Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study

Please cite this paper as: Barry et al. (2011) Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study. Influenza and Other Respiratory Viruses 5(5), 317–320. Aims To describe the public use of respiratory hygiene behaviours during the 2009 influenza pandemic and to test the feasibility of an observational method. Methods Respiratory behaviour was systematically observed at three public settings during August 2009 in the capital city of New Zealand (Wellington). Data on each coughing or sneezing event were collected. Results A total of 384 respiratory events were observed, at a rate of 0·8 cough/sneeze per observed‐person‐hour. Around a quarter of respiratory events (27·3%) were uncovered, and there was infrequent use of the responses recommended by health authorities (i.e., covering with a tissue or handkerchief at 3·4% and covering with elbow or arm at 1·3%). Respiratory event rates were higher in all settings that were ‘high flow’ (for people movement) compared to ‘low flow’ settings. Uncovered events were more common among people at the hospital entrance versus the hospital café [risk ratio (RR) = 7·8, 95% confidence interval (CI): 1·1–52·6] and when a person was located within 1 m of others (RR = 1·5, 95% CI: 1·1–1·9). Observing respiratory hygiene was found to be feasible in all of the selected public locations. There was good agreement between observing pairs about whether or not respiratory events occurred (inter‐observer correlation = 0·81) and for uncovered versus covered events (total Cohen’s kappa score = 0·70). Conclusions It was feasible to document respiratory hygiene behaviour in public urban settings during a influenza pandemic. Respiratory hygiene advice was not being adequately followed by this population towards the end of the first wave of the pandemic.     

Effective inhibitors of the essential kinase PknB and their potential as anti-mycobacterial agents

PknB is an essential serine/threonine kinase of Mycobacterium tuberculosis with possible roles in a number of signalling pathways involved in cell division and metabolism. We screened a library of >50,000 compounds for inhibitors of the in vitro phosphorylation of GarA (Rv1827) by PknB and identified a number of inhibitors. A program of synthetic medicinal chemistry was subsequently conducted around one class of inhibitors and was successful in generating ATP competitive inhibitors with potency in the nanomolar range. Compounds in this class showed cross-reactivity with the related M. tuberculosis kinase, PknF, but not with PknG in an in vitro autophosphorylation assay. These synthesised inhibitors were able to prevent the growth of M.?tuberculosis in an Alamar blue assay and in an intracellular model of infection, but only in the micromolar range. We attempted to determine if cell wall permeability was an explanation for the discrepancy between the potent in vitro compared with relatively poor in vivo activity, but found no evidence that the activity of the inhibitors could be improved by weakening the?cell wall. Despite a number of drug discovery efforts attempting to develop inhibitors against PknB, it?is yet to be reported that any such inhibitors prevent mycobacterial growth at submicromolar concentrations.     

BK Virus Nephropathy: Histological Evolution by Sequential Pathology

Reactivation of BK virus in renal allografts causes a destructive chronic infection. This single‐center retrospective cohort study describes the evolution of BK virus allograft nephropathy (BKVAN) from 63 kidneys (from 61 patients) using sequential histopathology (454 biopsies, averaging 7.8 ± 2.6 per kidney) followed for 60.1 mo. Uninfected protocol biopsies formulated time‐matched control Banff scores (n = 975). Interstitial inflammation occurred in 73% at diagnosis, correlating with viral histopathology (r = 0.413, p = 0.008) and amplifying early injury with accelerated interstitial fibrosis and tubular atrophy (IF/TA, p = 0.017) by 3 mo. Prodromal simian virus 40 large T antigen (SV40T)–negative inflammation with viremia preceded the histological diagnosis in 23.8%. Persistent subacute injury from viral cytopathic effect was associated with acute tubular necrosis and ongoing interstitial inflammation, culminating in IF/TA in 86.9%. Overall, cellular interstitial infiltration mitigated the intensity of subsequent tubular injury, SV40T, and tissue viral load, assessed by sequential paired histology (p < 0.001). Graft loss was predicted by high‐level viremia (hazard ratio [HR] 4.996, 95% CI 2.19–11.396, p < 0.001), deceased donor (HR 3.201, 95% CI 1.149–8.915, p = 0.026), and late acute rejection (HR 3.124, 95% CI 1.037–9.413, p = 0.043). Transplant failure occurred in 38.1%, with uncontrolled infection (58.3%) and SV40T‐negative chronic rejection (41.7%) causing losses. BKVAN is characterized by subacute virus‐induced tubular injury, inflammation, and progressive nephron destruction. Effective antiviral therapy remains an unmet clinical need.