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Introduction: In May 2020, The Communicable Diseases Network of Australia (CDNA) case definition introduced serological criteria to support the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We present findings that support the utility of SARS‐CoV‐2‐specific serology for public health investigations. Methods: From 24 January to 31 July 2020, the following information was collected from individuals with positive SARS‐CoV‐2‐specific immunofluorescence antibody tests: history of contact with COVID‐19 cases; recent travel; symptoms consistent with COVID‐19; and SARS‐CoV‐2 nucleic acid testing (NAT) results. Individuals were classified as confirmed or probable by CDNA criteria or additionally as possible (SARS‐CoV‐2‐specific IgG positive with compatible symptoms or epidemiologic risk) or indeterminate (SARS‐CoV‐2‐specific IgA/IgM positive only) cases. Results: A total of 10,595 individuals were tested in the six‐month period. Of these, 9.8% (1,037) individuals had positive SARS‐CoV‐2‐specific serology of which 566 (53.6%) were NAT‐confirmed COVID‐19 cases and 286 (27.6%) were part of a cruise ship outbreak sero‐survey. The remaining 185 individuals (NAT negative) were individually classified as serologically confirmed (4, 0.4%), probable (72, 6.9%) possible (66, 6.4%) and indeterminate (38, 3.7%) cases. Maternal antibody transfer was inferred in one infant and four were unclassified. Conclusion: SARS‐CoV‐2‐specific serology is a key diagnostic tool for retrospective identification of COVID‐19 infection. Implications for public health: SARS‐CoV‐2 specific serology can enhance the ability to find cases, link missing cases in clusters of infection and identify the epidemiological extent of SARS‐CoV‐2 outbreaks. A combination of epidemiological criteria, clinical criteria and a quantitative serological test can be used as an adjunct to classify SARS‐CoV‐2 cases. Our study confirms the low level of community transmission in NSW during the first year of the COVID‐19 pandemic

Direct acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment, but drug resistance could undermine proposed global elimination targets. Real-world studies are needed to inform the impact of widespread DAA treatment on antiviral resistance in the community. The prevalence and range of posttreatment resistance-associated substitutions (RASs) was determined in Australian patients with open access to DAAs through a wide range of prescribers. NS3, NS5A, and NS5B regions were amplified by polymerase chain reaction and analyzed by population sequencing. Clinically relevant RASs were identified using online databases (ReCALL and Geno2Pheno[hcv]). Of 572 samples, 60% were from genotype 3 and 27% from genotype 1a. Ninety-two percent of people failed a DAA regimen containing an NS5A inhibitor, including 10% with a pangenotype regimen. NS5A RASs were detected in 72% of people with genotype 1 and 80% with genotype 3. For genotype 1, there was a range of RASs across the NS5A region, while for genotype 3, the Y93H RAS predominated (72%). The prevalence of NS3 RASs was higher in people exposed to an NS3 inhibitor (35% vs. 3.9%; P < 0.0001). NS5B resistance was rare, with a single case of sofosbuvir resistance. Multiclass drug resistance was found in 33% of people exposed to both NS3 and NS5A inhibitors. Conclusion: The high prevalence of NS5A RASs among people failing DAA therapy reinforces the importance of specific retreatment regimens, ideally guided by resistance testing. The impact of multiclass drug resistance on retreatment in people exposed to both NS3 and NS5A inhibitors needs to be assessed in real-world studies. Surveillance for increasing antiviral resistance during treatment scale-up is essential to maintain the efficacy of current DAA regimens.

Background On 31 December 2019, the World Health Organization recognised clusters of pneumonia‐like cases due to a novel coronavirus disease (COVID‐19). COVID‐19 became a pandemic 71 days later. Aim To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID‐19 in Australia. Methods This is a retrospective, multi‐centre case series. All patients with confirmed COVID‐19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. Results The median age of our patient cohort was 42 years (IQR, 24–53 years) with six men and five women. Eight patients (72.7%) had returned from Wuhan, one from Shenzhen, one from Japan, and one from Europe. Possible human‐to‐human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co‐morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75–21), all patients were discharged. Conclusions This is a historical record of the first COVID‐19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID‐19 models of care and informing the management of COVID‐19 overtime as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection. This article is protected by copyright. All rights reserved.

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.

Rapid influenza diagnostic tests (RIDTs) can facilitate the appropriate prescription of antivirals for influenza, obviate the need for unnecessary testing and antibacterial agents and allow the implementation of infection control measures. However, the reported sensitivities and specificities of different RIDTs vary widely in clinical settings, as does assay ability to distinguish between influenza types and subtypes. To evaluate the performance of the Sofia Influenza A + B fluorescent immunoassay (FIA) for the detection of influenza A and B during the 2013 Southern Hemisphere influenza season, a total of 209 consecutive respiratory tract swabs from adult patients with an influenza-like illness were tested by both Sofia Influenza A + B and an in-house real-time, reverse transcription-polymerase chain reaction (RT-PCR) assay. Compared to RT-PCR, the sensitivity and specificity of the Sofia Influenza A + B FIA for detection of influenza A was 72.4% and 98.3%, respectively. Too few influenza B positive samples were available during the study to accurately assess the Sofia's performance for influenza B detection. The sensitivity of Sofia Influenza A + B FIA for both influenza A and B detection correlated with the amount of influenza RNA present in the sample as indicated indirectly by the RT-PCR cycle threshold (Ct). In conclusion, the Sofia Influenza A + B FIA continues to perform well as a RIDT with the circulating influenza strains of the 2013 Southern Hemisphere influenza season. J. Med. Virol. 87: 35–38, 2015. © 2014 Wiley Periodicals, Inc.

Primary infection with varicella zoster virus (VZV) occurs in immunocompromised and immunocompetent individuals. Clinical and asymptomatic reactivation with shedding of infectious virus and viremia may occur. The prevalence of VZV viremia is unknown. The aim of this study was to detect VZV viremia and quantify VZV DNA using quantitative polymerase chain reaction (qPCR) in blood from different populations. A qPCR-based method using EvaGreen® was used to quantify VZV DNA in 491 samples, including whole blood, plasma and buffy-coat, from patients hospitalized with varicella-associated disease (Group 1, n=10) and three groups with no VZV disease: individuals with a first clinical diagnosis of central nervous system demyelination (Group 2, n=213) with their age and sex-matched controls (Group 3, n=218); and HIV-infected individuals (Group 4, n=50). VZV-specific IgG antibody titres were measured in Group 3. The proportion positive for viremia and mean detectable VZV DNA load (copies/ml) were: Group 1: 100% (10/10) and 4.6 × 10(6) ± 1.4 × 10(7) ; Group 2: 4% (9/213) and 1.5 × 10(3) ± 1.8 × 10(4) ; Group 3: 8% (17/218) and 1.1 × 10(3) ± 7.8 × 10(3) ; Group 4: 12% (6/50) and 7.7 × 10(1) ± 2.8 × 10(2) . VZV DNA load and IgG titres were not significantly correlated (Group 3 only). VZV load in Group 1 was significantly elevated compared to Groups 2-4 (P

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

Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.

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.

A simple clinical screening (CS) tool for respiratory virus (RV) infection was introduced and evaluated in a single hematology ward, as part of a strategy to reduce nosocomial RV infection. Up to 6 clinical symptoms or signs were scored and a predefined threshold score of ≥2 prompted paired nose/throat swab (NTS) collection for RV testing. The criterion standard for RV infection was positive immunofluorescence (IF) or polymerase chain reaction (PCR) for 7 and 15 viruses, respectively. The tool was shown to be most beneficial at excluding infection at a threshold score of 1 (negative predictive value [NPV] 89%, [95% confidence interval 78–96%], sensitivity 85% [70–94%], specificity 35% [27–43%]), compared with a score of 2 (NPV 85% [76–91%], sensitivity 63% [46–77%], specificity 57% [48–65%]) at a prevalence of 22%. The tool's ability to diagnose infection was limited (positive predictive value 27% and 29% at thresholds 1 and 2). The sensitivity of IF compared with PCR was 45% for the 7 viruses common to both, and 23% for the extended virus panel detected by PCR. An algorithm incorporating CS, paired NTS collection at a threshold of 1 symptom or sign, and sensitive testing including PCR can guide infection control measures in hospitalized hematopoietic stem cell transplant recipients.

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).

Relatively few international comparisons of the incidence of influenza related to climate parameters have been performed, particularly in the Eastern hemisphere. In this study, the incidence of influenza and climate data such as temperature, relative humidity, and rainfall, from cities at different latitudes with contrasting climates: Singapore, Hong Kong (China), Ulaanbaatar (Mongolia), Vancouver (Canada), and three Australian cities (Brisbane, Melbourne and Sydney) were examined to determine whether there was any overall relationship between the incidence of influenza and climate. Applying time-series analyses to the more comprehensive datasets, it was found that relative humidity was associated with the incidence of influenza A in Singapore, Hong Kong, Brisbane, and Vancouver. In the case of influenza B, the mean temperature was the key climate variable associated with the incidence of influenza in Hong Kong, Brisbane, Melbourne, and Vancouver. Rainfall was not significantly correlated with the incidence of influenza A or B in any of these cities.

Objective: Active surveillance to determine influenza disease burden in children admitted to hospital with influenza-like illness (ILI). Methods: A prospective hospital-based cohort study conducted June–October 2006 in children

Twenty rapid antigen assays were compared for their ability to detect influenza using dilutions of virus culture supernatants from human isolates of influenza A H5N1 (clade 1 and 2 strains), H3N2 and H1N1 viruses, and influenza B. There was variation amongst the rapid antigen assays in their ability to detect different influenza viruses. Six of the 12 assays labeled as distinguishing between influenza A and B had comparable analytical sensitivities for detecting both influenza A H5N1 strains, although their ability to detect influenza A H3N2 and H1N1 strains varied. The two assays claiming H5 specificity did not detect either influenza A H5N1 strains, and the two avian influenza-specific assays detected influenza A H5N1, but missed some influenza A H3N2 virus supernatants. Clinical trials of rapid antigen tests for influenza A H5N1 are limited. For use in a pandemic where novel influenza strains are circulating (such as the current novel influenza A H1N1 09 virus), rapid antigen tests should ideally have comparable sensitivity and specificity for the new strains as for co-circulating seasonal influenza strains.

A 49-year-old health care worker received varicella vaccine in accordance with current Australian guidelines. She developed streptococcal toxic shock syndrome, complicated by acute atraumatic dislocation of the right wrist secondary to poststreptococcal reactive arthritis - to our knowledge, the first report of spontaneous wrist dislocation as a complication in this condition. Vaccination was accompanied by prolonged viraemia with the varicella vaccine strain - also, we believe, the first report of this in an immunocompetent patient.

Screening for polyoma BK virus (BK) using nucleic testing (NAT) is recommended for kidney and kidney-pancreas transplant recipients, but the performance characteristics of quantitative BK NAT at different thresholds of plasma BK viral loads are unclear. We aim to evaluate the diagnostic accuracy of quantitative BK NAT as an add-on test to qualitative polyoma NAT for the diagnosis of BK virus-associated nephropathy (BKVAN) in kidney and kidney transplant recipients. We calculated the test sensitivity, specificity, and predictive values at the different thresholds of plasma BK viral load for BKVAN. At the recommended threshold of >1 × 10(3) serum BK copies/mL serum for test positivity, the sensitivity for BKVAN was 92.9% (95% confidence intervals [CI]: 66.1-99.8) and specificity 79.1% (95%: CI 67.4-88.1), with corresponding positive and negative predictive values of 42.0% (95% CI: 24.8-57.7%) and 98.6% (95% CI: 98.3-99.9%), respectively. The overall area under curve for the quantitative BK NAT was 0.92 (95% CI: 0.85-0.97). Quantitative BK NAT displays properties of high sensitivity and specificity that are fit for purpose as an add-on test to qualitative polyomavirus NAT for kidney and kidney-pancreas transplant recipients at risk of BKVAN.

Human herpes viruses 1 and 2 (HSV-1 and HSV-2) are among the most common human viral pathogens. Various epidemiological factors determine the infecting HSV type with significant changes in the epidemiology of genital herpes and HSV-1 infections especially in developed countries. Following transmission of HSV to a susceptible person, symptomatic or asymptomatic infection may result with localized disease, the most common manifestation. HSV then establishes latency in the dorsal root ganglia which enables subsequent reactivation. The risk and rate of reactivation are dependent on numerous host factors and the infecting viral subtype. The number of diagnostic tests has increased with molecular methods improving our understanding of asymptomatic viral shedding. Antiviral therapy ameliorates the clinical manifestations and improves survival in neurological disease. Prophylactic antiviral strategies have been formulated for recurrent disease, but vaccine trials do not yet show clinically relevant benefit. Key concepts Classification of human herpes viruses Structure and replication of HSV Pathogenesis of HSV Latency Immunological responses to HSV Epidemiology of HSV Interaction between HSV and HIV infection Clinical manifestations and complication Diagnostic modalities for HSV detection Antiviral therapy and strategies used in the treatment of HSV Preventative strategies and vaccines Keywords: herpes simplex viruses types 1 and 2; latency; primary infection; reactivation; first episode (nonprimary)

Three babies were referred with enteroviral meningitis and myocarditis during a 4-month period. During this same period there was an increased frequency of coxsackievirus B type 2 isolates reported to the National Centre for Disease Control. Myocarditis was simultaneous with meningitis in one baby, but delayed by 10 weeks in another, in whom myocarditis mimicked myocardial infarction. Two of the three mothers experienced abdominal pain, one with antepartum haemorrhage, which has been described previously with coxsackievirus infection in pregnancy. Diagnosis was made in two babies by polymerase chain reaction on cerebrospinal fluid.

• The Australian Government has an extensive stockpile of antivirals (neuraminidase inhibitors) to be used if an influenza pandemic occurs. • Neuraminidase inhibitors reduce the duration of the symptoms of seasonal influenza infection by 1 day on average, when used as treatment within 48 hours of disease onset. • Neuraminidase inhibitors prevent infection in up to 74% of people when administered as prophylaxis. • Resistance of seasonal influenza viruses to neuraminidase inhibitors is low. • The safety and efficacy (including resistance) of neuraminidase inhibitors against pandemic influenza or the virus of current concern in pandemic planning, influenza A/H5N1, is not known, and further research is needed.

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.