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Background: Global influenza‐associated acute respiratory infections contribute to 3–5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children < 5 years in developing countries. In Bangladesh, the inadequate availability of nationally representative, robust estimates of influenza‐associated hospitalizations limits allocation of resources for prevention and control measures. Methods: This study used data from the hospital‐based influenza surveillance (HBIS) system in Bangladesh from 2010 to 2019 and healthcare utilization surveys to determine hospital utilization patterns in the catchment area. We estimated annual influenza‐associated hospitalization numbers and rates for all age groups in Bangladesh using WHO methods, adjusted for a 6‐day‐a‐week enrollment schedule, selective testing of specimens from children under five, and healthcare‐seeking behavior, based on the proportion of symptomatic community participants seeking healthcare within the past week. We then estimated national hospitalization rates by multiplying age‐specific hospitalization rates with the corresponding annual national census population. Results: Annual influenza‐associated hospitalization rates per 100,000 population for all ages ranged from 31 (95% CI: 27–36) in 2011 to 139 (95% CI: 130–149) in 2019. Children < 5 years old had the highest rates of influenza‐associated hospitalization, ranging from 114 (95% CI: 90–138) in 2011 to 529 (95% CI: 481–578) in 2019, followed by adults aged ≥ 65 years with rates ranging from 46 (95% CI: 34–57) in 2012 to 252 (95% CI: 213–292) in 2019. The national hospitalization estimates for all ages during 2010–2019 ranged from 47,891 to 236,380 per year. Conclusions: The impact of influenza‐associated hospitalizations in Bangladesh may be considerable, particularly for young children and older adults. Targeted interventions, such as influenza vaccination for these age groups, should be prioritized and evaluated. [ABSTRACT FROM AUTHOR]

Background: Novel influenza viruses pose a potential pandemic risk, and rapid detection of infections in humans is critical to characterizing the virus and facilitating the implementation of public health response measures. Methods: We use a probabilistic framework to estimate the likelihood that novel influenza virus cases would be detected through testing in different community and healthcare settings (urgent care, emergency department, hospital, and intensive care unit [ICU]) while at low frequencies in the United States. Parameters were informed by data on seasonal influenza virus activity and existing testing practices. Results: In a baseline scenario reflecting the presence of 100 novel virus infections with similar severity to seasonal influenza viruses, the median probability of detecting at least one infection per month was highest in urgent care settings (72%) and when community testing was conducted at random among the general population (77%). However, urgent care testing was over 15 times more efficient (estimated as the number of cases detected per 100,000 tests) due to the larger number of tests required for community testing. In scenarios that assumed increased clinical severity of novel virus infection, median detection probabilities increased across all healthcare settings, particularly in hospitals and ICUs (up to 100%) where testing also became more efficient. Conclusions: Our results suggest that novel influenza virus circulation is likely to be detected through existing healthcare surveillance, with the most efficient testing setting impacted by the disease severity profile. These analyses can help inform future testing strategies to maximize the likelihood of novel influenza detection. [ABSTRACT FROM AUTHOR]

Seasonal influenza contributes substantially to acute respiratory disease in Indonesia and across the world. Influenza virus causes [approximately equal to] 3-5 million cases of severe illness (1) and [approximately equal [...]

Background: Global estimates showed an estimate of up to 650,000 seasonal influenza‐associated respiratory deaths annually. However, the mortality rate of seasonal influenza is unknown for most countries in the WHO Eastern Mediterranean Region, including Iran. We aimed to estimate the excess mortality attributable to seasonal influenza in Kerman province, southeast Iran for the influenza seasons 2006/2007–2011/2012. Methods: We applied a Serfling model to the weekly total pneumonia and influenza (PI) mortality rate during winter to define the epidemic periods and to the weekly age‐specific PI, respiratory, circulatory, and all‐cause deaths during non‐epidemic periods to estimate baseline mortality. The excess mortality was calculated as the difference between observed and predicted mortality. Country estimates were obtained by multiplying the estimated annual excess death rates by the populations of Iran. Results: We estimated an annual average excess of 40 PI, 100 respiratory, 94 circulatory, and 306 all‐cause deaths attributable to seasonal influenza in Kerman; corresponding to annual rates of 1.4 (95% confidence interval [CI] 1.1–1.8) PI, 3.6 (95% CI 2.6–4.8) respiratory, 3.4 (95% CI 2.1–5.2) circulatory, and 11.0 (95% CI 7.3–15.6) all‐cause deaths per 100,000 population. Adults ≥75 years accounted for 56% and 53% of all excess respiratory and circulatory deaths, respectively. At country level, we would expect an annual of 1119 PI to 8792 all‐cause deaths attributable to seasonal influenza. Conclusions: Our findings help to define the mortality burden of seasonal influenza, most of which affects adults aged ≥75 years. This study supports influenza prevention and vaccination programs in older adults. [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza‐associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. Method: For Denmark, Spain, and the United States, we estimated age‐stratified excess mortality for (i) all‐cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time‐series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. Results: The respective periods of weekly excess mortality for all‐cause and cause‐specific deaths were similar in their chronological patterns. Seasonal all‐cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3–6.1) and 14.3 (13.0–15.6) per 100,000 population, for the United States; 20.3 (15.8–25.0) and 24.0 (19.3–28.7) per 100,000 population for Denmark; and 22.9 (18.9–26.9) and 52.9 (49.1–56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all‐cause estimates. Discussion We observed fewer influenza‐associated deaths when we examined cause‐specific death categories compared with all‐cause deaths and observed the same trends in peaks in deaths with all death causes. Because all‐cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies. [ABSTRACT FROM AUTHOR]

Background: Data on influenza incidence during pregnancy in China are limited. Methods: From October 2015 to September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow‐up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. Results: In total, we enrolled 18 724 pregnant women median aged 28 years old, 37% in first trimester, 48% in second trimester, and 15% in third trimester, with seven self‐reported influenza vaccination during pregnancy. In the 18‐week epidemic period during October 2015 to September 2016, influenza incidence was 0.7/100 person‐months (95% CI: 0.5–0.9). In the cumulative 29‐week‐long epidemic during October 2016 to September 2017, influenza incidence was 1.0/100 person‐months (95% CI: 0.8–1.2). In the 11‐week epidemic period during October 2017 to September 2018, influenza incidence was 2.1/100 person‐months (95% CI: 1.9–2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza‐associated ARIs were mild, and <5.1% required hospitalization. Conclusions: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy. [ABSTRACT FROM AUTHOR]

Influenza burden estimates are essential to informing prevention and control policies. To complement recent influenza vaccine production capacity in Vietnam, we used acute respiratory infection (ARI) hospitalization data, severe acute respiratory infection (SARI) surveillance data, and provincial population data from 4 provinces representing Vietnam's major regions during 2014-2016 to calculate provincial and national influenza-associated ARI and SARI hospitalization rates. We determined the proportion of ARI admissions meeting the World Health Organization SARI case definition through medical record review. The mean influenza-associated hospitalization rates per 100,000 population were 218 (95% uncertainty interval [UI] 197-238) for ARI and 134 (95% UI 119-149) for SARI. Influenza-associated SARI hospitalization rates per 100,000 population were highest among children <5 years of age (1,123; 95% UI 946-1,301) and adults >65 years of age (207; 95% UI 186-227), underscoring the need for prevention and control measures, such as vaccination, in these at-risk populations. [ABSTRACT FROM AUTHOR]

Background: We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine.Methods: We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017-2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination.Results: Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01-3.38) for A(H1N1) than in those who did not report feverishness.Conclusions: Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population.Clinical Trials Registration: NCT03330132. [ABSTRACT FROM AUTHOR]

Background Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. Methods Community-dwelling older adults aged 65–82 years in Hong Kong were randomly allocated (October 2017–January 2018) to receive 2017–2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. Results Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. Conclusions In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. Clinical Trials Registration NCT03330132. [ABSTRACT FROM AUTHOR]

Background: Influenza causes substantial morbidity and mortality worldwide, however, reliable burden estimates from developing countries are limited, including India. We aimed to quantify influenza-associated mortality for India utilizing 2010-2013 nationally representative data sources for influenza virus circulation and deaths.Methods: Virological data were obtained from the influenza surveillance network of 10 laboratories led by National Institute of Virology, Pune covering eight states from 2010-2013. Death data were obtained from the nationally representative Sample Registration System for the same time period. Generalized linear regression with negative binomial distribution was used to model weekly respiratory and circulatory deaths by age group and proportion of specimens positive for influenza by subtype; excess deaths above the seasonal baseline were taken as an estimate of influenza-associated mortality counts and rates. Annual excess death rates and the 2011 India Census data were used to estimate national influenza-associated deaths.Results: Estimated annual influenza-associated respiratory mortality rates were highest for those ≥65 years (51.1, 95% confidence interval (CI) = 9.2-93.0 deaths/100 000 population) followed by those <5 years (9.8, 95% CI = 0-21.8/100 000). Influenza-associated circulatory death rates were also higher among those ≥65 years (71.8, 95% CI = 7.9-135.8/100 000) as compared to those aged <65 years (1.9, 95% CI = 0-4.6/100 000). Across all age groups, a mean of 127 092 (95% CI = 64 046-190,139) annual influenza-associated respiratory and circulatory deaths may occur in India.Conclusions: Estimated influenza-associated mortality in India was high among children <5 years and adults ≥65 years. These estimates may inform strategies for influenza prevention and control in India, such as possible vaccine introduction. [ABSTRACT FROM AUTHOR]

To detect changes in human-to-human transmission of influenza A(H7N9) virus, we analyzed characteristics of 40 clusters of case-patients during 5 epidemics in China in 2013-2017. Similarities in number and size of clusters and proportion of clusters with probable human-to-human transmission across all epidemics suggest no change in human-to-human transmission risk. [ABSTRACT FROM AUTHOR]

Background: No estimates of influenza‐associated mortality exist for India. Objective: To evaluate national mortality and viral surveillance data from India for assessing their appropriateness in estimating influenza‐associated mortality using varied analytic approaches. Methods: We reviewed influenza virus surveillance data from a national influenza surveillance network. We also reviewed national mortality data from Civil Registration System (CRS), Medical Certification of Cause of Death (MCCD) and the Sample Registration System (SRS). We compared and scored the different sources of mortality data using specific criteria, including the process of cause of death assignment, sample size, proportion of ill‐defined deaths, representativeness and availability of time series data. Each of these 5 parameters was scored on a scale from 1 to 5. To evaluate how to generate an influenza‐associated mortality estimate for India, we also reviewed 4 methodologic approaches to assess the appropriateness of their assumptions and requirements for these data sets. Results: The influenza virus surveillance data included year‐round sample testing for influenza virus and was found to be suitable for influenza mortality estimation modelling. Based on scoring for the 5 mortality data criteria, the SRS data had the highest score with 20 of 25 possible score, whereas MCCD and CRS scored 16 and 12, respectively. The SRS which used verbal autopsy survey methods was determined to be nationally representative and thus adequate for estimating influenza‐associated mortality. Evaluation of the modelling methods demonstrated that Poisson regression, risk difference and mortality multiplier methods could be applied to the Indian setting. Conclusion: Despite significant challenges, it is possible to estimate influenza‐associated mortality in India. [ABSTRACT FROM AUTHOR]

Background: Understanding the burden of influenza‐associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza‐associated SARI rates requires hospital‐based surveillance data and a population‐based denominator, which can be challenging to determine. Objectives: We present an application of the World Health Organization's recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza‐associated SARI, with lessons learned to help others calculate similar estimates. Methods: Using an existing SARI surveillance platform in Cambodia, we counted influenza‐associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual‐derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case‐patients resided. We used HAS methods to adjust the district‐level population denominator for the sentinel site and calculated the incidence rate of influenza‐associated SARI by dividing the number of influenza‐positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned. Results: We estimated an adjusted influenza‐associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza‐associated SARI cases in Svay Rieng Province after extrapolation. Conclusions: Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza‐associated SARI. [ABSTRACT FROM AUTHOR]

Background: H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation. Methods: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation. Results: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission. Conclusion: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus. [ABSTRACT FROM AUTHOR]

Background: The disease burden of influenza in China has not been well described, especially among young children. The aim of this study was to estimate the incidence of outpatient visits associated with influenza in young children in Suzhou, a city of more than 11 million residents in Jiangsu Province in eastern China.Methods: Influenza-like illness (ILI) was defined as the presence of fever (axillary temperature ≥38 °C) and cough or sore throat. We collected throat swabs for children less than 5 years of age with ILI who visited Suzhou University Affiliated Children's Hospital (SCH) outpatient clinic or emergency room between April 2011 and March 2014. Suzhou CDC, a national influenza surveillance network laboratory, tested for influenza viruses by real-time reverse transcription-polymerase chain reaction assay (rRT-PCR). Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza by rRT-PCR. To calculate the incidence of influenza-associated outpatient visits, we conducted community-based healthcare utilization surveys to determine the proportion of hospital catchment area residents who sought care at SCH.Results: The estimated incidence of influenza-associated ILI outpatient visits among children aged <5 years in the catchment area of Suzhou was, per 100 population, 17.4 (95 % CI 11.0-25.3) during April 2011-March 2012, 14.6 (95 % CI 5.2-26.2) during April 2012-March 2013 and 21.4 (95 % CI: 10.9-33.5) during April 2013-March 2014. The age-specific outpatient visit rates of influenza-associated ILI were 4.9, 21.1 and 21.2 per 100 children aged 0- <6 months, 6- <24 months and 24- <60 months, respectively.Conclusion: Influenza virus infection causes a substantial burden of outpatient visits among young children in Suzhou, China. Targeted influenza prevention and control strategies for young children in Suzhou are needed to reduce influenza-associated outpatient visits in this age group. [ABSTRACT FROM AUTHOR]

During February 2013-March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013-May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely. [ABSTRACT FROM AUTHOR]

Background: Influenza A (H1N1)pdm09 (2009 H1N1) re-circulated as the predominant virus from January through February 2011 in China. National surveillance of 2009 H1N1 as a notifiable disease was maintained to monitor potential changes in disease severity from the previous season. Methodology/Principal Findings: To describe the characteristics of hospitalized cases with 2009 H1N1 infection and analyze risk factors for severe illness during the 2010–2011winter season in China, we obtained surveillance data from hospitalized cases with 2009 H1N1 infection from November 2010 through May 2011, and reviewed medical records from 701 hospitalized cases. Age-standardized risk ratios were used to compare the age distribution of patients that were hospitalized and died due to 2009 H1N1 between the 2010–2011winter season to those during the 2009–2010 pandemic period. During the 2010–2011 winter season, children less than 5 years of age had the highest relative risk of hospitalization and death, followed by adults aged 65 years or older. Additionally, the relative risk of hospitalized cases aged 5–14 and 15–24 years was lower compared to children less than 5 years of age. During the winter season of 2010–2011, the proportions of adults aged 25 years or older for hospitalization and death were significantly higher than those during the 2009–2010 pandemic period. Being male, having a chronic medical condition, delayed hospital admission (≥3 days from onset) or delayed initiation of antiviral treatment (≥5 days from onset) were associated with severe illness among non-pregnant patients ≥2 years of age. Conclusions/Significance: We observed a change in high risk groups for hospitalization for 2009 H1N1 during the winter months immediately following the pandemic period compared to the high risk groups identified during the pandemic period. Our nationally notifiable disease surveillance system enabled us to understand the evolving epidemiology of 2009 H1N1 infection after the pandemic period. [ABSTRACT FROM AUTHOR]