Dissertation (D.P.H.)--University of Michigan.

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Community Medicine / Master / Master of Public Health

Background Chronic smokers are at risk of premature death associated with underlying pulmonary or cardiovascular diseases. Dual influenza and pneumococcal vaccination has been shown to prevent death and hospitalization secondary to pulmonary or cardiovascular diseases in elderly persons. Its effect in chronic smokers remained unknown. Methods This is a prospective randomized open-labeled trial conducted from April 2010 to March 2013, comprising adult patients aged less than 50 years who were chronic smokers. Subjects were randomly assigned into 4 groups. Group 1 (study group) patients received both trivalent influenza vaccine (TIV) and the 23-valent polysaccharide pneumococcal vaccine (PPV). There were 3 control groups: Group 2 patients received the TIV only. Group 3 patients received the PPV only and Group 4 patients did not receive any vaccines. The TIV used was the Vaxigrip® (Sanofi Pasteur, France) and the PPV used was the Pneumovax®23 (Merck, USA). All enrolled patients were follow-up for 24 months post vaccination. Patient details, Charlson comorbidity index, medications, subsequent hospitalization, diagnosis and mortality were recorded and analyzed. Results A total of 1006 subjects were enrolled and completed the study (Group PPV+TIV: 250; Group TIV: 254, Group PPV: 250 and Group None: 259). The baseline demographics and Charlson comorbidity index were similar among subjects in the 4 groups. The median age was 48 years and 85.9% were male patients. Significantly fewer subjects who received the dual vaccination (Group PPV+TIV) were hospitalized (p<0.001), with shorter mean length of stay (p<0.001), and less frequent hospitalization (p<0.001) for cardiovascular or respiratory diseases than no vaccination (Group None) or single vaccination (Group TIV and Group PPV). Multivariate analysis demonstrated that dual vaccination with PPV + TIV was the only independent factor associated with reduced risk of hospitalization (p<0.001; relative risk 0.288; 95% CI 0.101-0.154). There was no difference in mortality rate among the groups. Both vaccinations were well tolerated and no serious adverse events were reported. Conclusion Dual influenza and pneumococcal vaccinations prevented chronic smokers against hospitalization secondary to pulmonary or cardiovascular causes. Annual influenza and a single pneumococcal vaccination should be promoted among chronic smokers. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Masters Abstracts International, Volume: 46-01, page: 0339. Adviser: Cynthia L. Chappell. Includes bibliographical references.

published_or_final_version / Community Medicine / Master / Master of Public Health

An effective antibody response is essential for immunity against influenza virus infection and is the primary goal for vaccine development. In this study, codon optimized and wild type DNA vaccines expressing hemagglutinin (HA) antigens of human flu viruses A/H1N1/NewCal/20/99 (H1 serotype) were compared to test the antigenic differences of the constructs in mammalian systems. Furthermore, to determine if a prime-boost immunization strategy was more effective in eliciting a greater immune response, a codon optimized HA vaccine was administered as a prime in conjunction with the trivalent inactivated vaccine (TIV), Fluzone, as a boost and immune responses were measured. We found that protein expression and antibody response levels of HA antigens were increased with the codon optimized construct when compared to the wild type HA gene construct. Prime-boost vaccination of NZW rabbits was able to elicit a greater immune response when compared to TIV alone as measured by enzyme-linked immunosorbent assay (ELISA), hemagglutinin inhibition (HI) and neutralizing antibody (NAb) assays. Together, these studies indicate that optimal HA DNA vaccine formulations should be codon optimized and can be used as part of a prime-boost vaccination strategy.

The impact of influenza pandemics is felt most greatly in developing states, where the close proximity between humans and disease vectors, weak public health surveillance systems, and poor sanitation make these states particularly vulnerable to influenza pandemics. A vaccine is the most effective intervention to minimise the spread and impact of influenza, and yet, developing states are the least likely to have timely access to a vaccine during a pandemic. According to 'The Committee on Economic, Social and Cultural Rights General Comment No. 14: the Right to the Highest Attainable Standard of Health' there is a clear positive obligation for states to provide access to vaccines during an influenza pandemic, and this obligation is not waived or depleted merely because developing states have resource constraints. There has been a proliferation of literature recently which has considered access to medicines in developing states and the right-to-health. However, there has been little exploration of this issue in respect of pandemic influenza vaccines. This research explores the manner in which developing states procure influenza vaccines during a pandemic, and determines if the current international legal mechanisms which are available to developing states can be successfully used to enhance procurement, and increase the amount of vaccine developing states can access during a pandemic, to a point where they can discharge their right-to-health obligations. In doing so, I argue that the WHO Pandemic Influenza Preparedness Framework, and the flexibilities of the TRIPS Agreement are not able to enhance the procurement of pandemic influenza vaccines by developing states, to the point where states right-to-health obligations can be said to be discharged. From this, I propose an international 'Knowledge Clearing House as a solution to the problems in procurement which are identified in this research.

INTRODUÇÃO: Indivíduos infectados pelo HIV apresentam maior risco de quadros graves de infecção por influenza sazonal e, portanto, devem receber doses anuais da vacina contra gripe. No entanto, a capacidade dos indivíduos responderem às vacinas com títulos apropriados de anticorpos depende de variáveis como tipo de antígeno vacinal, idade e grau de comprometimento imunológico no momento da imunização. OBJETIVOS: 1) Avaliar a imunogenicidade da vacina contra influenza sazonal em 37 pacientes infectados pelo HIV, em comparação com 29 indivíduos não infectados pelo HIV 2) Realizar a vigilância dos episódios de infecções respiratórias durante o período de acompanhamento após a vacinação. MÉTODOS: Ambos os grupos receberam a vacina contra o vírus da influenza sazonal recomendada para o hemisfério sul em 2008. A resposta de anticorpos contra os antígenos H1N1, H3N2 e B foi medida em amostras de sangue extraídas 1-2h antes da vacinação (T0), após 1 mês (T1) e após 6 meses (T6; apenas no Grupo HIV). A vigilância dos sintomas respiratórios foi realizada através de telefonemas semanais, durante 6 meses após a vacinação. Em indivíduos sintomáticos para infecções respiratórios foram coletadas amostras de lavado nasofaríngeo para pesquisa de vírus respiratórios por Imunofluorescência e PCR: influenza A e B, parainfluenza 1, 2 e 3, adenovírus, metapneumovírus, vírus sincicial respiratório, rinovírus e coronavírus. RESULTADOS: A idade mediana da população de estudo foi de 12 (10-18) anos. No momento T1, ambos os grupos mostraram aumento significativo nos TMGs para todos os antígenos. Contudo, o grupo controle apresentou valores mais elevados para os antígenos A/H1N1 e A/H3N2 (p = 0,002 e 0,001, respectivamente). Houve maior aumento na porcentagem de indivíduos não infectados pelo HIV com títulos protetores A/H1N1 (96,6%) em comparação aos infectados pelo HIV (67,6%). No T1 (p=0,004). A porcentagem de indivíduos do grupo controle com aumento de quatro vezes ou mais nos títulos de anticorpos para A/H1N1 e A/H3N2 foram mais elevadas que no grupo HIV (p = 0,03 e 0,01, respectivamente). Agentes virais foram detectados em 39/60 (65%) dos episódios de infecção respiratória no grupo HIV e em 17/32 (53,1%) no grupo controle. Os vírus diagnosticados no grupo HIV e grupo controle foram respectivamente: adenovirus (8,6%), metapneumovirus (1,2%), rinovirus (16,8%), coronavirus (14,0 %) e influenza B (0,1%).CONCLUSÕES: A vacina sazonal contra os vírus da influenza foram imunogenicas em ambos os grupos. Ocorreram diferença nas taxas de soroproteção entre os grupos somente para o antígeno H1, que foi mais elevadas no grupo controle. O grupo controle também mostrou valores mais altos nos TMGs para os antígenos H1 e H3 depois da imunização. Os rinovirus (27,7%) e coronavirus (22,5%) foram os agentes mais prevalentes identificados no grupo infectado pelo HIV. No grupo controle, os vírus mais freqüentes foram os rinovirus (24,2%) e adenovirus (21,2%) / INTRODUCTION: Individuals infected with HIV are at higher risk for severe cases of seasonal influenza infection and therefore should receive annual doses of influenza vaccine. However, the ability to respond to vaccines respond appropriate antibodies titres depends on variables such as vaccine antigen, age and degree of immune impairment at immunization. OBJECTIVES: 1)To evaluate the immunogenicity of a seasonal influenza vaccine in 37 HIV-infected patients (HIV Group), compared to 29 uninfected individuals (Control Group) 2) To carry out a clinical and virological surveillance of influenza in this population during a follow-up period of six months. METHODS: Both groups received the vaccine against seasonal influenza virus recommended for the southern hemisphere in 2008. The antibody response against the antigens H1N1, H3N2 and B were measured in blood samples drawn at vaccination (T0), after 30 days (T1) and after 6 months (T6; only for HIV Group). Antibody titres >1:40 were considered protective against influenza infection A surveillance of respiratory symptoms was performed weekly by telephone calls for a post-vaccination follow-up period of 6 months. Samples were collected (nasal wash) if respiratory symptoms. DFA and real time PCR was used to diagnose influenza A virus (FLU A) and B (FLU B), respiratory syncytial virus (RSV), parainfluenza virus types 1, 2 and 3 ( Paraflu 1, 2 or 3), adenovirus, coronavirus, rhinovirus, metapneumovirus and bocavirus. RESULTS: The median age of the study population was 12 (10-18) years. At T0, there were no significant differences in the antibody geometric mean titres (GMTs) against all vaccine antigens between groups. One month after vaccination (T1), both groups showed significant increases in the antibody GMTs for all antigens. However, healthy controls showed higher values for antigens A/H1N1 and A/H3N2 (p = 0.002 and 0.001, respectively). There was a higher increase in the percentage of HIVuninfected subjects with protective A/H1N1 antibodies (96.6%) comparing to HIVinfected vaccinees (67.6%) at T1 (p = 0.004). The percentage in subjects control group with a fourfold or greater increase of A/H1N1 and A/H3N2 antibody titres was higher than that found in HIV group (p = 0.03 and p = 0.01, respectively. Viral agents were identified in 39/60 (65%) episodes of respiratory infections in HIV-infected group and in 17/32 episodes (53.1%) from the control group (P=0.273). The virus diagnosed in HIV group and control group were, respectively: Adenovirus (8;6), Metapneumovirus(1;2) Rinovirus(16;8), Coronavirus(14 ;0); Influenza B(0;1). CONCLUSIONS: The seasonal influenza vaccine was immunogenic in both groups. There were differences in seroprotection rates between groups only for AgH1, which was higher in the control group. The control group also showed a greater increase in GMTs for H1 and H3 antigens after immunization. Viral agents were identified in respiratory symptoms during the follow-up: Rhinoviruses (27.7%) and coronavirus (22.5%) were the most prevalent agents identified in HIV-infected individuals. In the control group, the viruses most frequently found were rhinoviruses (24.2%) and adenovirus (21.2%)