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Pandemic potential of a strain of influenza A (H1N1): early findings.

ABSTRACT: A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; >/=15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.

SUBMITTER: Fraser C

PROVIDER: S-EPMC3735127 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Pandemic potential of a strain of influenza A (H1N1): early findings.

Fraser Christophe C Donnelly Christl A CA Cauchemez Simon S Hanage William P WP Van Kerkhove Maria D MD Hollingsworth T Déirdre TD Griffin Jamie J Baggaley Rebecca F RF Jenkins Helen E HE Lyons Emily J EJ Jombart Thibaut T Hinsley Wes R WR Grassly Nicholas C NC Balloux Francois F Ghani Azra C AC Ferguson Neil M NM Rambaut Andrew A Pybus Oliver G OG Lopez-Gatell Hugo H Alpuche-Aranda Celia M CM Chapela Ietza Bojorquez IB Zavala Ethel Palacios EP Guevara Dulce Ma Espejo DM Checchi Francesco F Garcia Erika E Hugonnet Stephane S Roth Cathy C

Science (New York, N.Y.) 20090511 5934

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case ...[more]

PMID: 19433588

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Project description:INTRODUCTION: The clinical picture of the pandemic influenza A (H1N1)v ranges from a self-limiting afebrile infection to a rapidly progressive pneumonia. Prompt diagnosis and well-timed treatment are recommended. Chest radiography (CRx) often fails to detect the early interstitial stage. The aim of this study was to evaluate the role of bedside chest ultrasonography (US) in the early management of the 2009 influenza A (H1N1)v infection. METHODS: 98 patients who arrived in the Emergency Department complaining of influenza-like symptoms were enrolled in the study. Patients not displaying symptoms of acute respiratory distress were discharged without further investigations. Among patients with clinical suggestion of a community-acquired pneumonia, cases encountering other diagnoses or comorbidities were excluded from the study. Clinical history, laboratory tests, CRx, and computed tomography (CT) scan, if indicated, contributed to define the diagnosis of pneumonia in the remaining patients. Chest US was performed by an emergency physician, looking for presence of interstitial syndrome, alveolar consolidation, pleural line abnormalities, and pleural effusion, in 34 patients with a final diagnosis of pneumonia, in 16 having normal initial CRx, and in 33 without pneumonia, as controls. RESULTS: Chest US was carried out without discomfort in all subjects, requiring a relatively short time (9 minutes; range, 7 to 13 minutes). An abnormal US pattern was detected in 32 of 34 patients with pneumonia (94.1%). A prevalent US pattern of interstitial syndrome was depicted in 15 of 16 patients with normal initial CRx, of whom 10 (62.5%) had a final diagnosis of viral (H1N1) pneumonia. Patients with pneumonia and abnormal initial CRx, of whom only four had a final diagnosis of viral (H1N1) pneumonia (22.2%; P<0.05), mainly displayed an US pattern of alveolar consolidation. Finally, a positive US pattern of interstitial syndrome was found in five of 33 controls (15.1%). False negatives were found in two (5.9%) of 34 cases, and false positives, in five (15.1%) of 33 cases, with sensitivity of 94.1%, specificity of 84.8%, positive predictive value of 86.5%, and negative predictive value of 93.3%. CONCLUSIONS: Bedside chest US represents an effective tool for diagnosing pneumonia in the Emergency Department. It can accurately provide early-stage detection of patients with (H1N1)v pneumonia having an initial normal CRx. Its routine integration into their clinical management is proposed.

Project description:Pre-existing antibodies to influenza virus neuraminidase may provide protection against infection influenza viruses containing novel hemagglutinin (HA). The aim of our study was to evaluate serum neuraminidase-inhibiting (NI) antibodies against А/California/07/2009(H1N1) [H1N1/2009pdm] and А/New Caledonia/20/1999(H1N1) [H1N1/1999] influenza viruses in relation with the age of participants and hemagglutination-inhibition (HI) antibody levels. Anti-H1N1/2009pdm neuraminidase and anti-H1N1/1999 neuraminidase antibody levels were measured in total 219 serum samples from Russian healthy peoples of various ages examined before and a year after pandemic strain appearance. We adjusted peroxidase-linked lectin micro-procedure to measure NI antibody titers using the reassortant A/H7N1 influenza viruses based on A/equine/Prague/1/56(H7N7). Also, HI antibody titers were estimated against H1N1/2009pdm, H1N1/1999 and a panel of seasonal A/H1N1 influenza viruses.In sera samples collected during the fall of 2010, mean titers of specific HI and NI antibodies to H1N1/2009pdm were 2-2.1 times lower than antibody levels against H1N1/1999. Of the 163 individuals examined, 58 (35.6%) had NI anti-H1N1/2009pdm antibody titers > 1:20, compared to 93 (57.1%) who had NI anti-H1N1/1999 antibody titers > 1:20. There were low correlations between HI and NI antibody levels against either H1N1/1999 or H1N1/2009pdm in the same serum samples. The 24 adults born between 1957 and 1977 expressed very low levels of NI antibodies to A/H1N1 influenza viruses. Persons with low HI anti-H1N1/2009pdm titers but positive to seasonal A/H1N1 demonstrated significantly higher NI anti-A/H1N1 antibody titers than unexposed subjects. In 2005 cross-reactive NI anti-H1N1/2009pdm antibody titers > 1:20 were detected among 7.1% of young people.Our study confirmed that contact with seasonal influenza viruses may have contributed to generating the cross-reacting anti-H1N1/2009pdm NI antibodies which were detected in the sera of 18-20 years old people examined before the pandemic virus active circulation. The lowest levels of antibodies to the neuraminidase of N1 subtype were in the group of participants born during the circulation of influenza A/H2N2 or A/H3N2 viruses. The low correlation between HI and NI antibody titers suggests that NI antibody detection can be used as an additional test to evaluate the immune response after influenza infections or immunizations.

Project description:Background: Pandemic H1N1 influenza A is a newly emerging strain of human influenza that is easily transmitted between people and has spread globally to over 116 countries. Human infection leads to symptoms ranging from mild to severe with lower respiratory complications observed in a small but significant number of infected individuals. Little is currently known about host immunity and Pandemic H1N1 influenza infections. Methods: We examined the pathogenic potential of the pandemic influenza A vaccine strain, A/California/07/2009 (H1N1), in ferrets, and characterized the host immune responses using microarray analysis. Gene expression profiles in lung tissue were compared with those from ferrets infected with A/Brisbane/59/2007. Results: Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of ISGs were expressed early, correlated to lung pathology, and abruptly decreased expression in 5 days. Interestingly, the drop in innate immune gene expression was replaced by a significant increase in the expression of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-pandemic influenza H1N1 antibodies were also observed on day 7, commensurate with the elimination of viral load. Conclusions: We propose that the innate phase of host immunity causes lung pathology and a delay or failure to effectively switch to the adaptive phase contributes to morbidity and mortality during severe human pandemic H1N1 influenza A infections. Keywords: influenza, immune response, cytokines, chemokines, lung infection, time course In the experiment with influenza A/California/07/2009 (H1N1),15 ferrets were randomly allocated to 5 groups: Day 0 (before infection), and Day 3, 5, 7 and 14 (post infection) with 3 biological replicates for each group. Likewise, a second experiment with A/Brisbane/59/2007 (H1N1) was carried out using the same experimental groups, except for a group in Day 2, instead Day 3. Ferrets were euthanized and lung tissue was excised for RNA purification on the scheduled date. The subsequent gene expression analysis was performed with Affymetrix GeneChip Canine Genome 2.0 Array. Day 0 groups were used as control.

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Pandemic potential of a strain of influenza A (H1N1): early findings.

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Pandemic potential of a strain of influenza A (H1N1): early findings.

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