Lung Infection—A Public Health Priority

Harvard School of Public Health, Boston, Massachusetts, USA.
PLoS Medicine (Impact Factor: 14.43). 03/2006; 3(2):e76. DOI: 10.1371/journal.pmed.0030076
Source: PubMed


The pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities, argues Mizgerd.

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    • "Infectious pneumonias are a leading cause of worldwide morbidity and mortality, with a greater annual burden of disease than HIV, malaria, and tuberculosis (Mizgerd, 2006). The bacterium Yersinia pestis is an infamous example of an easily transmitted pathogen that causes respiratory infections. "
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    ABSTRACT: Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis. The bacterial protease Pla contributes to disease progression and manipulation of host immunity, but the mechanisms by which this occurs are largely unknown. Here we show that Pla degrades the apoptotic signaling molecule Fas ligand (FasL) to prevent host cell apoptosis and inflammation. Wild-type Y. pestis, but not a Pla mutant (Δpla), degrades FasL, which results in decreased downstream caspase-3/7 activation and reduced apoptosis. Similarly, lungs of mice challenged with wild-type Y. pestis show reduced levels of FasL and activated caspase-3/7 compared to Δpla infection. Consistent with a role for FasL in regulating immune responses, Δpla infection results in aberrant proinflammatory cytokine levels. The loss of FasL or inhibition of caspase activity alters host inflammatory responses and enables enhanced Y. pestis outgrowth in the lungs. Thus, by degrading FasL, Y. pestis manipulates host cell death pathways to facilitate infection.
    Cell host & microbe 04/2014; 15(4):424-34. DOI:10.1016/j.chom.2014.03.005 · 12.33 Impact Factor
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    • "The World Health Organization (WHO) estimates that lower respiratory tract infections account for nearly 35% of all deaths from infectious diseases, causing an annual mortality of nearly 4 million adults and children. Thus, bacterial pneumonia is a significant cause of mortality worldwide 1. "
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    ABSTRACT: Objective: In the acute stage of infectious diseases such as pneumonia and sepsis, sequelae hypercytokinemia and cytokine storm are often observed simultaneously. During bacterial infections, activated polymorphonuclear leukocytes (PMNs) cause inflammation and organ dysfunction in severely ill patients. Gene expression of the triggering receptor on myeloid cells (TREM)-1 and G-coupled-protein receptor kinase (GRK)-2 in PMNs isolated from patients was analysed to identify genes correlated with the severity of pathophysiological conditions. Methods: mRNA levels of TREM1 and GRK2 in the PMNs from 26 patients (13 with pneumonia, 5 with severe sepsis, and 8 with septic shock) were analysed by using quantitative real-time PCR. The synthesised soluble form (s)TREM-1 was incubated with normal PMNs to investigate its biological functions in vitro. Results: Copies of TREM1 transcript were 0.7- to 2.1-fold higher in patients with pneumonia compared to those of normal subjects; the average fold-change was 1.1-fold. The mRNA levels of patients suffering from severe sepsis and septic shock were 0.34- and 0.33-fold lower compared to those of healthy subjects, respectively. TREM1 mRNA levels in 5 of 26 patients in convalescent stages recovered to normal levels. The mRNA levels of GRK2 in the PMNs of patients were also downregulated. The synthesised sTREM-1 upregulated the mRNA levels of TREM1 in normal PMNs. Conclusions: TREM1 mRNA levels were inversely correlated with the severity of pathophysiological conditions in acute bacterial infections. The gene expression levels of TREM1 in PMNs isolated from patients with bacterial infections may be used as a surrogate biomarker for determining the severity.
    International journal of medical sciences 01/2014; 11(2):215-21. DOI:10.7150/ijms.7231 · 2.00 Impact Factor
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    • "Acute respiratory tract infection (ARTI) is a persistent and pervasive public health issue and a great burden to both families and the wider society. Acute low respiratory tract infection is a particular problem, being the principal cause of morbidity and mortality in young people worldwide [1] [2] [3]. The most common viral causes of ARTI worldwide include respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), influenza viruses (IFVs), enteroviruses (EVs), adenoviruses (ADVs), human rhinoviruses (HRVs), human metapneumovirus (hMPV), and human coronaviruses (HCoVs) 229E, OC43, NL63, and HKU1. "
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    ABSTRACT: The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.
    Clinical and Developmental Immunology 12/2013; 2013(5):210490. DOI:10.1155/2013/210490 · 2.93 Impact Factor
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