suggested that the peptides may act directly on the influenza virion rather than via receptor-based mechanisms. Influenza virus-infected mice treated with LL-37 had lower concentrations of pro-inflammatory cytokines in the lung than did infected animals that had not been treated with cathelicidin peptides. These data suggest that treatment of influenza-infected individuals with cathelicidin-derived therapeutics, or modulation of endogenous cathelicidin production may provide significant protection against disease