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Background Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza-like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere. Objectives To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009. Methods Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Sequencing data of 5′UTR and VP4/VP2 coding regions on RT-PCR-positive specimens were analysed. Results Human rhinoviruses were detected by real-time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5′UTR and VP4/VP2 on HRV-positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5′UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032). Conclusion Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships.

Please cite this paper as: Khandaker et al. (2012) Comparing the use of, and considering the need for, lumbar puncture in children with influenza or other respiratory virus infections. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12039. Background The clinical presentation of influenza in infancy may be similar to serious bacterial infection and be investigated with invasive procedures like lumbar puncture (LP), despite very limited evidence that influenza occurs concomitantly with bacterial meningitis, perhaps because the diagnosis of influenza is very often not established when the decision to perform LP is being considered. Methods A retrospective medical record review was undertaken in all children presenting to the Children’s Hospital at Westmead, Sydney, Australia, in one winter season with laboratory-confirmed influenza or other respiratory virus infections (ORVIs) but excluding respiratory syncytial virus, to compare the use of, and reflect on the need for, the performance of invasive diagnostic procedures, principally LP, but also blood culture, in influenza and non-influenza cases. We also determined the rate of concomitant bacterial meningitis or bacteraemia. Findings Of 294 children, 51% had laboratory-confirmed influenza and 49% had ORVIs such as parainfluenza viruses (34%) and adenoviruses (15%). Of those with influenza, 18% had a LP and 71% had a blood culture performed compared with 6·3% and 55·5% in the ORVI group (for both P

Please cite this paper as: Blyth et al. (2013) The impact of bacterial and viral co-infection in severe influenza. Influenza and Other Respiratory Viruses 7(2) 168–176. Background Many questions remain concerning the burden, risk factors and impact of bacterial and viral co-infection in patients with pandemic influenza admitted to the intensive care unit (ICU). Objectives To examine the burden, risk factors and impact of bacterial and viral co-infection in Australian patients with severe influenza. Patients/Methods A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. Results Co-infection was identified in 23·3–26·9% of patients with severe influenza A infection: viral co-infection, 3·2–3·4% and bacterial co-infection, 20·5–24·7%. Staphylococcus aureus was the most frequent bacterial co-infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co-infection were younger [mean difference in age = 8·46 years (95% CI: 0·18–16·74 years)], less likely to have significant co-morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77–11·96)] compared to those without co-infection. Conclusions Bacterial or viral co-infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co-infected patients being younger and with fewer co-morbidities, no significant difference in outcomes was observed. It is likely that co-infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease. Empiric antibiotics with staphylococcal activity should be strongly considered in all patients with severe influenza A infection.

Please cite this paper as: MacIntyre et al. (2011) A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2010.00198.x. Background We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). Methods A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza-like illness (ILI), laboratory-confirmed respiratory virus infection and influenza. A convenience no-mask/respirator group of 481 health workers from nine hospitals was compared. Findings The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory-confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention-to-treat analysis, when P values were adjusted for clustering, non-fit-tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no-mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high-risk procedures were not. Interpretation Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 (http://www.anzctr.org.au).

Background Rapid influenza diagnostic tests (RIDTs) have an important role in clinical decision-making; however, the performances of currently available assays vary widely. Objectives We evaluated the performance of the Alere™ i Influenza A&B (Alere™ iNAT), a rapid isothermal nucleic acid amplification assay that has recently received FDA clearance, for the detection of influenza A and B viruses during the Australian influenza season of 2013. Results were compared to two other RIDTs tested in parallel; Quidel Sofia® Influenza A+B fluorescent immunoassay (FIA) and Alere™ BinaxNOW® Influenza A & B immunochromatographic (ICT) assay. Methods A total of 202 paired nasopharyngeal swabs collected from patients ≥16 years old with an influenza-like illness (ILI) were eluted in 2 ml of universal transport medium (UTM) that was used to perform all three RIDTs in parallel. Reverse-transcription polymerase chain reaction (RT-PCR) was used as the reference standard. Results Compared to RT-PCR, Alere™ iNAT detected 77·8% influenza A positive samples versus 71·4% and 44·4% for the Quidel Sofia® Influenza A+B FIA and BinaxNOW® Influenza A & B ICT assay, respectively. For influenza B, Alere™ iNAT detected 75% of those positive by RT-PCR, versus 33·3% and 25·0% for Sofia® and BinaxNOW®, respectively. The specificity of Alere™ iNAT was 100% for influenza A and 99% for influenza B. Conclusions Alere™ i Influenza A&B is a promising new rapid influenza diagnostic assay with potential point-of-care applications.

Please cite this paper as: Blyth et al. (2013) The impact of bacterial and viral co‐infection in severe influenza. Influenza and Other Respiratory Viruses 7(2) 168–176. Background Many questions remain concerning the burden, risk factors and impact of bacterial and viral co‐infection in patients with pandemic influenza admitted to the intensive care unit (ICU). Objectives To examine the burden, risk factors and impact of bacterial and viral co‐infection in Australian patients with severe influenza. Patients/Methods A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. Results Co‐infection was identified in 23·3–26·9% of patients with severe influenza A infection: viral co‐infection, 3·2–3·4% and bacterial co‐infection, 20·5–24·7%. Staphylococcus aureus was the most frequent bacterial co‐infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co‐infection were younger [mean difference in age = 8·46 years (95% CI: 0·18–16·74 years)], less likely to have significant co‐morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77–11·96)] compared to those without co‐infection. Conclusions Bacterial or viral co‐infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co‐infected patients being younger and with fewer co‐morbidities, no significant difference in outcomes was observed. It is likely that co‐infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease. Empiric antibiotics with staphylococcal activity should be strongly considered in all patients with severe influenza A infection.

Background Residents of nursing homes and long-term care facilities are at a higher risk of outbreaks of influenza and of serious complications of influenza than those in the community. In late July 2005, a 90-bed chronic care psycho-geriatric hospital in Sydney, Australia, reported cases of influenza-like illness (ILI) occurring amongst its residents. Methods An investigation to confirm the outbreak, and its cause, was undertaken. Influenza vaccination levels amongst residents, and the effects of antiviral drugs used for prevention and treatment, were assessed. Oseltamivir was only given to the residents, in the form of both treatment and prophylaxis. Results A total of 22 out of 89 residents met the clinical case definition of ILI with onset on or after 27 July 2005. This represents an attack rate of 25%. Oseltamivir was commenced on day 9 of the outbreak. Influenza B was identified in six residents as the causative agent of the outbreak. No deaths or acute hospitalization were recorded for this outbreak and there were no further reported cases after the introduction of oseltamivir. Vaccine effectiveness was 75% and the strain of influenza B isolated was well matched to that year’s vaccine. Conclusions There are few data on the use of oseltamivir in influenza B outbreaks. Early antiviral intervention appeared to curtail this outbreak of influenza B in a chronic care facility. We found high vaccine effectiveness in this frail, institutionalized population, highlighting the importance of influenza vaccination for residents of chronic care facilities.

To the editor: On 11 June 2009, the World Health Organisation (WHO) raised the influenza pandemic alert to Level 6 (defined as ‘sustained community level outbreaks in at least one other country in another WHO region’) because of the emergence of a novel influenza A/H1N1 subtype. 1 Australia’s first laboratory confirmed case of pandemic (H1N1) 2009 virus, a NSW woman who had visited Los Angeles, was reported in the second week of May 2009. Within a month, 1336 laboratory confirmed cases had been identified, the majority of them in Victoria, rising to nearly 20 000 Australia‐wide by the end of July. Given the lack of a specific vaccine against the pandemic (H1N1) 2009 virus, mitigation measures in Australia have so far focused on identifying, treating, and isolating people who have the disease, and educating the public about the steps that individuals can take to reduce transmission. Antiviral medications have been deployed as both treatment and prophylaxis. Clinical trials of the pandemic (H1N1) 2009 vaccine are currently underway; however, it is unclear when and to whom the vaccine will be made available. Healthcare workers (HCWs) and those on the ‘front line’ will be the first to be vaccinated; there will be a lag time for members of the general public. Non‐pharmacological public health interventions including use of face masks are therefore likely to play a vital role in mitigating disease spread, particularly in developing countries. Medical masks are unfitted devices worn by an infected person, HCW or member of the public to reduce transfer of potentially infectious respiratory tract material between individuals. They are designed to be disposable. Surgical masks are specifically designed to protect patients from contamination of wounds during surgical procedures. In contrast, a respirator is a fitted device that protects the wearer against inhalation of harmful contaminated material. Respirators can be disposable or reusable and are recommended for use in high‐risk activities (e.g. aerosol‐generating procedures) in healthcare settings. The National Institute for Occupational Safety and Health (NIOSH) regulates the testing and certification of respiratory protection equipment. 2 The NIOSH tests filters for the effects of loading (particle burden), temperature, and relative humidity and requires a minimum filtration efficiency of 95%, 99% or 99·97% using neutralized 0·075‐mm count median diameter solid aerosols at 85 l/min. Filters can be certified for a range of efficiency classes (e.g. 95%, 99% or 100%) as well as for their ability to withstand degradation as a result of loading or oil mist exposures. N95 filters are not permitted to have more than 5% of the challenge aerosol concentration penetrate the filter, and would be expected to have less aerosol penetration with either larger or smaller particles than the size used in certification testing. In 1973, a letter to the editor of the New England Journal of Medicine from Jack Resnick, MD, 3 suggested ‘…perhaps the ancient oriental custom of wearing gauze or cloth, surgical‐type masks during a cold has some merit? Perhaps Western society has another lesson to learn by observing the oriental customs besides acupuncture.’ He proposed that this matter be studied in a rigorous manner. Since then, there have been many studies on the filtration efficiency under controlled laboratory settings, but until recently there has been limited study as to whether masks or respirators will provide clinically relevant protection in healthcare settings. Most data have been derived from at best observational settings and frequently has been based on anecdotal rather than controlled trials evidence. 4 , 5 , 6 Jefferson summarized these data in his systematic review of the literature in 2007; 7 two papers were included which focused specifically on N95 masks. 8 , 9 Although the authors concluded from the pooled estimate of effect that the intervention effectiveness was 91%, this evidence was thin as the studies included showed inconsistencies and failed to adequately describe the use of controls. Jefferson and colleagues concluded that more experimental studies were needed to identify the effectiveness of wearing face masks or respirators in reducing exhaled infectious viral particles. 7 In 2009, we reported the first prospective cluster‐randomized trial comparing surgical masks, non‐fit‐tested P2 masks (N95 equivalent) and no masks in prevention of influenza‐like illness (ILI) in households. 10 Intention to treat analysis showed no significant difference in the relative risk of ILI in the mask groups compared with the control group. However, less than half of the subjects wore masks ‘most of the time’. Adherence to mask use significantly reduced the risk of ILI‐associated infection, with a hazard ratio of 0·26 (95% CI 0·09–0·77; P = 0·015). A recently reported randomized trial showed a significant benefit of both hand hygiene and face masks (worn by the index case and contacts) in preventing influenza transmission in households, although adherence to the face mask intervention was low among household contacts. 11 Surgical masks and N95 respirators have been recognized as an important non‐invasive technology to use during this new pandemic period. However, there are many factors which may compromise the overall effectiveness of these measures. Poor training, lack of guidance and consistency in the use of masks, improper use and for N95 respirators, the need for fit‐testing, may limit their usefulness. Data from the SARS experience in Toronto illustrated the need for training and monitoring; Loeb and colleagues (2004) found that nine of 32 (28%) nurses entering a SARS patient’s room did not consistently wear appropriate respiratory protection. 12 There is also the problem of workplace acceptance. In a logistics exercise undertaken during the peak of seasonal influenza activity in 2007 in Australia, compliance by emergency department staff, with N95 mask wearing was found to be low, with only 36·1% of participants wearing the mask ‘occasionally’ in week one and only 18·8% by week four. Many staff reported that they found the mask hot and hard to breathe through, and others reported that they had problems both communicating with patients and storing the mask between uses. 13 Much time and effort has been devoted to developing an optimal strategy for the use of pandemic vaccines and antivirals, in addition to non‐pharmaceutical measures. However, comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non‐pharmaceutical pandemic planning decisions. Despite the lack of high level evidence, recommendations on the use of face masks and respirators for HCWs are made by many health authorities. To ensure that HCWs wear face masks to protect themselves during this time, cultural attitudes and the physical discomfort and mechanical issues associated with long‐term respirator use must be addressed. Other factors that affect the use of personal protective equipment, such as staff and management attitudes about the value of respirator use, fatigue and the availability of replacement masks, also need to be considered.