Influenza-associated mortality in Yancheng, China, 2011-15

Introduction: The Yangtze river delta in eastern China, centred on Shanghai, is one of the most populated regions of the world with more than 100 million residents. We examined the impact of influenza on excess mortality in Yancheng, a prefecture-level city with 8.2 million population located 250km north of Shanghai, during 2011-2015. Methods: We obtained individual data on deaths by date, age, sex and cause in Yancheng from the Chinese Centers for Disease Control and Prevention, and used these to derive weekly rates of mortality from respiratory causes, respiratory and cardiovascular causes combined, and all causes. We used data on influenza-like illnesses and laboratory detections of influenza to construct a proxy measure of the weekly incidence of influenza virus infections in the community. We used regression models to estimate the association of influenza activity with mortality and excess mortality by age, cause and influenza type/subtype. Results: We estimated that an annual average of 4.59 (95% confidence interval: 3.94, 7.41) excess respiratory deaths per 100,000 persons were associated with influenza, which was 4.6% of all respiratory deaths in the years studied. Almost all influenza-associated excess deaths occurred in persons ≥65 years. Influenza A(H3N2) had the greatest impact on mortality and was associated with around 50% of the influenza-associated respiratory deaths in the 5 years studied. Conclusions: Influenza has a substantial impact on respiratory mortality in Yancheng, mainly in older adults. Influenza vaccination has the potential to reduce disease burden, and cost-effectiveness analysis could be used to compare policy options.published_or_final_versio

Quantification of Influenza Virus RNA in Aerosols in Patient Rooms

The potential for human influenza viruses to spread through fine particle aerosols remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital rooms. METHODS AND FINDINGS: We sampled the air in 2-bed patient isolation rooms for four hours, placing cyclone samplers at heights of 1.5m and 1.0m. We collected ten air samples each in the presence of at least one patient with confirmed influenza A virus infection, and tested the samples by reverse transcription polymerase chain reaction. We recovered influenza A virus RNA from 5/10 collections (50%); 4/5 were from particles>4 μm, 1/5 from 1-4 μm, and none in particles<1 μm. CONCLUSIONS: Detection of influenza virus RNA in aerosols at low concentrations in patient rooms suggests that healthcare workers and visitors might have frequent exposure to airborne influenza virus in proximity to infected patients. A limitation of our study was the small sample size. Further studies should be done to quantify the concentration of viable influenza virus in healthcare settings, and factors affecting the detection of influenza viruses in fine particles in the air.published_or_final_versio

The Hurdles From Bench to Bedside in the Realization and Implementation of a Universal Influenza Vaccine

Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements in vaccine design are needed to increase the strength, breadth, and duration of immunity against diverse strains that circulate during regular epidemics, occasional pandemics, and from animal reservoirs. Universal vaccine strategies that target more conserved regions of the virus, such as the hemagglutinin (HA)-stalk, or recruit other cellular responses, such as T cells and NK cells, have the potential to provide broader immunity. Many pre-pandemic vaccines in clinical development do not utilize new vaccine platforms but use "tried and true" recombinant HA protein or inactivated virus strategies despite substantial leaps in fundamental research on universal vaccines. Significant hurdles exist for universal vaccine development from bench to bedside, so that promising preclinical data is not yet translating to human clinical trials. Few studies have assessed immune correlates derived from asymptomatic influenza virus infections, due to the scale of a study required to identity these cases. The realization and implementation of a universal influenza vaccine requires identification and standardization of set points of protective immune correlates, and consideration of dosage schedule to maximize vaccine uptake

Viral shedding and transmission potential of asymptomatic and pauci-symptomatic influenza virus infections in the community

Influenza virus infections are associated with a wide spectrum of disease. However, few studies have investigated in detail the epidemiology and virology of asymptomatic and mild illness with influenza virus infections. METHODS: In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals who were household contacts of symptomatic persons with laboratory-confirmed influenza, to identify secondary infections. Information from daily symptom diaries was used to classify infections as symptomatic (with at least two signs/symptoms of: fever ≥37.8°C, headache, myalgia, cough, sore throat, runny nose and sputum), pauci-symptomatic (with one symptom only), or asymptomatic (reporting none of these symptoms). We compared the patterns of influenza viral shedding between these groups. RESULTS: We identified 235 virologically-confirmed secondary cases of influenza virus infection in the household setting, including 31 (13%) pauci-symptomatic and 25 (11%) asymptomatic cases. The duration of viral RNA shedding was shorter and declined more rapidly in pauci-symptomatic and asymptomatic cases compared with symptomatic cases. The mean levels of influenza viral RNA shedding in asymptomatic and pauci-symptomatic cases were approximately 1 to 2 log10 copies lower than in symptomatic cases. CONCLUSIONS: The presence of influenza viral shedding in influenza patients with very few or no symptoms reflects their potential for transmitting the virus to close contacts. These findings suggest that further research is needed to investigate the contribution of persons with asymptomatic or clinically mild influenza virus infections to influenza virus transmission in household, institutional, and community settings

Influenza virus RNA in aerosols in patient rooms

Parallel Session 6: New Advances in Diagnostic

Diagnostic performance of the Sofia Analyzer in outpatient clinics

Poster Sessions: no. P-496BACKGROUND: Rapid influenza diagnostic tests (RIDTs) are frequently used to allow timely indication of influenza virus infections at the point of care, informing clinical management and infection control measures. The objective of our study was to assess the diagnostic accuracy of the Sofia Influenza A+B Fluorescent Immunoassay Analyzer (Quidel, San Diego, CA) compared to RTPCR in outpatient clinics. METHOD: We recruited patients with acute respiratory illness (ARI) from January 2013 through April 2015 in outpatient clinics in Hong Kong. ARI was defined as having ≥2 of the following signs or symptoms: fever ≥37.8°C, cough, sore throat, runny nose, headache, myalgia and phlegm. Two respiratory specimens were collected from each participant for testing by the Sofia Analyzer according to the manufacturer’s instructions and subsequent testing by quantitative RT-PCR for influenza A and B respectively. We estimated the point estimates and the exact binomial 95% confidence intervals for the measures of diagnostic accuracy for the Sofia RIDT; and assessed the associations of the covariates including viral load and age with the result of the RIDT by logistic regression. RESULTS: Data were available from 1230 outpatients. The Sofia RIDT had an overall sensitivity of 77% (95% CI 71-82%) and specificity of 91% (95% CI 89-92%) for influenza virus infection confirmed to RT-PCR; a sensitivity and specificity of 74% (95% CI 68-81%) and 97% (95% CI 96-98%) for influenza A, and 77% (95% CI 63-87%) and 94% (95% CI 92-95%) for influenza B respectively. The Sofia RIDT had a threshold for high sensitivity at viral loads 5 log10 copies/ml or above for both Influenza A and B. Viral load remained significantly associated with a positive RIDT result after adjusting for days since symptom onset, age and sex (adjusted OR: 1.98, 95% CI: 1.83-2.15). A prevalence of influenza of 22% would be required for the Sofia RIDT to correctly detect more than 70% of influenza virus infections while a prevalence of 10% would give the test a positive predictive value of 49%. CONCLUSION: Compared to other RIDTs, the estimated sensitivity and specificity for Sofia RIDT is considered high and moderate respectively, and has good positive predictive value during influenza epidemics

Assessment of enhanced influenza vaccination finds that FluAd conveys an advantage in mice and older adults

OBJECTIVES: Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S-IIV). METHODS: We tested four vaccines in parallel, FluZone high dose, FluBlok and FluAd versus S-IIV in a randomised controlled trial of older adults and in a mouse infection model to assess immunogenicity, protection from lethal challenge and mechanisms of action. RESULTS: In older adults, FluAd vaccination stimulated a superior antibody profile, including H3-HA antibodies that were elevated for up to 1 year after vaccination, higher avidity H3HA IgG and larger HA stem IgG responses. In a mouse model, FluAd also elicited an earlier and larger induction of HA stem antibodies with increased germinal centre responses and upregulation and long-term expression of B-cell switch transcription factors. Long-term cross-reactive memory responses were sustained by FluAd following lethal heterosubtypic influenza challenge, with reduced lung damage and viral loads, coinciding with increased T- and B-cell recall. Advantages were also noted for the high-dose FluZone vaccine in both humans and mice. CONCLUSION: The early, broadly reactive and long-lived antibody response of FluAd indicates a potential advantage of this vaccine, particularly in years when there is a mismatch between the vaccine strain and the circulating strain of influenza viruses

Quantification of influenza virus RNA in aerosols in pediatrics patient rooms

Poster Sessions: no. P-101BACKGROUND: Children are considered as the key driver of influenza transmission, and the potential for human influenza viruses to spread through fine particle aerosols from children remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital pediatrics patient rooms. METHOD: We sampled the air in 5-bed pediatrics patient rooms for four hours, placing two cyclone air samplers at different distances from the bed with pediatrics patient with laboratory-confirmed influenza infection. We collected air samples in 3 size fractions, and tested the samples by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: We collected air samples in 10 occasions with at least one pediatrics patient with laboratory-confirmed influenza infection in the patient room. We recovered influenza A virus RNA from 7/10 collections (70%): influenza A virus RNA can be recovered in particles>4µm in 7/10, in particles 1-4µm in 3/10, and in particles<1µm in 4/10 collections. CONCLUSION: Frequent detection of influenza virus RNA in aerosols in the proximity of pediatric patients suggests that children could have an important contribution to influenza transmission via the aerosol route