Human infection from avian-like influenza A (H1N1) viruses in pigs, China

In investigating influenza in an immunodeficient child in China, in December 2010, we found that the influenza virus showed high sequence identity to that of swine. Serologic evidence indicated that viral persistence in pigs was the source of infection. Continued surveillance of pigs and systemic analysis of swine influenza isolates are needed.     

Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States

As a result of human-to-pig transmission, pandemic influenza A (H1N1) 2009 virus was detected in pigs soon after it emerged in humans. In the United States, this transmission was quickly followed by multiple reassortment between the pandemic virus and endemic swine viruses. Nine reassortant viruses representing 7 genotypes were detected in commercial pig farms in the United States. Field observations suggested that the newly described reassortant viruses did not differ substantially from pandemic (H1N1) 2009 or endemic strains in their ability to cause disease. Comparable growth properties of reassortant and endemic viruses in vitro supported these observations; similarly, a representative reassortant virus replicated in ferrets to the same extent as did pandemic (H1N1) 2009 and endemic swine virus. These novel reassortant viruses highlight the increasing complexity of influenza viruses within pig populations and the frequency at which viral diversification occurs in this ecologically important viral reservoir.     

Seroconversion to pandemic (H1N1) 2009 virus and cross-reactive immunity to other swine influenza viruses

To assess herd immunity to swine influenza viruses, we determined antibodies in 28 paired serum samples from participants in a prospective serologic cohort study in Hong Kong who had seroconverted to pandemic (H1N1) 2009 virus. Results indicated that infection with pandemic (H1N1) 2009 broadens cross-reactive immunity to other recent subtype H1 swine viruses.     

An elastase-dependent attenuated heterologous swine influenza virus protects against pandemic H1N1 2009 influenza challenge in swine

Influenza virus infections continue to cause production losses in the agricultural industry in addition to being a human public health concern. The primary method to control influenza is through vaccination. However, currently used killed influenza virus vaccines must be closely matched to the challenge virus. The ability of an elastase-dependent live attenuated influenza A virus was evaluated to protect pigs against the pandemic H1N1 2009 influenza virus. Pigs vaccinated intranasally or intratracheally with the elastase-dependent swine influenza virus (SIV) vaccine had significantly reduced macroscopic and microscopic lung lesions and lower viral loads in the lung and in nasal swabs. Thus, elastase-dependent SIV mutants can be used as live-virus vaccines against swine influenza in pigs. In addition, low levels of cross-neutralizing antibodies to H1N1 2009 were elicited prior to challenge by the swine adapted H1N1 avian strain vaccine.     

Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice

Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza.     

CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses

A novel strain of H1N1 influenza A virus (pH1N1) emerged in 2009, causing a worldwide pandemic. Several studies suggest that this virus is antigenically more closely related to human influenza viruses that circulated prior to 1957 than viruses of more recent seasonal influenza varieties. The extent to which individuals who are naïve to the 2009 pH1N1 virus carry cross-reactive CD8+ T cells is not known, but a certain degree of reactivity would be expected since there is substantial conservation among the internal proteins of the virus. In the present study, we examined the production of multiple cytokines in response to virus from CD8+ T cells in healthy adult subjects, between 18 and 50 years of age (born post 1957), who had no evidence of exposure to the 2009 pH1N1 virus, and had blood collected prior to the emergence of the pandemic in April of 2009. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with a panel of live viruses, and assayed by intracellular cytokine staining and flow cytometry. Although results were variable, most subjects exhibited cytokine positive CD8+ T cells in response to pH1N1. Cytokine producing cells were predominantly single positive (IL2, IFNγ, or TNFα); triple-cytokine producing cells were relatively rare. This result suggests that although many adults carry cross-reactive T cells against the emergent pandemic virus, these cells are in a functionally limited state, possibly because these subjects have not had recent exposure to either seasonal or pandemic influenza strains.     

Serologic survey of pandemic influenza A (H1N1 2009) in Beijing, China

Objective

To examine the frequency and distribution of antibodies against pandemic influenza A (H1N1 2009) [H1N1] in populations in Beijing and elucidate influencing factors.

Methods

In January 2010, a randomized serologic survey of pandemic influenza A (H1N1 2009) was carried out. Six districts that were randomly selected with a total of 4601 participants involved in the survey have their antibody level tested by hemagglutination inhibition assay.

Results

Among the 4601 participants, the overall seropositive rate for pandemic influenza A (H1N1 2009) antibodies was 31.7%. The seropositivity prevalence in participants who received the pandemic H1N1 vaccination was 60.9%. Only 53.1% of the pandemic influenza A (H1N1 2009) seropositive individuals who had not received the vaccination experienced respiratory tract infection symptoms. Multivariate logistic regression revealed that factors such as age, occupation, dwelling type, whether the participant's family included students in school, and the vaccination history with pandemic influenza A (H1N1 2009) were associated with antibody titers (p < 0.05).

Conclusions

Our data indicated that almost 30.0% of the residents had appropriate antibody titers against pandemic influenza A (H1N1 2009) in Beijing, and these titers may provide an immune barrier.     

The 2009 influenza A (H1N1) pandemic

Prior to 2009, The Netherlands had prepared itself extensively for a potential pandemic. Multidisciplinary guidelines had been drafted to control transmission and limit adverse outcomes for both a phase of early incidental introduction and for a phase with widespread transmission. The Ministry of Health had ensured a supply and distribution schedule for antivirals and negotiated a contract for vaccine purchases. During the pandemic, existing surveillance was expanded, the established infectious disease response structure was activated, and the previously prepared protocols for communication, diagnostics, use of antivirals, and vaccination implementation were operationalized and implemented. When the pandemic turned out to be less severe than many had anticipated, risk communication and rapid modification of guidelines and communication became a major challenge. Antivirals and pandemic vaccines were reserved for those at high risk for severe outcomes only. Overall, the impact of the pandemic was comparable to the impact of an average seasonal influenza epidemic, but with a shift in (severe) outcomes from the very young and elderly toward young adults. Established prepared protocols enabled timely coordinated responses. In preparing for the worst, sufficient attention must be given to preparing for a mild scenario as well.     

Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1 influenza virus in pigs

The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North American H1 SIV, it is unknown if vaccines currently used in U.S. swine would cross-protect against infection with the pandemic A/H1N1. The objective of this study was to evaluate the efficacy of inactivated vaccines prepared with North American swine influenza viruses as well as an experimental homologous A/H1N1 vaccine to prevent infection and disease from 2009 pandemic A/H1N1. All vaccines tested provided partial protection ranging from reduction of pneumonia lesions to significant reduction in virus replication in the lung and nose. The multivalent vaccines demonstrated partial protection; however, none was able to prevent all nasal shedding or clinical disease. An experimental homologous 2009 A/H1N1 monovalent vaccine provided optimal protection with no virus detected from nose or lung at any time point in addition to amelioration of clinical disease. Based on cross-protection demonstrated with the vaccines evaluated in this study, the U.S. swine herd likely has significant immunity to the 2009 A/H1N1 from prior vaccination or natural exposure. However, consideration should be given for development of monovalent homologous vaccines to best protect the swine population thus limiting shedding and the potential transmission of 2009 A/H1N1 from pigs to people.     

Reassortment between swine influenza A viruses increased their adaptation to humans in pandemic H1N1/09

In April 2009, pandemic H1N1/09 influenza, which originated from swine influenza, appeared in North America, and it has since spread globally among humans. It is important to know how swine influenza A virus broke the host barrier to cause a pandemic. We analyzed 673 strains of human, avian, and swine influenza viruses and assessed the internal genes PB2, PB1, PA, NP, M, and NS. Here we found accumulation of mutations in segments that were retained as well as introduced due to genetic reassortment of viruses. The retained segments may have to mutate to accommodate new segments. The mutations caused by interaction among segments retained and introduced due to reassortment between swine influenza viruses may have increased the adaptation of the virus to humans, leading to pandemic H1N1/09. We indicate the sites that probably contributed to the acquisition of efficient human-to-human transmission.     

Imported pigs may have introduced the first classical swine influenza viruses into Mainland China

ObjectivesThe first classical swine influenza A H1N1 viruses were isolated in Mainland China in 1991. To aid surveillance of swine influenza viruses as part of pandemic preparedness, we sought to identify their origin.MethodsWe sequenced and phylogenically analyzed 19 swine influenza viruses isolated in 1991 and 1992 in China and compared them with viruses isolated from other regions during the same period.ResultsAll 19 swine influenza viruses analyzed in our study shared the highest similarity with the classical swine influenza virus A/Swine/Maryland/23239/1991 (H1N1). Phylogenetic trees of eight segmented genes exhibited similar topology, with all segments in the cluster of classical swine influenza viruses. In addition, antigenic analysis also indicated that the tested isolated were related to classical swine influenza isolates.ConclusionsClassical swine H1N1 influenza viruses were predominant in Beijing pig herds during this period. Since both antibody and virus detections did not indicate the presence of CS H1N1 before 1991 in Mainland China, we combined with the data on pigs imported to and exported from China and concluded that these viruses might spread to China via pigs imported from North America and that they could affect the genetic evolution and transmission dynamics of swine influenza viruses in Hong Kong.     

The association of seasonal influenza vaccination with pandemic influenza H1N1 2009 infection

In 2010 Skowronski and colleagues reported that seasonal influenza vaccine appeared to increase the risk of pandemic influenza H1N1 2009 (pH1N1) infection during the first pandemic wave in Canada [1]. They suggested a number of possible explanations for their unexpected finding: firstly, that the results were an artefact of selection bias or confounding; secondly, that the results were due to partial mediation through a biological mechanism; and thirdly, that the results were due to a direct immune mechanism, such as antibody dependent enhancement [1]. In a recent paper in Vaccine, Rosella and colleagues have investigated in detail the first of these possibilities, confirming that it is unlikely an unidentified confounder could have explained the findings [2].     

Distribution and risk factors of 2009 pandemic influenza A (H1N1) in mainland China

Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.     

Severe illness from 2009 pandemic influenza A (H1N1)--Utah, 2009-10 influenza season

Influenza-associated hospitalizations have been a reportable condition in Utah since 2005, and surveillance for influenza hospitalizations has been a valuable tool for identifying and tracking the population impact of serious influenza illness. During the 2009 influenza A (H1N1) pandemic, Utah public health officials used comparisons with hospitalization data from three previous influenza seasons to rapidly assess the impact of 2009 H1N1 and enable public health authorities to target persons at greatest risk for severe illness. This report summarizes the results of that assessment, which determined that 1,327 2009 H1N1 hospitalizations were reported, compared with an average of 435 seasonal influenza hospitalizations during three previous influenza seasons, and 25.5% of 2009 H1N1 hospitalizations resulted in severe illness (intensive-care unit [ICU] admission or death), compared with 14.0% of seasonal influenza hospitalizations. In addition, 2009 H1N1 disproportionately affected racial/ethnic minorities, pregnant women, and residents of Salt Lake County (the state's most densely populated county). During the 4-month "spring wave" of the H1N1 pandemic, a greater percentage of hospitalizations (30.9%) resulted in severe illness than during the 9-month "fall wave" (23.0%). Surveillance for influenza hospitalizations can provide essential data to public health authorities that will help them identify those populations at greatest risk for severe illness.     

北京市2009年甲型H1N1流感疫情分析

目的 分析北京市2009年甲型H1N1流感流行病学特征.方法 采用SPSS11.0软件,对北京市2009年甲型H1N1流感确诊病例的流行病学特征进行描述与分析.结果 2009年北京市共确诊甲型H1N1流感10 802例,重症、危重症病例621例,死亡73例,病死率为0.7%(73/10 802);北京市甲型H1N1流感流行过程可分为输入期、传播期、扩散期、稳中有降期等4个阶段;感染者以青少年为主,占47.9%(5169/10 802),男女性别比为1.3:1;职业分布以学生最多,占52.2%(5 639/10 802),重症、危重症病例及死亡病例均以离退人员为多,分别为15.9%(99/621)及23.3%(17/73);10月份达到流行高峰.结论 北京市2009年甲型H1N1流感病例以青少年学生为主,重症、危重症病例及死亡病例均以离退人员为多.     

2009年广东省甲型H1N1流感流行特征分析

目的分析2009年广东省甲型H1N1流感大流行的流行特征,为采取相应的防控措施提供科学依据。方法收集中国疾病监测信息报告管理系统及广东省流感监测系统的流感样病例监测、病原学监测及暴发疫情监测数据,采用描述性流行病学方法分析2009年广东省甲型H1N1流感的流行特征,并用流感监测数据来估算广东省2009年到医院就诊者中的甲型H1N1流感病例数。结果2009年5月18日广东省报告首例甲型H1N1流感病例,截止2009年12月31日共有21个地级市累计报告甲型H1N1流感确诊病例9 784例,其中重症病例346例,危重病例141例,死亡36例;每周报告甲型H1N1流感病例数占全年病例总数的构成比高峰与流感监测的甲型H1N1流感就诊指数高峰相一致,均出现在2009年11月,并在12月回落,且流感样病例就诊指数也降至警戒线(5%)以下,与季节性流感高峰(7月)完全不同。从病例输入到社区传播可划分为:以国外病例输入为主的输入散发期(5月18日至6月17日);出现聚集性病例,病例主要局限于珠江三角洲的有限传播期(6月18日至7月30日);在全省流感监测网络中连续检出甲型H1N1流感核酸阳性病例为特征的持续传播期(7月31日至8月31日);病例以学校暴发为特征并在全省各市蔓延的广泛传播期(9月1日至12月31日)。分析834例临床资料完整的病例的临床表现主要以发热(95.56%)、咳嗽(59.11%)、咽痛(42.45%)等呼吸道症状为主。估算广东省2009年到医院就诊者中甲型H1N1流感感染数不少于270万例。结论广东省2009年甲型H1N1流感流行高峰出现在11月份,为单月高峰,多数病例临床表现温和,推算在全人群中感染率尚在低水平。     

Coverage and predictors of vaccination against 2009 pandemic H1N1 influenza in Madrid, Spain

This study aimed to ascertain the coverage of vaccination against pandemic influenza in individuals aged over 6 months for whom vaccination is indicated due to a chronic health condition using as data source clinical information recorded in the primary care clinical history.Of all those for whom vaccination was indicated (1,114,632), 14.6% (162,616) finally received the vaccine. There were statistically significance differences in coverage for sex (16.5% for men and 13.1% for women), age groups (5% for people under 30 years and 20% for those over 60), number of chronic conditions (11.1% for one condition, 22.5% for two conditions, and 31.3% for three or more conditions) and depending on the chronic health condition considered.The probability of being vaccinated increased with male sex, age, number of indications, type of medical card (lower among no income) and having been vaccinated against 2009 season influenza.We concluded that the coverage finally reached for those people with an indication due to chronic health condition in the H1N1 campaign was much lower than expected and wished. It is essential to investigate the different factors that could have intervened in the behavior of the population so that more efficient approaches can be adopted in future influenza pandemics.