Viral pneumonitis is increased in obese patients during the first wave of pandemic A(H1N1) 2009 virus.
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ABSTRACT: INTRODUCTION: There is conflicting data as to whether obesity is an independent risk factor for mortality in severe pandemic (H1N1) 2009 influenza (A(H1N1)pdm09). It is postulated that excess inflammation and cytokine production in obese patients following severe influenza infection leads to viral pneumonitis and/or acute respiratory distress syndrome. METHODS: Demographic, laboratory and clinical data prospectively collected from obese and non-obese patients admitted to nine adult Australian intensive care units (ICU) during the first A(H1N1)pdm09 wave, supplemented with retrospectively collected data, were compared. RESULTS: Of 173 patients, 100 (57.8%), 73 (42.2%) and 23 (13.3%) had body mass index (BMI) <30 kg/m(2), ≥30 kg/m(2) (obese) and ≥40 kg/m(2) (morbidly obese) respectively. Compared to non-obese patients, obese patients were younger (mean age 43.4 vs. 48.4 years, p = 0.035) and more likely to develop pneumonitis (61% vs. 44%, p = 0.029). Extracorporeal membrane oxygenation use was greater in morbidly obese compared to non-obese patients (17.4% vs. 4.7%, p = 0.04). Higher mortality rates were observed in non-obese compared to obese patients, but not after adjusting for severity of disease. C-reactive protein (CRP) levels and hospital length of stay (LOS) were similar. Amongst ICU survivors, obese patients had longer ICU LOS (median 11.9 vs. 6.8 days, p = 0.017). Similar trends were observed when only patients infected with A(H1N1)pdm09 were examined. CONCLUSIONS: Among patients admitted to ICU during the first wave of A(H1N1)pdm09, obese and morbidly obese patients with severe infection were more likely to develop pneumonitis compared to non-obese patients, but mortality rates were not increased. CRP is not an accurate marker of pneumonitis.
Project description:In the 2009 H1N1 pandemic, the United Kingdom experienced two waves of infection, the first in the late spring and the second in the autumn. Given the low level of susceptibility to the pandemic virus expected to be remaining in the population after the second wave, it was a surprise that a substantial third epidemic occurred in the UK population between November 2010 and February 2011, despite no evidence for any significant antigenic evolution of the pandemic virus. Here, we use a mathematical model of influenza transmission embedded within a Bayesian synthesis inferential framework to jointly analyze syndromic, virological, and serological surveillance data collected in England in 2009-2011 and thereby assess epidemiological mechanisms which might have generated the third wave. We find that substantially increased transmissibility of the H1N1pdm09 virus is required to reproduce the third wave, suggesting that the virus evolved and increased fitness in the human host by the end of 2010, or that the very cold weather experienced in the United Kingdom at that time enhanced transmission rates. We also find some evidence that the preexisting heterologous immunity which reduced attack rates in adults during 2009 had substantially decayed by the winter of 2010, thus increasing the susceptibility of the adult population to infection. Finally, our analysis suggests that a pandemic vaccination campaign targeting adults and school-age children could have mitigated or prevented the third wave even at moderate levels of coverage.
Project description:In temperate countries, death rates increase in winter, but influenza epidemics often cause greater increases. The death rate time series that occurs without epidemic influenza can be called a seasonal baseline. Differentiating observed death rates from the seasonally oscillating baseline provides estimated influenza-associated death rates. During 2003-2009 in New South Wales, Australia, we used a Serfling approach with robust regression to estimate age-specific weekly baseline all-cause death rates. Total differences between weekly observed and baseline rates during May-September provided annual estimates of influenza-associated death rates. In 2009, which included our first wave of pandemic (H1N1) 2009, the all-age death rate was 6.0 (95% confidence interval 3.1-8.9) per 100,000 persons lower than baseline. In persons ?80 years of age, it was 131.6 (95% confidence interval 126.2-137.1) per 100,000 lower. This estimate is consistent with a pandemic virus causing mild illness in most persons infected and sparing older persons.
Project description:BackgroundObesity has been identified as an independent risk factor for severe or fatal infection with 2009 pandemic H1N1 influenza (2009 pH1N1), but was not previously recognized for previous pandemic or seasonal influenza infections.ObjectivesOur aim was to evaluate the role of obesity as an independent risk factor for severity of infection with 2009 pH1N1, seasonal H1N1, or a pathogenic H1N1 influenza virus.MethodsDiet-induced obese (DIO) and their non-obese, age-matched control counterparts were inoculated with a 2009 pH1N1, A/California/04/2009 (CA/09), current seasonal H1N1, A/NY/312/2001 (NY312), or highly pathogenic 1918-like H1N1, A/Iowa/Swine/1931 (Sw31), virus.ResultsFollowing inoculation with CA/09, DIO mice had higher mortality (80%) than control mice (0%) and lost more weight during infection. No effect of obesity on morbidity and mortality was observed during NY312 or Sw31 infection. Influenza antigen distribution in the alveolar regions of the lungs was more pronounced in DIO than control mice during CA/09 infection at 3 days post-inoculation (dpi), despite similar virus titers. During CA/09 infection, localized interferon-β and proinflammatory cytokine protein responses in the lungs were significantly lower in DIO than control mice. Conversely, serum cytokine concentrations were elevated in DIO, but not control mice following infection with CA/09. The effect of obesity on differential immune responses was abrogated during NY312 or Sw31 infection.ConclusionsTogether, these data support epidemiologic reports that obesity may be a risk factor for severe 2009 pandemic H1N1 influenza infection, but the role of obesity in seasonal or highly virulent pandemic influenza infection remains unclear.
Project description:BackgroundHospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic.MethodsTwo panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels.ResultsOf the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%-13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%-31.8%), as compared with 4.0% (95% CI 0.0%-11.9%) in Winnipeg and 8.9% (95% CI 0.0%-18.8%) in the rest of the province.InterpretationWe estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.
Project description:The 1918 influenza A virus caused the most devastating pandemic, killing approximately 50 million people worldwide. Immunization with 1918-like and classical swine H1N1 virus vaccines results in cross-protective antibodies against the 2009 H1N1 pandemic influenza, indicating antigenic similarities among these viruses. In this study, we demonstrate that vaccination with the 2009 pandemic H1N1 vaccine elicits 1918 virus cross-protective antibodies in mice and humans, and that vaccination or passive transfer of human-positive sera reduced morbidity and conferred full protection from lethal challenge with the 1918 virus in mice. The spread of the 2009 H1N1 influenza virus in the population worldwide, in addition to the large number of individuals already vaccinated, suggests that a large proportion of the population now have cross-protective antibodies against the 1918 virus, greatly alleviating concerns and fears regarding the accidental exposure/release of the 1918 virus from the laboratory and the use of the virus as a bioterrorist agent.
Project description:In contrast to seasonal influenza virus infections, which typically cause significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused severe infection in young adults. This phenomenon was attributed to the presence of cross-protective antibodies acquired by older individuals during previous exposures to H1N1 viruses. However, this hypothesis could not be empirically tested. To address this question, we compared viral replication and the development of the immune response in naïve young adult and aged female rhesus macaques infected with A/California/04/2009 H1N1 (CA04) virus. We show higher viral loads in the bronchoalveolar lavage (BAL) fluid and nasal and ocular swabs in aged animals, suggesting increased viral replication in both the lower and upper respiratory tracts. T cell proliferation was higher in the BAL fluid but delayed and reduced in peripheral blood in aged animals. This delay in proliferation correlated with a reduced frequency of effector CD4 T cells in old animals. Aged animals also mobilized inflammatory cytokines to higher levels in the BAL fluid. Finally, we compared changes in gene expression using microarray analysis of BAL fluid samples. Our analyses revealed that the largest difference in host response between aged and young adult animals was detected at day 4 postinfection, with a significantly higher induction of genes associated with inflammation and the innate immune response in aged animals. Overall, our data suggest that, in the absence of preexisting antibodies, CA04 infection in aged macaques is associated with changes in innate and adaptive immune responses that were shown to correlate with increased disease severity in other respiratory disease models.
Project description:BackgroundIn April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.Methods and findingsAnonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n= 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n=100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.ConclusionsAfter the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.
Project description:To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus infection, we profiled cellular miRNAs of lung tissue from BALB/c mice infected with influenza virus BJ501 and a mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1)(PR8) as a comparison.
Project description:During May 2009-April 2010, we analyzed 692 samples of pandemic (H1N1) 2009 virus from patients in Mexico. We detected the H275Y substitution of the neuraminidase gene in a specimen from an infant with pandemic (H1N1) 2009 who was treated with oseltamivir. This virus was susceptible to zanamivir and resistant to adamantanes and oseltamivir.
Project description:The emergence of the pandemic 2009 H1N1 influenza A virus in humans and subsequent discovery that it was of swine influenza virus lineages raised concern over the safety of pork. Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that pork harvested from pandemic influenza A H1N1 infected swine is safe to consume when following standard meat hygiene practices.