Epidemiological Characteristics of Influenza A and B in Macau, 2010–2018

Virologica Sinica - Influenza is one of the major respiratory diseases in humans. Macau is a tourist city with high density of population and special population mobility. The study on the...     

Influenza Illness and Hospitalizations Averted by Influenza Vaccination in the United States, 2005–2011

Context

The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits.

Objective

To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons.

Design

Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination).

Results

We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage.

Conclusions

Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.     

Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010–11 Seasons: A Test-negative Observational Study

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.     

Influenza Vaccination Guidelines and Vaccine Sales in Southeast Asia: 2008–2011

Background

Southeast Asia is a region with great potential for the emergence of a pandemic influenza virus. Global efforts to improve influenza surveillance in this region have documented the burden and seasonality of influenza viruses and have informed influenza prevention strategies, but little information exists about influenza vaccination guidelines and vaccine sales.

Methods

To ascertain the existence of influenza vaccine guidelines and define the scope of vaccine sales, we sent a standard three-page questionnaire to the ten member nations of the Association of Southeast Asian Nations. We also surveyed three multinational manufacturers who supply influenza vaccines in the region.

Results

Vaccine sales in the private sector were <1000 per 100,000 population in the 10 countries. Five countries reported purchasing vaccine for use in the public sector. In 2011, Thailand had the highest combined reported rate of vaccine sales (10,333 per 100,000). In the 10 countries combined, the rate of private sector sales during 2010–2011 (after the A(H1N1)2009pdm pandemic) exceeded 2008 pre-pandemic levels. Five countries (Indonesia, Malaysia, Singapore, Thailand and Vietnam) had guidelines for influenza vaccination but only two were consistent with global guidelines. Four recommended vaccination for health care workers, four for elderly persons, three for young children, three for persons with underlying disease, and two for pregnant women.

Conclusions

The rate of vaccine sales in Southeast Asia remains low, but there was a positive impact in sales after the A(H1N1)2009pdm pandemic. Low adherence to global vaccine guidelines suggests that more work is needed in the policy arena.     

Estimating Influenza Deaths in Canada, 1992–2009

Background

Poisson regression modelling has been widely used to estimate the disease burden attributable to influenza, though not without concerns that some of the excess burden could be due to other causes. This study aims to provide annual estimates of the mortality and hospitalization burden attributable to both seasonal influenza and the 2009 A/H1N1 pandemic influenza for Canada, and to discuss issues related to the reliability of these estimates.

Methods

Weekly time-series for all-cause mortality and regression models were used to estimate the number of deaths in Canada attributable to influenza from September 1992 to December 2009. To assess their robustness, the annual estimates derived from different parameterizations of the regression model for all-cause mortality were compared. In addition, the association between the annual estimates for mortality and hospitalization by age group, underlying cause of death or primary reason for admission and discharge status is discussed.

Results

The crude influenza-attributed mortality rate based on all-cause mortality and averaged over 17 influenza seasons prior to the 2009 A/H1N1 pandemic was 11.3 (95%CI, 10.5 - 12.1) deaths per 100 000 population per year, or an average of 3,500 (95%CI, 3,200 - 3,700) deaths per year attributable to seasonal influenza. The estimated annual rates ranged from undetectable at the ecological level to more than 6000 deaths per year over the three A/Sydney seasons. In comparison, we attributed an estimated 740 deaths (95%CI, 350–1500) to A(H1N1)pdm09. Annual estimates from different model parameterizations were strongly correlated, as were estimates for mortality and morbidity; the higher A(H1N1)pdm09 burden in younger age groups was the most notable exception.

Interpretation

With the exception of some of the Serfling models, differences in the ecological estimates of the disease burden attributable to influenza were small in comparison to the variation in disease burden from one season to another.     

Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

Background

Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010.

Methods

We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR.

Results

Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3).

Conclusions

Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children.     

Influenza and Other Respiratory Viruses Detected by Influenza-Like Illness Surveillance in Leyte Island,the Philippines, 2010–2013

This study aimed to determine the role of influenza-like illness (ILI) surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6%) cases. Among the cases sampled, 1,637 (75.6%) were children aged <5 years. 874 (43.0%) cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV) were predominantly detected (both were 25.7%) followed by human rhinovirus (HRV) (17.5%). The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%). In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively.     

Relationship between Humidity and Influenza A Viability in Droplets and Implications for Influenza’s Seasonality

Humidity has been associated with influenza’s seasonality, but the mechanisms underlying the relationship remain unclear. There is no consistent explanation for influenza’s transmission patterns that applies to both temperate and tropical regions. This study aimed to determine the relationship between ambient humidity and viability of the influenza A virus (IAV) during transmission between hosts and to explain the mechanisms underlying it. We measured the viability of IAV in droplets consisting of various model media, chosen to isolate effects of salts and proteins found in respiratory fluid, and in human mucus, at relative humidities (RH) ranging from 17% to 100%. In all media and mucus, viability was highest when RH was either close to 100% or below ∼50%. When RH decreased from 84% to 50%, the relationship between viability and RH depended on droplet composition: viability decreased in saline solutions, did not change significantly in solutions supplemented with proteins, and increased dramatically in mucus. Additionally, viral decay increased linearly with salt concentration in saline solutions but not when they were supplemented with proteins. There appear to be three regimes of IAV viability in droplets, defined by humidity: physiological conditions (∼100% RH) with high viability, concentrated conditions (50% to near 100% RH) with lower viability depending on the composition of media, and dry conditions (<50% RH) with high viability. This paradigm could help resolve conflicting findings in the literature on the relationship between IAV viability in aerosols and humidity, and results in human mucus could help explain influenza’s seasonality in different regions.     

Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010

Background

Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model.

Methods

A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated.

Results

The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10–20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10–20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups.

Conclusion

This analysis suggests that over half the people vaccinated against A/H1N1p in Norway during the 2009 pandemic may already have been infected by A/H1N1p before being vaccinated.     

Influenza Hemifusion Phenotype Depends on Membrane Context: Differences in Cell–Cell and Virus–Cell Fusion

Influenza viral entry into the host cell cytoplasm is accomplished by a process of membrane fusion mediated by the viral hemagglutinin protein. Hemagglutinin acts in a pH-triggered fashion, inserting a short fusion peptide into the host membrane followed by refolding of a coiled-coil structure to draw the viral envelope and host membranes together. Mutations to this fusion peptide provide an important window into viral fusion mechanisms and protein–membrane interactions. Here, we show that a well-described fusion peptide mutant, G1S, has a phenotype that depends strongly on the viral membrane context. The G1S mutant is well known to cause a “hemifusion” phenotype based on experiments in transfected cells, where cells expressing G1S hemagglutinin can undergo lipid mixing in a pH-triggered fashion similar to virus but will not support fusion pores. We compare fusion by the G1S hemagglutinin mutant expressed either in cells or in influenza virions and show that this hemifusion phenotype occurs in transfected cells but that native virions are able to support full fusion, albeit at a slower rate and 10–100 × reduced infectious titer. We explain this with a quantitative model where the G1S mutant, instead of causing an absolute block of fusion, alters the protein stoichiometry required for fusion. This change slightly slows fusion at high hemagglutinin density, as on the viral surface, but at lower hemagglutinin density produces a hemifusion phenotype. The quantitative model thus reproduces the observed virus–cell and cell–cell fusion phenotypes, yielding a unified explanation where membrane context can control the observed viral fusion phenotype.     

Influenza Excess Mortality from 1950–2000 in Tropical Singapore

Introduction

Tropical regions have been shown to exhibit different influenza seasonal patterns compared to their temperate counterparts. However, there is little information about the burden of annual tropical influenza epidemics across time, and the relationship between tropical influenza epidemics compared with other regions.

Methods

Data on monthly national mortality and population was obtained from 1947 to 2003 in Singapore. To determine excess mortality for each month, we used a moving average analysis for each month from 1950 to 2000. From 1972, influenza viral surveillance data was available. Before 1972, information was obtained from serial annual government reports, peer-reviewed journal articles and press articles.

Results

The influenza pandemics of 1957 and 1968 resulted in substantial mortality. In addition, there were 20 other time points with significant excess mortality. Of the 12 periods with significant excess mortality post-1972, only one point (1988) did not correspond to a recorded influenza activity. For the 8 periods with significant excess mortality periods before 1972 excluding the pandemic years, 2 years (1951 and 1953) had newspaper reports of increased pneumonia deaths. Excess mortality could be observed in almost all periods with recorded influenza outbreaks but did not always exceed the 95% confidence limits of the baseline mortality rate.

Conclusion

Influenza epidemics were the likely cause of most excess mortality periods in post-war tropical Singapore, although not every epidemic resulted in high mortality. It is therefore important to have good influenza surveillance systems in place to detect influenza activity.     

The Effect of Age and Recent Influenza Vaccination History on the Immunogenicity and Efficacy of 2009–10 Seasonal Trivalent Inactivated Influenza Vaccination in Children

Background

There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.

Methods and Findings

We conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history.

Conclusions

Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.     

The Burden of Influenza and RSV among Inpatients and Outpatients in Rural Western Kenya, 2009–2012

Background

In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources.

Methods

We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested.

Results

The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8–3.9) among children <5 years and 0.3 (95% CI 0.2–0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0–6.8) among children <5 years and 0.1 (95% CI 0.0–0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6–34.7) among children <5 years and 3.8 (95% CI 2.6–5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0–35.4) among children <5 years and 0.8 (95% CI 0.3–1.9) among persons ≥5 years.

Conclusions

Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.     

Avian Influenza Virus Surveillance in Wild Birds in Georgia: 2009–2011

The Caucasus, at the border of Europe and Asia, is important for migration and over-wintering of wild waterbirds. Three flyways, the Central Asian, East Africa-West Asia, and Mediterranean/Black Sea flyways, converge in the Caucasus region. Thus, the Caucasus region might act as a migratory bridge for influenza virus transmission when birds aggregate in high concentrations in the post-breeding, migrating and overwintering periods. Since August 2009, we have established a surveillance network for influenza viruses in wild birds, using five sample areas geographically spread throughout suitable habitats in both eastern and western Georgia. We took paired tracheal and cloacal swabs and fresh feces samples. We collected 8343 swabs from 76 species belonging to 17 families in 11 orders of birds, of which 84 were real-time RT-PCR positive for avian influenza virus (AIV). No highly pathogenic AIV (HPAIV) H5 or H7 viruses were detected. The overall AIV prevalence was 1.6%. We observed peak prevalence in large gulls during the autumn migration (5.3–9.8%), but peak prevalence in Black-headed Gulls in spring (4.2–13%). In ducks, we observed increased AIV prevalence during the autumn post-moult aggregations and migration stop-over period (6.3%) but at lower levels to those observed in other more northerly post-moult areas in Eurasia. We observed another prevalence peak in the overwintering period (0.14–5.9%). Serological and virological monitoring of a breeding colony of Armenian Gulls showed that adult birds were seropositive on arrival at the breeding colony, but juveniles remained serologically and virologically negative for AIV throughout their time on the breeding grounds, in contrast to gull AIV data from other geographic regions. We show that close phylogenetic relatives of viruses isolated in Georgia are sourced from a wide geographic area throughout Western and Central Eurasia, and from areas that are represented by multiple different flyways, likely linking different host sub-populations.     

Mortality and Life Expectancy in Homeless Men and Women in Rotterdam: 2001–2010

Background

Data on mortality among homeless people are limited. Therefore, this study aimed to describe mortality patterns within a cohort of homeless adults in Rotterdam (the Netherlands) and to assess excess mortality as compared to the general population in that city.

Methods

Based on 10-year follow-up of homeless adults aged ≥ 20 years who visited services for homeless people in Rotterdam in 2001, and on vital statistics, we assessed the association of mortality with age, sex and type of service used (e.g. only day care, convalescence care, other) within the homeless cohort, and also compared mortality between the homeless and general population using Poisson regression. Life tables and decomposition methods were used to examine differences in life expectancy.

Results

During follow-up, of the 2096 adult homeless 265 died. Among the homeless, at age 30 years no significant sex differences were found in overall mortality rates and life expectancy. Compared with the general Rotterdam population, mortality rates were 3.5 times higher in the homeless cohort. Excess mortality was larger in women (rate ratio [RR] RR 5.56, 95% CI 3.95–7.82) as compared to men (RR 3.31, 95% CI 2.91–3.77), and decreased with age (RR 7.67, 95% CI 6.87–8.56 for the age group 20–44 and RR 1.63, 95% CI 1.41–1.88 for the age group 60+ years). Life expectancy at age 30 years was 11.0 (95% CI 9.1–12.9) and 15.9 (95% CI 10.3–21.5) years lower for homeless men and women compared to men and women in the general population respectively.

Conclusion

Homeless adults face excessive losses in life expectancy, with greatest disadvantages among homeless women and the younger age groups.     

Molecular Epidemiology and Vaccine Compatibility Analysis of Seasonal Influenza Viruses in Wuhan, 2016–2019

Virologica Sinica - Influenza viruses (FLUV) cause high morbidity and mortality annually in the world and pose a serious threat to the public health. Wuhan, as an important transportation hub in...     

Spatial,Temporal and Genetic Dynamics Characteristics of Influenza B Viruses in China, 1973–2018

Annual influenza B virus epidemics and outbreaks cause severe influenza diseases in humans and pose a threat to public health. China is an important epidemic area of influenza B viruses. However, the spatial, temporal transmission pathways and the demography history of influenza B viruses in China remain unknown. We collected the haemagglutinin gene sequences sampled of influenza B virus in China between 1973 and 2018. A Bayesian Markov chain Monte Carlo phylogeographic discrete approach was used to infer the spatial and temporal phylodynamics of influenza B virus. The Bayesian phylogeographic analysis of influenza B viruses showed that the North subtropical and South subtropical zones are the origins of the Victoria and Yamagata lineage viruses, respectively. Furthermore, the South temperate and North subtropical zones acted as transition nodes in the Victoria lineage virus dispersion network and that the North subtropical and Mid subtropical zones acted as transition nodes in the Yamagata lineage virus dispersion network. Our findings contribute to the knowledge regarding the spatial and temporal patterns of influenza B virus outbreaks in China.