This thesis deals with problems of vaccination, which is today a very discussed topic. Thesis is focused on general information about immunization, vaccine calendar, safety and legislation on vaccination. In the thesis is also examined public opinion about vaccination. The thesis is mainly focused on optional vaccination against pneumococcal infections. Specifically looks at the factors which influence consumer decision-making in the selection of pneumococcal vaccines. Compared are the two competing preparations, Synflorix and Prevenar. The objective of the thesis is to identify and compare factors influencing the consumer choice of vaccine against pneumococcal infections.

A Bordetella pertussis é a bactéria causadora da coqueluche, doença infectocontagiosa que tem reemergido em diversos países apesar das altas coberturas vacinais. Como os indivíduos mais afetados são crianças menores de seis meses de idade, a vacinação de gestantes com uma dose de vacina adsorvida contra tétano, difteria e coqueluche (B. pertussis acelular - dTpa) foi proposta. O objetivo é promover a transferência de altos títulos de anticorpos maternos ao feto e recémnascido, resultando na sua proteção até que o seu esquema vacinal esteja concluído. Esta estratégia é empregada em diversos países e no final de 2014 foi introduzida no Brasil. Entretanto, pouco se sabe sobre sua eficácia, efetividade e interação com a posterior vacinação da criança, que é realizada com a formulação de células inteiras (DTP), enquanto outros países substituíram-na pela formulação acelular (DTPa). Sabe-se que a vacinação materna induz anticorpos que ajudam a proteger recém-nascidos da infecção, mas podem, também, neutralizar a vacinação da criança, diminuindo a eficiência vacinal, além de promover a transferência de antígenos para o feto, induzindo desvio do perfil de resposta. Esses aspectos são particularmente importantes e devem ser investigados quando novos programas de vacinação materna são implantados. Sendo assim, o objetivo do presente estudo foi avaliar a resposta celular contra B. pertussis em parturientes e neonatos no dia do parto, e em lactentes após vacinação completa contra a coqueluche com DTP no primeiro ano de vida, comparando-se o grupo proveniente de mães que foram vacinadas durante a gestação com as que não receberam a dose de reforço. As células mononucleares do sangue periférico e de cordão umbilical dos participantes foram isoladas e estimuladas com antígeno bacteriano ou antígeno policlonal em cultura. Após o tempo estipulado, verificou-se o perfil de expressão gênica por qPCR nas células e a concentração de citocinas de interesse em sobrenadante, por meio de citometria de fluxo. Os dados obtidos mostram que a vacina na gestação induz resposta celular favorável à proteção contra infecção em gestantes, com produção de citocinas de perfil Th1 após estímulo antigênico, enquanto que nos neonatos poucas citocinas estavam acima dos limites de detecção. Quando se comparou a resposta de lactentes nascidos de mães vacinadas ou não durante a gestação, não foi encontrada diferença significativa nos níveis de citocinas produzidos, sugerindo que os anticorpos maternos presentes durante o desenvolvimento fetal e os primeiros meses de vida das crianças não interferiu no processo de reconhecimento e geração de resposta específica. Apesar do número amostral limitado, este trabalho mostra um panorama da interação da vacinação materna com a resposta celular à vacinação da criança no seu primeiro ano de vida, mostrando que a princípio a dose de reforço com dTpa durante a gestação é capaz de gerar resposta celular protetora nas gestantes, prevenindo-as de transmitir a doença a seus filhos, e a resposta humoral produzida não interfere na geração de resposta celular de seus filhos após o seu próprio esquema de imunização. / Bordetella pertussis is the bacterial agent of whooping cough, an infectious and contagious re-emerging disease despite high vaccine coverage. As the most affected are children younger than six months of age, a dose of tetanus/diphtheria/pertussis vaccine (acellular pertussis - Tdap) in pregnancy was proposed. It is aimed to promote the transfer of high maternal antibodies\' titres to the foetus and newborns, resulting in their protection until their own vaccination scheme is completed. This strategy is present in several countries, and it was implemented in Brazil by the end of 2014. However, little is known about its efficacy, effectiveness and interaction with the subsequent child\'s vaccination, which comprehends the whole-cell formulation (DTP), while other countries replaced it for the acellular version (DTaP). Maternal vaccination induces antibodies that would protect newborns from infection, but they can also neutralize the effect of the child vaccination, reducing the vaccine efficiency. Besides, it can promote the transfer of antigens to the foetus, which can induce deviation in the response pattern. These aspects are particularly important and should be investigated when new maternal vaccination programs are implemented. Therefore, the aim of this project was to evaluate the cellular response against B. pertussis in women at labour and their neonates, as in young children after complete pertussis vaccination by the first year of life, comparing groups from vaccinated and non-vaccinated women during pregnancy. Peripheral blood and cord blood mononuclear cells were isolated and stimulated with bacterial or polyclonal antigen in culture. After the stipulated time the gene expression profile and cytokine concentration were evaluated by qPCR and flow cytometry. Data from the present study show that pregnancy vaccination inducing favourable cellular response for protection against infection in pregnant women, with Th1 cytokines\' production upon antigenic stimulus, while in newborns few cytokines were detected above the detection limit. When comparing children\'s response, born either from vaccinated or unvaccinated mothers, cytokine levels were not significantly different, suggesting that maternal antibodies present during foetal development and first months of life do not interfere with recognition and cellular response generation to vaccination. Despite limited sample size, this work shows a broader view of interaction between maternal and child vaccination, showing that the Tdap boost dose during pregnancy may be able to generate protective response in women, preventing them to transmit the disease to children, and the induced humoral response may not interfere in generating cellular response in children after their own vaccination.

Marek’s disease (MD) is an oncogenic disease affecting chickens and is estimated to cost the worldwide poultry industry $1-2 billion annually. The causative agent of MD, Marek’s disease virus (MDV), provides a welldocumented example of virus virulence evolution occurring over a period of sixty years. The reason behind this evolution is unknown, although certain untested hypotheses have been suggested. These include vaccination (with increasingly potent vaccines) and other aspects of industrialisation, such as the decreased cohort duration of successive generations and an increased stocking density of the broiler flocks. In this thesis, four sections of work are undertaken. First, estimation of epidemiological parameters is tackled: virulence of MDV is quantified by looking at host mortality and virus shedding rates in vaccinated and unvaccinated birds. This is achieved via maximum likelihood estimation and Bayesian McMC techniques. Second, viral fitness is quantified by defining multiple lifetime fitness functions using the parameters previously estimated to understand the direction and force of virulence selection for different farm environments. Third, the impact of an outbreak of MDV on a broiler flock is examined by simulating a whole flock of birds. This provides an epidemiological understanding of the virus at the flock level and can help elucidate methods for disease control and surveillance and can also give a fitness measure to understand on-farm evolution of the virus. Fourth, a between-farm model is analysed to evaluate which MDV strains are able to persist in a network structure of farms and how this might be affected by biosecurity measures, different farm networks, farm size, bird lifespan and vaccination. This provides insights into how quickly a different strain can invade a farm network and the plausibility of it becoming endemic. Parameter estimation results show that the time to death for an infected bird decreases and its virus shedding rate increases with previous definitions of virulence in the literature. Model results suggest that the choice of fitness measure alters the conclusions reached. Increasing the amount of demographic structure introduced into the fitness measure shows that neither vaccine introduction nor decreasing a bird’s lifespan changes the ability of more virulent virus strains to outcompete less virulent strains. In any environment, more virulent strains are always selected for. Epidemiological results suggest that vaccination allows a low prevalence of virus on a farm although there are no deaths from the disease itself. Analogous results for between-farm spread suggest that if on-farm cleaning efficiency is low enough, a high prevalence of disease throughout a network of vaccinated flocks can exist but the farms themselves show no signs of increased mortality from the disease. The hypotheses for explaining the increase in virulence of MDV may not be consistent with the results of this work. Despite previous arguments that vaccines are driving the evolution of virulence ofMDV, this first quantitative work on the subject demonstrates that this might not be the case. This work also formulates new hypotheses to explain why MDV virulence has increased over the past sixty years which will pave the way for ongoing research in the area of virulence evolution in farm environments.

Shiga producing E. coli (STEC) O157 is a zoonotic pathogen. In humans STEC O157 causes bloody diarrhoea and potentially fatal renal failure. Cattle are the major reservoir, where bacteria are limited to the intestinal tract and do not cause clinical signs of disease. Previous studies indicate that shiga toxins produced by STEC O157, suppress STEC-specific cellular immune responses in vivo. This study aimed to initially examine the humoral immune response in cattle following natural challenge and the effects of a toxoid vaccination on this humoral STEC specific-immune response. We determined a statistically significant suppression in Tir specific IgA in STEC O157 positive cattle compared to O157 negative cattle but not in super shedding cattle. Following toxoid vaccination we determined a significant increase in flagellin specific IgG1 antibody levels in toxoid vaccinated animals despite lower numbers of positive faecal samples compared to placebo vaccinated controls. These results suggest that shiga toxins produced by STEC O157 are actively suppressing the STEC specific immune response in natural colonisation. To clarify this suppression further calves were orally challenged with STEC O157 (either a PT21/28 Stx2c+, PT32 Stx2c+ or PT21/28 Stx2a+Stx2c+ strain) and their STEC specific immune responses monitored. STEC specific systemic antibody responses were variable and weak in some cases. STEC specific local antibody responses were only significantly increased following challenge with the PT21/28 Stx2a+Stx2c+ challenge. Transcripts for genes associated with immune responses, and in particular B cell activation, at the terminal rectum were analysed by reverse transcriptase quantitative PCR. Suppression of IL2RA transcripts was observed in calves challenged with PT21/28 Stx2a+Stx2c+ compared to control calves but not with the other two STEC O157 strains tested. This study also aimed to determine the effects of cattle colonisation with STEC O157 on the immune response to a non-bacterial T-cell dependent antigen, ovalbumin (OVA). Cattle were orally challenged with either a PT21/28 Stx2c+, PT32 Stx2c+ or PT21/28 Stx2a+Stx2c+ strain or unchallenged. Calves were subcutaneously immunised with OVA five days post challenge, on two separate occasions with a two week interval. Lymphocytes from lymph nodes local to the immunisation site demonstrated significantly increased OVA-specific proliferation and OVA-specific activation of CD4+ and CD8+ cells in calves that were challenged with the PT21/28 Stx2c+ strain (but not with the other two challenge strains), compared to unchallenged controls. These results indicate that colonisation with STEC O157 can alter local adaptive immune responses to non-bacterial antigens in a strain dependent manner, unexpectedly enhancing the immune response rather than suppressing it. Circulating T cell responses were unaffected. In conclusion this study provides some further evidence of adaption of the host immune response by STEC O157, which is strain dependent, and variable. It seems unlikely from the data in this study that STEC O157 colonisation is having a major impact on the responses of cattle to other vaccines or infections in the field.

Bakgrund: Föräldrar som står inför valet att vaccinera sina barn är inte alla gånger eniga om vaccinets för- och nackdelar. Information om vaccinen cirkulerar på internet och via sociala medier. För läsaren blir det en utmaning att veta vilken given information som är trovärdig. Mötet med vården blir därmed en central punkt där föräldrar kan söka vägledning och få sina farhågor bemötta. Syfte: Syftet med studien är att belysa vilka diskussioner som förs på offentliga forum och Facebookgrupper som kan ligga till grund för tveksamhet eller avståndstagande till det svenska barnvaccinationsprogrammet samt hur mötet med vården beskrivs av föräldrar som avböjer att vaccinera sina barn. Metod: Kvalitativ metod med beskrivande design har använts. Inlägg från en offentlig Facebookgrupp samt sex diskussionstrådar från forumet Familjeliv.se sammanställdes och analyserades med systematisk textkondensering. Resultat: Resultatet påvisar olika komplexa motargument och farhågor om vaccin som ingår i det svenska barnvaccinationsprogrammet. Farhågorna rör biverkningar, vaccinets innehåll och tidpunkten för vaccinering. Vissa upplevde vaccinationen som onödig då det idag finns tillgång till modern sjukvård, hygien och sanitet samt att vaccinet ändå inte ger ett hundraprocentigt skydd. Bristen på tillit för myndigheter och läkemedelsföretag var ytterligare en faktor som visade sig ligga till grund för skepticismen kring vaccin. I mötet med vården beskriver människor känslor av uppgivenhet och undergivenhet. Vikten av att diskutera inför ett beslut kring vaccination utan dispyter poängteras, vilket enligt resultatet är något som inte alltid sker. Slutsats: Ett ökat förtroende för vården måste skapas genom tydligare riktlinjer för kommunikation kring vaccination samt tillgänglighet till information som besvarar människors farhågor.

Student Number : 9903144J - MSc (Med) dissertation - Faculty of Health Sciences / Since the introduction of vaccination against hepatitis B virus (HBV) infection in South Africa, at least one case of infection despite vaccination has occurred. The purpose of this study was to determine whether this infection was the result of mutations within the region of the surface (S) gene encoding the a determinant epitopes of the hepatitis B surface antigen, which permitted viral vaccine-escape. HBV DNA was extracted from the serum and liver tissue of the patient and amplified within the complete 3 215 bp genome and S gene, respectively. Following cloning, sequencing revealed a minor population displaying unique or uncommon S gene mutations that resulted in C138R, C139R, K141R, P142L, T143A, N146D, and T148A amino acid substitutions in the clones from the serum, and C139Y and D144N in the clones from the liver. Such isolates may represent South African HBV vaccine-escape mutants that caused chronic infection in the host prior to their reversion to wild-type.

Many in the biomedical community have praised the recently released Human Papillomavirus (HPV) vaccine, Gardasil, for having the potential to significantly reduce the disease burden of cervical cancer and genital warts. However, complex intersections of ideology, morality, and politics have made this new vaccine considerably contested, particularly as public debate has turned to the ethics of state-mandated HPV vaccination for 11-12 year old girls. Subsequently, the extent to which mandatory vaccinations are accepted by parents and implications regarding the infringement of these coercive measures on their rights to make health care decisions for their children has become powerfully positioned in public discourse. This research seeks to examine how mothers of girls conceptualize Gardasil and the potential mandates in order to illuminate the multi-faceted socio-cultural context of risk embedded within this immunization. Major themes that emerged from in-depth interviews include diverse perceptions of the risk of HPV for their daughter(s) specifically, children as actual or potential sexual beings, concerns about vaccine safety, mistrust of pharmaceutical companies and government collusion, and conceiving of vaccination against HPV as imbued with a either a moral or cancer prevention subtext. The need for collaboration and communication between the medical and governmental institutions who promote vaccines such as Gardasil and the public who politically and socially consumes them has been apparent throughout my research. Applied anthropologists have a unique role to play by situating diverse stakeholder perspectives across interdisciplinary fields in order to develop more appropriate and informed policies.

Cervical cancer is the most common human papilloma virus (HPV) -associated cancer and is the second leading cause of death in the world. Vaccination against HPV is essential to reduce the incidence of HPV and subsequent morbidity and mortality. According to the Centers for Disease Control and Prevention (CDC), approximately 79 million Americans are currently infected with HPV. The site for this DNP project was a 163-bed facility with inpatient and outpatient services in the southern United States. The vaccination rate at the site was 48%. The facility lacked educational interventions to prepare and remind providers to offer HPV vaccine. The purpose of this DNP project was to address a significant gap by increasing clinician knowledge through the development of educational materials, the design and implementation of training sessions for staff, and the development of protocols that require providers to offer the vaccine to every eligible patient and to call the patient and remind them of appointments for vaccine injections. The academic center for evidence-based practice star model was used to translate knowledge into nursing practice to improve outcomes change. For this project, a panel of 10 experts from the facility was formed to conduct a formative and summative evaluation of the educational materials and protocols. The findings of the study showed an acceptance of the plan suggesting the importance of the educational materials and the educational process to increase HPV vaccination rates, which can thereby reduce death and disease associated with HPV through the empowerment of the clinicians to provide necessary and appropriate care.

In the United States, 79 million people are currently infected with Human Papilloma Virus (HPV) and it is estimated that an additional 14 to 20 million people will be infected with HPV every year. Infection with HPV increased to 52.7 % of preventable infections within the United States in 2012, and 39.6% of the infected population are adolescents engaged in sexual activities. The practice-focused question that this project addressed was: To what extent can an educational program influence the HPV vaccination rate in a small family practice clinic located in Texas? The main purpose of this project was to increase education within the clinic community using a quality improvement approach and guided by Healthy People Goals 2020. Barriers to HPV vaccination were validated through focus group discussion held with clinic staff. Parental resistance was due to a misconception that the vaccine would lead to sexual promiscuity in the adolescent population, and that a single dose is adequate protection. A bilingual educational session was held with 15 clinic staff members with the purpose of enhancing knowledge, influencing parental attitudes and beliefs, providing patient educational tools, and thereby increasing vaccination acceptance by 37.8% within an underserved and vulnerable population. The results of the focus group and educational sessions were presented to an expert panel made up of five community leaders and the senior clinic leader who approved the approach and suggested additional ways to promote HPV vaccination. Clinic leadership agreed to adjust policy mandating use of the educational materials with clinic patients. Positive social change will result from the integration of this educational approach into clinic practice by increasing vaccination acceptance.

Human papillomavirus (HPV) is the most common sexually transmitted virus, and is causally related to several cancers. HPV vaccination rates are far below HealthyPeople 2020 targets and vary across geographic, socioeconomic, and demographic populations. The purpose of this research was to test the relationships among socioeconomic and demographic variables, HPV vaccination, social vulnerability, and physician recommendation within select local areas in the United States. Fundamental cause theory and behavioral economics informed this quantitative secondary analysis of National Immunization Survey-Teen and Social Vulnerability Index data (n = 43,271). Statistical analyses included chi-square and binomial logistic regression. Teens whose mothers had less than a college degree were more likely to initiate the HPV vaccine series (p < .01), while teens living in Hidalgo County and Houston were less likely to initiate the series (p < .001). Younger teens (p < .001), males (p < .001) and teens whose mothers had some college (p < .01) were less likely to complete the series, while older teens (p < .001) and teens living in Philadelphia and Houston (p < .01) were more likely to complete the series. Fewer teens in Bexar County received a physician recommendation (p < .01); there was no difference between vaccine initiation and select local area. These findings highlight the need to consider local sociodemographic influences on underlying disparities in health and physician behavior. Informed interventions may produce positive social change by reducing variance in health care quality, tailoring public health efforts to local needs, and moving persons experiencing disparities in health outcomes toward a healthy future.