Children hospitalised with influenza-associated pneumonia during the 2009 pandemic displayed increased disease severity.

AIM: The precise role of the influenza virus in the morbidity of hospitalised paediatric pneumonia cases is unknown. We identified how many cases hospitalised during the 2009 pandemic had influenza-associated pneumonia and assessed their severity. METHODS: Children admitted to three Israeli medical centres during the 2009 influenza pandemic with radiologically confirmed pneumonia were prospectively screened for influenza. We compared the clinical, laboratory and radiologic findings for positive and negative cases. RESULTS: The pandemic H1N1 virus was detected in 89 (30%) of the 297 patients hospitalised for pneumonia and 55% of the Paediatric Intensive Care Unit admissions for pneumonia. There were no significant differences in the rates of underlying disease between the two groups. Logistic regression analysis revealed that children with pandemic H1N1 virus-associated pneumonia had significantly increased disease severity than those without, with a higher incidence of hypoxemia (41.6% versus 24%) with a relative risk (RR) of 2.2, higher rate of paediatric intensive care unit admission (16.9% versus 5.8%, RR of 2.7) and higher rate of mechanical ventilation (10.1% versus 2.4%, RR:4.4). CONCLUSION: During the 2009 influenza pandemic, 30% of children hospitalised for pneumonia had the influenza infection and these children displayed increased disease severity.

Characterization of the Increase in Narcolepsy following the 2009 H1N1 Pandemic in Sweden.

(1) Background: In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. We performed an analysis of the increase, with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. (2) Methods: Data for narcolepsy patients (ICD code G 47.4, both type 1 and type 2) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, were retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register. (3) Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed. The sex ratio did not change significantly during the study period. (4) Conclusions: Our results support an association between the increased prevalence of narcolepsy cases and Pandemrix vaccination, but the effect of the virus itself cannot be ruled out as a contributing factor.

Dynamic social representations of the 2009 H1N1 pandemic: Shifting patterns of sense-making and blame.

We investigate dynamics of public perceptions of the 2009 H1N1 influenza pandemic to understand changing patterns of sense-making and blame regarding the outbreak of emerging infectious diseases. We draw on social representation theory combined with a dramaturgical perspective to identify changes in how various collectives are depicted over the course of the pandemic, according to three roles: heroes, villains and victims. Quantitative results based on content analysis of three cross-sectional waves of interviews show a shift from mentions of distant collectives (e.g., far-flung countries) at Wave 1 to local collectives (e.g., risk groups) as the pandemic became of more immediate concern (Wave 2) and declined (Wave 3). Semi-automated content analysis of media coverage shows similar results. Thematic analyses of the discourse associated with collectives revealed that many were consistently perceived as heroes, villains and victims.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

STUDY OBJECTIVES: Increased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed. METHODS: Individual records of narcolepsy patients were collected from 15 of 42 hospitals across China known to diagnose cases. Incidence was estimated assuming the representativeness of these hospitals. Age-specific incidence, epidemiological and clinical characteristics of patients were evaluated before, during, and after the 2009 H1N1 pandemic. Sensitivity analyses were conducted by including NT1 cases only and excluding the effect of the 2009 H1N1 vaccination. RESULTS: Average annual incidence was 0.79 per 100 000 person-years (PY) from 1990 to 2017 and 1.08 per 100 000 PY from 2003 to 2017. Incidence increased 4.17 (95% CI 4.12, 4.22) and 1.42 (95% CI 1.41, 1.44) fold during and after the 2009 H1N1 pandemic when compared to baseline. These results were robust in sensitivity analyses. Patients with the onset of narcolepsy during the pandemic period were younger (notably in 5-9-year-old strata), and the age shift toward younger children reversed to baseline following the pandemic. CONCLUSIONS: Increased incidence of narcolepsy was observed during the 2009 H1N1 pandemic period. This is likely to be associated with the circulation of the wild type A(H1N1)pdm09 virus. This observation should be considered for future influenza pandemic preparedness plans.

Accounting for cross-immunity can improve forecast accuracy during influenza epidemics.

Previous exposure to influenza viruses confers cross-immunity against future infections with related strains. However, this is not always accounted for explicitly in mathematical models used for forecasting during influenza outbreaks. We show that, if an influenza outbreak is due to a strain that is similar to one that has emerged previously, then accounting for cross-immunity explicitly can improve the accuracy of real-time forecasts. To do this, we consider two infectious disease outbreak forecasting models. In the first (the "1-group model"), all individuals are assumed to be identical and cross-immunity is not accounted for. In the second (the "2-group model"), individuals who have previously been infected by a related strain are assumed to be less likely to experience severe disease, and therefore recover more quickly, than immunologically naive individuals. We fit both models to estimated case notification data (including symptomatic individuals as well as laboratory-confirmed cases) from Japan from the 2009 H1N1 influenza pandemic, and then generate synthetic data for a future outbreak by assuming that the 2-group model represents the epidemiology of influenza infections more accurately. We use the 1-group model (as well as the 2-group model for comparison) to generate forecasts that would be obtained in real-time as the future outbreak is ongoing, using parameter values estimated from the 2009 epidemic as informative priors, motivated by the fact that without using prior information from 2009, the forecasts are highly uncertain. In the scenario that we consider, the 1-group model only produces accurate outbreak forecasts once the peak of the epidemic has passed, even when the values of important epidemiological parameters such as the lengths of the mean incubation and infectious periods are known exactly. As a result, it is necessary to use the more epidemiologically realistic 2-group model to generate accurate forecasts. Accounting for cross-immunity driven by exposures in previous outbreaks explicitly is expected to improve the accuracy of epidemiological modelling forecasts during influenza outbreaks.

Eurasian Avian-like M1 Plays More Important Role than M2 in Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.

Reassortant variant viruses generated between 2009 H1N1 pandemic influenza virus [A(H1N1)pdm09] and endemic swine influenza viruses posed a potential risk to humans. Surprisingly, genetic analysis showed that almost all of these variant viruses contained the M segment from A(H1N1)pdm09, which originated from Eurasian avian-like swine influenza viruses. Studies have shown that the A(H1N1)pdm09 M gene is critical for the transmissibility and pathogenicity of the variant viruses. However, the M gene encodes two proteins, M1 and M2, and which of those plays a more important role in virus pathogenicity remains unknown. In this study, the M1 and M2 genes of A(H1N1)pdm09 were replaced with those of endemic H3N2 swine influenza virus, respectively. The chimeric viruses were rescued and evaluated in vitro and in mice. Both M1 and M2 of H3N2 affected the virus replication in vitro. In mice, the introduction of H3N2 M1 attenuated the chimeric virus, where all the mice survived from the infection, compared with the wild type virus that caused 100 % mortality. However, the chimeric virus containing H3N2 M2 was still virulent to mice, and caused 16.6% mortality, as well as similar body weight loss to the wild type virus infected group. Compared with the wild type virus, the chimeric virus containing H3N2 M1 induced lower levels of inflammatory cytokines and higher levels of anti-inflammatory cytokines, whereas the chimeric virus containing H3N2 M2 induced substantial pro-inflammatory responses, but higher levels of anti-inflammatory cytokines. The study demonstrated that Eurasian avian-like M1 played a more important role than M2 in the pathogenicity of A(H1N1)pdm09 in mice.

Comparative epidemiology between the 2009 H1N1 influenza and COVID-19 pandemics.

In a short time, humanity has experienced two pandemics: the influenza A virus pandemic (pH1N1) in 2009 and the coronavirus disease 2019 (COVID-19) pandemic in 2020. Therefore, it is likely that the general population will erroneously seek to compare the two pandemics and adopt similar attitudes in facing them. However, the two pandemics have their intrinsic characteristics that distinguish them considerably; for example, the virulence of the infectious agents and the availability of treatment and vaccine. Consequently, given this knowledge gap between the pH1N1 and COVID-19 pandemics, we conducted this review to clarify and summarize, above all, the epidemiological historical aspects of these two viruses of great importance to global public health.

Impacts of Road Traffic Network and Socioeconomic Factors on the Diffusion of 2009 Pandemic Influenza A (H1N1) in Mainland China.

The 2009 pandemic influenza virus caused the majority of the influenza A virus infections in China in 2009. It arrived in several Chinese cities from imported cases and then spread as people travelled domestically by all means of transportation, among which road traffic was the most commonly used for daily commuting. Spatial variation in socioeconomic status not only accelerates migration across regions but also partly induces the differences in epidemic processes and in responses to epidemics across regions. However, the roles of both road travel and socioeconomic factors have not received the attention they deserve. Here, we constructed a national highway network for and between 333 cities in mainland China and extracted epidemiological variables and socioeconomic factors for each city. We calculated classic centrality measures for each city in the network and proposed two new measures (SumRatio and Multicenter Distance). We evaluated the correlation between the centrality measures and epidemiological features and conducted a spatial autoregression to quantify the impacts of road network and socioeconomic factors during the outbreak. The results showed that epidemics had more significant relationships with both our new measures than the classic ones. Higher population density, higher per person income, larger SumRatio and Multicenter Distance, more hospitals and college students, and lower per person GDP were associated with higher cumulative incidence. Higher population density and number of slaughtered pigs were found to advance epidemic arrival time. Higher population density, more colleges and slaughtered pigs, and lower Multicenter Distance were associated with longer epidemic duration. In conclusion, road transport and socioeconomic status had significant impacts and should be considered for the prevention and control of future pandemics.

Integration analysis of a miRNA-mRNA expression in A549 cells infected with a novel H3N2 swine influenza virus and the 2009 H1N1 pandemic influenza virus.

Swine are reservoirs for anthropogenic/zoonotic influenza viruses, and the prevalence and repeated introduction of the 2009 H1N1 pandemic influenza virus (pdm/09) into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans. However, studies aiming to identify miRNAs involved in the transfer of novel swine influenza virus infection to human cells are rare. In this investigation, from the view of small RNA, microarrays and high-throughput sequencing were used to detect differentially expressed miRNAs and mRNAs after human lung epithelial cells were infected with the following three stains of influenza viruses: a novel H3N2 swine influenza virus reassorted with pdm/09 fragments, pdm/09 and classical swine influenza virus. A miRNA-mRNA interaction map was generated to show the correlation between miRNAs related to infection by the viruses with human infective potential/capability. The expression of 4 miRNAs (hsa-miR-96-5p, hsa-miR-140-5p, hsa-miR-30a-3p and hsa-miR-582-5p) and 5 relevant mRNAs (RCC1, ERVFRD-1, RANBP1, SCARB2 and RPS29) was determined. The integration analysis indicated that these candidates have rarely been reported to be associated with influenza virus. Focusing on miRNA expression changes could reveal novel reassortant viruses with human infective potential that may provide insight into future pandemics.

Intra-host viral variability in children clinically infected with H1N1 (2009) pandemic influenza.

Recent in-depth genetic analyses of influenza A virus samples have revealed patterns of intra-host viral genetic variability in a variety of relevant systems. These have included laboratory infected poultry, horses, pigs, chicken eggs and swine respiratory cells, as well as naturally infected poultry and horses. In humans, next generation sequencing techniques have enabled the study of genetic variability at specific positions of the viral genome. The present study investigated how 454 pyrosequencing could help unravel intra-host genetic diversity patterns on the full-length viral hæmagglutinin and neuraminidase genes from human H1N1 (2009) pandemic influenza clinical cases. This approach revealed unexpected patterns of co-infection in a 3-week old toddler, arising from rapid and complex reassortment phenomena on a local epidemiological scale. It also suggested the possible existence of very low frequency mutants resistant to neuraminidase inhibitors in two untreated patients. As well as revealing patterns of intra-host viral variability, this report highlights technical challenges in the appraisal of scientifically and medically relevant topics such as the natural occurrence of homologous recombination or very low frequency drug-resistant variants in influenza virus populations.

Influenza infection control practices in labor and delivery units during the 2009 H1N1 influenza pandemic.

OBJECTIVE: To assess the presence and usefulness of written policies and practices on infection control consistent with the Center for Disease Control and Prevention's (CDC) guidance in hospital labor and delivery (L&D) units during the 2009 H1N1 influenza pandemic. SETTING: Online survey. PARTICIPANTS: Of 11,845 eligible nurses, 2,641 (22%) participated. This analysis includes a subset of 1,866 nurses who worked exclusively in L&D units. METHODS: A cross-sectional descriptive evaluation was sent to 12,612 members from the Association of Women's Health, Obstetric, and Neonatal Nurses (AWHONN) who reported working in labor, delivery, postpartum, or newborn care settings during the 2009 H1N1 influenza pandemic. RESULTS: Respondents (73.8%) reported that CDC guidance was very useful for infection control in L&D settings during the pandemic. We assessed the presence of the following infection control written policies, consistent with CDC's guidance in hospital L&D units, during the 2009 H1N1 influenza pandemic and their rate of implementation most of the time: questioning women upon arrival about recent flu-like symptoms (89.4%, 89.9%), immediate initiation of antiviral medicines if flu suspected or confirmed (65.2%, 49%), isolating ill women from healthy women immediately (90.7%, 84.7%), ask ill women to wear masks during L&D (67%, 57.7%), immediately separating healthy newborns from ill mothers (50.9%, 42.4%), and bathing healthy infants when stable (58.4%, 56.9%). Reported written policies for five of the six practices increased during the pandemic. Five of six written policies remained above baseline after the pandemic. CONCLUSIONS: Respondents considered CDC guidance very useful. The presence of written policies is important for the implementation of infection control practices by L&D nurses.

Influenza A (H1N1) 2009 Pandemic Calm Down the Prevalence of Acute Hepatitis A in the Latter Half of 2009: Korean Population Study / 대한소화기학회지

BACKGROUND/AIMS: There was a spiking incidence of acute hepatitis A (AHA) in 2009 summer, but it went down drastically after an outbreak of influenza A (H1N1). We assessed the relationship between 2009 H1N1 pandemic and AHA prevalence from August to December 2009. METHODS: We compared AHA cases nationwide and in our hospital for the period from the latter half of 2008 to the end of 2010. H1N1 cases in our hospital from August 2009 to December 2009 were included in the study and the correlation between 2009 H1N1 pandemic and AHA prevalence was assessed. RESULTS: The national surveillance system reported 2,233, 7,895, 15,231 and 7,660 AHA cases from 2007 to 2010, respectively. A similar trend was noted in our hospital in the same periods. Although the national total incidence was increased in 2009, it showed steep decreasing trend line in the final 21 weeks of 2009 (weeks 32-52), as compared with 2008 and 2010. The mean weekly incidence percentage (AHA cases in a week/total in a year) in weeks 32-52 of 2009 was 1.17+/-0.55%, significantly lower than that in 2008 and 2010 (1.61+/-0.43% and 1.56+/-0.51%; p<0.001). Furthermore, we found a significant negative correlation between 2009 H1N1 pandemic and AHA in our hospital for weeks 32-52 of 2009 (r=-0.597; p<0.001). CONCLUSIONS: The widespread occurrence of 2009 H1N1 pandemic highlighted the benefits of health care and good hygiene, such as effective hand washing and wearing of masks, which may have also interrupted hepatitis A virus transmission.