Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications for infection control: a review

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.

Comparison of influenza surveillance systems in Australia, China, Malaysia and expert recommendations for influenza control.

BACKGROUND: The Western Pacific Region (WPR) is exposed each year to seasonal influenza and is often the source of new influenza virus variants and novel pathogen emergence. National influenza surveillance systems play a critical role in detecting emerging viruses, monitoring influenza epidemics, improving public disease awareness and promoting pandemic preparedness, but vary widely across WPR countries. The aim of this study is to improve existing influenza surveillance systems by systematically comparing selected WPR influenza surveillance systems. METHODS: Three national influenza surveillance systems with different levels of development (Australia, China and Malaysia) were compared and their adherence to World Health Organization (WHO) guidance was evaluated using a structured framework previously tested in several European countries consisting of seven surveillance sub-systems, 19 comparable outcomes and five evaluation criteria. Based on the results, experts from the Asia-Pacific Alliance for the Control of Influenza (APACI) issued recommendations for the improvement of existing surveillance systems. RESULTS: Australia demonstrated the broadest scope of influenza surveillance followed by China and Malaysia. In Australia, surveillance tools covered all sub-systems. In China, surveillance did not cover non-medically attended respiratory events, primary care consultations, and excess mortality modelling. In Malaysia, surveillance consisted of primary care and hospital sentinel schemes. There were disparities between the countries across the 5 evaluation criteria, particularly regarding data granularity from health authorities, information on data representativeness, and data communication, especially the absence of publicly available influenza epidemiological reports in Malaysia. This dual approach describing the scope of surveillance and evaluating the adherence to WHO guidance enabled APACI experts to make a number of recommendations for each country that included but were not limited to introducing new surveillance tools, broadening the use of specific existing surveillance tools, collecting and sharing data on virus characteristics, developing immunization status registries, and improving public health communication. CONCLUSIONS: Influenza monitoring in Australia, China, and Malaysia could benefit from the expansion of existing surveillance sentinel schemes, the broadened use of laboratory confirmation and the introduction of excess-mortality modelling. The results from the evaluation can be used as a basis to support expert recommendations and to enhance influenza surveillance capabilities.

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. MethodsWe conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. ResultsOf 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. ConclusionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.

Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome

INTRODUCTION@#Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS.@*METHODS@#Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H@*RESULTS@#A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; @*CONCLUSION@#COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTION@#Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.@*METHODS@#This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.@*RESULTS@#In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.@*CONCLUSION@#In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant.

The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 {gamma}{delta} T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Detection of Air and Surface Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Hospital Rooms of Infected Patients

Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. We aimed to detect SARS-CoV-2 surface and air contamination and study associated patient-level factors. 245 surface samples were collected from 30 airborne infection isolation rooms of COVID-19 patients, and air sampling was conducted in 3 rooms. Air sampling detected SARS-CoV-2 PCR-positive particles of sizes >4 {micro}m and 1-4 {micro}m in two rooms, which warrants further study of the airborne transmission potential of SARS-CoV-2. 56.7% of rooms had at least one environmental surface contaminated. High touch surface contamination was shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.010).

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.

Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2

To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.

Clustering, climate and dengue transmission.

Dengue is currently the most rapidly spreading vector-borne disease, with an increasing burden over recent decades. Currently, neither a licensed vaccine nor an effective anti-viral therapy is available, and treatment largely remains supportive. Current vector control strategies to prevent and reduce dengue transmission are neither efficient nor sustainable as long-term interventions. Increased globalization and climate change have been reported to influence dengue transmission. In this article, we reviewed the non-climatic and climatic risk factors which facilitate dengue transmission. Sustainable and effective interventions to reduce the increasing threat from dengue would require the integration of these risk factors into current and future prevention strategies, including dengue vaccination, as well as the continuous support and commitment from the political and environmental stakeholders.

Risk factors and time-trends of cytomegalovirus (CMV), syphilis, toxoplasmosis and viral hepatitis infection and seroprevalence in human immunodeficiency virus (HIV) infected patients

<p><b>INTRODUCTION</b>Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore.</p><p><b>MATERIALS AND METHODS</b>This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed.</p><p><b>RESULTS</b>Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006).</p><p><b>CONCLUSION</b>This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.</p>

Clinical evaluation of an in-house human immunodeficiency virus (HIV) genotyping assay for the detection of drug resistance mutations in HIV-1 infected patients in Singapore

<p><b>INTRODUCTION</b>Human immunodeficiency virus type 1 (HIV-1) genotyping resistance test (GRT) is essential for monitoring HIV-1 drug resistance mutations (DRMs). High cost and HIV-1 genetic variability are challenges to assay availability in Singapore. An in-house Sanger sequencing-based GRT method was developed at the Communicable Disease Centre (CDC), Singapore's HIV national treatment reference centre for both subtype B and non-subtype B HIV-1.</p><p><b>MATERIALS AND METHODS</b>The in-house GRT sequenced the fi rst 99 codons of protease (PR) and 244 codons of reverse transcriptase (RT) in the pol gene. The results were compared with the Food and Drug Administration (FDA)-approved ViroSeq™ HIV-1 Genotyping System.</p><p><b>RESULTS</b>Subtype assignment for the 46 samples were as follows: 31 (67.4%) CRF01_AE, 14 (30.5%) subtype B and 1 (2.1%) subtype C. All 46 samples had viral load of ≥500 copies/mL, and were successfully amplified by the in-house primer sets. Compared to the ViroSeq™ test, our in-house assay showed drug-resistance conferring codon concordance of 99.9% at PR and 98.9% at RT, and partial concordance of 0.1% at PR and 1.1% at RT. No discordant result was observed.</p><p><b>CONCLUSION</b>The assay successfully identified DRMs in both subtype AE and B, making it suitable for the efficient treatment monitoring in genetically diverse population. At less than half of the running cost compared to the ViroSeq™ assay, the broadly sensitive in-house assay could serve as a useful addition to the currently limited HIV genotyping assay options for resource-limited settings, thereby enhancing the DRM surveillance and monitoring in the region.</p>

Causes of death and factors associated with early death among human immunodeficiency virus (HIV)-infected persons in Singapore: pre-highly active antiretroviral therapy (HAART) and Peri-HAART

<p><b>INTRODUCTION</b>Highly active antiretroviral therapy (HAART) has greatly changed the epidemiology of human immunodefi ciency virus (HIV) mortality. The aim of this study is to compare the causes of death and factors associated with early death in HIV-infected persons in the pre- and peri-highly active antiretroviral therapy (HAART) periods.</p><p><b>MATERIALS AND METHODS</b>We conducted a retrospective review of 483 HIV-infected persons who were diagnosed with HIV from 1985 to 2000, and had died within 5 years of the diagnosis. We examined the temporal change in the primary causes of death between those who were diagnosed in the pre-HAART (1985 to 1995) and peri-HAART (1996 to 2000) periods, and compared the demographic and clinical characteristics of the 2 groups.</p><p><b>RESULTS</b>During the peri-HAART period, HIV encephalopathy, cryptococcal meningitis, and lymphoma were no longer the leading causes of death. Opportunistic infections remained important causes of death. Early deaths from the peri-HAART period were older (60 years and above) at diagnosis (Adj OR 7.50; 95% CI, 1.78 to 31.58), more likely to be divorced (Adj OR 5.05, 95% CI, 1.96 to 13.02) and tended to have a low baseline CD4 cell count of <50 cells/ uL (Adj OR 2.18, 95% CI, 1.14 to 4.16) , and were more likely to have received HAART (Adj OR 5.19; 95% CI, 2.22 to 12.12) than early deaths from the pre-HAART period.</p><p><b>CONCLUSION</b>In the peri-HAART era, HIV-infected persons who died within 5 years of diagnosis were those who were older (≥60 years), divorced, or who presented with very late-stage disease (CD4 <50) at diagnosis. More targeted public health interventions, such as targeted public health messages and outreach to increase access to HIV testing and treatment should be developed for these subpopulations.</p>

Causes of death in hospitalised HIV-infected patients at a National Referral Centre in Singapore: a retrospective review from 2008 to 2010

<p><b>INTRODUCTION</b>Highly active antiretroviral therapy (HAART) has improved outcomes for individuals infected with human immunodeficiency virus (HIV). This study describes the causes of death in hospitalised HIV-positive patients from 2008 to 2010 in Tan Tock Seng Hospital, the national referral centre for HIV management in Singapore.</p><p><b>MATERIALS AND METHODS</b>Data were retrospectively collected from HIV-positive patients who died in Tan Tock Seng Hospital from January 2008 to December 2010.</p><p><b>RESULTS</b>Sixty-seven deaths occurred in the study period. A majority of patients died of non-acquired immune deficiency syndrome (AIDS)-defining illnesses (54.7%). The median CD4 count was 39.5 (range, 20.0 to 97.0), and 7 patients had HIV viral loads of <200 copies/mL. There were 27 deaths due to opportunistic infections, 27 due to non AIDS-defining infections, 4 due to non AIDS-associated malignancies. This study also describes 3 deaths due to cardiovascular events, and 1 due to hepatic failure. Patients who had virologic suppression were more likely to die from non AIDS-defining causes.</p><p><b>CONCLUSION</b>Causes of death in HIV-positive patients have changed in the HAART era. More research is required to further understand and address barriers to testing and treatment to further improve outcomes in HIV/AIDS.</p>

Older age at initial presentation to human immunodeficiency virus (HIV) care and treatment at the Communicable Disease Centre (CDC) in Singapore, 2006 to 2011

<p><b>INTRODUCTION</b>The incidence of newly diagnosed older patients diagnosed with human immunodeficiency virus (HIV) has increased worldwide in recent years. In this study, we compared the demographics and clinical presentation of younger and older patients in our HIV sentinel cohort.</p><p><b>MATERIALS AND METHODS</b>Among all HIV patients presenting to the Communicable Disease Centre (CDC), Singapore from 2006 to 2011, 793 were randomly included in our cohort, representing about 50% of the patients seen during that period. We collected demographic, clinical, laboratory, and outcome data from patient records to compare younger (<50 years old) and older (≥50 years old) HIV patients.</p><p><b>RESULTS</b>Older patients comprised 27.1% of our HIV cohort and presented with lower median CD4 T cell counts (65 cells/mm³, interquartile range [IQR]: 27 to 214 cells/mm³) compared to younger patients (250 cells/mm³, IQR: 74 to 400 cells/mm³; P <0.001). The median time from HIV diagnosis to initiation of antiretroviral therapy (ART) differed significantly for both age groups as well (49 days for patients <50 years old, IQR: 18 to 294 days; versus 35 days for patients ≥50 years old, IQR: 14 to 102 days; P = 0.008). More of our younger patients were single (72.2%) or homosexual (44.1%), in contrast to older patients, of whom 48.8% were married and 84.7% were heterosexual.</p><p><b>CONCLUSION</b>Upon comparison of our younger and older patients, we identified distinct differences in risk transmission and clinical presentation. Increased awareness of older patients at risk of HIV may improve time to diagnosis among this age group.</p>

Dengue knowledge, attitudes, and practices among primary care physicians in Singapore

<p><b>INTRODUCTION</b>Dengue fever remains a significant public health concern in Singapore. Appropriate, timely diagnosis and risk stratification for severe disease are crucial in the optimal management of this illness. In the outpatient setting, the primary care physician plays a key role in dengue diagnosis, management, and triage. We present a descriptive analysis of the variations in dengue knowledge, attitudes, and practices among primary care physicians (PCPs) in Singapore.</p><p><b>MATERIALS AND METHODS</b>A survey of 25 multiple-choice questions was mailed to 2000 PCPs in Singapore. Responses were analysed by physician age group (21-40, 41-60, and >61) and practice setting (government subsidised polyclinic or private practice).</p><p><b>RESULTS</b>Of the 3 questions assessing dengue knowledge, 89.9% chose 2 or 3 of the preferred responses. Half of the respondents utilised dengue diagnostic tests at least 50% of the time, and 75% used serology when doing so. Older respondents and those from private practices used diagnostic tests more often than their counterparts, and both groups favoured non-serology tests. About 85% of surveyed PCPs monitored confirmed or suspected cases daily, and one-third referred patients to a hospital always or often.</p><p><b>CONCLUSIONS</b>While no major gaps in knowledge about dengue were identified in PCPs in Singapore, there were significant variations in clinical practice by physician age group and practice setting. The results of this survey provide a useful opportunity to identify strengths and areas in need of improved awareness in primary care management of dengue.</p>

When less is more: can we abandon prophylactic platelet transfusion in Dengue fever?

Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion-in the absence of major bleeding-is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice.

Influenza B outbreak among influenza-vaccinated welfare home residents in Singapore

<p><b>INTRODUCTION</b>Outbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control.</p><p><b>MATERIALS AND METHODS</b>During the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples.</p><p><b>RESULTS</b>The overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received.</p><p><b>CONCLUSIONS</b>A mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks.</p>