Progress in research of influenza vaccination in pregnant women / 中华流行病学杂志

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.

Network pharmacological analysis and experimental study of Pulsatilla chinensis against inflammatory injury caused by pneumonia in mice infected with influenza virus FM_1 / 中国中药杂志

Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.

Research progress on active components and mechanism of Isatidis Radix for influenza virus / 中国中药杂志

Isatidis Radix is the dried root of the Isatis indigotica, with pharmacological effects such as heat-clearing and detoxification, cooling blood and pharyngeal relief, antibacterial and anti-inflammatory effects. It is often used clinically to prevent and treat influenza and other diseases. In this paper, relevant domestic and foreign literatures in recent years were summarized, and it was found that Isatidis Radix lignans, indole alkaloids, polysaccharides, etc. were the main active components against influenza virus. Then its pharmacological effects and the mechanism of action were reviewed, providing a basis for in-depth research on the antiviral effect of Isatidis Radix.

Factores ambientales relacionados con la presentación de virus influenza A en aves silvestres / Environmental factors related to Influenza A virus occurrence in wild birds

RESUMEN La investigación y el interés por el virus influenza aviar han aumentado considerablemente en las últimas décadas en respuesta a los brotes de influenza aviar de alta patogenicidad en aves de corral y a su potencial zoonótico. Las aves silvestres acuáticas son el principal reservorio del virus en la naturaleza, por lo tanto, la comprensión de la dinámica de infección del virus influenza A (VIA) en estas poblaciones es fundamental para entender su potencial de persistencia en el ambiente y sus posibilidades de transmisión hacia aves domésticas y humanos. Se ha identificado que factores ambientales (como temperatura, precipitaciones, vegetación y características del paisaje, entre otros) pueden tener un importante rol en el mantenimiento y diseminación del virus en las zonas de concentración de aves silvestres. Sin embargo, los estudios que incluyen aspectos ecológicos del virus y que exploran la interacción entre la prevalencia del VIA en aves silvestres y el ambiente, continúan siendo escasos. En esta revisión se resumen los esfuerzos de investigación que se han realizado para identificar a los factores ambientales involucrados en la persistencia y transmisión del VIA en lugares de concentración de aves silvestres y cómo estos factores pueden incidir en la prevalencia del virus en estas poblaciones, generando diferencias en la presentación de la infección entre distintas zonas geográficas.

ABSTRACT Research and interest in avian influenza virus have increased considerably in recent decades in response to highly pathogenic avian influenza outbreaks in poultry and its zoonotic potential. Wild waterfowl are the main reservoir of the virus, therefore studying the dynamics of influenza A virus (IAV) infection in these populations is essential in order to understand its potential persistence in the environment and transmission to poultry and humans. It has been identified that environmental factors (such as temperature, rainfall, vegetation and landscape characteristics, among others) can play an important role in the maintenance and dissemination of the virus in the areas of concentration of wild birds. However, studies that include ecological aspects of the virus and explore the interaction between the prevalence of IAV in wild birds and environmental factors remain scarce. This review summarizes research efforts that have been made to identify the environmental factors involved in the persistence and transmission of IAV in areas of wild bird concentration and how these factors may influence the prevalence of the virus in these populations, generating differences in the presentation of the infection among different geographical areas.

Plano brasileiro de preparação para enfrentamento de uma pandemia de Influenza / Brazilian plan to prepare for confrontation of an Influenza pandemic

As mais diversas pandemias passadas deixaram um legado na história com um número significativo de óbitos e de pessoas enfermas. Essa experiência é capaz de mostrar a necessidade de elaboração de Planos de Preparação para Enfrentamento de Pandemias, flexíveis e capazes de dar resposta que o problema requer. Assim, o propósito desta revisão é proporcionar informações relativas a preparação e respostas antes, durante e depois de uma pandemia de influenza, cumprir seu papel na organização do Sistema Único de Saúde, além de servir como guia aos gestores das unidades federadas, subsidiando-os na estratégia para enfrentamento de situações de emergência. O plano contém diretrizes gerais que são essenciais à ação dos serviços de saúde. O processo e as respostas a uma possível pandemia de influenza devem ser mais importantes que os detalhes específicos que podem ser inaplicáveis a uma nova situação. De acordo com essa afirmativa é que procuramos apresentar um plano conciso com a certeza de que uma ameaça ou uma pandemia de influenza aumenta o nível de exigência de necessidade de uma ação integrada. Pelo caráter genérico, o Plano Nacional apresenta orientações gerais necessárias à intervenção não só do setor saúde e específicas, face a uma situação de emergência. A conseqüência, a conveniência e as respostas específicas devem ser continuamente revisadas e atualizadas. De modo geral, o Plano reúne as diretrizes de acordo com os períodos e fases e os planos específicos por área, contendo as medidas e os procedimentos que devem ser adotados, encontram-se anexos sob forma de links.

Comparison of antigenic mutation during egg and cell passage cultivation of H3N2 influenza virus

Factores sociodemográficos y fisiopatológicos asociados a la tuberculosis del sistema nervioso central en un Hospital Público de Lima-Perú, 2014-2017 / Sociodemographic and physiopathological factors associated with tuberculosis of the central nervous system in a Public Hospital of Lima-Peru, 2014-2017

Objetivo: Determinar los factores sociodemográficos y fisiopatológicos de la neurotuberculosis (NTB) en los pacientes registrados en el Programa de Control de la Tuberculosis (PCT) del Hospital Nacional Dos de Mayo. Materiales y Métodos: Se realizó un estudio transversal analítico, desarrollado entre Julio del 2014 y Julio del 2017. Se diseñó una ficha que incluyó datos sociodemográficos, fisiopatológicos y las características al diagnóstico. Se obtuvieron las razones de prevalencia (RP) crudos y ajustados, con intervalos de confianza al 95%. Resultados: Participaron 1038 pacientes. El 16% de toda la población y de 34% de las tuberculosis extra pulmonares tenia NTB. La forma clínica más frecuente fue la meningoencefalitis tuberculosa (MEC TB) (96%). Dentro de las manifestaciones clínicas destacaron las convulsiones (22%), cefalea (20%), signos meníngeos (18%) y trastorno del sensorio (16%). La presencia de NTB estuvo asociada al diagnóstico de VIH (RPa: 2,06; IC95%: 1,53-2,76; Valor p<0,001), condición de alcoholismo (RPa: 1,53; IC95%: 1,04-2,25; Valor p=0,030) y género femenino (RPa: 1,40; IC95%: 1,06-1,84; Valor p=0,019). Conclusiones: El diagnóstico de VIH, condición de alcoholismo y el género femenino son factores asociados a mayor frecuencia de NTB en el Hospital Dos de Mayo.

Objective: To determine the sociodemographic and physiopathological factors of neurotuberculosis (NTB) in the patients registered in the Tuberculosis Control Program (TCP) of the Hospital Nacional Dos de Mayo. Materials and Methods: Analytical cross- sectional study, developed between July 2014 and 2017 July. We designed a card that included data sociodemographic, pathophysiological and the diagnostic characteristics. Were obtained prevalence ratio (RP) raw and adjusted, with 95% confidence intervals. Results: 1038 patients participated. 16% of the entire population and 34% of the extrapulmonary tuberculosis had NTB. The most common clinical form was tuberculous meningoencephalitis (MEC TB) (96%). Within the clinical manifestations emphasized the seizures (22%), headache (20%), meningeal signs (18%) and sensory disorder (16%). The presence of NTB was associated with the diagnosis of HIV (aPR: 2.06, 95%CI: 1.53-2.76, P value <0.001), alcoholism (aPR: 1.53, 95%CI: 1.04-2.25, p value = 0.030) and female gender (aPR: 1.40, 95%CI: 1.06-1.84, p value = 0.019). Conclusions: The diagnosis of HIV, condition of alcoholism and the female gender are factors associated with increased frequency of NTB in the Hospital Dos de Mayo.

Conocimientos sobre enfermedades tipo influenza en estudiantes de Medicina de la Universidad de Guayaquil, Ecuador / Knowledge about influenza-like illnesses in medical students at Guayaquil University, Ecuador

RESUMEN Fundamento: las enfermedades tipo influenza son de fácil contagio y sus vías de transmisión difíciles de controlar si no son tratadas adecuadamente. Objetivo: determinar los conocimientos que poseen los estudiantes de pregrado y posgrado de la Facultad de Ciencias Médicas de la Universidad de Guayaquil sobre las enfermedades tipo influenza. Métodos: se realizó un estudio descriptivo transversal durante el mes de febrero de 2018. Se utilizaron métodos teóricos: análisis-síntesis e inducción-deducción, y empíricos: la encuesta en forma de cuestionario para indagar sobre el conocimiento de los estudiantes sobre la influenza. Resultados: la totalidad de ellos refirió poseer conocimientos sobre el tema. El 96,32 % de los de pregrado identificaron como más frecuentes la transmisión de tipo viral y el contagio por contacto con persona enferma; mientras en posgrado el 100 % expresó conocimientos al respecto; la complicación habitual más señalada fue la automedicación referida por el 72 % en pregrado y en el posgrado por el 57 %. En relación con las medidas preventivas, manifestaron conocerlas el 87 % y 89 % en el pregrado y posgrado respectivamente. Conclusiones: se comprobó que el grado de conocimientos sobre las enfermedades tipo influenza en cuanto a transmisión, etiología, acciones de protección y medidas preventivas en estos estudiantes de la Facultad de Ciencias Médicas de la Universidad de Guayaquil es aceptable, pero aún persisten algunas carencias identificadas en el estudio realizado.

ABSTRACT Background: influenza is an easily transmitted disease and its way of transmission is difficult to control if it is not properly treated. Objective: to determine the knowledge undergraduate and graduate students have on influenza-like disease at Guayaquil University Medical Sciences Faculty. Methods: a cross-sectional descriptive study was carried out at Guayaquil University Medical Sciences Faculty, during the month of February 2018. Theoretical methods were used: analysis-synthesis and induction-deduction, and empirical methods: the survey in the form of a questionnaire to inquire about students' knowledge on influenza. Results: all the students reported having knowledge on influenza. 96,32 % of the undergraduates identified the transmission of viral type by contact with the sick person as more frequent; in postgraduate studies 100 % expressed knowledge in this regard; the most common complication was self-medication referred by 72 % of undergraduate students in 72 % and in postgraduate students by 57 %. In relation to preventive measures, 87 % and 89 % expressed knowledge in undergraduate and postgraduate respectively. Conclusions: it was found that the degree of knowledge on the influenza-like disease in terms of transmission, etiology, protective actions and preventive measures in these students at Guayaquil University Medical Sciences Faculty is acceptable. There are still some shortcomings identified in the study carried out.

Seasonality and etiology of croup in pediatric patients hospitalized with lower respiratory tract infections: A long-term study between 2009 and 2017

PURPOSE: Croup is a common respiratory disease in children. The aim of this study was to analyze the epidemiology, etiology, and seasonal variations of respiratory virus infections in children with croup. METHODS: From October 2009 to September 2017, children admitted with croup to Gachon University Gil Medical Center under the age of 18 years were enrolled in this study. We retrospectively reviewed patients' medical records. RESULTS: A total of 1,053 of 27,330 patients (3.9%) infected with lower respiratory infections were diagnosed as having croup. In the age distribution, croup was most common (50.0%) in children aged 1 to <2 years. There were 2 peaks, the major in summer (July to August) and the minor in spring (March to May). Parainfluenza virus type 1 (15.8%) was most prevalent and coincided with the summer peaks of croup. Influenza virus type B and parainfluenza virus type 3 were the most frequent etiologic agents in a spring peak of croup. Although parainfluenza virus type 1 was predominant of all ages, human coronavirus was a significant cause of croup in children younger than 1 year, whereas influenza virus played an important role in children above the age of 3 years. CONCLUSION: Seasonality and epidemiology of croup varied with age and regions. Two peaks of seasonal fluctuation were in summer and spring, which were related to the seasonality of respiratory viruses in croup. These results may be helpful in planning clinical and research needs.

Development of a HA1-specific enzyme-linked immunosorbent assay against pandemic influenza virus A H1N1

PURPOSE: Enzyme-linked immunosorbent assay (ELISA) has been used in the diverse field to evaluate influenza virus infection; for the surveillance, diagnosis, efficacy evaluation, and development of the vaccine. The aim of this study was to establish an ELISA for detecting HA strain-specific antibodies using recombinant pandemic A H1N1 (pH1N1) HA1 (rHA1) protein. MATERIALS AND METHODS: rHA1 was produced in baculovirus system. The clinical performance of the developed ELISA was validated using human serum samples, by comparison with standard methods for detecting a neutralizing antibody; hemagglutination inhibition (HI) assay and microneutralization test (MNT). The ability of the ELISA system to evaluate the efficacy test of an influenza vaccine was explored by measuring antibody levels in the serum of vaccinated mice. RESULTS: Our ELISA could detect anti-rHA1 antibody in influenza-infected patients and vaccinated subjects. Compared to HI assay and MNT as reference methods, our method showed good performance in detection of anti-rHA1 antibody. Detection of the anti-rHA1 antibody in vaccinated mice and its correlation with titers in HI assay was also proved in a mice model. CONCLUSION: An ELISA system using rHA1 of pH1N1 influenza virus was developed, and showed good clinical performance in diagnosis of influenza virus infection and evaluation of the vaccination efficacy in both human and animal models.

Modification of the Conventional Influenza Epidemic Models Using Environmental Parameters in Iran / 대한의료정보학회지

OBJECTIVES: The association between the spread of infectious diseases and climate parameters has been widely studied in recent decades. In this paper, we formulate, exploit, and compare three variations of the susceptible-infected-recovered (SIR) model incorporating climate data. The SIR model is a well-studied model to investigate the dynamics of influenza viruses; however, the improved versions of the classic model have been developed by introducing external factors into the model. METHODS: The modification models are derived by multiplying a linear combination of three complementary factors, namely, temperature (T), precipitation (P), and humidity (H) by the transmission rate. The performance of these proposed models is evaluated against the standard model for two outbreak seasons. RESULTS: The values of the root-mean-square error (RMSE) and the Akaike information criterion (AIC) improved as they declined from 8.76 to 7.05 and from 98.12 to 93.01 for season 2013/14, respectively. Similarly, for season 2014/15, the RMSE and AIC decreased from 8.10 to 6.45 and from 117.73 to 107.91, respectively. The estimated values of R(t) in the framework of the standard and modified SIR models are also compared. CONCLUSIONS: Through simulations, we determined that among the studied environmental factors, precipitation showed the strongest correlation with the transmission dynamics of influenza. Moreover, the SIR+P+T model is the most efficient for simulating the behavioral dynamics of influenza in the area of interest.

Comparison of clinical severity between single- and coinfections of respiratory syncytial virus and influenza virus with common respiratory viruses

PURPOSE: Multiple virus infections may affect clinical severity. We investigated the effect of coinfection of respiratory syncytial virus (RSV) and influenza virus with other respiratory viruses on clinical severity. METHODS: Data from 634 samples of a single tertiary hospital between September 2014 and April 2015 were analyzed for clinical characteristics (fever duration and O2 need, steroid use, and ICU care) between single infection and coinfection of RSV (n=290) and influenza virus (n=74) with 16 common respiratory viruses from hospitalized children. RESULTS: The RSV coinfection group (n=109) (3.1±2.7 days) showed significantly longer fever duration than the RSV single infection group (n=181) (2.6±2.6 days) (P=0.04), while there was no difference in O2 need, steroid use or ICU care in the 2 groups. The influenza coinfection group (n=38) showed significantly higher O2 need than the influenza single infection group (n=36) (21.1% vs. 5.6%, P=0.05), while there was no difference in fever duration between the 2 groups. CONCLUSION: The results indicate that RSV and Influenza coinfections can increase clinical severity and that the severity may be influenced by the nature of coinfecting viruses.

Viral etiology of acute respiratory infections in children in Southern Iran

Abstract INTRODUCTION: Prevalence of influenza A virus (Flu-A), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) was assessed in children with acute respiratory infections (ARIs). METHODS: Nasopharyngeal aspirates and throat swabs were subjected to real-time polymerase chain reaction (PCR) to detect RSV and Flu-A and to conventional PCR to detect hMPV. RESULTS: Of the 156 children assessed, 93 (59.6%) carried at least one virus, with 35.9% positive for RSV, 14.1% for hMPV, and 9.6% for Flu-A. The prevalence of co-infections was 2.6%. CONCLUSIONS: The high detection rate may reflect increased sensitivity of real-time PCR compared to traditional PCR and viral culture.

A Study on Factors Associated with Duration of Influenza Virus Shedding in Children / 계명의대학술지

To prevent the spread of influenza among infants and adolescents attending kindergartens and schools, proper quarantining of those who are ill is necessary. In this study, the rapid antigen test (RAT) was performed in patients to investigate the factors affecting the duration of virus shedding. The study included pediatric patients who were diagnosed with influenza by RAT at Daedong Hospital between November 2016 and April 2019. We identified the influenza subtype, age, gender, fever duration, oseltamivir medications, and time gap between fever subsided and RAT examination through chart review. A total of 330 patients were examined at discharge. The average age for RAT positive and negative patients was 6.32 ± 4.26 years and 8.47 ± 4.54 years, respectively. The average duration of fever for the RAT positive patients was 3.84 ± 1.09 days, and for those who were RAT negative was 4.191 ± 1.39. The average number of doses oseltamivir for RAT positive and negative patients was 7.68 ± 1.57 and 8.72 ± 1.37, respectively. The RAT was performed 24 to 48 hours after fever subsided (TG 24–48H group). At this time, 60 patients were positive and the rate of positive expression was 55.56%. Of the TG 48–72H group, 36 patients (26.09%) were positive. Of the TG 72–96H group, 18 patients (21.43%) were positive. Age, fever duration, number of doses oseltamivir and time gap after fever subsided were the factors that influenced the duration of influenza virus shedding. These factors should be considered during the quarantining influenza patients.

Antibody responses after vaccination against equine influenza in Korea in 2016–2018 / 대한수의학회지

Equine influenza (EI) is the main cause of respiratory illness in equines across the globe and is caused by equine influenza A virus (EIV-A), which has impacted the equine industry internationally because of the marginal mortality and high morbidity. In the present study, the immune responses after equine influenza vaccination were evaluated in 4,144 horses in Korea using the hemagglutination inhibition (HI) assay. The equine influenza virus (EIV), A/equine/South Africa/4/03 (H3N8), was used as the antigen in the HI assay. The mean seropositive rates were 89.2% (97.4% in 2016, 77.6% in 2017, and 92.4% in 2018). This paper highlights the advances in understanding the effects of vaccines and control strategies for mitigating the emerging menace by EIV.

Characteristics and Outcomes of Patients with Pulmonary Acute Respiratory Distress Syndrome Infected with Influenza versus Other Respiratory Viruses / 결핵

BACKGROUND: Although the frequency of respiratory viral infection in patients with pulmonary acute respiratory distress syndrome (ARDS) is not uncommon, clinical significance of the condition remains to be further elucidated. The purpose of this study was to compare characteristics and outcomes of patients with pulmonary ARDS infected with influenza and other respiratory viruses. METHODS: Clinical data of patients with pulmonary ARDS infected with respiratory viruses January 2014–June 2018 were reviewed. Respiratory viral infection was identified by multiplex reverse transcription–polymerase chain reaction (RT-PCR). RESULTS: Among 126 patients who underwent multiplex RT-PCR, respiratory viral infection was identified in 46% (58/126): 28 patients with influenza and 30 patients with other respiratory viruses. There was no significant difference in baseline and clinical characteristics between patients with influenza and those with other respiratory viruses. The use of extracorporeal membrane oxygenation (ECMO) was more frequent in patients with influenza than in those with other respiratory viruses (32.1% vs 3.3%, p=0.006). Co-bacterial pathogens were more frequently isolated from respiratory samples of patients with pulmonary ARDS infected with influenza virus than those with other respiratory viruses. (53.6% vs 26.7%, p=0.036). There were no significant differences regarding clinical outcomes. In multivariate analysis, acute physiology and chronic health evaluation II was associated with 30-mortality (odds ratio, 1.158; 95% confidence interval, 1.022–1.312; p=0.022). CONCLUSION: Respiratory viral infection was not uncommon in patients with pulmonary ARDS. Influenza virus was most commonly identified and was associated with more co-bacterial infection and ECMO therapy.

Estimating Influenza-associated Mortality in Korea: The 2009–2016 Seasons / 예방의학회지

OBJECTIVES: Estimating influenza-associated mortality is important since seasonal influenza affects persons of all ages, causing severe illness or death. This study aimed to estimate influenza-associated mortality, considering both periodic changes and age-specific mortality by influenza subtypes. METHODS: Using the Microdata Integrated Service from Statistics Korea, we collected weekly mortality data including cause of death. Laboratory surveillance data of respiratory viruses from 2009 to 2016 were obtained from the Korea Centers for Disease Control and Prevention. After adjusting for the annual age-specific population size, we used a negative binomial regression model by age group and influenza subtype. RESULTS: Overall, 1 859 890 deaths were observed and the average rate of influenza virus positivity was 14.7% (standard deviation [SD], 5.8), with the following subtype distribution: A(H1N1), 5.0% (SD, 5.8); A(H3N2), 4.4% (SD, 3.4); and B, 5.3% (SD, 3.7). As a result, among individuals under 65 years old, 6774 (0.51%) all-cause deaths, 2521 (3.05%) respiratory or circulatory deaths, and 1048 (18.23%) influenza or pneumonia deaths were estimated. Among those 65 years of age or older, 30 414 (2.27%) all-cause deaths, 16 411 (3.42%) respiratory or circulatory deaths, and 4906 (6.87%) influenza or pneumonia deaths were estimated. Influenza A(H3N2) virus was the major contributor to influenza-associated all-cause and respiratory or circulatory deaths in both age groups. However, influenza A(H1N1) virus–associated influenza or pneumonia deaths were more common in those under 65 years old. CONCLUSIONS: Influenza-associated mortality was substantial during this period, especially in the elderly. By subtype, influenza A(H3N2) virus made the largest contribution to influenza-associated mortality.