miR-466 is putative negative regulator of Coxsackie virus and Adenovirus Receptor.

This study aimed at elucidating how Coxsackie B virus (CVB) perturbs the host's microRNA (miRNA) regulatory pathways that lead to antiviral events. The results of miRNA profiling in rat pancreatic cells infection models revealed that rat rno-miR-466d was up-regulated in CVB infection. Furthermore, in silico studies showed that Coxsackie virus and Adenovirus Receptor (CAR), a cellular receptor, was one of the rno-miR-466d targets involved in viral entry. Subsequent experiments also proved that both the rno-miR-466d and the human hsa-miR-466, which are orthologs of the miR-467 gene family, could effectively down-regulate the levels of rat and human CAR protein expression, respectively.

Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination.

BACKGROUND: Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question. AIMS: The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future. METHODS: A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults. FINDINGS: Among 212 students, 17-23-year-old, born after adoption of neonatal immunization, 2 (0.9%) were HBsAg positive, 40 (18.9%) were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs <10 mIU/mL, 29.0% and 56.5% were 10-100 and >100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047). At 2-4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10-100 mIU/mL. CONCLUSIONS: Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.

Photodynamic inactivation of bacteria and viruses using two monosubstituted zinc(II) phthalocyanines.

A zinc(II) phthalocyanine substituted with a triamino moiety and its tri-N-methylated analogue have been prepared and characterized with various spectroscopic methods. Both compounds remain non-aggregated in N,N-dimethylformamide and in water containing 0.05% Cremophor EL (v/v), and can generate singlet oxygen effectively. The photodynamic activities of these compounds have been examined against a range of bacterial strains, including the Gram-positive methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC BAA-43, and the Gram-negative Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Both photosensitizers are highly cytotoxic, particularly for the two Gram-positive strains, for which as low as 5 nM of dye is required to induce a 4-log reduction of their viability. The tri-N-methylated derivative has also been shown to be able to effectively inhibit the growth of a series of clinical strains of Staphylococcus aureus and Escherichia coli, and biofilms of methicillin-resistant Staphylococcus aureus ATCC 67928 and ATCC 68507, and Staphylococcus epidermidis ATCC 35984. In addition, the photodynamic inactivation of a range of viruses using these two compounds has also been investigated. Both compounds are highly photocytotoxic against the enveloped viruses influenza A virus (H1N1) and herpes simplex virus type 1 (HSV1), but exhibit no significant cytotoxicity toward the non-enveloped viruses adenovirus type 3 (Ad3) and coxsackievirus (Cox B1).

Oligolysine-conjugated zinc(II) phthalocyanines as efficient photosensitizers for antimicrobial photodynamic therapy.

A series of zinc(II) phthalocyanines conjugated with an oligolysine chain (n=2, 4, and 8) were synthesized and characterized by using various spectroscopic methods. As shown by using UV/Vis and fluorescence spectroscopic methods, these compounds were nonaggregated in N,N-dimethylformamide, and gave a weak fluorescence emission and high singlet oxygen quantum yield (Φ(Δ) =0.86-0.89) as a result of their di-α-substitution. They became slightly aggregated in water with 0.05 % Cremophor EL, but they could still generate singlet oxygen effectively. The antimicrobial photodynamic activities of these compounds were then examined against various bacterial strains, including the Gram-positive methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC BAA-43, and the Gram-negative Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Generally, the dyes were much more potent toward the Gram-positive bacteria. Only 15 to 90 nM of these photosensitizers was required to induce a 4 log reduction in the cell viability of the strains. For Escherichia coli, the photocytotoxicity increased with the length of the oligolysine chain. The octalysine derivative showed the highest potency with a 4 log reduction concentration of 0.8 µM. Pseudomonas aeruginosa was most resistant to the photodynamic treatment. The potency of the tetralysine derivative toward a series of clinical strains of Staphylococcus aureus was also examined and found to be comparable with that toward the nonclinical counterparts. Moreover, the efficacy of these compounds in photodynamic inactivation of viruses was also examined. They were highly photocytotoxic against the enveloped viruses influenza A virus (H1N1) and herpes simplex virus type 1 (HSV1), but exhibited no significant cytotoxicity against the nonenveloped viruses adenovirus type 3 (Ad3) or coxsackievirus (Cox B1). The octalysine derivative also showed the highest potency with an IC(50) value of 0.05 nM for the two enveloped viruses.

Bench to bed evidences for pharmacokinetic and pharmacodynamic interactions involving oseltamivir and chinese medicine.

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although C max, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P < 0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P < 0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe.

Clinical and virologic factors associated with reduced sensitivity of rapid influenza diagnostic tests in hospitalized elderly patients and young children.

Rapid influenza diagnostic tests (RIDTs) are commonly used by clinicians to guide patient management. Data on sensitivities among hospitalized patients are limited. Here, we evaluated the clinical and virologic factors affecting the sensitivities of 2 commercially available RIDTs (BinaxNOW Influenza A&B and QuickVue Influenza A+B) on nasopharyngeal aspirate (NPA) specimens collected from elderly patients and young children hospitalized for influenza. Influenza cases and age-matched negative controls were prospectively enrolled during the 2011-2012 influenza season in Hong Kong. NPA specimens were collected at presentation before antiviral treatment. Real-time reverse transcription-PCR (RT-PCR) results were used as references for the sensitivity analyses. One hundred patients (57 influenza cases and 43 controls) were studied. Both RIDTs had 100% specificities. The sensitivities of the BinaxNOW Influenza A&B and QuickVue Influenza A+B tests were 70% and 82%, respectively. For both tests, the sensitivities were lower in cases with presentation times beyond 2 days of illness onset than for those within this time (50 to 71% versus 85 to 91%, respectively). There were trends toward lower sensitivities for influenza B than for influenza A (66 to 81% versus 76 to 84%, respectively), among young children than among the elderly patients (63 to 78% versus 80 to 88%, respectively), and among cases with pneumonia than those without pneumonia (75% versus 82 to 94%, respectively). The sensitivities of the RIDTs decreased with reduced NPA viral RNA levels (5.6 to 15.0% reduction per 1-log decrease), which declined progressively after illness onset (Spearman's rho, -0.47 [P < 0.05] and -0.66 [P < 0.001] for influenza A and B, respectively). Collectively, late presentation, a low NPA viral load, and probably lower respiratory manifestation are factors associated with reduced sensitivities of RIDTs for diagnosing influenza in hospitalized patients. A negative RIDT result should be interpreted with caution.

Knowledge, attitude, practice and barriers on vaccination against human papillomavirus infection: a cross-sectional study among primary care physicians in Hong Kong.

This study explored the knowledge, attitude, practice and barriers to prescribe human papillomavirus (HPV) vaccines among private primary care physicians in Hong Kong. A self-administered questionnaire survey was conducted by sending letters to doctors who had joined a vaccination program for school girls. From 720 surveys sent, 444 (61.7%) completed questionnaires were returned and analyzed. For knowledge, few responded to questions accurately on the prevalence of cervical HPV (27.9%) and genital wart infection (13.1%) among sexually active young women in Hong Kong, and only 44.4% correctly answered the percentage of cervical cancers caused by HPV. For attitude, most agreed that HPV vaccination should be fully paid by the Government (68.3%) as an important public health strategy. Vaccination against HPV was perceived as more important than those for genital herpes (52.2%) and Chlamydia (50.1%) for adolescent health, and the majority selected adolescents aged 12-14 years as the ideal group for vaccination. Gardasil(®) (30.9%) and Cervarix(®) (28.0%) were almost equally preferred. For practice, the factors influencing the choice of vaccine included strength of vaccine protection (61.1%), long-lasting immunity (56.8%) and good antibody response (55.6%). The most significant barriers to prescribe HPV vaccines consisted of parental refusal due to safety concerns (48.2%), and their practice of advising vaccination was mostly affected by local Governmental recommendations (78.7%). A substantial proportion of physicians had recommended HPV vaccines for their female clients/patients aged 18-26 years for protection of cervical cancer (83.8%) or both cervical cancer and genital warts (85.5%). The knowledge on HPV infection was low among physicians in Hong Kong. Prescription of HPV vaccine was hindered by the perceived parental concerns and was mostly relied on Governmental recommendations. Educational initiatives should be targeted towards both physicians and parents, and the Government should consider full subsidy to enhance vaccine uptake rate.

Replication and transcription activities of ribonucleoprotein complexes reconstituted from avian H5N1, H1N1pdm09 and H3N2 influenza A viruses.

Avian influenza viruses pose a serious pandemic threat to humans. Better knowledge on cross-species adaptation is important. This study examined the replication and transcription efficiency of ribonucleoprotein complexes reconstituted by plasmid co-transfection between H5N1, H1N1pdm09 and H3N2 influenza A viruses, and to identify mutations in the RNA polymerase subunit that affect human adaptation. Viral RNA polymerase subunits PB1, PB2, PA and NP derived from influenza viruses were co-expressed with pPolI-vNP-Luc in human cells, and with its function evaluated by luciferase reporter assay. A quantitative RT-PCR was used to measure vRNA, cRNA, and mRNA levels for assessing the replication and transcription efficiency. Mutations in polymerase subunit were created to identify signature of increased human adaptability. H5N1 ribonucleoprotein complexes incorporated with PB2 derived from H1N1pdm09 and H3N2 viruses increased the polymerase activity in human cells. Furthermore, single amino acid substitutions at PB2 of H5N1 could affect polymerase activity in a temperature-dependent manner. By using a highly sensitive quantitative reverse transcription-polymerase chain reaction, an obvious enhancement in replication and transcription activities of ribonucleoproteins was observed by the introduction of lysine at residue 627 in the H5N1 PB2 subunit. Although less strongly in polymerase activity, E158G mutation appeared to alter the accumulation of H5N1 RNA levels in a temperature-dependent manner, suggesting a temperature-dependent mechanism in regulating transcription and replication exists. H5N1 viruses can adapt to humans either by acquisition of PB2 from circulating human-adapted viruses through reassortment, or by mutations at critical sites in PB2. This information may help to predict the pandemic potential of newly emerged influenza strains, and provide a scientific basis for stepping up surveillance measures and vaccine production.

Role of human Toll-like receptors in naturally occurring influenza A infections.

BACKGROUND: We investigated the roles of Toll-like receptors (TLRs) in naturally occurring influenza. METHODS: A prospective, case - control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset <48 hours, before treatment) were compared with age-/gender-matched controls. TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs - total, myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of RLRs (RIG-1, MDA-5) was evaluated using real-time PCR. Concomitant signaling molecules expression, plasma cytokine/chemokine concentrations, and respiratory tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with TLR-specific ligands for cytokine responses. RESULTS: Forty two patients with influenza (24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients' mean age was 68 ± 16 years; 81% had respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: -0.46 to -0.69 for TLR9, TLR8, and TLR3; P-values <0.05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho-MAPKs, IκB) and inflammatory cytokines (IL-6, sTNFR-1, CCL2/MCP-1; CXCL10/IP-10, IFN-γ) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls. CONCLUSIONS: Our results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza.

Influenza B lineage circulation and hospitalization rates in a subtropical city, Hong Kong, 2000-2010.

BACKGROUND: A need for quadrivalent vaccines to cover both lineages of influenza B has been raised. Information on the circulation status of influenza B lineages and the associated hospitalization rates is important to assist evidence-based decision making. This retrospective study revealed the situation in a subtropical city over a 10-year period. METHODS: Sequences of 268 influenza B isolates were analyzed to identify the circulating pool of virus lineages for each year. Hospital records and population census data were used to estimate annual age-specific hospitalization rates. RESULTS: Cocirculation with 2 influenza B lineages was found in 9 of the 10 years. Only in 6 of the 10 years had the vaccine strain successfully matched with the lineage that was found in >50% of the circulating pool. Six years were predominated by one lineage (occupying >80% of the circulating pool), and these years had higher (average, 1.4-fold) hospitalization rates. Matching between vaccine and circulating lineage was achieved only in 2 of the 6 "predominated years." The Yamagata lineage accounted for most (5/6) of the predominated years. Overall, 24% of influenza admissions were due to influenza B, and influenza B contributed to a higher proportion (41.9%) among children and young teenagers (5-14 years old). CONCLUSIONS: Cocirculation with 2 influenza B lineages is common in the subtropical region. To predict the next predominant lineage proves to be difficult. Influenza B accounts for a substantial fraction of influenza-associated hospitalizations, especially among children and young teenagers. Quadrivalent vaccines may improve the effectiveness of influenza vaccination programs.

Seroprevalence of hepatitis E virus in Hong Kong, 2008-2009.

The public health impact of hepatitis E virus (HEV) infection varies across the world. An HEV vaccine has been recently approved for clinical use in China. Population-specific seroprevalence data are essential for cost-effective assessment of vaccination programs. Here, a cross-sectional study was performed to provide an update on the local seroprevalence of HEV. An archive of serum samples submitted for virological investigation between 2008 and 2009 to a general hospital was used. A total of 450 samples with equal numbers from each gender covering the age groups from 1-10 to >80 years (25 samples per group) were tested for HEV immunoglobulin G (IgG) by enzyme-linked immunoassay. Age- and gender-specific seroprevalence were determined. The HEV IgG positive rate increased from 8% among 1-10 years to 56% among >80 years. The increase in prevalence was constant throughout all age groups without a steeper slope or plateau observed from any age group. The overall positive rate among males was significantly higher than among females (32.9% vs. 24.4%, P = 0.048). The best-fitted seroprevalence curves also suggested a higher positive rate for males across all age groups. Increased HEV IgG positivity was noted in comparison with historical local studies. Collectively, the prevalence of HEV in Hong Kong has increased over the past decade. A large proportion of the population is still susceptible to infection, and all age groups are at risk. Territory-wide vaccination program should be considered.

A "pre-seasonal" hospital outbreak of influenza pneumonia caused by the drift variant A/Victoria/361/2011-like H3N2 viruses, Hong Kong, 2011.

BACKGROUND: Beginning from late 2011 and early 2012, increasing circulation of antigenically drifted influenza A/Victoria/361/2011-like H3N2 viruses within genotype 3 of the A/Victoria/208/2009 clade have been reported in multiple European countries and elsewhere. Whether these emerging viruses are associated with increased disease severity is unclear. OBJECTIVES: To report the clinical and virological findings of a moderately severe hospital outbreak of A/Victoria/361/2011-like viruses that occurred in November 2011 in Hong Kong. STUDY DESIGN: Clinical and virological hospital outbreak investigation. RESULTS: The outbreak occurred in an adult psychiatric ward in November 2011, a time well before the usual local seasonal influenza winter peak. Altogether, 7 patients and 1 healthcare-worker were affected (mean age, 47 [range, 34-61] years). The attack rates among patients and healthcare-workers were 33% (7/21) and 7% (1/15), respectively. Pneumonia developed in 38% (3/8) of cases; none had underlying immunocompromised conditions. High nasopharyngeal viral loads were detected. All cases responded to antiviral treatment. Multiple amino acid mutations with reference to earlier A(H3N2) vaccine strains were mapped to key antigenic sites on hemagglutinin; however, no critical mutations on receptor binding sites were detected. Viral sequence variations jeopardized the performance of molecular diagnostic assays. CONCLUSIONS: Severe disease and pneumonia occurred in a substantial proportion of non-immunocompromised adults in a hospital outbreak attributed to the emerging antigenically drifted A/Victoria/361/2011-like H3N2 viruses. Close monitoring of the transmission of this drift variant is required. Further studies are also necessary to determine virus virulence.

Polymerase activity of hybrid ribonucleoprotein complexes generated from reassortment between 2009 pandemic H1N1 and seasonal H3N2 influenza A viruses.

BACKGROUND: A novel influenza virus (2009 pdmH1N1) was identified in early 2009 and progressed to a pandemic in mid-2009. This study compared the polymerase activity of recombinant viral ribonucleoprotein (vRNP) complexes derived from 2009 pdmH1N1 and the co-circulating seasonal H3N2, and their possible reassortants. RESULTS: The 2009 pdmH1N1 vRNP showed a lower level of polymerase activity at 33°C compared to 37°C, a property remenisence of avian viruses. The 2009 pdmH1N1 vRNP was found to be more cold-sensitive than the WSN or H3N2 vRNP. Substituion of 2009 pdmH1N1 vRNP with H3N2-derived-subunits, and vice versa, still retained a substantial level of polymerase activity, which is probably compartable with survival. When the 2009 pdmH1N1 vRNP was substituted with H3N2 PA, a significant increase in activity was observed; whereas when H3N2 vRNP was substituted with 2009 pdmH1N1 PA, a significant decrease in activity occurred. Although, the polymerase basic protein 2 (PB2) of 2009 pdmH1N1 was originated from an avian virus, substitution of this subunit with H3N2 PB2 did not change its polymerase activity in human cells. CONCLUSIONS: In conclusion, our data suggest that hybrid vRNPs resulted from reassortment between 2009 pdmH1N1 and H3N2 viruses could still retain a substantial level of polymerase activity. Substituion of the subunit PA confers the most prominent effect on polymerase activity. Further studies to explore the determinants for polymerase activity of influenza viruses in associate with other factors that limit host specificity are warrant.

Seasonal influenza A virus in feces of hospitalized adults.

In a cohort of hospitalized adults with seasonal influenza A in Hong Kong, viral RNA was frequently (47%) detected in stool specimens. Viable virus was rarely isolated. Viral RNA positivity had little correlation with gastrointestinal symptoms and outcomes. In vitro studies suggested low potential for seasonal influenza viruses to cause direct intestinal infections.

Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.

BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1) influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation). Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years), and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%), although severe pneumonia with hypoxemia (54.0% vs 28.3%) and ICU admissions (25.4% vs 1.9%) were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal) and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17)-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01). This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10)unit increase; P = 0.002), and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01) in influenza infections. PBMCs in seasonal influenza patients were activated and expressed cytokines ex vivo (e.g. IL-6, CXCL8/IL-8, CCL2/MCP-1, CXCL10/IP-10, CXCL9/MIG); their 'responsiveness' to stimuli was shown to change dynamically during the illness course. CONCLUSIONS: A hyperactivated proinflammatory, but suppressed adaptive-immunity (Th1/Th17)-related cytokine response pattern was found in severe pH1N1 pneumonia, different from seasonal influenza. Cytokine/immune-dysregulation may be important in its pathogenesis.

Seroprevalence of varicella zoster virus among pregnant women in Hong Kong: comparison with self-reported history.

OBJECTIVE: To compare seroprevalence (serum IgG titre) with self-reported history of varicella zoster virus (VZV) infection among pregnant women in Hong Kong. METHODS: Pregnant women undergoing first trimester Down screening over a 3-months period were recruited for the study. RESULTS: Positive immunity was found in 477 (95.4%) of the 500 recruited women, and those with positive, negative, or uncertain history of infection had similarly high seroprevalence (96.4, 90.5, 95.9% respectively). The mean age of infection from self-recalled history was 8.61 (SD 4.69) years, and only 3% recalled infection after age 18. Insufficient knowledge on the disease and vaccination was demonstrated. CONCLUSIONS: Despite the absence of a routine vaccination programme, VZV immunity was high among pregnant women, the majority being infected during childhood and infection above age 18 was very rare. Hence, universal antenatal screening or vaccination for all women in the reproductive age would not be cost-effective in Hong Kong.

Seasonal influenza vaccination predicts pandemic H1N1 vaccination uptake among healthcare workers in three countries.

The aim of this study was to identify the common barriers and facilitators for acceptance of pandemic influenza vaccination across different countries. This study utilized a standardized, anonymous, self-completed questionnaire-based survey recording the demographics and professional practice, previous experience and perceived risk and severity of influenza, infection control practices, information of H1N1 vaccination, acceptance of the H1N1 vaccination and reasons of their choices and opinions on mandatory vaccination. Hospital-based doctors, nurses and allied healthcare workers in Hong Kong (HK), Singapore (SG) and Leicester, United Kingdom (UK) were recruited. A total of 6318 (HK: 5743, SG: 300, UK: 275) questionnaires were distributed, with response rates of 27.1% (HK), 94.7% (SG) and 94.5% (UK). The uptake rates for monovalent 2009 pandemic H1N1 vaccine were 13.5% (HK), 36.2% (SG) and 41.3% (UK). The single common factor associated with vaccine acceptance across all sites was having seasonal influenza vaccination in 2009. In UK and HK, overestimation of side effect reduced vaccination acceptance; and fear of side effect was a significant barrier in all sites. In HK, healthcare workers with more patient contact were more reluctant to accept vaccination. Drivers for vaccination in UK and HK were concern about catching the infection and following advice from health authority. Only a small proportion of respondents agreed with mandatory pandemic influenza vaccination (HK: 25% and UK: 42%), except in Singapore where 75.3% were in agreement. Few respondents (<5%) chose scientific publications as their primary source of information, but this group was more likely to receive vaccination. The acceptance of pandemic vaccine among healthcare workers was poor (13-41% of respondents). Breaking barriers to accept seasonal influenza vaccination should be part of the influenza pandemic preparedness plan. Mandatory vaccination even during pandemic is likely to arouse substantial discontent.

Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza?

BACKGROUND: It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza. METHODS: A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754). RESULTS: Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age <35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%; >65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P < .001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes. CONCLUSIONS: Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival.

Possible role of aerosol transmission in a hospital outbreak of influenza.

BACKGROUND: We examined the role of aerosol transmission of influenza in an acute ward setting. METHODS: We investigated a seasonal influenza A outbreak that occurred in our general medical ward (with open bay ward layout) in 2008. Clinical and epidemiological information was collected in real time during the outbreak. Spatiotemporal analysis was performed to estimate the infection risk among patients. Airflow measurements were conducted, and concentrations of hypothetical virus-laden aerosols at different ward locations were estimated using computational fluid dynamics modeling. RESULTS: Nine inpatients were infected with an identical strain of influenza A/H3N2 virus. With reference to the index patient's location, the attack rate was 20.0% and 22.2% in the "same" and "adjacent" bays, respectively, but 0% in the "distant" bay (P = .04). Temporally, the risk of being infected was highest on the day when noninvasive ventilation was used in the index patient; multivariate logistic regression revealed an odds ratio of 14.9 (95% confidence interval, 1.7-131.3; P = .015). A simultaneous, directional indoor airflow blown from the "same" bay toward the "adjacent" bay was found; it was inadvertently created by an unopposed air jet from a separate air purifier placed next to the index patient's bed. Computational fluid dynamics modeling revealed that the dispersal pattern of aerosols originated from the index patient coincided with the bed locations of affected patients. CONCLUSIONS: Our findings suggest a possible role of aerosol transmission of influenza in an acute ward setting. Source and engineering controls, such as avoiding aerosol generation and improving ventilation design, may warrant consideration to prevent nosocomial outbreaks.