Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.

Multiple Sources of Genetic Diversity of Influenza A Viruses during the Hajj.

Outbreaks of respiratory virus infection at mass gatherings pose significant health risks to attendees, host communities, and ultimately the global population if they help facilitate viral emergence. However, little is known about the genetic diversity, evolution, and patterns of viral transmission during mass gatherings, particularly how much diversity is generated by in situ transmission compared to that imported from other locations. Here, we describe the genome-scale evolution of influenza A viruses sampled from the Hajj pilgrimages at Makkah during 2013 to 2015. Phylogenetic analysis revealed that the diversity of influenza viruses at the Hajj pilgrimages was shaped by multiple introduction events, comprising multiple cocirculating lineages in each year, including those that have circulated in the Middle East and those whose origins likely lie on different continents. At the scale of individual hosts, the majority of minor variants resulted from de novo mutation, with only limited evidence of minor variant transmission or minor variants circulating at subconsensus level despite the likely identification of multiple transmission clusters. Together, these data highlight the complexity of influenza virus infection at the Hajj pilgrimages, reflecting a mix of global genetic diversity drawn from multiple sources combined with local transmission, and reemphasize the need for vigilant surveillance at mass gatherings.IMPORTANCE Large population sizes and densities at mass gatherings such as the Hajj (Makkah, Saudi Arabia) can contribute to outbreaks of respiratory virus infection by providing local hot spots for transmission followed by spread to other localities. Using a genome-scale analysis, we show that the genetic diversity of influenza A viruses at the Hajj gatherings during 2013 to 2015 was largely shaped by the introduction of multiple viruses from diverse geographic regions, including the Middle East, with only little evidence of interhost virus transmission at the Hajj and seemingly limited spread of subconsensus mutational variants. The diversity of viruses at the Hajj pilgrimages highlights the potential for lineage cocirculation during mass gatherings, in turn fuelling segment reassortment and the emergence of novel variants, such that the continued surveillance of respiratory pathogens at mass gatherings should be a public health priority.

HSV-2 incidence by sex over four age periods to age 38 in a birth cohort.

OBJECTIVES: To examine herpes simplex virus type 2 (HSV-2) incidence over four periods to age 38 in a birth cohort, and to compare risks for men and women, taking into account sexual behaviour. METHODS: At ages 21, 26, 32 and 38, participants in the Dunedin Multidisciplinary Health and Development Study were invited to provide serum for HSV-2 serology, and information on sexual behaviour. HSV-2 incidence rates were calculated for four age periods, and comparisons made by sex and period, taking into account number of sexual partners. RESULTS: By age 38, 17.3% of men and 26.8% of women had ever been seropositive for HSV-2. Incidence peaked for women from age 21 to 26 (19.1 per 1000 person-years) and men from age 26 to 32 (14.1 per 1000 person-years); it fell markedly for both from age 32 to 38 (5.1 and 6.8 per 1000 person-years for men and women, respectively). Overall risk was significantly higher for women: adjusted incidence rate ratio 1.9 (95% CI 1.4 to 2.7); the sex difference was most marked from age 21 to 26 (3.4, 95% CI 1.9 to 6.3). CONCLUSIONS: Our findings are consistent with a greater biological susceptibility to HSV-2 among women, and with the increasing risk to the early/mid-20s for women and late 20s/early 30s for men, being driven by an increasing pool of prevalent infection. The reduced risk in the mid-30s is consistent with declining infectivity of long-term prevalent infections.

Pandemic clinical case definitions are non-specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia.

BACKGROUND: During the early phases of the 2009 pandemic, subjects with influenza-like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus. FINDINGS: Between 25th May and 7th June 2009, during the pandemic CONTAIN phase, A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466 (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09 testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative samples were tested for other respiratory viruses using a real-time multiplex PCR assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of samples. CONCLUSIONS: In the very early stages of a new pandemic, limiting testing to only the novel virus will miss other clinically important co-circulating respiratory pathogens.

MAMBRA's impact on IPV symptoms of incarcerated and formerly incarcerated women.

This repeated measures, descriptive study investigated the effect of Music and Account-Making for Behavioral-Related Adaptation (MAMBRA), a group psychoeducation music intervention, on symptoms reported by 41 incarcerated and community women survivors of intimate partner violence (IPV). Psychosocial measurements included: the Center for Epidemiologic Studies Depression Scale; Speilberger State Anxiety Inventory; Rosenberg's Self Esteem Scale; the UCLA Loneliness Scale, version 3; and the Index of Spouse Abuse. MAMBRA was administered over four sessions for five groups of women. Through descriptive and univariate statistics, psychosocial measures positively changed across the MAMBRA sessions. These findings suggest MAMBRA impacted IPV symptoms and may be an efficacious intervention. Future longitudinal studies with diverse samples are warranted.

Varicella zoster virus quantitation in blood from symptomatic and asymptomatic individuals.

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<0.001); the latter were not significantly different from each other (P=0.05). VZV genotypes from clades 1-5 were identified in Group 1. VZV DNA was detected but at low frequency and viral load in both immunocompetent and immunocompromised individuals asymptomatic for VZV infection, compared to individuals with active VZV infection.

Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity.

Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring the duration of specific SARS-CoV-2 cellular immunity. In this regard, we previously identified T cell epitope-derived peptides within topologically and structurally essential regions of SARS-CoV-2 spike and nucleocapsid proteins by applying an immunoinformatics pipeline. In this study, we selected 30 spike- and nucleocapsid-derived peptides and assessed whether these peptides induce T cell responses and avoid major mutations found in SARS-CoV-2 variants of concern. Our peptide pool was highly specific, with only a single peptide driving cross-reactivity in people unexposed to SARS-COV-2, and immunogenic, inducing a polyfunctional response in CD4+ and CD8+ T cells from COVID-19 recovered individuals. All peptides were immunogenic and individuals recognized broad and diverse peptide repertoires. Moreover, our peptides avoided most mutations/deletions associated with all four SARS-CoV-2 variants of concern while retaining their physicochemical properties even when genetic changes are introduced. This study contributes to an evolving definition of individual CD4+ and CD8+ T cell epitopes that can be used for specific diagnostic tools for SARS-CoV-2 T cell responses and is relevant to the development of variant-resistant and durable T cell-stimulating vaccines.

Circulation of influenza and other respiratory viruses during the COVID-19 pandemic in Australia and New Zealand, 2020-2021.

Objective: Circulation patterns of influenza and other respiratory viruses have been globally disrupted since the emergence of coronavirus disease (COVID-19) and the introduction of public health and social measures (PHSMs) aimed at reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Methods: We reviewed respiratory virus laboratory data, Google mobility data and PHSMs in five geographically diverse regions in Australia and New Zealand. We also described respiratory virus activity from January 2017 to August 2021. Results: We observed a change in the prevalence of circulating respiratory viruses following the emergence of SARS-CoV-2 in early 2020. Influenza activity levels were very low in all regions, lower than those recorded in 2017-2019, with less than 1% of laboratory samples testing positive for influenza virus. In contrast, rates of human rhinovirus infection were increased. Respiratory syncytial virus (RSV) activity was delayed; however, once it returned, most regions experienced activity levels well above those seen in 2017-2019. The timing of the resurgence in the circulation of both rhinovirus and RSV differed within and between the two countries. Discussion: The findings of this study suggest that as domestic and international borders are opened up and other COVID-19 PHSMs are lifted, clinicians and public health professionals should be prepared for resurgences in influenza and other respiratory viruses. Recent patterns in RSV activity suggest that these resurgences in non-COVID-19 viruses have the potential to occur out of season and with increased impact.

Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis.

BACKGROUND: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however. METHODS: Prospective cohort of 198 persons with clinically definite MS, followed 2002-5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein-Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression. RESULTS: For the 145 persons with relapsing-remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. DISCUSSION: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing-remitting MS clinical course.

Comparison of a rapid antigen test with nucleic acid testing during cocirculation of pandemic influenza A/H1N1 2009 and seasonal influenza A/H3N2.

The rapid diagnosis of influenza is critical in optimizing clinical management. Rapid antigen tests have decreased sensitivity in detecting pandemic influenza A/H1N1 2009 virus compared to seasonal influenza A subtypes (53.4% versus 74.2%, P < 0.001). Nucleic acid tests should be used to detect pandemic influenza virus when rapid antigen tests are negative.

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye.

BACKGROUND: Reactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample. RESULTS: EBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 10(2) to 1.3 × 10(8) copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 10(3) to 2.0 × 10(5) copies/ml in infectious mononucleosis (n = 7), 7.5 × 10(4) to 1.1 × 10(5) copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 10(2) to 5.6 × 10(3) copies/ml in HIV-infected patients (n = 12), and 2.0 × 10(2) to 9.1 × 10(4) copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11). CONCLUSION: Two sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.

Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects.

In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-gamma in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1(+) and/or 16 HSV2(+) patients using (51)Cr-release cytotoxicity and IFN-gamma ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to individual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of individual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1(+)/HSV2(-) and HSV1(-)/HSV2(+) subjects, but the sites of recognition differed within the 20-mers where their sequences were divergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.

Facemask against viral respiratory infections among Hajj pilgrims: A challenging cluster-randomized trial.

BACKGROUND: In this large-scale cluster-randomized controlled trial (cRCT) we sought to assess the effectiveness of facemasks against viral respiratory infections. METHODS AND RESULTS: Over three consecutive Hajj seasons (2013, 2014, 2015) pilgrims' tents in Makkah were allocated to 'facemask' or 'no facemask' group. Fifty facemasks were offered to participants in intervention tents, to be worn over four days, and none were offered to participants in control tents. All participants recorded facemask use and respiratory symptoms in health diaries. Nasal swabs were collected from the symptomatic for virus detection by reverse transcription polymerase chain reaction. Clinical symptoms and laboratory results were analyzed by 'intention- to-treat' and 'per-protocol'. A total of 7687 adult participants from 318 tents were randomized: 3864 from 149 tents to the intervention group, and 3823 from 169 tents to the control group. Participants were aged 18 to 95 (median 34, mean 37) years, with a male to female ratio of 1:1.2. Overall, respiratory viruses were detected in 277 of 650 (43%) nasal/pharyngeal swabs collected from symptomatic pilgrims. Common viruses were rhinovirus (35.1%), influenza (4.5%) and parainfluenza (1.7%). In the intervention arm, respectively 954 (24.7%) and 1842 (47.7%) participants used facemasks daily and intermittently, while in the control arm, respectively 546 (14.3%) and 1334 (34.9%) used facemasks daily and intermittently. By intention-to-treat analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.9 to 2.1, p = 0.18) nor against clinical respiratory infection (OR, 1.1; 95% CI, 0.9 to 1.4, p = 0.40). Similarly, in a per-protocol analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (OR 1.2, 95% CI 0.9-1.7, p = 0.26) nor against clinical respiratory infection (OR 1.3, 95% CI 1.0-1.8, p = 0.06). CONCLUSION: This trial was unable to provide conclusive evidence on facemask efficacy against viral respiratory infections most likely due to poor adherence to protocol.

Evaluation of twenty rapid antigen tests for the detection of human influenza A H5N1, H3N2, H1N1, and B viruses.

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.

Upstairs and downstairs: socio-economic and gender interactions in herpes simplex virus type 2 seroprevalence in australia.

BACKGROUND: This study investigates socio-economic differentials in herpes simplex virus type 2 (HSV-2) seroprevalence in Australian men and women using individual and geographic measures of socio-economic status. METHODS: HSV-2 seropositivity among men and women aged over 25 years was investigated by levels of individual and area-based measures of socio-economic status (SES) in a series of Poisson regression models, variously adjusting for age, country of birth, marital status, indigenous status, and urban/rural residence as potential confounders. Serum and socio-demographics were collected during 1999 and 2000 in a population-based Australia-wide prevalence survey. RESULTS: HSV-2 seroprevalence was significantly lower in areas of low SES than in high SES areas among both men (P for trend <0.001) and women (P for trend = 0.004) for all ages. A similar pattern was evident for individual education level for men with lower rates of HSV-2 in respondents with lower educational achievement (relative risk = 0.77, 95% CI 0.61-0.97, P = 0.024). In contrast, HSV-2 prevalence was higher for women with lower individual levels of education for all ages (relative risk = 1.22, 95% CI 1.04-1.44, P = 0.017). Analyses stratifying HSV-2 prevalence for individual education level by area-based SES showed the highest prevalence of HSV-2 in women with the lowest education level residing in the highest SES areas. This pattern was not evident in men, with a greater concordance between individual and area-based SES. CONCLUSION: HSV-2 seroprevalence is not consistently distributed across individual and area measures of SES, suggesting that upward and downward mixing between social strata in men and women is an important mode of HSV-2 transmission.

An Exploratory Study Using Cortisol to Describe the Response of Incarcerated Women IPV Survivors to MAMBRA Intervention.

Objective. To determine if incarcerated women survivors of IPV had a physiological response to the Music and Account-Making for Behavioral-Related Adaptation (MAMBRA) intervention, as measured by cortisol levels. Methods. A single-group repeated measures designed exploratory study was used to pilot-test MAMBRA. A convenience sample (n = 33) was recruited in a Midwestern women's correctional facility. Serving as their own control, participants provided demographics and pre-/post-MAMBRA salivary samples while attending four MAMBRA sessions. Baseline data were compared to participants' data collected over the remaining 3 MAMBRA sessions. Data were analyzed with descriptive and univariate statistics with an alpha of .05 and post-hoc power of .65. Results. Participants were predominantly White (52%), single (80%), and early middle-aged ([Formula: see text]), with a history of physical/nonphysical spousal abuse. Using a subsample (n = 26), salivary cortisol decreased between the pre-/post-MAMBRA over the sessions (F(3,75) = 4.59, p < .01). Conclusion. Participants had a physiological response to the MAMBRA intervention as evidenced by the decreased cortisol between the pre-/post-MAMBRA. This is the first step in examining MAMBRA's clinical utility as an intervention for female IPV survivors. Future longitudinal studies will examine MAMBRA's effectiveness given this change in cortisol.

No resting place: African American women at the crossroads of violence.

Seeking safe places after leaving abusive relationships is often an intricate process for African American women. Survivor-victims of gender violence frequently experience ongoing trauma because of race, ethnicity, class, sexual orientation, and other stigmatizing social identities. All too often, women of color must handle leaving the gender violence simultaneously with the ongoing threat of cultural violence. The intersection of gender and cultural violence (e.g., racism, discrimination) complicate African American women's ability to obtain and sustain safe environments. These intersections are critical crossroads in African American women's lives. The results of this womanist and Black feminist study are presented in an alternative way to highlight the primacy of respondents' voices. In addition, suggestions to inform the practice of research with African American women are included.

A randomized study of standard versus double dose oseltamivir for treating influenza in the community.

BACKGROUND: The neuraminidase inhibitors are the treatment of choice for influenza virus infection. Oseltamivir-resistant (OsR) strains of influenza A(H1N1)pdm09 are described, but the effect of higher dose oseltamivir on efficacy, safety and emergence of resistance has not been addressed in the developed setting in outpatients. The objectives of the study were to compare standard dose (SD) versus double dose (DD) oseltamivir regimens for frequency of detecting OsR influenza virus, clinical disease resolution, virological clearance and adverse events. METHODS: This was an unblinded randomized controlled trial of community-based patients with confirmed influenza. Participants were randomized to a 5-day regimen of either SD or DD oseltamivir. RESULTS: Of 52 participants (aged 4.8-54.8 years), 25 received SD and 27 DD oseltamivir. Clinical resolution did not differ by dosing regimen (P=0.43); neither did virological clearance differ for either influenza A (P=0.20) or B (P=0.70). Adverse events, predominantly gastrointestinal, were greater with DD than SD (P=0.04). One OsR strain was detected prior to treatment and two individuals developed OsR strains during treatment, one each on SD and DD. Those with OsR strains did not appear to have a different clinical course. CONCLUSIONS: DD oseltamivir did not appear to provide a clinical or virological advantage, nor reduce the emergence of oseltamivir resistance, but our study was underpowered. Adverse events occurred more frequently on DD compared to SD oseltamivir.

Pilot Randomised Controlled Trial to Test Effectiveness of Facemasks in Preventing Influenza-like Illness Transmission among Australian Hajj Pilgrims in 2011.

Studies to determine the effectiveness of facemasks in preventing influenza have been inconclusive, largely due to small sample size. The Hajj pilgrimage, where the incidence of influenza and other respiratory infections is high, provides an excellent opportunity to test the effectiveness of facemasks against syndromic and laboratory-confirmed infections. Hence, a pilot study was conducted among Australian pilgrims to assess the feasibility of such a large-scale trial in the coming years. At the 2011 Hajj, tents were randomised to 'supervised mask use' versus 'no supervised mask use'. Pilgrims with ILI symptoms for ≤3 days were recruited as 'cases' and those who slept within 2 meters of them as 'contacts'. Surgical facemasks were provided to cases and contacts in the 'mask' tents, but not in the 'control' tents. Pilgrims in both groups were given diaries to record their respiratory symptoms. Nasal or pharyngeal swabs were collected from the cases and contacts with ILI for point-of-care and nucleic acid tests. A total of 22 tents were randomised to 'mask' (n=12) or 'control' (n=10). There were 164 pilgrims recruited; 75 in 'mask' and 89 in 'control' group. Mask use compliance was 76% in the 'mask' group and 12% in the 'control' group. Based on developing syndromic ILI, less contacts became symptomatic in the 'mask' tents compared to the 'control' tents (31% versus 53%, p= 0.04). However, laboratory results did not show any difference between the two groups. This pilot study shows that a large trial to assess the effectiveness of facemasks use at Hajj is feasible.