Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness

Abstract

Background A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. Methods The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n¼283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician's discretion. 27 inflammatory mediators were measured in a subset of the patients (n¼64) using a multiplex immunoassay. Results 39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n¼13), influenza virus (n¼8), respiratory syncytial virus (n¼6), human metapneumovirus (n¼3), coronavirus NL63 (n¼2), parainfluenza virus (n¼2), adenovirus (n¼1) and newly discovered viruses (n¼4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon g-inducible

Human parainfluenza virus serotypes differ in their kinetics of replication and cytokine secretion in human tracheobronchial airway epithelium

“…In addition to attracting Th1 cells, these CXCR3 ligands also antagonize CCR3-mediated Th2 cell migration, further enhancing Th1 polarization of effector T cell recruitment (Loetscher et al, 2001; Sallusto et al, 1998; Xanthou et al, 2003). With regards to respiratory illness, IP-10 has been suggested as a biomarker for viral (as opposed to non-viral) ARI, and our data indicate that all three PIV serotypes are potent inducers of IP-10 (Bafadhel et al, 2011; Sumino et al, 2010). CXC chemokine concentrations were much higher than those of the CC chemokines, with basolateral IP-10 and I-TAC concentrations above 100 and 50 ng/mL, respectively.…”

Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study

“…Interferon (IFN)-γ-induced protein 10 (IP-10/CXCL10) appears to contribute to the pathogenesis of several diseases and has been suggested as a potential biomarker of viral infection1011, late-onset bacterial infection in premature infants12, and a promising biomarker of sepsis and septic shock1314. Combined analysis of IP-10 and IFN-γ has also been reported as a useful biomarker for diagnosis and monitoring therapeutic efficacy in patients with active tuberculosis151617, and both remain detectable in the urine of patients with pulmonary diseases in the absence of renal dysfunction18.…”

Trivalent influenza vaccine and febrile adverse events in Australia, 2010: Clinical features and potential mechanisms

“…These findings compelled us to explore whether rapid, cytokine driven, febrile reactions to IP-10 has been implicated in immune response to several viruses, including influenza A 14 , and was recently shown to be a useful biomarker of respiratory infection itself. 17 The chemokine also serves as a useful biomarker of human IFN-β responses and strongly correlates with febrile responses in multiple sclerosis patients treated with recombinant IFN-β. 18 Elevated pyrogenic cytokine responses have been previously associated with febrile seizure events.…”