Influenza Disease Burden Research Articles

Post-disappearance scenarios: policy implications following the potential disappearance of B/Yamagata lineage influenza viruses.

The COVID-19 pandemic and related preventive measures reduced influenza virus circulation, notably causing the disappearance of the B/Yamagata lineage of influenza viruses. In this Perspective, we discuss the implications that this development may have for global influenza epidemiology, and the adjustments that may need to be implemented concerning surveillance strategies and practices, laboratory safety protocols, and influenza vaccine formulations. The disappearance of the B/Yamagata lineage might indeed alter the dynamics of the influenza disease burden (although in a way that is difficult to predict at the moment), and associated diagnostic practices, and may also necessitate updated biosafety levels and revised influenza surveillance strategies. Furthermore, the World Health Organization (WHO) recommended in September 2023 the exclusion of B/Yamagata antigens from future vaccines, with a shift towards trivalent vaccines or modified quadrivalent vaccines; this new scenario underscores the importance of robust global respiratory virus surveillance, effective communication with healthcare professionals and the population to maintain trust in vaccines, and a collaborative approach among health policymakers and vaccine manufacturers to navigate this epidemiological change.

Systematic Review on Influenza Burden in Emerging Markets in 2018–2023—An Evidence Update to Guide Influenza Vaccination Recommendations

Background: Influenza is a contagious respiratory illness responsible for seasonal epidemics and with potential to cause pandemics. The decline in influenza-related studies published since 2018 resulted in data gaps, particularly in emerging markets. Methods: This systematic review searched for studies in six databases and gray literature sources to define the clinical burden of influenza and influenza-like illness (ILIs) and their associated sequelae among humans across emerging markets. Eligible studies were published in English, Spanish, or Chinese between January 2018 and September 2023 and conducted in Asia, the Middle East, Africa, and Latin America. Results: In total, 256 articles were included, mostly on lab-confirmed influenza infections (n = 218). Incidences of lab-confirmed influenza cases in Asia (range 540–1279 cases/100,000 persons) and Sub-Saharan Africa (range 34,100–47,800 cases/100,000 persons) were higher compared to Latin America (range 0.7–112 cases/100,000 persons) and the Middle East and North Africa (range 0.1–10 cases/100,000 persons). Proportions of lab-confirmed influenza cases and influenza-associated outcomes (i.e., hospitalization, ICU admission and death) varied widely across regions. Temporal variation in influenza trend was observed before and during the COVID-19 pandemic. Conclusions: In conclusion, influenza causes significant disease burden in emerging markets. Robust large real-world studies using a similar methodology are needed to have more accurate estimates and compare studies within age groups and regions. Continuous monitoring of influenza epidemiology is important to inform vaccine programs in emerging markets with heavy influenza disease burden.

Epidemiology and population-based incidence of influenza in two communities, Bandung district, West Java, Indonesia, 2008–2011

Influenza surveillance is important for monitoring influenza virus circulation and disease burden to inform influenza prevention and control measures. The aim of this study was to describe the epidemiology and to estimate the incidence of influenza in two communities in West Java, Indonesia, before and after the 2009 H1N1 pandemic. A population-based surveillance study in the community health care setting was conducted to estimate the annual incidence of influenza. A real-time reverse transcription polymerase chain reaction (RT-PCR) assay was used for influenza case ascertainment. A population census was implemented to calculate the population at risk and estimate community health care utilization rate. The mean annual incidence of influenza A and B, adjusted for healthcare utilization, was 1.6 (95%CI: 1.3–2.0) and 0.7 (95%CI: 0.5–1.0) per 1000 persons, respectively, with the most affected group being young and school-age children. The annual cumulative incidence of influenza A for children under five in 2009, 2010, and 2011 was 7.0 (95%CI: 4.4–11.2), 10.6 (95%CI: 7.3–15.4), and 6.3 (95%CI: 3.8–10.2). For influenza B was 4.3 (95%CI: 2.4–7.8), 2.0 (95%CI: 0.8–4.7), and 0.4 (95%CI: 0.1–2.8), respectively. This study highlights that the incidence of influenza among young and school-age children is consistently higher compared to adults and the elderly throughout these periods. These populations are potential targets for influenza vaccination in Indonesia.

Characterizing the seasonal influenza disease burden attributable to climate variability: A nationwide time-series modelling study in Japan, 2000−2019

BackgroundAmbient temperature and humidity are established environmental stressors with regard to influenza infections; however, mapping disease burden is difficult owing to the complexities of the underlying associations and differences in vulnerable population distributions. In this study, we aimed to quantify the burden of influenza attributable to non-optimal ambient temperature and absolute humidity in Japan considering geographical differences in vulnerability. MethodsThe exposure−lag−response relationships between influenza incidence, ambient temperature, and absolute humidity in all 47 Japanese prefectures for 2000−2019 were quantified using a distributed lag non-linear model for each prefecture; the estimates from all the prefectures were then pooled using a multivariate mixed-effects meta-regression model to derive nationwide average associations. Association between prefecture-specific indicators and the risk were also examined. Attributable risks were estimated for non-optimal ambient temperature and absolute humidity according to the exposure−lag−response relationships obtained before. ResultsA total of 25,596,525 influenza cases were reported during the study period. Cold and dry conditions significantly increased influenza incidence risk. Compared with the minimum incidence weekly mean ambient temperature (29.8 °C) and the minimum incidence weekly mean absolute humidity (20.2 g/m3), the cumulative relative risks (RRs) of influenza in cold (2.5 °C) and dry (3.6 g/m3) conditions were 2.79 (95% confidence interval [CI]: 1.78−4.37) and 3.20 (95% CI: 2.37−4.31), respectively. The higher RRs for cold and dry conditions were associated with geographical and climatic indicators corresponding to the central and northern prefectures; demographic, socioeconomic, and health resources indicators showed no clear trends. Finally, 27.25% (95% empirical CI [eCI]: 5.54−36.35) and 32.35% (95% eCI: 22.39−37.87) of all cases were attributable to non-optimal ambient temperature and absolute humidity (6,976,300 [95% eCI: 1,420,068−9,306,128] and 8,280,981 [95% eCI: 8,280,981−9,693,532] cases), respectively. ConclusionsThese findings could help identify the most vulnerable populations in Japan and design adaptation policies to reduce the attributable burden of influenza due to climate variability.

Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination

IntroductionThe objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of...

Influenza disease burden and the need for highly immunogenic vaccines in older adults: a narrative review

Influenza disease burden and the need for highly immunogenic vaccines in older adults: a narrative review

Analysis of influenza vaccination status and immunization strategy in high-risk population

Influenza is a contagious respiratory disease caused by influenza viruses, and the burden of severe disease is commonly seen in high risk populations. Influenza vaccination is an effective way to prevent influenza and its complications, especially for high risk populations. Although some countries have included influenza vaccine in their national immunization programs, influenza vaccination rates remain low globally in high risk populations. The influenza vaccine in China is still a non-immunization program vaccine that is voluntarily vaccinated at its own expense, and the influenza vaccine immunization strategy is different across the country. There is still a gap between the vaccination rate of the influenza vaccine and that of developed countries. It is an urgent problem to further optimize the whole population immunization strategy of influenza vaccine in China, strengthen the publicity of the whole population immunization strategy of influenza vaccine, and reduce the disease burden of influenza in China.

Revisiting influenza-hospitalisation estimates from the Burden of Influenza and Respiratory Syncytial Virus Disease (BIRD) project using different extrapolation methods.

Revisiting influenza-hospitalisation estimates from the Burden of Influenza and Respiratory Syncytial Virus Disease (BIRD) project using different extrapolation methods.

Healthcare-seeking behaviours of patients with acute respiratory infection: a cross-sectional survey in a rural area of southwest China

ObjectivesThis study aimed to assess the healthcare-seeking behaviour and related factors of people with acute respiratory symptoms in the rural areas of central and western China to estimate the disease...

Respiratory Syncytial Virus and Influenza During the COVID-19 Pandemic: A Two-center Experience.

The aim of the study was to determine the burden of respiratory syncytial virus (RSV) and influenza disease during the COVID-19 pandemic at 2 Austrian urban pediatric centers between October 1, 2019 and April 30, 2022. We performed a retrospective observational 2-center study on RSV- and influenza virus-associated hospitalizations in infants and children up to 18 years at the University Hospital of Graz and the Clinic Donaustadt of Vienna from October 1, 2019 to April 30, 2022. Hospitalization had to be associated with the infectious disease, proven by polymerase chain reaction, including presence of respiratory symptoms. Demographic data including underlying diseases and treatment strategies were compared between centers and diseases, respectively. There were 826 cases in Graz and 379 in Vienna with significant more RSV cases in Graz and more influenza cases in Vienna (RSV: 76% vs. 59%, influenza: 24% vs. 41%; both P < 0.001). One death occurred in Graz due to RSV and another due to influenza in Vienna. Seasonality only slightly differed between centers and severity of diseases was not aggravated when measured by pediatric intensive care unit admission rates, need for supplemental oxygen and respiratory support between first and last seasons. Treatment regimen differed regarding higher use of antibiotics and rates of intravenous fluids in Vienna compared to higher rates of bronchodilators, corticosteroids and nose drops in Graz. We observed higher numbers of hospitalizations due to both viruses after the lockdown but not increased severity of the diseases; and mortality remained extremely low. Preventive measures should be implemented with high priority especially focused on infants with underlying diseases.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making.

Modeling the value of an emergency department influenza vaccination program

BackgroundSeasonal influenza continues to present a significant annual burden as the vaccination rate in the United States is 51.8%. Emergency Department (ED) based influenza programs have been successfully implemented and improve vaccine uptake, reduce incidence and costs, and improve outcomes. ObjectiveTo develop a predictive model to assess preventable influenza cases, hospitalizations, fatalities, and incremental cost avoidance based on the unvaccinated population. MethodsA retrospective cohort of ED encounters limited to Medicare and Medicaid populations was performed across 14 tertiary care hospital EDs and six freestanding EDs for 2020. The total number of unvaccinated individuals was identified to determine the potential impact of an ED vaccination campaign. The average cost and loss per inpatient stay was identified from prior industry Medicare benchmark data and was utilized to extrapolate Medicaid losses. Results from published cost-effectiveness studies identified the vaccination thresholds to prevent one additional case of influenza, one additional hospitalization, and one additional fatality. ResultsA total of 39,463 unvaccinated individuals were identified, with 14,064 classified as Medicare, and 25,379 classified as Medicaid. Assuming a 95% target outreach, 90% medical eligibility, and 70% acceptance rate, 414 influenza cases would be prevented (266 Medicaid, 148 Medicare), 28 hospitalizations would be prevented (18 Medicaid, 10 Medicare), and eight deaths would be prevented (5 Medicaid, 3 Medicare). Accordingly, a reduction in admissions would prevent $409,360 in total inpatient medical costs and $36,232 in losses to healthcare systems. ConclusionAn ED-based influenza vaccination program would have a measurable impact on patient influenza disease burden and associated medical expenditures.

Impact of Influenza Vaccination on the Burden of Severe Influenza in the Elderly: Spain, 2017-2020.

Annual influenza vaccination is the main strategy to reduce the burden of seasonal influenza epidemics and is recommended for the elderly in most countries with influenza vaccination strategies, with the main objective of preventing hospitalizations and mortality associated with seasonal influenza in this age group. Studies from different countries have estimated the benefits of seasonal influenza vaccination programs in the elderly, preventing a considerable number of cases, hospitalizations and deaths every year. A study measured the number of medically attended confirmed influenza cases in primary care that are prevented annually by vaccination in the population aged 65 and older in Spain, the Netherlands and Portugal, but estimates of the impact of the national influenza vaccination program in the prevention of severe disease in Spain are lacking. The two objectives of this study were to estimate the burden of severe influenza disease in the Spanish population and to measure the impact of influenza vaccination in the prevention of these outcomes in the population aged 65 years and older. Using influenza surveillance systems put in place before the COVID-19 pandemic, we conducted a retrospective observational study to estimate the burden of hospitalizations and ICU admissions in Spain between 2017-18 and 2019-20, by season and age group. Burden estimates for the 65+ group, combined with vaccine effectiveness (VE) and vaccination coverage (VC) data, were used as input data in an ecological, observational study to estimate the impact of the influenza vaccination program on the elderly. We found a higher burden of severe influenza disease in seasons 2017-18 and 2018-19, with A(H3N2) circulation, and in the youngest and oldest age groups. In those aged 65 and older, we estimated an average of 9900 influenza hospitalizations and 1541 ICU admissions averted by vaccination each year. Seasonal influenza vaccination was able to prevent between 11 and 26% influenza hospitalizations and around 40% ICU admissions in the elderly in the three pre-pandemic seasons. In conclusion, our study complements previous analyses in the primary care setting in Spain and demonstrates the benefits of the annual influenza vaccination program in the prevention of severe influenza disease in the elderly, even in seasons with moderate VE.

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands.

Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7years of age. These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.

Estimation of influenza incidence and analysis of epidemic characteristics from 2009 to 2022 in Zhejiang Province, China.

Influenza infection causes a huge burden every year, affecting approximately 8% of adults and approximately 25% of children and resulting in approximately 400,000 respiratory deaths worldwide. However, based on the number of reported influenza cases, the actual prevalence of influenza may be greatly underestimated. The purpose of this study was to estimate the incidence rate of influenza and determine the true epidemiological characteristics of this virus. The number of influenza cases and the prevalence of ILIs among outpatients in Zhejiang Province were obtained from the China Disease Control and Prevention Information System. Specimens were sampled from some cases and sent to laboratories for influenza nucleic acid testing. Random forest was used to establish an influenza estimation model based on the influenza-positive rate and the percentage of ILIs among outpatients. Furthermore, the moving epidemic method (MEM) was applied to calculate the epidemic threshold for different intensity levels. Joinpoint regression analysis was used to identify the annual change in influenza incidence. The seasonal trends of influenza were detected by wavelet analysis. From 2009 to 2021, a total of 990,016 influenza cases and 8 deaths were reported in Zhejiang Province. The numbers of estimated influenza cases from 2009 to 2018 were 743,449, 47,635, 89,026, 132,647, 69,218, 190,099, 204,606, 190,763, 267,168 and 364,809, respectively. The total number of estimated influenza cases is 12.11 times the number of reported cases. The APC of the estimated annual incidence rate was 23.33 (95% CI: 13.2 to 34.4) from 2011 to 2019, indicating a constant increasing trend. The intensity levels of the estimated incidence from the epidemic threshold to the very high-intensity threshold were 18.94 cases per 100,000, 24.14 cases per 100,000, 141.55 cases per 100,000, and 309.34 cases per 100,000, respectively. From the first week of 2009 to the 39th week of 2022, there were a total of 81 weeks of epidemics: the epidemic period reached a high intensity in 2 weeks, the epidemic period was at a moderate intensity in 75 weeks, and the epidemic period was at a low intensity in 2 weeks. The average power was significant on the 1-year scale, semiannual scale, and 115-week scale, and the average power of the first two cycles was significantly higher than that of the other cycles. In the period from the 20th week to the 35th week, the Pearson correlation coefficients between the time series of influenza onset and the positive rate of pathogens, including A(H3N2), A (H1N1)pdm2009, B(Victoria) and B(Yamagata), were - 0.089 (p = 0.021), 0.497 (p < 0.001), -0.062 (p = 0.109) and - 0.084 (p = 0.029), respectively. In the period from the 36th week of the first year to the 19th week of the next year, the Pearson correlation coefficients between the time series of influenza onset and the positive rate of pathogens, including A(H3N2), A (H1N1)pdm2009, B(Victoria) and B(Yamagata), were 0.516 (p < 0.001), 0.148 (p < 0.001), 0.292 (p < 0.001) and 0.271 (p < 0.001), respectively. The disease burden of influenza has been seriously underestimated in the past. An appropriate method for estimating the incidence rate of influenza may be to comprehensively consider the influenza-positive rate as well as the percentage of ILIs among outpatients. The intensity level of the estimated incidence from the epidemic threshold to the very high-intensity threshold was calculated, thus yielding a quantitative standard for judging the influenza prevalence level in the future. The incidence of influenza showed semi-annual peaks in Zhejiang Province, including a main peak from December to January of the next year followed by a peak in summer. Furthermore, the driving factors of the influenza peaks were preliminarily explored. While the peak in summer was mainly driven by pathogens of A(H3N2), the peak in winter was alternately driven by various pathogens. Our research suggests that the government urgently needs to address barriers to vaccination and actively promote vaccines through primary care providers.

Agent-based model of the impact of higher influenza vaccine efficacy on seasonal influenza burden

Current influenza vaccines have limited effectiveness. COVID-19 vaccines using mRNA technology have demonstrated very high efficacy, suggesting that mRNA vaccines could be more effective for influenza. Several such influenza vaccines are in development. FRED, an agent-based modeling platform, was used to estimate the impact of more effective influenza vaccines on seasonal influenza burden. Simulations were performed using an agent-based model of influenza that included varying levels of vaccination efficacy (40-95 % effective). In some simulations, level of infectiousness and/or length of infectious period in agents with breakthrough infections was also decreased. Impact of increased and decreased levels of vaccine uptake were also modeled. Outcomes included number of symptomatic influenza cases estimated for the US. Highly effective vaccines significantly reduced estimated influenza cases in the model. When vaccine efficacy was increased from 40% to a maximum of 95%, estimated influenza cases in the US decreased by 43% to>99%. The base simulation (40% efficacy) resulted in∼28 million total yearly cases in the US, while the most effective vaccine modeled (95% efficacy) decreased estimated cases to∼22,000. Highly effective vaccines could dramatically reduce influenza burden. Model estimates suggest that even modest increases in vaccine efficacy could dramatically reduce seasonal influenza disease burden.

Estimation of seasonal influenza disease burden using sentinel site data in Pakistan 2017-2019: A cross-sectional study.

The influenza A(H1N1)pdm09 pandemic highlighted the need for reliable disease burden estimation from low- and middle-income countries like Pakistan. We designed retrospective age-stratified estimation of influenza-related severe acute respiratory infections (SARIs) incidence in Islamabad Pakistan 2017-2019. The catchment area was mapped on SARI data from one designated influenza sentinel site and other healthcare facilities in the Islamabad region. The incidence rate was calculated as per 100,000 for each age group with 95% confidence interval. The catchment population for the sentinel site was 0.7 million against the total denominator of 1.015 million, and incidence rates were adjusted. During January 2017 to December 2019, among 13,905 hospitalizations, 6715 (48%) patients were enrolled; 1208 of these (18%) were positive for influenza. During 2017, influenza A/H3 dominated with 52% detections followed by A(H1N1)pdm09 (35%) and influenza B (13%). Furthermore, elderly 65+ years age group had highest hospitalizations and influenza positive. The incidence rates of all cause respiratory and influenza-related SARI were highest among children >5years; highest incidence was found in 0 to 11 month/year group with 424/100,000 cases and lowest in 5-15 years 56/100,000. The estimated average annual influenza-associated hospitalization percentage was 29.3% during the study period. Influenza accounts for a significant proportion of respiratory morbidity and hospitalization. These estimates would enable governments for evidence-based decisions and priority allocation of health resources. It is necessary to test for other respiratory pathogens for more clear disease burden estimation.

Top 5 questions about this year's flu vaccination

CDC estimates that the United States will experience a high influenza disease burden for the 2022–2023 season. CDC surveillance data from late October 2022 show that there have been more than 880,000 flu infections nationwide so far this season, including 6,900 hospitalizations and 360 deaths, making for an unusually early and brutal cycle.

Characteristics of Respiratory Syncytial Virus versus Influenza Infection in Hospitalized Patients of Peru: A Retrospective Observational Study.

Respiratory syncytial virus (RSV) and influenza infections are important causes of respiratory illness associated with hospitalizations in children in Peru; however, comparisons of RSV and influenza hospitalization across all age groups are not available in Peru. Therefore, we conducted an observational, retrospective study between May 2015 and October 2021 using hospitalization from RSV and influenza infection data obtained from SUSALUD (open data) in Peru to compare the baseline characteristics of sex, age, region, and infection type. For the study, 2696 RSV-infected and 1563 influenza-infected hospitalized patients from different age groups were included. Most hospitalizations from RSV infection and the influenza virus occurred in children <5 years of age (86.1% vs. 32.2%, respectively). Compared with influenza infection, RSV infection was less likely to occur in individuals ≥5 years of age (adjusted odds ratio (aOR) = 0.07; 95% confidence interval (CI), 0.06–0.08; p < 0.0001; compared to <5 years of age), and more likely to occur in highlands (aOR = 1.75; 95% CI, 1.46–2.07; p < 0.0001, compared to coast region), and jungle region (aOR = 1.75; 95% CI, 1.27–2.41; p = 0.001, compared to coast region). Among the respiratory complications, RSV pneumonia was less likely to occur between different age groups (aOR = 0.29; 95% CI, 0.22–0.37; p < 0.0001, compared to <5 years of age), compared with influenza pneumonia. These findings on the RSV-hospitalization and its complications are helpful for health services planning and may increase awareness of the Peruvian population’s RSV and influenza disease burden.

Technical guidelines for seasonal influenza vaccination in China (2022-2023)

Technical guidelines for seasonal influenza vaccination in China (2022-2023)