Thesis advisor: Kathleen Dunn / Nearly a century ago, a deadly pandemic swept the globe, taking with it over 25 million lives. This pandemic was caused by the elusive Spanish influenza of 1918. Although many decades have passed since this pandemic, research has yet to uncover the exact origin of the Spanish influenza and the cause of its increased virulence. By examining the current research on the Spanish influenza, some of the secrets of this virus can be uncovered. Most of today's research supports the theory that the hemagglutinin receptor of the Spanish influenza was the most likely source of its potency and that it was an amalgamation of swine and human strains created from a common avian strain that created this virus. Based upon the information that has been uncovered, there is a considerable chance that the Spanish influenza or a similar strain could return in the future. The processes of recombination and reassortment create an endless amount of genetic variants of the virus and any one of them has the potential to be lethal. Although a natural emergence of lethal influenza is a potential threat, the artificial reconstruction of the Spanish influenza or another lethal strain for the purposes of bioterrorism may be an even bigger threat. Thus, it is necessary for researchers to press on with their search for the secrets of the Spanish influenza so that a future outbreak can be avoided. As researchers continue to do their job, the government must also take action and develop the most efficient approach to protecting the public from deadly strains of influenza. / Thesis (BS) — Boston College, 2003. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology. / Discipline: College Honors Program.

Os pacientes com doenças reumáticas crônicas exibem um risco aumentado de contrair infecções. Consequentemente, sua vacinação é indispensável. Há relatos da produção de anticorpos antifosfolípides e tromboses após infecções e vacinação nesta população, exceto em síndrome antifosfolípide (SAF) primária. O objetivo principal deste estudo foi avaliar a curto e longo prazos um painel de anticorpos antifosfolípides após a vacinação contra influenza A/H1N1 (sem adjuvante) em SAF primária e controles saudáveis. Quarenta e cinco pacientes com SAF primária e 33 controles saudáveis foram imunizados e prospectivamente avaliados antes da vacinação e 3 semanas e 6 meses após a vacinação. Os anticorpos antifosfolípides foram determinados por ensaio imunoenzimático (ELISA) e incluíram os anticorpos IgG e IgM a seguir: anticardiolipina (aCL), anti-beta2glicoproteína I (anti-beta2GPI), anti-anexina V, anti-fosfatidilserina e anti-protrombina. O anticorpo anti-Sm foi igualmente determinado por ELISA e o anti-DNA dupla hélice, por imunofluorescência indireta. Avaliamos clinicamente à ocorrência de tromboses arterial e venosa. A frequência pré-vacinação de pelo menos um anticorpo antifosfolípide foi significativamente maior nos pacientes com SAF primária comparados aos controles (58% vs 24%, p = 0,0052). A frequência global de anticorpos antifosfolípides pré-vacinação e 03 semanas e 06 meses após a vacinação permaneceu inalterada tanto em pacientes (p = 0,89) como em controles (p = 0,83). A frequência de cada anticorpo específico nos dois grupos permaneceu estável nas três avaliações (p > 0,05). A frequência de cada anticorpo mantevese invariável nos pacientes tratados com cloroquina (p > 0,05). Em 3 semanas, 2 pacientes com SAF primária deselvolveram um anticorpo antifosfolípide novo porém transitório (aCL IgG e IgM), enquanto que em 6 meses novos anticorpos foram observados em 6 pacientes e nenhum apresentou altos títulos. Anti-Sm e anti-DNA dupla hélice foram negativos e nenhuma nova trombose arterial ou venosa foi observada durante o estudo. Este foi o primeiro estudo a demonstrar que a vacina contra influenza pandêmica em pacientes com SAF primária não induz tromboses e uma produção significante de anticorpos antifosfolípides a curto e longo prazos. (ClinicalTrials.gov, #NCT01151644). / Chronic rheumatic disease patients exhibit an increased risk for infections. Therefore, vaccination is imperative. Antiphospholipid antibodies (aPL) and thrombosis triggering after infections and vaccination in this population were reported, except for primary antiphospholipd syndrome (PAPS). Study\'s main objective was short and long-term evaluation of a panel of antiphospholipid autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in primary antiphospholipid syndrome patients and healthy controls. Forty-five PAPS and 33 healthy controls were immunized with A/H1N1 pandemic influenza vaccine. They were prospectively assessed at pre-vaccination, 3 weeks and 6 months after vaccination. aPL autoantibodies were determined by an enzyme-linked immunosorbent assay (ELISA) and included IgG/IgM: anticardiolipin (aCL), anti-beta2GPI; anti-annexin V, anti-phosphatidyl serine and antiprothrombin antibodies. Anti-Sm was determined by ELISA and anti-dsDNA by indirect immunfluorescence. Arterial and venous thrombosis were also clinically assessed. Pre-vaccination frequency of at least one aPL antibody was significantly higher in PAPS patients versus controls (58% vs. 24%, p=0.0052). The overall frequencies of aPL antibody at pre-vaccination, 3 weeks and 6 months after immunization remained unchanged in patients (p=0.89) and controls (p=0.83). The frequency of each antibody specificity for patients and controls remained stable in the three evaluated period (p > 0.05). The frequency of each antibody kept invariable in PAPS patients under chloroquine treatment (p > 0.05). At 3 weeks, 2 PAPS patients developed a new but transient aPL antibody (aCL IgG and IgM), whereas at 6 months new aPL antibodies were observed in 6 PAPS patients and none had high titer. Anti-Sm and anti-dsDNA autoantibodies were uniformly negative and no new arterial or venous thrombosis were observed throughout the study. This was the first study to demonstrate that pandemic influenza vaccine in PAPS patients does not trigger short and long-term thrombosis or a significant production of aPL related antibodies. (ClinicalTrials.gov, #NCT01151644)

Introdução: A vacinação contra a influenza pandêmica A/H1N1 resultou em soroproteção em mais de 85% dos indivíduos saudáveis. Entretanto, dados em pacientes com artrite reumatoide (AR) são escassos. Objetivos: O objetivo deste estudo é avaliar a imunogenicidade e a segurança em curto prazo da vacina contra influenza pandêmica A/H1N1 em pacientes com AR e a influência da atividade da doença e da medicação nesta resposta. Métodos: Trezentos e quarenta pacientes adultos com AR em seguimento e tratamento regular e 234 controles saudáveis foram examinados antes e 21 dias após receber uma dose da vacina sem adjuvante contra influenza A/California/7/2009. A atividade da doença (DAS28), o tratamento em uso e os títulos de anticorpos também foram avaliados. As taxas de soroproteção (títulos de anticorpos >= 1:40) e soroconversão (percentagem de pacientes com aumento de título de anticorpos maior ou igual a 4, se o título pré- vacinal fosse maior ou igual a 1:10; ou título pós-vacinal de pelo menos 1:40, se o título pré-vacinal era menor que 1:10), as médias geométricas dos títulos (MGT) e o fator de incremento das médias geométricas (FI-MGT) foram calculados. Os eventos adversos foram também registrados. Resultados: Os pacientes com AR e os controles tinham taxas pré-vacinais de soroproteção (10,8% vs. 11,5%) e MGT (8,0 vs. 9,3) comparáveis (p>0,05). Após a vacinação, foi observada redução significativa na resposta dos pacientes com AR versus controles (p<0,001) em todos os desfechos sorológicos: taxas de soroproteção (60,0 vs. 82,9%) e soroconversão (53,2% vs. 76,9%), MGT (57,5 vs. 122,9) e FI-MGT (7,2 vs. 13,2). A atividade de doença não prejudicou a soroproteção ou a soroconversão e se manteve estável em 97,4% dos pacientes. O metotrexato e o abatacepte foram associados à redução da resposta vacinal. A vacinação foi bem tolerada, com poucos efeitos adversos. Conclusão: Os dados confirmaram tanto a segurança em curto prazo como, diferente da maioria dos trabalhos com influenza sazonal, a redução da soroproteção em pacientes com AR, não relacionada à atividade de doença e à maioria das medicações em uso (com exceção do metotrexato e do abatacepte). A extrapolação da resposta imunológica de uma vacina para outra pode não ser possível e estratégias específicas de imunização (possivelmente em duas doses) podem ser necessárias / Background: Pandemic influenza A/H1N1 vaccination yielded seroprotection in more than 85% of healthy individuals. However, similar data are scarce in rheumatoid arthritis (RA) patients. Objectives: The objective of this study is to evaluate the immunogenicity and the short-term safety of anti- pandemic influenza A/H1N1 vaccine in RA patients, and the influence of disease activity and medication to the response. Methods: Three hundred and forty adult RA patients in regular follow-up and treatment, and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 vaccine. Disease activity (DAS28), current treatment and anti-pandemic influenza A/H1N1 antibody titres were also evaluated. Seroprotection (antibody titre >=1:40) and seroconversion (the percentage of patients with a fourfold or greater increase in antibody titre, if prevaccination titre was 1:10 or greater, or a postvaccination titre of 1:40 or greater, if prevaccination titre was less than 1:10) rates, geometric mean titres (GMT) and factor increase in geometric mean titre (FI-GMT) were calculated and adverse events registered. Results: RA patients and controls showed similar (p>0.05) prevaccination seroprotection (10.8% vs. 11.5%) and GMT (8.0 vs. 9.3). After vaccination a significant reduction (p<0.001) was observed in all endpoints in RA patients versus controls: seroprotection (60.0 vs. 82.9%; p<0.0001) and seroconversion (53.2% vs. 76.9%) rates, GMT (57.5 vs. 122.9) and FI-GMT (7.2 vs. 13.2). Disease activity did not preclude seroprotection or seroconversion and remained unchanged in 97.4% of patients. Methotrexate and abatacept were associated with reduced responses. Vaccination was well tolerated with minimal adverse events. Conclusions: The data confirmed both short-term anti-pandemic A/H1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate and abatacept). Extrapolation of xii immune responses from one vaccine to another may therefore not be possible and specific immunization strategies (possibly booster) may be needed

The methodologies of systems design, rooted in engineering and in cognitivist conceptions of human action, have been stretched to the limit by the complexity of uses to which information and communication technologies are being turned. Within segments of the broader design community there has been a `turn to the social' - a perception that there is a need now for richer stories about the everyday practices systems designers build tools to support. This thesis is presented as a contribution to the corpus of `richer stories' about the what, how, why, when and where of information gathering. The thesis presents findings from an ethnographic study of newsroom information gathering at a UK daily newspaper. Adopting an analytical perspective based upon cultural-historical activity theory (CHAT), it describes and analyses journalistic information gathering on two mutually constitutive levels; that of activity and that of artefact mediation. Its starting point is that neither information gathering, nor the artefacts of information gathering, can be understood without consideration of the social, cultural and historical contexts within which they are situated. Ethnographic data is drawn upon to argue that journalistic information gathering can only be understood within the particular context of the `story lifecycle'. Stories are the principal object of journalistic enterprise, and the thesis examines in detail how everyday working practices are oriented towards this lifecycle. Based on an analysis of the artefacts of newsroom information gathering, and of the discourses of information systems designers, it is also argued that the discourses of systems designers over-emphasise the importance of the category `information'. In particular it is argued that sources are how journalists orient themselves in the vast, heterogeneous information spaces they simultaneously inhabit and populate. The background to these discussions is the often controversial relationship between ethnography, theory and systems design. This relationship is examined and it is argued that the CHAT perspective provides design ethnographers with an opportunity to move from ethnographic intuition to design insight. It is also argued that at a more pragmatic level, CHAT helps the fieldworker navigate the apparently never-ending mass of `potentially interesting material' any field experience throws up.

No description available.

While the last century of medical discoveries has made a significant impact on improving the lives of human populations across the globe, a perfect solution to the yearly infection cycle from the influenza virus has yet to be discovered. Although vaccines stand the best chance at targeting yearly epidemics, new treatment options must be created to combat the arrival of rapidly mutating and antiviral-resistant strains of the virus that could lead to another pandemic such as the 1918 Spanish flu that killed millions worldwide. We describe a method to create functionally enhanced monoclonal antibodies targeting influenza via genetic engineering of fragment crystallizable glycan structures. Muscle and liver cell lines were lentivirally-transduced to produce the broadly neutralizing antibody, Fi6v3, while also overexpressing a critical glycosylation enzyme, B-1,4-N-acetyl-glucosaminyltransferase III. Secreted antibodies were tested for effector functionality using a Natural Killer cell degranulation assay and an antibody-dependent cellular phagocytosis assay. Results conclude that modified antibodies from both muscle and liver cells lines exhibit enhanced function in comparison to their unmodified counterparts, providing support to the future creation of an influenza prophylactic or treatment option using antibodies with the ability to more effectively activate innate immune killing mechanisms.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-01-22T11:05:18Z No. of bitstreams: 1 AndresadaCunhaSuaresDissertacaoParcial2017.pdf: 145410 bytes, checksum: 5bf4fccd3f065ddfa1b74986b17838b7 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-01-22T11:06:04Z (GMT) No. of bitstreams: 1 AndresadaCunhaSuaresDissertacaoParcial2017.pdf: 145410 bytes, checksum: 5bf4fccd3f065ddfa1b74986b17838b7 (MD5) / Made available in DSpace on 2018-01-22T11:06:04Z (GMT). No. of bitstreams: 1 AndresadaCunhaSuaresDissertacaoParcial2017.pdf: 145410 bytes, checksum: 5bf4fccd3f065ddfa1b74986b17838b7 (MD5) Previous issue date: 2017-08-07 / UCB / Respiratory diseases, including influenza virus infection and its complications are major causes of mortality particularly in the elderly. Influenza vaccination has emerged as a national strategy to reduce the impact on mortality from respiratory diseases in the elderly and has been managed since 1999. This study aimed to evaluate the impact of influenza vaccination on the mortality trend from respiratory diseases in the Brazilian elderly population (??? 60 years), in the period from 2008 to 2014. Deaths from respiratory diseases associated with influenza were analyzed according to gender and age and compared to vaccination coverage against influenza in the study population. This observational, longitudinal mixed-type ecological study combined different time periods and territories in different age groups. Secondary data from the Mortality Information System of the Ministry of Health (SIM / MS), National Immunization Program Information System (NIP-SI) and estimates from the Brazilian Institute of Geography and Statistics (IBGE) were used. Mortality rates for selected causes were related with the age of the study population. Moreover, higher mortality rates were observed among men and among residents in the South and Southeast regions of Brazil. Mortality coefficients did not show a significant increase in the year 2009 when the first pandemic of the 21st century occurred due to Pandemic Influenza (H1N1). Mortality rates from respiratory diseases and influenza vaccination coverage were not correlated. The present study assessed the impact of influenza vaccination on mortality rates of elderly people nationwide through a historical data series. However the seasonality of influenza virus must be considered in order to determine preventive actions and guide local public health policies. / As doen??as respirat??rias, entre elas a infec????o pelo v??rus influenza e suas complica????es, constituem importante causa de mortalidade particularmente entre os idosos. A vacina????o contra esta doen??a surgiu como estrat??gia nacional de impacto na redu????o da morbimortalidade de idosos por doen??as do aparelho respirat??rio e vem sendo administrada desde 1999. O objetivo do presente estudo foi avaliar o impacto da vacina????o contra influenza no comportamento da mortalidade por doen??as respirat??rias na popula????o idosa brasileira (??? 60 anos), no per??odo de 2008 a 2014. Foi realizada an??lise da ocorr??ncia de ??bitos por doen??as respirat??rias associadas ?? influenza, segundo sexo e faixa et??ria estratificada, comparando com a cobertura vacinal contra a gripe na popula????o em estudo. Trata-se de estudo observacional, do tipo ecol??gico longitudinal misto, combinando diferentes per??odos de tempo e agregado territorial em diferentes faixas et??rias definidas, utilizando-se dados secund??rios do Sistema de Informa????es em Mortalidade do Minist??rio da Sa??de (SIM/MS), Sistema de Informa????es do Programa Nacional de Imuniza????o (SI-PNI) e estimativas do Instituto Brasileiro de Geografia e Estat??stica (IBGE). Observaram-se tend??ncias crescentes nas taxas de mortalidade com o aumento da idade da popula????o em estudo. Al??m disso, valores mais elevados desses indicadores foram observados em homens e nos residentes nas regi??es Sul e Sudeste. Os coeficientes de mortalidade n??o mostraram eleva????o significativa no ano de 2009, no qual ocorreu a primeira pandemia do s??culo XXI pela Influenza Pand??mica (H1N1). Ao comparar a taxa de mortalidade por doen??as respirat??rias e a cobertura vacinal contra influenza n??o foi observado o resultado desejado de redu????o de ??bitos com o aumento da cobertura. O presente estudo demonstrou uma avalia????o macro da cobertura vacinal contra influenza no perfil de mortalidade de idosos ao mostrar o panorama nacional atrav??s de uma s??rie hist??rica. Entretanto, ?? preciso considerar a sazonalidade do v??rus influenza com vistas a determinar a????es preventivas e subsidiar pol??ticas de sa??de loco regionais voltadas para a especificidade de cada regi??o.

O vírus influenza A (IAV) é um agente zoonótico de grande relevância tanto para saúde humana como animal. A influenza suína teve seu primeiro reconhecimento clínico em 1918, em suínos do Meio Oeste dos EUA, coincidindo com a pandemia de influenza em humanos. Desde então, o IAV permanece como um importante patógeno para a indústria suinícola em todo o mundo. A grande variabilidade genética destes vírus é causada por dois principais mecanismos genéticos: mutações pontuais e recombinações genéticas. A influenza é endêmica em muitos países e a emergências de recombinantes tem desafiado o controle e o diagnóstico desta enfermidade. No Brasil, a infecção pelo IAV em suínos (swIAV) não está bem caracterizada; poucos relatos evidenciam a prevalência deste agente antes do ano de 2009, especialmente no Estado do Rio Grande do Sul, que alberga um dos maiores rebanhos de suínos do Brasil. Em vista disso, este trabalho teve como objetivo investigar ocorrência de swIAV em alguns rebanhos suínos comerciais do Estado do Rio Grande do Sul, Brasil, no período de 2013-2014, e determinar os tipos e subtipos de vírus circulantes naquelas propriedades. O primeiro capítulo deste estudo reporta os aspectos clínicos, patológicos e virológicos da ocorrência de influenza suína e co-infecções identificadas em seis propriedades suinícolas selecionadas na região do Vale do Taquari. Neste estudo foram analisados suabes nasais coletados de 66 animais e 6 amostras de tecido pulmonar de suínos com sinais de infecção respiratória. A detecção viral foi feita através de uma PCR de triagem e confirmada através do isolamento viral em células MDCK. A identificação dos subtipos virais foi feita através de uma PCR em Tempo Real (rRT-PCR) para o subtipo A(H1N1)pdm09 ou através de uma PCR multiplex (RT-PCR) para outros subtipos de swIAV. A detecção de agentes bacterianos foi realizada apenas nas amostras de tecido pulmonar, através da pesquisa de genomas bacterianos por PCR. O subtipo A(H1N1)pdm09 foi identificado em 4/6 granjas e o subtipo H1N2 em 2/6 granjas. Além disso, agentes envolvidos no complexo respiratório dos suínos foram identificados em todas as granjas; Pasteurella multocida foi identificada em 5/6 granjas e Mycoplasma hyopneumoniae em 3/6 granjas. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) e PCV2 (1/6) também foram detectados. O segundo capítulo deste estudo teve como objetivo o sequenciamento do genoma completo de um novo recombinante H1N2 de origem humana, detectado em suínos. O genoma completo foi gerado através de uma RT-PCR. Os produtos foram purificados e submetidos ao sequenciamento utilizando a plataforma MiSeq (illumina). A análise filogenética revelou que as sequencias dos genes HA e NA correspondem a genes de IAV de origem humana, enquanto que as sequencias dos genes que codificam as proteínas internas do vírus (PB1, PB2, PA, NP, M e NS) correspondem a genes de amostras do vírus A(H1N1)pdm09. O terceiro capítulo reporta o sequenciamento completo dos genomas de 8 amostras de vírus influenza identificados nas populações de suínos amostradas. Foram identificados dois subtipos virais de origem humana (H1N2 e H3N2), além do vírus A(H1N1)pdm09. Os subtipos de origem humana possuem os genes HA e NA similares a vírus sazonais de humanos e os genes internos são estreitamente relacionados com o vírus A(H1N1)pdm09. / Influenza A virus (IAV) is a zoonotic agent of great relevance to human and animal health. Swine influenza was first recognized clinically in pigs in the Midwestern U.S., in 1918, coinciding with the human influenza pandemic. Since that time swine influenza has remained of importance to the swine industry throughout the world. The great genetic variability of influenza viruses is caused by two main genetic mechanisms: point mutations (antigenic drift) and gene reassortment (antigenic shift). Influenza is endemic in pigs in many countries and the emergence of new viruses has been challenging its control and diagnostics. Influenza virus (swIAV) infection in Brazilian swine population is not well characterized, and little evidence existed of swIAV circulation before 2009, especially in Rio Grande do Sul State, which hosts one of the largest swine populations in Brazil. Thus, this study aimed to investigate the occurrence of IAV in commercial swine herds in the state of Rio Grande do Sul, Brazil, between 2013-2014 and to know the types and subtypes of swine influenza viruses that are circulating in these herd. The first chapter of this study reports the clinical, pathological and virological aspects of the occurrence of swine influenza and related co-infections in six pig properties of the Taquari Valley region. In this study were analyzed nasal swabs collected from 66 animals and six lung tissue samples from pigs showing clinical signs of respiratory disease. IAV detection was performed by PCR screening and confirmed by virus isolation in MDCK cells and hemagglutination (HA). Influenza A subtyping was performed by real-time reverse transcription PCR (rRT-PCR) to detect the 2009 H1N1pandemic A(H1N1)pdm09; other swIAV subtypes were identifieded by multiplex RT-PCR. Bacterial infections were identified through detection of bacterial genomes by PCR, only in lung samples. Influenza A was detected by screening PCR in 46/66 swab samples and from 5/6 lungs. Virus was recovered from pigs of the six herds. Subtype A(H1N1)pdm09 was detected in 4/6 herds and H1N2 in the other 2/6 herds. In lung tissues, further agents involved in porcine respiratory disease complex were detected in all cases; Pasteurella multocida was identified in 5/6 samples and Mycoplasma hyopneumoniae in 3/6. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) and PCV2 (1/6) were also detected. The aim of the second chapter was to sequence the whole-genome of a novel human-like H1N2 swine influenza virus. Wholegenome sequences were generated by RT-PCR. Amplicons were purified followed by sequencing in the MiSeq sequencing platform (Illumina). Phylogenetic analyses revealed that the HA and NA genes clustered with influenza viruses of human lineage, whereas the internal genes (PB1, PB2, PA, NP, M and NS) clustered with the A(H1N1)pdm09. The third chapter reports the genetic sequencing of the full genomes of eight swine influenza viruses circulating in the sampled pig population. Two swine human-like subtypes (H1N2 and H3N2) and the A(H1N1)pdm09 virus were identified. The human-like subtypes have the HA and NA genes similar to the human seasonal strains and the internal genes are closely related to the virus A(H1N1)pdm09.

Thesis. 1979. M.S.--Massachusetts Institute of Technology. Alfred P. Sloan School of Management. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND DEWEY. / Includes bibliographical references. / M.S.

The swine-origin H1N1 influenza A pandemic virus (A(H1N1)pdm09) was detected in the human population in March 2009. Due to its antigenic novelty, the majority of individuals were susceptible to the virus and the pandemic quickly disseminated around the globe. Rapid characterization of the epidemic was required in order to help inform interventions and determine the risk posed to public health. Widespread sampling and sequencing of virus isolates enabled early characterization of the virus using phylogenetic analysis and continued surveillance over the subsequent three years of global circulation. Throughout this thesis, Bayesian phylogenetic methods are employed to investigate how quickly evolutionary parameters can be accurately and precisely estimated from pandemic genome sequence data and explore how selection has acted across the A(H1N1)pdm09 genome over its period of transition to a seasonal influenza lineage. It is shown that accurate estimates of the evolutionary rate, date of emergence and initial exponential growth rate of the virus can be obtained with high precision from analysis of 100 genome sequences, thereby helping to characterize the virus just 2 months after the first cases were reported. In order to account for variation in growth rates of influenza epidemics between localized outbreaks around the globe, a hierarchical phylogenetic model is employed for analysis of pandemic and seasonal influenza data. The results suggest that the A(H1N1)pdm09 lineage spread more easily and with greater variation between populations during its first pandemic wave than either seasonal influenza lineage in previous seasons. The birth-death epidemiology model has been shown to provide more precise estimates of the basic reproductive number than the coalescent in analysis of HIV epidemic data. Analysis of pandemic influenza data carried out here suggests that the model assumptions are less applicable to influenza and in fact thebirth-death epidemiology model loses accuracy more rapidly than coalescent models as data increased during the pandemic. The effects of an increasingly immune global host population over the pandemic and subsequent influenza seasons were investigated using robust counting of substitutions across the genome. Results suggest that antigenic genes were under a greater selective pressure to evolve than internally expressed genes and the rate of non-synonymous substitution was highest across all segments immediately after emergence in the human population. Bayesian phylogenetics is increasingly being employed as an important tool for rapid characterization of novel infectious disease epidemics. As such, the work carried out here aims to determine the accuracy and applicability of existing evolutionary models with pandemic sequence data sampled over a range of temporal and spatial scales to help better inform similar analyses of future epidemics.