Protective essential oil attenuates influenza virus infection: An in vitro study in MDCK cells

<p>Abstract</p> <p>Background</p> <p>Influenza is a significant cause of morbidity and mortality. The recent pandemic of a novel H1N1 influenza virus has stressed the importance of the search for effective treatments for this disease. Essential oils from aromatic plants have been used for a wide variety of applications, such as personal hygiene, therapeutic massage and even medical practice. In this paper, we investigate the potential role of an essential oil in antiviral activity.</p> <p>Methods</p> <p>We studied a commercial essential oil blend, On Guard™, and evaluated its ability in modulating influenza virus, A/PR8/34 (PR8), infection in Madin-Darby canine kidney (MDCK) cells. Influenza virus was first incubated with the essential oil and infectivity in MDCK cells was quantified by fluorescent focus assay (FFA). In order to determine the mechanism of effects of essential oil in viral infection inhibition, we measured hemagglutination (HA) activity, binding and internalization of untreated and oil-treated virus in MDCK cells by flow cytometry and immunofluorescence microscopy. In addition, the effect of oil treatment on viral transcription and translation were assayed by relative end-point RT-PCR and western blot analysis.</p> <p>Results</p> <p>Influenza virus infectivity was suppressed by essential oil treatment in a dose-dependent manner; the number of nascent viral particles released from MDCK cells was reduced by 90% and by 40% when virus was treated with 1:4,000 and 1:6,000 dilutions of the oil, respectively. Oil treatment of the virus also decreased direct infection of the cells as the number of infected MDCK cells decreased by 90% and 45% when virus was treated with 1:2,000 and 1:3,000 dilutions of the oil, respectively. This was not due to a decrease in HA activity, as HA was preserved despite oil treatment. In addition, oil treatment did not affect virus binding or internalization in MDCK cells. These effects did not appear to be due to cytotoxicity of the oil as MDCK cell viability was only seen with concentrations of oil that were 2 to 6 times greater than the doses that inhibited viral infectivity. RT-PCR and western blotting demonstrated that oil treatment of the virus inhibited viral NP and NS1 protein, but not mRNA expression.</p> <p>Conclusions</p> <p>An essential oil blend significantly attenuates influenza virus PR8 infectivity <it>in vitro </it>without affecting viral binding or cellular internalization in MDCK cells. Oil treated virus continued to express viral mRNAs but had minimal expression of viral proteins, suggesting that the antiviral effect may be due to inhibition of viral protein translation.</p

Seasonal Influenza Vaccine Effectiveness among Children Aged 6 to 59 Months in Southern China

In China the protective effect of seasonal influenza vaccine has only been assessed in controlled clinical trials and proven to be highly effective. However, the post-licensure effectiveness of influenza vaccine has not been examined. In our study all influenza cases from the 19 surveillance sites in Guangzhou were laboratory confirmed during 2009 and 2010. Controls were randomly selected from children aged 6 to 59 months in the Children's Expanded Programmed Immunization Administrative Computerized System. 2529 cases and 4539 controls were finally enrolled. After adjusting for gender, age and area of residence, the vaccine effectiveness of full vaccination was 51.79% and 57.78% in the 2009 and 2010 influenza season, respectively. Partial vaccination provided 39.38% and 35.98% protection to children aged 24 to 59 months in 2009 and 2010, respectively, and no protective effect was observed among younger children. Full vaccination is highly protective and partial vaccination is protective for older children. Influenza vaccination in general should be encouraged, and full vaccination should be particularly encouraged because its protective effect is much stronger than that of partial vaccination

Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends

Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections.Influenza activity data from 2003-04 through 2007-08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003-04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90).This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003-04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior

Clinical outcomes of seasonal influenza and pandemic influenza A (H1N1) in pediatric inpatients

<p>Abstract</p> <p>Background</p> <p>In April 2009, a novel influenza A H1N1 (nH1N1) virus emerged and spread rapidly worldwide. News of the pandemic led to a heightened awareness of the consequences of influenza and generally resulted in enhanced infection control practices and strengthened vaccination efforts for both healthcare workers and the general population. Seasonal influenza (SI) illness in the pediatric population has been previously shown to result in significant morbidity, mortality, and substantial hospital resource utilization. Although influenza pandemics have the possibility of resulting in considerable illness, we must not ignore the impact that we can experience annually with SI.</p> <p>Methods</p> <p>We compared the outcomes of pediatric patients ≤18 years of age at a large urban hospital with laboratory confirmed influenza and an influenza-like illness (ILI) during the 2009 pandemic and two prior influenza seasons. The primary outcome measure was hospital length of stay (LOS). All variables potentially associated with LOS based on univariable analysis, previous studies, or hypothesized relationships were included in the regression models to ensure adjustment for their effects.</p> <p>Results</p> <p>There were 133 pediatric cases of nH1N1 admitted during 2009 and 133 cases of SI admitted during the prior 2 influenza seasons (2007-8 and 2008-9). Thirty-six percent of children with SI and 18% of children with nH1N1 had no preexisting medical conditions (p = 0.14). Children admitted with SI had 1.73 times longer adjusted LOS than children admitted for nH1N1 (95% CI 1.35 - 2.13). There was a trend towards more children with SI requiring mechanical ventilation compared with nH1N1 (16 vs.7, p = 0.08).</p> <p>Conclusions</p> <p>This study strengthens the growing body of evidence demonstrating that SI results in significant morbidity in the pediatric population. Pandemic H1N1 received considerable attention with strong media messages urging people to undergo vaccination and encouraging improved infection control efforts. We believe that this attention should become an annual effort for SI. Strong unified messages from health care providers and the media encouraging influenza vaccination will likely prove very useful in averting some of the morbidity related to influenza for future epidemics.</p

Validation of Statistical Models for Estimating Hospitalization Associated with Influenza and Other Respiratory Viruses

BACKGROUND: Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza and adenovirus. METHODS AND FINDINGS: We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization. CONCLUSION: The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong

Comparing estimates of influenza-associated hospitalization and death among adults with congestive heart failure based on how influenza season is defined

<p>Abstract</p> <p>Background</p> <p>There is little consensus about how the influenza season should be defined in studies that assess influenza-attributable risk. The objective of this study was to compare estimates of influenza-associated risk in a defined clinical population using four different methods of defining the influenza season.</p> <p>Methods</p> <p>Using the Studies of Left Ventricular Dysfunction (SOLVD) clinical database and national influenza surveillance data from 1986–87 to 1990–91, four definitions were used to assess influenza-associated risk: (a) three-week moving average of positive influenza isolates is at least 5%, (b) three-week moving average of positive influenza isolates is at least 10%, (c) first and last positive influenza isolate are identified, and (d) 5% of total number of positive isolates for the season are obtained. The clinical data were from adults aged 21 to 80 with physician-diagnosed congestive heart failure. All-cause hospitalization and all-cause mortality during the influenza seasons and non-influenza seasons were compared using four definitions of the influenza season. Incidence analyses and Cox regression were used to assess the effect of exposure to influenza season on all-cause hospitalization and death using all four definitions.</p> <p>Results</p> <p>There was a higher risk of hospitalization associated with the influenza season, regardless of how the start and stop of the influenza season was defined. The adjusted risk of hospitalization was 8 to 10 percent higher during the influenza season compared to the non-influenza season when the different definitions were used. However, exposure to influenza was not consistently associated with higher risk of death when all definitions were used. When the 5% moving average and first/last positive isolate definitions were used, exposure to influenza was associated with a higher risk of death compared to non-exposure in this clinical population (adjusted hazard ratios [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.29 and adjusted HR, 1.19; 95% CI, 1.06 to 1.33, respectively).</p> <p>Conclusion</p> <p>Estimates of influenza-attributable risk may vary depending on how influenza season is defined and the outcome being assessed.</p

Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009

<p>Abstract</p> <p>Background</p> <p>There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness.</p> <p>Methods</p> <p>Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households.</p> <p>Results</p> <p>Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05).</p> <p>Conclusions</p> <p>Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.</p

Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction

In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score ≥11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection

Model Selection in Time Series Studies of Influenza-Associated Mortality

Background: Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and valid estimate for the health impact of influenza. Methods: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. The performance of these criteria was evaluated by the bias and root-mean-square error (RMSE) of estimates from the pre-determined coefficients of influenza proxy variable. These four criteria were subsequently applied to an empirical hospitalization dataset to confirm the findings of simulation study. Results: GCV consistently provided smaller biases and RMSEs for the influenza coefficient estimates than QAIC, QBIC and PACF, under the different simulation scenarios. Sensitivity analysis of different pre-determined influenza coefficients, study periods and lag weeks showed that GCV consistently outperformed the other criteria. Similar results were found in applying these selection criteria to estimate influenza-associated hospitalization. Conclusions: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. These findings shall help standardize the Poisson modeling approach for influenza disease burden studies. © 2012 Wang et al.published_or_final_versio