Neurological events related to influenza A (H1N1) pdm09

Objectives

To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection.

Design

A search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.”

Setting

Only papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included.

Sample

We included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included.

Main outcome measures

Demographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection.

Results

The retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed.

Conclusions

Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.     

Excess mortality impact of two epidemics of pandemic influenza A(H1N1pdm09) virus in Hong Kong

Hong Kong experienced two large epidemics of pandemic influenza A(H1N1pdm09). We used regression methods to estimate the excess mortality associated with each epidemic. The first epidemic of H1N1pdm09 peaked in September 2009 and was associated with 2·13 [95% confidence interval (CI): −8·08, 11·82] excess all-cause deaths per 100 000 population. The second epidemic of H1N1pdm09 in early 2011 was associated with 4·72 [95% CI: −0·70, 10·50] excess deaths per 100 000 population. More than half of the estimated excess all-cause deaths were attributable to respiratory causes in each epidemic. The reasons for substantial impact in the second wave remain to be clarified.     

Influenza surveillance from November 2008 to 2011; including pandemic influenza A(H1N1)pdm09 in Bhutan

Objective Describe the influenza A(H1N1) pandemic in Bhutan. Design Observational study from sentinel surveillance sites. Setting Bhutan remains isolated, with only one to two flights a day at the lone airport, no trains, and only three major roads that enter from India. Main outcome measures PCR positive human respiratory samples Results The first case of A(H1N1)pdm09 infection was detected in Bhutan in July 2009, 3 months after the virus was first reported in Mexico in April 2009. During the official WHO pandemic period (11 June 2009 to 8 August 2010), a total of 2149 samples were collected and tested by RT‐PCR of which 22.7% (487) were confirmed A(H1N1)pdm09; H3N2, H1N1, and B were positive in 2.2%, 1.1%, and 7.2%, respectively. The highest rate of A(H1N1)pdm09 cases (57.4%) was detected in the 6‐20 year‐old age group. Importantly, Bhutan increased from 3 sentinel sites in April 2009 to 11 a year later, and in April 2010 established PCR capability for influenza. Conclusions Despite relative isolation, the A(H1N1)pdm09 reached Bhutan within 3 months of identification in Mexico. The H1N1 pandemic has made Bhutan more prepared for epidemics in the future.     

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross‐reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13–23. Background Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross‐reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were immunised by particle‐mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses. Results We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross‐reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross‐reactive immune responses against a recent 2005 H3N2 virus challenge. Conclusions DNA vaccines based on pandemic or recent seasonal influenza genes induced cross‐reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross‐protective immunity against both contemporary and long‐time drifted viruses.     

Counting pandemic deaths: comparing reported numbers of deaths from influenza A(H1N1)pdm09 with estimated excess mortality

Background

During the wave 1 of the influenza A(H1N1)pdm09 virus, Norway appeared to be suffering from high mortality rates. However, by the end of the pandemic, it was widely reported that the number of deaths were much lower than previous years.

Objectives

The mortality burden from influenza is often assessed by two different approaches: counting influenza‐certified deaths and estimating the mortality burden using models. The purpose of this study is to compare the number of reported deaths with results from two different models for estimating excess mortality during the pandemic in Norway. Additionally, mortality estimates for the pandemic season are compared with non‐pandemic influenza seasons.

Methods

Numbers on reported influenza A(N1h1)pdm09 deaths are gived by the Cause of Death Registry at Statistics Norway and an ad hoc registry at the Norwegian Institute of Public Health. Overall and Pnemumonia and Influenza certified mortality is modeled using Poission regression, adjusting for levels of reported influenza‐like illness and seasonal and year‐to‐year variation.

Results and conclusions

Modelling results suggest that the excess mortality in older age groups is considerably lower during the pandemic than non‐pandemic seasons, but there are indications of an excess beyond what was reported during the pandemic. This highlights the benefits of both methods and the importance of explaining where these numbers come from.     

Transmission dynamics of pandemic influenza A(H1N1)pdm09 virus in humans and swine in backyard farms in Tumbes,Peru

Objectives

We aimed to determine the frequency of pH1N1 transmission between humans and swine on backyard farms in Tumbes, Peru.

Design

Two‐year serial cross‐sectional study comprising four sampling periods: March 2009 (pre‐pandemic), October 2009 (peak of the pandemic in Peru), April 2010 (1st post‐pandemic period), and October 2011 (2nd post‐pandemic period).

Sample

Backyard swine serum, tracheal swabs, and lung sample were collected during each sampling period.

Main outcome measures

We assessed current and past pH1N1 infection in swine through serological testing, virus culture, and RT‐PCR and compared the results with human incidence data from a population‐based active surveillance cohort study in Peru.

Results

Among 1303 swine sampled, the antibody prevalence to pH1N1 was 0% pre‐pandemic, 8% at the peak of the human pandemic (October 2009), and 24% in April 2010 and 1% in October 2011 (post‐pandemic sampling periods). Trends in swine seropositivity paralleled those seen in humans in Tumbes. The pH1N1 virus was isolated from three pigs during the peak of the pandemic. Phylogenetic analysis revealed that these viruses likely represent two separate human‐to‐swine transmission events in backyard farm settings.

Conclusions

Our findings suggest that human‐to‐swine pH1N1 transmission occurred during the pandemic among backyard farms in Peru, emphasizing the importance of interspecies transmission in backyard pig populations. Continued surveillance for influenza viruses in backyard farms is warranted.     

Seroprevalence of antibody to influenza A(H1N1)pdm09 attributed to vaccination or infection,before and after the second (2010) pandemic wave in Australia

Objectives

Historical records of influenza pandemics demonstrate variability in incidence and severity between waves. The influenza A(H1N1)pdm09 pandemic was the first in which many countries implemented strain-specific vaccination to mitigate subsequent seasons. Serosurveys provide opportunity to examine the constraining influence of antibody on population disease experience.

Design

Changes in the proportion of adults seropositive to influenza A(H1N1)pdm09over the 2009/10 (summer) interepidemic period and 2010 (winter) influenza season were measured to determine whether there was a temporal relationship with vaccine distribution and influenza activity, respectively.

Setting

Australia.

Sample

Plasma samples were collected from healthy blood donors from seven cities at the end of the first wave (November 2009), and before (March/April 2010) and after (November 2010) the subsequent influenza season.

Main outcome measures

Haemagglutination inhibition (HI) assays were performed to assess reactivity of plasma against A(H1N1)pdm09, and the proportion seropositive (HI titre ≥ 40) compared over time, by age group and location.

Results

Between the 2009 and 2010 influenza seasons, the seropositive proportion rose from 22% to 43%, an increase observed across all ages and sites. Brisbane alone recorded a significant rise in seropositivity over the 2010 influenza season – from a baseline of 35% to 53%. The seropositive proportion elsewhere was ≥40% pre-season, and did not rise over winter.

Conclusions

A vaccine-associated increase in seropositive proportion preceding the influenza season correlated with low levels of disease activity in winter 2010. These observations support the role of immunisation in mitigating the ‘second wave’ of A(H1N1)pdm09, with timing critical to ensure sustained herd protection.     

Clinical epidemiology and predictors of outcome in children hospitalised with influenza A(H1N1)pdm09 in 2009: a prospective national study

Background

There are few large-scale, prospective studies of influenza A(H1N1)pdm09 in children that identify predictors of adverse outcomes.

Objectives

We aimed to examine clinical epidemiology and predictors for adverse outcomes in children hospitalised with influenza A(H1N1)pdm09 in Australia.

Methods

Active hospital surveillance in six tertiary paediatric referral centres (June–September, 2009). All children aged <15 years admitted with laboratory-confirmed influenza A(H1N1)pdm09 were studied.

Results

Of 601 children admitted with laboratory-confirmed influenza, 506 (84·2%) had influenza A(H1N1)pdm09. Half (51·0%) of children with influenza A(H1N1)pdm09 were previously healthy. Hospital stay was longer in children with pre-existing condition (mean 6·9 versus 4·9 days; P = 0·02) as was paediatric intensive care unit (PICU) stay (7·0 versus 2·3 days; P = 0·005). Rapid diagnosis decreased both antibiotic use and length of hospital and PICU stay. Fifty (9·9%) children were admitted to a PICU, 30 (5·9%) required mechanical ventilation and 5 (0·9%) died. Laboratory-proven bacterial co-infection and chronic lung disease were significant independent predictors of PICU admission (OR 6·89, 95% CI 3·15–15·06 and OR 3·58, 95% CI 1·41–9·07, respectively) and requirement for ventilation (OR 5·61, 95% CI 2·2–14·28 and OR 5·18, 95% CI 1·8–14·86, respectively). Chronic neurological disease was a predictor of admission to PICU (OR 2·30, 95% CI 1·14–4·61).

Conclusions

During the 2009 pandemic, influenza was a major cause of hospitalisation in tertiary paediatric hospitals. Co-infection and underlying chronic disease increased risk of PICU admission and/or ventilation. Half the children admitted were previously healthy, supporting a role for universal influenza vaccination in children.     

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands

Background

Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality.

Methods

The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group.

Results

Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52–5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77–4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09–2.94%). For 55–59 through 85+ years, the case-fatality risk was estimated to double with every 3.7 years of age.

Conclusions

These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.     

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.     

Epidemiological aspects of pandemic influenza A(H1N1) virus from 2009 to 2011 in Iran

Please cite this paper as: Yavarian et al. (2012). Epidemiological aspects of pandemic influenza A(H1N1) virus from 2009 to 2011 in Iran. Influenza and Other Respiratory Viruses 6(601), e74–e76.     

Post‐pandemic influenza A (H1N1) 2009 virus infection in pregnant women in Ceará, Brazil

Objective

The aim of this study was to present results of the post-pandemic phase of A(H1N1)pdm09 virus infection in pregnant women in Ceará, Brazil, during the January–June 2012 influenza season.

Results

One hundred and fifty-four nasopharyngeal swab samples were collected from pregnant women admitted to hospitals with suspected severe acute respiratory infection (SARI). Fifty-three (34·4%) had laboratory-confirmed A(H1N1)pdm09 virus infection with 15 (28·3%) outpatients and 38 (71·7%) hospitalized. Five (9·4%) women were in the first trimester of pregnancy, 20 (37·7%) in the second trimester of pregnancy, and 24 (45·2%) in the third trimester of pregnancy. Three had no information about the time of pregnancy. Six samples from newborns were also analyzed, of which three were nasopharyngeal swab positive for A(H1N1)pdm09. These swabs were collected immediately after birth, with the exception of one that was collected on the day after birth.

Conclusion

Our findings suggest that transplacental transfer of influenza viruses could occur as a result of severe illness in pregnancy. It is therefore important to encourage women to be vaccinated against influenza in order to avoid pregnancy complications.     

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.     

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。