Influenza Transmission Research Articles

Analisis Kestabilan dan Kontrol Optimum pada Model Penyebaran Penyakit Influenza dengan Adanya Populasi Cross-Immune

Influenza is a respiratory tract infection known as flu. Caused by an RNA virus from Orthomyxoviridae family. This thesis aims to analyze the stability of the equilibrium point in the mathematical model of influenza transmission with Cross-Immune population and applying optimal control variables in the form of prevention and treatment. In this mathematical model of influenza transmission with Cross-Immune population, we obtain two equilibriums namely, the non- endemic equilibrium and the endemic equilibrium. Local stability and the existence of endemic equilibrium depend on the basic reproduction number (R0). The spread of influenza does not occur in the population when R0 < 1 and the spread of influenza persist in the population when R0 > 1. Furthermore, the problem of control variables in the mathematical model of influenza transmission is determined through the Pontryagin Maximum Principle method. The numerical simulation results show that treatment efforts are more effective in suppressing the spread of influenza disease than prevention efforts. However, giving control variables in the form of prevention and treatment at the same time is very effective in minimizing the number of human populations expose to and infected with influenza.

Shortening Duration of Swine Exhibitions to Reduce Risk for Zoonotic Transmission of Influenza A Virus.

Reducing zoonotic influenza A virus (IAV) risk in the United States necessitates mitigation of IAV in exhibition swine. We evaluated the effectiveness of shortening swine exhibitions to <72 hours to reduce IAV risk. We longitudinally sampled every pig daily for the full duration of 16 county fairs during 2014–2015 (39,768 nasal wipes from 6,768 pigs). In addition, we estimated IAV prevalence at 195 fairs during 2018–2019 to test the hypothesis that <72-hour swine exhibitions would have lower IAV prevalence. In both studies, we found that shortening duration drastically reduces IAV prevalence in exhibition swine at county fairs. Reduction of viral load in the barn within a county fair is critical to reduce the risk for interspecies IAV transmission and pandemic potential. Therefore, we encourage fair organizers to shorten swine shows to protect the health of both animals and humans.

Interruption of Influenza Transmission under Public Health Emergency Response for COVID-19: a Study Based on Real-World Data from Beijing, China

To estimate the effect of the corona virus disease 2019 (COVID-19) control measures taken to mitigate community transmission in many regions, we analyzed data from the influenza surveillance system in Beijing from week 27 of 2014 to week 26 of 2020. We collected weekly numbers of influenza-like illness (ILI) cases, weekly positive proportion of ILI cases, weekly ILI case proportion in outpatients, and the dates of implementation of COVID-19 measures. We compared the influenza activity indicators of the 2019/2020 season with the preceding five seasons and built two ARIMAX models to estimate the effectiveness of COVID-19 measures declared since January 24, 2020 by the emergency response. Based on the observed data, compared to the preceding five influenza seasons, ILIs, positive proportion of ILIs, and duration of the influenza epidemic period in 2019/2020 had increased from 13% to 54%; in particular, the number of weeks from the peak to the end of the influenza epidemic period had decreased from 12 to 1. According to ARIMAX model forecasting, after considering natural decline, weekly ILIs had decreased by 48.6%, weekly positive proportion had dropped by 15% in the second week after the emergency response was declared, and COVID-19 measures had reduced by 83%. We conclude that the public health emergency response can significantly interrupt the transmission of influenza.

Transmission Patterns of Seasonal Influenza in China between 2010 and 2018.

Background Understanding the transmission source, pattern, and mechanism of infectious diseases is essential for targeted prevention and control. Though it has been studied for many years, the detailed transmission patterns and drivers for the seasonal influenza epidemics in China remain elusive. Methods In this study, utilizing a suite of epidemiological and genetic approaches, we analyzed the updated province-level weekly influenza surveillance, sequence, climate, and demographic data between 1 April 2010 and 31 March 2018 from continental China, to characterize detailed transmission patterns and explore the potential initiating region and drivers of the seasonal influenza epidemics in China. Results An annual cycle for influenza A(H1N1)pdm09 and B and a semi-annual cycle for influenza A(H3N2) were confirmed. Overall, the seasonal influenza A(H3N2) virus caused more infection in China and dominated the summer season in the south. The summer season epidemics in southern China were likely initiated in the “Lingnan” region, which includes the three most southern provinces of Hainan, Guangxi, and Guangdong. Additionally, the regions in the south play more important seeding roles in maintaining the circulation of seasonal influenza in China. Though intense human mobility plays a role in the province-level transmission of influenza epidemics on a temporal scale, climate factors drive the spread of influenza epidemics on both the spatial and temporal scales. Conclusion The surveillance of seasonal influenza in the south, especially the “Lingnan” region in the summer, should be strengthened. More broadly, both the socioeconomic and climate factors contribute to the transmission of seasonal influenza in China. The patterns and mechanisms revealed in this study shed light on the precise forecasting, prevention, and control of seasonal influenza in China and worldwide.

Temperature and influenza transmission: Risk assessment and attributable burden estimation among 30 cities in China

BackgroundMany studies have explored the epidemiological characteristics of influenza. However, most previous studies were conducted in a specific region without a national picture which is important to develop targeted strategies and measures on influenza control and prevention. ObjectivesTo explore the association between ambient temperature and incidence of influenza, to estimate the attributable risk from temperature in 30 Chinese cities with different climatic characteristics for a national picture, and to identify the vulnerable populations for national preventative policy development. MethodsDaily meteorological and influenza incidence data from the 30 Chinese cities over the period 2016–19 were collected. We estimated the city-specific association between daily mean temperature and influenza incidence using a distributed lag non-linear model and evaluated the pooled effects using multivariate meta-analysis. The attributable fractions compared with reference temperature were calculated. Stratified analyses were performed by region, sex and age. ResultsOverall, an N-shape relationship between temperature and influenza incidence was found in China. The cumulative relative risk of the peak risk temperature (5.1 °C) was 2.13 (95%CI: 1.41, 3.22). And 60% (95%eCI: 54.3%, 64.3%) of influenza incidence was attributed to ambient temperature during the days with sensitive temperatures (1.6°C–14.4 °C). The ranges of sensitive temperatures and the attributable disease burden due to temperatures varied for different populations and regions. The residents in South China and the children aged ≤5 and 6–17 years had higher fractions attributable to sensitive temperatures. ConclusionsTailored preventions targeting on most vulnerable populations and regions should be developed to reduce influenza burden from sensitive temperatures.

Subtypes specified environmental dependence of seasonal influenza virus

Understanding the role of meteorological factors in the transmission dynamics of respiratory infectious diseases remains challenging. Our study was to comprehensively investigate the nonlinear effects of environmental factors on influenza transmission, based on multi-region surveillance data from mainland China. An approach related to time-varying reproduction number (Rt) was proposed, which extracts the environment-related components from Rt to estimate the relationship between environmental factors and influenza transmission based on a mixed-effects regression model. Nonlinear relationships for absolute humidity (the lowest transmission was observed at absolute humidity of 12 g/m3) and mean temperature (the lowest transmission was observed at the mean temperature of 18 °C) with influenza transmission were observed. Influenza transmission holds almost constant with the average precipitation below 1 mm or sunshine hour below 9 h/day, but increases for the precipitation and decreases for the sunshine hour afterward. The environmental dependence varies across subtypes: A(H3N2) maintains relatively higher transmission in high temperature and humidity conditions, compared with other influenza subtypes. Overall, the subtypes specified environmental dependence of influenza transmission could explain 23.1 %, 29.2 % and 27.1 % of the variations for A(H1N1)pdm09, A(H3N2) and B-lineage in China. The projected seasonal transmission rates based on our approach could be used as a valuable seasonal proxy to model the influenza dynamics under various meteorological spaces. Finally, our approach is also applicable to obtain novel insights into the impact of environmental factors on other respiratory infectious diseases.

Reducing zoonotic avian influenza transmission at household poultry slaughter using a behaviour change tool for limited literacy audiences.

Human infections in Egypt with highly pathogenic avian influenza (HPAI) likely due to airborne transmission of HPAI virus (HPAIV) during home slaughter of poultry predominately affect women and children, who are the primary caregivers of household poultry. This study developed a safe contained poultry slaughter procedure to reduce airborne HPAIV and zoonotic infections and simultaneously created an educational outreach tool for teaching the modified procedure. The tool designed for limited literacy audiences used two illustrated posters and handouts for teaching the safe contained poultry slaughter procedure. The posters were developed with advice of animal health professionals and then refined by target audience women's focus groups. These women's focus groups proved to be the critical step for assuring the understanding, acceptance, effectiveness and accuracy of the outreach tool. The safe contained poultry slaughter procedure was designed to be low or no cost, sustainable by using a universal implement found in village households and designed as a minor variation of standard poultry halal slaughter. It was crafted to be culturally appropriate and religiously acceptable.

Reconstruction of molecular evolution of human influenza A H1N1/2009 virus in Iran and neighboring countries.

In this study, the time and path of transmission of H1N1 serotype influenza A viruses in Iran and neighboring countries have been investigated by using Bayesian phylogeography analysis on the sequences extracted from the gene bank. We obtained all hemagglutinin (HA) and neuraminidase (NA) nucleotide sequences of influenza H1N1 available up to December 25, 2020, from Iran and its neighboring countries (i.e., Pakistan, Afghanistan, Turkmenistan, Armenia, Azerbaijan, Turkey, and Iraq). We also performed a Bayesian Markov chain Monte Carlo method to infer the evolutionary dynamic and the most recent common ancestor for the HA and NA sequences. Based on the extracted sequences, the age of emergence of H1N1 influenza virus serotype was older in Iran compared to neighboring countries, and with some degree of uncertainty, it seems Tehran had a key role and epicenter of transmission to other cities within Iran. The mean time of the most recent common ancestor of H1N1 viruses was 1989 (95% HPD: 1980-1994) for HA and NA as well. Along with ordinary measures like resource management, diagnostic approaches, and preparedness to fight against viruses that were in place, continuous monitoring, and screening of H1N1 serotype influenza virus in the country, especially by implementation of feasible, effective, and innovative measures at borderline should be initiated and identified gaps and shortage that should be a priority for virus control. It is also important for countries to have a regional monitoring program in addition to internal monitoring programs, as well as to start a virus molecular care program.

Ferrets as a model for tuberculosis transmission.

Even with the COVID-19 pandemic, tuberculosis remains a leading cause of human death due to a single infectious agent. Until successfully treated, infected individuals may continue to transmit Mycobacterium tuberculosis bacilli to contacts. As with other respiratory pathogens, such as SARS-CoV-2, modeling the process of person-to-person transmission will inform efforts to develop vaccines and therapies that specifically impede disease transmission. The ferret (Mustela furo), a relatively inexpensive, small animal has been successfully employed to model transmissibility, pathogenicity, and tropism of influenza and other respiratory disease agents. Ferrets can become naturally infected with Mycobacterium bovis and are closely related to badgers, well known in Great Britain and elsewhere as a natural transmission vehicle for bovine tuberculosis. Herein, we report results of a study demonstrating that within 7 weeks of intratracheal infection with a high dose (>5 x 103 CFU) of M. tuberculosis bacilli, ferrets develop clinical signs and pathological features similar to acute disease reported in larger animals, and ferrets infected with very-high doses (>5 x 104 CFU) develop severe signs within two to four weeks, with loss of body weight as high as 30%. Natural transmission of this pathogen was also examined. Acutely-infected ferrets transmitted M. tuberculosis bacilli to co-housed naïve sentinels; most of the sentinels tested positive for M. tuberculosis in nasal washes, while several developed variable disease symptomologies similar to those reported for humans exposed to an active tuberculosis patient in a closed setting. Transmission was more efficient when the transmitting animal had a well-established acute infection. The findings support further assessment of this model system for tuberculosis transmission including the testing of prevention measures and vaccine efficacy.

The spatial and temporal effects of Fog–Haze pollution on the influenza transmission

The energy-intensive industrial economy results in frequent Fog–Haze weather which increases the risk of influenza spread and brings new challenges for the prevention and control of influenza. Therefore, the study of spread mechanics and controlling strategies of influenza based on Fog–Haze will be scientifically meaningful. Considering that when the concentration of Fog–Haze is low, Fog–Haze contributes to the number of infectious individuals and Fog–Haze suppresses the transmission of the influenza virus when the concentration of Fog–Haze is high, we establish the Fog–Haze dynamics model. Then we prove the global existence and boundedness of the solution, and the global asymptotic stability of the solution is given by constructing a suitable Lyapunov functional. Under the Fog–Haze weather, we study the influenza virus transmission model that incorporates the incidence rate to reflect the Fog–Haze-dependent saturation effect and investigate the effect of Fog–Haze pollution on the transmission of influenza. We show that the basic reproduction number [Formula: see text] determines the global dynamics of the system: if [Formula: see text], the disease-free equilibrium is global asymptotically stable; the unique endemic equilibrium is global asymptotically stable if [Formula: see text]. Simulations are carried out to validate the theoretical results. Our study provides further understanding of the dynamics of Fog–Haze and the effect of Fog–Haze pollution on the transmission of influenza.

Feasibility, Acceptability, and Barriers to Implementing Select Non-Pharmaceutical Interventions to Reduce the Transmission of Pandemic Influenza - United States, 2019.

This study aimed to assess the feasibility and acceptability of implementing non-pharmaceutical interventions (NPIs) reserved for influenza pandemics (voluntary home quarantine, use of face masks by ill persons, childcare facility closures, school closures, and social distancing at schools, workplaces, and mass gatherings). Public health officials in all 50 states (including Washington, DC) and 8 territories, and a random sample of 822 local health departments (LHDs), were surveyed in 2019. The response rates for the states/ territories and LHDs were 75% (44/ 59) and 25% (206/ 822), respectively. Most of the state/ territorial respondents stated that the feasibility and acceptability of implementing NPIs were high, except for K-12 school closures lasting up to 6 weeks or 6 months. The LHD respondents also indicated that feasibility and acceptability were lowest for prolonged school closures. Compared to LHD respondents in suburban or urban areas, those in rural areas expressed lower feasibility and acceptability. Barriers to implementing NPIs included financial impact, compliance and difficulty in enforcement, perceived level of disease threat, and concerns regarding political implications. Proactive strategies to systematically address perceived barriers and promote disease prevention ahead of a new pandemic are needed to increase receptivity and consistent adoption of NPIs and other evidence-based countermeasures.

Evidence of transmission of influenza A and influenza B co-infection in healthcare workers.

Co-infection of influenza A and B has been reported, especially in outbreak situations, but epidemiological and clinical information is limited. We aimed to investigate an outbreak of influenza among health care workers in which the index case suffered from influenza A and B co-infection. We investigated the outbreak setting through the utilization of structural questionnaires, molecular methods, and serological tests. Among 13 persons, one index case and five confirmed secondary cases were confirmed. The overall influenza infection rate was 46.2% (6/13), with infection rates for influenza A and B at 38.5% (5/13) and 23.1% (3/13), respectively. Interestingly, one of the secondary cases had influenza A and B co-infection identical to the index case. There was no significant association between vaccination status and influenza infection. This study unveils the demonstration of human-to-human influenza A and B co-infection transmission for the first time. Surveillance systems, combined with epidemiological case investigation comprising molecular diagnosis, should be strengthened for future influenza outbreak preparedness.

Impact of COVID-19 on the Changing Patterns of Respiratory Syncytial Virus Infections.

Seasonal epidemics of respiratory syncytial virus (RSV) is one of the leading causes of hospitalization and mortality among children. Preventive measures implemented to reduce the spread of SARS-CoV-2, including facemasks, stay-at-home orders, closure of schools and local-national borders, and hand hygiene, may have also prevented the transmission of RSV and influenza. However, with the easing of COVID-19 imposed restrictions, many regions are noticing a delayed RSV outbreak. Some of these regions have also noted an increase in severity of these delayed RSV outbreaks partly due to a lack of protective immunity in the community following a lack of exposure from the previous season. Lessons learned from the COVID-19 pandemic can be implemented for controlling RSV outbreaks, including: (1) measures to reduce the spread, (2) effective vaccine development, and (3) genomic surveillance tools and computational modeling to predict the timing and severity of RSV outbreaks. These measures can help reduce the severity and prepare the health care system to deal with future RSV outbreaks by appropriate and timely allocation of health care resources.

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children.

BackgroundClinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients.MethodsWe compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity.ResultsChildren with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78–2.15; P = .32).ConclusionsDespite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Effects of baloxavir and oseltamivir antiviral therapy on the transmission of seasonal influenza in China: A mathematical modeling analysis.

New antiviral influenza treatments can effectively alleviate illness while reducing viral shedding. However, how such effects can translate into lower population infections of seasonal influenza in China remains unknown. To shed light on the public health impacts of novel antiviral agents for influenza, we constructed a dynamic transmission model to simulate the seasonal influenza epidemics in China. Two antivirus treatments, baloxavir and oseltamivir, were evaluated by estimating their impacts on the incidences of influenza infection in a single flu season. In the base-case analysis of a 10% antiviral treatment uptake rate, 2760 and 3420 per 10 000 persons contracted influenza under the treatment of baloxavir and oseltamivir, respectively. These incidence rates amounted to an 18.90% relative risk reduction (RRR) of infection associated with baloxavir in relation to oseltamivir. The corresponding RRR was 82.16% when the antiviral treatment uptake rate was increased to 35%. In addition, the peak of the prevalence of infected individuals per 10 000 persons under the baloxavir treatment was 177 (range: 93-274) fewer than that of oseltamivir. Our analyses suggest that the baloxavir treatment strategy reduces the incidence of influenza in China compared with oseltamivir in the setting of a seasonal flu epidemic. Also, increasing the uptake rate of antiviral treatment can potentially prevent millions of infections during a single flu season.

The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review

BackgroundNovel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community.MethodsPubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002–February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525).ResultsTwenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high (n = 1) and unclear (n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 (P < 0.05), but risk of bias was high (n = 7), unclear (n = 5) or low (n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent.ConclusionsTo our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.

The Collateral Benefit of COVID-19 Mitigation Strategies on Influenza.

The ongoing COVID-19 pandemic initiated the implementation of numerous disease mitigation strategies aimed to prevent transmission of the SARS-CoV-2. Given the similarity in mode of transmission, we posit that these strategies have also had a collateral benefit in minimizing the transmission of influenza during the 2020 to 2021 season in California. Five years of data including incidence of influenza-like illness (ILI), influenza hospitalization, and mortality related to influenza in California were analyzed. In each of these parameters, there was a marked decrease in influenza activity, suggesting the additional benefit of COVID-19 mitigation strategies on influenza prevention. Further study is recommended to determine which specific variables had greater impact on transmission of respiratory viruses, and therefore can be utilized to prevent future outbreaks of respiratory illness.

Was the Reduction in Seasonal Influenza Transmission during 2020 Attributable to Non-Pharmaceutical Interventions to Contain Coronavirus Disease 2019 (COVID-19) in Japan?

We quantified the effects of adherence to various non-pharmaceutical interventions (NPIs) on the seasonal influenza epidemic dynamics in Japan during 2020. The total monthly number of seasonal influenza cases per sentinel site (seasonal influenza activity) reported to the National Epidemiological Surveillance of Infectious Diseases and alternative NPI indicators (retail sales of hand hygiene products and number of airline passenger arrivals) from 2014–2020 were collected. The average number of monthly seasonal influenza cases in 2020 had decreased by approximately 66.0% (p < 0.001) compared to those in the preceding six years. An increase in retail sales of hand hygiene products of ¥1 billion over a 3-month period led to a 15.5% (95% confidence interval [CI]: 10.9–20.0%; p < 0.001) reduction in seasonal influenza activity. An increase in the average of one million domestic and international airline passenger arrivals had a significant association with seasonal influenza activity by 11.6% at lag 0–2 months (95% CI: 6.70–16.5%; p < 0.001) and 30.9% at lag 0–2 months (95% CI: 20.9–40.9%; p < 0.001). NPI adherence was associated with decreased seasonal influenza activity during the COVID-19 pandemic in Japan, which has crucial implications for planning public health interventions to minimize the health consequences of adverse seasonal influenza epidemics.

Unintended beneficial effects of COVID-19 on influenza-associated emergency department use in Korea

BackgroundNon-pharmaceutical interventions, including hand hygiene, wearing masks, and cough etiquette, and public health measures such as social distancing, used to prevent the spread of coronavirus disease 2019 (COVID-19), could reduce the incidence rate of respiratory viral infections such as influenza. We evaluated the effect of COVID-19 on the incidence of influenza in Korea. MethodsThis retrospective study included all patients who visited five urban emergency departments (EDs) during the influenza epidemic seasons of 2017–18, 2018–19, and 2019–20. Influenza was defined as ICD-10 codes J09, J10, and J11, determined from ED discharge records. The weekly incidence rates of influenza per 1000 ED visits during the 2019–20 season, when COVID-19 became a pandemic, were compared with those of 2017–18 and 2018–19. The actual incidence rate of the 2019–20 season was compared with the predicted value using a generalized estimation equation model based on 2017–18 and 2018–19 data. ResultsThe weekly influenza incidence rate decreased from 101.6 to 56.6 between week 4 and week 5 in 2020 when the first COVID-19 patient was diagnosed and public health measures were implemented. The weekly incidence rate during week 10 and week 22 of the 2019–20 season decreased most steeply compared to 2017–18 and 2018–19. The actual influenza incidence rate observed in the 2019–20 season was lower than the rate predicted in the 2017–18 and 2018–19 seasons starting from week 7 when a COVID-19 outbreak occurred in Korea. ConclusionsThe implementation of non-pharmaceutical interventions and public health measures for the COVID-19 epidemic effectively reduced the transmission of influenza and associated ED use in Korea. Implementing appropriate public health measures could reduce outbreaks and lessen the burden of influenza during future influenza epidemics.

Influenza A virus undergoes compartmentalized replication in vivo dominated by stochastic bottlenecks

Transmission of influenza A viruses (IAV) between hosts is subject to numerous physical and biological barriers that impose genetic bottlenecks, constraining viral diversity and adaptation. The bottlenecks within hosts and their potential impacts on evolutionary pathways taken during infection are poorly understood. To address this, we created highly diverse IAV libraries bearing molecular barcodes on two gene segments, enabling high-resolution tracking and quantification of unique virus lineages within hosts. Here we show that IAV infection in lungs is characterized by multiple within-host bottlenecks that result in “islands” of infection in lung lobes, each with genetically distinct populations. We perform site-specific inoculation of barcoded IAV in the upper respiratory tract of ferrets and track viral diversity as infection spreads to the trachea and lungs. We detect extensive compartmentalization of discrete populations within lung lobes. Bottleneck events and localized replication stochastically sample individual viruses from the upper respiratory tract or the trachea that become the dominant genotype in a particular lobe. These populations are shaped strongly by founder effects, with limited evidence for positive selection. The segregated sites of replication highlight the jackpot-style events that contribute to within-host influenza virus evolution and may account for low rates of intrahost adaptation.