Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.     

Effectiveness and safety of pandemic influenza A (H1N1) 2009 vaccine in healthcare workers at a university hospital in Japan

Pandemic influenza A (H1N1) virus (AH1pdm) emerged in April 2009. An inactivated, split-virus, unadjuvanted AH1pdm vaccine was manufactured in Japan, and vaccination was initiated with top priority for healthcare workers (HCWs) on October 19, 2009. A retrospective cohort study was conducted to evaluate the effectiveness of a single-dose vaccine for HCWs in a hospital in Japan. A total of 1,567 (84.5%) of 1,854 HCWs were vaccinated. Thirty-seven were infected with AH1pdm before the vaccine became available, and were excluded. The other 250 were not vaccinated for personal reasons. We analyzed the influenza infection rate with or without vaccination and related adverse events. Among the 1,817 HCWs without previous infection, 37 were infected with AH1pdm; 13 (5.2%) of 250 unvaccinated HCWs became infected, which was a significantly higher rate than the 24 (1.5%) of 1,567 vaccinated HCWs (P=0.001). Multivariate analysis revealed that age of 20-29 years was a risk factor for infection (adjusted odds ratio [aOR], 3.7; P<0.001), and that vaccination was a preventive factor (aOR, 0.20; P<0.001). Adverse events occurred in 549 of 1,060 HCWs, but most were mild. Although vaccination was carried out during AH1pdm epidemic expansion, the single-dose AH1pdm vaccine proved effective in HCWs, and severe adverse events were rare.     

Hospitalizations associated with pandemic influenza A (H1N1) 2009 in asthmatic children in Japan

BackgroundThe pandemic influenza A (H1N1) 2009 [pdm (H1N1) 2009] spread through the world in 2009, producing a serious epidemic in Japan. Since it was suggested early that asthma is a risk factor for an increased severity of the infection, the Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) organized a working group for countermeasures, and investigated asthmatic children admitted to the hospitals for pdm (H1N1) 2009 infection.MethodsAn appeal was made on the home page of the JSPACI to medical practitioners to input clinical information about asthmatic and non-asthmatic children (0–19 years) admitted to the hospital with pdm (H1N1) 2009 infection.ResultsA total of 862 children (390 with asthma, and 472 without asthma) from 61 medical centers were registered, and the data of 333 asthmatic children and 388 non-asthmatic children in all were entered in the analyses. The mean age was 7.4 ± 2.9 years in the asthma group and 6.9 ± 3.8 years in the non-asthma group. The percentage of children admitted for respiratory symptoms was significantly higher in the asthma group than in the non-asthma group (p < 0.001). There was no significant difference in the frequency of admission to the ICU or need for mechanical ventilation support between the two groups. No definite trend was detected in the relationship between the severity of asthma and the intensity of asthma attack. Antiviral drugs were administered within 24 hours in about 85% of the patients in both groups.ConclusionsAsthma may not be a risk factor for severe pdm (H1N1) 2009 infection in children.     

四川省2009甲型H1N1流感的流行病学特征

目的分析四川地区甲型H1N1流感流行病学特点,为今后新发传染病的防控提供参考。方法回顾性分析我院2009年收治的271例甲型H1N1流感病例的来源、年龄及时间分布。结果 1.271例甲型H1N1流感病例,男∶女为1.09∶1,随着病情加重发病年龄逐渐增加,病程亦逐渐延长;2.轻症患者均无基础疾病,危重症患者基础疾病较重症患者多且重;3.绝大多数患者年龄在10~30岁（211例,77.87%）,轻症及重症中无≤2岁及≥65岁的患者,危重症中≥65岁者2例;4.疫情早期（5~9月）患者均为轻症,以输入病例为主（52例,19.19%）,疫情后期以本土暴发病例为主（9月以后）有危重症出现。结论新发传染病疫情早期以轻症、输入病例为主,后期随着社区聚集性疫情,有重危症患者出现;患者年龄、基础疾病是该疾病严重程度的重要影响因素。     

2009年甲型H1N1流感大流行重症病例的治疗

本文就呼吸支持、药物治疗（抗病毒药物、皮质类固醇、抗菌药物、乌司他丁）、血浆疗法与营养支持及抗凝疗法等方面介绍了重症甲型H1N1流感的救治经验。随着病例的增加,这些经验对临床医生有很好的指导意义。     

Clinical presentation and lung function of children hospitalized with 2009 pandemic influenza A (H1N1) pneumonia

To determine the clinical presentation and subsequent lung function following pneumonia caused by 2009 pandemic influenza A (H1N1), pH1N1, in children aged 5-15 years hospitalized from June to September 2009, we contacted patients meeting the criterion 3-6 months post-hospitalization. Of the 88 patients contacted, 31 (35.2%) had pH1N1 and 57 (64.8%) had infections due to other viral pathogens (non-pH1N1), the mean age was 10.4 years and 52 (59%) were boys. Compared to non-pH1N1 patients, the pH1N1 patients were more likely to have a high fever (96.8% vs 77.2%, p = 0.03), sore throat (58.1% vs 33.3%, p = 0.03), and injected pharynx (80.6% vs 40.4%, p = 0.001). At 3-6 months after pneumonia onset, means for FVC, FEV1, FEV1/FVC, FEF25-75%, and PEF were within normal limit in both the pH1N1 and non-pH1N1 groups. Five (28%) of 18 pH1N1 children and 4 (20%) of 20 non-pH1N1 children had abnormal lung function results. All were restrictive type. In conclusion, pH1N1 pneumonia were more likely to present with high fever, sore throat, and pharyngeal injection than pneumonia from other viruses. About one quarter of the children who had pH1N1 had restrictive lung function 3-6 months after infection. This number did not differ from the non-pH1N1 group.     

Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis

The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection.     

Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine

Please cite this paper as: Deng et al. (2012). Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine. Influenza and Other Respiratory Viruses 6(3), e42–e47. Background Swine have receptors for both human and avian influenza viruses and are a natural host for influenza A viruses. The 2009 influenza A(H1N1) pandemic (H1N1pdm) virus that was derived from avian, human and swine influenza viruses has infected pigs in various countries. Objectives To investigate the relationship between the H1N1pdm viruses isolated from piggery outbreaks in Australia and human samples associated with one of the outbreaks by phylogenetic analysis, and to determine whether there was any reassortment event occurring during the human‐pig interspecies transmission. Methods Real‐time RT‐PCR and full genome sequencing were carried out on RNA isolated from nasal swabs and/or virus cultures. Phylogenetic analysis was performed using the Geneious package. Results The influenza H1N1pdm outbreaks were detected in three pig farms located in three different states in Australia. Further analysis of the Queensland outbreak led to the identification of two distinct virus strains in the pigs. Two staff working in the same piggery were also infected with the same two strains found in the pigs. Full genome sequence analysis on the viruses isolated from pigs and humans did not identify any reassortment of these H1N1pdm viruses with seasonal or avian influenza A viruses. Conclusions This is the first report of swine infected with influenza in Australia and marked the end of the influenza‐free era for the Australian swine industry. Although no reassortment was detected in these cases, the ability of these viruses to cross between pigs and humans highlights the importance of monitoring swine for novel influenza infections.     

福建省甲型H1N1流感血清流行病学调查

目的了解甲型H1N1流感(甲流)大流行前后福建省人群甲流血清流行病学特征。方法采集2008年甲流流行前血清标本800例和2010年1-4月甲流流行后不同地区血清标本1250例,以血凝抑制试验方法(HI)检测血清HI抗体。结果甲流流行后人群HI抗体≥1∶10和≥1∶40的阳性率分别从流行前的6.5%和0.63%上升为52.72%和36.24%（P<0.01）,HI抗体几何平均滴度（GMT）从5.39上升为18.26（P<0.01）。流行后各年龄组人群HI抗体都显著高于流行前,以6-17岁为最高,HI抗体≥1∶10和≥1∶40的阳性率及GMT分别达到74.02%、57.22%和38.15,显著高于其他年龄组（P<0.01）。男女性之间HI抗体差异无统计学意义（P>0.05）。福州市人群HI抗体水平显著高于其他设区市。在接种甲流疫苗的人群中,HI抗体≥1∶10和≥1∶40的阳性率分别为83.84%和64.62%,GMT为46.62,分别显著高于未接种疫苗人群的32.72%, 18%和7.48（P<0.01）。结论甲流流行后福建省人群HI抗体显著提高,已形成一定的免疫屏障,但应加强重点年龄组人群疫苗接种,防控甲流流行出现反弹。     

Impact of the 2009/2010 influenza A (H1N1) pandemic on trends in influenza hospitalization, diagnostic testing, and treatment

Analysis of a US hospitalization database demonstrated that more influenza patients were hospitalized and the age distribution of hospitalizations was younger during the 2009 (H1N1) influenza A pandemic compared with the three previous influenza seasons. The duration of hospital stay remained stable in all four seasons. A higher proportion of patients was treated with antivirals (P < 0·0001), comprised almost entirely of neuraminidase inhibitors, and the proportion was highest in those with influenza confirmed by diagnostic testing (P < 0·0001). Approximately one-third remained untreated. Young children had the lowest rate of neuraminidase-inhibitor treatment during the 2009 pandemic (P < 0·05).     

Clinical aspects of 2009 pandemic influenza A (H1N1) virus infection in Austria

Purpose

To describe the clinical features, risk factors for severe disease and effectiveness of oseltamivir in patients with 2009 pandemic influenza A (H1N1) virus infection.

Methods

In a prospective, cross-sectional, multicentre study, data on 540 patients with confirmed 2009 H1N1 infection from seven Austrian hospitals were collected using a standardised online case-history form.

Results

The median age of the patients was 19.3 years (range 26 days–90.8 years); point-of-care testing yielded false-negative results in 60.2% of the 176 cases tested. The most common symptoms were fever, cough, fatigue and headache. Overall, 343 patients (63.5%) were hospitalised, 49 (9.1%) were admitted to an intensive care unit (ICU) and 14 (4.1%) died. Case fatality rates were highest (9.1%) in those aged 65 years or older. Factors significantly associated with a higher risk for ICU admission included age, neurological disease, adipositas, and both interstitial pathology and lobular pathology on chest X-ray. No association with pregnancy, malignancy or immunosuppressive therapy was detected. Antiviral treatment significantly reduced the duration of fever by 0.66 days and lowered the risk of ICU admission, but had no significant benefit on survival.

Conclusions

During the 2009 H1N1 influenza pandemic, elderly or obese patients and those with neurological disease had an increased risk for severe H1N1 infection in Austria. Pregnancy was not associated with a higher risk for severe disease in the later phase of the 2009 H1N1 pandemic. Antiviral treatment provided a minimal effect on the symptoms of influenza but reduced the risk of admission to an ICU.     

Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients

The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory-confirmed Dutch cases were examined. An episode lasted a median of 7·5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. Severity of each symptom was rated highest in the first few days. Furthermore, diarrhoea was negatively associated with viral load, but not with faecal excretion of influenza virus. Cases with comorbidities appeared to have higher viral loads than the cases without, suggesting a less effective immune response. These results complement information obtained through traditional surveillance.     

Pandemic influenza A (2009 H1N1) in children with acute lymphoblastic leukaemia

Pandemic influenza A (2009‐H1N1) usually results in mild clinical illness, but in some individuals it can be life‐threatening. There are no reports of this disease among paediatric patients with acute lymphoblastic leukaemia (ALL). We report ten consecutive patients with ALL and pandemic influenza treated in a single institution. Median age was 7 years (range: 3–12). All were treated with oseltamivir. There were no deaths. Two patients under intensive chemotherapy developed pneumonia and one required ventilatory support. ALL patients under maintenance treatment had mild disease. In conclusion, in our series only patients under intensive treatment developed a moderate to severe disease.